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BackgroundWe identified host single-nucleotide variants (SNVs) associated with neurocognitive impairment (NCI) in perinatally HIV-infected (PHIV) children.MethodsWhole-exome sequencing (WES) was performed on 217 PHIV with cognitive score for age (CSA)

Objective Design Setting Population Methods Main outcome measures Results Conclusions To evaluate the associations of plasma polybrominated diphenyl ether (PBDE) concentrations in early pregnancy with gestational weight gain (GWG).Prospective cohort study.US‐based, multicentre cohort of pregnant women.We used data from 2052 women without obesity and 397 women with obesity participating in the NICHD Fetal Growth Studies – Singleton Cohort, with first‐trimester plasma PBDE concentrations and weight measurements throughout pregnancy.We applied generalised linear models and Bayesian kernel machine regression (BKMR) to evaluate both the individual and joint associations of PBDEs with measures of GWG, adjusting for potential confounders.Total GWG (kg), total and trimester‐specific GWG velocities (kg/week), and GWG categories and trajectory groups.Mean pre‐pregnancy BMIs were 23.6 and 34.5 kg/m2 for women without and with obesity, respectively. Among women without obesity, there were no associations of PBDEs with any GWG measure. Among women with obesity, one standard deviation increase in log‐transformed PBDE 47 was associated with a 1.87 kg higher total GWG (95% CI 0.39–3.35) and a 0.05 kg/week higher total GWG velocity (95% CI 0.01–0.09). Similar associations were found for PBDE 47 in BKMR among women with obesity, and PBDE 47, 99 and 100 were associated with lower odds of being in the low GWG trajectory group.PBDEs were not associated with GWG among individuals without obesity. Among those with obesity, only PBDE 47 showed consistent positive associations with GWG measures across multiple statistical methods. Further research is needed to validate this association and explore potential mechanisms. [ABSTRACT FROM AUTHOR]

Background: Racial and ethnic disparities persist in preterm birth (PTB) and gestational age (GA) at delivery in the United States. It remains unclear whether exposure to environmental chemicals contributes to these disparities. Objectives: We applied recent methodologies incorporating environmental mixtures as mediators in causal mediation analysis to examine whether racial and ethnic disparities in GA at delivery and PTB may be partially explained by exposures to polybrominated diphenyl ethers (PBDEs), a class of chemicals used as flame retardants in the United States. Methods: Data from a multiracial/ethnic US cohort of 2008 individuals with lowrisk singleton pregnancies were utilized, with plasma PBDE concentrations measured during early pregnancy. We performed mediation analyses incorporating three forms of mediators: (1) reducing all PBDEs to a weighted index, (2) selecting a PBDE congener, or (3) including all congeners simultaneously as multiple mediators, to evaluate whether PBDEs may contribute to the racial and ethnic disparities in PTB and GA at delivery, adjusted for potential confounders. Results: Among the 2008 participants, 552 self-identified as non-Hispanic White, 504 self-identified as non-Hispanic Black, 568 self-identified as Hispanic, and 384 self-identified as Asian/Pacific Islander. The non-Hispanic Black individuals had the highest mean ΣPBDEs, the shortest mean GA at delivery, and the highest rate of PTB. Overall, the difference in GA at delivery comparing non-Hispanic Black to non-Hispanic White women was -0.30 (95% CI: -0.54, -0.05) weeks. This disparity reduced to -0.23 (95% CI: -0.49, 0.02) and -0.18 (95% CI: -0.46, 0.10) weeks if fixing everyone's weighted index of PBDEs to the median and the 25th percentile levels, respectively. The proportion of disparity mediated by the weighted index of PBDEs was 11.8%. No statistically significant mediation was found for PTB, other forms of mediator(s), or other racial and ethnic groups. Conclusion: PBDE mixtures may partially mediate the Black vs. White disparity in GA at delivery. While further validations are needed, lowering the PBDEs at the population level might help reduce this disparity. [ABSTRACT FROM AUTHOR]

Context The association between women's stress and pregnancy glucose levels remain unclear, specifically when considering the preconception period as a sensitive window of exposure. Objective We investigated whether preconception perceived stress was associated with glucose levels during pregnancy among women attending a fertility center (2004-2019). Methods Before conception, women completed a psychological stress survey using the short version of the validated Perceived Stress Scale 4 (PSS-4), and blood glucose was measured using a 50-gram glucose load test during late pregnancy as a part of screening for gestational diabetes. Linear and log-binomial regression models were used to assess associations of total PSS-4 scores with mean glucose levels and abnormal glucose levels (≥ 140 mg/dL), adjusting for age, body mass index, race, smoking, education, physical activity, primary infertility diagnosis, number of babies, and mode of conception. Results Psychological stress was positively associated with mean abnormal glucose levels. The adjusted marginal means (95% CI) of mean glucose levels for women in the first, second, and third tertiles of psychological stress were 115 (110, 119), 119 (115, 123), and 124 (119, 128), and mg/dL, respectively (P for trend =.007). Also, women in the second and third tertiles of psychological stress had 4% and 13% higher probabilities of having abnormal glucose compared with women in the first tertile of psychological stress (P trend =.01). Conclusion These results highlight the importance of considering preconception when evaluating the relationship between women's stress and pregnancy glucose levels. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the association of plasma insulin levels and their trajectories from birth to childhood with the timing of menarche. RESEARCH DESIGN AND METHODS: This prospective study included 458 girls recruited at birth between 1998 and 2011 and followed prospectively at the Boston Medical Center. Plasma nonfasting insulin concentrations were measured at two time points: at birth (cord blood) and in childhood (age 0.5–5 years). Age at menarche was obtained from a pubertal developmental questionnaire or abstracted from electronic medical records. RESULTS: Three hundred six (67%) of the girls had reached menarche. The median (range) age at menarche was 12.4 (9–15) years. Elevated plasma insulin concentrations at birth (n = 391) and in childhood (n = 335) were each associated with an earlier mean age at menarche: approximately 2 months earlier per doubling of insulin concentration (mean shift, −1.95 months, 95% CI, −0.33 to −3.53, and −2.07 months, 95% CI, −0.48 to −3.65, respectively). Girls with overweight or obesity in addition to elevated insulin attained menarche about 11–17 months earlier, on average, than those with normal weight and low insulin. Considering longitudinal trajectories (n = 268), having high insulin levels both at birth and in childhood was associated with a roughly 6 months earlier mean age at menarche (mean shift, −6.25 months, 95% CI, −0.38 to −11.88), compared with having consistently low insulin levels at both time points. CONCLUSIONS: Our data showed that elevated insulin concentrations in early life, especially in conjunction with overweight or obesity, contribute to the earlier onset of menarche, suggesting the need for early screening and intervention. [ABSTRACT FROM AUTHOR]