Maternal exposure to criteria air pollutants and congenital heart defects in offspring: results from the national birth defects prevention study

Abstract

Background: Epidemiologic literature suggests that exposure to air pollutants is associated with fetal development.

Objectives: We investigated maternal exposures to air pollutants during weeks 2-8 of pregnancy and their associations with congenital heart defects.

Methods: Mothers from the National Birth Defects Prevention Study, a nine-state case-control study, were assigned 1-week and 7-week averages of daily maximum concentrations of carbon monoxide, nitrogen dioxide, ozone, and sulfur dioxide and 24-hr measurements of fine and coarse particulate matter using the closest air monitor within 50 km to their residence during early pregnancy. Depending on the pollutant, a maximum of 4,632 live-birth controls and 3,328 live-birth, fetal-death, or electively terminated cases had exposure data. Hierarchical regression models, adjusted for maternal demographics and tobacco and alcohol use, were constructed. Principal component analysis was used to assess these relationships in a multipollutant context.

Results: Positive associations were observed between exposure to nitrogen dioxide and coarctation of the aorta and pulmonary valve stenosis. Exposure to fine particulate matter was positively associated with hypoplastic left heart syndrome but inversely associated with atrial septal defects. Examining individual exposure-weeks suggested associations between pollutants and defects that were not observed using the 7-week average. Associations between left ventricular outflow tract obstructions and nitrogen dioxide and between hypoplastic left heart syndrome and particulate matter were supported by findings from the multipollutant analyses, although estimates were attenuated at the highest exposure levels.

Conclusions: Using daily maximum pollutant levels and exploring individual exposure-weeks revealed some positive associations between certain pollutants and defects and suggested potential windows of susceptibility during pregnancy.

Figure 1

Estimated adjusted ORs and 95% CIs between CHDs and 7-week average of daily maxima/24-hr measures of criteria air pollutants, National Birth Defects Prevention Study 1997–2006 (for PM_2.5, 1999–2006). Abbreviations: APVR, anomalous pulmonary venous return; ASD, atrial septal defect; AVSD, atrioventricular septal defect; COA, coarctation of the aorta; dTGA, transposition of the great arteries; HLHS, hypoplastic left heart syndrome; LVOTO, left ventricular outflow tract obstructions; PVS, pulmonary valve stenosis; RVOTO, right ventricular outflow tract obstructions; TAPVR, total anomalous pulmonary venous return; TOF, tetralogy of Fallot; VSD_pm, perimembranous ventricular septal defects. Other conotruncal category includes common truncus, interrupted aortic arch–type B and type not specified, double outlet right ventricle defects, and conoventricular septal defects. A double slash (//) indicates truncation of the results. Squares indicate defect groupings; circles indicate individual defects. Defect groupings include all individual defects listed underneath with the following additions: LVOTO, IAA‑type A; APVR, partial APVR; RVOTO, Ebstein’s anomaly; Septal, muscular venricular septal defects (VSD_muscular), except for PM_2.5. VSD_muscular were collected only in the first year of study when no PM_2.5 data were available. Those defects could not be analyzed within the hierarchical regression due to limited sample size. ORs were estimated from hierarchical regression models. First stage was a polytomous logistic model, adjusted for maternal race/ethnicity, age educational attainment, household income, maternal smoking status and alcohol consumption during early pregnancy, nativity, and site-specific heart defect ratio. Second stage was a linear model with indicator variables for defect, defect grouping, and level of exposure. For all pollutants except O₃, the three categories of exposure are as follows: 10th centile to < 50th centile, 50th centile to < 90th centile, and ≥ 90th centile, with the referent level being < 10th centile among controls. For ozone, the three categories of exposure were 25th to < 50th centile, 50th centile to < 75th centile, and ≥ 75th centile, with the referent grouping being below the 25th centile. Pollutant levels that define the category cut points are provided in Table 2. See Supplemental Material, Table S2, for corresponding numeric data.

Figure 2

Estimated adjusted ORs and 95% CIs of pulmonary valve stenosis for categorical measures of 1-week averages of daily maxima/24-hr measures of criteria air pollutants, plotted for weeks 2–8 of pregnancy, National Birth Defects Prevention Study 1997–2006 (for PM_2.5, 1999–2006). ORs were estimated from hierarchical regression models. First stage was a polytomous logistic model, adjusted for maternal race/ethnicity, age, educational attainment, household income, maternal smoking status and alcohol consumption during early pregnancy, nativity, and site-specific heart defect ratio. Second stage was a linear model with indicator variables for defect, defect grouping, and level of exposure. For all pollutants except O₃, the three categories of exposure are as follows: 10th centile to < 50th centile, 50th centile to < 90th centile, and ≥ 90th centile, with the referent level being < 10th centile among controls. For O₃, the three categories of exposure were 25th to < 50th centile, 50th centile to < 75th centile, and ≥ 75th centile, with the referent grouping being < 25th centile. Pollutant levels that define the category cut points are provided in Table 2. See Supplemental Material, Table S4, for corresponding numeric data.

Figure 3

Estimated adjusted ORs and 95% CIs between CHDs and pollutant factors identified through PCA within the National Birth Defects Prevention Study, 1999–2006. Abbreviations: APVR, anomalous pulmonary venous return; ASD, atrial septal defect; AVSD, atrioventricular septal defect; COA, coarctation of the aorta; dTGA, transposition of the great arteries; HLHS, hypoplastic left heart syndrome; LVOTO, left ventricular outflow tract obstructions; PVS, pulmonary valve stenosis; RVOTO, right ventricular outflow tract obstructions; TOF, tetralogy of Fallot; VSD_pm, perimembranous ventricular septal defects. Other conotruncal category includes common truncus, IAA‑type B and -NOS, double outlet right ventricle defects, and conoventricular septal defects. A double slash (//) indicates truncation of the results. Squares indicate defect groupings; circles indicate individual defects. Defect groupings include all individual defects listed underneath with the following additions: LVOTO, IAA‑type A; APVR, total and partial APVR; RVOTO, Ebstein’s anomaly. Those defects could not be analyzed within the hierarchical regression due to limited sample size. Loadings represent the relative weight of each of the original pollutant variables used to obtain the value of the computed factor. ORs were estimated from hierarchical regression models. First stage was a polytomous logistic model, adjusted for maternal race/ethnicity, age educational attainment, household income, maternal smoking status and alcohol consumption during early pregnancy, nativity, and site-specific heart defect ratio. Second stage was a linear model with indicator variables for defect, defect grouping, and level of exposure. For all factors, the three categories of exposure are as follows: 10th centile to < 50th centile, 50th centile to < 90th centile, and ≥ 90th centile, with the referent level being < 10th centile among controls. Pollutant levels which define the category cutpoints are provided in Table 2. See Supplemental Material, Table S5, for corresponding numeric data.