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Objectives To determine the effect of gestational age at delivery on maternal and neonatal outcomes in preterm prelabor rupture of membranes (PPROM) and assess various predictors of neonatal and infant mortality in these pregnancies. Methods United States birth data from CDC-National Center for Health Statistics natality database for years 2004–2008 was used to identify singleton pregnancies with PPROM and delivery from 32 0/7 to 36 6/7 weeks. Controls were singletons at 37–40 weeks, without PPROM. Maternal and neonatal complications reported by all states were analyzed along with neonatal outcomes such as chorioamnionitis and hyaline membrane disease, reported by a subgroup of states. OR (95% CI) were calculated after adjusting for preeclampsia, diabetes, chronic hypertension, maternal race, and infant sex. Results There were 134,502 PPROM cases and similar number of controls. There was a significant decrease in need for prolonged ventilation, hyaline membrane disease, 5 min Apgar score Conclusions We provide population-based evidence showing a decrease in neonatal complications and death with advancing gestational age in PPROM. Gestational age at delivery in pregnancies with PPROM is the strongest predictor of mortality risk.

Objectives: SARS-CoV-2 infection triggers a significant maternal inflammatory response. There is a dearth of information regarding whether maternal SARS-CoV-2 infection at admission for delivery or SARS-CoV-2 vaccination triggers an inflammatory response in the fetus. This study aims at evaluating fetal inflammatory response to maternal SARS-CoV-2 infection or SARS-CoV-2 vaccination compared to control group. Design, Participants, Setting, and Methods: A prospective cohort study was performed with a total of 61 pregnant women who presented for delivery at a single medical center (William Beaumont Hospital, Royal Oak, MI). All mothers were tested for SARS-CoV-2 infection using polymerase chain reaction (PCR) on admission to labor and delivery unit. Three groups were evaluated: 22 pregnant with a positive SARS-CoV-2 test (case group), 23 pregnant women with a negative SARS-CoV-2 test (control group), and 16 pregnant women who had recent SAR-CoV-2 vaccination and a negative SARS-CoV-2 test (vaccine group). At delivery, cord blood was collected to determine the levels of IL-6, C-reactive protein (CRP), and SARS-CoV-2 nucleocapsid IgG and IgM antibodies. In all cases, the newborn had a negative PCR test or showed no clinical findings consistent with SARS-CoV-2 infection. Results: Mean (SD) IL-6 level was not significantly different for the three groups: case group 9.00 ± 3.340 pg/mL, control group 5.19 ± 0.759 pg/mL, and vaccine group 7.11 ± 2.468 pg/mL (p value 0.855). Pairwise comparison also revealed no statistical difference for IL-6 concentrations with p values for case versus control, case versus vaccine, and control versus vaccine = 0.57, 0.91, and 0.74, respectively. Similarly, there was no statistically significant difference in the frequency of elevated IL-6 (>11 pg/mL) between groups (p value 0.89). CRP levels across the three groups were not statistically significant different (p value 0.634). Pairwise comparison of CRP levels among the different groups was also not statistically different. SARS-CoV-2 nucleocapsid IgG was positive in 12 out of 22 cord blood samples in the case group, 2 out of 23 of the control group (indicating old resolved maternal infection), and 0 out of 16 of the vaccine group. SARS-CoV-2 nucleocapsid IgM was negative in all cord blood samples of the case group, control group, and vaccine group. Limitations: A total number of 61 mothers enrolled in the study which represents a relatively small number of patients. Most patients with positive SARS-CoV-2 PCR were mainly asymptomatic. In addition, our vaccine group received the mRNA-based vaccines (mRNA1273 and BNT162b2). We did not study fetal response to other SARS-CoV-2 vaccines. Conclusion: In our prospective cohort, neither IL-6 nor CRP indicated increased inflammation in the cord blood of newborns of SARS-CoV-2-infected or vaccinated mothers.

To identify maternal second and third trimester urine metabolomic biomarkers for the detection of fetal congenital heart defects (CHDs). This was a prospective study. Metabolomic analysis of randomly collected maternal urine was performed, comparing pregnancies with isolated, non-syndromic CHDs versus unaffected controls. Mass spectrometry (liquid chromatography and direct injection and tandem mass spectrometry, LC–MS–MS) as well as nuclear magnetic resonance spectrometry, 1H NMR, were used to perform the analyses between 14 0/7 and 37 0/7 weeks gestation. A total of 36 CHD cases and 41 controls were compared. Predictive algorithms using urine markers alone or combined with, clinical and ultrasound (US) (four-chamber view) predictors were developed and compared. A total of 222 metabolites were identified, of which 16 were overlapping between the two platforms. Twenty-three metabolite concentrations were found in significantly altered in CHD gestations on univariate analysis. The concentration of methionine was most significantly altered. A predictive algorithm combining metabolites (histamine, choline, glucose, formate, methionine, and carnitine) plus US four-chamber view achieved an AUC = 0.894; 95% CI, 0814–0.973 with a sensitivity of 83.8% and specificity of 87.8%. Enrichment pathway analysis identified several lipid related pathways that are dysregulated in CHD, including phospholipid biosynthesis, phosphatidylcholine biosynthesis, phosphatidylethanolamine biosynthesis, and fatty acid metabolism. This could be consistent with the increased risk of CHD in diabetic pregnancies. We report a novel, noninvasive approach, based on the analysis of maternal urine for isolated CHD detection. Further, the dysregulation of lipid- and folate metabolism appears to support prior data on the mechanism of CHD.

DNA cytosine nucleotide methylation (epigenomics and epigenetics) is an important mechanism for controlling gene expression in cardiac development. Combined artificial intelligence and whole-genome epigenomic analysis of circulating cell-free DNA in maternal blood has the potential for the detection of fetal congenital heart defects.This study aimed to use genome-wide DNA cytosine methylation and artificial intelligence analyses of circulating cell-free DNA for the minimally invasive detection of fetal congenital heart defects.In this prospective study, whole-genome cytosine nucleotide methylation analysis was performed on circulating cell-free DNA using the Illumina Infinium MethylationEPIC BeadChip array. Multiple artificial intelligence approaches were evaluated for the detection of congenital hearts. The Ingenuity Pathway Analysis program was used to identify gene pathways that were epigenetically altered and important in congenital heart defect pathogenesis to further elucidate the pathogenesis of isolated congenital heart defects.There were 12 cases of isolated nonsyndromic congenital heart defects and 26 matched controls. A total of 5918 cytosine nucleotides involving 4976 genes had significantly altered methylation, that is, a P value of.05 along with ≥5% whole-genome cytosine nucleotide methylation difference, in congenital heart defect cases vs controls. Artificial intelligence analysis of the methylation data achieved excellent congenital heart defect predictive accuracy (areas under the receiver operating characteristic curve, ≥0.92). For example, an artificial intelligence model using a combination of 5 whole-genome cytosine nucleotide markers achieved an area under the receiver operating characteristic curve of 0.97 (95% confidence interval, 0.87-1.0) with 98% sensitivity and 94% specificity. We found epigenetic changes in genes and gene pathways involved in the following important cardiac developmental processes: "cardiovascular system development and function," "cardiac hypertrophy," "congenital heart anomaly," and "cardiovascular disease." This lends biologic plausibility to our findings.This study reported the feasibility of minimally invasive detection of fetal congenital heart defect using artificial intelligence and DNA methylation analysis of circulating cell-free DNA for the prediction of fetal congenital heart defect. Furthermore, the findings supported an important role of epigenetic changes in congenital heart defect development.

To evaluate measurement of levels of urine hyperglycosylated hCG, a form of hCG with abnormally branched oligosaccharide side chains, in conjunction with ultrasound biometry for Down syndrome risk prediction in an at-risk group.We prospectively measured urine hyperglycosylated hCG levels, humeral length, and nuchal thickness in women who had second-trimester amniocentesis. Urine hyperglycosylated hCG levels were measured by a two-step enzyme-immunometric assay using monoclonal antibody beta152. Humeral length, nuchal thickness, and hyperglycosylated hCG values were expressed as multiples of the median, and the Down syndrome screening efficiency of the three analytes plus age was determined. A receiver operating characteristic (ROC) curve was generated, and the area under the curve was used to assess the Down syndrome screening performance of the algorithm.There were 23 cases of Down syndrome among 1016 singleton pregnancies. Mean gestational age (+/- standard deviation) was 16.1 +/- 1.2 weeks at the time of amniocentesis. Mean maternal age was 37.1 +/- 3.2 years. Biometry and measurement of hyperglycosylated hCG levels had a 91.3% detection rate at a 3.2% false-positive rate and a 100% detection rate at a 10.7% false-positive rate. The area under the ROC curve was 0.986 (P.001), and that for measurement of hyperglycosylated hCG levels plus age was 0.941 (P.001). The area under the curve was significantly larger with combined biochemical and biometry markers compared with measurement of hyperglycosylated hCG levels plus age alone (P.02), proving that the former was superior to the latter.A new Down syndrome biochemical marker combined with ultrasound biometry had a high screening efficiency in a high-risk group. All cases of Down syndrome in this study population would have been detected at an amniocentesis rate of less than 10.7%. Our results appear superior to those found with other second-trimester algorithms. The combination is promising as an alternative to "automatic" genetic amniocentesis in women of advanced maternal age and other high-risk groups.

Objective The objective of the study was to examine the effect of selective fetoscopic laser photocoagulation (SFLP) vs serial amnioreduction (AR) on perinatal mortality in severe twin-twin transfusion syndrome (TTTS). Study Design This was a 5 year multicenter, prospective, randomized controlled trial. The primary outcome variable was 30 day postnatal survival of donors and recipients. Results There was no statistically significant difference in 30-day postnatal survival between SFLP or AR treatment for donors at 55% (11 of 20) vs 55% (11 of 20) ( P = 1.0, odds ratio [OR] 1, 95% confidence interval [CI] 0.242 to 4.14) or recipients at 30% (6 of 20) vs 45% (9 of 20) ( P = .51, OR 1.88, 95% CI 0.44 to 8.64). There was no difference in 30 day survival of 1 or both twins on a per-pregnancy basis between AR at 75% (15 of 20) and SFLP at 65% (13 of 20) ( P = .73, OR 1.62, 95% CI 0.34 to 8.09). Overall survival (newborns divided by the number of fetuses treated) was not statistically significant for AR at 60% (24 of 40) vs SFLP 45% (18 of 40) ( P = .18, OR 2.01, 95% CI 0.76 to 5.44). There was a statistically significant increase in fetal recipient mortality in the SFLP arm at 70% (14 of 20) vs the AR arm at 35% (7 of 20) ( P = .25, OR 5.31, 95% CI 1.19 to 27.6). This was offset by increased recipient neonatal mortality of 30% (6 of 20) in the AR arm. Echocardiographic abnormality in recipient twin Cardiovascular Profile Score is the most significant predictor of recipient mortality ( P = .055, OR 3.025/point) by logistic regression analysis. Conclusion The outcome of the trial did not conclusively determine whether AR or SFLP is a superior treatment modality. TTTS cardiomyopathy appears to be an important factor in recipient survival in TTTS.

Objective To review our experience with the planned intrapartum management of fetuses with suspected severe airway obstruction. Methods Retrospective review of prenatal presentations, intrapartum airway procurement methods, outcomes, and complications. Results All cases (N = 11) at our tertiary airway referral institution between 1995 and 2002 were reviewed. Obstruction was secondary to giant cervicofacial lymphangiomas (5), teratomas (2), epignathis (1), epulis (1), conjoined fetus (1), and tracheal foreign body (1). Elective cesarean delivery of the entire fetus was performed while maintaining fetal-placental circulation as long as possible. We found it necessary to deliver the entire fetus to improve airway exposure and decrease maternal hemorrhage. The airway was secured effectively in all cases. Conclusions Although full cesarean delivery of the fetus significantly reduces fetal-placental circulation times, in comparison with the formal ex utero intrapartum treatment (EXIT) procedure, airway access is improved, maternal complications may be decreased, and high airway procurement success is still safely achieved.