Person:

Rich-Edwards, Janet

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: 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.

Introduction: Body mass index (BMI) during adulthood is inversely related to the incidence of premenopausal breast cancer, but the role of body fatness earlier in life is less clear. We examined prospectively the relation between body fatness during childhood and adolescence and the incidence of breast cancer in premenopausal women. Methods: Participants were 109,267 premenopausal women in the Nurses' Health Study II who recalled their body fatness at ages 5, 10 and 20 years using a validated 9-level figure drawing. Over 12 years of follow up, 1318 incident cases of breast cancer were identified. Cox proportional hazards regression was used to compute relative risks (RRs) and 95% confidence intervals (CIs) for body fatness at each age and for average childhood (ages 5–10 years) and adolescent (ages 10–20 years) fatness.Results Body fatness at each age was inversely associated with premenopausal breast cancer incidence; the multivariate RRs were 0.48 (95% CI 0.35–0.55) and 0.57 (95% CI 0.39–0.83) for the most overweight compared with the most lean in childhood and adolescence, respectively (P for trend < 0.0001). The association for childhood body fatness was only slightly attenuated after adjustment for later BMI, with a multivariate RR of 0.52 (95% CI 0.38–0.71) for the most overweight compared with the most lean (P for trend = 0.001). Adjustment for menstrual cycle characteristics had little impact on the association. Conclusion: Greater body fatness during childhood and adolescence is associated with reduced incidence of premenopausal breast cancer, independent of adult BMI and menstrual cycle characteristics.