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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.

Objective: To develop a multi-step workflow for the isolation of circulating extravillous trophoblasts (cEVTs) by describing the key steps enabling a semi-automated process, including a proprietary algorithm for fetal cell origin genetic confirmation and copy number variant (CNV) detection. Methods: Determination of the limit of detection (LoD) for submicroscopic CNV was performed by serial experiments with genomic DNA and single cells from Coriell cell line biobank with known imbalances of different sizes. A pregnancy population of 372 women was prospectively enrolled and blindly analyzed to evaluate the current workflow. Results: An LoD of 800 Kb was demonstrated with Coriell cell lines. This level of resolution was confirmed in the clinical cohort with the identification of a pathogenic CNV of 800 Kb, also detected by chromosomal microarray. The mean number of recovered cEVTs was 3.5 cells per sample with a significant reverse linear trend between gestational age and cEVT recovery rate and number of recovered cEVTs. In twin pregnanices, evaluation of zygosity, fetal sex and copy number profiling was performed in each individual cell. Conclusion: Our semi-automated methodology for the isolation and single-cell analysis of cEVTS supports the feasibility of a cell-based noninvasive prenatal test for fetal genomic profiling.

The link between being pregnant and overweight or obese and the infectivity and virulence of the SARS CoV-2 virus is likely to be caused by SARS-CoV-2 spike protein glycosylation, which may work as a glycan shield. Methylglyoxal (MGO), an important advanced glycation end-product (AGE), and glycated albumin (GA) are the results of poor subclinical glucose metabolism and are indices of oxidative stress. Forty-one consecutive cases of SARS-CoV-2-positive pregnant patients comprising 25% pre-pregnancy overweight women and 25% obese women were recruited. The aim of our study was to compare the blood levels of MGO and GA in pregnant women with asymptomatic and symptomatic SARS-CoV-2 infection with pregnant women without SARS-CoV-2 infection with low risk and uneventful pregnancies and to evaluate the relative perinatal outcomes. The MGO and GA values of the SARS-CoV-2 cases were statistically significantly higher than those of the negative control subjects. In addition, the SARS-CoV-2-positive pregnant patients who suffered of moderate to severe COVID-19 syndrome had higher values of GA than those infected and presenting with mild symptoms or those with asymptomatic infection. Premature delivery and infants of a small size for their gestational age were overrepresented in this cohort, even in mild-asymptomatic patients for whom delivery was not indicated by the COVID-19 syndrome. Moreover, ethnic minorities were overrepresented among the severe cases. The AGE–RAGE oxidative stress axis on the placenta and multiple organs caused by MGO and GA levels, associated with the biological mechanisms of the glycation of the SARS-CoV-2 spike protein, could help to explain the infectivity and virulence of this virus in pregnant patients affected by being overweight or obese or having gestational diabetes, and the increased risk of premature delivery and/or low newborn weight.

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

The aim of the study was to evaluate the association between SARS-CoV-2 infection and serum hepatic biomarker levels among women with obstetric cholestasis.In this prospective study, we recruited all pregnant women admitted in our hospital with obstetric cholestasis. Among those with a concurrent SARS-CoV-2 infection, we evaluated the following serum hepatic biomarkers: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and biliar acids (BA).Among the 88 women enrolled in the study, 20 presented with a SARS-CoV-2 infection while 68 were negative. SARS-CoV-2 infected women were younger (mean age 30.5 ± 5.7 vs. 34.3 ± 5.4; p 0.01) and in a greater percentage of non-Caucasian ethnicity when compared to noninfected women (60.0% vs. 17.6%; p 0.01). Regarding levels of hepatic biomarkers, they showed higher levels of AST (111.5 ± 134.1 vs. 37.3 ± 43.4 UI/L; p = 0.02), ALT (132.2 ± 115.7 vs. 50.5 ± 73.173.1 UI/L; p 0.01), and BA (41.4 ± 46.8 vs. 18.4 ± 13.4 μmol/L; p = 0.04) compared to noninfected patients. No significant differences in maternal or fetal outcomes were found between infected and noninfected women.SARS-CoV-2 infection was associated with higher levels of liver enzymes in patients with obstetric cholestasis. This could be the result of a possible hepatic involvement in patients with SARS-CoV-2 infection.

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.

Background: Although fetal size is associated with adverse perinatal outcome, the relationship between fetal growth velocity and adverse perinatal outcome is unclear. Objective: This study aimed to evaluate the relationship between fetal growth velocity and signs of cerebral blood flow redistribution, and their association with birthweight and adverse perinatal outcome. Study Design: This study was a secondary analysis of the TRUFFLE-2 multicenter observational prospective feasibility study of fetuses at risk of fetal growth restriction between 32 +0 and 36 +6 weeks of gestation (n=856), evaluated by ultrasound biometry and umbilical and middle cerebral artery Doppler. Individual fetal growth velocity was calculated from the difference of birthweight and estimated fetal weight at 3, 2, and 1 week before delivery, and by linear regression of all available estimated fetal weight measurements. Fetal estimated weight and birthweight were expressed as absolute value and as multiple of the median for statistical calculation. The coefficients of the individual linear regression of estimated fetal weight measurements (growth velocity; g/wk) were plotted against the last umbilical-cerebral ratio with subclassification for perinatal outcome. The association of these measurements with adverse perinatal outcome was assessed. The adverse perinatal outcome was a composite of abnormal condition at birth or major neonatal morbidity. Results: Adverse perinatal outcome was more frequent among fetuses whose antenatal growth was

Background: Maternal cardiovascular changes, occurring since the beginning of pregnancy, are necessary for normal placentation and regular evolution of pregnancy. Objective: This study aimed to compare the hemodynamic profiles and cardiac remodeling of women with hypertensive disorders of pregnancy and either appropriate for gestational age fetuses or growth-restricted fetuses, women with normotensive pregnancies complicated by fetal growth restriction, and women with uncomplicated pregnancies, during pregnancy and the postpartum period. Study design: A prospective longitudinal case-control design was used for this study. Over the study period, 220 eligible women with singleton pregnancies were selected for the analysis and divided into 4 groups: (1) hypertensive disorders of pregnancy with appropriate for gestational age fetuses; (2) hypertensive disorders of pregnancy with fetal growth restriction; (3) normotensive fetal growth restriction; and (4) controls. Ultrasound fetal biometry and fetoplacental Doppler velocimetry were performed at recruitment. Maternal hemodynamic assessment using transthoracic echocardiography was performed at the time of recruitment by a dedicated cardiologist blinded to maternal clinical data. The same assessments were performed in 104 patients at 32 weeks (interquartile range, 24-40) after delivery by the same cardiologist. Results: During pregnancy, women in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction group showed significantly lower cardiac output and increased compared with those in the control group. These values were associated with concentric remodeling of the left ventricle owing to relatively increased wall thickness, which was not accompanied by an increase in left ventricular mass. Isolated fetal growth restriction presented similar but less important hemodynamic changes; however, there was no change in relative wall thickness. At postpartum follow-up, the hemodynamic parameters of women in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction and isolated-fetal-growth-restriction groups reverted to values similar to those of the control group. Only 8.3% of women in these groups experienced hypertension even in the postpartum period, and asymptomatic stage-B cardiac failure was observed for 17% at echocardiography. In the group of women with hypertensive disorders of pregnancy and appropriate for gestational age fetuses, cardiac output increased as in normal pregnancies, but total vascular resistance was significantly higher; hypertension then occurred, along with ventricular concentric hypertrophy and diastolic dysfunction. At postpartum follow-up, women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group showed significantly higher mean arterial pressure, total vascular resistance, and left ventricular mass compared with those in the control group. Persistent hypertension and asymptomatic stage-B cardiac failure were observed in 39.1% and 13% of women in the former group, respectively. Conclusion: Pregnancies with hypertensive disorders of pregnancy and fetal growth restriction and normotensive pregnancies with fetal growth restriction were associated with the hemodynamic profile of lower heart rate and cardiac output, most likely because of abnormal adaptation to pregnancy, as confirmed by abnormal changes from pregnancy to the postpartum period. The heart rates and cardiac output of women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group showed changes opposite to those observed in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction and fetal-growth-restriction groups. Obesity and other metabolic risk factors, significantly prevalent in women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group, predispose to hypertension and cardiovascular diseases during pregnancy and the postpartum period, potentially offering a window for personalized prevention. Such preventive strategies could differ in women with hypertensive disorders of pregnancy and fetal growth restriction characterized by poor early placental development.

Objectives Hypertensive disorders of pregnancy (HDP) and fetal growth restriction (FGR) of vascular placental origin are two main pregnancy complications associated with an increased incidence of poor outcomes. These conditions are both characterized by vascular dysfunction and syncytiotrophoblast oxidative stress. sFlt-1/PlGF ratio as an index of oxidative stress could be a valid diagnostic tool for predicting adverse perinatal outcomes in high risk population. Methods We recruited women affected by HDP, classified according to fetal growth or with isolated FGR. Women with an uneventful pregnancy were recruited as control group. Ultrasound data and sera sample were collected at recruitment. Perinatal complications were the main outcome of this diagnostic study. A survival analysis, a logistic regression model with all covariates and a predictive model based on a Random Forest and a Mean Decrease Gini index were performed. Results We recruited 350 consecutive singleton pregnancies. The 90 patients who suffered of perinatal complications had a significantly higher sFlt-1/PlGF ratio (267.2±271.2) at recruitment than those who did not (57±93.5), (p

Objectives: To analyze soluble Fms-like tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) ratio concentrations in COVID-19 pregnant patients with and without Hypertensive Disorders of Pregnancy (HDP), compared with non COVID-19 pregnant patients with HDP and a control group. Study design: We recruited and obtained a complete follow-up of 19 COVID-19 pregnant patients with HDP and of 24 COVID-19 normotensive pregnant patients. Demographic, clinical and sFlt-1/PlGF ratio findings were compared with a group of 185 non COVID-19 pregnant patients with HDP and 41 non COVID normotensive patients. Findings were based on univariate analysis and on a multivariate adjusted model, and a case by case analysis of COVID-19 pregnant patients with an abnormal sFlt-1/PlGF ratio > 38 at recruitment. Main outcome measures: sFlt-1/PlGF ratio. Results: We confirmed a significant higher prevalence of HDP in women affected by COVID-19 compared to control population. sFlt-1/PlGF ratio was found high in HDP patients, with and without of Sars-Cov2 infection. COVID-19 patients with worse evolution of the disease showed greater rates of obesity and other comorbidities. sFlt/PlGF ratio proved not to be helpful in the differential diagnosis of the severity of this infection. Conclusions: COVID-19 pregnant patients showed a higher prevalence of HDP compared to non COVID-19 controls, as well as higher comorbidity rates. In spite of the possible common endothelial target and damage, between Sars-Cov-2 infection and HDP, the sFlt1/PlGF ratio did not correlate with the severity of this syndrome.

Background: Existing evidence on the effects of race and ethnicity on pregnancy outcomes is restricted to individual studies done within specific countries and health systems. We aimed to assess the impact of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries, and to ascertain whether the magnitude of disparities, if any, varied across geographical regions. Methods: For this individual participant data (IPD) meta-analysis we used data from the International Prediction of Pregnancy Complications (IPPIC) Network of studies on pregnancy complications; the full dataset comprised 94 studies, 53 countries, and 4 539 640 pregnancies. We included studies that reported perinatal outcomes (neonatal death, stillbirth, preterm birth, and small-for-gestational-age babies) in at least two racial or ethnic groups (White, Black, south Asian, Hispanic, or other). For our two-step random-effects IPD meta-analysis, we did multiple imputations for confounder variables (maternal age, BMI, parity, and level of maternal education) selected with a directed acyclic graph. The primary outcomes were neonatal mortality and stillbirth. Secondary outcomes were preterm birth and a small-for-gestational-age baby. We estimated the association of race and ethnicity with perinatal outcomes using a multivariate logistic regression model and reported this association with odds ratios (ORs) and 95% CIs. We also did a subgroup analysis of studies by geographical region. Findings: 51 studies from 20 high-income and upper-middle-income countries, comprising 2 198 655 pregnancies, were eligible for inclusion in this IPD meta-analysis. Neonatal death was twice as likely in babies born to Black women than in babies born to White women (OR 2·00, 95% CI 1·44–2·78), as was stillbirth (2·16, 1·46–3·19), and babies born to Black women were at increased risk of preterm birth (1·65, 1·46–1·88) and being small for gestational age (1·39, 1·13–1·72). Babies of women categorised as Hispanic had a three-times increased risk of neonatal death (OR 3·34, 95% CI 2·77–4·02) than did those born to White women, and those born to south Asian women were at increased risk of preterm birth (OR 1·26, 95% CI 1·07–1·48) and being small for gestational age (1·61, 1·32–1·95). The effects of race and ethnicity on preterm birth and small-for-gestational-age babies did not vary across regions. Interpretation: Globally, among underserved groups, babies born to Black women had consistently poorer perinatal outcomes than White women after adjusting for maternal characteristics, although the risks varied for other groups. The effects of race and ethnicity on adverse perinatal outcomes did not vary by region. Funding: National Institute for Health and Care Research, Wellbeing of Women.

Introduction: The aim of this study was to investigate the relationships between maternal vascular malperfusions (MVM) and second trimester uterine arteries pulsatility index (UtA-PI) in cases of stillbirth (SB), compared to live-birth (LB) matched controls. Methods: This was a multicentre, observational, matched case-control study performed at five referral maternity centres over a 4-year period including SB and LB control pregnancies at high-risk for preeclampsia (PE) and/or fetal growth restriction (FGR), matched and stratified for UtA-PI MoM quartiles values of the SB cases. Logistic regression was used to assess the rates of each MVM finding, within each increasing MoM quartile subcategory in SB and matched LB controls. Results: 82 SB and 82 LB matched high-risk pregnancies were included. Placental hypoplasia, placental infarction, retroplacental hematoma, distal villous hypoplasia and accelerated villous maturation showed a significant correlation with UtA-PI. At univariable analysis, placental infarction and distal villous hypoplasia were more highly associated with the increasing quartile uterine Doppler measurements (odds ratio 2.24 and 2.23, respectively). Logistic regressions showed a significant positive and independent association between rates of retroplacental hematoma or distal villous hypoplasia and stillbirth within corresponding UtA-PI MoM quartiles (odds ratio 5.21 and 2.28, respectively). Discussion: We are providing evidence for characterization of two major etiological stillbirth categories, characterized by a positive or absent association with UtA-PI impairment and specific histopathological placental MVM lesions. Our results support a strict third trimester follow-up of cases with increased second trimester UtA-PI, in order to improve the reproductive chances of these pregnant patients.

Introduction: The aim of the present study was to evaluate fetal umbilical artery (UA) and middle cerebral artery (MCA) blood flow in patients with gestational diabetes (GD), in order to determine whether minimal anomalies of glucose metabolism may influence fetal placental function. Methods: UA and MCA flows were prospectively measured by transabdominal ultrasound in singleton pregnancies between 34 and 37 weeks of gestation. Results: The study included 35 women with GD and 217 nondiabetic patients. Middle cerebral pulsatility index (PI) was significantly higher in the GD group (mean MCA-PI = 1.82 ± 0.27 vs. 1.71 ± 0.26; p < 0.02). Likewise, MCA peak systolic velocity (MCA-PSV) was higher in the GD group compared to the non-GD group, though the difference was not significant (mean of MCA-PSV = 47.14 ± 8.45 vs. 47.09 ± 11.21; p = 0.98). UA-PI resulted higher in the non-GD group without significant differences (mean of UA-PI = 0.88 ± 0.14 vs. 0.86 ± 0.15; p = 0.32). Conclusions: Our study shows that even in cases of minimal metabolic derangements, GD is characterized by a significant variation in fetal Doppler velocimetry, particularly in the brain.

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.

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.

Background: The epidemiology of adenomyosis has been traditionally based on patients undergoing hysterectomy for gynecological indications, while its prevalence among hysterectomies performed for obstetric complications is unknown. The aim of this study was to assess the prevalence and clinical impact of adenomyosis diagnosed through histology among women undergoing pregnancy-related hysterectomy (PH). Methods: This was a retrospective cohort study. Women who delivered at a tertiary care regional obstetric hub in Milan between 2009 and 2020 were reviewed to identify cases of PH. Histopathological reports of surgical specimens were examined. Cases with adenomyosis were compared to those without adenomyosis for baseline characteristics, obstetric history and outcomes. Results: During the study period there were 71,061 births and a total of 130 PH, giving a PH incidence of 1.83 per 1000 deliveries. Adenomyosis cases were 18, giving a prevalence of 13.8%. Adenomyosis was associated with placenta previa (77.8 vs. 45.5%, p = 0.01), chorionamnionitis (27.8 vs. 5.4%, p = 0.008), lower gestational age at birth (32 ± 4.6 vs. 35.5 ± 3.6 weeks’ gestation, p = 0.0004), and intrauterine fetal demise among twin pregnancies (50 vs. 4.5%, p = 0.048). Conclusion: Adenomyosis entails a relevant impact on obstetric and perinatal outcomes related to PH. More evidence is needed on the clinical relevance of an ultrasonographic diagnosis of adenomyosis before conception.