Diverse mechanisms underlying the fetal growth course in gastroschisis and omphalocele.

BACKGROUND Gastroschisis and omphalocele are the 2 most common congenital fetal abdominal wall defects. Both malformations are commonly associated with small-for-gestational-age neonates. However, the extent and causes of growth restriction remain controversial in both gastroschisis and omphalocele without associated malformations or aneuploidy. OBJECTIVE This study aimed to examine the role of the placenta and the birthweight-to-placental weight ratio in fetuses with abdominal wall defects. STUDY DESIGN This study included all cases of abdominal wall defects examined at our hospital between January 2001 and December 2020, retrieving the data from the hospital's software. Fetuses with any other combined congenital anomalies, known chromosomal abnormalities, or lost to follow-up were excluded. Overall, 28 singleton pregnancies with gastroschisis and 24 singleton pregnancies with omphalocele met the inclusion criteria. Patient characteristics and pregnancy outcomes were reviewed. The primary outcome was to investigate the association between birthweight and placental weight in pregnancies with abdominal wall defects as measured after delivery. To correct for gestational age and to compare total placental weights, ratios between the observed and expected birthweights for the given gestational age in singletons were calculated. The scaling exponent β was compared with the reference value of 0.75. Statistical analysis was performed using GraphPad Prism (version 8.2.1; GraphPad Software, San Diego, CA) and IBM SPSS Statistics. A P value of <.05 indicated statistical significance. RESULTS Women pregnant with a fetus with gastroschisis were significantly younger and more often nulliparous. In addition, in this group, the gestational age of delivery was significantly earlier and almost exclusively for cesarean delivery. Of 28 children, 13 (46.7%) were born small for gestational age, only 3 of them (10.7%) had a placental weight <10th percentile. There is no correlation between birthweight percentiles and placental weight percentiles (P=not significant). However, in the omphalocele group, 4 of 24 children (16.7%) were born small for gestational age (<10th percentile), and all children also had a placental weight <10th percentile. There is a significant correlation between birthweight percentiles and placental weight percentiles (P<.0001). The birthweight-to-placental weight ratio differs significantly between pregnancies diagnosed with gastroschisis and pregnancies diagnosed with omphalocele (4.48 [3.79-4.91] vs 6.05 [5.38-6.47], respectively; P<.0001). Allometric metabolic scaling revealed that placentas complicated by gastroschisis and placentas complicated by omphalocele do not scale with birthweight. CONCLUSION Fetuses with gastroschisis displayed impaired intrauterine growth, which seemed to differ from the classical placental insufficiency growth restriction

Integrating Combined First Trimester Screening for Preeclampsia into Routine Ultrasound Examination.

Introduction The Fetal Medicine Foundation (FMF) London has developed a first trimester screening algorithm for preeclampsia (PE), based on maternal characteristics and past risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF). The aim of this study was to determine the feasibility of integrating PE screening into routine practice. Material and Methods All pregnancies with a fetal crown-rump length of 45 - 84 mm presenting to our ultrasound department between January 2014 and September 2020 were included in this analysis. Screening for PE was offered to singleton pregnancies only. The number of screening tests performed in the eligible population was assessed and the reasons for missed screenings identified with the help of the electronic clinical database. SPSS Statistics 25 and GraphPad version 8.0 for Windows were used for statistical analysis. Results 6535 pregnancies were included, 4510 (69.0%) of which were screened for PE. The percentage of patients being offered PE screening increased over the years from 63.1 to 96.7% (r s = 0.96; p = 0.003), while the rate of screenings performed in eligible patients remained stable at a median [range] of 86.2% [78.0 - 91.8%] (p = ns). 2025 (31.0%) pregnancies were not screened for PE, 1306 (64.5%) because they were not eligible for screening. 145 (2.2%) women explicitly declined PE screening; their background risk was lower than that of women who accepted screening. Conclusion Our study shows that integration of PE screening into the routine first trimester ultrasound scan is feasible and widely accepted by pregnant women and health care providers

Gestational diabetes is associated with SARS-CoV-2 infection during pregnancy: A case-control study.

AIM Individuals with SARS-CoV-2 infection and (pre-existing) diabetes, including pregnant women, present with more severe morbidity, as compared to non-diabetic subjects. To date, evidence is limited concerning the role of gestational diabetes (GDM) in severity of SARS-CoV-2 infection during pregnancy, or vice versa. The aim of our study was to investigate the prevalence of GDM in a SARS-CoV-2 infected pregnant population and evaluate risk factors for and from severe infection in these patients. METHODS A case-control study with prospective data collection for the case group and 1:2 matching with historical controls based on parity, BMI and ethnicity was conducted (n=224). GDM screening was performed at 26 weeks' gestation. Multivariate binary logistic regression analysis was performed to assess risk factors for GDM and inpatient COVID-19 management. RESULTS 34.6% of the patients in the case group suffered from GDM, vs. 16.1% in the control group (p=0.002). 35.7% patients were diagnosed with GDM after, vs. 33.3% before SARS-CoV-2 infection (OR (95%CI) 1.11(0.40-3.08), p=0.84), with no correlation between time point of infection and GDM diagnosis. SARS-CoV-2 (OR (95%CI) 2.79 (1.42, 5.47), p=0.003) and BMI (OR (95%CI) 1.12 (1.05, 1.19), p=0.001) were significant independent risk factors for GDM. CONCLUSION Data suggests that GDM increases the risk of infection in SARS-CoV-2 infected pregnant women. Meanwhile, SARS-CoV-2 during pregnancy might increase the risk of developing GDM. Vaccination and caution in using protective measures should be recommended to pregnant women, particularly when suffering from GDM

First-trimester glycosylated hemoglobin (HbA1c) and maternal characteristics in the prediction of gestational diabetes: An observational cohort study.

INTRODUCTION This study aimed to investigate the extent to which gestational diabetes mellitus (GDM) can be predicted in the first trimester by combining a marker of growing interest, glycosylated hemoglobin A1c (HbA1c), and maternal characteristics. MATERIAL AND METHODS This observational study was conducted in the outpatient obstetric department of our institution. The values of HbA1c and venous random plasma glucose were prospectively assessed in the first trimester of pregnancy. We determined maternal characteristics that were independent predictors from the regression analysis and calculated areas under the receiver-operating curves by combining the maternal age, body mass index, previous history of GDM, and first-degree family history for diabetes mellitus. Moreover we investigated the predictive capability of HbA1c to exclude GDM. Patients with a first-trimester HbA1c level of 6.5% (48 mmol/mol) or more were excluded. The study was registered at ClinicalTrials.gov ID: NCT02139254. RESULTS We included 785 cases with complete dataset. The prevalence of GDM was 14.7% (115/785). Those who developed GDM had significantly higher HbA1c and random plasma glucose values (p < 0.0001 and p = 0.0002, respectively). In addition, they had a higher body mass index, were more likely to have a history of GDM and/or a first-degree family history of diabetes. When these maternal characteristics were combined with the first-trimester HbA1c and random plasma glucose the combined area under the receiver operating characteristics curve was 0.76 (95% CI 0.70-0.81). CONCLUSIONS Our results indicate that HbA1c and random plasma glucose values combined with age, body mass index, and personal and family history, allow the identification of women in the first trimester who are at increased risk of developing GDM

Hypertensive disorders of pregnancy share common cfDNA methylation profiles.

Hypertensive disorders of pregnancy (HDP) contribute substantially to perinatal morbidity and mortality. Epigenetic changes point towards cardio-metabolic dysregulation for these vascular disorders. In early pregnancy, epigenetic changes using cell free DNA (cfDNA) are largely unexplored. We aimed to investigate these in HDP between 11 and 14 weeks of gestation by analysis of cfDNA methylation profiles in patients with hypertensive disorders. We identified patients without chronic hypertension but with subsequent development of preeclampsia (PE) (n = 11), with chronic hypertension (HT) but without PE development (n = 14), and lacking both PE and HT (n = 422). We matched patients according to PE risk factors into three groups (n = 5 each group): (1) PE: no HT but PE development, (2) HT: chronic hypertension but no PE and (3) Control: no PE or HT. We successfully optimized our cfDNA isolation process prior to whole genome bisulfite sequencing. Analysis of cfDNA methylation changes indicate a common predisposition in PE and HT groups, chiefly of maternal origin. Assessment of significant differentially methylated regions and annotated genes point towards a common cardiovascular predisposition in preeclampsia and hypertension groups in the first trimester. We postulate the pivotal role of the maternal cardiovascular system in HDP, which is already evident in the first trimester

Implementing preeclampsia screening in Switzerland (IPSISS) - first results from a multicentre registry.

Introduction The Fetal Medicine Foundation(FMF) London developed a first trimester combined screening algorithm for preterm preeclampsia(pPE) that allows a significantly higher detection of pregnancies at risk compared to conventional screening by maternal risk factors only. The aim of this trial is to validate this screening model in the Swiss population in order to implement this screening into routine first trimester ultrasound and to prescribe low dose aspirin 150mg(LDA) in patients at risk for pPE. Therefore, a multicentre registry study collecting screening and pregnancy outcome data was initiated in2020;these are the preliminary results. Methods Between June1st2020 and May31st2021 we included singleton pregnancies with pPE screening at the hospitals of Basel, Lucerne and Bern. Multiple of Medians(MoMs) of uterine artery pulsatility index(UtA-PI), mean arterial pressure(MAP), placental growth factor(PlGF) and pregnancy associated plasma protein A(PAPP-A) as well as risks were analysed as calculated by each centre's software and recalculated on the FMF online calculator for comparative reasons. Statistical analyses were performed by GraphPad Version9.1. Results During the study period 1027patients with singleton pregnancies were included. 174(16.9%) had a risk>1:100 at first trimester combined screening. Combining the background risk, MAP, UtA-PI and PlGF only, the cut-off to obtain a SPR of 11% is≥1:75. Outcomes were available for 968/1027(94.3%) patients, 951 resulted in live birth. 15(1.58%) developed classical PE, 23(2.42%) developed PE according to the ISSHP(International Society for the Study of Hypertension in Pregnancy) definition. Conclusion First trimester combined screening for PE and prevention with LDA results in a low prevalence of PE.The screening algorithm performs according to expectations, however the cut-off of>1:100 results in a SPR above the accepted range and a cut-off of≥1:75 should be considered for screening. More data are needed to evaluate, if these results are representative for the general Swiss population

The impact of regional origin on the incidence of gestational diabetes mellitus in a multiethnic European cohort

IntroductionWomen with migration background present specific challenges related to risk stratification and care of gestational diabetes mellitus (GDM). Therefore, this study aims to investigate the role of ethnic origin on the risk of developing GDM in a multiethnic European cohort.MethodsPregnant women were included at a median gestational age of 12.9 weeks and assigned to the geographical regions of origin: Caucasian Europe (n = 731), Middle East and North Africa countries (MENA, n = 195), Asia (n = 127) and Sub-Saharan Africa (SSA, n = 48). At the time of recruitment maternal characteristics, glucometabolic parameters and dietary habits were assessed. An oral glucose tolerance test was performed in mid-gestation for GDM diagnosis.ResultsMothers with Caucasian ancestry were older and had higher blood pressure and an adverse lipoprotein profile as compared to non-Caucasian mothers, whereas non-Caucasian women (especially those from MENA countries) had a higher BMI and were more insulin resistant. Moreover, we found distinct dietary habits. Non-Caucasian mothers, especially those from MENA and Asian countries, had increased incidence of GDM as compared to the Caucasian population (OR 1.87, 95%CI 1.40 to 2.52, p &lt; 0.001). Early gestational fasting glucose and insulin sensitivity were consistent risk factors across different ethnic populations, however, pregestational BMI was of particular importance in Asian mothers.DiscussionPrevalence of GDM was higher among women from MENA and Asian countries, who already showed adverse glucometabolic profiles at early gestation. Fasting glucose and early gestational insulin resistance (as well as higher BMI in women from Asia) were identified as important risk factors in Caucasian and non-Caucasian patients

Pränataldiagnostik im Jahr 2016

Zusammenfassung. Seit mehreren Jahrzehnten beschäftigt sich die Pränataldiagnostik mit der Entwicklung von Screening-Algorhythmen zur Berechnung des Trisomierisikos. Mit der Entdeckung der freien fetalen DNA (ffDNA), auch zell-freien DNA (cfDNA) genannt, im maternalen Blut wurde der vorgängig entwickelte Ersttrimester-Test (ETT) revolutioniert; der heute bei uns bereits weit verbreitet angewandte «nicht invasiven pränatalen Test» (NIPT) wurde entwickelt. Dessen exzellente Performance im Screening nach Trisomie 21 wurde in zahlreichen Studien bewiesen. Heute wird vor allem die Integration des NIPTs in den ETT diskutiert. Die Weiterentwicklung des cfDNA-Screenings führt zu immer vielfältigeren Testoptionen, welche die schwangere Frau und den behandelnden Arzt zum Teil vor komplexe Entscheidungen stellen. Auch die Interpretation des NIPTs wird dadurch immer komplizierter. Die Möglichkeiten, aber auch Grenzen dieser Screeningmethode zu verstehen ist von grosser Wichtigkeit in der Beratung der Schwangeren. </jats:p