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Maternal lipid profiles during pregnancy are associated with risk for preterm birth. This study investigates the association between maternal dyslipidemia and subsequent preterm birth among pregnant women in the state of California. Births were identified from California birth certificate and hospital discharge records from 2007-2012 (N = 2,865,987). Preterm birth was defined as <37 weeks completed gestation and dyslipidemia was defined by diagnostic codes. Subtypes of preterm birth were classified as preterm premature rupture of membranes (PPROM), spontaneous labor, and medically indicated, according to birth certificate data and diagnostic codes. The association between dyslipidemia and preterm birth was tested with logistic regression. Models were adjusted for maternal age at delivery, race/ethnicity, hypertension, pre-pregnancy body mass index, insurance type, and education. Maternal dyslipidemia was significantly associated with increased odds of preterm birth (adjusted OR: 1.49, 95%CI: 1.39, 1.59). This finding was consistent across all subtypes of preterm birth, including PPROM (adjusted OR: 1.54, 95%CI: 1.34, 1.76), spontaneous (adjusted OR: 1.51, 95%CI: 1.39, 1.65), and medically indicated (adjusted OR: 1.454, 95%CI: 1.282, 1.649). This study suggests that maternal dyslipidemia is associated with increased risk for all types of preterm birth.

Background Trans-differentiation of human-induced pluripotent stem cells into neurons via Ngn2-induction (hiPSC-N) has become an efficient system to quickly generate neurons a likely significant advance for disease modeling and in vitro assay development. Recent single-cell interrogation of Ngn2-induced neurons, however, has revealed some similarities to unexpected neuronal lineages. Similarly, a straightforward method to generate hiPSC-derived astrocytes (hiPSC-A) for the study of neuropsychiatric disorders has also been described. Results Here, we examine the homogeneity and similarity of hiPSC-N and hiPSC-A to their in vivo counterparts, the impact of different lengths of time post Ngn2 induction on hiPSC-N (15 or 21 days), and the impact of hiPSC-N/hiPSC-A co-culture. Leveraging the wealth of existing public single-cell RNA-seq (scRNA-seq) data in Ngn2-induced neurons and in vivo data from the developing brain, we provide perspectives on the lineage origins and maturation of hiPSC-N and hiPSC-A. While induction protocols in different labs produce consistent cell type profiles, both hiPSC-N and hiPSC-A show significant heterogeneity and similarity to multiple in vivo cell fates, and both more precisely approximate their in vivo counterparts when co-cultured. Gene expression data from the hiPSC-N show enrichment of genes linked to schizophrenia (SZ) and autism spectrum disorders (ASD) as has been previously shown for neural stem cells and neurons. These overrepresentations of disease genes are strongest in our system at early times (day 15) in Ngn2-induction/maturation of neurons, when we also observe the greatest similarity to early in vivo excitatory neurons. We have assembled this new scRNA-seq data along with the public data explored here as an integrated biologist-friendly web-resource for researchers seeking to understand this system more deeply: https://nemoanalytics.org/p?l=DasEtAlNGN2&g=NES . Conclusions While overall we support the use of the investigated cellular models for the study of neuropsychiatric disease, we also identify important limitations. We hope that this work will contribute to understanding and optimizing cellular modeling for complex brain disorders.

Background Identifying preterm infants at risk for mortality or major morbidity traditionally relies on gestational age, birth weight, and other clinical characteristics that offer underwhelming utility. We sought to determine whether a newborn metabolic vulnerability profile at birth can be used to evaluate risk for neonatal mortality and major morbidity in preterm infants. Methods This was a population-based retrospective cohort study of preterm infants born between 2005 and 2011 in California. We created a newborn metabolic vulnerability profile wherein maternal/infant characteristics along with routine newborn screening metabolites were evaluated for their association with neonatal mortality or major morbidity. Results Nine thousand six hundred and thirty-nine (9.2%) preterm infants experienced mortality or at least one complication. Six characteristics and 19 metabolites were included in the final metabolic vulnerability model. The model demonstrated exceptional performance for the composite outcome of mortality or any major morbidity (AUC 0.923 (95% CI: 0.917–0.929). Performance was maintained across mortality and morbidity subgroups (AUCs 0.893–0.979). Conclusions Metabolites measured as part of routine newborn screening can be used to create a metabolic vulnerability profile. These findings lay the foundation for targeted clinical monitoring and further investigation of biological pathways that may increase the risk of neonatal death or major complications in infants born preterm. Impact We built a newborn metabolic vulnerability profile that could identify preterm infants at risk for major morbidity and mortality. Identifying high-risk infants by this method is novel to the field and outperforms models currently in use that rely primarily on infant characteristics. Utilizing the newborn metabolic vulnerability profile for precision clinical monitoring and targeted investigation of etiologic pathways could lead to reductions in the incidence and severity of major morbidities associated with preterm birth.

ObjectivesTo investigate racial/ethnic differences in rehospitalization and mortality rates among premature infants over the first year of life.Study designA retrospective cohort study of infants born in California from 2011 to 2017 (n = 3,448,707) abstracted from a California Office of Statewide Health Planning and Development database. Unadjusted Kaplan–Meier tables and logistic regression controlling for health and sociodemographic characteristics were used to predict outcomes by race/ethnicity.ResultsCompared to White infants, Hispanic and Black early preterm infants were more likely to be readmitted; Black late/moderate preterm (LMPT) infants were more likely to be readmitted and to die after discharge; Hispanic and Black early preterm infants with BPD were more likely to be readmitted; Black LMPT infants with RDS were more likely to be readmitted and die after discharge.ConclusionsRacial/ethnic disparities in readmission and mortality rates exist for premature infants across several co-morbidities. Future studies are needed to improve equitability of outcomes.

Background Higher socioeconomic status (SES) has less impact on cardio-metabolic disease and preterm birth risk among Black women compared to White women, an effect called “diminishing returns.” No studies have tested whether this also occurs for pregnancy cardio-metabolic disease, specifically preeclampsia, or whether preeclampsia risk could account for race-by-SES disparities in birth timing. Methods A sample of 718,604 Black and White women was drawn from a population-based California cohort of singleton births. Education, public health insurance status, gestational length, and preeclampsia diagnosis were extracted from a State-maintained birth cohort database. Age, prenatal care, diabetes diagnosis, smoking during pregnancy, and pre-pregnancy body mass index were covariates. Results In logistic regression models predicting preeclampsia risk, the race-by-SES interaction (for both education and insurance status) was significant. White women were at lower risk for preeclampsia, and higher SES further reduced risk. Black women were at higher risk for preeclampsia, and SES did not attenuate risk. In pathway analyses predicting gestational length, an indirect effect of the race-by-SES interaction was observed. Among White women, higher SES predicted lower preeclampsia risk, which in turn predicted longer gestation. The same was not observed for Black women. Conclusions Compared to White women, Black women had increased preeclampsia risk. Higher SES attenuated risk for preeclampsia among White women, but not for Black women. Similarly, higher SES indirectly predicted longer gestational length via reduced preeclampsia risk among White women, but not for Black women. These findings are consistent with diminishing returns of higher SES for Black women with respect to preeclampsia.

Approximately 1–4% of children today are conceived using assisted reproductive technologies (ARTs), including in vitro fertilization (IVF). IVF is considered safe and the great majority of these children are healthy, yet there is increasing physiological and molecular evidence from animal models that ART is associated with postnatal metabolic and cardiovascular alterations. Understanding the mechanisms underlying these changes and determining whether they have biological significance is of paramount importance for optimizing the design of culture conditions and improving the health of ART children across the life course. In this review, we examine the evidence of molecular changes present in adult tissues of rodent offspring generated by preimplantation manipulation of gametes and embryos. Although embryo manipulation in vitro can induce common transcriptional effects in the blastocyst, transcriptional and metabolomic signatures in adult IVF tissues are largely tissue-specific. However, there is pervasive evidence of oxidative stress and metabolic dysfunction, indicating a lasting effect of IVF on molecular physiology.

IntroductionPrevious studies that used traditional multivariable and sibling matched analyses to investigate interpregnancy interval (IPI) and birth outcomes have reached mixed conclusions about a minimum recommended IPI, raising concerns about confounding. Our objective was to isolate the contribution of interpregnancy interval to the risk for adverse birth outcomes using propensity score matching.MethodsFor this retrospective cohort study, data were drawn from a California Department of Health Care Access and Information database with linked vital records and hospital discharge records (2007–2012). We compared short IPIs of < 6, 6–11, and 12–17 months to a referent IPI of 18–23 months using 1:1 exact propensity score matching on 13 maternal sociodemographic and clinical factors. We used logistic regression to calculate the odds of preterm birth, early-term birth, and small for gestational age (SGA).ResultsOf 144,733 women, 73.6% had IPIs < 18 months, 5.5% delivered preterm, 27.0% delivered early-term, and 6.0% had SGA infants. In the propensity matched sample (n = 83,788), odds of preterm birth were increased among women with IPI < 6 and 6–11 months (OR 1.89, 95% CI 1.71–2.0; OR 1.22, 95% CI 1.13–1.31, respectively) and not with IPI 12–17 months (OR 1.01, 95% CI 0.94–1.09); a similar pattern emerged for early-term birth. The odds of SGA were slightly elevated only for intervals < 6 months (OR 1.10, 95% CI 1.00–1.20, p < .05).DiscussionThis study demonstrates a dose response association between short IPI and adverse birth outcomes, with no increased risk beyond 12 months. Findings suggest that longer IPI recommendations may be overly proscriptive.

To determine whether maternal cardiovascular disease (CVD) risk factors predict preterm birth. Case control. California hospitals. 868 mothers with linked demographic information and biospecimens who delivered singleton births from July 2009 to December 2010. Logistic regression analysis was employed to calculate odds ratios for the associations between maternal CVD risk factors before and during pregnancy (including diabetes, hypertensive disorders and cholesterol levels) and preterm birth outcomes. Preterm delivery status. Adjusting for the other maternal CVD risk factors of interest, all categories of hypertension led to increased odds of preterm birth, with the strongest magnitude observed in the pre-eclampsia group (adjusted OR (aOR), 13.49; 95% CI 6.01 to 30.27 for preterm birth; aOR, 10.62; 95% CI 4.58 to 24.60 for late preterm birth; aOR, 17.98; 95% CI 7.55 to 42.82 for early preterm birth) and chronic hypertension alone for early preterm birth (aOR, 4.58; 95% CI 1.40 to 15.05). Diabetes (types 1 and 2 and gestational) was also associated with threefold increased risk for preterm birth (aOR, 3.06; 95% CI 1.12 to 8.41). A significant and linear dose response was found between total and low-density lipoprotein (LDL) cholesterol and aORs for late and early preterm birth, with increasing cholesterol values associated with increased risk (likelihood χ differences of 8.422 and 8.019 for total cholesterol for late and early, and 9.169 and 10.896 for LDL for late and early, respectively). Receiver operating characteristic curves using these risk factors to predict late and early preterm birth produced C statistics of 0.601 and 0.686. Traditional CVD risk factors are significantly associated with an increased risk of preterm birth; these findings reinforce the clinical importance of integrating obstetric and cardiovascular risk assessment across the healthcare continuum in women.

ObjectiveWe hypothesized second trimester serum cortisol would be higher in spontaneous preterm births compared to provider-initiated (previously termed ‘medically indicated’) preterm births.Study designWe used a nested case-control design with a sample of 993 women with live births. Cortisol was measured from serum samples collected as part of routine prenatal screening. We tested whether mean-adjusted cortisol fold-change differed by gestational age at delivery or preterm birth subtype using multivariable linear regression.ResultAn inverse association between cortisol and gestational age category (trend p = 0.09) was observed. Among deliveries prior to 37 weeks, the mean-adjusted cortisol fold-change values were highest for preterm premature rupture of the membranes (1.10), followed by premature labor (1.03) and provider-initiated preterm birth (1.01), although they did not differ statistically.ConclusionCortisol continues to be of interest as a marker of future preterm birth. Augmentation with additional biomarkers should be explored.

ObjectiveInflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia.Study designA sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios.ResultsHigher 5-α-pregnan-3β,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia.ConclusionsAmong women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth.