Faculty Bibliography

BACKGROUND AND OBJECTIVE: Few studies have examined the possible cardiometabolic consequences of World Trade Center-related exposures on children who lived and/or attended school near the disaster site. Our objective was to compare cardiometabolic profiles of participants in the World Trade Center Health Registry (WTCHR) with a matched comparison group. METHODS: We evaluated WTCHR enrollees who resided in New York City and were born between September 11, 1993 and September 10, 2001, and a matched comparison group. We assessed exposure to dust cloud, home dust, as well as traumatic exposure, and associations with blood pressure, arterial wall stiffness, body mass index (BMI), total cholesterol, triglycerides, HDL, and LDL. RESULTS: A total of 402 participants completed the study, 222 in the comparison group and 180 in the WTCHR group. In multivariable regression analysis, after adjusting for relevant confounders we detected a weak association between participation in the WTCHR group and lower BMI (-1.12kg/m2, 95% CI -2.11, -0.12; p = 0.03), which became non-significant after adjusting for multiple comparisons. With respect to traumatic and psychosocial exposures, the only association that persisted in our multivariable model, below our predefined level of significance, was between post-traumatic stress disorder and higher BMI (2.06kg/m2, 95% CI 0.37, 3.74; p = 0.02). CONCLUSIONS: Our findings do not support an association between self-reported exposures to the WTC disaster and adverse cardiometabolic profile. However, further longitudinal studies may better inform the full extent of WTC-related conditions associated with exposure to the disaster.

Adequate docosahexaenoic acid (DHA) is essential for the optimal growth and development of the fetus. Maternal DHA content fluctuates during pregnancy. The correlation of DHA content with dietary intake might be varied over the course of pregnancy. We aimed to compare the dietary DHA intake, estimated by a DHA-specific semiquantitative food frequency questionnaire (FFQ) against its blood content, among mid- and late-term pregnant women. A total of 804 Chinese pregnant women completed the tailored FFQ and provided fasting venous blood samples. Dietary DHA intake (mg/day) in the previous month was calculated from the FFQ using Chinese Food Composition Table. DHA concentrations (weight percent of total fatty acids) in plasma and erythrocytes were measured by capillary gas chromatography. Spearman correlation coefficients (r_s) between DHA intake and its relative concentrations were calculated. After adjustment for maternal age, pre-pregnancy body mass index, stage of pregnancy, parity, education level, ethnicity, and annual family income per capita, the correlation coefficients of DHA intake with its concentrations in plasma and erythrocytes were 0.35 and 0.33, respectively (p < 0.001). The correlations were relatively stronger among women in late pregnancy (r_s = 0.44 in plasma and 0.39 in erythrocytes) than those in mid-pregnancy (r_s = 0.25 and 0.26). The significant correlations were consistently observed in subgroups stratified by regions, except for erythrocytes in women living in a coastland area. Multiple regression analyses also indicated significant positive linear correlations between DHA intake and its plasma or erythrocytes concentrations (p < 0.001). In conclusion, dietary DHA intake, estimated by the FFQ, was positively correlated with its concentrations in plasma and erythrocytes in Chinese pregnant women, especially for women in late pregnancy, with the exception of the erythrocytes of those living in a coastland area.

Using a population-based birth cohort in upstate New York (2008-2010), we examined the determinants of brain-derived neurotrophic factor (BDNF) measured in newborn dried blood spots (n = 2,637). We also examined the association between neonatal BDNF and children's development. The cohort was initially designed to examine the influence of infertility treatment on child development but found no impact. Mothers rated children's development in five domains repeatedly through age 3 years. Socioeconomic and maternal lifestyle determinants of BDNF were examined using multivariable linear regression models. Generalized linear mixed models estimated odds ratios for neonatal BDNF in relation to failing a developmental domain. Smoking and drinking in pregnancy, nulliparity, non-White ethnicity/race, and prepregnancy obesity were associated with lower neonatal BDNF. Neonatal BDNF was not associated with failure for developmental domains; however, there was an interaction between BDNF and preterm birth. In preterm infants, a higher BDNF was associated with lower odds of failing any developmental domains, after adjusting for confounders and infertility treatment. This result was particularly significant for failure in communication. Our findings suggest that BDNF levels in neonates may be impacted by maternal lifestyle characteristics. More specifically, lower neonatal BDNF might be an early marker of aberrant neurodevelopment in preterm infants.

Children raised in economically disadvantaged households face increased risks of poor health in adulthood, suggesting that inequalities in health have early origins. From the child's perspective, exposure to economic hardship may begin as early as conception, potentially via maternal neuroendocrine-immune responses to prenatal stressors, which adversely impact neurodevelopment. Here we investigate whether socioeconomic disadvantage is associated with gestational immune activity and whether such activity is associated with abnormalities among offspring during infancy. We analyzed concentrations of five immune markers (IL-1β, IL-6, IL-8, IL-10, and TNF-α) in maternal serum from 1,494 participants in the New England Family Study in relation to the level of maternal socioeconomic disadvantage and their involvement in offspring neurologic abnormalities at 4 mo and 1 y of age. Median concentrations of IL-8 were lower in the most disadvantaged pregnancies [-1.53 log(pg/mL); 95% CI: -1.81, -1.25]. Offspring of these pregnancies had significantly higher risk of neurologic abnormalities at 4 mo [odds ratio (OR) = 4.61; CI = 2.84, 7.48] and 1 y (OR = 2.05; CI = 1.08, 3.90). This higher risk was accounted for in part by fetal exposure to lower maternal IL-8, which also predicted higher risks of neurologic abnormalities at 4 mo (OR = 7.67; CI = 4.05, 14.49) and 1 y (OR = 2.92; CI = 1.46, 5.87). Findings support the role of maternal immune activity in fetal neurodevelopment, exacerbated in part by socioeconomic disadvantage. This finding reveals a potential pathophysiologic pathway involved in the intergenerational transmission of socioeconomic inequalities in health.

BACKGROUND:Maternal retinol-binding protein 4 (RBP4) and lipids may relate to preeclampsia and preterm birth risk but longitudinal data are lacking. This study examines these biomarkers longitudinally during pregnancy in relation to preeclampsia and preterm birth risk. METHODS:Maternal serum samples from the Calcium for Preeclampsia Prevention (CPEP) trial were analyzed at baseline: average 15 gestational weeks; mid-pregnancy: average 27 weeks; and at >34 weeks. We measured RBP4, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and lipoprotein (a) (Lp(a)). Cross-sectional logistic regression analyses estimated the odds ratio (OR) and 95% confidence intervals (CI) for preterm preeclampsia (n = 63), term preeclampsia (n = 104), and preterm delivery (n = 160) associated with RBP4 and lipids at baseline and mid-pregnancy compared with controls (n = 136). Longitudinal trajectories across pregnancy were assessed using mixed linear models with fixed effects. Adjusted models included clinical and demographic factors. RESULTS:RBP4 concentrations at baseline and mid-pregnancy were associated with a 4- to 8-fold increase in preterm preeclampsia risk but were not associated with term preeclampsia. RBP4 measured mid-pregnancy was also associated with preterm birth (OR = 6.67, 95% CI: 1.65, 26.84). Higher triglyceride concentrations in mid-pregnancy were associated with a 2- to 4-fold increased risk for both preeclampsia and preterm birth. Longitudinal models demonstrate that both preterm preeclampsia and preterm birth cases had elevated RBP4 throughout gestation. CONCLUSIONS:Elevated RBP4 is detectable early in pregnancy and its strong relation with preterm preeclampsia merits further investigation and confirmation to evaluate its potential use as a predictor, particularly among high-risk women.

Background: The relation between breastfeeding and early motor development is difficult to characterize because of the problems in existing studies such as incomplete control for confounding, retrospective assessment of infant feeding, and even the assessment of some motor skills too early.Objective: We sought to estimate associations between infant feeding and time to achieve major motor milestones in a US cohort.Design: The Upstate New York Infant Development Screening Program (Upstate KIDS Study) enrolled mothers who delivered live births in New York (2008-2010). Mothers of 4270 infants (boys: 51.7%) reported infant motor development at 4, 8, 12, 18, and 24 mo postpartum; information on infant feeding was reported at 4 mo. Accelerated failure time models were used to compare times to standing or walking across feeding categories while adjusting for parental characteristics, daycare, region, and infant plurality, sex, rapid weight gain, and baseline neurodevelopmental test results. Main models were stratified by preterm birth status.Results: The prevalence of exclusive breastfeeding in preterm infants was lower than in term infants at 4 mo postpartum (8% compared with 19%). After adjustment for confounders, term infants who were fed solids in addition to breast milk at 4 mo postpartum achieved both standing [acceleration factor (AF): 0.93; 95% CI: 0.87, 0.99] and walking (AF: 0.93; 95% CI: 0.88, 0.98) 7% faster than did infants who were exclusively breastfed, but these findings did not remain statistically significant after correction for multiple testing. We did not identify feeding-associated differences in motor milestone achievement in preterm infants.Conclusion: Our results suggest that differences in feeding likely do not translate into large changes in motor development. The Upstate KIDS Study was registered at clinicaltrials.gov as NCT03106493.

Although the Child Behavior Checklist 1½-5's 12-item Diagnostic and Statistical Manual of Mental Disorders-Autism Spectrum Problems Scale (formerly called Pervasive Developmental Problems scale) has been used in several studies as an autism spectrum disorder screener, the base rate and stability of its items and its measurement model have not been previously studied. We therefore examined the structure, longitudinal invariance, and stability of the Child Behavior Checklist 1½-5's Diagnostic and Statistical Manual of Mental Disorders-Autism Spectrum Problems Scale in the diverse Generation R (Rotterdam) sample based on mothers' ratings at 18 months ( n = 4695), 3 years ( n = 4571), and 5 years ( n = 5752). Five items that seemed especially characteristic of autism spectrum disorder had low base rates at all three ages. The rank order of base rates for the 12 items was highly correlated over time ( Qs ⩾ 0.86), but the longitudinal stability of individual items was modest (phi coefficients = 0.15-0.34). Confirmatory factor analyses indicated that the autism spectrum disorder scale model manifested configural, metric, and scalar longitudinal invariance over the time period from 18 months to 5 years, with large factor loadings. Correlations over time for observed autism spectrum disorder scale scores (0.25-0.50) were generally lower than the correlations across time of the latent factors (0.45-0.68). Results indicated significant associations of the autism spectrum disorder scale with later autism spectrum disorder diagnoses.