Faculty Bibliography

BACKGROUND:We assessed the association between perfluorooctanoic acid (PFOA) and pregnancy outcome in an area with elevated exposure to PFOA from drinking water contaminated by chemical plant releases. METHODS:Serum PFOA was measured, and reproductive and residential histories were obtained during 2005-2006. We estimated serum PFOA levels at the time of pregnancy for 11,737 pregnancies occurring between 1990 and 2006, based on historical information on PFOA releases, environmental distribution, pharmacokinetic modeling, and residential histories. We assessed the association between PFOA and the odds of miscarriage, stillbirth, preeclampsia, preterm birth, term low birthweight, and birth defects, controlling for calendar time, age, parity, education, and smoking. PFOA exposure was evaluated as a continuous measure (with and without log transformation) and in quintiles, combining the lowest 2 quintiles (< 6.8 ng/mL) as the referent. RESULTS:Measures of association between PFOA and miscarriage, preterm birth, term low birthweight, and birth defects were close to the null. Odds of stillbirth were elevated in the fourth quintile only. For preeclampsia, the odds ratio was 1.13 (95% confidence interval = 1.00-1.28) for an interquartile shift in log-transformed PFOA, and the odds ratios were 1.1-1.2 across the upper 3 quintiles of exposure. CONCLUSIONS:In this large, population-based study in a region with markedly elevated PFOA exposure, we found no associations between estimated serum PFOA levels and adverse pregnancy outcomes other than possibly preeclampsia. Conclusions are tempered by inherent limitations in exposure reconstruction and self-reported pregnancy outcome information.

After the emergence of pandemic influenza viruses in 1957, 1968, and 2009, existing seasonal viruses were observed to be replaced in the human population by the novel pandemic strains. We have previously hypothesized that the replacement of seasonal strains was mediated, in part, by a population-scale boost in antibodies specific for conserved regions of the hemagglutinin stalk and the viral neuraminidase. Numerous recent studies have shown the role of stalk-specific antibodies in neutralization of influenza viruses; the finding that stalk antibodies can effectively neutralize virus alters the existing dogma that influenza virus neutralization is mediated solely by antibodies that react with the globular head of the viral hemagglutinin. The present study explores the possibility that stalk-specific antibodies were boosted by infection with the 2009 H1N1 pandemic virus and that those antibodies could have contributed to the disappearance of existing seasonal H1N1 influenza virus strains. To study stalk-specific antibodies, we have developed chimeric hemagglutinin constructs that enable the measurement of antibodies that bind the hemagglutinin protein and neutralize virus but do not have hemagglutination inhibition activity. Using these chimeric hemagglutinin reagents, we show that infection with the 2009 pandemic H1N1 virus elicited a boost in titer of virus-neutralizing antibodies directed against the hemagglutinin stalk. In addition, we describe assays that can be used to measure influenza virus-neutralizing antibodies that are not detected in the traditional hemagglutination inhibition assay.

Studies on ethnic differences in the risk of pre-eclampsia are limited. We linked birth records for 902,460 singleton births for the period 1995-2003 in New York City with hospital discharge data to evaluate the association between ethnicity and the risk of pre-eclampsia and compare risks between US-born and foreign-born women. Logistic regression models adjusted for maternal age, maternal education, parity, self-reported pre-pregnancy maternal weight, smoking during pregnancy and year of delivery were used to compare each ethnic group with non-Hispanic White women. The prevalence of pre-eclampsia in this study population was 3.2%. Among the major ethnic groups considered in our study, East Asian women had the lowest risk of pre-eclampsia (1.4%) and Mexican women had the highest risk (5.0%). Compared with non-Hispanic White women, there was a slightly decreased risk for East Asian women (adjusted OR = 0.8, [95% CI 0.7, 0.8]), similar risk for North African women (adjusted OR = 1.1, [95% CI 0.9, 1.3]), and increased risk for all other major ethnic groups (adjusted ORs: 1.3, 2.9), with the highest risk for Mexican women (adjusted OR = 2.9, [95% CI 2.7, 3.1]). No difference in risks was observed for US- vs. foreign-born women with the exception that foreign-born South-East Asian and Pacific Islanders had an increased risk of pre-eclampsia (adjusted OR = 1.8, [95% CI 1.0, 3.1]) relative to those born in the US. We concluded that there was ethnic heterogeneity in the development of pre-eclampsia among women in New York City and that Asian subgroups should be examined separately in future studies on ethnicity. Our results should contribute to screening for pre-eclampsia taking ethnic variation into account, and may help to suggest leads for the study of the aetiology of the condition.

BACKGROUND:Perfluorinated compounds (PFCs) are persistent environmental pollutants. Toxicology studies demonstrate the potential for perfluorooctanoic acid (PFOA) and other PFCs to affect human growth and development. Attention deficit/hyperactivity disorder (ADHD) is a developmental disorder with suspected environmental and genetic etiology. OBJECTIVES/OBJECTIVE:We examined the cross-sectional association between serum PFC concentration and parent or self-report of doctor-diagnosed ADHD with and without current ADHD medication. METHODS:We used data from the C8 Health Project, a 2005-2006 survey in a Mid-Ohio Valley community highly exposed to PFOA through contaminated drinking water, to study non-Hispanic white children 5-18 years of age. Logistic regression models were adjusted for age and sex. RESULTS:Of the 10,546 eligible children, 12.4% reported ADHD and 5.1% reported ADHD plus ADHD medication use. We observed an inverted J-shaped association between PFOA and ADHD, with a small increase in prevalence for the second quartile of exposure compared with the lowest, and a decrease for the highest versus lowest quartile. The prevalence of ADHD plus medication increased with perfluorohexane sulfonate (PFHxS) levels, with an adjusted odds ratio of 1.59 (95% confidence interval, 1.21-2.08) comparing the highest quartile of exposure to the lowest. We observed a modest association between perfluorooctane sulfonate and ADHD with medication. CONCLUSIONS:The most notable finding for PFOA and ADHD, a reduction in prevalence at the highest exposure level, is unlikely to be causal, perhaps reflecting a spurious finding related to the geographic determination of PFOA exposure in this population or to unmeasured behavioral or physiologic correlates of exposure and outcome. Possible positive associations between other PFCs and ADHD, particularly PFHxS, warrant continued investigation.

PURPOSE/OBJECTIVE:To compare the sexual behaviors of young people in South Africa (SA) and the United States (US) with the aim to better understand the potential role of sexual behavior in HIV transmission in these two countries that have strikingly different HIV epidemics. METHODS:Nationally representative, population-based surveys of young people aged 18-24 years from SA (n = 7,548) and the US (n = 13,451) were used for the present study. RESULTS:The prevalence of HIV was 10.2% in SA and <1% in the US. Young women and men in the US reported an earlier age of first sex than those in SA (mean age of coital debut for women: US [16.5], SA [17.4]; for men: US [16.4], SA [16.7]). The median number of lifetime partners is higher in the US than in SA: women: US (4), SA (2); men: US (4), SA (3). The use of condom at last sex is reported to be lower in the US than in SA: women: US (36.1%), SA (45.4%); men: US (48%), SA (58%). On average, young women in SA report greater age differences with their sex partners than young women in the US. CONCLUSION/CONCLUSIONS:Young people in the US report riskier sexual behaviors than young people in SA, despite the much higher prevalence of HIV infection in SA. Factors above and beyond sexual behavior likely play a key role in the ongoing transmission of HIV in South African youth, and thus should be urgently uncovered to develop maximally effective prevention strategies.

PURPOSE/OBJECTIVE:Smoking during pregnancy is strongly associated with increased risk of small for gestational age (SGA) and low birth weight, whereas elevated prepregnancy body mass index (BMI) is associated with a decreased risk of SGA and greater birth weight. We investigated the combined effect of prenatal smoking and prepregnancy BMI on risk of SGA and on birth weight. METHODS:A total of 34,928 singleton, term pregnancies in residents of New York City between 1995 and 2003 were evaluated in multivariable regression models of birth weight and risk of SGA. RESULTS:Increasing prepregnancy BMI reduced the risk of SGA and increased birth weight. The effect of prenatal smoking on birth weight and SGA diminished in women as their prepregnancy BMI increased, such that prenatal smoking did not significantly impact the risk of SGA among women who were overweight or obese before pregnancy. Prenatal smoking decreased mean birth weight by 187 g (95% confidence interval [CI] -337, -37) among underweight women, by 129 g(95% CI -170, -87) among normal weight women, by 46 g (95% CI -113, +20) among overweight women, and by 75 g (95% CI -162, +11) among obese women. CONCLUSIONS:This study suggests that the effect of smoking during pregnancy on SGA and birth weight is present in underweight and normal weight women but markedly reduced among obese and overweight women.

PURPOSE/OBJECTIVE:The purpose of this study is to describe the patterns of hospitalization for depression in the year after delivery in relation to social, demographic, and behavioral characteristics. METHODS:Data on births were linked to hospitalizations for depression over the subsequent year to describe the frequency and patterns of hospitalized postpartum depression among 2,355,886 deliveries in New York State from 1995 to 2004. We identified "definite postpartum depression" based on International Classification of Diseases (ICD) codes indicative of "mental disorders specific to pregnancy," and "possible postpartum depression" by ICD codes for hospitalization with any depressive disorders. RESULTS:In New York State, we identified 1363 women (5.8 per 10,000) who were hospitalized with definite postpartum depression, and 6041 women (25.6 per 10,000) with possible postpartum depression, with lower risks in the New York City area. Postpartum depression was more common in later years and among mothers who were older, Black, smokers, lacking private insurance, and with multiple gestations, and was rarer among Asians. For possible postpartum depression, socioeconomic gradients were enhanced. CONCLUSIONS:Risk of hospitalized postpartum depression is strongly associated with socioeconomic deprivation and varies markedly by ethnicity, with direct implications for screening and health services, also providing suggestions for etiologic studies.

PURPOSE/OBJECTIVE:The obesity epidemic raises concerns about the impact of excessive and insufficient weight gain during pregnancy. METHODS:We examined the association between gestational weight gain (GWG) and preterm birth, term small- and large-for-gestational-age (SGA and LGA), term birthweight, and term primary Cesarean delivery, considering prepregnancy body mass index (BMI) and ethnicity in a cohort of 33,872 New York City residents who gave birth between 1995 and 2003 and delivered in hospitals elsewhere in New York State. RESULTS:Preterm birth (<37 weeks' gestation) showed a modest U-shaped relationship, with projected GWG of <10 kg and 20+ kg associated with odds ratios of 1.4 and 1.3, respectively, relative to 10 to 14 kg. The pattern was stronger for preterm birth <32 weeks' and for underweight women with low GWG and overweight/obese women with high GWG. Term SGA decreased and term LGA and birthweight increased monotonically with increasing GWG. Primary Cesarean delivery followed the same pattern as LGA, but less strongly. CONCLUSIONS:Although the study is limited by potential selection bias and measurement error, our findings support the contention that GWG may be a modifiable predictor of pregnancy outcome that warrants further investigation, particularly randomized trials, to assess whether the relation is causal.

PURPOSE/OBJECTIVE:Living in a socioeconomically deprived neighborhood has been associated with an increased risk of adverse birth outcomes. However, variation in the effect of neighborhood deprivation among diverse ethnic groups has not been studied. METHODS:Using linked hospital discharge and birth data for 517,994 singleton live births in New York City from 1998 through 2002, we examined the association between neighborhood deprivation, preterm birth (PTB), and term low birthweight (TLBW) (>or=37 weeks and <2500g). Adjusted odds ratios (aORs) for PTB (<32 and 33-36 weeks) and TLBW were estimated using logistic regression. RESULTS:The aOR for PTB of less than 32 weeks for the highest quartile of deprivation compared to the lowest was 1.24 (95% confidence limit [CL] = 1.13, 1.36), for PTB 33-36 weeks was 1.06 (95% CL = 1.01, 1.11), and for TLBW was 1.19 (95% CL = 1.11, 1.27). Measures of association varied by ethnicity; aORs of the greatest magnitude for PTB were found among Hispanic Caribbean women (PTB < 32 weeks: aOR = 1.63, 95% CL = 1.27, 2.10; PTB 33-36 weeks: aOR = 1.32, 95% CL = 1.02, 1.70), and for TLBW among African women (aOR = 1.47, 95% CL = 1.02, 2.13). CONCLUSIONS:The mechanisms linking neighborhood deprivation to adverse birth outcomes may differ depending on individual ethnicity and/or cultural context and should be investigated in future research.