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Isabella NERI

Professore Associato
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto

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2023 - Healthy preterm newborns: Altered innate immunity and impaired monocyte function [Articolo su rivista]
De Biasi, Sara; Neroni, Anita; Nasi, Milena; Lo Tartaro, Domenico; Borella, Rebecca; Gibellini, Lara; Lucaccioni, Laura; Bertucci, Emma; Lugli, Licia; Miselli, Francesca; Bedetti, Luca; Neri, Isabella; Ferrari, Fabrizio; Facchinetti, Fabio; Berardi, Alberto; Cossarizza, Andrea

: Birth prior to 37 completed weeks of gestation is referred to as preterm (PT). Premature newborns are at increased risk of developing infections as neonatal immunity is a developing structure. Monocytes, which are key players after birth, activate inflammasomes. Investigations into the identification of innate immune profiles in premature compared to full-term infants are limited. Our research includes the investigation of monocytes and NK cells, gene expression, and plasma cytokine levels to investigate any potential differences among a cohort of 68 healthy PT and full-term infants. According to high-dimensional flow cytometry, PT infants have higher proportions of CD56+/- CD16+ NK cells and immature monocytes, and lower proportions of classical monocytes. Gene expression revealed lower proportions of inflammasome activation after in vitro monocyte stimulation and the quantification of plasma cytokine levels expressed higher concentrations of alarmin S100A8. Our findings suggest that PT newborns have altered innate immunity and monocyte functional impairment, and pro-inflammatory plasmatic profile. This may explain PT infants' increased susceptibility to infectious disease and should pave the way for novel therapeutic strategies and clinical interventions.

2022 - Carboplatin-paclitaxel in triple-negative metastatic breast cancer during pregnancy with neoplastic thrombosis [Articolo su rivista]
Monari, F.; Grandi, G.; Guidotti, I.; Torcetta, F.; Battista, R.; Coluccio, V.; Piombino, C.; Moscetti, L.; Neri, I.; Toss, A.

The treatment of breast cancer (BC) diagnosed during pregnancy is a challenging situation for the patient, family and healthcare providers. Here we describe the case of a 35-year-old woman diagnosed with a triple-negative breast cancer relapse during pregnancy. She previously underwent neoadjuvant chemotherapy without any response, subsequent left skin sparing mastectomy plus axillary node dissection and radiation therapy to the chest wall and supraclavicular lymph nodes. Two years later, during her first single pregnancy, the patient presented a subclavian vein thrombosis and a BC relapse to locoregional lymph nodes. At 24 weeks of gestation, a first line treatment with weekly paclitaxel and carboplatin was started. Considering the disease progression after two complete cycles of chemotherapy, the patient had an elective caesarean section at 32+6 weeks. A full-body CT-scan and a PET-scan after the delivery showed a massive neoplastic thrombosis involving the left jugular, brachiocephalic and internal mammary vein, as well the superior vena cava and the right atrium. Few data are available on platinum-based chemotherapy during pregnancy in BC patients. Nevertheless, the choice of therapy was conditioned by the previous absence of response to anthracycline and taxane. In case of BC diagnosis during pregnancy, a multidisciplinary management as in the case described is recommended to increase the chance of survival both for the patients and their babies.

2022 - Fetal head malposition and epidural analgesia in labor: a case-control study [Articolo su rivista]
Menichini, D.; Mazzaro, N.; Minniti, S.; Ricchi, A.; Molinazzi, M. T.; Facchinetti, F.; Neri, I.

Background: The fetal head malposition in labor leads to prolonged labor, cesarean delivery and increased perinatal morbidity. Epidural analgesia has been associated with fetal head malposition, but it remains unknown if this relation is causal. Objective: To compare the incidence of fetal malposition during labor and maternal/fetal outcomes, between women who received epidural analgesia with those who did not use the analgesic method. Study design: Case control study including 500 women with a single fetus in vertex position who gave birth at term at the Policlinic Hospital of Modena between May 2019 and July 2019. Two-hundred and fifty women belonged to the epidural analgesia (EA) group and 250 to the control group. Results: The rate of posterior occiput positions occurred 4 times more frequently in the EA group than in the control group (8.8% vs 2.2%, p =.004). Cesarean sections were significantly higher in the EA group (11.6% vs 1.6%, p <.0000) as well as the need for augmentation with oxytocin (20% vs 8%, p =.0001) compared to the control group, in which spontaneous delivery prevailed instead. Women with epidural had labors that lasted on average 7.0 h against the 3.30 h of controls (p <.0000). The length of 2nd stage of labor was 55 vs 30 min (p =.009), respectively. No differences in blood loss and Apgar score between groups. Early breastfeeding was significantly higher among controls (82% vs 92.8%, p =.0004). Conclusions: Women receiving epidural analgesia in labor have higher rate of fetal malposition, prolonged labors, and more cesarean sections than controls. However, further studies are required to confirm a causal association between EA and fetal head malposition.

2022 - First trimester metabolomics 1H-NMR study of the urinary profile predicts gestational diabetes mellitus development in obese women [Articolo su rivista]
Piras, C.; Neri, I.; Pintus, R.; Noto, A.; Petrella, E.; Monari, F.; Dessi, A.; Fanos, V.; Atzori, L.; Facchinetti, F.

Objective: Obesity is one of the main risk factors for the development gestational diabetes mellitus (GDM). Thus, we aim to identify changes in the urinary metabolomics profile of obese women at first trimester of pregnancy in order to predict later GDM diagnosis. Research design and methods: In this nested case-control study, urine samples collected in the first trimester of pregnancy obtained from obese women who developed GDM (n = 29) and obese women who did not develop diabetes (n = 25 NO GDM) were analyzed with Nuclear Magnetic Resonance spectroscopy combined with Multivariate Statistical Analysis. GDM diagnosis was obtained with one-step oral glucose load. Results: OPLS-DA significantly separated the GDM women from NO GDM women. Specifically, GDM women were characterized by a higher level of tryptophan, trigonelline, hippurate, and threonine, and lower levels of 1-methylnicotinamide, 3-hydroxykynurenine, glycocholate, isoleucine, kynurenine, and valine compared to NO GDM women. Conclusion: In a prevalently Caucasian population, the changes of some metabolites such as tryptophan, trigonelline, and branch-chained amino acids in the urinary profile of obese women in the first trimester are able to make unequivocal prediction of those which later test positive for GDM. This approach could be useful to diagnose much earlier obese women with GDM allowing lifestyle counselling and other interventions.

2022 - First-trimester prediction model for placental vascular disorders: an observational prospective study [Articolo su rivista]
Monari, Francesca; Spano' Bascio, Ludovica; Banchelli, Federico; Neri, Isabella; Bertucci, Emma; Ferrari, Francesca; Menichini, Daniela; D'Amico, Roberto; Facchinetti, Fabio

This study aims to develop a multivariable predictive model for the risk of placental vascular complications (PVC), by using biochemical, biophysical, anamnestic and clinical maternal features available at the first trimester. PVC include gestational hypertension, preeclampsia, placenta abruption, intrauterine growth restriction (IUGR), and stillbirth. Prospective study that included all singleton pregnancies attending the first-trimester aneuploidy screening (11 +0–12 +6 weeks) at Obstetrics Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. In a total of 503 women included in the analysis, 40 patients were in the PVC group. The final prediction model for PVC included the following independent variables: pre-pregnancy BMI ≥ 30 (OR = 2.65, 95% CI = 1.04; 6.75, p = 0.0415), increasing values of mean arterial pressure (OR = 1.06, 95% CI = 1.02; 1.10, p = 0.0008), PAPP-A < 2.40465 U/L (OR = 0.43, 95% CI = 0.19; 0.96, p = 0.0388) and decreasing values of PlGf (MoM) (OR = 0.28, 95% CI = 0.10; 0.79, p = 0.0153). The area under the ROC curve was 79.4% indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to − 2.562, which corresponds to a 7.2 % probability of having PVC. By using such a cut-off, the risk of PVC can be predicted in our sample with sensitivity equal to 82,4 % and specificity equal to 69,9 %. This model for early prediction of PVC is a promising tool to early identify women at greater risk for placenta vascular complications.

2022 - First-trimester prediction of gestational hypertension through the bioelectrical impedance analysis of the body composition [Articolo su rivista]
Menichini, D.; Spelta, E.; Rossi, E.; Monari, F.; DI VINCI, P. L.; Petrella, E.; Facchinetti, F.; Neri, I.

OBJECTIVE: Obesity is a risk factor for the development of gestational hypertension, with important consequences for both the mother and fetus. This prospective observational study aims to propose an early prediction model of hypertensive disorders in pregnancy among obese women, through the bioelectrical impedance analysis (BIA) at the first trimester, thus allowing early recognition of obese women that are at risk to develop gestational hypertension, in order to target preventive interventions. PATIENTS AND METHODS: Singleton obese women (BMI ≥ 30 kg/m2) between the 9th and 12th week of pregnancy were included in the study. The exclusion criteria were chronic diseases, like type 2 diabetes mellitus, hypertension, and other medical pre-existing conditions. Eligible women were followed up at 20, 28, and 36 weeks of gestation by measuring blood pressure, weight, and body composition with the use of the BIA. The diagnosis of gestational hypertension was made after the 20th week of gestation. Pregnancy and perinatal outcomes were then recorded. RESULTS: Of the 479 women included in the study, 85 (17.7%) developed gestational hypertension; the remaining 394 (82.3%) resulted to be normotensive. A higher rate of nulliparous women was found in the hypertensive group (50.6% vs. 37.6%, p = 0.02), together with a higher rate of induction of labor (55.3% vs. 40.9%, p = 0.02) and of small for gestational age (SGA) newborns (12.9% vs. 6.9%, p = 0.03). Significant differences emerged in the body composition between the two groups already from the first trimester, indeed women developing gestational hypertension showed elevated values of Total body Mass, FM, FFM, TBW (p < 0.02), and of leg's FM, FFM (p < 0.006). At the multivariate logistics regression, the risk of developing gestational hypertension resulted higher in women with elevated total body water levels in the first trimester (OR 1.10 95% CI 1.04 -1.92). CONCLUSIONS: The BIA is a rapid, easy, non-invasive, and inexpensive tool to evaluate the body composition of obese pregnant women. It represents a promising predictor of hypertensive disorders in pregnancy, which allows an early identification of the patients at risk of developing gestational hypertension, thus opening a window of opportunity for strictly monitoring and target preventive intervention.

2022 - Guidelines for Vascular Anomalies by the Italian Society for the study of Vascular Anomalies (SISAV) [Articolo su rivista]
Stillo, F.; Mattassi, R.; Diociaiuti, A.; Neri, I.; Baraldini, V.; Dalmonte, P.; Amato, B.; Ametrano, O.; Amico, G.; Bianchini, G.; Campisi, C.; Cattaneo, E.; Causin, F.; Cavalli, R.; Colletti, G.; Corbeddu, M.; Coppo, P.; De Fiores, A.; Di Giuseppe, P.; El Hachem, M.; Esposito, F.; Fulcheri, E.; Gandolfo, C.; Grussu, F.; Guglielmo, A.; Leuzzi, M.; Manunza, F.; Moneghini, L.; Monzani, N. A.; Nicodemi, E. M.; Occella, C.; Orso, M.; Pagella, F. G.; Paolantonio, G.; Pasetti, F.; Rollo, M.; Ruggiero, F.; Santecchia, L.; Spaccini, L.; Taurino, M.; Vaghi, M.; Vercellio, G.; Zama, M.; Zocca, A.; Aguglia, M.; Castronovo, E. L.; De Lorenzi, E.; Fontana, E.; Gusson, E.; Lanza, J.; Lizzio, R.; Mancardi, M. M.; Rosina, E.; Chiti, D.; Lugli, M.; Maleti, O.

2022 - Implementation of guidelines about women with previous cesarean section through educational/motivational interventions [Articolo su rivista]
Monari, Francesca; Menichini, Daniela; Bertucci, Emma; Neri, Isabella; Perrone, Enrica; Facchinetti, Fabio

Objective: The study reports the effect of a quality improvement project with an educational/motivational intervention, in northern Italy on the implementation of the trial of labor after Caesarean Section (CS). Method: A pre-post study design was used. Every birth center (23) of the Emilia-Romagna region was included. Gynecologists' opinion leaders were first trained about CS Italian recommendations. Barriers to implementation were discussed and shared. Educational/motivational interventions were implemented. Data of multipara with previous CS, with a single, cephalic pregnancy at term, were collected in 2 periods, before (2012-2014) and after (2017-2019) the intervention (2015-2016). The primary outcome was the rate of vaginal birth after CS (VBAC) and perinatal outcomes. Results: A total of 20,496 women were included. The VBAC rate increased from 18.1% to 23.1% after intervention (p<0.001). The likelihood of VBAC, adjusted for age ≥40, Caucasian, BMI ≥30, previous vaginal delivery, and labor induction, was increased by the intervention of 42% (OR=1.42, 95% CI 1.31-1.54). Neonatal well-being was improved by intervention, indeed neonates requiring resuscitation decreased from 2.1% to 1.6% (p=0.001). Conclusion: Educating and motivating gynecologists toward the trial of labor after CS is worth pursuing. Health quality improvement is demonstrated by increased VBAC even improving neonatal well-being.

2022 - Mode of Delivery in Women with Stillbirth: Results of an Area-Based Italian Prospective Cohort Study [Articolo su rivista]
Monari, F.; Menichini, D.; Salerno, C.; Donno, V.; Melis, B.; Neri, I.; Facchinetti, F.

Introduction: The choice of the mode of delivery, in case of stillbirth (SB) (fetus non-viable >22 weeks' gestation), should consider maternal preference, gestational age, bishop score, the clinical condition of the woman, and her previous obstetric history. However, despite these clear indications, data on the effective implementation of the latter are lacking. The aim of our study is to evaluate the different modes of delivery in an Italian population of SBs, according to gestational age, parity, causes of death, obstetric history, and maternal characteristics. Material and Methods: This is an area-based, prospective cohort study conducted in Emilia Romagna, Italy between January 2014 to December 2020. Data included all cases of SB (>22 weeks). Results: From 2014 to 2020, 783 SB occurred out of a total of 232.506 births, with a SB rate of 3.3 per 1000. Labor was spontaneous in 85 (11%). Of remnant, 567 (73.6%) were induced and 118 (15.3%) had no labor. The mode of delivery was vaginal in most of the cases (649/770, 84.3%) and by cesarean section in 121/770 (15.7%) of cases. Emergency CS was most frequent and performed in 89/121 (73.5%) of total CS, representing 11.5% of SB deliveries. Mode of induction did not differ in relation to gestational age at stillbirth, while vaginal delivery was significantly higher in women induced with prostaglandins (p = 0.000) respect to other methods. Nulliparous women had a significantly higher need for multiple methods of induction (p = 0.000) respect multiparous and obese women used more frequently prostaglandins (p = 0.03) than other methods. Women with a history of previous CS presented a significantly higher rate of repeated elective CS (p = 0.000). Moreover, emergency CS was performed more frequent in obese (p = 0.02), diabetic (p = 0.04) and hypertensive (p = 0.04) women and in SB caused by placenta disorders, namely in abruptio placentae (p = 0.000). In the case of chorioamnionitis and funisitis women significantly were induced with prostaglandin (p = 0.000) and delivered vaginally (p = 0.000). Conclusions: The method of induction of labor and the mode of delivery in case of SB did not depend on gestational age at the diagnosis of death, while they are related to placenta disorders representing a relevant condition leading to emergency CS also after diagnosis of fetal death. These data could help obstetric providers in managing the deliveries of stillborn infants.

2022 - Nutraceuticals and polycystic ovary syndrome: a systematic review of the literature [Articolo su rivista]
Menichini, D.; Ughetti, C.; Monari, F.; Di Vinci, P. L.; Neri, I.; Facchinetti, F.

Background This study proposes a review of nutraceuticals used in the treatment of typical symptoms of Polycystic Ovary Syndrome (PCOS). The aim is to provide a classification of the most widely used nutraceutical supplements identifying the most effective nutraceuticals on glucose and insulin metabolism, the androgenic hormone profile, fertility, ovulatory capacity, inflammation, and oxidative stress. Material and Methods We included randomized controlled trials on PCOS patients undergoing administration of nutraceuticals, in particular vitamin D, vitamin E, probiotics, and inositols. These administrations are variable in terms of dosage, single supplementation, or combined with other compounds, dosage, and duration of the intervention. Results The supplementation of inositols, at the physiologic ratio of 40: 1 of myo- and D-chiro-inositols, resulted to be the most effective in improving the glucose homeostasis and fertility, with a restoration of ovulatory capacity and menstrual regularity. Other nutraceuticals are particularly effective in reducing hyperandrogenism, with promising results demonstrated by the combinations of vitamin D and probiotics, vitamin E and coenzyme Q10, and the enrichment of inositol therapy with group B vitamins. An improvement in the inflammatory status and antioxidant capacity is obtained with the co-supplementation of probiotics and selenium or with vitamin E combined with omega 3. Conclusions Inositol supplementation is effective in the treatment of insulin resistance and fertility. Probiotics reduced hyperandrogenism, inflammatory and oxidative conditions, and resulted more effective when combined with selenium. Although these results proved to be satisfactory, further studies are needed with larger samples and a more homogeneous analysis of the outcomes.

2022 - Observation of Two New Excited Ξb0 States Decaying to Λb0 K-π+ [Articolo su rivista]
Aaij, R.; Abdelmotteleb, A. S. W.; Abellan Beteta, C.; Ackernley, T.; Adeva, B.; Adinolfi, M.; Afsharnia, H.; Agapopoulou, C.; Aidala, C. A.; Aiola, S.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Alfonso Albero, A.; Aliouche, Z.; Alkhazov, G.; Alvarez Cartelle, P.; Amato, S.; Amey, J. L.; Amhis, Y.; An, L.; Anderlini, L.; Andreianov, A.; Andreotti, M.; Archilli, F.; Artamonov, A.; Artuso, M.; Arzymatov, K.; Aslanides, E.; Atzeni, M.; Audurier, B.; Bachmann, S.; Bachmayer, M.; Back, J. J.; Baladron Rodriguez, P.; Balagura, V.; Baldini, W.; Baptista Leite, J.; Barbetti, M.; Barlow, R. J.; Barsuk, S.; Barter, W.; Bartolini, M.; Baryshnikov, F.; Basels, J. M.; Bashir, S.; Bassi, G.; Batsukh, B.; Battig, A.; Bay, A.; Beck, A.; Becker, M.; Bedeschi, F.; Bediaga, I.; Beiter, A.; Belavin, V.; Belin, S.; Bellee, V.; Belous, K.; Belov, I.; Belyaev, I.; Bencivenni, G.; Ben-Haim, E.; Berezhnoy, A.; Bernet, R.; Berninghoff, D.; Bernstein, H. C.; Bertella, C.; Bertolin, A.; Betancourt, C.; Betti, F.; Bezshyiko, I.; Bhasin, S.; Bhom, J.; Bian, L.; Bieker, M. S.; Bifani, S.; Billoir, P.; Birch, M.; Bishop, F. C. R.; Bitadze, A.; Bizzeti, A.; Bjorn, M.; Blago, M. P.; Blake, T.; Blanc, F.; Blusk, S.; Bobulska, D.; Boelhauve, J. A.; Boente Garcia, O.; Boettcher, T.; Boldyrev, A.; Bondar, A.; Bondar, N.; Borghi, S.; Borisyak, M.; Borsato, M.; Borsuk, J. T.; Bouchiba, S. A.; Bowcock, T. J. V.; Boyer, A.; Bozzi, C.; Bradley, M. J.; Braun, S.; Brea Rodriguez, A.; Brodski, M.; Brodzicka, J.; Brossa Gonzalo, A.; Brundu, D.; Buonaura, A.; Buonincontri, L.; Burke, A. T.; Burr, C.; Bursche, A.; Butkevich, A.; Butter, J. S.; Buytaert, J.; Byczynski, W.; Cadeddu, S.; Cai, H.; Calabrese, R.; Calefice, L.; Calero Diaz, L.; Cali, S.; Calladine, R.; Calvi, M.; Calvo Gomez, M.; Camargo Magalhaes, P.; Campana, P.; Campoverde Quezada, A. F.; Capelli, S.; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carli, I.; Carniti, P.; Carus, L.; Carvalho Akiba, K.; Casais Vidal, A.; Casse, G.; Cattaneo, M.; Cavallero, G.; Celani, S.; Cerasoli, J.; Cervenkov, D.; Chadwick, A. J.; Chapman, M. G.; Charles, M.; Charpentier, P.; Chatzikonstantinidis, G.; Chavez Barajas, C. A.; Chefdeville, M.; Chen, C.; Chen, S.; Chernov, A.; Chobanova, V.; Cholak, S.; Chrzaszcz, M.; Chubykin, A.; Chulikov, V.; Ciambrone, P.; Cicala, M. F.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Cobbledick, J. L.; Coco, V.; Coelho, J. A. B.; Cogan, J.; Cogneras, E.; Cojocariu, L.; Collins, P.; Colombo, T.; Congedo, L.; Contu, A.; Cooke, N.; Coombs, G.; Corredoira, I.; Corti, G.; Costa Sobral, C. M.; Couturier, B.; Craik, D. C.; Crkovska, J.; Cruz Torres, M.; Currie, R.; Da Silva, C. L.; Dadabaev, S.; Dai, L.; Dall'Occo, E.; Dalseno, J.; D'Ambrosio, C.; Danilina, A.; D'Argent, P.; Davies, J. E.; Davis, A.; De Aguiar Francisco, O.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Serio, M.; De Simone, D.; De Simone, P.; De Vries, J. A.; Dean, C. T.; Decamp, D.; Dedu, V.; Del Buono, L.; Delaney, B.; Dembinski, H. -P.; Dendek, A.; Denysenko, V.; Derkach, D.; Deschamps, O.; Desse, F.; Dettori, F.; Dey, B.; Di Cicco, A.; Di Nezza, P.; Didenko, S.; Dieste Maronas, L.; Dijkstra, H.; Dobishuk, V.; Dong, C.; Donohoe, A. M.; Dordei, F.; Dos Reis, A. C.; Douglas, L.; Dovbnya, A.; Downes, A. G.; Dudek, M. W.; Dufour, L.; Duk, V.; Durante, P.; Durham, J. M.; Dutta, D.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Ek-In, S.; Eklund, L.; Ely, S.; Ene, A.; Epple, E.; Escher, S.; Eschle, J.; Esen, S.; Evans, T.; Falabella, A.; Fan, J.; Fan, Y.; Fang, B.; Farry, S.; Fazzini, D.; Feo, M.; Fernandez Prieto, A.; Fernez, A. D.; Ferrari, F.; Ferreira Lopes, L.; Ferreira Rodrigues, F.; Ferreres Sole, S.; Ferrillo, M.; Ferro-Luzzi, M.; Filippov, S.; Fini, R. A.; Fiorini, M.; Firlej, M.; Fischer, K. M.; Fitzgerald, D. S.; Fitzpatrick, C.; Fiutowski, T.; Fkiaras, A.; Fleur

Two narrow resonant states are observed in the Λb0K-π+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Λb0K-π+ system indicates that these are excited Ξb0 baryons. The masses of the Ξb(6327)0 and Ξb(6333)0 states are m[Ξb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Ξb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Δm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Λb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Γ[Ξb(6327)0]<2.20(2.56) and Γ[Ξb(6333)0]<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξb0 resonances.

2021 - A first trimester prediction model for large for gestational age infants: a preliminary study [Articolo su rivista]
Monari, F.; Menichini, D.; Spano' Bascio, L.; Grandi, G.; Banchelli, F.; Neri, I.; D'Amico, R.; Facchinetti, F.

Background: Large for gestational age infants (LGA) have increased risk of adverse short-term perinatal outcomes. This study aims to develop a multivariable prediction model for the risk of giving birth to a LGA baby, by using biochemical, biophysical, anamnestic, and clinical maternal characteristics available at first trimester. Methods: Prospective study that included all singleton pregnancies attending the first trimester aneuploidy screening at the Obstetric Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. Results: A total of 503 consecutive women were included in the analysis. The final prediction model for LGA, included multiparity (OR = 2.8, 95% CI: 1.6–4.9, p = 0.001), pre-pregnancy BMI (OR = 1.08, 95% CI: 1.03–1.14, p = 0.002) and PAPP-A MoM (OR = 1.43, 95% CI: 1.08–1.90, p = 0.013). The area under the ROC curve was 70.5%, indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to − 1.378, which corresponds to a 20.1% probability of having a LGA infant. By using such a cut-off, the risk of LGA can be predicted in our sample with sensitivity of 55.2% and specificity of 79.0%. Conclusion: At first trimester, a model including multiparity, pre-pregnancy BMI and PAPP-A satisfactorily predicted the risk of giving birth to a LGA infant. This promising tool, once applied early in pregnancy, would identify women deserving targeted interventions. Trial registration: NCT04838431, 09/04/2021.

2021 - Author Correction: Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection (Nature Communications, (2021), 12, 1, (4677), 10.1038/s41467-021-24940-w) [Articolo su rivista]
De Biasi, S.; Tartaro, D. L.; Gibellini, L.; Paolini, A.; Quong, A.; Petes, C.; Awong, G.; Douglas, S.; Lin, D.; Nieto, J.; Galassi, F. M.; Borella, R.; Fidanza, L.; Mattioli, M.; Leone, C.; Neri, I.; Meschiari, M.; Cicchetti, L.; Iannone, A.; Trenti, T.; Sarti, M.; Girardis, M.; Guaraldi, G.; Mussini, C.; Facchinetti, F.; Cossarizza, A.

The original version of this Article contained an error in Table 1. The correct version of the first row of the 2nd, 3rd, 5th and 7th columns states ‘CTR’, ‘PN’, ‘CTR vs PN’ and ‘PN vs PP’, instead of the original, incorrect ‘HD’, ‘NP’, ‘CTR vs NP’ and ‘CTR vs PP’. This has been corrected in both the PDF and HTML versions of the Article.

2021 - Breastfeeding promotion and support: A quality improvement study [Articolo su rivista]
Menichini, D.; Zambri, F.; Govoni, L.; Ricchi, A.; Infante, R.; Palmieri, E.; Galli, M. C.; Molinazzi, M. T.; Messina, M. P.; Putignano, A.; Banchelli, F.; Colaceci, S.; Neri, I.; Giusti, A.

Background. Breastfeeding success is determined by early skin to skin contact, early initiation of breastfeeding, rooming-in, baby-led breastfeeding, creation of a favorable environment, specific training of health professionals, and continuity of care. Objective. To investigate the women's satisfaction regarding the care and support received in the first days after childbirth. Material and Methods. A questionnaire of 24 items was administered to mothers before discharge, from May to September 2019 at the University Hospital of Modena. Results. The predictive variables of exclusive breastfeeding were the delivery mode, age at birth and parity. The multivariate analysis showed that a high satisfaction score was associated with vaginal birth (OR=2.63, p=0.005), rooming-in during the hospitalization (OR=8.64, p<0.001), the skin to skin contact (OR=6.61, p=0.001) and the first latch-on within 1 hour after birth (OR=3.00, p=0.02). Conclusions. Mothers' satisfaction is one of the important factors of positive experience during hospital stay and of better health outcomes.

2021 - Effect of L-arginine supplementation in pregnant women with chronic hypertension and previous placenta vascular disorders receiving Aspirin prophylaxis: a randomized control trial [Articolo su rivista]
Monari, F.; Menichini, D.; Pignatti, L.; Basile, L.; Facchinetti, F.; Neri, I.

BACKGROUND: The aim of the study is to evaluate the effects of supplementation with Arginine (L-Arg) 3g, (together with Magnesium (Mg) 350 mg and Salicilate (Sal) 100 mg) on maternal blood pressure (BP), uterine artery doppler PI and neonatal outcomes in women with high-risk pregnancy for chronic hypertension (CH) and other previous placenta vascular disorders (PVD) already treated with low dose of aspirin (LDA), as recommended by guidelines. METHODS: We enrolled women affected by CH and other previous PVD referred to the High-Risk Clinic of the Department of Maternal and Child’s Health at the University Hospital of Modena and Reggio Emilia from September 2017 to June 2019. The study design was a controlled, randomized trial of oral supplementation of L-Arg 3g (together with Mg 350 mg and Sal extract 100 mg) + LDA 100 mg/day versus only LDA 100 mg/day. Inclusion criteria were: singleton pregnancy; diagnosis of chronic hypertension, previous preeclampsia <34 weeks, previous intrauterine growth restriction (IUGR) <10th centile or previous stillbirth (SB) related to placenta vascular disorders; gestational age <14 weeks. Each woman was enrolled between 12-14 weeks gestation and underwent 24-hour ambulatory BP monitoring with an automatic device (SpaceLab 92710, Critikon, WA), repeated at 18-20th and 24-26th weeks. Moreover Uterine artery Doppler ultrasound evaluation including PI were performed at 18-20 weeks gestation and repeated at 24-26th weeks. Pregnancy outcomes data were collected in a password protected database. RESULTS: Seventy-nine women agreed to participate in the study. No significant differences between the demographic characteristics in the two groups were found at enrolment (Group LDA + L-Arg: 30 patients versus Group LDA: 49 patients). In the LDA-L-Arg group there is no significant increase in both systolic (127.22±12.02 and 132.75±7.51 mmHg, P=0.002) and diastolic (75.85±8.53 and 83.63±6.05 mmHg, P=0.0000) BP values at 24-26 weeks reveled in the LDA group. The value of the uterine artery Doppler median PI>95th centile at 24-26 weeks show a significant reduction in the LDA+L-Arg group respect the LDA group (seven women, 23.3% vs. 21 women, 42.9%; P=0.04). A significantly lower percentage of women received new antihypertensive drugs in the LDA+ L-Arg group than the LDA group (6.7% vs. 24.5%) (P=0.02). There was neither statistically significant difference in perinatal outcomes between the two groups, except for trend of significance. CONCLUSIONS: Although we found only trends of improvements of perinatal outcomes in LDA+L-Arg group, considering the promising results on BP values, uterine artery PI and the low need to start a new antihypertensive treatment, thus the resulting impact in reducing pregnancy medicalization, number of maternal-fetal well-being monitoring visits and the need of induction of labor, we believe that further studies should be performed to enlarge our observation and clarify the role of L-Arg 3g supplementation as a protective integration in high-risk pregnancies already in prophylaxis with LDA.

2021 - Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection [Articolo su rivista]
De Biasi, S.; Tartaro, D. L.; Gibellini, L.; Paolini, A.; Quong, A.; Petes, C.; Awong, G.; Douglas, S.; Lin, D.; Nieto, J.; Galassi, F. M.; Borella, R.; Fidanza, L.; Mattioli, M.; Leone, C.; Neri, I.; Meschiari, M.; Cicchetti, L.; Iannone, A.; Trenti, T.; Sarti, M.; Girardis, M.; Guaraldi, G.; Mussini, C.; Facchinetti, F.; Cossarizza, A.

SARS-CoV-2 infection can affect all human beings, including pregnant women. Thus, understanding the immunological changes induced by the virus during pregnancy is nowadays of pivotal importance. Here, using peripheral blood from 14 pregnant women with asymptomatic or mild SARS-CoV-2 infection, we investigate cell proliferation and cytokine production, measure plasma levels of 62 cytokines, and perform a 38-parameter mass cytometry analysis. Our results show an increase in low density neutrophils but no lymphopenia or gross alterations of white blood cells, which display normal levels of differentiation, activation or exhaustion markers and show well preserved functionality. Meanwhile, the plasma levels of anti-inflammatory cytokines such as interleukin (IL)-1RA, IL-10 and IL-19 are increased, those of IL-17, PD-L1 and D-dimer are decreased, but IL-6 and other inflammatory molecules remain unchanged. Our profiling of antiviral immune responses may thus help develop therapeutic strategies to avoid virus-induced damages during pregnancy.

2021 - Estimation of fetal weight near term: comparison between ultrasound and symphysis-fundus evaluation by Johnson’s rule [Articolo su rivista]
Ricchi, A.; Pignatti, L.; Bufalo, E.; De Salvatore, C.; Banchelli, F.; Neri, I.

Introduction: The fetal weight estimation is commonly performed by ultrasound but the manual method is also applied in developing countries due to the lack of scan availability and in western countries for the management of low-risk pregnancy managed autonomously by the midwives. The most applied method to estimate fetal weight measures the longitudinal diameter of the symphysis-fundus according to Johnson’s rule. The aim of the present study is to evaluate the reliability of the symphysis-fundus method with respect to the ultrasound to estimate fetal weight in low risk pregnancies according to the classification of adequate, small and large for gestational age. Materials and methods: Two hundred twenty low-risk women referred to the clinic for the management of term pregnancy were enrolled for the study. The following data were collected: age, body mass index, parity, values of symphysis-fundus evaluation according to Johnson’s rule, ultrasound fetal weight estimation values, and birthweight. Results: Considering the whole sample, fetal weight was estimated similarly by the manual method and with the ultrasound (79.5 versus 85% of the cases; n.s.). However, in overweight women, the ultrasound better estimates fetal weight in respect to manual method (94.4 versus 80.3% of the cases; p &lt;.02) and similarly in obese women also ultrasound performed better in comparison to manual method (91.8 versus 71.4% of the cases; p &lt;.01). Conclusions: The manual evaluation could be considered a reliable method to assess fetal weight for the management of low-risk pregnancies near term to optimize the resources and also offer a safe nonmedical approach. Further studies should clarify the accuracy of the manual method to estimate fetal weight in overweight and obese women, also considering the great increase of the obesity incidence in the obstetric population.

2021 - Perinatal outcomes in women affected by different types of headache disorders: A prospective cohort study [Articolo su rivista]
Neri, I.; Menichini, D.; Monari, F.; Bascio, L. S.; Banchelli, F.; Facchinetti, F.

Objective: This study aims to investigate pregnancy and perinatal outcomes in women with tension-type headache, migraine without aura and migraine with aura by comparing them to women without any headache disorders. Study design: Prospective cohort study including singleton pregnancies attending the first trimester aneuploidy screening at the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. Results: A total of 515 consecutive women were included and headache disorders were reported in 43.5% of them (224/515). Tension-type headache was diagnosed in 24.3% of the cases, while 14% suffered from migraine without aura and 5.2% from migraine with aura. Birthweight was significantly lower in women affected by migraine with aura respective to other groups, and a significantly higher rate of small for gestational age infants was found in tension-type headache (10.4%) and in migraine with aura (24.9%) groups respective to the others (p &lt; 0.001). Moreover, the admission to the neonatal intensive care unit was significantly higher in all the headache groups (p = 0.012). Multivariate analysis showed that women presenting tension-type headache (OR 4.19, p = 0.004), migraine with aura (OR 5.37, p = 0.02), a uterine artery pulsatility index &gt;90th centile (OR 3.66, p = 0.01), low multiple of the median (MoM) of Pregnancy-associated plasma protein-A (PAPP-A) (OR 0.48, p = 0.05) and high MoM of Inhibin-A (OR 3.24, p = 0.03) at first trimester, are independently associated with the delivery of small for gestational age infants when compared to women without headache disorders. Conclusion: Migraine with aura and tension type headache expose women to an increased risk of delivering small for gestational age infants, in association with some utero-placenta markers evaluated at first trimester. These women with headache disorders have an additional indication to undergo first trimester aneuploidy screening and would possibly benefit from specific interventions.

2021 - Prevalence of low antithrombin levels in preeclamptic women and perinatal outcome [Articolo su rivista]
Neri, I.; Pignatti, L.; Furia, G.; Facchinetti, F.

Objective. The aim of this study is to evaluate the prevalence of low antithrombin levels in our population in order to assess an intervention trial feasibility. Methods. This is a retrospective study. A database was created by using queries to find out medical records of patients requiring hospitalization for preeclampsia or gestational hypertension or superimposed preeclampsia to chronic hypertension at Modena University Hospital between June 2015 and July 2019. Results. We screened 11845 deliveries. Overall, 221 (1.9%) cases of preeclampsia were identified. Antithrombin level was available for 201 women, thus included in the analysis. Median antithrombin value was 87% (IQ range: 77-98). The prevalence of low antithrombin levels was 9%. Antithrombin &lt; 80% was found in 21% of the subjects. The remnant showed normal values. Median antithrombin was significantly lower in severe respect with mild preeclampsia (83% ± 14 vs 89% ± 14, p = 0.003). The rate of small for gestational age was significantly higher in low antithrombin levels group (44.4% vs 22.4%, p = 0.042). Considering mean values, antithrombin levels were also significantly lower in case of small for gestational age (84% ± 14 vs 89% ± 14; p = 0.040). Conclusions. In our population, low antithrombin levels (1 in 10 patients) were associated with severity of preeclampsia, namely with small for gestational age babies. Data suggest this subpopulation as a better target for trials assessing the efficacy of antithrombin supplementation.

2021 - The appropriate counseling on prenatal screening test for foreign women in Emilia-Romagna [Articolo su rivista]
Menichini, Daniela; Sciutti, Giovanna; Miano, Maria Vittoria; Ricchi, Alba; Infante, Ramona; Molinazzi, Maria Teresa; Bertucci, Emma; Facchinetti, Fabio; Neri, Isabella

Objective: The increase in the migratory phenomenon entails the need to adapt obstetric care to the population which includes foreign pregnant women. In this context, it emerged a little adherence to the prenatal screening test among foreign women compared to Italian women, which is assumed to be attributable to an inadequate counseling. This study aims to evaluate midwife's perception of the&nbsp;&nbsp;counseling effectiveness in foreign women for the combined test and subsequently assess its adequacy through an external evaluation. Methods: this is a cross-sectional study conducted from September to November 2019. An ad hoc questionnaire was administered to midwives working in the territorial district of the Emilia-Romagna Region, investigating their counseling skills. Then an external evaluation of the counseling was conducted by observing the interview between the midwives and the patients (N = 10), to analyze its appropriateness. Results: Seventy-five midwives completed the questionnaire with a positive response rate of 57.2%. In general, 69.3% of midwives are satisfied with the training received from the regional course, but 85% found many difficulties in counseling foreign women. The 14% of midwives state that they always have the cultural and linguistic mediator available and 44% of them state that they use brochures translated into several foreign languages. In the interviews observed, the counseling to foreign women was found to be shorter and more limited than that provided to Italian women. Conclusions: Most of the consulting midwives declare that they feel prepared to perform a correct prenatal counseling also for foreign women, but the external evaluation of the interviews, and the regional data on adherence to the antenatal screening of foreign women, show many critical points. It becomes necessary to carry out further studies that investigate not only the counseling skills of midwives, but also the needs of assisted women about prenatal diagnosis.

2021 - Treatment of menopausal symptoms: concomitant modification of cortisol [Articolo su rivista]
Cagnacci, A.; Xholli, A.; Fontanesi, F.; Neri, I.; Facchinetti, F.; Palma, F.

OBJECTIVES: To evaluate whether change in menopausal symptoms is related to modification of 24-hour urinary cortisol. METHODS: Sixty-nine postmenopausal women were treated for their menopausal symptoms with either estrogen progestin therapy (0.3 mg conjugate equine estrogens and 1.5 mg medroxyprogesterone acetate; n = 25), phytoestrogens (75 mg isoflavones, twice daily; n = 21) or acupuncture (once a week; n = 23). Baseline and treatment-induced changes of total and subscale scores (vasomotor, depression, anxiety, somatization, sexuality) of the Greene's Climacteric Scale and of 24-hour urinary cortisol were evaluated. RESULTS: At baseline, 24-hour urinary cortisol was related to Greene's Climacteric Scale score (P &lt; 0.0001). Independent determinants (R2 = 0.319) were the Greene's subscales scores of depression (with a mean difference of 24-h cortisol for score unit expressed as beta coefficient of regression (b) of 4.91, 95% CI 2.14-7.7; P = 0.0007), and of somatization (b 3.04 95% CI 0.69-5.4; P = 0.012). The Greene's Climacteric Scale score (-5.67 ± 6.8; P = 0.0001) and 24-hour cortisol (-23.6 ± 45.7 μg/24 h; P = 0.0001) declined after 3 months of treatment. Changes of 24-hour cortisol values were linearly related to changes of total Greene's Climacteric Scale score with a mean change for unit score (b) of 2.10, 95% CI 0.47-3.73; P = 0.012). CONCLUSIONS: Present data indicate that greater reduction in menopausal symptoms is associated with a larger decrease in cortisol levels. Possible implication of this finding on the long-term consequences for women's health needs to be explored.

2021 - Vertebral artery dissection in term pregnancy after cervical spine manipulation: a case report and review the literature [Articolo su rivista]
Monari, F.; Busani, S.; Imbrogno, M. G.; Neri, I.; Girardis, M.; Ghirardini, A.; Cavalleri, F.; Facchinetti, F.

Background: Vertebral artery dissection is an uncommon, but potentially fatal, vascular event. This case aimed to describe the pathogenesis and clinical presentation of vertebral artery dissection in a term pregnant patient. Moreover, we focused on the differential diagnosis, reviewing the available evidence. Case presentation: A 39-year-old Caucasian woman presented at 38&nbsp;+&nbsp;4&nbsp;weeks of gestation with a short-term history of vertigo, nausea, and vomiting. Symptoms appeared a few days after cervical spine manipulation by an osteopathic specialist. Urgent magnetic resonance imaging of the head was obtained and revealed an ischemic lesion of the right posterolateral portion of the brain bulb. A subsequent computed tomography angiographic scan of the head and neck showed a right vertebral artery dissection. Based on the correlation of the neurological manifestations and imaging findings, a diagnosis of vertebral artery dissection was established. The patient started low-dose acetylsalicylic acid and prophylactic enoxaparin following an urgent cesarean section. Conclusion: Vertebral artery dissection is a rare but potential cause of neurologic impairments in pregnancy and during the postpartum period. It should be considered in the differential diagnosis for women who present with headache and/or vertigo. Women with a history of migraines, hypertension, or autoimmune disorders in pregnancy are at higher risk, as well as following cervical spine manipulations. Prompt diagnosis and management of vertebral artery dissection are essential to ensure favorable outcomes.

2021 - advanced midwifery practice: intrapartum ultrasonography to assess fetal head station and comparison with vaginal digital examination [Articolo su rivista]
Messina, M. P.; Piccioni, M. G.; Petrella, C.; Vitali, M.; Greco, A.; Ralli, M.; Ceccanti, M.; Ferraguti, G.; Neri, I.; Ricchi, A.; Fiore, M.; D'Angelo, A.

bacKGrOUNd: Vaginal digital examination is considered the gold standard to evaluate patients during labor and delivery. However, transperineal ultrasound has been suggested as an effective tool in determining fetal head station during labor. angle of progression (aOP), head-perineal distance (HPd) and head-symphysis distance (Hsd) are reliable parameters to assess fetal head station during labor. the study aims were to evaluate how midwives can use aOP, Hsd, HPd to assess the accuracy of digital vaginal exploration limited to the fetal head station. METHODS: Trained midwives for ultrasound analyses performed transperineal ultrasounds during the first stage of labor with 2d-convex probe in 62 pregnant women at term with a single fetus in cephalic presentation. immediately before the intrapartum ultrasound, the birth attendant performed a digital examination to assess cervical dilatation and head station. the ultrasound scans were compared to the digital vaginal examination through the tutschek’s formula. resUlts: aOP was wider in women who delivered vaginally without any complication if compared to “complicated delivery” group. HPd and Hsd were greater in women who underwent an operative vaginal delivery or caesarean section. the vaginal exploration accuracy was 34%, but when ±1 cm was considered as tolerated, the overall accuracy was 74.19%. cONclUsiONs: Midwives may include ultrasounds in their clinical practice after adequate training or under the supervision of an ultrasound professional as an adjunct tool during labor to evaluate its progress and prevent any deviation from physiology.

2020 - Blood pressure and cardiovascular risk factors in women treated for climacteric symptoms with acupuncture, phytoestrogens, or hormones [Articolo su rivista]
Palma, F.; Fontanesi, F.; Neri, I.; Xholli, A.; Facchinetti, F.; Cagnacci, A.

Objective: To evaluate the response of cardiovascular risk factors to the treatment of climacteric symptoms. Methods: In this prospective study, women reporting climacteric symptoms were randomized to 3 months of treatment with either acupuncture (n ¼ 19), phytoestrogens (75 mg soy isoflavones, BID; n ¼ 22), or low-dose hormone therapy (HT; 0.3 mg conjugated equine oestrogens plus 1.5 mg medroxyprogesterone acetate; n ¼ 20). Greene’s climacteric scale, blood pressure (BP), lipids, glucose, insulin, and homeostatic model assessment of insulin resistance were assessed before and after treatment. Observed changes were compared by analysis of variance. Results: HT and acupuncture reduced Greene climacteric score to a similar extent, but the effect of phytoestrogens was significantly lower (P &lt; 0.05). With acupuncture, systolic (-7.4 ± 15.3 mm Hg; P &lt; 0.05) and diastolic BP (-8.3 ± 7.7mm Hg; P &lt; 0.01) decreased, and the same occurred with phytoestrogens (-8.4 ± 9.0 mm Hg [P &lt; 0.01] and -6.6 ± 7.9 mm Hg [P &lt; 0.01]). Neither BP systolic (1.9 ± 17.5 mm Hg) nor BP diastolic (-1.4 ± 9.6 mm Hg) changed during HT. Low-density lipoprotein cholesterol decreased with phytoestrogens (-9.9 ± 19.6 mg/ dL; P &lt; 0.05), and triglycerides increased with both HT (34.5 ± 12.2 mg/dL; P &lt; 0.01) and phytoestrogens (17.41 ± 24.4 mg/dL; P &lt; 0.01). A slight but significant increase in homeostatic model assessment of insulin resistance (0.14 ± 0.5; P &lt; 0.05) was observed after HT. Conclusions: Treatment of climacteric symptoms with acupuncture and phytoestrogens, but not HT, is associated with a clear BP reduction, and phytoestrogens with potentially positive alterations in low-density lipoprotein cholesterol level.

2020 - Evaluation of midwifery students’ satisfaction with regards to clinical internship [Articolo su rivista]
Gemmellaro, G.; Ricchi, A.; Menichini, D.; Molinazzi, M. T.; Banchelli, F.; Infante, R.; Artioli, G.; Foa, C.; Neri, I.

Background and aim of the work. The clinical internship is fundamental for the training of the fu ture socio-health professional. Through the practical activity, the student develops professional skills, critical thinking and decision-making ability, internalizing the complexity of the professional role. While in the nursing field there are several tools for assessing the clinical experience of students, in the obstetric field there is a lack of validated tools. Therefore, the purpose of this work was to investigate the perception of the students of the Degree Course in Midwifery regarding the internship experience. Method. The study was conducted at the obstetric clinical internship where students carry out practical activities and involved all the students of the Degree Course in Midwifery at the University of Modena and Reggio Emilia. The data were collected through an anonymous online questionnaire (Google Model), which was inspired by the nursing CLES + T, simplified and adapted to the obstetric field. Results. In total, 54 students took part in the research (81.8% of all students enrolled in the degree program examined). They were mainly of Italian nationality (98.1%), women (94.4%), aged between 18-22 years (85.2%). In general, the third-year students were more satisfied with the internship experience than the second-and first-year students, most likely for having achieved a degree of autonomy of care, awareness and greater professional motivation. Conclusions. The results indicate the need to periodically investigate the quality and satisfaction of the clinical internships to ensure increasingly effective obstetric training. (

2020 - Fetal alcohol spectrum disorders awareness in health professionals: Implications for psychiatry [Articolo su rivista]
Messina, M. P.; D'Angelo, A.; Battagliese, G.; Coriale, G.; Tarani, L.; Pichini, S.; Rasio, D.; Parlapiano, G.; Fiore, M.; Petrella, C.; Vitali, M.; Ferraguti, G.; Ceccanti, M.; Bertoli, D.; Canepa, M.; Cappadona, R.; D'Alessio, A.; Danza, M.; Morese, A.; Paolino, A.; Pileri, F.; Pinna, N.; Neri, I.; Razzano, R.; Ricchi, A.; Rizzi, M.

Fetal Alcohol Spectrum Disorders (FASD) are a plethora of malformative conditions leading to mental retardation that affect newborns and children who have been exposed to alcohol during pregnancy or breastfeeding. FASD is a relevant topic for public health in Europe: European area is first in ranking for alcohol use during pregnancy with a prevalence of 25.2%. Italy ranked third among European countries with higher prevalence of FASD (45.0 per 1000 population). Furthermore, FASD could still be underestimated because of numerous undiagnosed and misdiagnosed cases. Aims of the study were to briefly summarize existing evidences about FASD and its psychiatric aspects to assess knowledge, attitudes and practice towards alcohol drinking during pregnancy in an Italian sample of health care professionals in order to provide information about FASD prevention. An anonymous online questionnaire containing the AUDIT-C, T-ACE model and the Drinking Motive Questionnaire was sent to 400 Italian healthcare professionals and students. The survey included socio-demographic information, questions about drinking habits and about knowledge, attitude and practice towards alcohol assumption during pregnancy. Among 320 respondents, 96.3% were women. AUDIT-C revealed that 52.4% were low risk drinkers but 27.6% were hazardous drinkers. The 90.6% of participants denied to ever attended a course about the fetus damage induced by alcohol consumption during pregnancy but 91.3% were willing to participate to professional update initiatives on the topic. Only 19.1% of participants talk regularly about the deleterious effects for the fetus of prenatal alcohol drinking to women and only 51.1% advise the 'zero alcohol' policy. Around 41% of participants tolerates the assumption of low-alcohol beverages. No differences were found between no drinkers and low and hazardous drinkers. In conclusion, data show that only specific and continuing updating for health care professionals about drinking habits may have impactful actions to prevent gestational alcohol intake in order to prevent the main cause of mental retardation in western countries.

2020 - Physical activity in low risk pregnant women: a cross-sectional study [Articolo su rivista]
Menichini, D.; Fanetti, O.; Molinazzi, M. T.; Facchinetti, F.; Ricchi, A.; Neri, I.

OBJECTIVES: The aim of this study is to analyze the quality and quantity of physical activity (PA) practiced by low-risk pregnant women before and during pregnancy. DESIGN: This cross-sectional study assesses the dietary habits, exercise habits and body mass index. We used an ad hoc health lifestyle multiple choice questionnaire. The data collection lasted 7 months, from the beginning of September 2018 to the end of March 2019. POPULATION: We recruited 175 Italian women with a singleton, low-risk pregnancy at 32-36 weeks of gestational age. RESULTS: In the periconceptional period, 52.6 % of women do not perform any PA. For the other 47.4% of women, the most practiced activities, both before and during gestation, are walking and swimming. Data on the sedentariness showed that about a quarter of the population remains inactive watching TV for more than two hours a day. Interestingly, the most statistically significant risk factor for sedentariness is the BMI &gt; 25 kg/m². Therefore, overweight or obese women are more likely to maintain a sedentary lifestyle during pregnancy. CONCLUSIONS AND IMPLICATION FOR THE PRACTICE: Our study highlighted a high rate of sedentariness in pregnancy, especially among overweight and obese women. Thus, it is important to undertake interventions aimed at informing pregnant women of various benefits that PA can bring. In particular, because of the significant association between sedentariness and BMI greater than 25 kg/m2, it results crucial to direct these recommendations particularly to overweight/obese pregnant women, addressing them to a healthy lifestyle.

2020 - Self-efficacy in breastfeeding support: A research on italian midwifery students [Articolo su rivista]
Prepelita, T; Ricchi, A; Messina, P; Molinazzi, Mt; Cappadona, R; Fieschi, L; Nespoli, A; Guana, M; Cervi, G; Parma, D; Mauri, Pa; Artioli, G; Banchelli, F; Foa, C; Neri, I.

2020 - Study of childbirth education classes and evaluation of their effectiveness [Articolo su rivista]
Ricchi, A.; La Corte, S.; Molinazzi, M. T.; Messina, M. P.; Banchelli, F.; Neri, I.

BACKGROUND: Childbirth education classes are antenatal support services offered to pregnant women or to the couple, aimed at increasing their knowledge regarding pregnancy, labour, delivery, breastfeeding, parenthood and newborn care. OBJECTIVE: The aim was to evaluate the effectiveness of Birthing Classes through the analysis of the occurrence of C-section, epidural analgesia, behavior during labor and delivery of the women who participated to the course as compared to those who did not attend it. Moreover, the level of satisfaction of pregnant women who attended the course was measured with a questionnaire of 20 items handed out after the delivery. METHODS: To measure the satisfaction level of pregnant women, in the period from February 2017 to October 2017, a questionnaire of 20 items was used. In order to analyze the results of the births the medical records were consulted. RESULTS: In the period of time going from February 2017 to October 2017 there were 147 women who have delivered and who have filled in the questionnaire. According to the multivariable analysis, there were no differences in the frequency of C-sections between the two groups (OR=0.8, 95%CI=0.3-1.7, p=0.503), whereas the frequency of epidural analgesia was lower in women who attended the Birthing Class (OR=0.3, 95%CI=0.1-0.9, p=0.036). We also observed that women who attended the Birthing Class: 1) had a higher likelihood of using breathing techniques during the labor (OR=5.5, 95%CI=1.5-20.0, p=0.009); 2) had a higher likelihood of taking advantage of the visualization exercises during the labor (OR=2.5, 95%CI=1.1-6.0, p=0.039). There was no other relevant difference between the two groups. DISCUSSION: The benefits of perinatal education are difficult to evaluate systematically, and further research would be required to determine real effects and agree upon reliable indicators of effectiveness. CONCLUSIONS: This study identified several positive factors that confirm the results of other studies indicating that antenatal classes are effective for women giving birth for the first time/nulliparous women, based on an analysis of childbirth outcomes, in order to improve maternal and neonatal health.

2020 - The impact of an early lifestyle intervention on pregnancy outcomes in a cohort of insulin-resistant overweight and obese women [Articolo su rivista]
Menichini, D.; Petrella, E.; Dipace, V.; Di Monte, A.; Neri, I.; Facchinetti, F.

Obese women are more likely to have decreased insulin sensitivity and are at increased risk for many adverse pregnancy outcomes. An early lifestyle intervention (LI) may have the potential to reduce the impact of insulin resistance (IR) on perinatal outcomes. We report post hoc analysis of an open-label randomized control trial that includes IR women with body-mass index ≥25 randomly assigned to a LI with a customized low glycemic index diet or to standard care (SC) involving generic counseling about healthy diet and physical activity. Women were evaluated at 16, 20, 28, and 36 weeks of gestation, at which times perinatal outcomes were collected and analyzed. An oral-glucose-tolerance test (OGTT) showed that women in the LI group had lower plasma glucose levels at 120 min at 16–18 weeks of gestation, and at 60 and 120 min at 24–28 weeks. More importantly, these women had a lower rate of large-for-gestational-age (LGA) infants (p = 0.04). Interestingly, the caloric restriction and low-glycemic index diet did not increase the rate of small-for-gestational-age (SGA) babies in the LI group. A lifestyle intervention started early in pregnancy on overweight and obese women had the potential to restore adequate glucose tolerance and mitigate the detrimental role of IR on neonatal outcomes, especially on fetal growth.

2019 - Breastfeeding pathologies: Analysis of prevalence, risk and protective factors [Articolo su rivista]
Govoni, L.; Ricchi, A.; Molinazzi, M. T.; Galli, M. C.; Putignano, A.; Artioli, G.; Foa, C.; Palmieri, E.; Neri, I.

Background and aim of the study: Breastfeeding is essential for the health of mothers and newborns, and it is recommended by WHO-UNICEF as the sole source of nutrition and protection for the first 6 months of life and beyond. In order to fully promote this practice, it is important to recognize early conditions that can lead to pathological breastfeeding. Aim: The study aims to analyze the prevalence and the possible risk or protective factors concerning the pathology of breastfeeding. Methods: For this observational study were consulted the medical records and the files of the Breastfeeding clinic of 1065 puerperal women, of the University Hospital of Modena, from January to August 2016. The data were processed with the SPSS Software. Results: In our study population, 532 (50%) puerperal women presented a breastfeeding-related disease, of which 330 (31%) had a disease affecting the mother (breast engorgement, fissures, a-/hypo-galactia, discontinuation of breastfeeding, galactocele, mastitis and candidiasis), 105 (9.9%) of the newborn (inadequate suction, neonatal jaundice, pathological weight loss, need for admission to NICU) and 97 (9.1%) of both the mother and the newborn. Discussions: It is evident from the results that the predicting factors of pathology in breastfeeding are present in pregnant women who give birth in an early gestational age and with high age, birth rate and nationality. Conclusions: Staff training courses are essential to respond to WHO-UNICEF recommendations and to improve the continuity of care for the mother-child dyad.

2019 - Food glycemic index changes in overweight/obese pregnant women enrolled in a lifestyle program: a randomized controlled trial [Articolo su rivista]
Facchinetti, F.; Vijai, V.; Petrella, E.; Gambigliani Zoccoli, S.; Pignatti, L.; Di Cerbo, L.; Neri, I.

BACKGROUND: The calculation of the glycemic index of food mirrors a rise in blood sugar levels. A low-glycemic index carbohydrate diet in pregnancy has been associated with normal infant birthweight. Thus, strategies to lower the food glycemic index could be successful in improving pregnancy outcomes. OBJECTIVE: The purpose of this study was to compare different prescribed diets on food glycemic index intake and its relationship with rate of large-for-gestational-age infants. STUDY DESIGN: At the 9th-12th week of gestation (with a gynecologist and a dietitian both present), 273 Italian women with a body mass index of ≥25 kg/m2 were assigned randomly either to a customized low-glycemic index diet that was detailed by a dietitian (customized intervention; n=139 women; 1800 kcal/d+30 minutes walking 4 times/wk) or to generic lifestyle advice (standard care; n=134 women) with counseling about a prudent diet and physical activity, according to Italian guidelines. At enrollment and at the 36th week of gestation, the food frequency questionnaire was completed. In 73 Italian foods, the glycemic index was assessed with the use of a classic formula (available carbohydrate×glycemic index prescribed/total carb content of the meal) then was subdivided according to meal pattern. The main outcome was the change in food- glycemic index. RESULTS: Sociodemographic features were similar between the groups. One hundred fifty-six women completed the study (customized intervention=81; standard care=75). The mean daily glycemic index decreased from 58.4±19 to 52.5±11.2 (P=.008) in the customized intervention group although it remained unchanged in the standard care group. After the intervention, women in the customized intervention group reported a significant decrease in the diet glycemic index at dinner compared with both lunch and breakfast values (P&lt;.02). Lower birthweight and fewer large-for-gestational-age infants were observed in the customized intervention group. CONCLUSION: A customized low-glycemic index, calorie-restricted diet that was associated with constant physical activity effectively reduced the food glycemic index. This reduced food glycemic index is associated with lower rate of large-for-gestational-age newborn infants.

2019 - Midwives autonomy in discharge women after physiological childbirth [Articolo su rivista]
Ricchi, A.; Covezzi, I. P.; Di Biase, L.; Saccani, G.; Galli, C.; Molinazzi, M. T.; Putignano, A.; Neri, I.

BACKGROUND: International literature identifies the midwife as the professional figure deals with women and newborns in the context of childbirth; it is however found to be still difficult to ensure this continuity of care. In Italy both the national laws and the indications of Emilia Romagna region promote this practice, ensuring the midwives management of the low risk women immediately after childbirth. The aim of the study is to investigate and describe the midwives autonomy as regards the post-partum discharge. METHODS: The computerised medical records were consulted to identify the mothers after childbirth who can be discharged independently by the obstetrician following the guidelines of the Emilia-Romagna region. RESULT S: A retrospective analysis of 1371 medical records related to the period January-June 2017 showed that 41% of discharges were managed handled by the midwives, while the remaining 59% by obstetricians. Fifty-seven percent of the women followed by the family counselling service were discharged by the obstetricians and 43% independently by the midwives. Considering the women followed by a private physician 62% were discharged by the obstetricians and 38% by the midwives. CONCLUSIONS: The study shows that, in a short time from the beginning of the project, the results as regards midwives autonomy were excellent. Indeed the midwives discharges does not differed significantly from the medical ones, and care continuity between the hospital and territory is strengthened. Further studies must include questionnaires concerning satisfaction of the mother not administered in this sample of women.

2019 - Relapse of atypical hemolytic uremic syndrome during pregnancy in a patient on eculizumab maintenance treatment: A case report [Articolo su rivista]
Fontana, F.; Alfano, G.; Bardhushi, E.; Ligabue, G.; Giovanella, S.; Neri, I.; Cappelli, G.

Objective: Rare disease Background: Atypical hemolytic uremic syndrome (aHUS) is a genetic disorder with uncontrolled complement activation leading to systemic thrombotic microangiopathy; kidneys are almost invariably involved. Eculizumab has dramatically improved the prognosis of aHUS and affected women in the childbearing age are more likely to consider pregnancy, even if this could represent a risk for disease reactivation. Pregnancies in women with aHUS during Eculizumab treatment have been reported, with no cases of aHUS relapse. Case Report: We report the case of a female patient affected by aHUS with no specific gene mutations who had a pregnancyassociated aHUS relapse at 26-weeks of gestation during maintenance Eculizumab treatment. The patient developed stage II acute kidney injury and microangiopathic hemolytic anemia. Delivery by cesarean section at week 27, plasma exchange sessions and several supplemental Eculizumab administrations were required. After appropriate treatment, the patient partially recovered kidney function; the baby had a prolonged stay in the intensive care unit and showed no signs of neurologic damage. Conclusions: Previous reports indicated that pregnancy-related aHUS relapses were unlikely in women undergoing Eculizumab treatment. Based on our case, we suggest caution in counselling pregnancy in women with aHUS treated with Eculizumab, especially in the absence of pathogenic mutations in complement-regulating genes. Clinicians should be aware of possible aHUS relapse in pregnancy during Eculizumab treatment.

2019 - The midwifery-led care model: A continuity of care model in the birth path [Articolo su rivista]
Ricchi, A.; Rossi, F.; Borgognoni, P.; Bassi, M. C.; Artioli, G.; Foa, C.; Neri, I.

Background and aim of the study: The birth path is affected by a fragmentation in the patient care process creating a discontinuity of this last one. The pregnant woman has to interface with many professionals both during the pregnancy the childbirth and the puerperium. However during the last ten years there has been an increasing of the pregnancy care operated by the midwife who is considered to be the operator with the right competences who can take care of every pregnancy and may avail herself of other professionals’ contributions in order to improve the outcomes of maternal and neonatal health. Aim: To verify whether there are proofs of effectiveness that support the caseload midwifery care model and if it is possible to apply this model in the birth path in Italy. Methods: A revision of literature has been done using some search engine (Google Bing) and specific databases (MEDLINE CINAHL Embase Home - There has also been a consultation of the Italian regulations the national guidelines and the recommendations of WHO. Results: The search string properly adapted to the three databases has given the following results: MEDLINE 64 articles CINAHL 94 articles Embase 88 articles. From this selection 14 articles have been extracted: 1 systematic review 3 controlled random trial 7 observational studies 3 qualitative studies. Conclusions: The caseload midwifery care seems to be an effective and reliable organisational/caring method. It responds to the criterions of quality and security to the needs of women not only during the pregnancy but also during the post-partum phase. For these reasons it seems very useful also for the birth path in the Italian reality. (

2018 - Acupuncture in Postdate Pregnancy Management [Articolo su rivista]
Neri, Isabella; Pignatti, Lucrezia; Fontanesi, Francesca; Facchinetti, Fabio

Pharmacological labor induction is obtained through prostaglandins application and/or oxytocin infusion; however, the use seems to be related to fetal and maternal side effects. Traditional Chinese Medicine advocates the use of acupuncture to soften the cervix and induce uterine contractions. at which presented for The primary outcome was the rate of women admitted for labour induction in case of prolonged pregnancy at 41&nbsp;+&nbsp;5&nbsp;weeks, and the secondary outcome was the rate of induction planning for other indications.

2018 - An early-customized low glycaemic-index diet prevents adverse pregnancy outcomes in overweight/obese women [Articolo su rivista]
Petrella, Elisabetta; Tamborrino, Valeria; Di Cerbo, Lidia; Neri, Isabella; Facchinetti, Fabio

To determine whether the prescription and follow-up of a behavioral program (customized nutritional advices and a constant physical activity) influences the occurrence of unfavorable maternal/neonatal outcomes among overweight/obese women.

2018 - Castor oil for induction of labour: a retrospective study [Articolo su rivista]
Neri, Isabella; Dante, Giulia; Pignatti, Lucrezia; Salvioli, Chiara; Facchinetti, Fabio

The aim of this study is to investigate the safety and efficacy of castor oil to induce labour.

2018 - Corrigendum to “Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV” [J Hepatol 68 (2018) 33–41](S0168827817322596)(10.1016/j.jhep.2017.08.019) [Articolo su rivista]
Karampatou, Aimilia; Han, Xue; Kondili, Loreta A.; Taliani, Gloria; Ciancio, Alessia; Morisco, Filomena; Critelli, Rosina Maria; Baraldi, Enrica; Bernabucci, Veronica; Troshina, Giulia; Guarino, Maria; Tagliavini, Simonetta; D'Ambrosio, Federica; Bristot, Laura; Turco, Laura; Rosato, Stefano; Vella, Stefano; Trenti, Tommaso; Neri, Isabella; La Marca, Antonio; Manthena, Shivaji; Goldstein, Andrea S.; Bruno, Savino; Bao, Yanjun; Gonzalez, Yuri Sanchez; Villa, Erica

It has come to our attention that the PITER framework investigator, Alessandro Federico, was incorrectly listed as F. Alessandro in the original manuscript. Please note that the correct name of this author is Alessandro Federico (2nd University of Naples). The correct list of PITER investigators is in the footnote below.

2018 - Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV [Articolo su rivista]
Karampatou, Aimilia; Han, Xue; Kondili, Loreta A; Taliani, Gloria; Ciancio, Alessia; Morisco, Filomena; Critelli, Rosina Maria; Baraldi, Enrica; Bernabucci, Veronica; Troshina, Giulia; Guarino, Maria; Tagliavini, Simonetta; D'Ambrosio, Federica; Bristot, Laura; Turco, Laura; Rosato, Stefano; Vella, Stefano; Trenti, Tommaso; Neri, Isabella; LA MARCA, Antonio; Manthena, Shivaji; Goldstein, Andrea S; Bruno, Savino; Bao, Yanjun; Gonzalez, Yuri Sanchez; Villa, Erica; Andreone, Pietro

Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+.

2018 - Survey of students of the degree course in obstetrics, on learning using case based learning (cbl) method in the area of professional teachings [Articolo su rivista]
Ricchi, A.; Martelli, E.; Molinazzi, M. T.; Vaccari, S.; Messina, M. P.; Banchelli, F.; Neri, I.

Background. Case Based Learning (CBL) is a teaching methodology that, starting from a case associated with real life situations, is able to stimulate students to investigate, reflect and discuss to find the solution to the case. Objective. The aim of this study is to investigate the satisfaction and the educational impact on the students of the Obstetrics Degree Course on Learning Case Based Learning CBL (on real clinical cases) Methods. The observational study was carried out through the presentation of real clinical cases to a sample of 43 students of a degree course in Obstetrics and giving them questionnaires of evaluation regarding satisfaction and educational impact, using measurement scales which ranged from 1 (very bad) to 5 (excellent). Results. The higher satisfaction was towards the tutor’s exhibition capacity and the integration between participants, for 2 nd and 3 rd year students, respectively. Likewise, the highest educational impact was associated with the effectiveness of the tutor facilitator. Differences in the degree of satisfaction were observed between the two students cohorts, in particular regarding relevance of the topics, as satisfaction was higher in 2 nd year students (p=0.021), and regarding work times, as satisfaction was higher in 3 rd year students (p=0.042). No significant differences in the educational impact were observed between 2 nd and 3 rd year students. Discussions. Studies were examined to compare the effectiveness of Case Based Learning (CBL) to the use of other teaching methodologies. Conclusion. The results of the study highlight that the knowledge and skills acquired by Case Based Learning were useful and applicable in the workplace.

2017 - Adherence to a lifestyle programme in overweight/obese pregnant women and effect on gestational diabetes mellitus: a randomized controlled trial [Articolo su rivista]
Bruno, Raffaele; Petrella, Elisabetta; Bertarini, Valentina; Pedrielli, Giulia; Neri, Isabella; Facchinetti, Fabio

This study aims to determine whether the prescription of a detailed lifestyle programme in overweight/obese pregnant women influences the occurrence of gestational diabetes (GDM), and if this kind of prescription increases the adherence to a healthier lifestyle in comparison to standard care. The study was designed as a randomized controlled trial, with open allocation, enrolling women at 9-12 weeks of pregnancy with a BMI ≥ 25 kg/m(2) . The women assigned to the Intervention group (I = 96) received a hypocaloric, low-glycaemic, low-saturated fat diet and physical activity recommendations. Those assigned to the Standard Care group (SC = 95) received lifestyle advices regarding healthy nutrition and exercise. Follow-up was planned at the 16(th) , 20(th) , 28(th) and 36(th) weeks. A total of 131 women completed the study (I = 69, SC = 62). The diet adherence was higher in the I (57.9%) than in the SC (38.7%) group. GDM occurred less frequently in the I (18.8%) than in the SC (37.1%, P = 0.019) group. The adherent women from either groups showed a lower GDM rate (12.5% vs. 41.8%, P &lt; 0.001). After correcting for confounders, the GDM rate was explained by allocation into the I group (P = 0.034) and a lower BMI category (P = 0.039). The rates of hypertension, preterm birth, induction of labour, large for gestational age babies and birthweight &gt; 4000 g were significantly lower in I group. The incidence of small for gestational age babies was not different. These findings demonstrate that the adherence to a personalized, hypocaloric, low-glycaemic, low-saturated fat diet started early in pregnancy prevents GDM occurrence, in women with BMI ≥ 25 kg/m(2) .

2017 - Vaginal alpha-lipoic acid shows an anti-inflammatory effect on the cervix, preventing its shortening after primary tocolysis. A pilot, randomized, placebo-controlled study [Articolo su rivista]
Grandi, G.; Pignatti, L.; Ferrari, F.; Dante, G.; Neri, I.; Facchinetti, F.

Introduction: Inflammation might be an important underlying cause of preterm birth. Our aim is to explore whether vaginal administration α-lipoic acid reduces cervical inflammation and shortening after primary tocolysis. Materials and methods: Singleton pregnancies between 24–30 weeks remaining undelivered after hospitalization for preterm labor were randomly allocated to placebo (20 women, 15 analyzed) or vaginal ALA 400 mg (active ingredient 10 mg) daily (20 women, 17 analyzed) for 30 days. A cervical swab to quantify pro-inflammatory (IL1, IL2, IL6, IL8, TNFα) and anti-inflammatory (IL4, IL10) cytokines as well as transvaginal ultrasound cervical length measurement (CL) were performed before and after treatment. Results: The % changes of pro-inflammatory cytokines do not differ between treatment groups, while IL4 significantly increases by vaginal ALA in comparison to placebo (118.0 ± 364.3% versus 29.9 ± 103.5%, p = 0.012). Combined anti-inflammatory cytokines show same trend (292.5 ± 208.5% versus 64.5 ± 107.4, p = 0.03). CL remains similar in vaginal ALA group (from 23.1 ± 6.6 to 20.80 ± 7.9 mm), while it significantly decreased in placebo group (from 20.4 ± 6.5 to 13.8 ± 7.5 mm, p &lt; 0.001 versus Baseline; p = 0.003 versus vaginal ALA). Conclusion: Vaginal ALA significantly stimulates anti-inflammatory ILs in the cervix of undelivered women after a preterm labor episode. This effect is associated with a stabilization of the CL.

2016 - Acupressure on Self-Reported Sleep Quality During Pregnancy [Articolo su rivista]
Neri, Isabella; Bruno, Raffaele; Dante, Giulia; Facchinetti, Fabio

The aim of this study was to investigate the short-term effect of acupression at the H7 point on sleep quality during pregnancy. After oral consent had been obtained, the midwife invited the women claiming to have poor sleep quality and anxiety symptoms to complete the Pittsburgh Sleep Quality Index questionnaire and the State-Trait Anxiety Inventory-1. Then, the same midwife, previously trained by an expert acupuncturist (I.N.), advised the women to put on the wrist overnight compression H7 Insomnia Control half an hour before going to bed and to take it off upon awakening, for 10 consecutive days and thereafter every odd day (active group). Women refusing to wear the device for low compliance toward acupression were considered as the control group. After 2 weeks, a second questionnaire evaluation was completed. In the active, but not in the control, group, a significant improvement of sleep quality was observed after H7 device application. The study suggests that H7 acupression applied for 2 weeks improves sleep quality in pregnant women. This preliminary result should serve to stimulate further studies on the long-term effects of acupression.

2016 - Adverse perinatal outcome in subsequent pregnancy after stillbirth by placental vascular disorders [Articolo su rivista]
Monari, Francesca; Pedrielli, Giulia; Vergani, Patrizia; Pozzi, Elisa; Mecacci, Federico; Serena, Caterina; Neri, Isabella; Facchinetti, Fabio

Objective: To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders. Study Design: A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was "adverse neonatal outcome", including perinatal death, fetal growth restriction, early preterm birth <33+6 weeks, hypoxicischemic encephalopathy, intracranial hemorrhage or respiratory distress. Results: Out of 364 index pregnancies, 320 women (87.9%) had a subsequent pregnancy during the study period. Forty-seven had an early pregnancy loss. Out of 273 babies, 67 (24.5%) had an adverse perinatal outcome, including 1 SB and 1 early neonatal death (3.7/1000). Women who had a SB related to placental vascular disorders (39.6%), were at higher risk of an adverse neonatal outcome compared with women whose SB was unexplained or resulted from other causes (Adj. OR = 2.1, 95%CI: 1.2-3.8). Moreover, also obesity independently predicts an adverse perinatal outcome (Adj OR = 2.1, 95%CI: 1.1-4.3). Conclusion: When previous SB is related to placental vascular disorders there is a high risk for adverse neonatal outcomes in the subsequent pregnancy. Maternal obesity is an additional risk factor.

2016 - Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial [Articolo su rivista]
Santamaria, Angelo; Di Benedetto, Antonino; Petrella, Elisabetta; Pintaudi, Basilio; Corrado, Francesco; D’Anna, Rosario; Neri, Isabella; Facchinetti, Fabio

Objective: To evaluate whether myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) rate in overweight women. Methods: In an open-label, randomized trial, myo-inositol (2 g plus 200 μg folic acid twice a day) or placebo (200 μg folic acid twice a day) was administered from the first trimester to delivery in pregnant overweight non-obese women (pre-pregnancy body mass index ≥ 25 and < 30 kg/m2). The primary outcome was the incidence of GDM. Results: From January 2012 to December 2014, 220 pregnant women were randomized at two Italian University hospitals, 110 to myo-inositol and 110 to placebo. The incidence of GDM was significantly lower in the myo-inositol group compared to the placebo group (11.6% versus 27.4%, respectively, p = 0.004). Myo-inositol treatment was associated with a 67% risk reduction of developing GDM (OR 0.33; 95% CI 0.15–0.70). Conclusions: Myo-inositol supplementation, administered since early pregnancy, reduces GDM incidence in overweight non-obese women.

2016 - Perinatal and maternal outcomes in a midwife-led centre in Italy: a comparison with standard hospital assistance [Articolo su rivista]
Dante, Giulia; Neri, Isabella; Bruno, R; Salvioli, Chiara; Facchinetti, Fabio

Abstract BACKGROUND: In many countries midwives are the primary providers of care for childbearing women. The aim of the present study was to compare the outcomes of childbirth occurring in the birth benter (midwifery-lead) vs. the traditional delivery room organization (doctor-lead) of the Policlinico of Modena Hospital. METHODS: A prospective observational study was conducted over four years. At 35-36th week, women with a single, uneventful pregnancy, being classified at low-risk according to The National Institute for Health and Care Excellence (NICE) guidelines on intrapartum care, were offered to deliver with standard care assistance (SC) in a doctors-led unit or in the Birth Centre (BC). RESULTS: The number of women included was 3156. Overall emergency cesarean sections were lower in BC vs. SC group, and a significant decrease in the rate of augmentation of labor with intravenous oxytocin, in the use of episiotomy and operative deliveries in women of BC were recorded more than in the SC group. More women with intact perineum were present in BC group, while no significant differences in perineal tears was described between groups. CONCLUSIONS: Our results suggest that midwifery care can result in a decrease of medical interventions during labor, namely a reduction of cesarean section and episiotomy rate. Also, the BC remains a valid option for women who satisfy low-risk criteria and wish to give birth in a hospital setting. In Italy the concern to education of all midwives, obstetricians and women at a global level is urgently required, with specific focus on ethics, communication and philosophy of care to enable normalization and humanization of birth.

2016 - The Ratio of MI to DCI and Its Impact in the Treatment of Polycystic Ovary Syndrome: Experimental and Literature Evidences [Capitolo/Saggio]
Facchinetti, F.; Dante, G.; Neri, I.

Myo-inositol (MI) and d-chiro-inositol (DCI), two second messengers of insulin in various insulin-dependent processes, are implicated in polycystic ovary syndrome (PCOS). MI and DCI exert distinct functions in insulin signaling. While MI is involved in the activation of glucose transporters and glucose utilization, DCI is mainly involved in the glycogen synthesis. At ovarian level, MI plays a pivotal role in the FSH signaling while DCI promotes insulin-dependent androgen synthesis. Although MI and DCI fulfill different roles, often their biological activities are confused. A key point is the physiological plasma ratio of 40:1, between MI and DCI, in healthy subjects. It was shown in the PCOS treatment the efficacy of therapies based on the restoration of the appropriate MI:DCI ratio, in such a way as to prompt a new approach in the researches and clinical trials. Moreover, it has been demonstrated that MI is able to increase oocyte and sperm cell quality, opening new possibilities to assisted reproduction technology (ART). With the aim to clarify these two sets of issues and answer a number of research questions and also to develop future studies, the International Consensus Conference on myo- and d-chiro-inositol in obstetrics and gynecology was held in Florence in 2013. In this chapter are summarized the main conclusions on MI and DCI and the role of MI in ART.

2015 - A challenging case of pregnancy with placenta accreta and very rare irregular antibodies versus Cromer blood group system: a case report [Articolo su rivista]
Busani, Stefano; VOLPI GHIRARDINI, Annamaria; Petrella, Elisabetta; Neri, Isabella; Casari, Federico; Venturelli, Donatella; De Santis, Mario; Montagnani, Giuliano; Facchinetti, Fabio; Girardis, Massimo

ntroduction: This report describes the challenges of treating a pregnant woman who had a rare case of critical placenta accreta with concurrent Cromer system anti-Tc(a) and anti-Kidd A alloantibodies. No previous case of such alloimmunization in a patient with placenta accreta has been reported. Case presentation: A 28-year-old African woman with anti-Cromer Tc(a) antibodies, anti-Kidd A antibodies and placenta accreta was admitted to the obstetric emergency department at our university hospital with persistent vaginal bleeding. Her rare Cromer blood group system antibodies had been diagnosed 1 month earlier; no compatible blood had been found despite a worldwide search. We performed a cesarean section after placement of Fogarty balloons in her uterine arteries with preoperative endovascular interventional radiology. Other therapeutic interventions included preoperative iron administration to raise hemoglobin and the scheduled predeposit of autologous blood. Intraoperative therapeutic management was aimed at preventing coagulopathy and massive bleeding. With the use of alternative medical techniques determined during perioperative planning, her intraoperative blood loss was only 1000mL, despite the placenta accreta. She was discharged from the hospital 4 days after cesarean section. Conclusions: To the best of our knowledge, this is the first report of an alloimmunized patient with two different alloantibodies and concurrent high risk of bleeding because of placenta accreta. The close collaboration among obstetricians, anesthesiologists, interventional radiologists, blood bank pathologists and intensive care doctors prevented serious consequences in this patient. The exceptional feature of this case is the patient's double risk: the placenta accreta and the inability to transfuse compatible blood. These two extreme situations challenged the multidisciplinary medical team.

2015 - Herbal Supplements in Pregnancy: Effects on Conceptions and Delivery [Capitolo/Saggio]
Facchinetti, F.; Dante, G.; Neri, I.

Before and during pregnancy, women are apprehensive about the potential toxicity of conventional medicines, so they use herbal remedies (HR) to complement or to replace them, although much current practice is not evidence-based. The current stage of knowledge is still inadequate to sufficiently inform clinicians, researchers, and the public about the benefits or potential risks of the use of HR for female infertility treatments. The extent of herbal remedies use in pregnancy has been widely researched throughout the world. Epidemiological studies reported a wide range of use of herbal remedies in pregnancy. Too few studies have been devoted to safety and efficacy of singular herbs. With the exception of ginger, there are no consistent data to support the use of any other herbal supplement during pregnancy.

2015 - Lifestyle-induced maternal body composition changes and birthweight in overweight/obese pregnant women [Articolo su rivista]
Bruno, R; Petrella, E; Bertarini, V; Neri, I; Facchinetti, F

Introduction: Obesity and excessive gestational weight gain (GWG) have been associated with higher occurrence of large for gestational age (LGA) babies, and several interventions have been proposed to limit GWG, which, however, does not reflect adequately the subtle changes in body composition that happens during pregnancy. The aim of this study is to evaluate if the variations of body composition, induced by a lifestyle program intended to limit GWG and measured through bioelectrical impedence analysis (BIA), could affect the newborns' weight in overweight/obese women. Methods: One hundred and thirty-nine women with BMI &gt;= 25 kg/m(2) were enrolled between 9th-12th week and a lifestyle program, consisting of low glycemic diet with caloric restriction and physical activity, was prescribed to them. BIA was performed at enrolment and at 35th-36th week. Data regarding the newborns' weight were collected from clinical charts after delivery. Results: Women who exceeded recommended range of GWG had an higher occurrence of LGA babies. Analysing the body composition, fat free mass (FFM) showed a direct correlation with the birthweight centile, even after correcting for BMI at enrolment, age and gestational diabetes mellitus. Interestingly, women who had an increase in fat mass (FM) and visceral FM throughout pregnancy had an higher occurrence of small for gestational age (SGA) babies. Conclusion: The increase in FM and visceral FM during pregnancy in overweight/obese women is linked to a higher occurrence of SGA babies.

2015 - Myo-inositol Supplementation for Prevention of Gestational Diabetes in Obese Pregnant Women: A Randomized Controlled Trial [Articolo su rivista]
Dʼanna, Rosario; Di Benedetto, Antonino; Scilipoti, Angela; Santamaria, Angelo; Interdonato, Maria Lieta; Petrella, Elisabetta; Neri, Isabella; Pintaudi, Basilio; Corrado, Francesco; Facchinetti, Fabio

OBJECTIVE: To evaluate whether myo-inositol supplementation, an insulin sensitizer, reduces the rate of gestational diabetes mellitus (GDM) and lowers insulin resistance in obese pregnant women. METHODS: In an open-label, randomized trial, myo-inositol (2 g plus 200 micrograms folic acid twice a day) or placebo (200 micrograms folic acid twice a day) was administered from the first trimester to delivery in pregnant obese women (prepregnancy body mass index 30 or greater. We calculated that 101 women in each arm would be required to demonstrate a 65% GDM reduction in the myo-inositol group with a statistical power of 80% (0.05). The primary outcomes were the incidence of GDM and the change in insulin resistance from enrollment until the diagnostic oral glucose tolerance test. RESULTS: From January 2011 to April 2014, 220 pregnant women at 12-13 weeks of gestation were randomized at two Italian university hospitals, 110 to myo-inositol and 110 to placebo. Most characteristics were similar between groups. The GDM rate was significantly reduced in the myo-inositol group compared with the control group, 14.0% compared with 33.6%, respectively (P.001; odds ratio 0.34, 95% confidence interval 0.17-0.68). Furthermore, women treated with myo-inositol showed a significantly greater reduction in the homeostasis model assessment of insulin resistance compared with the control group, -1.0±3.1 compared with 0.1±1.8 (P.048). CONCLUSION: Myo-inositol supplementation, started in the first trimester, in obese pregnant women seems to reduce the incidence in GDM through a reduction of insulin resistance.

2015 - Poor Folate Intake in a North Italian Pregnant Population: an Epidemiological Survey [Articolo su rivista]
Dante, Giulia; Morani, Letizia; Bronzetti, Daisy; Garutti, Paola; Neri, Isabella; Calapai, Gioacchino; Facchinetti, Fabio

Background The association between folic acid (FA) insufficiency and congenital malformations has been demonstrated in over the past two decades. The aim of the present study was to investigate the use and timing of folate intake among a large sample of pregnant women in a north Italian region. Methods A multicentre prospective cohort study was conducted over a 14-month period in the maternity wards of five general hospitals (2301 women). Data were collected via a face-to-face interview. Results Seven hundred sixty women (33%) took at least one product containing FA. Seven hundred thirty-three (31.8%) women consumed multivitamins containing 413 (17.9%) consumed products containing FA only and 17 (0.7%) 15mg of levofolinic acid. Only 0.9% of all women took FA before pregnancy 72.5% of women who consumed FA started during the first trimester. The most common dosage was 0.4mg (19.4%). Conclusions Very few women in the population are taking FA before pregnancy. Moreover, while most women consuming FA started in the first trimester, it is likely that they did so after closure of the neural tube. An important action is the recommendation that periconceptional supplementation programmes be promoted.

2015 - Safety of physical examination alone for managing well-appearing neonates ≥35 weeks gestation at risk for early-onset sepsis [Articolo su rivista]
Berardi, Alberto; Fornaciari, Sara; Rossi, Cecilia; Patianna, Viviana; Bacchi Reggiani, Maria Letizia; Ferrari, Filippo; Neri, Isabella; Ferrari, Fabrizio

Objective: The published data to support recommendations for prevention and management of well-appearing at-risk newborns (WAARNs) for early-onset sepsis (EOS) are limited.Methods: Retrospective cohort study comparing two different strategies for managing WAARNs (≥35 weeks gestation) during a 6-year period (Period 1, from 2005 to 2007; Period 2, from 2009 to 2011). WAARNs were defined as healthy-appearing neonates evaluated because of risk factors for EOS. Laboratory evaluation plus simplified physical examination (Period 1) was compared with physical examination alone (PEA, Period 2). The use of antibiotics, the length of stay, the timeliness of diagnosis and the risk of falling ill immediately after hospital discharge in both periods were also compared.Results: WAARNs receiving empirical antibiotics were 14/500 (Period 1) and 3/500 (Period 2, p = 0.01). Median length of stay was 4 (Period 1) and 3 days (Period 2, p = 0.04). Symptoms of EOS were earlier than laboratory evaluation results in 42/44 neonates. Severe disease was diagnosed within 6 h of life in all neonates. No WAARNs presented with EOS following hospital discharge.Conclusions: WAARNs managed through PEA received less unnecessary antibiotics and had a shorter length of stay. They had no increased risk of severe complications or increased risk of becoming ill following hospital discharge.

2014 - Acupuncture in post-date pregnancy: a pilot study. [Articolo su rivista]
Neri, Isabella; F., Monari; C. S., Midwife; Facchinetti, Fabio

Pharmacological labor induction is obtained through intracervical/vaginal prostaglandins and/or oxytocin infusion; however, the use of these agents produces fetal and maternal side effects. Traditional Chinese medicine advocates the use of acupuncture to soften the cervix and induce uterine contractions. The aim of the present study is to investigate the effect of acupuncture to induce labor. Acupuncture was applied in post-date pregnancies one week before a planned induction; the primary outcome was the rate of women submitted to labor induction for prolonged pregnancy at week 41 + 5.After informed consent, 221 undelivered women ranging between 40 + 2/40 + 6 gestational age were considered eligible for the study and 202 were randomized to receive acupuncture or observation. Sessions of acupuncture were planned every odd day from the randomization till 41a week plus 4 days. At 41 + 5 week a pharmacological induction of labor was planned.The total rate of labor induction did not significantly differ between observation and acupuncture group (20\% versus 17\%). Moreover no differences were found as far as the indications to induce labor, in particular "prolonged pregnancy" was similar between groups (8/96 versus 5/99). To investigate between-group differences in time elapsed between inclusion and delivery, survival analysis was performed excluding women requiring labor induction: women receiving acupuncture showed a trend to deliver earlier than women in the observation group (p < 0.09).The present study demonstrated that acupuncture applied every odd day for one week seems ineffective in reducing the rate of labor induction performed for prolonged pregnancy at 41 + 5 weeks. Previous reports reached similar conclusions, independently of the different timing, duration and mode of stimuli application.

2014 - Dietary interventions, lifestyle changes, and dietary supplements in preventing gestational diabetes mellitus: a literature review [Articolo su rivista]
Facchinetti, Fabio; Dante, Giulia; Petrella, Elisabetta; Neri, Isabella

Gestational diabetes mellitus (GDM) is associated with increased rates of fetal morbidity and mortality, both during the pregnancy and in the postnatal life. Current treatment of GDM includes diet with or without medications, but this management is expensive and poorly cost-effective for the health care systems. Strategies to prevent such condition would be preferable with respect to its treatment. The aim of this literature review was to evaluate studies reporting the efficacy of the most used approaches to prevent GDM as well as evidences of efficacy and safety of dietary supplementations. Systematic literature searches were performed in electronic databases, covering the period January 1983 to April 2014. Randomized controlled clinical trials were included. Quality of the articles was evaluated with the Jadad scale. We did not evaluate those articles that were already entered in the most recent systematic reviews, and we completed the research with the trials published thereafter. Of 55 articles identified, 15 randomized controlled trials were eligible. Quality and heterogeneity of the studies cannot allow firm conclusions. Anyway, trials in which only intake or expenditure has been targeted mostly reported negative results. On the contrary, combined lifestyle programs including diet control (orienting food intake, restricting energy intake) associated with moderate but continuous physical activity exhibit better efficacy in reducing GDM prevalence. The results from dietary supplements with myoinositol or probiotics are promising. The actual evidences provide enough arguments for implementing large-scale, high-quality randomized controlled trials looking at the possible benefits of these new approaches for preventing GDM.

2014 - Gestational weight gain in overweight and obese women enrolled in a healthy lifestyle and eating habits program [Articolo su rivista]
Petrella, Elisabetta; Malavolti, M; Bertarini, V; Pignatti, Lucrezia; Neri, Isabella; Battistini, N. C; Facchinetti, Fabio

OBJECTIVES: To determine whether changes in lifestyle in women with BMI &gt; 25 could decrease gestational weight gain and unfavorable pregnancy outcomes. METHODS: Women with BMI &gt; 25 were randomized at 1st trimester to no intervention or a Therapeutic Lifestyle Changes (TLC) Program including diet (overweight: 1700 kcal/day, obese: 1800 kcal/day) and mild physical activity (30 min/day, 3 times/week). At baseline and at the 36th week women filled-in a Food Frequency Questionnaire. OUTCOMES: gestational weight gain, gestational diabetes mellitus, gestational hypertension, preterm delivery. Data stratified by BMI categories. RESULTS: Socio-demographic features were similar between groups (TLC: 33 cases, CONTROLS: 28 cases). At term, gestational weight gain in obese women randomized to TLC group was lower (6.7 ± 4.3 kg) versus controls (10.1 ± 5.6 kg, p = 0.047). Gestational diabetes mellitus, gestational hypertension and preterm delivery were also significantly lower. TLC was an independent factor in preventing gestational weight gain, gestational diabetes mellitus, gestational hypertension. Significant changes in eating habits occurred in the TLC group, which increased the number of snacks, the intake of fruits-vegetables and decreased the consumption of sugar. CONCLUSIONS: A caloric restriction associated to changes in eating behavior and constant physical activity, is able to reduce gestational weight gain and related pregnancy complications in obese women.

2014 - Herbal therapies in pregnancy: what works? [Articolo su rivista]
G., Dante; G., Bellei; Neri, Isabella; Facchinetti, Fabio

The aim of this article is two-fold: to report the prevalence of herbal products used by pregnant women and to evaluate the evidence of efficacy and safety of the most popular remedies.Of the 671 articles identified, 15 randomized controlled trials (RCTs) and 16 non-RCTs were eligible. Ginger was the most investigated remedy and it was consistently reported to ameliorate nausea and vomiting in pregnancy. Although raspberry, blue cohosh, castor oil, and evening primrose oil are believed to facilitate labor in traditional medicine, very few scientific data support such indication. Moreover, they have been associated with severe adverse events. Data on the safety of Hypericum perforatum in pregnancy or lactation are reassuring, whereas efficacy was demonstrated only in nonpregnant individuals. There is still insufficient evidence regarding the efficacy and safety of Echinacea, garlic, and cranberry in pregnancy.Epidemiological studies reported a wide range of use of herbal remedies in pregnancy. Too few studies have been devoted to the safety and efficacy of singular herbs. With the exception of ginger, there are no consistent data to support the use of any other herbal supplement during pregnancy. Severe adverse events have been reported using blue cohosh and evening primrose oil.

2014 - Metabolic alterations in HIV-infected pregnant women: moving to metabolic tailoring of antiretroviral drugs. [Articolo su rivista]
Guaraldi, Giovanni; Stentarelli, Chiara; A. D., Da Silva; K., Luzi; Neri, Isabella; M., Cellini; E., Petrella; E., Garlassi; Menozzi, Marianna; Facchinetti, Fabio; Mussini, Cristina

The most striking effect of increased survival and improved quality of life in HIV-infected women undergoing antiretroviral therapy is the feasibility of motherhood-desire satisfaction. However, such advantages are often associated with drug-related metabolic toxicities, particularly relevant in the pregnancy context. Recent guidelines provide recommendations and trends for the use of antiretroviral therapy in pregnant women, but current literature falls short of providing specific insights on the need for metabolic monitoring and treatment in HIV-infected pregnant women. In this review we provide specific insight into the state-of-the-art of: detection, evaluation, and management of metabolic alterations in this special population. Pregnancy is in fact a metabolic transition process, potentially associated with specific diseases in the mother, in the newborn, and in the adulthood of the child. We will not simply discuss antiretroviral therapy metabolic toxicities, but rather their interaction with the physiological metabolic changes occurring during pregnancy. Close monitoring is needed to diagnose metabolic alterations that can lead to adverse outcomes in the mother, in the newborn, and potentially in adulthood. Lifestyle interventions and an appropriate metabolic tailoring of antiretroviral therapy drugs need to be considered in the prevention and treatment of metabolic alteration during pregnancy.

2014 - The l-arginine/nitric oxide pathway is impaired in overweight/obese pregnant women [Articolo su rivista]
Petrella, Elisabetta; Pignatti, Lucrezia; Neri, Isabella; Facchinetti, Fabio

To evaluate the l-arginine/NO system and its role in insulin signaling and endothelial function during the pregnancy of women of different BMI categories.

2013 - ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population [Articolo su rivista]
Anzivino, Claudia; Odoardi, Maria Rosaria; Meschiari, Erica; Baldelli, Enrica; Facchinetti, Fabio; Neri, Isabella; Ruggiero, Giuseppe; Zampino, Rosa; Bertolotti, Marco; Loria, Paola; Carulli, Lucia

Background: Genetic alterations in the ATP-binding cassette subfamily B member 4 (ABCB4) and ATPbinding cassette subfamily B member 11 (ABCB11) have been associated to the onset of intrahepatic cholestasis of pregnancy (ICP) in predisposed women. Aims: To identify new and/or frequent ABCB4 and ABCB11 genes variants in a cohort of Italian patients with ICP and to evaluate the possible pathogenetic role for the novel mutations identified. Methods: DNA of 33 unrelated Italian women with obstetric cholestasis were screened for mutations in the entire coding sequence of ABCB4 and ABCB11 genes. Polymerase chain reaction and automated sequencing was performed on the 27 coding exons of both genes. Results: Genotyping revealed 11 mutations, 5 of whom were novel variants: 2 localized on ABCB4 (p.I587DfsX603, p.I738LfsX744) and 3 on ABCB11 (p.V284D, p.Q558H, p.P731S). The most severe phenotypes were associated with the variants p.I587DfsX603, p.I738LfsX744 and p.V284D. Moreover, the already described mutation p.N510S found in ABCB4 seems to be strictly involved in the onset of ICP in that particular patient. Conclusions: Our data support the hypothesis of a significant involvement of ABCB4 mutations in the onset of ICP, but also confirm an important role for ABCB11 mutations in increasing the susceptibility to cholestasis of pregnancy.

2012 - Headache and adverse pregnancy outcomes: a prospective study [Articolo su rivista]
L., Marozio; Facchinetti, Fabio; G., Allais; R. E., Nappi; M., Enrietti; Neri, Isabella; E., Picardo; C., Benedetto


Monari, Francesca; Alberico, S; Avagliano, L; Cetin, I; Cozzolino, S; Gargano, G; Marozio, L; Mecacci, F; Neri, Isabella; Tranquilli, Al; Venturini, P; Facchinetti, Fabio

OBJECTIVE: To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death. STUDY DESIGN: In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption - PVD). In the remnant 79 cases, no cause of death or associated condition was found. Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed. RESULTS: Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR=3.2, 95\% CI: 1.3-8.3, p=0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR=8.9, 95\%CI 1.2-70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR=3.8, 95\% CI: 1.3-13.5). CONCLUSION: These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia.

2011 - Acupuncture treatment as breastfeeding support: preliminary data. [Articolo su rivista]
Neri, Isabella; G., Allais; V., Vaccaro; S., Minniti; G., Airola; P., Schiapparelli; C., Benedetto; Facchinetti, Fabio

This article investigates the efficacy of acupuncture for the maintenance of breastfeeding during the first 3 months of a newborn's life.After written informed consent was obtained, 90 women were randomly divided into two groups: acupuncture treatment or observation. Acupuncture sessions were performed twice weekly for 3 weeks (total six sessions). The control group made weekly visits to the clinic and the midwife observed their breastfeeding, giving routine care. In both groups, a semistructured clinical assessment of breastfeeding quality was carried out by the midwife at enrollment and after 3 weeks. Moreover, in both groups a telephone interview was conducted by the midwife at the third month of the infants' lives, regarding the continuation of breastfeeding.No significant difference in the exclusive breastfeeding rate before treatment was observed between acupuncture and observation groups (51.2\% versus 48.8\%). However, at 3 weeks post-enrollment, exclusive breastfeeding was significantly lower in the observation group than in the acupuncture group (60\% versus 100\%; p < 0.03). At the third month of the newborns' lives, breastfeeding was reported in 35\% of the acupuncture group, compared to 15\% of the observation group (p < 0.03).Such preliminary data suggest that 3 weeks of acupuncture treatment were more effective than observation alone in maintaining breastfeeding until the third month of the newborns' lives.

2011 - Stillbirth: issues and new insights [Articolo su rivista]
Facchinetti, Fabio; Ferrari, Francesca; Monari, Francesca; Neri, Isabella

Disparities in stillbirth (SB) are mainly related to socioeconomic factors. Developing countries have a SB rate five-times higher than that of developed countries, one-third of which occur intrapartum. Instead, in developed countries the access to antenatal care became the first preventive intervention for SB. In this article, we summarize strategies for SB prevention in the developing and developed world. Moreover, we report a critical evaluation of the six most used classification systems, highlighting the best performer. Similarly, we summarize the necessary diagnostic examinations for an appropriate classification of SB. Some of the new lines of investigation are reported here. However, any new finding on the cause of SB has to acknowledge a model of interpretation that takes into account a triad; the fetus and its characteristics, the uterine environment and the circumstances of death.

2010 - L-arginine supplementation in women with chronic hypertension: impact on blood pressure and maternal and neonatal complications. [Articolo su rivista]
Neri, Isabella; Monari, Francesca; Sgarbi, L.; Berardi, A.; Masellis, G.; Facchinetti, Fabio

To evaluate L-arginine (L-Arg) supplementation in pregnant women with chronic hypertension and its effects on blood pressure (BP) and maternal and neonatal complications.We enrolled 80 women affected by mild chronic hypertension referred to the High Risk Clinic of the Mother-Infant Department of the University of Modena and Reggio Emilia. Each woman after obtaining oral consent was randomized to receive oral L-Arg versus placebo and thereafter submitted to 24-h ambulatory BP monitoring. The primary outcome was BP change after 10-12 weeks of treatment. Secondary outcomes were as follows: percentage of women on antihypertensive treatment at delivery, maternal, and fetal outcome.The BP changes after 10-12 weeks of treatment did not differ between groups. A lower percentage of women received antihypertensive drugs in the L-Arg group than the placebo group. The incidence of superimposed preeclampsia indicated delivery before the 34th weeks and certain neonatal complications tended to be higher in the placebo group.L-Arg supplementation in pregnant women with mild chronic hypertension does not significantly affect overall BP but is associated with less need for antihypertensive medications and a trend toward fewer maternal and neonatal complications. The results of the study were limited by the small sample size and by the exclusion of women with severe chronic hypertension. In our policy, these patients needed many hypertensive drugs and were normally managed by the cardiologist. Nevertheless, considering the promising results on maternal and fetal outcome, we believe that further studies should be performed to confirm such data and to clarify the role of L-Arg as a protective supplement in high-risk pregnancy.

2009 - Angiotensin-converting enzyme and adducin-1 polymorphisms in women with preeclampsia and gestational hypertension. [Articolo su rivista]
C., Mandò; P., Antonazzo; S., Tabano; S., Zanutto; P., Pileri; E., Somigliana; F., Colleoni; A., Martinelli; A., Zolin; C., Benedetto; L., Marozio; Neri, Isabella; Facchinetti, Fabio; M., Miozzo; I., Cetin

The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the Adducin-1 (ADD1) G460W nonsense single nucleotide polymorphism (SNP) have previously been associated to hypertension, whereas their association with preeclampsia (PE) and gestational hypertension (GH) is still controversial. We genotyped ACE I/D, ADD1 G460W, and ADD1 S586C polymorphisms in 672 unrelated pregnant women: 204 PE (81/204 mild PE), 56 GH, and 412 controls, evaluating both their single and combined effects on these pathologies. The genotype combination of the 3 polymorphisms was not statistically different in cases versus controls, nor were ACE and ADD1 polymorphisms in GH. Nevertheless, the distribution of ACE genotypes was different in PE. This was confirmed in mild PE, whereas no significance was found in severe PE. This could suggest that different factors may lead to mild and severe PE, with ACE polymorphism playing a more important role in the mild form.

2009 - Application of acupuncture in labor [Relazione in Atti di Convegno]
Neri, I.; Ricchi, A.; Salvioli, C.; Facchinetti, F.

2009 - Computerized Evaluation of Fetal Heart Rate during Tocolytic Treatment: Comparison between Atosiban and Ritodrine. [Articolo su rivista]
Neri, Isabella; Monari, Francesca; Herbert, Valensise; Barbara, Vasapollo; Facchinetti, Fabio; Volpe, Annibale

We compared the effects of ritodrine and atosiban treatments on fetal cardiovascular behavior by computerized nonstress test (c-NST) analysis. Women diagnosed with preterm labor were randomized to receive either atosiban or ritodrine. A c-NST was performed at least 12 hours after the last corticosteroid administration. Differences in fetal cardiovascular behavior were evident when treatment was given before 30 weeks' gestation. Ritodrine induced higher fetal heart rates, lower long-term variation values, and lower low:high-frequency ratios compared with atosiban. Atosiban induced higher gestational ages at delivery and higher birth weights than ritodrine. The mean Apgar scores were similar for atosiban and ritodrine groups at 1 and 5 minutes. No 5-minute Apgar score was &lt; 7. With respect with atosiban, ritodrine treatment induces tachycardia and a lower variability of fetal heart rate. Such changes could be erroneously interpreted as signal of fetal distress, namely at lower gestational age.

2008 - L-arginine and hypertension in pregnancy [Relazione in Atti di Convegno]
Neri, I.; Monari, F.; De Pace, V.; Facchinetti, F.; Volpe, A.

2007 - Effects of three different stimulations (acupuncture, moxibustion, acupuncture plus moxibustion) of BL.67 acupoint at small toe on fetal behavior of breech presentation [Articolo su rivista]
Neri, Isabella; De Pace, V; Venturini, P; Facchinetti, Fabio

The aim of the study was to evaluate cardiovascular effects and fetal behavior during moxibustion, acupuncture or acupuncture plus moxibustion applied on the BL.67 acupoint of women (beside the outer corner of the 5th toenail) in fetal breech presentation. During the acupoint stimulation (20 min, two times a week), the women were submitted to computerized non-stress test. Fourteen cases were treated by both acupuncture and moxibustion, 15 cases by moxibustion and 10 cases by acupuncture. In 56% of cases, fetal position was converted from breech position to cephalic one; the success share was 80% for moxibustion, 28% for acupuncture, 57% for acupuncture plus moxibustion; the conversion, on average, was achieved after 3 sessions. Statistical analysis indicated that acupuncture plus moxibustion was able to reduce fetal heart rate during the application of stimuli while acupuncture and moxibustion separately did not affect such parameter. Moreover, moxibustion and acupuncture with moxibustion reduced fetal movements while acupuncture only appears ineffective. The present study suggests that fetal movements were reduced by both acupuncture plus moxibustion and moxibustion and that fetal heart rate was reduced just by acupuncture plus moxibustion. The mechanisms leading the effect on fetal heart rate and fetal movements remain to be clarified. Even though further studies are needed, such preliminar report mainly investigated the impact of different stimula on the BL.67 acupoint. Unfortunately these small series of data do not allow us to draw any conclusion about the effectiveness of the different treatments.

2007 - L-arginine supplementation in patients with gestational hypertension: A pilot study [Articolo su rivista]
Facchinetti, Fabio; Saade, Gr; Neri, Isabella; Pizzi, C; Longo, M; Volpe, Annibale

Objective: To evaluate the effects of L-arginine (L-Arg) supplementation on clinical outcomes and blood pressure (BP) changes in patients with gestational hypertension. Methods: Patients with gestational hypertension and proteinuria (n = 28, &gt; 300 mg/ 24 h) and those without proteinuria (n = 46) were randomized in a double-blind design to receive either L-Arg (20g/500 mL intravenously daily, for 5 days followed by 4g/day orally for 2 weeks) or placebo (PL). The primary outcome variable was time from randomization to delivery (Latency). Automated BP readings were obtained every 2 hours, between 8.00 am and 8.00 pm daily, untill the sixth day after treatment. Results: At inclusion, gestational age and proportions of patients with proteinuria did not differ significantly between the PL and L-Arg group, Latency was significantly longer in the L-Arg group compared with the PL group (19.5 +/- 16.9 vs. 31.7 +/- 25.2 days; p = 0.008). Compared with baseline, both systolic and diastolic BP 6 days after treatment were significantly reduced in the L-Arg group but not in the PL group. The subgroup of patients without proteinuria randomized to the group receiving L-Arg showed a trend to prolong pregnancy, to attenuate the evolution to PE, and to reduce the rate of low birth weight. Conclusions: The treatment with L-Arg seems promising in prolonging pregnancy and reducing blood pressure, particularly in patients with gestational hypertension and without proteinuria. This benefit should be confirmed in larger studies with the power to evaluate the effectiveness of L-Arg in preventing the development to preeclampsia.

2006 - Effect of L-arginine on blood pressure in pregnancy-induced hypertension: A randomized placebo-controlled trial [Articolo su rivista]
Neri, Isabella; Jasonni, Valerio; Gori, Gf; Blasi, I; Facchinetti, Fabio

Objective. To evaluate the antihypertensive efficacy of L-arginine (L-Arg) repeated infusions in women affected by gestational hypertension. Methods. The women were referred to obstetric units in order to assess their clinical conditions and to exclude the presence of severe fetal and/or maternal complications. Inclusion criteria were: maternal age range 16 - 45 years, diagnosis of gestational hypertension without proteinuria ( patients normotensive until the 20th week), and gestational age ranging between 24 and 36 weeks. Each woman was allocated to receive either L-arginine ( 20 g/500 mL) or placebo treatment through an i.v. line. The infusion was carried out in the morning from 8 a. m. to 10 a. m. and it was repeated for the next four consecutive days. Systolic and diastolic blood pressure values as well as heart rate were recorded with the patient in an upright, seated position at 08: 00, 12: 00, 16: 00 and 20: 00 h. Results. Maternal clinical features such as age, height, weight, and gestational age at inclusion were similar between groups. Both systolic and diastolic blood pressures were reduced by treatment, the effect of L-arginine being significantly higher than that of the placebo ( systolic values F = 8.59, p<0.005; diastolic values F = 3.36; p<0.001). Twenty women assigned to the L-Arg group (32.2%) and 23 to the placebo group (37.7%) were concomitantly treated with antihypertensives before starting the study. Analyzing the subgroup of patients not receiving antihypertensive drugs we found that L-arginine was superior to placebo in lowering systolic ( F = 5.42, p<0.005) and diastolic ( F = 2.20, p<0.005) blood pressure values. Conclusions. In conclusion, these data support the use of L-Arg as an antihypertensive agent for gestational hypertension especially in view of the other beneficial effects nitric oxide donors display in pregnancy. Further, L-Arg seems well tolerated since in this sample none of the patients reported adverse effects requiring study interruption.

2006 - Effects of L-arginine infusion on vascular reactivity and nitric oxide metabolites production in normotensive and preeclamtic women. [Abstract in Rivista]
De Pace, V; Neri, Isabella; Volpe, Annibale; Facchinetti, Fabio


2006 - Hyperemesis gravidarum complicated by Wernicke encephalopathy: Background, case report, and review of the literature [Articolo su rivista]
Chiossi, G; Neri, Isabella; Cavazzuti, Milena; Basso, G; Facchinetti, Fabio

Wernicke encephalopathy (WE) is a rare but known complication of severe hyperemesis gravidarum caused by thiamine deficiency. This article presents an unusual case that occurred at our institution and reviews the 48 previously published cases of WE in pregnancy. Considering all the 49 cases, the mean (standard deviation) patients' age was 26.7 +/- 4.9 years, the mean gestational age when WE manifested was 14.3 +/- 3.4 weeks, and the mean duration of vomiting and feeding difficulties was 7.7 +/- 2.8 weeks. Wernicke's classic triad (confusion, ocular abnormalities, and ataxia) manifested in only 46.9% (23 of 49) of the patients. Confusion affected 63.3% (31 of 49) of the patients, ocular signs 95.9% (47 of 49) and symptoms 57.1% (28 of 49), and ataxia 81.6% (40 of 49). Deterioration of consciousness affected 53.1% (26 of 49) of the subjects and memory impairment 61.2% (30 of 49). Complete remission of the disease occurred in only 14 of 49 cases. Symptom resolution required months and permanent impairments were common. The overall pregnancy loss rate, directly (spontaneous fetal loss) and indirectly (planned abortion) attributable to WE, was 47.9% (23 of 49). The diagnosis of WE is clinical and can be rapidly confirmed by magnetic resonance imaging. We emphasize the importance of thiamine supplementation to women with prolonged vomiting in pregnancy, especially before intravenous or parenteral nutrition. We also underline the necessity to promptly replace vitamin B1 when neurologic symptoms and/or signs develop in a patient with hyperemesis gravidarum.

2005 - Acupuncture versus pharmacological approach to reduce Hyperemesis gravidarum discomfort. [Articolo su rivista]
Neri, Isabella; G., Allais; P., Schiapparelli; I., Blasi; C., Benedetto; Facchinetti, Fabio

Several reports have suggested the use of acupuncture as a useful treatment for hyperemesis gravidarum (HG), in particular the effects on nausea intensity was underlined. The aim of this study was to compare the efficacy of acupuncture sessions plus acupressure with a metoclopramide/vitamin B12 treatment.In this study we randomized 88 pregnant patients suffering from HG to receive either acupuncture sessions plus acupressure (acupuncture group) or metoclopramide infusion (metoclopramide group) supplemented by vitamin B12 complex. Somatic symptoms and the ability to achieve the daily routine activity (functioning) were evaluated. Acupuncture sessions were performed at the hospital twice a week for 2 weeks according to the traditional Chinese medicine criteria. Acupression was applied for 6-8 h/day. In the metoclopramide group, patients received at hospital metoclopramide infusion (20 mg/500 mL saline for 60 min) twice a week for 2 weeks. An oral supplementation with vitamin B12 complex (30 mg/day) was also prescribed.Both treatments reduced vomiting episodes and then nausea intensity with a consequent improvement in the rate of food intake. The effect of acupuncture seems to be progressive, increasing at the end of treatment whereas pharmacological approach has a prompt effect in responders remaining stable thereafter. Moreover, acupuncture was significantly more effective than drugs in improving functioning.In our study for the first time acupuncture, applied accordingly to Chinese formula, was compared to drugs demonstrating the same effect of both treatments on HG symptoms. Interestingly, functioning was significantly improved just by acupuncture. Even if the effect of acupuncture on HG discomfort remains to be confirmed, the reports on the effect of acupuncture on psychosocial variables could represent a further advantage of acupuncture application and provide an incentive to widen the base of the research.

2005 - Detection of a novel dystrophin gene mutation through carrier analysis performed during prenatal diagnosis in a case with intragenic recombination [Articolo su rivista]
Percesepe, Antonio; M., Ferrari; D., Coviello; M., Zanussi; M., Castagni; Neri, Isabella; M., Travi; Forabosco, Antonino; S., Tedeschi

Objectives To report a multi-technical approach to Duchenne muscular dystrophy (DMD) mutation testing through carrier analysis, in the prenatal diagnosis of a male foetus without a known mutation segregating in the family and with inconclusive results of linkage analysis. Methods Haplotype analysis with the DMD region markers for assigning the carrier status of the mother and for prenatal diagnosis of foetal DNA; serniquantitative multiplex analysis of maternal and foetal DNA for the promoter and for 34 exons of the DMD gene; sequencing analysis of the maternal and foetal DNA for confirmation of the results. Results Because of an intragenic recombination of the DMD gene in foetal DNA, haplotype analysis gave inconclusive results. Semiquantitative PCR analysis displayed a pattern compatible with a heterozygous exon 60 mutation in the mother´s DNA, while foetal DNA showed a normal migration pattern. Sequencing analysis confirmed the presence of a novel 7 base-pair deletion in exon 60 of the DMD gene in the mother and excluded the deletion in the foetus. Conclusion Semiquantitative PCR results allowed the DMD mutation detection in the mother and the exclusion in the foetus, showing its crucial importance in prenatal diagnosis in those cases where linkage analysis is not conclusive. Copyright

2005 - Potential effects of nutrients on placental function and fetal growth [Relazione in Atti di Convegno]
Di Renzo, G C; Clerici, G; Neri, I; Facchinetti, F; Caserta, G; Alberti, A

2004 - Acupuncture plus moxibustion to resolve breech presentation: a randomized controlled study [Articolo su rivista]
Neri, Isabella; Airola, G.; Contu, G.; Allais, G.; Facchinetti, Fabio; Benedetto, C.

OBJECTIVE: In many Western countries breech presentation is an indication for elective Cesarean section. In order to correct fetal presentation, the stimulation of the acupoint BL67 by moxibustion, acupuncture or both has been proposed. Since no studies had previously been carried out on Western populations, pregnant Italian women at 33-35 weeks gestational age carrying a fetus in breech presentation were enrolled in a randomized, controlled trial involving an active BL67 point stimulation and an observation group. METHODS: A total of 240 women at 33-35 weeks of gestation carrying a fetus in breech presentation were randomized to receive active treatment (acupuncture plus moxibustion) or to be assigned to the observation group. Bilateral acupuncture plus moxibustion was applied at the BL67 acupoint (Zhiyin). The primary outcome of the study was fetal presentation at delivery. RESULTS: Fourteen cases dropped out. The final analysis was thus made on 226 cases, 114 randomized to observation and 112 to acupuncture plus moxibustion. At delivery, the proportion of cephalic version was lower in the observation group (36.7%) than in the active-treatment group (53.6 %) (p = 0.01). Hence, the proportion of Cesarean sections indicated for breech presentation was significantly lower in the treatment group than in the observation group (52.3% vs. 66.7%, p = 0.03). CONCLUSIONS: Acupuncture plus moxibustion is more effective than observation in revolving fetuses in breech presentation. Such a method appears to be a valid option for women willing to experience a natural birth

2004 - Effects of acute L-arginine infusion on non-stress test in hypertensive pregnant women [Articolo su rivista]
Neri, Isabella; Blasi, I.; Facchinetti, Fabio

OBJECTIVE: The present report evaluates the effect of acute L-arginine administration on fetal heart variables by a computerized non-stress test (NST) analysis. METHODS: Fifteen pregnant women at 30-34 weeks of gestational age affected by mild to moderate gestational hypertension were enrolled in the study. The study was performed in the second and third days of hospitalization. Each woman received both active (Arg) or placebo treatment (Placebo), in a double-blind, randomized, cross-over design. Women received saline infusion for 40 min, then they were infused with either placebo (saline infusion prepared by Damor Pharmaceutics and labeled as Arg-B) or Arg (L-Arg 20 g/500 ml labeled as Arg-A). RESULTS: Multiple analysis of variance (MANOVA) indicated that both placebo and Arg infusion were unable to affect cardiac variables and fetal movements. As far as maternal blood pressure changes were concerned, MANOVA indicated that active treatment showed an acute hypotensive effect on both systolic (F=8.98, p<0.001) and diastolic values (F=15.78, p>0.001). Conversely, placebo infusion does not seems to have induced any change. Considering each time of infusion we observed that Arg treatment was able to lower systolic and diastolic blood pressure after the 40 min of infusion, with this effect persisting for 20 min. CONCLUSIONS: These data indicate that the acute, intravenous administration of high-dose L-arginine does not induce significant changes in fetal heart rate (FHR), whereas it lowers maternal blood pressure. Such conclusions are reinforced by the observation that saline administration in the same pregnant women was neutral for both FHR and maternal blood pressure values. According to previous studies, it seems conceivable that maternal L-arginine treatment enters the fetal circulation by crossing the placenta. The lack of changes in FHR, however, suggests that no significant hemodynamic changes were induced by the treatment. Contrary to what happens in the mother, this may possibly be due to a low, if any, conversion of L-arginine to nitric oxide in the fetus.

2004 - Intravenous L-arginine is a new anti-hypertensive agent for pregnant women [Abstract in Rivista]
Neri, Isabella; Jasonni, Valerio; Gori, G; Blasi, I; Facchinetti, Fabio


2004 - Polyethylene glycol electrolyte solution (Isocolan) for constipation during pregnancy: An observational open-label study [Articolo su rivista]
Neri, Isabella; Blasi, I; Castro, P; Grandinetti, G; Ricchi, A; Facchinetti, Fabio

To evaluate the efficacy of a polyethylene glycol electrolyte solution (PEG-4000) in pregnant women affected by constipation, 40 consecutive pregnant women from 6 to 38 weeks' gestation were enrolled in this preliminary study. Constipation was defined as spontaneous evacuation less than four times a week or the presence of symptoms Such as defecation pain, rectal urgency, tenestmus, anal injury, or abdominal pain. A PEG-4000 solution (Isocolan, also marketed in the United States as Golitely/Nulitely) was administered for 15 days at a dose of 250 mL by mouth once or twice a day. The number of bowel movements per week, the presence or absence of liquid stools, tenesmus, urgency, defecation pain, anal lesions, and abdominal pain were evaluated before and after 15 days of treatment. Treatment with PEG-4000 significantly increased the evacuation episodes per week (from 1.66 +/- 0.48 to 3.16 +/- 1.05; P <.01), and constipation was resolved in 27 of 37 women (73%). Defecation pain, anal injury, and abdominal pain significantly improved after PEG-4000 administration. Improvement occurred in both patients with new-onset constipation during pregnancy as well as patients with a history of constipation before pregnancy. These preliminary findings that PEG-4000 may be an effective choice for the treatment of constipation during (C) 2004 by the American College of Nurse-Midwives.

2003 - La trasmissione verticale di HIV nell’era della HAART [Abstract in Atti di Convegno]
Guaraldi, Giovanni; Ikonomou, A.; Orlando, G.; Borghi, R.; Verrocchi, G. L.; Neri, Isabella; Facchinetti, Fabio; Cellini, M.; Esposito, Roberto

L'introduzione della HAART in gravidanza ha ridotto la trasmissione verticale di HIV a una prevalenza attuale minore del 2%.

2002 - Eleutherococcus senticosus reduces cardiovascular stress response in healthy subjects: a randomized, placebo-controlled trial [Articolo su rivista]
Facchinetti, Fabio; Neri, Isabella; M., Tarabusi

The number of studies devoted to the scientific evaluation of phytotherapy is rapidly increasing since Western patients seem more oriented towards so-called ´alternative medicine´. Bearing such arguments in mind we decided to address attention to Eleutherococcus senticosus, a root of the Ginseng family known for thousands of years in China as a remedy for psychological distress. Forty-five paid, healthy volunteers (20 males, 25 females) were recruited. Entry criteria were. good health, age 18-30 years, student and a Symptoms Rating Test score <10. At screening evaluation subjects were randomized to receive orally either placebo (PI group) or Eleutherococcus senticosus (Es group) for 30 days, in a double-blind design. Subjects were submitted to a stressful cognitive task, the Stroop Colour-Word test (Stroop CW), both before and after treatment. Stroop CW increased heart rate (HR) and systolic BP in every subject. In females there was a greater response than in males in terms of both systolic and diastolic BP. For both genders, the HR response to Stroop CW was reduced by Es treatment while no changes were found after Pl. In females, systolic BP was also reduced in Es group while it remained unchanged in PI group. This study demonstrated that treatment with Eleutherococcus senticosus is able to reduce cardiovascular responses to stress in healthy young volunteers, while placebo was ineffective. Eleutherococcus senticosus is confirmed to be helpful for stress adaptation. Copyright

2002 - Non-stress test changes during acupuncture plus moxibustion on BL67 point in breech presentation. [Articolo su rivista]
Neri, Isabella; M., Fazzio; S., Menghini; Volpe, Annibale; Facchinetti, Fabio

We assessed fetal heart variability and activity using a computerized non-stress test (NST) during acupuncture plus moxibustion on the BL67 point. For comparison, the same changes were assessed during placebo acupuncture (minimal acupuncture) in the same subjects.Twelve pregnant women in the 33rd week of gestation, carrying singletons in the breech presentation were enrolled in the study. In a single-blind design, each woman received a first session of minimal acupuncture followed 1-2 days later by true acupuncture. During the sessions, women were monitored using computerized non-stress testing starting 20 minutes before the stimuli and continuing for 20 minutes after treatment.During true acupuncture a significant reduction in fetal baseline heart rate, and more accelerations and movement were observed. During minimal acupuncture, there were no significant changes in these variables. No signs of fetal distress or changes in short- or long-term variability were noted, and there were no uterine contractions.In our study population, acute application of acupuncture plus moxibustion did not cause fetal distress as assessed by either fetal heart rate decelerations or changes in either short- or long-term variability. Considering that the modifications in fetal movement and heart rate occurred in true but not during minimal acupuncture, we could consider that such changes are related to the effect of the acupuncture stimulation. The mechanisms leading to the cephalic version remain to be clearly established.

2001 - Pituitary LH reserve suggests high risk of bulimia in amenorrheic women. [Articolo su rivista]
R. E., Nappi; Neri, Isabella; F., Veneroni; F., Polatti; F., Piccinini; Facchinetti, Fabio

The present study was aimed at investigating a) the risk of having bulimia in a heterogeneous population of secondary amenorrhea; b) the LH and FSH secretion under basal and stimulated conditions (GnRH challenge) according to the presence of bulimic risk in our study population; c) the clinical and endocrine factors predictive of the bulimic risk in amenorrheic women. Amenorrheic women (n=73; age: 23.1+/-4.8 yrs; BMI:20.2+/-2.2 kg/m2) filled in a self rating scale for bulimia (BITE) and were classified accordingly, as being at low risk (score <10), at medium risk (score between 10 and 24), and at high risk (score > or =25) of having bulimia. In each subject basal mean plasma LH levels were calculated over one hour, sampling every 10 minutes, while in a subgroup of 45 patients the area under the curve (AUC) of plasma LH and FSH levels following a challenge with two doses of GnRH (10+10 microg, every two hours), sampling every 15 minutes, was also evaluated. High risk of bulimia was present in 12.3\% of the population whereas 45.2\% showed a low risk and 42.5\% were at medium risk of developing the disorder. Mann-Whitney U test revealed that basal LH values were differently distributed with significantly lower levels (P<0.046) in amenorrheic women at high risk of bulimia in comparison with amenorrheic women at low risk. The AUC of LH secretion following the first challenge of GnRH was significantly higher in amenorrheic women with a high risk of bulimia in respect with both groups of women at low (P<0.034) and medium (P<0.009) risk. A similar result was found with FSH AUC following the first GnRH challenge (P<0.04 high risk vs low risk and P<0.014 high risk vs medium risk). In a multiple regression analysis, the best model predicting the risk of bulimia (BITE total score) included both the LH response to GnRH challenge and BMI. In conclusion, when facing secondary amenorrhea at first consultation, long before a precise pathophysiologic diagnosis of the disease, low basal plasma LH levels and LH response to GnRH challenge may allow one to suspect the presence of abnormal eating pattern of bulimic type.

2001 - The PFA-100 system for the assessment of platelet function in normotensive and hypertensive pregnancies. [Articolo su rivista]
M., Marietta; I., Castelli; F., Piccinini; Neri, Isabella; M., Bertesi; Facchinetti, Fabio; G., Torelli

Platelet function was studied in 30 pregnant women: 14 normotensive (C), and 16 affected by pregnancy-induced hypertension (PIH). Platelet aggregometry (PA) on platelet-rich plasma according to Born was compared with the new PFA-100 System (Dade International Inc, Miami, USA). This device evaluates platelet function (expressed in seconds as closure time, CT) in anticoagulated whole blood ex vivo at high shear rates. PA (expressed as percentage of light transmission) and CT were measured at baseline and after incubation with L-Arginine (L-Arg). MANOVA for repeated measures showed that L-Arg incubation significantly decreased PA (F=7.2, P < 0.05) and increased CT (F=6.05, P < 0.05) in the whole population of pregnant women. Moreover, we analysed separately both parameters in C and in PIH subjects. No differences in PA were found in both groups, neither at baseline nor after L-Arginine incubation. In contrast, CT was significantly longer in PIH in comparison to C before (95.9 s vs. 84 s, P < 0.05) as well after (115 s vs. 92 s, P < 0.05) L-Arginine incubation. Data from PFA-100 confirm our previous reports that during pregnancy the L-Arginine: Nitric Oxide pathway regulates platelet function. In hypertensive patients a significant decrease in platelet function was found by using the PFA-100 system.

2000 - Cardiotocography analysis during the BL67 acupoint stimulus for breech presentation [Articolo su rivista]
Neri, I.; Ternelli, G.; Facchinetti, F.; Volpe, A.

The BL67 acupuncture stimulus represents an effective and easy method to obtain the conversion of fetus in breech presentation. Notwithstanding this, traditional medicine still has several doubts about the safety of this technique. The aim of the present study is to prove that BL67 acupuncture stimuli application leads to no fetal risk, and that it doesn't induce any increase in uterine contractility. Actually, using computerized cardiotocography in 10 pregnant women who underwent acupuncture because of breech presentation, it was proved that either decrease or increase in fetal heartbeat or any changing in fetal heart rate hasn't occur both during and after the acupuncture practice, while was shown a decreasing in fetal movements. Moreover it was observed no uterine contractility during the observation period after the acupuncture session. It's so possible to conclude from this first experience that BL67 acupuncture stimulus absolutely causes no fetal risk and, what's more, in contrast to what is so often thought, the acute effect of acupuncture is to induce a quiet state in the fetus.

2000 - Increased L-citrulline/L-arginine plasma ratio in severe preeclampsia. [Articolo su rivista]
C., Benedetto; L., Marozio; Neri, Isabella; M., Giarola; Volpe, Annibale; Facchinetti, Fabio

To evaluate nitric oxide (NO) production in patients with pregnancy-induced hypertension or preeclampsia and in controls.Four groups of pregnant women were included: 17 patients with pregnancy-induced hypertension, ten with mild or moderate preeclampsia, 17 with severe preeclampsia, and 44 normotensive women matched for weeks of gestation at blood sampling with the cases. Plasma levels of L-citrulline and L-arginine were measured by using high-performance liquid chromatography.The mean plasma levels of L-citrulline and the ratio of L-citrulline to L-arginine, which reflects NO production, were higher in women with severe preeclampsia than in controls, patients with pregnancy-induced hypertension, and patients with mild or moderate preeclampsia.Nitric oxide production is enhanced in severe preeclampsia, possibly as a compensatory phenomenon for the increased synthesis and release of vasoconstrictors and platelet-aggregating agents.

2000 - Mood Disturbances: Effect of HRT versus socioeconomic and personality factors [Altro]
Cagnacci, Angelo; Neri, Isabella; Tarabusi, M.


2000 - Nitric oxide in the prevention of pre-eclampsia [Articolo su rivista]
C., Picciolo; N., Roncaglia; Neri, Isabella; F., Pasta; A., Arreghini; Facchinetti, Fabio

Objective The purpose of this study was to determine whether nitric oxide improved maternal and fetal outcome in women at high risk for recurrent pre-eclampsia. Study design A total of 68 patients at risk for developing pre-eclampsia were randomly allocated into two arms: one included patients treated with glyceryl trinitrate transdermal patch (5 mg/24 h, Schwarz-Pharma, Italy) for 14-16 h/day, starting from the 16th until the 38th week and one consisting of patients undergoing observation only. Results The occurrence of pre-eclampsia was similar in the two groups, being 31.6% in the treated women and 23.4% in the untreated ones. The patients treated with glyceryl trinitrate showed a neonatal birth weight, gestational age at delivery, rate of emergency Caesarean section and rate of premature delivery similar to those of the untreated group. At entry, the bilateral notches on the uterine arteries were similar. At the 24th week, patients treated with glyceryl trinitrate showed a significant reduction in the bilateral notch (p < 0.05). No change in the umbilical artery and middle-cerebral artery pulsatility indices were observed in the two groups. Conclusions Nitric oxide donor significantly improved uteroplacental blood flow. No change in fetal outcome was observed.

2000 - Nonpharmacological treatment of Hyperemesis gravidarum [Articolo su rivista]
Neri, I.; Fazzio, M.; Facchinetti, F.

Hyperemesis gravidarum, with severe nausea and vomiting causing in patients weight loss and dehydration, is a real discomforting situation for pregnant women and for their family and working life. Currently the conventional treatments of Hyperemesis includes simple advises concerned how to eat and drugs such as metoclopramide, corticosteroids and group B complex vitamins, since it was shown their effectiveness in improving nausea and vomiting and their safety. Anyway still now no one of this drug could totally eliminate the symptoms, maybe because the Hyperemesis gravidarum has a multifactorial ethiology. For this reason, in the last ten years a non pharnmacological approach had been proposed. It was proved in severals works that acupuncture treatment, by the PC6 point stimulation, improves the Hyperemesis symptoms in half of the cases studied, but because of some methodologic mistakes is still impossible to confirm its real effectiveness. In a new study, real acupuncture versus sham acupuncture, patients were randomised in three different groups, according to Traditional Chinese Medicine. Notwithstanding the rigour of the study, there are still some limits in it, for instance sham acupuncture is still not considered a believable placebo. Moreover the only study published for the phytotherapy is about the use of ginger (Zingiber Officinale) in pregnant women with Hyperemesis; these women were treated with ginger (250 mg four time in a day) or with placebo. Ginger didn't improve nausea and vomiting more than placebo.

2000 - Platelet responsiveness to L-arginine in hypertensive disorders of pregnancy [Articolo su rivista]
Neri, Isabella; F., Piccinini; M., Marietta; Facchinetti, Fabio; Volpe, Annibale

Objective: In chronically hypertensive (CH), preeclamptic (PE), and normotensive pregnant women (N), we investigated ex vivo platelet aggregation in response to L-arginine (L-Arg) and sodium nitroprusside (SN), which are respectively the substrate and donor of nitric oxide (NO). Methods: Platelet aggregation was determined with a dual-channel aggregometer by measuring transmittance of light through the sample in comparison to platelet poor plasma, as a reference. Aggregation induced by adenosine diphosphate was continuously recorded for 3 min and measured before and after preincubation with L-Arg and SN. Results: Preincubation with L-Arg significantly reduced platelet aggregation in N and CH patients (p < 0.05) but not in PE women. Preincubation with SN affected aggregation in PE women also (p < 0.001). No correlation was found between platelet response to L-Arg or SN stimuli and the severity of hypertensive disorders expressed as week of gestation at delivery or birth weight. Conclusions: The present study demonstrates that a decreased platelet sensitivity to L-Arg characterizes PE women, whereas SN maintains its antithrombotic power. This impairment seems to be specific for PE, because platelets of CH patients utilize L-Arg normally. This finding supports the involvement of the L-Arg-NO pathway in the pathogenesis of the procoagulative features of PE and probably in the onset of the disease. The maintained response to SN in PE patients suggests a possible therapeutical use of NO donors in the disease.

Neri, Isabella; H., Valensise; Facchinetti, Fabio; S., Menghini; C., Romanini; Volpe, Annibale

The objective of the present study is to compare the effectiveness of transdermal glyceryl-trinitrate versus oral nifedipine in lowering blood pressure in patients affected by pregnancy-induced hypertension (PIH). Thirty-six consecutive pregnant women have been evaluated at different gestational ages after the diagnosis of PIH or preeclampsia (PE). After a 24-h ambulatory blood pressure monitoring, patients were allocated to three groups: those receiving oral nifedipine and those receiving transdermal glyceryl-trinitrate in a continuous (24 h/day) or intermittent (16 h/day) administration. A second blood pressure monitoring was performed after 2 weeks of treatment. Systolic and diastolic blood pressure were compared by using the Cosinor method looking at mesor, amplitude, and acrophase. Baseline systolic and diastolic blood pressure was similar among the three groups. Neither the transdermal glyceryl-trinitrate administered for 24 or 16 h nor oral nifedipine affected systolic and diastolic blood pressure. Analysis of variance showed that the posttreatment values were similar among the groups. Further studies are needed to verify the possible use of transdermal glyceryl-trinitrate sis an antihypertensive drug during pregnancy.

1999 - Disagio psicologico della sindrome climaterica: effetto del tempo [Relazione in Atti di Convegno]
Facchinetti, Fabio; Piccinini, F; Neri, Isabella; Cagnacci, Angelo; Volpe, Annibale


1999 - Effect of L-Arginine load on platelet aggregation: a comparison between normotensive and preeclamptic pregnant women [Articolo su rivista]
Facchinetti, Fabio; Neri, Isabella; Piccinini, F; Marietta, M; Torelli, U; Bruschettini, Pl; Volpe, Annibale

Background In the present study we hypothesized that a derangement of the L-Arginine-Nitric Oxide system could be involved in the development of the hypercoagulative status found during preeclampsia. In order to verify such hypothesis we have compared the effects of Nitric Oxide substrate, L-Arginine on platelet aggregation. Moreover, we have also measured the L-Citrulline plasma levels as a stechiometric metabolite resulting from the conversion L-Arginine to Nitric Oxide. Methods. Nine preeclamptic women and 11 normotensive pregnant women were enrolled for the study. Subjects were infused with saline and with 30gr of L-Arginine. Blood samples were drawn during the saline infusion (30 min), during L-Arginine administration (30 min) and 30 min thereafter. ADP and Collagen-induced platelet aggregation was studied as per Born with a dual-channel aggregometer (Chrono-Log, Mascia Brunelli, Italy) and L-Citrulline was measured by HPLC. Results. In normotensive women the infusion significantly decreased ADP and Collagen-induced aggregation after 15 minutes of L-Arginine load; whereas no effects were observed in preeclamptic women. Similarly in normotensive but not in preeclamptic women L-Arginine load was able to increase L-Citrulline plasma levels. Conclusions. In normotensive women the in vivo L-Arginine administration decreases platelet aggregation with an increase of L-Citrulline plasma levels. On the contrary, no effects were observed in preeclamptic women. These findings confirm that a hypercoagulative status characterizes preeclampsia and that such phenomenon could be explained by a derangement of the platelet L-Arginine-Nitric Oxide pathway.

1999 - Effect of long-term local or systemic hormone replacement therapy on post-menopausal mood disturbances. Influences of socio-economic and personality factors. [Articolo su rivista]
Cagnacci, Angelo; Neri, Isabella; M., Tarabusi; Volpe, Annibale; Facchinetti, Fabio

To clarify the effect exerted by hormone replacement therapy (HRT) versus socio-economic and personality factors in improving postmenopausal mood disorders.The effect of the 1-year administration of systemic hormone replacement therapy (HRT; n = 22) or a vaginal cream of estriol (n = 14) versus no treatment (n = 26) was evaluated on mood states of anxiety, depression, somatization and inadequacy, as evaluated by the symptom rating test (SRT) scale. Results were correlated with the woman socio-economic status, and her capability to cope with daytime distresses, as evaluated by the Coping Style questionnaire.A spontaneous decline of all SRT scores, except that of inadequacy, was observed in the group with no treatment. In comparison HRT induced a greater improvement of only the SRT score of inadequacy (P < 0.01) and to a lesser extent of anxiety (P < 0.06). Similarly, vaginal estriol induced a greater decline of the SRT score of inadequacy (P < 0.01). Multiple regression analysis showed that modifications of the total SRT score and the SRT score of anxiety were related mainly to socio-economic factors, while those of the SRT score of depression were related only to the coping style of the woman. The decline of somatization was related only to time since the menopause while, the reduction of the SRT score of inadequacy was only the consequence of therapy, either systemic or local.In a 1-year period improvement of post-menopausal psychological discomfort, is spontaneous and independent of therapy. Only symptoms of inadequacy are improved by the hormonal therapy. Likely, the perceived menopausal 'losses' make the woman to feel inadequate and the use of sex-related hormones is capable to improve this feeling.

1999 - Effetti del trattamento a lungo termine sui disturbi dell’ umore in postmenopausa: influenza dei fattori psicosociali [Altro]
Facchinetti, Fabio; Piccinini, F; Neri, Isabella; Cagnacci, Angelo; Volpe, Annibale


1999 - L-arginine infusion reduces blood pressure in preeclamptic women through nitric oxide release [Articolo su rivista]
Facchinetti, Fabio; M., Longo; F., Piccinini; Neri, Isabella; Volpe, Annibale

OBJECTIVE: This study, investigates the biochemical and cardiovascular effects of L-arginine administration in normotensive pregnant women and women with preeclampsia. METHODS: The study groups consisted of 12 women with uncomplicated pregnancies and 17 preeclamptic patients, four of whom were on antihypertensive treatment. In both groups, saline infusion was started, followed by 30 g L-arginine administration, and finally more saline. Blood pressure was recorded every 5 minutes and blood samples were collected for measurement of serum citrulline, arginine, and nitrite levels. Amino acid assays were done by using high-performance liquid chromatography with fluorometric detection. RESULTS: L-Arginine infusion was associated with a significant reduction of blood pressure in both groups, the decrease being greater in the women with preeclampsia. Baseline serum citrulline and arginine level were nor significantly, different between the two groups. L-Citrulline levels were significantly increased during infusion of L-arginine, and the increase was significantly lower in the women with preeclampsia. Serum nitrite levels were increased only in controls and not in preeclampsia patients. The total citrulline production stimulated by L-arginine was related inversely to baseline blood pressure values and was unrelated to clinical parameters such as gestational age at delivery, birth weight, and Apgar score. CONCLUSIONS: L-Arginine load in pregnant women is associated with increased nitric oxide (NO) production and hypotension. Despite a reduced ability to produce NO, patients with preeclampsia may benefit from L-arginine supplementation. Overall, these findings partially support the hypothesis that preeclampsia is characterized by a dysfunction of the L-arginine-NO pathway. Copyright (C) 1999 by the Society for Gynecologic Investigation.

1999 - Platelet reactivity during estrogen replacement treatment in postmenopausal women [Abstract in Rivista]
Marietta, M; Castelli, I; Cagnacci, Angelo; Malmusi, S; Bertesi, M; Piccinini, F; Neri, Isabella; Facchinetti, Fabio; Torelli, G.


1998 - Assessment of platelet function in pregnancy with the PFA-100 (TM) system [Abstract in Atti di Convegno]
Marietta, M; Neri, Isabella; Piccinini, F; Facchinetti, Fabio; Bertesi, M; Torelli, Giuseppe

Assessment of platelet function in pregnancy with the PFA-100 (TM) system

1998 - Barber-Say syndrome: Report of a new case [Articolo su rivista]
Mazzanti, L; Bergamaschi, R; Neri, Isabella; Perri, A; Patrizi, A; Cacciari, E; Forabosco, Antonino

We present a girl with lax, redundant skin, ectropion, bulbous nose, macrostomia, and absence of mammary glands, To our knowledge, she represents the fourth described case of Barber-Say Syndrome (BSS), BSS and ablepharon macrostomia syndrome (AMS) share common and distinctive clinical manifestations that involve the same structure of the skin and adnexa, We hypothesize that they may derive from a defective regulation of the same gene. Am. J, Med. Genet, 78:188-191, 1998.

1998 - Reduction of serum citrulline levels in women at term toward the day of labor onset [Articolo su rivista]
Facchinetti, Fabio; Valensise, H; Neri, Isabella; Menghini, S; Romanini, C; Volpe, Annibale

Objective. To test the hypothesis that labor onset could be the result of a reduced release of nitric oxide (NO). Study design. Out of 91 consecutive healthy nulliparous women at term serum citrulline (Cit) and arginine (Arg) levels were measured at least twice in 37 subjects, by the means of HPLC with fluorometric detection. Twenty cases underwent a spontaneous onset of labor (group A) while in 17 cases labor was induced (group B) because of pregnancy prolongation or amniotic fluid reduction. Results. Cit and Arg levels were unaffected by the gestational age. In group A, Cit levels undergo a progressive decrease toward the day of labor (from 32.9 +/- 4.7 mu M/L the day -18,-5 to 27.7 +/- 7.8 the day -4,0; p=0.012) whilst they remained stable in group B (from 33.3 +/- 7.7 to 34.2 +/- 9.2). No significant changes were observed in Arg levels. Cit/Arg ratio remained stable in group A whereas it showed a trend to increase in group B. Conclusion. These data indirectly suggest a reduced release of NO toward term. This phenomenon could play a permissive role in the spontaneous onset of labor of healthy nulliparous women.

1998 - The L-arginine-nitric oxide system regulates platelet aggregation in pregnancy [Articolo su rivista]
Neri, Isabella; M., Marietta; F., Piccinini; Volpe, Annibale; Facchinetti, Fabio

OBJECTIVE: To investigate the ex vivo platelet aggregation in response to a substrate (L-arginine [L-Arg]) and a donor (sodium nitroprusside [SN]) of nitric oxide (NO) in nonpregnant women and in normotensive pregnancies. METHODS: Platelet aggregation was studied with a dual-channel aggregometer and expressed as a percentage of light transmission. Measurements were done at baseline and after preincubation with scalar doses of L-Arg and SN. The intraplatelet L-citrulline (L-Cit) levels were measured by high-performance liquid chromotography (HPLC). RESULTS: In both groups, the baseline aggregation values were similar for adenosine diphosphate (ADP) and collagen stimuli. Wilcoxon tank-sum testing demonstrated that in both groups the addition of L-Arg had a significant effect on aggregation: Doses of 50 to 5000 mu mol decreased ADP-induced aggregation. Conversely, collagen-induced aggregation was affected only by the highest dose of L-Arg. Sodium nitroprusside administered in doses of 2.5 to 250.0 nmol decreased ADP- and collagen-induced platelet aggregation equally. ADP-induced aggregation values obtained after (SN) incubation were positively correlated with gestational age. Intraplatelet L-Cit levels showed a significant rise after the incubation with L-Arg, and this effect was negatively correlated with gestational age. CONCLUSION: The L-Arg-NO system regulates platelet aggregation during pregnancy. Moreover, a physiologic reduction of platelet sensitivity to the antithrombotic effect of NO occurs. (J Soc Gynecol Invest 1998; 5:192-196). Copyright (C) 1998 by the Society for Gynecologic Investigation.

1997 - Coping style and climacteric symptoms in a clinical sample of postmenopausal women [Articolo su rivista]
Neri, Isabella; Demyttenaere, K; Facchinetti, Fabio

Hormonal changes as well or sociocultural and personal factors account for climacteric symptoms. The aim of this study is to investigate in a clinical population the correlation between the severity of hot flashes and vaginal dryness and the 'coping-ineffectiveness of coping' construct. Out 120 women consecutively referring to the University Menopause Clinic, 85 subjects were evaluated for their climacteric complaints including anxiety and depression and for their coping style assessed with the Italian version of the Utrechtse Coping Lijst. Daily hot flashes and severe vaginal dryness were reported by almost half of the studied population, regression analyses were performed in order to investigate how much of the variance in such symptoms was explained by the psychosocial variables and by the coping mechanisms. A more recent menopause, a lower educational level and an active coping predict a higher severity of hot flashes; a longer time since last menstrual period and a coping of avoidance predict a higher severity of vaginal dryness. The present study suggests that the severity of hot flashes and vaginal dryness among a clinical sample of postmenopausal women is not only determined by biological and social variables, but personal resources also explain part of the variance of such climacteric complaints.

1997 - Effects of a yeast-based dietary supplementation on premenstrual syndrome - A double-blind placebo-controlled study [Articolo su rivista]
Facchinetti, Fabio; Nappi, Re; Sances, Mg; Neri, Isabella; Grandinetti, G; Genazzani, A.

A dietary approach has proven to be effective in alleviating symptoms of premenstrual syndrome. In our previous studies, magnesium improved premenstrual irritability and mood scoings. In this double-blind, placebo-controlled study, we evaluated the effects of a new dietetic preparation (Sillix Donna(R), Giuliani) in 40 patients affected by mild to moderate premenstrual syndrome. Premenstrual symptoms were scored in both follicular and luteal phases, at baseline, at 2nd, 4th and 6th month of treatment by using the Menstrual Distress Questionnaire (MDQ). Twenty patients were randomised to receive the active preparation and 20 placebo. MDQ scores at baseline were similar in the two groups. Five patients of the placebo group dropped out because of treatment failure. No side effects were observed. Both treatments reduced symptoms already in the 2nd month, but the active preparation was more effective at all time controls (p < 0.05); at the 6th month it significantly reduced premenstrual MDQ scores to 18% of baseline values, placebo only to 73%. These data demonstrate that Sillix Donna is effective in reducing premenstrual distress.

1997 - L-arginine infusion decreases platelet aggregation through an intraplatelet nitric oxide release [Articolo su rivista]
M., Marietta; Facchinetti, Fabio; Neri, Isabella; F., Piccinini; Volpe, Annibale; Torelli, Giuseppe


Facchinetti, Fabio; S., De Martis; Neri, Isabella; A. S., Caputo; Volpe, Annibale


1996 - Effects of L-arginine on utero-placental circulation in growth-retarded fetuses [Articolo su rivista]
Neri, Isabella; V., Mazza; Volpe, Annibale; Mc, Galassi; Facchinetti, Fabio

Background. To evaluate the effects of L-arginine (ARG) infusion, the nitric oxide as substrate, on the utero-placental circulation at third trimester. Methods. Three groups of nine pregnant women each were infused i.v. with 30 g ARG, for 30 minutes. One group served as control, and the two remnants were composed by patients with intrauterine growth retardation with (IUGR-B) or without (IUGR-A) increased resistances in the utero-placental circulation. Changes of blood flow velocity waveforms of both uterine arteries and umbilical artery were recorded for 60 minutes. Blood pressure, serum nitrites/nitrates and growth hormone levels were also measured. Results. No hemodynamic changes in utero-umbilical circulation were observed during infusion in any of the three groups. Considering the uterine arteries separately as placental and non-placental sided we found a significant decrease of non-placental side resistances in IUGR-B women. Indeed, the pulsatility index was lowered by 14%, in respect of baseline value. Serum nitrites/nitrates as well as serum growth hormone levels were significantly increased by ARG, in every woman, irrespective of the presence of fetal growth retardation. Blood pressure remained unaffected during infusion in every woman. Conclusions. These findings suggest that L-arginine infusion affects utero-placental circulation in patients with IUGR associated with increased uterine resistances. Such an action is specific and appears possibly to be mediated by a release of nitric oxide.

1996 - L-arginine infusion reduces preterm uterine contractions [Articolo su rivista]
Facchinetti, Fabio; Neri, Isabella; Genazzani, Andrea Riccardo

In order to investigate the role of nitric oxide in preterm labor, 10 women presenting with preterm onset of uterine contractions were infused with L-Arginine. In comparison to saline infusion, L-Arginine significantly reduced the number of contractions, together with an increase of both serum growth hormone and nitrates levels. These findings demonstrate that the enhancement of endogenous nitric oxide production through its physiological donor, L-Arginine, is able to transiently reduce preterm uterine spontaneous contractility.

Bono, G; Neri, Isabella; Granella, F; Genazzani, Ar; Facchinetti, Fabio

The aims of this study were to evaluate the relationships occurring between pain complaints and postmenopausal status, and to look at the correlation between such complaints and other symptoms commonly related to the climacterium A clinical sample of 99 consecutive postmenopausal patients requiring medical help were studied: 36 complained of muscle-skeletal pains whereas 33 presented with headache limiting daily activity Climacteric syndrome, level of distress, coping style and bone mineral density were assessed with appropriate questionnaires and instruments. Neither bone mineral density, nor body mass index nor time since menopause were associated with either headaches or muscle-skeletal pains. According to the logistic regression being younger, being without a job, suffering from insomnia and having a lower ability in self-support by the means of comforting ideas predicts suffering from headache. A high level of distress and an avoidance behavior to problem facing predict the presence of pain complaints. In such cases the ineffectiveness of the coping mechanism (i.e. avoid the problem) could be the reason for the increased level of psychological distress. These findings indicate that complaining of pains or headache is not dependent upon postmenopausal status. Individual coping strategies and their effectiveness seem the main reasons for the presence of disabling musculoskeletal pains or headache.

Facchinetti, Fabio; Neri, Isabella; Genazzani, Ar

The aim of this study is the evaluation of predictive factors in the onset of labour after pre-induction cervical ripening with prostaglandins. We enrolled 112 consecutive singleton term pregnancies (37-42.3 weeks) with unfavourable cervix and intact membranes, requiring induction of labour because prolonged pregnancy (59%) or maternal/fetal complications (41%). Treatment consisted of the cervical application (once or twice, 12 h apart) of prostaglandin E(2) gel (Upjohn, Italy). Uterine activity was monitored by external cardio-tocography before and during the next 2 h. Two patients showed uterine hyperstimulation and acute fetal distress requiring caesarean section. Sixty percent of patients went to labour and delivered without further stimulations. In this group the rate of caesarean section (9.1%) was lower than in patients failing to onset labour (68.2%). According to the logistic regression three factors positively predicted the onset of labour: first-hour uterine contractility, basal uterine activity and gestational age. The first-hour contractility in particular, represents the myometrial sensitivity to prostaglandin E(2) and may become a practical marker of spontaneous onset of labour in patients undergoing cervical ripening.

Neri, Isabella; G. C., Di Renzo; G., Caserta; A., Gallinelli; Facchinetti, Fabio


1994 - Menstrual-related mood changes in patients with oligomenorrhea. [Articolo su rivista]
Facchinetti, Fabio; Neri, Isabella; M., Fava; A. R., Genazzani

In order to evaluate the role of negative anticipation on self-report of premenstrual symptoms, we studied 13 oligomenorrheic and 12 control women with regular menses. Both hormonal and psychological measures (using the Symptom Rating Test) were obtained once a week for 5-9 weeks. The presence of ovulatory cycles was confirmed by progesterone levels > or = 3.0 ng/ml. In both groups, there was a significant increase in the total Symptom Rating Test score during the premenstrual phase with respect to the intermenstrual period. As far as specific symptoms were concerned, MANOVA showed significant premenstrual fluctuations in anxiety, depression, somatic symptoms, and inadequacy in both groups. These results suggest that premenstrual discomfort may be unrelated to both cycle length and negative anticipation of one's menses.

1994 - Opioid peptide modulation of stress-induced plasma steroid changes in the frog Rana esculenta. [Articolo su rivista]
G., Mosconi; O., Carnevali; Facchinetti, Fabio; Neri, Isabella; A., Polzonetti Magni

The present paper aims to evaluate whether a neuroendocrine system including opioids accounts for the effects of stress in the frog, Rana esculenta. Using an acute-stress paradigm, the involvement of hypothalamic opioid peptides was investigated biochemically as well as by in vivo studies. HPLC and RIA investigations confirm the presence of beta-endorphin-like peptides in the brain of this frog. Several immunoreactive peaks are present, two of them coeluting with beta-endorphin and acetyl beta-endorphin reference peptides. Quantitative evaluation revealed that the beta-EP content of 24-hr captured animals was higher than that in fresh captured ones. The stress paradigm applied here was consistent with the measurement of plasma androgens and corticosterone levels in females after short-captivity confinement. In comparison with fresh-captured animals, a sharp decrease of these levels was found within 10-24 hr after capture. These effects were reversed by naltrexone, a long-acting opioid antagonist, after 24 hr of treatment. In fact, in the captive animals injected with 100 ng of naltrexone, the plasma androgen titers remained low at the 10th hour postcapture, but rose to the control levels within 24 hr. A similar effect was found for the plasma corticosterone levels. These data demonstrate that, in this anuran, endogenous opioids could mediate the stress-induced inhibition of gonadal function, and perhaps the inhibition of the hypothalamus-pituitary-adrenal axis.

1993 - Characteristics of headache at menopause: a clinico-epidemiologic study. [Articolo su rivista]
Neri, Isabella; F., Granella; R., Nappi; G. C., Manzoni; Facchinetti, Fabio; A. R., Genazzani

The prevalence and characteristics of primary headaches in a large sample of postmenopausal women were investigated. Seventy-six out of 556 women (13.7\%) were affected by headache of either the migraine or tension type. In 82\% of cases onset had preceded the menopause. The postmenopausal course of headaches with a premenopausal onset differed according to type of headache and type of menopause. Indeed, while migraine improved in almost two-thirds of cases, tension-type headache worsened or did not change in 70\% of cases. However, in women who had undergone surgical ovariectomy, the natural course of migraine was worse than in those who had a physiological menopause (P = 0.003). Among the symptoms covered by the Kuppermann Index, only anxiety and insomnia were correlated with headache. The favourable course of migraine in the postmenopausal period can be attributed primarily to the absence of variations in sex hormone levels although psychological factors also seem to play a fundamental role.

1993 - Ovarian melanotropic peptides in two teleostean fishes. [Articolo su rivista]
Facchinetti, Fabio; A., Polzonetti Magni; Neri, Isabella; A., Gallinelli; G., Alessandrini; M., Vallarino


1993 - The association of menstrual migraine with the premenstrual syndrome. [Articolo su rivista]
Facchinetti, Fabio; Neri, Isabella; E., Martignoni; L., Fioroni; G., Nappi; A. R., Genazzani

To investigate the comorbidity of premenstrual syndrome (PMS) and menstrual migraine, the Menstrual Distress Questionnaire (MDQ) was prospectively administered for two consecutive menstrual cycles to 22 patients with menstrual migraine, 12 cases with migraine without aura and 15 patients with PMS. MDQ scores varied throughout the menstrual cycle in each patient group, the wider changes being shown by patients with PMS. Fourteen menstrual migraine patients and 4 migraine without aura patients achieved diagnostic criteria for PMS over two menstrual cycles. In these patients MDQ scores did not differ from PMS sufferers at any stage of the menstrual cycle. The premenstrual increase of each cluster of PMS symptoms was identical in menstrual migraine and PMS subjects with the exception of negative affect. We suggest that PMS symptoms should be taken into account in the IHS diagnostic criteria for menstrual migraine.

1992 - Psychosomatic disorders related to gynecology. [Articolo su rivista]
Facchinetti, Fabio; K., Demyttenaere; L., Fioroni; Neri, Isabella; A. R., Genazzani

In this paper current issues on four psychosomatic disorders related to gynecology will be reviewed. The history, nosological problems and psychoneuroendocrine correlates of psychogenic amenorrhea have been summarized taking into account the important role of psychological factors in inducing loss of menses. Definition and diagnostic problems in assessing menstrually related disorders (formerly premenstrual syndrome) have been reviewed, looking at this syndrome as a disorder of adaptation to the cyclical changes of neuroendocrine functions. The impact of stress on fertility and, on the other hand, the effects of infertility on psychological well-being have been pointed out trying to ascertain the pathways involved in these mutual relationships. Finally, the issue of mood changes at menopause and the effects of steroid replacement on affective state have been discussed. As a whole, these evidences indicate the importance of a close cooperation between gynecologist and psychiatrist in the management of gynecological disorders.

Martignoni, E; Neri, Isabella; Granella, F; Manzoni, Gc; Facchinetti, Fabio; Genazzani, Ar


Sances, G; Neri, Isabella; Nappi, Re; Sacco, S; Martignoni, E.