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BackgroundWorldwide, 10% of babies are born preterm, defined as a live birth before 37 weeks of gestation. Preterm birth is the leading cause of neonatal death, and survivors face lifelong risks of adverse outcomes. New approaches with large sample sizes are needed to identify strategies to predict and prevent preterm birth. The primary aims of the Washington University Prematurity Research Cohort Study were to conduct three prospective projects addressing possible causes of preterm birth and provide data and samples for future research.Study designPregnant patients were recruited into the cohort between January 2017 and January 2020. Consenting patients were enrolled into the study before 20 weeks' gestation and followed through delivery. Participants completed demographic and lifestyle surveys; provided maternal blood, placenta samples, and cord blood; and participated in up to three projects focused on underlying physiology of preterm birth: cervical imaging (Project 1), circadian rhythms (Project 2), and uterine magnetic resonance imaging and electromyometrial imaging (Project 3).ResultsA total of 1260 participants were enrolled and delivered during the study period. Of the participants, 706 (56%) were Black/African American, 494 (39%) were nulliparous, and 185 (15%) had a previous preterm birth. Of the 1260 participants, 1220 (97%) delivered a live infant. Of the 1220 with a live birth, 163 (14.1%) had preterm birth, of which 74 (6.1%) were spontaneous preterm birth. Of the 1220 participants with a live birth, 841 participated in cervical imaging, 1047 contributed data and/or samples on circadian rhythms, and 39 underwent uterine magnetic resonance imaging. Of the 39, 25 underwent electromyometrial imaging.ConclusionWe demonstrate feasibility of recruiting and retaining a diverse cohort in a complex prospective, longitudinal study throughout pregnancy. The extensive clinical, imaging, survey, and biologic data obtained will be used to explore cervical, uterine, and endocrine physiology of preterm birth and can be used to develop novel approaches to predict and prevent preterm birth.

Evolution of cis-regulatory sequences depends on how they affect gene expression and motivates both the identification and prediction of cis-regulatory variants responsible for expression differences within and between species. While much progress has been made in relating cis-regulatory variants to expression levels, the timing of gene activation and repression may also be important to the evolution of cis-regulatory sequences. We investigated allele-specific expression (ASE) dynamics within and between Saccharomyces species during the diauxic shift and found appreciable cis-acting variation in gene expression dynamics. Within-species ASE is associated with intergenic variants, and ASE dynamics are more strongly associated with insertions and deletions than ASE levels. To refine these associations, we used a high-throughput reporter assay to test promoter regions and individual variants. Within the subset of regions that recapitulated endogenous expression, we identified and characterized cis-regulatory variants that affect expression dynamics. Between species, chimeric promoter regions generate novel patterns and indicate constraints on the evolution of gene expression dynamics. We conclude that changes in cis-regulatory sequences can tune gene expression dynamics and that the interplay between expression dynamics and other aspects of expression is relevant to the evolution of cis-regulatory sequences.

Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in parturition would display accelerated evolution along the human and/or higher primate phylogenetic lineages to decrease the length of gestation and promote delivery of a smaller fetus that transits the birth canal more readily. Further, we tested whether current variation in such accelerated genes contributes to preterm birth risk. Evidence from allometric scaling of gestational age suggests human gestation has been shortened relative to other primates. Consistent with our hypothesis, many genes involved in reproduction show human acceleration in their coding or adjacent noncoding regions. We screened >8,400 SNPs in 150 human accelerated genes in 165 Finnish preterm and 163 control mothers for association with preterm birth. In this cohort, the most significant association was in FSHR, and 8 of the 10 most significant SNPs were in this gene. Further evidence for association of a linkage disequilibrium block of SNPs in FSHR, rs11686474, rs11680730, rs12473870, and rs1247381 was found in African Americans. By considering human acceleration, we identified a novel gene that may be associated with preterm birth, FSHR. We anticipate other human accelerated genes will similarly be associated with preterm birth risk and elucidate essential pathways for human parturition.

Introduction. Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is a relatively uncommon but traumatic condition occurring in the later stage of pregnancy as a complication of severe preeclampsia or eclampsia. Prompt brain computed tomography (CT) or magnetic resonance imaging (MRI) and a multidisciplinary management approach are required to improve perinatal outcome. Case. A 37-year-old, Gravida 6, Para 1-0-4-1, Hispanic female with a history of chronic hypertension presented at 26 weeks and 6 days of gestational age. She was noted to have hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome accompanied by fetal growth restriction (FGR), during ultrasound evaluation, warranting premature delivery. The infant was delivered in stable condition suffering no permanent neurological deficit. Conclusion. HELLP syndrome is an uncommon and traumatic obstetric event which can lead to neurological deficits if not managed in a responsive and rapid manner. The central aggravating factor seems to be hypertension induced preeclamptic or eclamptic episode and complications thereof. The syndrome itself is manifested by hemolytic anemia, increased liver enzymes, and decreasing platelet counts with a majority of neurological defects resulting from hemorrhagic stroke or subarachnoid hemorrhage (SAH). To minimize adverse perinatal outcomes, obstetric management of this medical complication must include rapid clinical assessment, diagnostic examination, and neurosurgery consultation.

Introduction. Amniotic band syndrome and sequence are a relatively rare condition in which congenital anomalies occur as a result of the adherence and entrapment of fetal parts with coarse fibrous bands of the amniotic membrane. A large percentage of reported cases have an atypical gestational history. The frequency of this obstetric complication is not affected by fetal gender, genetic abnormality, or prenatal infection. Case. A 21-year-old, G1P0 female parturient at 18 weeks and 5 days with a single intrauterine gestation during a routine ultrasound evaluation was noted to have amniotic band sequence. The pregnancy was subsequently complicated by preterm premature rupture of membranes with oligohydramnios, resulting in a surviving neonate scheduled for rehabilitative treatment. Conclusion. Amniotic band syndrome is an uncommon congenital anomaly resulting in multiple disfiguring and disabling manifestations. Several theories are proposed with most involving early rupture of the amnion and entanglement of fetal parts by amniotic bands. This syndrome can be manifested by development of multiple malformations, with the majority of the defects being limb abnormalities of a disorganized nature, as in the case we present. In the absence of a clear etiology of consequential congenital abnormalities, obstetric management guidelines should use shared decision models to focus on the quality of life for the offspring.