Person:

Rich-Edwards, Janet

Background: Shorter stature is associated with greater all cause and heart disease mortality, but taller stature with increased risk of cancer mortality. Though childhood environment is important in determining height, limited data address how maternal depression affects linear growth in children. We examined the relationships between antenatal and postpartum depressive symptoms and child height and linear growth from birth to age 3 years in a U.S. sample. Methods: Subjects were 872 mother-child pairs in Project Viva, a prospective pre-birth cohort study. The study population is relatively advantaged with high levels of income and education and low risk of food insecurity. We assessed maternal depression at mid-pregnancy (mean 28 weeks' gestation) and 6 months postpartum with the Edinburgh Postnatal Depression Scale (score > = 13 on 0–30 scale indicating probable depression). Child outcomes at age 3 were height-for-age z-score (HAZ) and leg length. HAZ was also available at birth and ages 6 months, 1, 2, and 3 years. Findings: Seventy (8.0%) women experienced antenatal depression and 64 (7.3%) experienced postpartum depression. The mean (SD) height for children age 3 was 97.2 cm (4.2), with leg length of 41.6 cm (2.6). In multivariable linear regression models, exposure to postpartum depression was associated with greater HAZ (0.37 [95% confidence interval: 0.16, 0.58]) and longer leg length (0.88 cm [0.35, 1.41]). The relationship between postpartum depression and greater HAZ was evident starting at 6 months and continued to age 3. We found minimal relationships between antenatal depression and child height outcomes. Conclusion: Our findings do not support the hypothesis that maternal depression is associated with reduced height in children in this relatively advantaged sample in a high-income country.

Fish and other seafood may contain organic mercury but also beneficial nutrients such as n-3 polyunsaturated fatty acids. We endeavored to study whether maternal fish consumption during pregnancy harms or benefits fetal brain development. We examined associations of maternal fish intake during pregnancy and maternal hair mercury at delivery with infant cognition among 135 mother–infant pairs in Project Viva, a prospective U.S. pregnancy and child cohort study. We assessed infant cognition by the percent novelty preference on visual recognition memory (VRM) testing at 6 months of age. Mothers consumed an average of 1.2 fish servings per week during the second trimester. Mean maternal hair mercury was 0.55 ppm, with 10% of samples > 1.2 ppm. Mean VRM score was 59.8 (range, 10.9–92.5). After adjusting for participant characteristics using linear regression, higher fish intake was associated with higher infant cognition. This association strengthened after adjustment for hair mercury level: For each additional weekly fish serving, offspring VRM score was 4.0 points higher [95% confidence interval (CI), 1.3 to 6.7]. However, an increase of 1 ppm in mercury was associated with a decrement in VRM score of 7.5 (95% CI, –13.7 to –1.2) points. VRM scores were highest among infants of women who consumed > 2 weekly fish servings but had mercury levels ≤1.2 ppm. Higher fish consumption in pregnancy was associated with better infant cognition, but higher mercury levels were associated with lower cognition. Women should continue to eat fish during pregnancy but choose varieties with lower mercury contamination.

Background: Nutrients, hormones and growth factors in dairy foods may stimulate growth hormone (GH), insulin-like growth factor I (IGF-I), and raise the ratio of IGF-I to its binding protein, IGFBP-3. We conducted pilot studies in Mongolia and Massachusetts to test the extent to which milk intake raised somatotropic hormone concentrations in prepubertal children. Methods: In Ulaanbaatar, we compared plasma levels before and after introducing 710 ml daily whole milk for a month among 46 10–11 year old schoolchildren. In a randomized cross-over study in Boston, we compared plasma hormone levels of 28 6–8 year old girls after one week of drinking 710 ml lowfat (2%) milk with their hormone levels after one week of consuming a macronutrient substitute for milk. Results: After a month of drinking whole milk, Mongolian children had higher mean plasma levels of IGF-I (p less than 0.0001), IGF-I/IGFBP-3 (p less than 0.0001), and 75th percentile of GH levels (p = 0.005). After a week of drinking lowfat milk, Boston girls had small and non-significant increases in IGF-1, IGF-1/IGFBP-3 and GH. Conclusion: Milk drinking may cause increases in somatotropic hormone levels of prepubertal girls and boys. The finding that milk intake may raise GH levels is novel, and suggests that nutrients or bioactive factors in milk may stimulate endogenous GH production.

Background: Previous studies have shown that women have higher urinary concentrations of several phthalate metabolites than do men, possibly because of a higher use of personal care products. Few studies have evaluated the association between phthalate metabolites, diabetes, and diabetes-related risk factors among women. Objective: We explored the association between urinary phthalate metabolite concentrations and diabetes among women who participated in a cross-sectional study. Methods: We used urinary concentrations of phthalate metabolites, analyzed by the Centers for Disease Control and Prevention, and self-reported diabetes of 2,350 women between 20 and 79 years of age who participated in the NHANES (2001–2008). We used multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for urinary creatinine, sociodemographic characteristics, dietary factors, and body size. A secondary analysis was conducted for women who did not have diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose (FBG), homeostasis model assessment–estimated insulin resistance, and glycosylated hemoglobin A1c. Results: After adjusting for potential confounders, women with higher levels of mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and three di-(2-ethylhexyl) phthalate metabolites (ΣDEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. Women in the highest quartile for MBzP and MiBP had almost twice the odds of diabetes [OR = 1.96 (95% CI: 1.11, 3.47) and OR = 1.95 (95% CI: 0.99, 3.85), respectively] compared with women in the lowest quartile. Nonmonotonic, positive associations were found for MnBP and ΣDEHP, whereas MCPP appeared to have a threshold effect. Certain phthalate metabolites were positively associated with FBG and insulin resistance. Discussion: Urinary levels of several phthalates were associated with prevalent diabetes. Future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes.

Background: Fully understanding the determinants and sequelae of fetal growth requires a continuous measure of birth weight adjusted for gestational age. Published United States reference data, however, provide estimates only of the median and lowest and highest 5th and 10th percentiles for birth weight at each gestational age. The purpose of our analysis was to create more continuous reference measures of birth weight for gestational age for use in epidemiologic analyses. Methods: We used data from the most recent nationwide United States Natality datasets to generate multiple reference percentiles of birth weight at each completed week of gestation from 22 through 44 weeks. Gestational age was determined from last menstrual period. We analyzed data from 6,690,717 singleton infants with recorded birth weight and sex born to United States resident mothers in 1999 and 2000. Results: Birth weight rose with greater gestational age, with increasing slopes during the third trimester and a leveling off beyond 40 weeks. Boys had higher birth weights than girls, later born children higher weights than firstborns, and infants born to non-Hispanic white mothers higher birth weights than those born to non-Hispanic black mothers. These results correspond well with previously published estimates reporting limited percentiles. Conclusions: Our method provides comprehensive reference values of birth weight at 22 through 44 completed weeks of gestation, derived from broadly based nationwide data. Other approaches require assumptions of normality or of a functional relationship between gestational age and birth weight, which may not be appropriate. These data should prove useful for researchers investigating the predictors and outcomes of altered fetal growth.

Background: Excessive gestational weight gain promotes poor maternal and child health outcomes. Weight misperception is associated with weight gain in non-pregnant women, but no data exist during pregnancy. The purpose of this study was to examine the association of misperceived pre-pregnancy body weight status with excessive gestational weight gain. Methods: At study enrollment, participants in Project Viva reported weight, height, and perceived body weight status by questionnaire. Our study sample comprised 1537 women who had either normal or overweight/obese pre-pregnancy BMI. We created 2 categories of pre-pregnancy body weight status misperception: normal weight women who identified themselves as overweight ('overassessors') and overweight/obese women who identified themselves as average or underweight ('underassessors'). Women who correctly perceived their body weight status were classified as either normal weight or overweight/obese accurate assessors. We performed multivariable logistic regression to determine the odds of excessive gestational weight gain according to 1990 Institute of Medicine guidelines. Results: Of the 1029 women with normal pre-pregnancy BMI, 898 (87%) accurately perceived and 131 (13%) overassessed their weight status. 508 women were overweight/obese, of whom 438 (86%) accurately perceived and 70 (14%) underassessed their pre-pregnancy weight status. By the end of pregnancy, 823 women (54%) gained excessively. Compared with normal weight accurate assessors, the adjusted odds of excessive gestational weight gain was 2.0 (95% confidence interval [CI]: 1.3, 3.0) in normal weight overassessors, 2.9 (95% CI: 2.2, 3.9) in overweight/obese accurate assessors, and 7.6 (95% CI: 3.4, 17.0) in overweight/obese underassessors. Conclusion: Misperceived pre-pregnancy body weight status was associated with excessive gestational weight gain among both normal weight and overweight/obese women, with the greatest likelihood of excessive gain among overweight/obese underassessors. Future interventions should test the potential benefits of correcting misperception to reduce the likelihood of excessive gestational weight gain.

Background: One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD) in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder. Methods and design: We are using the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype1000 women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD. The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary-adrenal axis, the locus coeruleus/noradrenergic system, and the limbic-frontal neuro-circuitry of fear. The secondary, exploratory aim of this study is to dissect genetic influences on PTSD in the broader genetic and environmental context for the candidate genes that show significant association with PTSD in detection analyses. This will involve: conducting conditional tests to identify the causal genetic variant among multiple correlated signals; testing whether the effect of PTSD genetic risk variants is moderated by age of first trauma, trauma type, and trauma severity; and exploring gene-gene interactions using a novel gene-based statistical approach. Discussion: Identification of liability genes for PTSD would represent a major advance in understanding the pathophysiology of the disorder. Such understanding could advance the development of new pharmacological agents for PTSD treatment and prevention. Moreover, the addition of PTSD assessment data will make the NHSII cohort an unparalleled resource for future genetic studies of PTSD as well as provide the unique opportunity for the prospective examination of PTSD-disease associations.

Background: Animal data show that decreased activity of placental 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which potently inactivates glucocorticoids (e.g. cortisol) to inert forms (cortisone), allows increased access of maternal glucocorticoids to the fetus and 'programs' hypertension. Data in humans are limited. We examined in humans the association between venous umbilical cord blood glucocorticoids, a potential marker for placental 11β-HSD2 enzyme activity, and blood pressure at age 3 years. Methods: Among 286 newborns in Project Viva, a prospective pre-birth cohort study based in eastern Massachusetts, we measured cortisol (F) and cortisone (E) in venous cord blood and used the ratio of F/E as a marker for placental 11β-HSD2 activity. We measured blood pressure (BP) when the offspring reached age 3 years. Using mixed effects regression models to control for BP measurement conditions, maternal and child characteristics, we examined the association between the F/E ratio and child BP. Results: At age 3 years, each unit increase in the F/E ratio was associated with a 1.6 mm Hg increase in systolic BP (95% CI 0.0 to 3.1). The F/E ratio was not associated with diastolic blood pressure or birth weight for gestational age z-score. Conclusion: A higher F/E ratio in umbilical venous cord blood, likely reflecting reduced placental 11β-HSD2 activity, was associated with higher systolic blood pressure at age 3 years. Our data suggest that increased fetal exposure to active maternal glucocorticoids may program later systolic blood pressure.

Objective: Lactation has been associated with reduced maternal risk of type 2 diabetes, the metabolic syndrome, and cardiovascular disease. We examined the relationship between breastfeeding duration and maternal adipokines at 3 years postpartum. Research Design and Methods: We used linear regression to relate the duration of lactation to maternal leptin, adiponectin, ghrelin, and peptide YY (PYY) at 3 years postpartum among 570 participants with 3-year postpartum blood samples (178 fasting), prospectively collected lactation history, and no intervening pregnancy in Project Viva, a cohort study of mothers and children. Results: A total of 88% of mothers had initiated breastfeeding, 26% had breastfed (\geq 12) months, and 42% had exclusively breastfed for (\geq 3) months. In multivariate analyses, we found that duration of total breastfeeding was directly related to PYY and ghrelin, and exclusive breastfeeding duration was directly related to ghrelin (predicted mean for never exclusively breastfeeding: 790.6 pg/mL vs. (\geq 6) months of exclusive breastfeeding: 1,008.1 pg/mL; P < 0.01) at 3 years postpartum, adjusting for pregravid BMI, gestational weight gain, family history of diabetes, parity, smoking status, and age. We found a nonlinear pattern of association between exclusive breastfeeding duration and adiponectin in multivariate-adjusted models. Conclusions: In this prospective cohort study, we found a direct relationship between the duration of lactation and both ghrelin and PYY at 3 years postpartum.

Objectives To prospectively assess the joint association of birth weight and established lifestyle risk factors in adulthood with incident type 2 diabetes and to quantitatively decompose the attributing effects to birth weight only, to adulthood lifestyle only, and to their interaction. Design: Prospective cohort study. Setting: Health Professionals Follow-up Study (1986-2010), Nurses’ Health Study (1980-2010), and Nurses’ Health Study II (1991-2011). Participants: 149 794 men and women without diabetes, cardiovascular disease, or cancer at baseline. Main outcome measure Incident cases of type 2 diabetes, identified through self report and validated by a supplementary questionnaire. Unhealthy lifestyle was defined on the basis of body mass index, smoking, physical activity, alcohol consumption, and the alternate healthy eating index. Results: During 20-30 years of follow-up, 11 709 new cases of type 2 diabetes were documented. The multivariate adjusted relative risk of type 2 diabetes was 1.45 (95% confidence interval 1.32 to 1.59) per kg lower birth weight and 2.10 (1.71 to 2.58) per unhealthy lifestyle factor. The relative risk of type 2 diabetes associated with a combination of per kg lower birth weight and per unhealthy lifestyle factor was 2.86 (2.26 to 3.63), which was more than the addition of the risk associated with each individual factor, indicating a significant interaction on an additive scale (P for interaction<0.001). The attributable proportions of joint effect were 22% (95% confidence interval 18.3% to 26.4%) to lower birth weight alone, 59% (57.1% to 61.5%) to unhealthy lifestyle alone, and 18% (13.9% to 21.3%) to their interaction. Conclusion: Most cases of type 2 diabetes could be prevented by the adoption of a healthier lifestyle, but simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases.