Methods: We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´- DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models.
Results: Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´- DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´- DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL).
We investigated relationships between ambient levels of air pollution during pregnancy and birth weight in a cohort of 406,627 full-term births occurring between 1994 and 2004 in the five central counties of metropolitan Atlanta, Georgia. Pollutants examined included CO, nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), particulate matter ≤ 10 μm in diameter (PM10), PM2.5 (2.5 chemical component measurements that are rarely available on a daily basis and have not been previously assessed in relation to measures of fetal growth. We focused on two gestational windows of a priori interest based on previous air pollution studies, studies of maternal active and passive smoking, and toxicologic evidence: the first month of gestation and the third trimester. In a novel use of distributed lag models, we used a data-based approach to explore associations in each of the 9 months of gestation to identify other potentially vulnerable gestational windows.
Study population. We obtained vital record data for births to mothers residing in the five central counties of the Atlanta metropolitan area (Clayton, Cobb, DeKalb, Fulton, and Gwinnett counties) from the Office of Health Information and Policy, Georgia Division of Public Health. The study area included an area with a radius of 16 miles (25.7 km) at its narrowest and 32 miles (51.5 km) at its widest [see Supplemental Material, (doi:10.1289/ehp.1002785)]. We restricted analysis to full-term infants to separate the pathologies of reduced fetal growth from reduced pregnancy duration (i.e., preterm birth); results of our preterm birth analyses are reported separately (). The cohort included singleton non-Hispanic African-American, non-Hispanic Caucasian, and Hispanic infants who reached at least 37 weeks of gestation and were born between 1 January 1994 and 31 December 2004 without major structural congenital birth defects (n = 417,280). Of these, 10,653 infants (2.5%) were excluded because of missing data. Gestational age was determined using the reported last menstrual period (LMP) date; if LMP date was missing, we substituted the clinical estimate (1.3% of records). After exclusions, 406,627 full-term births were eligible for analysis. Study protocols were approved by Emory University Institutional Review Board.
Conclusions: Results provide some support for an effect of ambient air pollution in late pregnancy on birth weight in full-term infants.
shows the results from models assessing effect modification by race and ethnicity for pollutant concentrations in the third trimester. The pollution × race interaction terms were statistically significant for CO, O3, PM10, PM2.5, and PM2.5–10. Overall, we observed more statistically significant associations between air pollutants and birth weight in the Hispanic and non-Hispanic black groups than in the non-Hispanic white group. Notably, the association between PM2.5 water-soluble metals and birth weight was statistically significant and of similar magnitude for all three racial and ethnic groups.
Mean change in birth weight (Δg) and 95% confidence intervals (CI) for ambient air pollutant concentrations in the first month of pregnancy and the third trimester for full-term births in five-county Atlanta.
Mean change in birth weight (Δg) and 95% confidence intervals (CI) for ambient air pollution levels in the third trimester for full-term births in five-county Atlanta by race and ethnicity.
Maternal and infant characteristics [n (%)] for full-term births in five-county Atlanta and for births within 4 miles of a monitoring station, 1 January 1994 to 31 December 2004.
We investigated relationships between ambient concentrations of 12 pollutants during two a priori gestational windows of interest and birth weight in full-term infants. In the five-county analysis, we observed little evidence of an association between air pollution concentrations in the first month of gestation and reduced birth weight; we observed one association between PM2.5 nitrate and increased birth weight. Third-trimester concentrations of four pollutants (NO2, SO2, PM2.5 elemental carbon, and PM2.5 water-soluble metals) were associated with small decreases in birth weight. The capture-area analyses, which used measurements close to the maternal residence, provided little support for the associations observed in the five-county analysis, although confidence intervals were wide. The capture-area analyses did show an association between CO levels in the first month of gestation and decreased birth weight.
In the five-county cohort, the mean ± SD birth weight among full-term infants was 3,405 ± 477 g; for births within 4 miles of a monitor, the mean birth weight was 3,350 ± 475 g. shows maternal and infant characteristics for these cohorts. Compared with the full five-county cohort, mothers residing within 4 miles of a monitor were younger, less educated, and more likely to be non-Hispanic black and unmarried.
Citation: Lenters V, Portengen L, Rignell-Hydbom A, Jönsson BA, Lindh CH, Piersma AH, Toft G, Bonde JP, Heederik D, Rylander L, Vermeulen R. 2016. Prenatal phthalate, perfluoroalkyl acid, and organochlorine exposures and term birth weight in three birth cohorts: multi-pollutant models based on elastic net regression. Environ Health Perspect 124:365–372;
Because ambient air pollution levels exhibit strong seasonal variation, and other risk factors for reduced birth weight may also vary by season (), we smoothly controlled for seasonal trends using parametric cubic splines on the date of conception. We adjusted for long-term temporal trends in birth weight using a second cubic spline with one knot per year; a cubic term without knots was used in the distributed lag analyses. We also assessed potential confounding by mean temperature and mean dew point over the gestational window of interest.