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

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

Fetal RHD Screening in RH1 Negative Pregnant Women: Experience in Switzerland.

RH1 incompatibility between mother and fetus can cause hemolytic disease of the fetus and newborn. In Switzerland, fetal RHD genotyping from maternal blood has been recommended from gestational age 18 onwards since the year 2020. This facilitates tailored administration of RH immunoglobulin (RHIG) only to RH1 negative women carrying a RH1 positive fetus. Data from 30 months of noninvasive fetal RHD screening is presented. Cell-free DNA was extracted from 7192 plasma samples using a commercial kit, followed by an in-house qPCR to detect RHD exons 5 and 7, in addition to an amplification control. Valid results were obtained from 7072 samples, with 4515 (64%) fetuses typed RHD positive and 2556 (36%) fetuses being RHD negative. A total of 120 samples led to inconclusive results due to the presence of maternal or fetal RHD variants (46%), followed by women being serologically RH1 positive (37%), and technical issues (17%). One sample was typed false positive, possibly due to contamination. No false negative results were observed. We show that unnecessary administration of RHIG can be avoided for more than one third of RH1 negative pregnant women in Switzerland. This reduces the risks of exposure to a blood-derived product and conserves this limited resource to women in actual need

The greater incidence of small for gestational age newborns after gonadotropin-stimulated in vitro fertilization with a supra-physiological estradiol level on ovulation trigger day.

INTRODUCTION Reproductive scientists have postulated various risk factors for lower birthweight following conventional gonadotropin stimulated in vitro fertilization compared to spontaneously conceived children: parental factors (age, health, duration of subfertility, and smoking habits); ovarian stimulation; laboratory procedures; the number of oocytes retrieved; and the number of embryos transferred. Our aim was to investigate the impact of gonadotropin stimulation and serum estradiol level on the risk of a newborn's being small for gestational age. MATERIAL AND METHODS We conducted a cohort study (2010-2016) of singletons (n = 155) born either after conventional gonadotropin stimulated in vitro fertilization (using ≥150 IU/d human gonadotropin for stimulation) or after natural cycle in vitro fertilization without any stimulation. We analyzed perinatal outcomes using birthweight percentiles, as they adjust for gestational age and sex. RESULTS The proportion of small for gestational age was 11.8% following conventional gonadotropin stimulated in vitro fertilization, and 2.9% after natural-cycle in vitro fertilization (P = 0.058). The odds of small for gestational age were significantly higher with supra-physiological estradiol levels in maternal serum on ovulation trigger day (unadjusted odds ratio 4.58; 95% confidence interval 1.35 to 15.55; P = 0.015). It remained significant after adjusting for maternal height, age, and body mass index (adjusted odds ratio 3.83; 95% confidence interval 1.06 to 13.82; P = 0.041). CONCLUSIONS We found an associated risk of children being born small for gestational age after conventional gonadotropin stimulated in vitro fertilization compared to natural-cycle in vitro fertilization. This higher risk is significantly associated with supra-physiological estradiol levels. We propose a reduction in the dosage of gonadotropin to minimize the risk of small for gestational age and future health consequences. This article is protected by copyright. All rights reserved

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is &lt;10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical &amp; Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200

[Preterm Birth Screening: What Does Really Make Sense?]

Preterm Birth Screening: What Does Really Make Sense? Abstract. Spontaneous preterm birth is a syndrome triggered by multiple mechanisms. In view of the pathophysiological heterogeneity of preterm birth, a single biomarker cannot show the required high negative and positive predictive values. From a clinical point of view, anamnesis, sonographic measurement of cervical length, and placental alpha-microglobulin-1 (PAMG-1) testing from cervico-vaginal secretion are established. Further prospective, large-scale longitudinal studies must validate the combined use of new biomarkers

FIRST TRIMESTER SCREENING FOR PREECLAMPSIA - A SYSTEMATIC REVIEW.

Objective: To increase the detection rate of preterm preeclampsia (PE) first trimester combined screening tests are being developed. The aim of this review is to create an overview of the currently investigated screening markers, algorithms and their validations.Methods: Comprehensive review of the literature concerning first trimester screening for PEResults and conclusions: Studies investigating a total of 160 biochemical, 6 biophysical and 14 ultrasound markers could be identified. Of the 21 algorithms published, mainly the algorithm published by the Fetal Medicine Foundation London has been validated. This algorithm performes significantly better than screening by anamnestic risk factors only

Systemic Inflammation in Pregnant Women With Periodontitis and Preterm Prelabor Rupture of Membranes: A Prospective Case-Control Study.

Aims: Periodontal disease is associated with adverse pregnancy outcome, but the underlying pathophysiologic mechanism is still unknown. In this prospective, longitudinal, non-interventional case-control study, 45 women with preterm premature rupture of membranes and 26 controls with uncomplicated pregnancies were examined at three time-points (T1: 20-34 weeks of gestations; T2: within 48 h after delivery; T3: 4-6 weeks post partum). Examinations included subgingival, blood, vaginal, and placenta sampling for microbiologic, cytokine, and histology assessment. Objective of this study was to test the hypothesis that systemic inflammatory changes and not specific bacteria are predominantly involved in the association between periodontal disease and adverse pregnancy outcome. Results: Demographic data and gestational age at T1 were comparable between groups. While there was no correlation between vaginal and gingival fluid microbiome, cytokine levels in the assessed compartments differed between cases, and controls. Vaginal smears did not show a higher rate of abnormal flora in the cases at the onset of preterm premature rupture of membranes. Number and variety of bacteria in the case group placental membranes and vagina were higher, but these bacteria were not found in membranes at birth. Conclusions: On the basis of our results we speculate that an inflammatory pathway sequentially involving periodontal tissue, maternal serum, and finally vaginal compartment contributes to the underlying pathomechanism involved in preterm premature rupture of membranes associated with periodontitis