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OBJECTIVE: The objective of this study was to investigate the feasibility of examining the fetal heart with Tomographic Ultrasound Imaging (TUI) using four-dimensional (4D) volume datasets acquired with spatiotemporal image correlation (STIC). MATERIAL AND METHODS: One hundred and ninety-five fetuses underwent 4D ultrasonography (US) of the fetal heart with STIC. Volume datasets were acquired with B-mode (n=195) and color Doppler imaging (CDI) (n=168), and were reviewed offline using TUI, a new display modality that automatically slices 3D/4D volume datasets, providing simultaneous visualization of up to eight parallel planes in a single screen. Visualization rates for standard transverse planes used to examine the fetal heart were calculated and compared for volumes acquired with B-mode or CDI. Diagnoses by TUI were compared to postnatal diagnoses. RESULTS: (1) The four- and five-chamber views and the three-vessel and trachea view were visualized in 97.4% (190/195), 88.2% (172/195), and 79.5% (142/195), respectively, of the volume datasets acquired with B-mode; (2) these views were visualized in 98.2% (165/168), 97.0% (163/168), and 83.6% (145/168), respectively, of the volume datasets acquired with CDI; (3) CDI contributed additional diagnostic information to 12.5% (21/168), 14.2% (24/168) and 10.1% (17/168) of the four- and five-chamber and the three-vessel and trachea views; (4) cardiac anomalies other than isolated ventricular septal defects were identified by TUI in 16 of 195 fetuses (8.2%) and, among these, CDI provided additional diagnostic information in 5 (31.3%); (5) the sensitivity, specificity, positive- and negative-predictive values of TUI to diagnose congenital heart disease in cases where both B-mode and CDI volume datasets were acquired prenatally were 92.9%, 98.8%, 92.9% and 98.8%, respectively. CONCLUSION: Standard transverse planes commonly used to examine the fetal heart can be automatically displayed with TUI in the majority of fetuses undergoing 4D US with STIC. Due to the retrospective nature of this study, the results should be interpreted with caution and independently confirmed before this methodology is introduced into clinical practice. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate whether neonatal morbidity differs in spontaneous compared with indicated preterm births in extremely premature neonates., Study Design: This is a retrospective cohort study including births ≤28 weeks at a single institution from 2011 to 2020. Births were categorized as either medically indicated or spontaneous preterm deliveries. The primary outcome was inhospital mortality and serious morbidity in survivors. t -tests, Fisher's exact tests, chi-square tests, and logistic regression models were utilized as appropriate. p  < 0.05 was significant., Results: Two hundred and twenty-seven births were included, with two-thirds representing spontaneous births (65.6%, 149/227) and one-third categorized as medically indicated births (34.4%, 78/227). Inhospital mortality was more common in the spontaneous preterm birth group ( p  = 0.04), while inhospital morbidity did not significantly vary between the medically indicated and spontaneous birth groups ( p  = 0.32). There was no difference in inhospital morbidity or mortality by maternal race. In multivariate models of inhospital morbidity and mortality, gestational age was the only significant predictor of adverse outcomes., Conclusion: Despite inhospital mortality being more common in spontaneous preterm births, inhospital mortality and significant morbidity are best accounted for by gestational age alone., Key Points: · Inhospital death is more common in spontaneous preterm births.. · Perinatal outcomes do not differ on the basis of racial/ethnic group.. · Gestational age is the best predictor of inhospital morbidity and mortality.., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Fetal aqueductal stenosis (AS) affects approximately 1:1,000 pregnancies. Obstruction of cerebral spinal fluid circulation occurs at the aqueduct of Sylvius, leading to progressive hydrocephalus and macrocephaly, which often necessitates cesarean section (CS). The purpose of this study was to describe maternal outcomes associated with fetal AS., Methods: This study is conducted through the North American Fetal Therapy Network (NAFTNet). Subjects with a prenatal diagnosis of severe fetal central nervous system ventriculomegaly were recruited and followed longitudinally. Maternal events around the delivery of fetuses with AS were recorded and analyzed., Results: Thirty-seven subjects with fetal AS confirmed by neonatal neuroimaging were analyzed. The average gestational age at delivery was 36.7 weeks. Overall, 86% were delivered by CS, and 62% of these were elective. Ninety-one percent of CSs were performed through a Pfannenstiel abdominal incision. A classical uterine incision was required in 13% of cesarean deliveries. The peripartum complication rate was 27%., Conclusion: Women carrying a fetus with AS were at risk for preterm birth, cesarean delivery, a classical uterine incision, and peripartum complications. These data highlight the maternal morbidity associated with fetal AS and the potential benefit of in utero therapy not only for neonatal outcomes but also for maternal outcomes., (© 2024 S. Karger AG, Basel.)

Introduction: Prenatally diagnosed congenital lung malformations (CLMs) are monitored via ultrasound and measured by congenital pulmonary airway malformation volume ratios (CVRs) which can predict postnatal respiratory symptoms. This study compared CVR to postnatal lesion size to help guide prenatal counseling., Methods: A retrospective chart review evaluated the prenatal imaging and postnatal outcomes for patients who were prenatally diagnosed with CLMs and had a postnatal computed tomography (CT) scan at one institution., Results: Fifty-seven patients were included. Four had symptoms requiring urgent resection. The remaining were discharged and had clinic follow-up with CT scan to determine next steps: five had no identified lesions, eight had lesions whose diagnosis did not warrant an operation, and 40 had lesions whose diagnosis rendered size a factor in operative decision-making. Of these 40, 26/40 patients (65%) underwent elective resection (median maximum CVR 0.97; median lesion size 4 cm) and 14/40 patients (35%) were observed without resection (median maximum CVR 0.5; median lesion size 3 cm). There was a positive correlation between prenatal CVR and postnatal lesion size, with R-squared = 0.46. Maximum CVRs were better than last CVRs when predicting whether postnatal CT size would fall above or below our institution's level of recommended resection, with an area under the curve of 0.85 and a CVR cut-point of 0.61., Conclusions: For newborns with asymptomatic CLMs, higher maximum CVRs correlated with larger size on postnatal CT. A maximum CVR ≤0.6 was correlated with a smaller postnatal CT size that may be eligible for nonoperative management. While these results are not intended to recommend surgery based on higher CVRs alone, this information could potentially be used to reassure expectant parents whose babies' prenatal imaging demonstrate lower maximum CVRs., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: A critical component of an evidence-based reassessment of in-utero intervention for fetal aqueductal stenosis (fetal AS) is determining if the prenatal diagnosis can be accurately made at a gestational age amenable to in-utero intervention., Methods: A multicenter, prospective, observational study was conducted through the North American Fetal Therapy Network (NAFTNet). Pregnancies complicated by severe central nervous system (CNS) ventriculomegaly (lateral ventricle diameter &gt;15 mm) not secondary to a primary diagnosis (myelomeningocele, encephalocele, etc.) were recruited at diagnosis. Imaging and laboratory findings were recorded in an online REDCap database. After evaluation, investigators were asked to render their degree of confidence in the diagnosis of fetal AS. The prenatal diagnosis was compared to the postnatal diagnosis obtained through neonatal neuroimaging. Performance characteristics of ultrasound and magnetic resonance imaging (MRI) were calculated, as was the mean gestational age at diagnosis., Results: Between April 2015 and October 2022, eleven NAFTNet centers contributed 64 subjects with severe fetal CNS ventriculomegaly. Of these, 56 had both prenatal and postnatal diagnoses recorded. Ultrasound revealed 32 fetal AS true positives, 4 false positives, 7 false negatives, and 13 true negatives, rendering a sensitivity of 0.82, a specificity of 0.76, a positive predictive value of 0.89, and a negative predictive value of 0.65. The mean gestational age at diagnosis by ultrasound was 25.5 weeks (std +/- 4.7 weeks). The proportion of agreement (true positive + true negative/n) was highest at 24 weeks gestation. For fetal MRI (n = 35), the sensitivity for fetal AS was 0.95, specificity was 0.69, positive predictive value was 0.84, and negative predictive value was 0.90. MRI was performed at 25 weeks on average., Conclusion: The prenatal diagnosis of fetal AS can be made with accuracy at a gestational age potentially amenable to in-utero intervention. Only 7% of subjects were incorrectly diagnosed prenatally with fetal AS by ultrasound and 11% by MRI. Diagnostic accuracy of fetal AS will likely improve with increased experience., (© 2024 S. Karger AG, Basel.)

Measurement of blood flow to the brain in neonates would be a very valuable addition to the medical diagnostic armamentarium. Such conditions such as assessment of closure of a patent ductus arteriosus (PDA) would greatly benefit from such an evaluation. However, measurement of cerebral blood flow in a clinical setting has proven very difficult and, as such, is rarely employed. Present techniques are often cumbersome, difficult to perform and potentially dangerous for very low birth weight (VLBW) infants. We have been developing an ultrasound blood volume flow technique that could be routinely used to assess blood flow to the brain in neonates. By scanning through the anterior fontanelles of 10 normal, full-term newborn infants, we were able to estimate total brain blood flows that closely match those published in the literature using much more invasive and technically demanding methods. Our method is safe, easy to do, does not require contrast agents and can be performed in the baby's incubator. The method has the potential for monitoring and assessing blood flows to the brain and could be used to routinely assess cerebral blood flow in many different clinical conditions., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: Placental blood flow analysis is complicated by having both maternal and fetal flow components. Using the Fast Fourier Transform (FFT) of the umbilical venous pulse wave spectra (PW) envelope, we could simultaneously assess maternal/fetal blood flow in the placenta and investigate if normal and intrauterine growth restriction (IUGR)/pre-eclamptic pregnancies could be distinguished., Methods: This retrospective study included normal gestations (N = 11) and gestations with IUGR, pre-eclampsia, or both (N = 13). Umbilical vein PW were acquired and spectral envelopes were identified as a function of time and analyzed by FFT. Base-10 logarithms of the ratios of the maternal/fetal spectral peaks (LRSP) were compared in normal and IUGR/pre-eclamptic populations (two-tailed t-test). Body mass index (BMI), gestational age at scan time, placental position, and weight-normalized umbilical vein blood volume flow (two-tailed t-test, analysis of variance [ANOVA] analysis) were tested. P < .05 was considered significant., Results: The LRSP for normal and IUGR/pre-eclamptic pregnancies were 0.141 ± 0.180 and -0.072 ± 0.262 (mean ± standard deviation), respectively (P = .033). We detected differences between normal gestations and combinations of LRSP and weight-normalized umbilical venous blood flows. Placental effects based on LRSPs and blood flow may act synergistically in cases with both pre-eclampsia and IUGR (P = .014). No other significant associations were seen., Conclusions: In this preliminary study, we showed that umbilical venous flow contains markers related to placental maternal/fetal blood flow, which can be used to assess IUGR and pre-eclampsia. When coupled with umbilical cord blood flow, this new marker may potentially identify the primary causes of the two conditions., (© 2021 American Institute of Ultrasound in Medicine.)

Objective: The ideal time for birth in pregnancies diagnosed with vasa previa remains unclear. We conducted a systematic review aiming to identify the gestational age at delivery that best balances the risks for prematurity with that of pregnancy prolongation in cases with prenatally diagnosed vasa previa., Data Sources: Ovid MEDLINE, PubMed, CINAHL, Embase, Scopus, and Web of Science were searched from inception to January 2022., Study Eligibility Criteria: The intervention analyzed was delivery at various gestational ages in pregnancies prenatally diagnosed with vasa previa. Cohort studies, case series, and case reports were included in the qualitative synthesis. When summary figures could not be obtained directly from the studies for the quantitative synthesis, authors were contacted and asked to provide a breakdown of perinatal outcomes by gestational age at birth., Methods: Study appraisal was completed using the National Institutes of Health quality assessment tool for the respective study types. Statistical analysis was performed using a random-effects meta-analysis of proportions., Results: The search identified 3435 studies of which 1264 were duplicates. After screening 2171 titles and abstracts, 140 studies proceeded to the full-text screen. A total of 37 studies were included for analysis, 14 of which were included in a quantitative synthesis. Among 490 neonates, there were 2 perinatal deaths (0.4%), both of which were neonatal deaths before 32 weeks' gestation. In general, the rate of neonatal complications decreased steadily from <32 weeks' gestation (4.6% rate of perinatal death, 91.2% respiratory distress, 11.4% 5-minute Apgar score <7, 23.3% neonatal blood transfusion, 100% neonatal intensive care unit admission, and 100% low birthweight) to 36 weeks' gestation (0% perinatal death, 5.3% respiratory distress, 0% 5-minute Apgar score <7, 2.9% neonatal blood transfusion, 29.2% neonatal intensive care unit admission, and 30.9% low birthweight). Complications then increased slightly at 37 weeks' gestation before decreasing again at 38 weeks' gestation., Conclusion: Prolonging pregnancies until 36 weeks' gestation seems to be safe and beneficial in otherwise uncomplicated pregnancies with antenatally diagnosed vasa previa., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Maternal prenatal status, as encapsulated by that to which a mother is exposed through diet and environment, is a key determinant of offspring health and disease. Alterations in DNA methylation (DNAm) may be a mechanism through which suboptimal prenatal conditions confer disease risk later in life. One-carbon metabolism (OCM) is critical to both fetal development and in supplying methyl donors needed for DNAm. Plasma concentrations of one-carbon metabolites across maternal first trimester (M1), maternal term (M3), and infant cord blood (CB) at birth were tested for association with DNAm patterns in CB from the Michigan Mother and Infant Pairs (MMIP) pregnancy cohort. The Illumina Infinium MethylationEPIC BeadChip was used to quantitatively evaluate DNAm across the epigenome. Global and single-site DNAm and metabolite models were adjusted for infant sex, estimated cell type proportions, and batch as covariates. Change in mean metabolite concentration across pregnancy (M1 to M3) was significantly different for S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), betaine, and choline. Both M1 SAH and CB SAH were significantly associated with the global distribution of DNAm in CB, with indications of a shift toward less methylation. M3 SAH and CB SAH also displayed significant associations with locus-specific DNAm in infant CB (FDR<0.05). Our findings underscore the role of maternal one-carbon metabolites in shifting the global DNAm pattern in CB and emphasizes the need to closely evaluate how dietary status influences cellular methylation potential and ultimately offspring health., (Copyright © 2022. Published by Elsevier Inc.)

Study Objectives: Habitual snoring has been associated with hypertensive disorders of pregnancy. However, exactly when blood pressure (BP) trajectories diverge between pregnant women with and without habitual snoring is unknown. Moreover, the potentially differential impact of chronic vs pregnancy-onset habitual snoring on maternal BP trajectories during pregnancy has not been examined. This study compared patterns of BP across pregnancy in 3 groups of women: those with chronic habitual snoring, those with pregnancy-onset habitual snoring, and nonhabitual snoring "controls.", Methods: In a cohort study of 1,305 pregnant women from a large medical center, participants were asked about habitual snoring (≥ 3 nights/week) and whether their symptoms began prior to or during pregnancy. Demographic, health, and BP data throughout pregnancy were abstracted from medical charts. Linear mixed models were used to examine associations between habitual snoring-onset and pregnancy BP trajectories., Results: A third of women reported snoring prior to pregnancy (chronic snoring) and an additional 23% reported pregnancy-onset snoring. Mean maternal age (SD) was 29.5 (5.6), 30 (6), and 30.5 (5.7) years in controls, chronic, and pregnancy-onset snoring, respectively. Overall, women with pregnancy-onset snoring had higher mean systolic BP and diastolic BP compared to those with chronic habitual snoring or nonhabitual snoring. In gestational week-specific comparisons with controls, systolic BP became significantly higher around 18 weeks' gestation among women with pregnancy-onset snoring and in the third trimester among women with chronic snoring. These differences became detectable at 1 mm Hg and increased thereafter, reaching 3 mm Hg-BP difference at 40 weeks' gestation in women with pregnancy-onset snoring relative to controls. Pairwise mean differences in diastolic BP were significant only among women with pregnancy-onset snoring relative to controls, after 15 weeks' gestation., Conclusions: Pregnancy-onset and chronic maternal snoring are associated with higher BPs beginning in the second and third trimester, respectively. Pregnancy BP trajectories could identify critical windows for enhanced BP surveillance; the divergent BP trajectories suggest that the 2 groups of women with habitual snoring in pregnancy may need to be considered separately when gestational time intervals are evaluated for increased BP monitoring., Citation: Dunietz GL, Hao W, Shedden K, et al. Maternal habitual snoring and blood pressure trajectories in pregnancy. J Clin Sleep Med. 2022;18(1):31-38., (© 2022 American Academy of Sleep Medicine.)

Introduction: Uterine incision based on the placental location in open maternal-fetal surgery (OMFS) has never been evaluated in regard to maternal or fetal outcomes., Objective: The aim of this study was to investigate whether an anterior placenta was associated with increased rates of intraoperative, perioperative, antepartum, obstetric, or neonatal complications in mothers and babies who underwent OMFS for fetal myelomeningocele (fMMC) closure., Methods: Data from the international multicenter prospective registry of patients who underwent OMFS for fMMC closure (fMMC Consortium Registry, December 15, 2010-June 31, 2019) was used to compare fetal and maternal outcomes between anterior and posterior placental locations., Results: The placental location for 623 patients was evenly distributed between anterior (51%) and posterior (49%) locations. Intraoperative fetal bradycardia (8.3% vs. 3.0%, p = 0.005) and performance of fetal resuscitation (3.6% vs. 1.0%, p = 0.034) occurred more frequently in cases with an anterior placenta when compared to those with a posterior placenta. Obstetric outcomes including membrane separation, placental abruption, and spontaneous rupture of membranes were not different among the 2 groups. However, thinning of the hysterotomy site (27.7% vs. 17.7%, p = 0.008) occurred more frequently in cases of an anterior placenta. Gestational age (GA) at delivery (p = 0.583) and length of stay in the neonatal intensive care unit (p = 0.655) were similar between the 2 groups. Fetal incision dehiscence and wound revision were not significantly different between groups. Critical clinical outcomes including fetal demise, perinatal death, and neonatal death were all infrequent occurrences and not associated with the placental location., Conclusions: An anterior placental location is associated with increased risk of intraoperative fetal resuscitation and increased thinning at the hysterotomy closure site. Individual institutional experiences may have varied, but the aggregate data from the fMMC Consortium did not show a significant impact on the GA at delivery or maternal or fetal clinical outcomes., (© 2021 S. Karger AG, Basel.)

Objective: Obstetricians infrequently encounter conjoined twins. Much of the clinical care literature focuses on postnatal management from a neonatology and pediatric surgery perspective; guidance on obstetrical management is limited. We outline steps for prenatal evaluation, obstetrical care, and delivery planning., Study Design: Experiences with two cases of conjoined twins., Results: We identified several points throughout the planning, delivery, and postnatal process that are important to highlight for optimizing clinical outcome, patient safety, and parental satisfaction., Conclusion: After diagnosis, patients should be referred to a center experienced in the management of conjoined twins. Specialists in fields including maternal fetal medicine, pediatric surgery, neonatology, and radiology play a vital role in the management of these patients. Early referral allows for timely family counseling and decision-making. Prenatal evaluation beyond the first trimester should include a detailed ultrasound, fetal echocardiogram, and fetal MRI. 3D printed life-sized models can improve delivery planning and patient understanding., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Emerging literature has shown that women with sleep-disordered breathing (SDB) have increased risk for gestational hypertension/preeclampsia and gestational diabetes. Case reports suggest an association between maternal apnea and fetal heart rate deceleration but data are lacking on how maternal sleep impacts fetal health. Since decelerations may be associated with adverse outcomes, we sought to determine whether fetal heart rate decelerations were associated with SDB. A cohort study of third trimester pregnant women with a singleton fetus was conducted. Participants underwent a home sleep test with continuous portable electronic fetal monitoring. SDB was defined as a respiratory disturbance index (RDI)≥10 events/hour. The temporality between a respiratory event and fetal heart rate decelerations was determined to be present if a deceleration occurred < 30 s after a respiratory event. Forty women were included with mean (±SD) age, BMI, and gestational age of 32.0±5.5 years, 37.1±8.0 kg/m 2 , and 34.6±2.4 weeks respectively. Overall, n=23 (57.5%) women had SDB. Thirty-seven late decelerations were observed in 18 women; of these, 84% were temporally associated with a respiratory event. Nine of the 18 women (50%) had SDB. Ten prolonged decelerations were observed in 6 women of which nine (90%) were temporally associated with a respiratory event. Five of the six women (83%) had an RDI≥10. These initial data suggest that, in this population, the majority of both late and prolonged fetal heart rate decelerations occur with a maternal respiratory event. Since respiratory events are characteristic of maternal SDB, this raises the possibility that SDB may influence fetal well-being., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Abstract: This study evaluated the technical feasibility of 2-dimensional transvaginal shear wave elastography to quantify cervical stiffness in nonpregnant and pregnant women and established normal values in each group. With institutional review board approval, we performed a prospective study with an age-matched historical control design. Sixteen premenopausal nonpregnant women without cervical pathology and 17 low-risk pregnant women (gestational age 17-33 weeks) were enrolled. Cervical shear wave speeds were measured on a SuperSonic Aixplorer machine. The mean shear wave speeds of anterior cervix were 4.96 ± 1.96 m/s in nonpregnant women and 1.92 ± 0.31 m/s in pregnant women. No significant stiffness difference was found between the anterior and posterior cervix (P = 0.15). The upper cervix was stiffer than the lower cervix in the pregnant women (P = 0.00012). Transvaginal shear wave elastography reveals that cervix at a midterm gestation is significantly softer than nonpregnant cervix (P < 0.0001) and suggests a spatial stiffness gradient along the length of the cervix, consistent with histopathology and limited elastography literature. Our results indicate the potential of transvaginal shear wave elastography to provide objective and quantitative estimates of cervical stiffness, especially during pregnancy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We are studying a new method for estimating blood volume flow that uses 3-dimensional ultrasound to measure the total integrated flux through an ultrasound-generated Gaussian surface that intersects the umbilical cord. This method makes none of the assumptions typically required with standard 1-dimensional spectral Doppler volume flow estimates. We compared the variations in volume flow estimates between techniques in the umbilical vein., Methods: The study was Institutional Review Board approved, and all 12 patients gave informed consent. Because we had no reference standard for the true umbilical vein volume flow, we compared the variations of the measurements for the flow measurement techniques. At least 3 separate spectral Doppler and 3 separate Gaussian surface measurements were made along the umbilical vein. Means, standard deviations, and coefficients of variation (standard deviation/mean) for the flow estimation techniques were calculated for each patient. P < .05 was considered significant., Results: The ranges of the mean volume flow estimates were 174 to 577 mL/min for the spectral Doppler method and 100 to 341 mL/min for the Gaussian surface integration (GSI) method. The mean standard deviations (mean ± SD) were 161 ± 95 and 45 ± 48 mL/min for the spectral Doppler and GSI methods, respectively (P < .003). The mean coefficients of variation were 0.46 ± 0.17 and 0.18 ± 0.14 for the spectral Doppler and GSI methods respectively (P < 0.002)., Conclusions: The new volume flow estimation method using 3-dimensional ultrasound appears to have significantly less variation in estimates than the standard 1-dimensional spectral Doppler method., (© 2020 American Institute of Ultrasound in Medicine.)

Introduction: Open fetal surgery requires a hemostatic hysterotomy that minimizes membrane separation. For over 30 years, the standard of care for hysterotomy in the gravid uterus has been the AutoSuture Premium Poly CS*-57 stapler., Objective: In this study, we sought to test the feasibility of hysterotomy in a rhesus monkey model with the Harmonic ACE®+7 Shears., Methods: A gravid rhesus monkey underwent midgestation hysterotomy at approximately 90 days of gestation (2nd trimester; term = 165 ± 10 days) using the Harmonic ACE®+7 Shears. A two-layer uterine closure was completed and the dam was monitored by ultrasound intermittently throughout the pregnancy. At 58 days after hysterotomy (near term), a final surgery was performed to evaluate the uterus and hysterotomy site., Results: A 3.5-cm hysterotomy was completed in 2 min 7 s. The opening was hemostatic and the membranes were sealed. Immediately after closure and throughout the pregnancy, ultrasound revealed intact membranes without separation and normal amniotic fluid levels. At term, the scar was well healed without signs of thinning or dehiscence., Conclusions: The Harmonic ACE®+7 Shears produced a hemostatic midgestation hysterotomy with membrane sealing in the rhesus monkey model. Importantly, healing was acceptable., (© 2020 S. Karger AG, Basel.)

Aim: To classify the association between the maternal lipidome and DNA methylation in cord blood leukocytes. Materials & methods: Untargeted lipidomics was performed on first trimester maternal plasma (M1) and delivery maternal plasma (M3) in 100 mothers from the Michigan Mother-Infant Pairs cohort. Cord blood leukocyte DNA methylation was profiled using the Infinium EPIC bead array and empirical Bayes modeling identified differential DNA methylation related to maternal lipid groups. Results: M3-saturated lysophosphatidylcholine was associated with 45 differentially methylated loci and M3-saturated lysophosphatidylethanolamine was associated with 18 differentially methylated loci. Biological pathways enriched among differentially methylated loci by M3 saturated lysophosphatidylcholines were related to cell proliferation and growth. Conclusion: The maternal lipidome may be influential in establishing the infant epigenome.

Purpose: Prenatal risk assessment of congenital diaphragmatic hernia (CDH) relies on prenatal ultrasound (U/S) and fetal magnetic resonance imaging (MRI). When the modalities differ in prognosis, it is unclear which is more reliable., Methods: Retrospective chart review identified cases of prenatally diagnosed CDH from 4/2010-6/2018 meeting inclusion criteria. Demographic, radiologic, and postnatal outcomes data were collected. Ultrasound- versus MRI-based prognosis (mild, moderate, and severe) was compared with clinical outcomes. Kappa measures compared congruency in disease severity scaling between imaging modalities, while logistic regression and receiver operating characteristics curves compared the ability of each modality to predict outcomes., Results: Forty-two patients met criteria. Both U/S- and MRI-based prognosis categories differentiated for survival. MRI categories differentiated for ECMO use, surgical repair, and defect type. O/e TFLV better discriminated for survivors and defect type than o/e LHR. Seventeen (40.5%) had discordant prenatal prognostic categories. In 13/17 (76.5%), o/e TFLV predicted higher severity when compared to o/e LHR, but sample size was insufficient to compare accuracy in cases of discordance., Conclusions: Clinical outcomes suggest fetal MRI may more accurately predict severe pulmonary hypoplasia compared to prenatal ultrasound. Our analysis suggests fetal MRI is a valuable adjunct in the prenatal evaluation of CDH., Level of Evidence: Level III., Type of Study: Retrospective Review., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Major alterations in metabolism occur during pregnancy enabling the mother to provide adequate nutrients to support infant development, affecting birth weight (BW) and potentially long-term risk of obesity and cardiometabolic disease. We classified dynamic changes in the maternal lipidome during pregnancy and identified lipids associated with Fenton BW z-score and the umbilical cord blood (CB) lipidome. Lipidomics was performed on first trimester maternal plasma (M1), delivery maternal plasma (M3), and CB plasma in 106 mother-infant dyads. Shifts in the maternal and CB lipidome were consistent with the selective transport of long-chain polyunsaturated fatty acids (PUFA) as well as lysophosphatidylcholine (LysoPC) and lysophosphatidylethanolamine (LysoPE) species into CB. Partial correlation networks demonstrated fluctuations in correlations between lipid groups at M1, M3, and CB, signifying differences in lipid metabolism. Using linear models, LysoPC and LysoPE groups in CB were positively associated with BW. M1 PUFA containing triglycerides (TG) and phospholipids were correlated with CB LysoPC and LysoPE species and total CB polyunsaturated TGs. These results indicate that early gestational maternal lipid levels influence the CB lipidome and its relationship with BW, suggesting an opportunity to modulate maternal diet and improve long-term offspring cardiometabolic health.

Background: Congenital diaphragmatic hernia (CDH) is a potentially lethal birth defect, and identifying prenatal predictors of outcome is important. Observed-to-expected total fetal lung volume (o/e TFLV) has been shown to be a predictor of severity and useful in risk stratification but is variable due to different TFLV formulas., Objectives: To calculate o/e TFLV for CDH patients part of a twin gestation using the unaffected sibling as an internal control and comparing these values to those calculated using published formulas for TFLV., Methods: Seven twin gestations with one fetus affected by CDH were identified between 2006 and 2017. The lung volume for each twin was calculated using magnetic resonance imaging (MRI), and o/e TFLV was calculated using the unaffected twin's TFLV. This percentage was then compared to the o/e TFLV calculated using published formulas., Results: Lung volumes in the unaffected twins were within normal ranges at the lower end of the spectrum. No single TFLV formula was found to correlate perfectly. Intraclass correlation coefficient estimate was most consistent for o/e TFLV calculated with the Meyers formula and supported by Bland-Altman plots., Conclusions: O/e TFLV measured in CDH/non-CDH twin gestations using the unaffected sibling demonstrated agreement with o/e TFLV calculated using the Meyers formula. We urge the fetal community to standardize the method, use, and interpretation of fetal MRI in the prenatal evaluation of CDH., (© 2019 S. Karger AG, Basel.)

Background: Advances in prenatal imaging is increasing detection of abnormally dilated bowel. There is no literature to date defining the criteria for a dilated rectum or its association with postnatal pathology. The aim of this study is to investigate the clinical significance of a prenatally identified dilated rectum., Methods: A retrospective review was performed of all cases of "dilated bowel" on prenatal ultrasound between January 2000 and December 2017 at a single institution. We excluded ventral wall defects from review and sought to include only cases of a prominent or dilated rectum. Collected data included prenatal bowel measurements, postnatal diagnoses, need for surgical intervention, and outcomes. Descriptive statistics were applied., Results: One hundred and ninety-three cases of prenatal "dilated bowel" were identified in which 12 (6.2%) had specifically visualized a prominent or dilated rectum. Nine of these (75.0%) had no rectal or intestinal abnormality on postnatal evaluation and were discharged feeding and defecating normally. The remaining three cases exhibited clinical pathology necessitating additional management: (1) meconium plug, (2) jejunal atresia with cecal perforation, and (3) rectal perforation with retroperitoneal abscess. All three had rectal biopsies with identification of ganglionated submucosa., Conclusions: Although a prenatal dilated rectum is a normal variant in the vast majority of cases, it may be associated with a gastrointestinal abnormality requiring surgical intervention. Interestingly, there were no cases of Hirschsprung's disease or anorectal malformations in this cohort. These results, in conjunction with continued efforts to identify and define rectal dilation, are useful for prenatal counseling and postnatal evaluation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Exposures to endocrine disrupting chemicals and metals are near ubiquitous worldwide, and their potential impact on children is a major public health concern. This pilot study was designed to characterize exposures to phthalates, phenols and metals among pregnant women in the first trimester, and to examine associations with fetal biometrics and birth weight. A total of 41 chemicals and elements were analyzed in urine from 56 mothers with full-term newborns from the Michigan Mother-Infant Pairs study. Bivariate analyses identified predictors of exposure biomarkers. Associations between birth weight, Fenton z-scores and second trimester fetal biometrics with toxicants were examined via multivariable linear regression. An average of 30 toxicants were detected in maternal urine. Fast food consumption was associated with several phthalate metabolites, phenols and metals, and canned food consumption with bisphenol F (P &lt;0.05). Mono (3-carboxypropyl) phthalate was significantly associated with higher birth weight and Fenton z-score while the opposite was observed for bisphenol S. Estimated femur length from ultrasonography was significantly inversely associated with arsenic, barium and lead. While limited by sample size, this study is one of the first to evaluate birth outcomes with respect to emerging endocrine disrupting chemicals and to examine associations between toxicants and fetal biometrics. Exposure assessment was provided by the National Institute of Environmental Health Sciences' Children's Health Exposure Analysis Resource (NIEHS CHEAR), a resource available to children's studies with the goal of combining data across cohorts in an effort to characterize the impact of toxicants on child health from birth and beyond.

Background: Although fetal ultrasound, fetal MRI and postnatal CT are now widely used in the evaluation of congenital lung malformations (CLM), their diagnostic accuracy remains undefined., Objective: To correlate prenatal and postnatal imaging studies with pathological data after CLM resection., Design: Retrospective, descriptive case series study., Setting: A North American tertiary care centre., Patients: One hundred and three consecutive lung resections for a suspected CLM between 1 January 2005 and 31 December 2015., Main Outcome Measures: Diagnostic accuracy of imaging diagnosis compared with pathological evaluation., Results: Pathological diagnoses included congenital pulmonary airway malformation ((CPAM) n=45, 44%), bronchopulmonary sequestration (BPS; n=25, 24%), CPAM/BPS hybrid lesions (n=22, 21%) and pleuropulmonary blastoma (n=2, 2%). Fetal ultrasound detected 85 (82.5%) lesions and correctly diagnosed whether or not a lesion was a CPAM in 75% of cases (sensitivity 93%, specificity 32%). Fetal MRI had a similar concordance rate (73%) but was superior in correctly determining whether a systemic feeding vessel was present in 80% of cases (sensitivity 71%, specificity 88%) compared with an ultrasound accuracy rate of 72% (sensitivity 49%, specificity 93%). By comparison, postnatal CT correctly diagnosed whether a CPAM was present in 84% of cases (sensitivity 86%, specificity 77%) and whether a systemic feeding vessel was present in 90% of cases (sensitivity 92%, specificity 88%)., Conclusions: Fetal ultrasound remains an important tool in the detection and evaluation of congenital lung malformations. However, it does not correctly predict histology in approximately 25% of prenatally detected CLMs and remains limited by relatively poor sensitivity for systemic feeding vessels pathognomic for a bronchopulmonary sequestration. These data suggest the importance of obtaining additional cross-sectional imaging, preferably a postnatal CT scan, in all patients to help counsel families and to guide in the optimal management of these lesions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We hypothesized that surgical energy could be used to create hysterotomies in open fetal surgery., Study Design: Initial studies compared the LigaSure Impact and Harmonic ACE + 7 Shears in the efficiency of hysterotomy and thermal damage. Pregnant ewes at an estimated gestational age (EGA) of 116 to 120 days (term = 145; n  = 7) underwent hysterotomy using either device. Hysterotomy edges were resected, and thermal injury extent was determined by histopathological assessment. Upon determining a superior device, subsequent studies compared this to the AutoSuture Premium Poly CS*-57 Stapler in uterine healing. Pregnant ewes ( n  = 6) at an EGA of 87 to 93 days underwent 6-cm hysterotomy in each gravid horn with either the stapler ( n  = 5) or Harmonic ( n  = 5) followed by closure and animal recovery. After 37 to 42 days, uterine healing was assessed by evaluating tensile strength and histopathology., Results: Thermal damage was more extensive with the LigaSure ( n  = 11 hysterotomies) than with the Harmonic ( n  = 11; 5.6 ± 1 vs. 3.1 ± 0.6 mm; p  < 0.0001);therefore, the Harmonic was selected for healing studies. Gross scar appearance and tensile strength were the same between the Harmonic and stapler. The stapler caused more fibrosis (4/7 samples with "moderate" fibrosis vs. 0/8 with the Harmonic; p  = 0.02)., Conclusion: The Harmonic ACE + 7 caused less thermal injury than the LigaSure Impact and performed similar to the CS*-57 Stapler in uterine healing with continued gestation., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Open maternal-fetal surgery for fetal myelomeningocele results in reduction in neonatal morbidity related to spina bifida but may be associated with fetal, neonatal, and maternal complications in subsequent pregnancies., Objective: The objective of this study was to ascertain obstetric risk in subsequent pregnancies after open maternal-fetal surgery for fetal myelomeningocele closure., Study Design: An international multicenter prospective observational registry created to track and report maternal, obstetric, fetal/neonatal, and subsequent pregnancy outcomes following open maternal-fetal surgery for fetal myelomeningocele was evaluated for subsequent pregnancy outcome variables. Institutional Review Board approval was obtained for the registry., Results: From 693 cases of open maternal-fetal surgery for fetal myelomeningocele closure entered into the registry, 77 subsequent pregnancies in 60 women were identified. The overall live birth rate was 96.2%, with 52 pregnancies delivering beyond 20 weeks gestational age and median gestational age at delivery of 37 (36.3-37.1) weeks. The uterine rupture rate was 9.6% (n = 5), resulting in 2 fetal deaths. Maternal transfusion was required in 4 patients (7.7%)., Conclusion: The risk of uterine rupture or dehiscence in subsequent pregnancies with associated fetal morbidity after open maternal-fetal surgery is significant, but is similar to that reported for subsequent pregnancies after classical cesarean deliveries. Future pregnancy considerations should be included in initial counseling for women contemplating open maternal-fetal surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Despite improvements in fetal survival for pregnancies affected by twin-twin transfusion syndrome since the introduction of laser photocoagulation, prematurity remains a major source of neonatal morbidity and mortality., Objective: To investigate the indications and factors influencing the timing of delivery following laser treatment, we collected delivery information regarding twin-twin transfusion syndrome cases in a large multicenter cohort., Study Design: Eleven North American Fetal Therapy Network (NAFTNet) centers conducted a retrospective review of twin-twin transfusion syndrome patients who underwent laser photocoagulation. Clinical, demographic and ultrasound variables including twin-twin transfusion syndrome stage, and gestational age at treatment and delivery were recorded. Primary and secondary maternal and fetal indications for delivery were identified. Univariate analysis was used to select candidate variables with significant correlation with latency and GA at delivery. Multivariable Cox regression with competing risk analysis was utilized to determine the independent associations., Results: A total of 847 pregnancies were analyzed. After laser, the average latency to delivery was 10.11 ± 4.8 weeks and the mean gestational age at delivery was 30.7 ± 4.5 weeks. Primary maternal indications for delivery comprised 79% of cases. The leading indications included spontaneous labor (46.8%), premature rupture of membranes (17.1%), and placental abruption (8.4%). Primary fetal indications accounted for 21% of cases and the most frequent indications included donor non-reassuring status (20.5%), abnormal donor Dopplers (15.1%), and donor growth restriction (14.5%). The most common secondary indications for delivery were premature rupture of membranes, spontaneous labor and donor growth restriction. Multivariate modeling found gestational age at diagnosis, stage, history of prior amnioreduction, cerclage, interwin membrane disruption, procedure complications and chorioamniotic membrane separation as predictors for both gestational age at delivery and latency., Conclusion: Premature delivery after laser therapy for twin-twin transfusion syndrome is primarily due to spontaneous labor, preterm premature rupture of membranes and non-reassuring status of the donor fetus. Placental abruption was found to be a frequent complication resulting in early delivery. Future research should be directed toward the goal of prolonging gestation after laser photocoagulation to further reduce morbidity and mortality associated with twin-twin transfusion syndrome., Competing Interests: The authors report no conflicts of interest.

Background: Sleep-disordered breathing (SDB) is linked to adverse pregnancy outcomes. However, little is known about the association of SDB with timing of delivery. We examined the association of snoring frequency, a key SDB marker, and snoring intensity, a correlate of SDB severity, with time-to-delivery among a cohort of pregnant women., Methods: In this prospective cohort study, 1483 third trimester pregnant women were recruited from the University of Michigan prenatal clinics. Women completed a questionnaire about their sleep, and demographic and pregnancy information was abstracted from medical charts. After exclusion of those with hypertension or diabetes, 954 women were classified into two groups by their snoring onset timing, chronic or pregnancy-onset. Within each of these groups, women were divided into four groups based on their snoring frequency and intensity: non-snorers; infrequent-quiet; frequent-quiet; or frequent-loud snorers. Cox proportional hazard regression models were used to investigate the association between snoring frequency and intensity and time-to-delivery, adjusting for maternal characteristics., Results: Chronic snoring was reported by half of the pregnant women, and of those, 7% were frequent-loud snorers. Deliveries before 38 weeks' gestation are completed occurred among 25% of women with chronic, frequent-loud snoring. Compared with pre-pregnancy non-snorers, women with chronic frequent-loud snoring had an increased hazard ratio for delivery (adjusted hazard ratio 1.60, 95% confidence interval 1.04, 2.45)., Conclusions: Snoring frequency and intensity is associated with time-to-delivery in women absent of hypertension or diabetes. Frequent-loud snoring may have a clinical utility to identify otherwise low-risk women who are likely to deliver earlier., (© 2018 John Wiley & Sons Ltd.)

Background: Hypertensive disorders of pregnancy (HDP) are linked to excessive maternal weight and frequent snoring. However, pathways between maternal excessive weight, pregnancy-onset snoring, and HDP are only partially estimated. We examined and quantified the total and direct associations between excessive maternal weight and incident HDP and their indirect pathway through pregnancy-onset snoring., Methods: Third trimester pregnant women enrolled from prenatal clinics of a large tertiary medical center. Sleep data were collected through a questionnaire. Demographic and pregnancy information and first trimester maternal weight were abstracted from medical charts. After exclusion of women with prepregnancy hypertension and/or chronic snoring, causal mediation analysis was used to estimate the total and direct association between maternal weight and incident HDP and their indirect association through pregnancy-onset snoring. The proportion of the mediated association through pregnancy-onset snoring from the total association of maternal weight and HDP was also quantified., Results: After excluding those with chronic hypertension and/or snoring, the final sample included 1,333 pregnant women. In adjusted analysis, excessive maternal weight was directly associated with incident HDP; odds ratio (OR) = 1.87 (95% confidence interval (CI) 1.30, 2.70). Pregnancy-onset snoring significantly mediated the association between maternal weight and incident HDP; OR = 1.08 (95% CI 1.01, 1.17). The mediated pathway accounted for 15% of the total association between maternal weight and incident HDP., Conclusions: Pregnancy-onset snoring mediates the association between maternal weight and incident HDP in women without prepregnancy snoring or hypertension. These findings demonstrate the relative contributions of excessive maternal weight and pregnancy-onset snoring to incident HDP.

Objective: To investigate whether maternal obstructive sleep apnea (OSA) is associated with changes in fetal growth trajectory., Study Design: Retrospective review of pregnant women who underwent overnight polysomnography. Fetal growth was estimated using sonographic biometric measurements obtained during routine prenatal care. Customized estimated fetal weight and birth weight centiles were calculated and impaired fetal growth was defined as birth weight <10th centile or a slowing of fetal growth by >33% during the last trimester. Logistic regression models were used to determine the relationship between maternal OSA and altered fetal growth after adjusting for potential covariates., Results: There were 48 women without and 31 women with OSA. There were no differences in the proportion of infants with birth weight <10th centile between women with and without OSA (23 vs. 25%, p = 1.0), However, the presence of maternal OSA was predictive of impaired fetal growth (aOR 3.9, 95% CI 1.2-12.6). Logistic regression models were repeated using only a slowing of fetal growth in the 3rd trimester (excluding birth weight <10th centile) and OSA predicted a slowing in fetal growth across the 3rd trimester (aOR 3.6, 95% CI 1.4-9.4). Fourteen additional women were treated with positive airway pressure during pregnancy; fetal growth was not significantly different in these women compared to controls., Conclusion: Obstructive sleep apnea is independently associated with altered fetal growth, which appears to be ameliorated with use of positive airway pressure.

Objectives: To investigate the association between umbilical vein blood volume flow and the condition of preeclampsia in an at-risk maternal patient cohort. Umbilical vein volume flow was quantified by a 3-dimensional (3D) sonographic technique that overcomes several limitations of standard sonographic flow measurement methods., Methods: A total of 35 patients, each with a singleton pregnancy, were recruited to provide 5 patients with preeclampsia, derived as a subset from a 26-patient at-risk group, and 9 patients with normal pregnancies. An ultrasound system equipped with a 2.0-8.0-MHz transducer was used to acquire multivolume 3D color flow and power mode data sets to compute the mean umbilical vein volume flow in patients with normal pregnancies and preeclampsia., Results: The gestational ages of the pregnancies ranged from 29.7 to 34.3 weeks in the patients with preeclampsia and from 25.9 to 34.7 weeks in the patients with normal pregnancies. Comparisons between patients with normal pregnancies and those with preeclampsia showed weight-normalized flow with a moderately high separation between groups (P = .11) and depth-corrected, weight-normalized flow with a statistically significant difference between groups (P = .035). Umbilical vein volume flow measurements were highly reproducible in the mean estimate, with an intrapatient relative SE of 12.1% ± 5.9% and an intrameasurement relative SE of 5.6% ± 1.9 %. In patients who developed pregnancy-induced hypertension or severe pregnancy-induced hypertension, umbilical vein volume flow suggested gestational hypertensive disorder before clinical diagnosis., Conclusions: Results indicate that mean depth-corrected, weight-normalized umbilical vein volume flow is reduced in pregnancies complicated by preeclampsia and that volume flow may indicate hypertensive disorder earlier in gestation. Volume flow measurements are highly reproducible, and further study in a larger clinical population is encouraged to determine whether 3D volume flow can complement the management of preeclampsia and, in general, at-risk pregnancy., (© 2017 by the American Institute of Ultrasound in Medicine.)

Twins represent 1%-2% of all pregnancies, yet continue to account for a disproportionate share of neonatal adverse events including neonatal intensive care admission, morbidity, and mortality. Ultrasonography is central to the proper diagnosis of the type of twinning. Ideally, ultrasonography is performed before 14 weeks of gestation to determine chorionicity and amnionicity. Correct identification of the chorionicity in a twin pregnancy facilitates proper counseling and management of the gestation, including ultrasonography follow-up. Herein, the different types of twinning are reviewed, together with the implications for ultrasonography monitoring of each specific type of twin gestation., (© 2018 International Federation of Gynecology and Obstetrics.)

Twin gestations are increasing in prevalence worldwide, and are potentially subject to medical complications which present uniquely complex ethical and psychosocial challenges for the pregnant patient and obstetrician to navigate. In this article, we explore these issues as they relate to medical decision-making in cases of discordant growth and discordant anomalies in both monochorionic and dichorionic twin pregnancies, including those affected by twin-twin transfusion syndrome, with particular attention to scenarios in which the individual fetuses hold competing interests. For each of these scenarios, we consider how decisions may positively or negatively impact one or both fetuses, and how familiarity with population outcomes, as well as sensitivity to the complex psychosocial circumstances surrounding these pregnancies, can support and inform shared decision-making., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Primary hydrothorax is a congenital anomaly affecting 1 in 10,000-15,000 pregnancies. The natural history of this condition is variable with some fetuses having spontaneous resolution and others showing progression. The associated pulmonary hypoplasia leads to increased perinatal morbidity and mortality. Optimal prenatal intervention remains controversial., Methods: After obtaining the Institutional Review Board approval, a retrospective review of all patients evaluated for a fetal pleural effusion in the Fetal Diagnosis and Treatment Center at The University of Michigan, between 2006 and 2016 was performed. Cases with secondary etiologies for an effusion or when families decided to pursue elective termination were excluded., Results: Pleural effusions were identified in 175 patients. Primary hydrothorax was diagnosed in 15 patients (8%). The effusions were bilateral in 13/15 cases (86%) and 10/15 (66%) had hydrops at presentation. All 15 patients with primary hydrothorax underwent prenatal intervention. Thoracentesis was performed in 14/15 cases (93%). Shunt placement was performed in 10/15 cases (66%). Shunt migration was seen in four patients (40%) and all of these underwent prenatal shunt replacement. Overall survival was 76%. The rates of prematurity and preterm premature rupture of membranes were 69% and 35%, respectively., Conclusions: Fetal intervention for the treatment of primary hydrothorax is effective, and it appears to confer a survival advantage. Both the fetuses and the mothers tolerated the procedures well. Preterm labor and preterm premature rupture of membranes remain an unsolved problem. Further studies are needed to understand the mechanisms behind the development of fetal hydrothorax., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Sacrococcygeal teratoma (SCT) with intraspinal extension is rare. There is a risk of paraplegia associated with prolonged spinal cord compression. We present the case of an infant with a prenatal diagnosis of an SCT with a large intraspinal component that was causing compression of the lower spinal cord. Ultrasound at 33 weeks showed bilateral lower extremity and foot movement without hydrops or cardiac failure. Multidisciplinary decision was made to administer betamethasone and proceed with Cesarean delivery at 34 weeks. A vigorous live-born female was delivered and a multilevel laminectomy was performed at day of life 4. The pelvic resection was performed at 4 months. Pathology revealed mature teratoma. She had an uncomplicated postoperative course, is ambulatory, continent of stool, and has no evidence of recurrence. We conclude that intraspinal extension of SCT should be evaluated prenatally with ultrasound and fetal MRI. If there is concern for spinal cord compression, early delivery and urgent decompressive laminectomy may diminish the neurologic sequelae of prolonged spinal cord compression. Since these cases are rare, risks of prematurity need to be weighed against the neurologic risks. These infants should be treated with a multidisciplinary approach., (© 2017 S. Karger AG, Basel.)

Endocrine disrupting chemicals (EDCs) pose a public health risk through disruption of normal biological processes. Identifying toxicoepigenetic mechanisms of developmental exposure-induced effects for EDCs, such as phthalates or bisphenol A (BPA), is essential. Here, we investigate whether maternal exposure to EDCs is predictive of infant DNA methylation at candidate gene regions. In the Michigan Mother-Infant Pairs (MMIP) cohort, DNA was extracted from cord blood leukocytes for methylation analysis by pyrosequencing (n = 116) and methylation changes related to first trimester levels of 9 phthalate metabolites and BPA. Growth and metabolism-related genes selected for methylation analysis included imprinted (IGF2, H19) and non-imprinted (PPARA, ESR1) genes along with LINE-1 repetitive elements. Findings revealed decreases in methylation of LINE-1, IGF2, and PPARA with increasing phthalate concentrations. For example, a log unit increase in ΣDEHP corresponded to a 1.03 [95% confidence interval (CI): -1.83, -0.22] percentage point decrease in PPARA methylation. Changes in DNA methylation were also inversely correlated with PPARA gene expression determined by RT-qPCR (r = -0.34, P = 0.02), thereby providing evidence in support of functional relevance. A sex-stratified analysis of EDCs and DNA methylation showed that some relationships were female-specific. For example, urinary BPA exposure was associated with a 1.35 (95%CI: -2.69, -0.01) percentage point decrease in IGF2 methylation and a 1.22 (95%CI: -2.27, -0.16) percentage point decrease in PPARA methylation in females only. These findings add to a body of evidence suggesting epigenetically labile regions may provide a conduit linking early exposures with disease risk later in life and that toxicoepigenetic susceptibility may be sex specific.

Objective: Perinatal loss (stillbirth or early infant death) is often a sudden, unexpected event for families. We evaluated who communicates the loss to the parents and who is there for support at the delivery or death., Study Design: We conducted a mail survey of 900 bereaved and 500 live-birth mothers to assess emotional, physical and reproductive health outcomes., Results: We had a 44% response rate at 9 months after birth or loss from 377 bereaved mothers and 232 with surviving infants. Bereaved women were less likely to have hospital staff or family members present at delivery. African-American (versus Caucasian) mothers were half as likely to have first heard about their stillbirth from a physician or midwife., Conclusion: This is the first large study documenting who communicates perinatal death to families and who is present for support. Hospitals should be aware that many bereaved families may lack support at critical times.

Maternal hyperglycemia is a risk factor for fetal cardiac anomalies. This study aimed to assess the effect of high glucose on human induced pluripotent stem cell-derived cardiomyocyte self-assembly into 3D microtissues and their calcium handling. Stem cells were differentiated to beating cardiomyocytes using established protocols. On the final day of the differentiation process, cells were treated with control media, 12 mM glucose, or 12 mM mannitol (an osmolality control). Once beating, the cardiac cells were dissociated with trypsin, collected, mixed with collagen, and plated into custom-made silicone micro molds in order to generate 3D cardiac microtissues. A time-lapse microscope took pictures every 4 h to quantify the kinetics of cellular self-assembly of 3D cardiac tissues. Fiber widths were recorded at 4-h intervals and plotted over time to assess cardiomyocyte 3D fiber self-assembly. Microtissue calcium flux was recorded with optical mapping by pacing microtissues at 0.5 and 1.0 Hz. Exposure to high glucose impaired the ability of cardiomyocytes to self-assemble into compact microtissues, but not their ability to spontaneously contract. Glucose-exposed cardiomyocytes took longer to self-assemble and finished as thicker fibers. When cardiac microtissues were paced at 0.5 and 1.0 Hz, those exposed to high glucose had altered calcium handling with shorter calcium transient durations, but larger amplitudes of the calcium transient when compared to controls. Additional studies are needed to elucidate a potential mechanism for these findings. This model provides a novel method to assess the effects of exposures on the cardiomyocytes' intrinsic abilities for organogenesis in 3D.