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To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). A prospective European multicenter observational study included women with a singleton pregnancy, 32 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.ZIEL: Beurteilung der longitudinalen Variation der umbilikozerebralen Ratio (UCR) der Pulsatilitätsindizes bei später fetaler Wachstumsrestriktion (FGR). Eine prospektive europäische multizentrische Beobachtungsstudie schloss Frauen mit Einlingsschwangerschaft (32 856 Frauen hatten 2770 Messungen; 696 (81 %) hatten mehr als eine Messung (Median 3, IQR 2–4). Bei Einschluss hatten 63 (7 %) eine UCR ≥ 0,9. Diese entbanden früher und hatten ein niedrigeres Geburtsgewicht und eine höhere Inzidenz für einen unerwünschten Outcome (30 % vs. 9 %, relatives Risiko 3,2; 95 %-KI 2,1–5,0) im Vergleich zu Frauen mit normaler UCR bei Einschluss. Wiederholte Messungen nach abnormaler UCR bei Einschluss waren in 67 % (95 %-KI 55–80) erneut abnormal, aber nach einer normalen UCR betrug die Wahrscheinlichkeit, eine abnormale UCR zu finden, 6 % (95 %-KI 5–7 %). Das Risiko für einen kombinierten unerwünschten Outcome war ähnlich, wenn man den ersten oder den nachfolgenden UCR-Wert verwendete. Eine abnormale UCR ist wahrscheinlich bei einer späteren Messung wieder abnormal, während nach einer normalen UCR die Wahrscheinlichkeit einer abnormalen UCR bei wöchentlicher Wiederholung 5–7 % beträgt. Wiederholte Messungen sagen das Ergebnis nicht besser voraus als die erste Messung, was höchstwahrscheinlich darauf zurückzuführen ist, dass die am stärksten gefährdeten Föten nach einer abnormalen UCR entbunden werden.

Introduction The aim of our study is to describe the management of a maternity ward in a referral center during the COVID-19 pandemic and 2020 lockdown. Methods This is a retrospective single-center study. We analyzed the records of all women consecutively admitted to our delivery ward during lockdown and compared them with those of women admitted in the same period in 2019. Results The number of patients (1260) admitted to our department in 2020 was similar (1215) to that in 2019. Among patients admitted during lockdown, 50 presented with a Sars-CoV-2 infection (3.9%). In 2020, the number of antenatal check-ups was lower than in 2019 [7.9 (1.5) vs 8.2 (1.3), p

Introduction We investigated association between sociodemographic characteristics and COVID‐19 disease among pregnant women admitted to our unit, the largest high‐risk maternity unit in the Milan metropolitan area. Methods Between March 1, 2020 and April 30, 2020, 896 pregnant women were admitted to our Institution and tested for COVID‐19. We collected information regarding their sociodemographic characteristics. Additional information on geographical area of residence, number of family members, number of family members tested positive for COVID‐19, and clinical data was collected for women tested positive for COVID‐19. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of developing COVID‐19 according to sociodemographic characteristics were estimated by unconditional logistic regression models. Results Among the 896 women enrolled, 50 resulted positive for COVID‐19. Pregnant women aged ≥35 years had a significantly lower risk of developing the infection (crude OR = 0.29; 95% CI:0.16–0.55). Conversely, foreign women (crude OR = 3.32; 95% CI:1.89–5.81), unemployed women (crude OR = 3.09; 95% CI: 1.77–5.40), and women with an unemployed partner (crude OR = 3.16; 95% CI: 1.48–6.79) showed a significantly higher risk of infection. Ethnicity was positively associated with the risk of developing COVID‐19 (mutually adjusted OR = 2.15; 95% CI:1.12–4.11) in the multivariate analysis. Foreign women with COVID‐19 were more likely to have a lower education level (p

To evaluate fetal ventricular diastolic function in pregnancies of women with gestational diabetes (GD), to determine whether minimal anomalies of glucose metabolism may influence fetal cardiac function. Fetal ventricular filling time was measured by transabdominal ultrasound in singleton pregnancies between 34 and 37 weeks of gestation. We used a measurement which consists in the ratio between the diastolic time and the whole cardiac cycle time. The study included 35 women with a GD and 217 non-diabetic. Right ventricular filling time (RVFT) was significantly lower in the GD group (mean of RVFT = 39.2 ± 4.4 vs 43.6 ± 4.6; p < 0.01). Likewise, left ventricular filling time (LVFT) was shorter in the GD group compared to the non-GD group, though the difference was not significant (mean of LVFT = 43.6 ± 4.6 vs 44.6 ± 5.5; p = 0.33). Fetal right cardiac function is altered also in pregnancies where gestational diabetes is well controlled.

OBJECTIVE: In this study we describe the management of women with gestational diabetes (GD) and an ongoing Sars-Cov-2 infection. The aim of the study is to evaluate whether the COVID-19 infection can further complicate pregnancies and thus if the protocol we usually use for GDM pregnancies is also applicable to patients who have contracted a Sars-Cov-2 infection. METHODS: This is a retrospective study analysing all pregnant women with gestational diabetes and a concomitant COVID-19 infection admitted to our Institution for antenatal care between March 1st and April 30th 2020. RESULTS: Among pregnant women with GD and a concomitant COVID-19 infection, the mean age was 32,9 (SD 5,6) years. Two patients (33%) were of Caucasian ethnicity while four (67%) were non-Caucasian. All patients were diagnosed with COVID-19 during the third trimester of pregnancy. Two women were asymptomatic while four were symptomatic. Only two patients (33,3%) received treatment with insulin. None of the patients required intensive care or mechanical ventilation. No complications were found among the newborns. CONCLUSION: the COVID-19 infection was not found to worsen the prognosis of GD patients or of their offspring. Glycaemic monitoring, diet therapy and insulin, when needed, are sufficient for a good metabolic control and a favourable maternal and fetal outcome.

Folate (vitamin B9) is widely accepted to protect against fetal neural tube defects. The main sources of dietary folate are folic acid-fortified foods and folic acid-containing dietary supplements. However, folic acid is inactive in the human body and must be converted by the liver into the active molecule 5-methyltetrahydrofolate (5-MTHF). 5-MTHF functions as a methyl donor in many metabolic reactions, including the conversion of homocysteine into methionine, the biosynthesis of glycine from serine, and the biosynthesis of DNA precursor molecules. Therefore, folate is fundamental for growth, especially in the embryonic and fetal stages. Prescription of folic acid to women in the preconception period and during pregnancy is a consolidated practice. However, it can pose health risks in certain conditions, such as megaloblastic anemia, where it will conceal megaloblastic anemia due to vitamin B12 deficiency and in cases of reduced hepatic transformation of folic acid (e.g. due to genetic variants or during some pharmacotherapies). Some of these risks can be avoided by supplementation with 5-MTHF rather than folic acid. Because 5-MTHF does not require activation, it is immediately available to mother and fetus and does not accumulate in blood like folic acid does in cases of reduced hepatic transformation. This paper reviews the advantages and disadvantages of folate supplementation with folic acid versus 5-MTHF, with a focus on maternal and fetal health.

In the context of SARS-CoV-2 pandemic, the hospital management of mother-infant pairs poses to obstetricians and neonatologists previously unmet challenges. In Lombardy, Northern Italy, 59 maternity wards networked to organise the medical assistance of mothers and neonates with suspected or confirmed SARS-CoV-2 infection. Six “COVID-19 maternity centres” were identified, the architecture and activity of obstetric and neonatal wards of each centre was reorganised, and common assistance protocols for the management of suspected and proven cases were formulated. Here, we present the key features of this reorganization effort, and our current management of the mother-infant dyad before and after birth, including our approach to rooming-in practice, breastfeeding and neonatal follow-up, based on the currently available scientific evidence. Considered the rapid diffusion of COVID-19 all over the world, we believe that preparedness is fundamental to assist mother-infant dyads, minimising the risk of propagation of the infection through maternity and neonatal wards.

Objectives aPL, the serum biomarkers of APS, are the most common acquired causes of pregnancy morbidity (PM). This study investigates the impact of aPL positivity fulfilling classification criteria (‘criteria aPL’) and at titres lower than thresholds considered by classification criteria (‘low-titre aPL’) on PM and assesses the effectiveness of low-dose aspirin (LDASA), low molecular weight heparin (LMWH) and HCQ in reducing the probability of PM (PPM). Methods Longitudinal data on 847 pregnancies in 155 women with persistent aPL at any titre and 226 women with autoimmune diseases and negative aPL were retrospectively collected. A generalized estimating equations model for repeated measures was applied to quantify PPM under different clinical situations. Results EUREKA is a novel algorithm that accurately predicts the risk of aPL-associated PM by considering aPL titres and profiles. aPL significantly impact PPM when at low titres and when fulfilling classification criteria. PPM was further stratified upon the aPL tests: aCL IgG/IgM and anti-β2-glycoprotein I (β2GPI) IgM, alone or combined, do not affect the basal risks of PPM, an increase occurs in case of positive LA or anti-β2GPI IgG. LDASA significantly affects PPM exclusively in women with low-titre aPL without anti-β2GPI IgG. The LDASA + LMWH combination significantly reduces PPM in all women with low-titre aPL and women with criteria aPL, except those carrying LA and anti-β2GPI IgG. In this group, the addition of HCQ further reduces PPM, although not significantly. Conclusion EUREKA allows a tailored therapeutic approach, impacting everyday clinical management of aPL-positive pregnant women.

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hipertensió gestacional; Preeclampsia Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hipertension gestacional; Preeclampsia Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Gestational hypertension; Preeclampsia Background It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. Objective This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. Study Design This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21 st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. Results We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32–2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25–2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17–3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99–2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99–5.49) and 6.26 (95% confidence interval, 4.35–9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63–2.86; risk ratio, 2.53; 95% confidence interval, 1.44–4.45; and risk ratio, 2.84; 95% confidence interval, 1.67–4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32–2.35), 2.07 (95% confidence interval, 1.20–3.57), and 2.77 (95% confidence interval, 1.66–4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. Conclusion COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19. The study was supported by the COVID-19 Research Response Fund from the University of Oxford (Ref 0009083). A.T.P. is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the National Institute for Health Research (NIHR) Biomedical Research Centre funding scheme. The funding organization had no involvement in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication.

INTRODUCTION The objective of the present study is to compare the sonographic measurement of subcutaneous adipose thickness and visceral adipose thickness during 1st trimester screening for aneuploidies between non-diabetic pregnant women and patients who develop 1st trimester or 2nd trimester gestational diabetes mellitus (GDM). MATERIAL AND METHODS Adipose thickness was measured by transabdominal ultrasound imaging in pregnant women attending our clinic for screening for fetal aneuploidies between 11 and 13 weeks of gestation. During the 1st trimester all patients were evaluated for fasting glycemia in accordance with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations. Patients with confirmed fasting glycemia (FPG) ≥92 mg/dL were diagnosed as 1st trimester GDM. Patients with FPG

OBJECTIVE To determine variations in cord blood gas (CBG) parameters after 3-minute delayed cord clamping (DCC) in vaginal deliveries (VDs) and caesarean deliveries (CDs) at term without fetal distress. DESIGN Prospective observational study. SETTING University hospital. SAMPLE CBG from 97 VDs and 124 CDs without fetal distress. METHODS Comparison of paired arterial-venous CBG parameters drawn at birth from the unclamped cord and after 3-minutes DCC for VDs and CDs. MAIN OUTCOME MEASURES Base excess, bicarbonate, haematocrit and haemoglobin from both arterial and venous cord blood, lactate, neonatal outcomes, partial pressure of oxygen (pO2 ), partial pressure of carbon dioxide (pCO2 ), pH, and postpartum haemorrhage. RESULTS Arterial cord blood pH, bicarbonate ( HCO3- , mmol/l), and base excess (BE, mmol/l) decreased significantly after 3-minute DCC both in VDs (pH = 7.23 versus 7.27; P

To assess the added value of Doppler parameters, maternal history, and intrapartum clinical characteristics for the prediction of emergency delivery due to non-reassuring fetal status in low-risk pregnancies.This was a prospective cohort of low-risk pregnancies undergoing ultrasound assessment at 40 weeks' gestation within 7 days of delivery. The main outcome was emergency cesarean section due to non-reassuring fetal status. The association between Doppler parameters, intrapartum clinical characteristics, and maternal history was performed by logistic regression. The predictive performance of the constructed models was assessed by receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC).From 403 included pregnancies, 18.6% (In low-risk pregnant woman at term, the addition of MCA Z-score to a previous model comprising maternal history and intrapartum clinical findings, significantly improves the prediction of emergency delivery due to non-reassuring fetal status.

The ductus venosus plays a critical role in circulatory adaptation to hypoxia in fetal growth restriction but the mechanisms still remain controversial. Increased shunting of blood through the ductus venosus under hypoxic conditions has been shown in animal and human studies. The hemodynamic laws governing the accelerated flow in this vessel suggest that any dilation at its isthmus, which increases the blood flow shunting to the heart, is associated with a low, absent or reversed a-wave and a high pulsatility index. Cardiac dysfunction associated with increased atrial pressure as well as reduced ventricular compliance might be predominant mechanisms determining the profile of ductus venosus velocity waveforms in severe fetal growth restriction with signs of hypoxic compromise. Understanding the pathophysiology of the ductus venosus will underpin translation of the hypotheses developed through biostatistics toward explaining with more confidence Doppler changes in the fetal circulation in predicting clinical outcomes.

Background Evidence on the outcome of SARS-CoV-2 infection in pregnancy is generally reassuring but yet not definitive. Methods To specifically assess the impact of SARS-CoV-2 infection in late pregnancy, we prospectively recruited 315 consecutive women delivering in a referral hospital located in Lombardy, Italy in the early phase of the epidemic. Restriction of the recruitment to this peculiar historical time period allowed to exclude infections occurring early in pregnancy and to limit the recall bias. All recruited subjects underwent a nasopharyngeal swab to assess the presence of Sars-Cov-2 using Real-time PCR. In addition, two different types of antibodies for the virus were evaluated in peripheral blood, those against the spike proteins S1 and S2 of the envelope and those against the nucleoprotein of the nucleocapsid. Women were considered to have had SARS-CoV-2 infection in pregnancy if at least one of the three assessments was positive. Results Overall, 28 women had a diagnosis of SARS-CoV-2 infection in pregnancy (8.9%). Women diagnosed with the infection were more likely to report one or more episodes of symptoms suggestive for Covid-19 (n = 11, 39.3%) compared to unaffected women (n = 39, 13.6%). The corresponding OR was 4.11 (95%CI: 1.79–9.44). Symptoms significantly associated with Covid-19 in pregnancy included fever, cough, dyspnea and anosmia. Only one woman necessitated intensive care. Pregnancy outcome in women with and without SARS-CoV-2 infection did not also differ. Conclusions SARS-CoV-2 infection is asymptomatic in three out of five women in late pregnancy and is rarely severe. In addition, pregnancy outcome may not be markedly affected.

Introduction A potential complication of term prelabor rupture of membranes (term PROM) is chorioamnionitis with an increased burden on neonatal outcomes of chronic lung disease and cerebral palsy. The purpose of the study was to analyze the efficacy of a standing clinical protocol designed to identify women with term PROM at low risk for chorioamnionitis, who may benefit from expectant management, and those at a higher risk for chorioamnionitis, who may benefit from early induction. Material and methods This retrospective study enrolled all consecutive singleton pregnant women with term PROM. Subjects included women with at least one of the following factors: white blood cell count ≥ 15×100/μL, C-reactive protein ≥ 1.5 mg/dL, or positive vaginal swab for beta-hemolytic streptococcus. These women comprised the high risk (HR) group and underwent immediate induction of labor by the administration of intravaginal dinoprostone. Women with none of the above factors and those with a low risk for chorioamnionitis waited for up to 24 hours for spontaneous onset of labor and comprised the low-risk (LR) group. Results Of the 884 consecutive patients recruited, 65 fulfilled the criteria for HR chorioamnionitis and underwent immediate induction, while 819 were admitted for expectant management. Chorioamnionitis and Cesarean section rates were not significantly different between the HR and LR groups. However, the prevalence of maternal fever (7.7% vs. 2.9%; p = 0.04) and meconium-stained amniotic fluid was significantly higher in the HR group than in LR group (6.1% vs. 2.2%; p = 0.04). This study found an overall incidence of 4.2% for chorioamnionitis, 10.9% for Cesarean section, 0.5% for umbilical artery blood pH < 7.10, and 1.9% for admission to the neonatal intensive care unit. Furthermore, no confirmed cases of neonatal sepsis were encountered. Conclusions A clinical protocol designed to manage, by immediate induction, only those women with term PROM who presented with High Risk factors for infection/inflammation achieved similar maternal and perinatal outcomes between such women and women without any risks who received expectant management. This reduced the need for universal induction of term PROM patients, thereby reducing the incidence of maternal and fetal complications without increasing the rate of Cesarean sections.

The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the pathophysiology of the placenta and its impact on pregnancy outcome has not yet been fully elucidated. Here, we present a comprehensive clinical, morphological, and molecular analysis of placental tissues from pregnant women with and without SARS-CoV-2 infection. SARS-CoV-2 could be detected in half of placental tissues from SARS-CoV-2-positive women. The presence of the virus was not associated with any distinctive pathological, maternal, or neonatal outcome features. SARS-CoV-2 tissue load was low in all but one patient who exhibited severe placental damage leading to neonatal neurological manifestations. The placental transcriptional response induced by high viral load of SARS-CoV-2 showed an immunopathology phenotype similar to autopsy lung tissues from patients with severe coronavirus disease 2019. This finding contrasted with the lack of inflammatory response in placental tissues from SARS-CoV-2-positive women with low viral tissue load and from SARS-CoV-2-negative women. Importantly, no evidence of vertical transmission of SARS-CoV-2 was found in any newborns, suggesting that the placenta may be an effective maternal-neonatal barrier against the virus even in the presence of severe infection. Our observations suggest that severe placental damage induced by the virus may be detrimental for the neonate independently of vertical transmission.

Background: Evidence on the outcome of Covid-19 in pregnancy is generally reassuring but yet not definitive. Methods: To specifically assess the impact of Covid-19 in the second half of pregnancy, we prospectively recruited 315 consecutive women delivering in a referral hospital located in Lombardy, Italy in the early phase of the epidemic. Restriction of the recruitment to this peculiar historical time period allowed to exclude infections occurring early in pregnancy and to limit the recall bias. All recruited subjects underwent a nasopharyngeal swab to assess the presence of Sars-Cov-2 using Real-time PCR. In addition, two different types of antibodies for the virus were evaluated in peripheral blood, those against the spike proteins S1 and S2 of the envelope and those against the nucleoprotein of the nucleocapsid. Women were considered to have had Covid-19 in pregnancy if at least one of the three assessments was positive. Results: Overall, 28 women had a diagnosis of Covid-19 in pregnancy (8.9%). Women diagnosed with the infection were more likely to report one or more episodes of symptoms suggestive for Covid-19 (n=11, 39.3%) compared to unaffected women (n=39, 13.6%). The corresponding OR was 4.11 (95%CI: 1.79-9.44). Symptoms significantly associated with Covid-19 in pregnancy included fever, cough, dyspnea and anosmia. Only one woman necessitated intensive care. Pregnancy outcome in women with and without Covid-19 did not also differ. Conclusions: Covid-19 is asymptomatic in three out of five women in the second half of pregnancy and is rarely severe. In addition, pregnancy outcome may not be significantly affected.

The placental methylation pattern is crucial for the regulation of genes involved in trophoblast invasion and placental development, both key events for fetal growth. We investigated LINE-1 methylation and methylome profiling using a methylation EPIC array and the targeted methylation sequencing of 154 normal, full-term pregnancies, stratified by birth weight percentiles. LINE-1 methylation showed evidence of a more pronounced hypomethylation in small neonates compared with normal and large for gestational age. Genome-wide methylation, performed in two subsets of pregnancies, showed very similar methylation profiles among cord blood samples while placentae from different pregnancies appeared very variable. A unique methylation profile emerged in each placenta, which could represent the sum of adjustments that the placenta made during the pregnancy to preserve the epigenetic homeostasis of the fetus. Investigations into the 1000 most variable sites between cord blood and the placenta showed that promoters and gene bodies that are hypermethylated in the placenta are associated with blood-specific functions, whereas those that are hypomethylated belong mainly to pathways involved in cancer. These features support the functional analogies between a placenta and cancer. Our results, which provide a comprehensive analysis of DNA methylation profiling in the human placenta, suggest that its peculiar dynamicity can be relevant for understanding placental plasticity in response to the environment.

Introduction: Trophoblastic invasion and placental growth are critical for pregnancy outcome. The placental volume can be assessed by 3 D ultrasound using Virtual Organ Computer-aided Analysis (VOCAL). Epidemiological and clinical data suggest that there are two different clinical phenotypes of hypertensive disorders of pregnancy (HDP) that coexist at any gestational age: HDP associated to fetal growth impairment and HDP associated to appropriate for gestational age fetal growth. The aim of this study was to determine whether placental volume in the first trimester of pregnancy differs between women with HDP associated or not to fetal growth impairment and uncomplicated pregnancies. Methods: This is a retrospective cross-sectional study of prospectively recruited data in which maternal characteristics, Doppler velocimetry of uterine arteries, and three-dimensional (3 D) volume of the placenta were collected at 11 + 1 − 13 + 6 gestational weeks. The placental quotient (PQ) was calculated as placental volume/crown rump length. Results: In a 2-year period, we prospectively collected first trimester data of 1322 women. For the purposes of this cross-sectional study, 57 women that delivered a SGA fetus, 34 that developed HDP-AGA, and six that developed HDP-SGA, respectively, were included in the study as cases. The control group was made of 117 uncomplicated pregnancies. The PQ was higher in women with uncomplicated pregnancies (PQ median 16.36 cm3/cm) than in all other study groups (PQ in SGA: 13.02 cm3/cm, p

BackgroundThe impact of the Covid-19 infection on patients with chronic endocrine disease is not fully known. We describe here the first case of a pregnant woman with Covid-19 acute infection and non-classical congenital adrenal hyperplasia (NCAH).Case descriptionA woman at 36 weeks of gestation was referred to our Maternity Hospital for premature rupture of membranes (PROM). Her medical history was positive for NCAH on chronic steroid replacement till the age of 17 years (cortisone acetate and dexamethasone, both in the morning). At admission, her naso-oro-pharyngeal swab resulted positive for SARS-CoV-2. Due to hyperpyrexia and late preterm PROM, cesarean section was planned, and she was started on a 100 mg-bolus of hydrocortisone, followed by continuous infusion of 200 mg/24 h. A female neonate in good clinical condition and with a negative nasopharyngeal Covid-19 swab was delivered. On secondpostpartumday, the mother was in good condition and was switched to oral steroid therapy. On thirdpostpartumday she worsened, with radiological signs of acute pulmonary embolism. Oro-tracheal intubation and mechanical ventilation were started, and she was switched back to intravenous steroid therapy. On April 30, pulmonary embolism was resolved, and on May 13th she was discharged in good condition.ConclusionsWe report the first case of Covid-19 acute infection that occurred in late-pregnancy in a woman with NCAH on chronic steroid replacement. The management of the patient in a reference center with early involvement of a multidisciplinary team granted prompt care and adequate protection for all the involved sanitary operators.

Objectives: This study aimed to present a statistical method for assessing potential differences between fetal growth standard curves and local curve population. Methods: This was an observational repeated measures longitudinal study. We used a simulation model to generate random distribution of the international population from the IG-21st for fetal AC using the original equations of means and standard deviations (SD) obtained by the fractional polynomial method. A general linear model (GLM) allowed us to calculate new equations originating from simulated intergrowth-21st data (SIM_IG21st) and to compare them, by visual inspection of the estimated coefficients and their 95% CI, with the original published. We used further GLMs for evaluating the goodness of fitting of our local curve and comparing the relative equations of means and SD with those of SIM_IG21st. Finally, the impact of percentile differences between the 2 curves was quantified. Results: SIM_IG21st data yielded very similar coefficients than those of IG-21st reference to such an extent that means and SD and percentiles of interest were identical to the original. The comparison between SIM_IG21st curve and local curves showed a nonsignificant intercept and a slight difference of the 2 slopes (GA and GA3) for the equations of the mean. As a result, the local curve resulted in greater AC values. A difference in the intercept but not in the slopes (GA2, GA3, and GA3 * lnGA) was instead reported for the equations of the SD. In the percentile comparison, the local curve resulted in an overestimation of the 3rd and the 10th percentile that corresponded to the 4th and 12th percentiles of SIM_IG21st, respectively. Conclusion: This statistical method allows sonographers to assess potential differences between standard curves and local curve population, enabling a more proper identification of abnormal growth trajectories.

Background Maternal dietary habits are contributors of maternal and fetal health; however, available data are heterogeneous and not conclusive. Methods Nutrient intake during pregnancy was assessed in 503 women with uncomplicated pregnancies, using the validated Food Frequency Questionnaire developed by the European Prospective Investigation into Cancer and Nutrition (EPIC-FFQ). Results In all, 68% of women had a normal body mass index at the beginning of pregnancy, and 83% of newborns had an appropriate weight for gestational age. Maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and placental weight were independently correlated with birth weight. GWG was not related to the pre-pregnancy BMI. EPIC-FFQ evaluation showed that 30% of women adhered to the European Food Safety Authority (EFSA) ranges for macronutrient intake. In most pregnant women (98.1%), consumption of water was below recommendations. Comparing women with intakes within EFSA ranges for macronutrients with those who did not, no differences were found in BMI, GWG, and neonatal or placental weight. Neither maternal nor neonatal parameters were associated with the maternal dietary profiles. Conclusions In our population, maternal pre-pregnancy BMI, GWG, and placental weight are determinants of birth weight percentile, while no association was found with maternal nutrition. Future studies should explore associations through all infancy. Impact Maternal anthropometrics and nutrition status may affect offspring birth weight. In 503 healthy women, maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and placental weight were independently correlated to neonatal birth weight. GWG was not related to the pre-pregnancy BMI. In all, 30% of women respected the EFSA ranges for macronutrients. Neither maternal nor neonatal parameters were associated with maternal dietary profiles considered in this study. Maternal pre-pregnancy BMI, GWG, and placental weight are determinants of neonatal birth weight percentile, while a connection with maternal nutrition profiles was not found.

Recent evidence supports elective induction of labor at 39 weeks in low-risk pregnancies to improve maternal and perinatal outcomes. This evidence includes the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management). However, concerns have been raised on the external validity of the ARRIVE trial, especially with regard to the demographic and clinical characteristics of the pregnant women recruited.This study compared the outcomes in a cohort of consecutive pregnant women, who fulfilled the criteria of the ARRIVE trial and were managed expectantly in an Italian referral academic hospital, with those reported in the expectant and induction arms of the ARRIVE trial.This was a retrospective single-center study. Consecutive low-risk nulliparous women who fulfilled the ARRIVE trial criteria were evaluated for eligibility at 36-38 weeks of gestation. Those who neither developed complications nor delivered spontaneously before 39 weeks were eligible for this comparative analysis. Maternal and fetal growth and wellbeing were screened and monitored from 36 to 38 weeks of gestation.A total of 1696 patients met the established criteria at recruitment. Of these, 343 spontaneously delivered in39 weeks, 82 delivered because of maternal indication, and 37 for fetal indication. A total of 1234 pregnant women were eligible for comparison with the elective induction and the expectant management groups of the ARRIVE trial. The socioeconomic status was significantly better, maternal age was significantly higher, and body mass index was significantly lower in our cohort. Cesarean section rate in our cohort was lower than that of the expectant group of the ARRIVE trial (18.7 vs. 22.2%;In our cohort, expectant management in low-risk pregnancies with late preterm screening of feto-maternal well-being seemed to achieve better maternal and perinatal outcomes than a universal policy of induction at 39 weeks. The results of the ARRIVE trial should be carefully evaluated in different demographic and clinical settings and cannot be extended to the general population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global health emergency [1, 2], with Lombardy being the epicenter of this outbreak in Italy [3].

Coronavirns disease 2019 is a pandemic viral disease affecting also obstetric patients and uncertainties exist about the prognostic role of inflammatory biomarkers and hemocytometry values in patients with this infection. To clarify that, we assessed the values of several inflammatory biomarkers and hemocytometry variables in a cohort of obstetric patients hospitalized with coronavirus disease 2019 and we correlated the values at admission with the need of oxygen supplementation during the hospitalization. Overall, among 27 (61%) pregnant women and 17 (39%) post-partum women, 6 (14%) patients received oxygen supplementation and 2 (4%) required admission to intensive care unit but none died. During hospitalization neutrophils (p=0.002), neutrophils to lymphocytes ratio (p=0.037) and C reactive protein (p

Evidence on the prevalence and outcome of Covid-19 in pregnancy is yet inconclusive. To draw more information on this issue, we prospectively recruited 315 consecutive women delivering in a referral hospital located in Lombardy, Italy and evaluated the proportion of women who had Covid-19 in pregnancy. All recruited subjects underwent a nasopharyngeal swab to assess the presence of Sars-Cov-2 using Real-time PCR. In addition, two different type of antibodies for the virus were evaluated in peripheral blood, those against the spike proteins S1 and S2 of the envelope and those against the nucleoprotein of the nucleocapsid. Women were considered to have had Covid-19 in pregnancy if at least one of the assessment was positive. Overall, 28 women had a diagnosis of Covid-19 in pregnancy (8.9%, 95%CI: 6.2-12.5%), in line with the local general population. Women diagnosed with the infection were more likely to report one or more episodes of symptoms suggestive for Covid-19 (n=11, 39.3%) compared to unaffected women (n=39, 13.6%). The corresponding OR was 4.11 (95%CI: 1.79-9.44). Symptoms significantly associated with Covid-19 in pregnancy included fever, cough, dyspnea and anosmia. Only one woman necessitated intensive care. No maternal deaths occurred. Pregnancy outcome in women with and without Covid-19 did not also differ. In conclusion, women in the second half of pregnancy do not appear to be more susceptible to Covid-19 and its complications. In addition, the study suggests that pregnancy outcome may not be significantly affected.

Introduction We investigated the role of body mass index (BMI) and maternal age on the risk of late-term induction, prolonged induction time and caesarean section (CS) after induction. Material and Methods This is a retrospective, observational study. All women without any fetal or maternal pathological condition, uterine scars or any other indication for an elective caesarean birth and had a singleton foetus in the cephalic position at term were included. Results A total of 4006 women had a spontaneous onset of labour and 612 were induced for a late-term pregnancy. Labour induction was significantly more common in overweight (Adj Odds Ratio (OR) 1.48 95%CI 1.22–1.78) and obese (Adj OR 1.63 95%CI 1.24–2.14) women. Among induced women, a BMI ≥ 30 was a risk factor for a prolonged induction time in both nulliparous (AdjOR 2.4, 95%CI 1.02–5.67) and multiparous women (AdjOR 4.24, 95%CI 1.02–17.6). A BMI > 25–29.9 was significantly associated with a prolonged induction time only in nulliparous women (AdjOR 1.86 95%CI 1.05–3.30). A CS was more frequent in overweight (AdjOR 1.74, 95% CI 1.052.89) and obese women (AdjOR 2.72, 95%CI 1.42–5.25). Nulliparous women ageed 30–34 years had an induction time longer than women Conclusions The results of this study suggest that a BMI > 25 kg/m2 at term of pregnancy is a risk factor for the induction of labour during a late-term pregnancy, a prolonged induction time and higher caesarean section rate.

Objective To report mode of delivery and immediate neonatal outcome in women infected with COVID‐19. Design Retrospective study. Setting Twelve hospitals in northern Italy. Participants Pregnant women with COVID‐19‐confirmed infection who delivered. Exposure COVID 19 infection in pregnancy. Methods SARS‐CoV‐2‐infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co‐morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. Main outcome and measures Data on mode of delivery and neonatal outcome. Results In all, 42 women with COVID‐19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0–72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7–59.0) cases: in eight cases the indication was unrelated to COVID‐19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8–61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3–61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1–45.6) were admitted to a critical care unit. Two women with COVID‐19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS‐Cov‐2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. Conclusions Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS‐Cov‐2 transmission to the newborn. Tweetable abstract This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS‐Cov‐2 transmission to the newborn., Tweetable abstract This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS‐Cov‐2 transmission to the newborn. This article includes Author Insights, a video abstract available at https://vimeo.com/rcog/authorinsights16278

Rubinstein–Taybi syndrome is a rare genetic multisystem disorder with an estimated prevalence between 1 per 100,000–125,000 live births. Diagnosis is usually clinical and subsequent to birth. In fact, the rarity of the syndrome and the presence of aspecific morphologic anomalies make prenatal diagnosis challenging. The aim of our work is to analyze ultrasonographic findings, detectable with a combination of 2D and 3D techniques, which may increase the sensitivity of in utero diagnosis of this condition. We report a case of a sonographic prenatal diagnosis of broad and angulated thumbs and halluces and of an abnormal ductus venosus at 21 weeks of gestational age. These findings allowed us to suspect Rubinstein–Taybi syndrome. An accurate ultrasonographic examination may allow a prenatal diagnosis of those syndromes which are usually diagnosed after birth.

Objective: To evaluate the association between fetal growth restriction (FGR) and maternal hemodynamic parameters using multivariable analysis, adjusting for major confounding factors, such as hypertensive disorders of pregnancy (pre-eclampsia and gestational hypertension). Methods: A prospective cohort study was conducted between January 2013 and April 2016. Two cohorts of patients were recruited, between 24 and 39 weeks of gestation, in a high-risk outpatient setting. These cohorts comprised 49 appropriate-for-gestational-age singleton fetuses and 93 that were FGR (abdominal circumference (AC) at recruitment in the second half of pregnancy ≤ 10th percentile with a previous normal AC at 20–22 weeks). Maternal echocardiography was performed at the time of enrolment and included hemodynamic parameters of systolic and diastolic function and cardiac remodeling indices. Data were analyzed using a multivariable generalized linear model to estimate the association of FGR with maternal hemodynamic parameters after adjusting for significant confounding factors. Results: In the multivariable analysis, after adjustment for hypertensive disorders of pregnancy and smoking, FGR was associated with a 14% increase in maternal total vascular resistance, 16% reduction in cardiac output, 13% reduction in left ventricular mass and 11% reduction in heart rate; similar results were observed for the corresponding indexed parameters. Hypertensive disorders of pregnancy in the absence of FGR were associated with a 25% increase in total vascular resistance, 16% increase in left ventricular mass and 14% reduction in diastolic function; similar results were observed for the corresponding indexed parameters. Conclusion: FGR is significantly and independently associated with several maternal hemodynamic parameters, even after adjustment for major confounding factors, such as hypertensive disorders of pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

In response to the World Health Organization (WHO) statements and international concerns regarding the coronavirus disease 2019 (COVID-19) outbreak, FIGO has issued the following guidance for the management of pregnant women at the four main settings of pregnancy: (1) ambulatory antenatal care in the outpatient clinics; (2) management in the setting of the obstetrical triage; (3) intrapartum management; and (4) postpartum management and neonatal care. We also provide guidance on the medical treatment of pregnant women with COVID-19 infection.

Background Neonatal lupus syndrome is an acquired disease caused by the transplacental passage of anti-SSA/Ro antibodies. Congenital heart block (CHB) represent the most serious manifestation. The rate of CHB in anti-SSA/Ro positive pregnant woman varies among studies ranging from 1 to 5% in different populations. Aim of our study was to assess the prevalence of CHB in a cohort of anti-SSA/Ro positive pregnant women prospectively followed up in 2 Italian tertiary referral centers. Methods Patients underwent monthly clinical examination and data regarding the disease and pregnancy course were recorded. Moreover, fetal heart rates were assessed weekly by Doppler ultrasound from the 14th to the 26th gestational week. Results Between 2010 and 2018 we recorded data of 286 pregnancies, with the following maternal diagnosis: SLE in 73 (25.3%), Sjogren Syndrome in 52 (18%), undifferentiated connective tissue disease in 59 (20.6%), asymptomatic Ro/SSA carriers in 50 (17.4%) and other connective tissue disease in the remaining. In 5 pregnancies (1.7%) a third-degree CHB was diagnosed. In all these 5 pregnancies, anti-SSA/Ro positivity was established after CHB detection and the mothers were initially labeled as SSA/Ro carriers. Conclusions Even if the incidence of CHB as a whole was comparable to that reported in previous studies, none of the pregnancies prospectively followed before and during pregnancy developed CHB. These data suggest that a strict follow up and proper treatment of anti-SSA/Ro positive patients with an established autoimmune disease before and during pregnancy can reduce the risk.

Objectives The objective of this study was the analysis of B-Cell Activating Factor (BAFF) levels in pregnancies affected by PE, and in pregnancies affected by fetal growth restriction without Hypertensive disorders and its possible correlation with pulse wave velocity and cardiac output. Study design Prospective study of 69 women at 24–40 weeks gestation. Haemodynamic function was assessed in those with Pre-eclampsia (PE, n = 19), fetal growth restriction (FGR, n = 10) and healthy pregnancies (n = 40). Maternal venous BAFF levels at recruitment were measured using ELISA. We analysed the relationship between BAFF and cardiac output (CO), and BAFF and PWV (pulse wave velocity); the gold standard for assessing arterial stiffness. PWV was measured with an oscillometric device and CO using inert gas rebreathing technique. PWV and CO were converted to gestation adjusted indices (z scores). Main outcome measures The association between BAFF levels in PE and FGR, and the relationship of BAFF with PWV and CO. Results BAFF was higher in PE (p = 0.03) but not in FGR (p = 0.83) when compared to healthy pregnancies. There was a positive correlation between BAFF levels and z score PWV (r = 0.25, p = 0.04), but not CO (r = −0.01, p = 0.91). BAFF levels did not change with gestational age. (r = 0.012, p = 0.925). Conclusions These findings provide evidence of a possible contribution of BAFF to both maternal inflammation and arterial dysfunction associated with PE. Though no relationship was found with another disorder of placentation: normotensive FGR, this condition is not thought to be associated with maternal inflammation.

Introduction: Postpartum depression is commonly experienced by mothers worldwide and is associated with anxiety disorders, parenting stress, and other forms of distress, which may lead to a complex illness condition. Several studies have investigated the risk factors for this disorder, including biological and socio-demographic variables, medical and obstetric factors, and psychological and relational dimensions. The present study aimed to describe the psychological status of mothers up to 12 months postpartum, and to investigate the predictors of depressive symptoms at 12 months postpartum, considering obstetric factors along with psychological and relational variables. Methods: A sample of 137 women completed a questionnaire composed of a sheet on anamnestic and obstetric information and the following scales: Wijma Delivery Experience Questionnaire; State-Trait Anxiety Inventory; Edinburgh Postnatal Depression Scale; Parenting Stress Index (Short Form); Dyadic Adjustment Scale; and Multidimensional Scale of Perceived Social Support. Data were collected at four assessment times: 2–3 days, 3 months, 6 months, and 12 months postpartum. Results: Findings showed that the highest percentage of women with clinically significant symptoms of anxiety (state and trait) and depression was found at 12 months postpartum, which indicated that this was the most critical time. The quality of childbirth experience and trait anxiety at three months postpartum emerged as significant predictors of postpartum depression at 12 months. Conclusion: Our findings highlight the importance of providing stable programs (such as educational programs) to mothers in the first year postpartum. Furthermore, because the quality of the childbirth experience is one of the most important predictors of PPD at 12 months postpartum, effort should be made by healthcare professionals to guarantee a positive experience to all women to reduce possible negative long-term consequences of this experience.

Low molecular weight heparin has been extensively evaluated for the prevention of preeclampsia in high-risk pregnant women; however, the results from these trials have been conflicting. This review discusses the potential mechanisms of action of low molecular weight heparin for the prevention of severe preeclampsia, how to optimize the selection of high-risk women for participation in future trials, and the importance of trial standardization.