Person:

Burris, Heather H.

Background: Both higher and lower fetal growth are associated with cardio-metabolic health later in life, suggesting that prenatal developmental programming determines long-term cardiovascular disease risk. Epigenetic mechanisms, which orchestrate fetal growth and development, may offer insight on the early programming of health and disease. We investigated whether birth weight-for-gestational is associated with DNA methylation at birth and mid-childhood, measured via the Infinium 450K array. Methods/results Participants were from Project Viva, a pre-birth cohort of pregnant women and their children in Eastern Massachusetts. After exclusion of participants with maternal type 1 or 2 diabetes and gestational age <34 weeks, we used DNA methylation assays from 476 venous umbilical cord blood samples and a subset of 235 who additionally had peripheral blood samples available in mid-childhood (age 7–10 years). Among 392,918 CpG sites analyzed, birth weight-for-gestational age z-score was associated with cord blood DNA methylation at 34 CpGs (false discovery rate P < 0.05), after adjusting for maternal age, race/ethnicity, education, smoking, parity, delivery mode, pre-pregnancy BMI, gestational diabetes status, child sex, and estimated cord blood cell proportions based on a cord blood reference panel. Two of these CpGs were previously reported in epigenome-wide analyses of birth weight, and several other CpGs map to genes relevant to fetal growth and development. Namely, higher birth weight-for-gestational age was associated with higher methylation at four CpGs at the PBX1 locus (e.g., β (95% CI) for lead signal at cg06750897 = 1.9 (1.2, 2.6)), which encodes a transcription factor that regulates embryonic development. Birth weight-for-gestational age was also associated with mid-childhood blood DNA methylation at four of the 34 CpGs identified in cord blood analyses, including sites at the PBX1 locus described. Conclusions: We identified CpG sites where birth weight-for-gestational age was associated with DNA methylation at birth, and for a subset of these sites, birth weight-for-gestational age was also associated with DNA methylation at mid-childhood. Electronic supplementary material The online version of this article (doi:10.1186/s13148-016-0285-3) contains supplementary material, which is available to authorized users.

Objective: We aimed to study whether prenatal vitamin (PNV) use protects against low 25(OH)D levels in all women and particularly in obese and black women who are both at risk of vitamin D deficiency and poor pregnancy outcomes. Study design We studied 1019 women enrolled in a prospective study at Brigham and Women’s Hospital in Boston, 2007–2009. We used multivariable logistic regression to analyze associations of PNV use and odds of vitamin D deficiency defined as 25(OH)D levels < 50 nmol/L. Results: 56% of black and 86% of white women reported pre- and/or post-conceptional PNV use. 75% of black and 19% of white women were vitamin D deficient in the first trimester. PNV use among black women was not associated with vitamin D deficiency (adjusted OR 1.0, 95%CI 0.4, 2.3) but was among white women (3.5, 95%CI 2.1, 5.8)(Interaction P<0.01). Conclusions: Ongoing trials of vitamin D supplementation during pregnancy should consider potential effect modification by race/ethnicity.

Background: The American College of Obstetricians and Gynecologists and the American Psychiatric Association both recommend pharmacotherapy for perinatal depression when the benefits outweigh the risks. While minority adults are less likely to use antidepressant medications compared to Non-Hispanic Whites, whether this pattern occurs among pregnant women is unclear. Objective: We sought to determine the frequency of antidepressant medication use reported during ambulatory care visits for pregnant women and whether these rates varied by race. Methods: We combined the 2006–2010 National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) to obtain nationally representative estimates of outpatient preventive care visits for pregnant women. We then obtained estimates of the prevalence of reported depression and antidepressant use during outpatient visits for pregnant women. To determine whether these estimates varied by race, we used multivariable logistic regression analyses accounting for survey design using SAS 9.2 (PROC SURVEYLOGISTIC) to estimate odds ratios of reported antidepressant use after adjustment for age, insurance status and region of the country. Results: Antidepressant use was reported during 2.2% of all outpatient visits for pregnant women. Providers indicated a depression diagnosis in 4.5% of visits. Among visits for depressed pregnant women, providers reported antidepressant use 25.4% of the time for all visits. Antidepressant use during pregnancy varied significantly by race/ethnicity. Among visits for Non-Hispanic White women, 3.1% included a code for antidepressant use vs. just 1.0% for Non-White women (P<0.0001). After adjustment for age, insurance status, and region of the country, this association persisted with Non-Hispanic White (vs. Non-White) pregnant women having higher odds of antidepressant use (adjusted OR 3.3, 95% CI 2.1, 5.3). Conclusion: Non-Hispanic White women were more likely than Non-White women to be using antidepressants during pregnancy. Whether differences in antidepressant use by race/ethnicity indicates over-treatment of non-Hispanic White women or under-treatment of minorities remains unclear. This disparity warrants investigation with the goal of optimizing maternal mental health while minimizing potential adverse sequelae of antidepressants on developing fetuses.

Background: Risk factors for maternal vitamin D deficiency and preterm birth overlap but the distribution of 25-hydroxyvitamin D (25(OH)D) levels among preterm infants is not known. We aimed to determine associations between 25(OH)D levels and gestational age.

Methods: We measured umbilical cord plasma levels of 25(OH)D from 471 infants born at Brigham and Women’s Hospital in Boston. We used generalized estimating equations to determine whether preterm (<37 weeks’ gestation) or very preterm (<32 weeks’ gestation) infants had greater odds of 25(OH)D levels < 20 ng/ml than more mature infants. We adjusted for potential confounding by season of birth, maternal age, race, marital status and singleton or multiple gestation.

Results: Mean cord plasma 25(OH)D level was 34.0 ng/ml (range 4.1 to 95.3, and SD 14.1). Infants born before 32 weeks’ gestation had increased odds of 25(OH)D levels < 20 ng/ml in unadjusted (OR 2.2, 95% CI 1.1, 4.3) and adjusted models (OR 2.4, 95% CI 1.2, 5.3) compared to more mature infants.

Conclusion: Infants born < 32 weeks’ gestation are at higher risk than more mature infants for low 25(OH)D levels. Further investigation of the relationships between low 25(OH)D levels and preterm birth and its sequelae is thus warranted.

Preterm birth is a major cause of infant morbidity and mortality and a potential risk factor for adult chronic disease. With over 15 million infants born preterm worldwide each year, preterm birth poses a global health concern. There is a possible association between air pollution and preterm birth, though studies have been inconsistent, likely due to variation in study design. How air pollution induces health effects is uncertain; however, studies have repeatedly demonstrated the effects of air pollution on epigenetic modifications. More recent evidence suggests that epigenetics may, in turn, be linked to preterm birth. Discovery of environmentally modifiable epigenetic processes connected to preterm birth may help to identify women at risk of preterm birth, and ultimately lead to development of new preterm birth prevention measures.