Race, the Vaginal Microbiome, and Spontaneous Preterm Birth.

Previous studies have investigated the associations between the vaginal microbiome and preterm birth, with the aim of determining whether differences in community patterns meaningfully alter risk and could therefore be the target of intervention. We report on vaginal microbial analysis of a nested case-control subset of the Pregnancy, Infection, and Nutrition (PIN) Study, including 464 White women (375 term birth and 89 spontaneous preterm birth, sPTB) and 360 Black women (276 term birth and 84 sPTB). We found that the microbiome of Black women has higher alpha-diversity, higher abundance of Lactobacillus iners, and lower abundance of Lactobacillus crispatus. However, among women who douche, there were no significant differences in microbiome by race. The sPTB-associated microbiome exhibited a lower abundance of L. crispatus, while alpha diversity and L. iners were not significantly associated with sPTB. For each order of magnitude increase in the normalized relative abundance of L. crispatus, multivariable adjusted odds of sPTB decreased by approximately 20% (odds ratio, 0.81; 95% confidence interval, 0.70, 0.94). When we considered the impact of douching, associations between the microbiome and sPTB were limited to women who do not douche. We also observed strong intercorrelations between a range of maternal factors, including poverty, education, marital status, age, douching, and race, with microbiome effect sizes in the range of 1.8 to 5.2% in univariate models. Therefore, race may simply be a proxy for other socially driven factors that differentiate microbiome community structures. Future work will continue to refine reliable microbial biomarkers for preterm birth across diverse cohorts. IMPORTANCE Approximately 10% of all pregnancies in the United States end in preterm birth, and over 14% of pregnancies end in preterm birth among Black women. Knowledge on the associations between vaginal microbiome and preterm birth is important for understanding the potential cause and assessing risk of preterm birth. Our study is one of the largest studies performed to date to investigate the associations between vaginal microbiome and spontaneous preterm birth (sPTB), with stratified design for Black and White women. We found that the vaginal microbiome was different between Black and White women. The vaginal microbiome was associated with sPTB, and a lower abundance of L. crispatus increased the risk of sPTB independent of racial differences in microbial community structures. Furthermore, we also found that vaginal douching obscured the associations between vaginal microbiome, race, and preterm birth, suggesting that vaginal douching is an important factor to consider in future studies.

Reference Intervals for Clinical Chemistry Analytes for Transgender Men and Women on Stable Hormone Therapy.

BACKGROUND: Gender-affirming hormone therapy with either estradiol or testosterone is commonly prescribed for transgender individuals. Masculinizing or feminizing hormone therapy may impact clinical chemistry analytes, but there is currently a lack of published reference intervals for the transgender population. METHODS: Healthy transgender and nonbinary individuals who had been prescribed either estradiol (n = 93) or testosterone (n = 82) for at least 12 months were recruited from primary care and internal medicine clinics specializing in transgender medical care. Electrolytes, creatinine, urea nitrogen, enzymes (alkaline phosphatase, ALK; alanine aminotransferase, ALT; aspartate aminotransferase, AST; gamma-glutamyltransferase, GGT), hemoglobin A1c, lipids [total cholesterol, high-density lipoprotein (HDL), triglycerides], and high-sensitivity C-reactive protein (hsCRP) were measured on 2 clinical chemistry platforms. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines. RESULTS: There was minimal impact of gender-affirming hormone therapy on electrolytes, urea nitrogen, hemoglobin A1c, and hsCRP. In general, the enzymes studied shifted toward affirmed gender. Creatinine values for both transgender cohorts overlaid the reference interval for cisgender men, with no shift toward affirmed gender for the estradiol cohort. The effects on lipids were complex, but with a clear shift to lower HDL values in the testosterone cohort relative to cisgender women. CONCLUSIONS: Transgender individuals receiving either masculinizing or feminizing hormone therapy showed significant changes in some analytes that have sex-specific variation in the cisgender population. The clearest shifts toward affirmed gender were seen with enzymes for the estradiol and testosterone cohorts and with creatinine and HDL in the testosterone cohort.

Is prenatal diet associated with the composition of the vaginal microbiome?

BACKGROUND: The vaginal microbiome has been associated with adverse pregnancy outcomes, but information on the impact of diet on microbiome composition is largely unexamined. OBJECTIVE: To estimate the association between prenatal diet and vaginal microbiota composition overall and by race. METHODS: We leveraged a racially diverse prenatal cohort of North Carolina women enrolled between 1995 and 2001 to conduct this analysis using cross-sectional data. Women completed food frequency questionnaires about diet in the previous 3 months and foods were categorised into subgroups: fruits, vegetables, nuts/seeds, whole grains, low-fat dairy, sweetened beverages and red meat. We additionally assessed dietary vitamin D, fibre and yogurt consumption. Stored vaginal swabs collected in mid-pregnancy were sequenced using 16S taxonomic profiling. Women were categorised into three groups based on predominance of species: Lactobacillus iners, Lactobacillus miscellaneous and Bacterial Vaginosis (BV)-associated bacteria. Adjusted Poisson models with robust variance estimators were run to assess the risk of being in a specific vagitype compared to the referent. Race-stratified models (Black/White) were also run. RESULTS: In this study of 634 women, higher consumption of dairy was associated with increased likelihood of membership in the L. crispatus group compared to the L. iners group in a dose-dependent manner (risk ratio quartile 4 vs. 1: 2.01, 95% confidence interval 1.36, 2.95). Increased intake of fruit, vitamin D, fibre and yogurt was also associated with increased likelihood of membership in L. crispatus compared to L. iners, but only among black women. Statistical heterogeneity was only detected for fibre intake. There were no detected associations between any other food groups or risk of membership in the BV group. CONCLUSIONS: Higher consumption of low-fat dairy was associated with increased likelihood of membership in a beneficial vagitype, potentially driven by probiotics.

The relationship of cumulative psychosocial adversity with antepartum depression and anxiety.

BACKGROUND: Exposure to multiple psychosocial risk factors may increase vulnerability for mental health conditions during pregnancy. This analysis examined the relationship of a novel psychosocial adversity index with the co-occurrence and persistence of depression and anxiety throughout pregnancy. METHODS: This cross-sectional analysis included 1797 pregnant women screened in the second/third trimesters for depression and anxiety symptoms and for eight contextual and individual psychosocial factors. The factors were summed to create a psychosocial adversity index; reporting four or more factors indicated high adversity. Elevated symptoms in both trimesters indicated persistent depression/anxiety and elevated symptoms at the same trimester indicated comorbid symptoms. The associations between the psychosocial adversity index and mental health were estimated. RESULTS: Compared with a low psychosocial adversity index, women reporting a high level of psychosocial adversities had 2.06 (95% confidence interval [CI]: 1.51-2.82) times higher adjusted odds of only depressive or anxiety symptoms, and 5.57 (95% CI: 3.95-7.85) times higher adjusted odds of comorbid symptoms. The associations for persistent symptoms were of similar direction and magnitude. CONCLUSION: High psychosocial adversity was associated with persistent and comorbid depressive symptoms and anxiety during pregnancy. Assessing psychosocial adversity can help identify women at increased risk who would benefit from tailored mental health interventions.

Reproductive Endocrinology Reference Intervals for Transgender Women on Stable Hormone Therapy.

BACKGROUND: Transgender women and nonbinary people seeking feminizing therapy are often prescribed estrogen as a gender-affirming hormone, which will alter their reproductive hormone axis. Testosterone, estradiol, and other reproductive hormones are commonly evaluated to assess therapy, but reference intervals specific to transgender women have not been established. The objective of this study was to derive reference intervals for commonly measured analytes related to reproductive endocrinology in a cohort of healthy gender nonconforming individuals on stable feminizing hormone therapy. METHODS: Healthy transgender individuals who had been prescribed estrogen (n = 93) for at least a year were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Total testosterone and estradiol were measured using immunoassay and mass spectrometry; LH, FSH, sex hormone binding globulin, prolactin, progesterone, anti-mullerian hormone (AMH), and dehydroepiandrosterone sulfate (DHEAS) were measured using immunoassay; free testosterone was calculated. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines. RESULTS: The distribution of results for transgender women was different than what would be expected from cisgender men or women across all measurements. Use of spironolactone was associated with changes in the result distribution of AMH, FSH, LH, and progesterone. Compared to liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS), immunoassay was sufficient for the majority of estradiol and total testosterone measurements; free testosterone added little clinical value beyond total testosterone. CONCLUSION: Reference intervals specific to transgender women should be applied when evaluating reproductive endocrine analytes. Spironolactone is a significant variable for result interpretation of some tests.

Reproductive Endocrinology Reference Intervals for Transgender Men on Stable Hormone Therapy.

BACKGROUND: Gender-affirming therapy with testosterone is commonly prescribed to aid in the masculinization of transgender men. Sex-hormone concentrations are routinely measured, but interpretation of results can be difficult due to the lack of published reference intervals. METHODS: Healthy transgender individuals who had been prescribed testosterone (n = 82) for at least a year were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Total testosterone and estradiol were measured using immunoassay and mass spectrometry; LH, FSH, SHBG, prolactin, progesterone, anti-Müllerian hormone (AMH), and dehydroepiandrosterone sulfate (DHEAS) were measured using immunoassay; free testosterone was calculated. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines. RESULTS: When evaluating general endocrine laboratory tests in people using masculinizing hormones, reference intervals for cisgender men can be applied for total and free testosterone and SHBG and reference intervals for cisgender women can be applied for prolactin. Reference intervals for estradiol, LH, FSH, AMH, and DHEAS differ from those used for cisgender men and cisgender women, and therefore should be interpreted using intervals specific to the transmasculine population. For testosterone and estradiol, results from immunoassays were clinically equivalent to mass spectrometry. CONCLUSION: Masculinizing hormones will alter the concentrations of commonly evaluated endocrine hormones. Providers and laboratories should use appropriate reference intervals to interpret the results of these tests.

Race/Ethnicity, Gender, and Trajectories of Depressive Symptoms Across Early- and Mid-Life Among the Add Health Cohort.

While disparities in depressive symptoms by race/ethnicity and gender have been documented, left unclear is how such status characteristics intersect to influence mental health, particularly across early life and among a diverse set of population subgroups. This study investigates how intra- and inter-individual trends in depressive symptoms unfold across a 30-year span (ages 12-42) and are structured by the intersection of race/ethnicity and gender among White, Black, Hispanic, and Asian American young adults (N = 18,566). Analyses use data from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of adolescents who have been followed through their fourth decade of life. We draw on Waves I-IV and a representative subsample of the brand new Wave V data. Growth curve models indicated depressive symptoms decreased across adolescence and young adulthood before increasing in the early 30s. Racial/ethnic minorities reported more depressive symptoms than Whites. Women reported more depressive symptoms than men and experienced especially steep increases in their late 30s. Racial/ethnic-gender disparities remained stable with age, except for Hispanic-White disparities among women and Asian American-White disparities among men, which narrowed with age. Overall, findings demonstrate dynamic inequalities across a longer period of the life span than was previously known, as well as heterogeneity in trajectories of poor mental health within and between racial/ethnic-gender groups. Results also suggest that Black and Asian American women experience the highest mental health risks and that interventions for reducing disparities in depressive symptoms should focus on adults in their late 20s/early 30s, particularly women of color.

The Association Between Acculturation and Prenatal Psychosocial Stress Among Latinas.

Latinas experience high levels of stress in pregnancy, however few studies have investigated how acculturation affects pregnancy mental health among Latinas. The goal of this study was to determine if acculturation was associated with pregnancy stress among pregnant, predominantly Puerto Rican women. Participants (n = 1426) were enrolled in Proyecto Buena Salud, a prospective cohort study of Latinas. Acculturation on a bi-dimensional scale that allows for identification with both Latina and continental US cultures (i.e., bi-cultural vs. high or low acculturation) was measured in early pregnancy via the Psychological Acculturation Scale (PAS), language preference, and generation in the US. Stress was measured in early and mid/late pregnancy using Cohen's 14-item Perceived Stress Scale. After adjustment for risk factors, women with bicultural acculturation had significantly lower stress in overall pregnancy (ß = - 2.15, 95% CI - 3.5, - 0.81) and in mid/late pregnancy (ß = - 2.35, 95% CI - 3.92, - 0.77) as compared to women with low acculturation. There were no significant associations between proxies of acculturation (i.e., language preference and generation) and stress. Bicultural psychological acculturation was associated with lower stress in pregnancy, while proxies of acculturation were not. Bi-dimensional measures of psychological acculturation should be considered in future studies of maternal mental health.

Association of antepartum depression, generalized anxiety, and posttraumatic stress disorder with infant birth weight and gestational age at delivery.

BACKGROUND: Low- and middle-income countries bear a disproportionate burden of preterm birth (PTB) and low infant birth weight (LBW) complications where affective and anxiety disorders are more common in the antepartum period than in industrialized countries. OBJECTIVE: To evaluate the extent to which early pregnancy antepartum depression, generalized anxiety disorder, and posttraumatic stress disorder (PTSD) are associated with infant birth weight and gestational age at delivery among a cohort of pregnant women in Peru. METHODS: Our prospective cohort study consisted of 4408 pregnant women. Antepartum depression, generalized anxiety, and PTSD were assessed in early pregnancy using the Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale-7 and PTSD Checklist - Civilian Version, respectively. Pregnancy outcome data were obtained from medical records. Multivariable linear and logistic regression procedures were used to estimate adjusted measures of association (ß coefficients and odds ratios) and 95% confidence intervals (CI). RESULTS: After adjusting for confounders, women with antepartum generalized anxiety (32.6% prevalence) had higher odds of LBW (adjusted odds ratio (OR)=1.47; 95%CI: 1.10-1.95) and were more likely to deliver small for gestational age (OR = 1.39; 95%CI: 1.01-1.92) infants compared to those without anxiety. Compared to those without PTSD, women with PTSD (34.5%) had higher odds of delivering preterm (OR = 1.28; 95%CI: 1.00-1.65) yet PTSD was not associated with LBW nor gestational age at delivery. Women with antepartum depression (26.2%) were at no increased risk of delivering a preterm, low-birth-weight or small-for-gestational-age infant. LIMITATIONS: Our ability to make casual inferences from this observational study is limited; however, these findings are consistent with prior studies. CONCLUSION: Generalized anxiety disorder during pregnancy appeared to increase odds of delivering a low-birth-weight or small-for-gestational-age infant, while PTSD was associated with increased odds of delivering preterm. Our findings, and those of others, suggest antenatal care should be tailored to screen for and provide additional mental health services to patients.

The Depths of Despair Among US Adults Entering Midlife.

OBJECTIVES: To test whether indicators of despair are rising among US adults as they age toward midlife and whether this rise is concentrated among low-educated Whites and in rural areas. METHODS: We used data from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of US adolescents in 1994. Our sample was restricted to individuals who participated in 1 or more of 5 waves (1994-2017) and self-identified as non-Hispanic White, non-Hispanic Black, or Hispanic (n = 18 446). We examined change in indicators of despair from adolescence to adulthood using multilevel regression analysis, testing for differences by race/ethnicity, education, and rurality. RESULTS: We found evidence of rising despair among this cohort over the past decade. This increase was not restricted to low-educated Whites or to rural areas. CONCLUSIONS: Results suggest that generally rising despair among the young adult cohort now reaching midlife that cuts across racial/ethnic, educational, and geographic groups may presage rising midlife mortality for these subgroups in the next decade.

Hematology reference intervals for transgender adults on stable hormone therapy.

BACKGROUND: The complete blood count (CBC) is a cornerstone of patient care. Several of the normal values for the components of the CBC differ by sex and, therefore, male-specific and female-specific reference intervals are required to interpret these laboratory results. Transgender individuals are often prescribed hormone therapy to affirm their gender, with resulting serum hormone concentrations similar to those of cisgender individuals. Gender-specific reference intervals for transgender men and women have not been established for any laboratory measurements, including hematology. We established clinically relevant hematological reference intervals for transgender individuals receiving stable hormone therapy. METHODS: Healthy transgender individuals prescribed testosterone (n = 79) or estrogen (n = 93) for ≥12 months were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Concentrations for hemoglobin, hematocrit, MCV, MCHC, and RDWCV, as well as counts for red cells, white cells, and platelets, were evaluated. Results were interpreted in reference to the overall distribution of values and relative to serum estradiol and total testosterone concentrations. Calculated reference intervals were compared to established cisgender reference intervals. RESULTS: Regardless of serum hormone concentration, individuals prescribed testosterone or estrogen had hematology parameters that were not clinically different from cisgender males and females, respectively. CONCLUSION: The hematology parameters for transgender men and women receiving stable hormone therapy should be evaluated against the cisgender male and cisgender female reference ranges, respectively and does not require concurrent sex hormone analysis. Care providers can utilize this observation to aid in interpretation of hematology laboratory values for transgender people.

Developing an Inclusive and Welcoming LGBTQ Clinic.

People who identify as lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) are underserved and face barriers to knowledgeable health care. Most health systems are ill prepared to provide care that addresses the needs of the LGBTQ community. Basic steps to developing an LGBTQ welcoming health care program are presented. It can be adapted to diverse health care models, from obstetrics and gynecology and other primary care services whether public or private and to hospitals and specialty clinics. This LGBTQ inclusive health care model was developed in collaboration with the LGBTQ community, a multidisciplinary team of health care providers, and professionals of Law and Information Technology.

Physical activity and depressive symptoms during pregnancy among Latina women: a prospective cohort study.

BACKGROUND: Latina women are at increased risk for antenatal depressive disorders, which are common during pregnancy and are associated with elevated risk for poor maternal health and birth outcomes. Physical activity is a potential mechanism to reduce the likelihood of depressive symptoms. The purpose of the study was to assess whether total and domain-specific physical activity in early pregnancy reduced risk for elevated antenatal depressive symptoms in mid-late pregnancy in a population of Latina women at high-risk for depression. METHODS: Data from 820 Latina participants in the prospective cohort study Proyecto Buena Salud was examined using multivariable logistic regression. Total, moderate/vigorous, and domain-specific physical activity (household/caregiving, occupational, sports/exercise, transportation) were assessed using the Pregnancy Physical Activity Questionnaire. The Edinburgh Postnatal Depression Scale was used to assess depressive symptoms and identify women with elevated symptoms indicative of at least probable minor depression and probable major depression. RESULTS: A total of 25.9% of participants experienced at least probable minor depression and 19.1% probable major depression in mid-late pregnancy. After adjusting for important risk factors, no significant associations were observed between total physical activity (4th Quartile vs.1st Quartile OR = 1.02, 95% CI = 0.61, 1.71; p-trend = 0.62) or meeting exercise guidelines in pregnancy (OR = 0.96, 95% CI = 0.65, 1.41) and at least probable minor depression; similarly, associations were not observed between these measures and probable major depression. There was a suggestion of increased risk of probable major depression with high levels of household/caregiving activity (4th Quartile vs 1st Quartile OR = 1.51, 95% CI = 0.93, 2.46), but this was attenuated and remained not statistically significant after adjustment. When we repeated the analysis among women who did not have elevated depressive symptoms in early pregnancy (n = 596), findings were unchanged, though a nonsignificant protective effect was observed for sport/exercise activity and probable major depression in fully adjusted analysis (OR = 0.63, 95% CI = 0.30, 1.33). CONCLUSION: Among Latina women at high-risk for antenatal depression, early pregnancy physical activity was not associated with elevated depressive symptoms in mid-to-late pregnancy.

Prenatal Perceived Stress and Adverse Birth Outcomes Among Puerto Rican Women.

BACKGROUND: Preterm birth and low birthweight contribute substantially to the disproportionately high infant mortality rates experienced by Puerto Ricans in the United States. The purpose of this study was to examine whether the timing and pattern of prenatal psychosocial stress increased risk of adverse birth outcomes in this high-risk population. MATERIALS AND METHODS: Proyecto Buena Salud was a prospective cohort study conducted from 2006 to 2011 among predominantly Puerto Rican women. Participants (n = 1,267) were interviewed in early, mid-, and late pregnancy. We evaluated associations between early and mid-pregnancy stress (Perceived Stress Scale) and preterm birth and low birthweight, and stress at each pregnancy time point and small for gestational age (SGA). RESULTS: Elevated levels of perceived stress in mid-pregnancy increased risk for preterm birth and low birthweight in adjusted analyses, with a linear trend observed for each increasing quartile of stress (ptrend = 0.01). Women in the highest quartile of stress experienced three times the risk for preterm birth (odds ratio [OR] = 3.50, confidence interval [95% CI]: 1.38-8.87) and low birthweight (OR = 3.53, 95% CI = 1.27-9.86) compared with women in the lowest quartile. Early pregnancy stress was not associated with preterm birth or low birthweight. Increase in stress from early to late pregnancy increased risk for SGA (OR = 1.90, 95% CI = 1.01-3.59); no associations were found between stress at any timepoint and SGA. CONCLUSION: Elevated levels of mid-pregnancy perceived stress increased risk for preterm birth and low birthweight, and an increase in stress over the course of pregnancy increased risk for SGA in a population of predominantly Puerto Rican women.

State-Level Immunization Information Systems: Potential for Childhood Immunization Data Linkages.

Objectives Sources of immunization data include state registries or immunization information systems (IIS), medical records, and surveys. Little is known about the quality of these data sources or the feasibility of using IIS data for research. We assessed the feasibility of collecting immunization information for a national children's health study by accessing existing IIS data and comparing the completeness of these data against medical record abstractions (MRA) and parent report. Staff time needed to obtain IIS and MRA data was assessed. Methods We administered a questionnaire to state-level IIS representatives to ascertain availability and completeness of their data for research and gather information about data formats. We evaluated quality of data from IIS, medical records, and reports from parents of 119 National Children's Study participants at three locations. Results IIS data were comparable to MRA data and both were more complete than parental report. Agreement between IIS and MRA data was greater than between parental report and MRA, suggesting IIS and MRA are better sources than parental report. Obtaining IIS data took less staff time than chart review, making IIS data linkage for research a preferred choice. Conclusions IIS survey results indicate data can be obtained by researchers using data linkages. IIS are an accessible and feasible child immunization information source and these registries reduce reliance on parental report or medical record abstraction. Researchers seeking to link IIS data with large multi-site studies should consider acquiring IIS data, but may need strategies to overcome barriers to data completeness and linkage.

Depression During Pregnancy and Adverse Birth Outcomes Among Predominantly Puerto Rican Women.

Objectives To examine associations between depression and preterm birth and small-for gestational age (SGA) among women of predominantly Puerto Rican descent, a population who experiences disparities in adverse birth outcomes and one of the highest infant mortality rates in the United States. Methods Proyecto Buena Salud (PBS) was a prospective cohort study conducted from 2006 to 2011 at a large tertiary care center in Western Massachusetts. Caribbean Islander (i.e., Puerto Rican and Dominican Republic) women were interviewed in early, mid and late pregnancy. Among 1262 participants, associations between depression, assessed using the Edinburgh Postnatal Depression Scale, and risk of preterm birth and small-for-gestational age (SGA) were evaluated. Results Women with at least probable minor depression [odds ratio (OR) = 1.77 (95% confidence interval (CI) = 1.02, 3.07)] or probable major depression [OR = 1.82 (95% CI = 1.01, 3.25)] in mid-pregnancy had an increased risk of SGA compared to non-depressed women in adjusted analyses. Borderline significant associations were observed between increasing levels of depressive symptom scores in early and mid-pregnancy [OR = 1.05 (95% CI = 1.00, 1.11) and OR = 1.04 (95% CI = 1.00, 1.09), respectively] and each additional trimester of exposure to probable major depression across mid- to late pregnancy [OR = 1.66 (95% CI = 1.00, 2.74)] and SGA. Late pregnancy depression was not associated with SGA; depression during pregnancy was not associated with preterm birth. Conclusions for Practice In this population of predominantly Puerto Rican women, mid-pregnancy depression increased risk for SGA. Findings can inform culturally appropriate, targeted interventions to identify and treat pregnant women with depression.

The National Children's Study: An Introduction and Historical Overview.

The National Children's Study (NCS) was an ambitious attempt to map children's health and development in a large representative group of children in the United States. In this introduction, we briefly review the background of the NCS and the history of the multiple strategies that were tested to recruit women and children. Subsequent articles then detail the protocols and outcomes of 4 of the recruitment strategies. It is hoped that lessons learned from these attempts to define a study protocol that could achieve the initial aims of the NCS will inform future efforts to conceptualize and execute strategies to provide generalizable insights on the longitudinal health of our nation's children.

In utero exposures to environmental organic pollutants disrupt epigenetic marks linked to fetoplacental development.

While the developing fetus is largely shielded from the external environment through the protective barrier provided by the placenta, it is increasingly appreciated that environmental agents are able to cross and even accumulate in this vital organ for fetal development. To examine the potential influence of environmental pollutants on the placenta, we assessed the relationship between polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and several epigenetic marks linked to fetoplacental development. We measured IGF2/H19 imprint control region methylation, IGF2 and H19 expression, IGF2 loss of imprinting (LOI) and global DNA methylation levels in placenta (n = 116) collected in a formative research project of the National Children's Study to explore the relationship between these epigenetic marks and the selected organic environmental pollutants. A positive association was observed between global DNA methylation and total PBDE levels (P <0.01) and between H19 expression and total PCB levels (P = 0.04). These findings suggest that differences in specific epigenetic marks linked to fetoplacental development occur in association with some, but not all, measured environmental exposures.

Maternal Serum 25-Hydroxyvitamin D Concentrations during Pregnancy and Infant Birthweight for Gestational Age: a Three-Cohort Study.

BACKGROUND: In response to inconsistent findings, we investigated associations between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and infant birthweight for gestational age (BW/GA), including potential effect modification by maternal race/ethnicity and infant sex. METHODS: Data from 2558 pregnant women were combined in a nested case-control study (preterm and term) sampled from three cohorts: the Omega study, the Pregnancy, Infection and Nutrition study, and the Pregnancy Outcomes and Community Health study. Maternal 25(OH)D concentrations were sampled at 4 to 29 weeks gestation (80% 14-26 weeks). BW/GA was modelled as sex and gestational age-specific birthweight z-scores. General linear regression models (adjusting for age, education, parity, pre-pregnancy body mass index, season at blood draw, and smoking) assessed 25(OH)D concentrations in relation to BW/GA. RESULTS: Among non-Hispanic Black women, the positive association between 25(OH)D concentrations and BW/GA was of similar magnitude in pregnancies with female or male infants [beta (ß) = 0.015, standard error (SE) = 0.007, P = 0.025; ß = 0.018, SE = 0.006, P = 0.003, respectively]. Among non-Hispanic White women, 25(OH)D-BW/GA association was observed only with male infants, and the effect size was lower (ß = 0.008, SE = 0.003, P = 0.02). CONCLUSIONS: Maternal serum concentrations of 25(OH)D in early and mid-pregnancy were positively associated with BW/GA among non-Hispanic Black male and female infants and non-Hispanic White male infants. Effect modification by race/ethnicity may be due, in part, to overall lower concentrations of 25(OH)D in non-Hispanic Blacks. Reasons for effect modification by infant sex remain unclear.

Exploring the associations between microRNA expression profiles and environmental pollutants in human placenta from the National Children's Study (NCS).

The placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children's Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas. Environmental pollutants measured in these placentas included dichlorodiphenyldichloroethylene (DDE), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A moderated t-test was used to identify a panel of differentially expressed miRNAs, which were further analyzed using generalized linear models. We observed 112 miRNAs consistently expressed in >70% of the samples. Consistent with the literature, miRNAs located within the imprinted placenta-specific C19MC cluster, specifically mir-517a, mir-517c, mir-522, and mir-23a, are among the top expressed miRNA in our study. We observed a positive association between PBDE 209 and miR-188-5p and an inverse association between PBDE 99 and let-7c. Both PCBs and Cd were positively associated with miR-1537 expression level. In addition, multiple let-7 family members were downregulated with increasing levels of Hg and Pb. We did not observe DDE or BPA levels to be associated with placental miRNA expression. This is the first birth cohort study linking environmental pollutants and placental expression of miRNAs. Our results suggest that placental miRNA profiles may signal in utero exposures to environmental chemicals.