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.Citation: Stingone JA, Luben TJ, Daniels JL, Fuentes M, Richardson DB, Aylsworth AS, Herring AH, Anderka M, Botto L, Correa A, Gilboa SM, Langlois PH, Mosley B, Shaw GM, Siffel C, Olshan AF, National Birth Defects Prevention Study. 2014. Maternal exposure to criteria air pollutants and congenital heart defects in offspring: results from the National Birth Defects Prevention Study. Environ Health Perspect 122:863–872; http://dx.doi.org/10.1289/ehp.1307289

Associations between exposure to ambient benzene and PM2.5 during pregnancy and the risk of selected birth defects in offspring

“…Several studies have examined the association between maternal exposure to ambient air pollution and congenital heart defects, orofacial clefts, and spina bifida (Agay-Shay et al, 2013; Dadvand et al, 2011aDadvand et al, , 2011bDolk et al, 2010;Gilboa et al, 2005;Hansen et al, 2009;Hwang and Jaakkola, 2008;Lupo et al, 2011;Marshall et al, 2010;Padula et al, 2013a;Padula et al, 2013bPadula et al, , 2013cRamakrishnan et al, 2013;Rankin et al, 2009;Ritz et al, 2002;Schembari et al, 2014;Stingone et al, 2014;Strickland et al, 2009;Vinikoor-Imler et al, 2013). However, benzene and (until recently) PM 2.5 have been understudied pollutants in fetal development.…”

“…Exposure has been reported to impact fetal growth (Le et al, 2012;Rich et al, 2009), birth weight (Morello-Frosch et al, 2010;Wilhelm et al, 2012), preterm birth (Chang et al, 2012;Rudra et al, 2011), as well as pregnancy conditions such as preeclampsia Wu et al, 2009;Wu et al, 2011). Several studies have also examined the association between exposure to air pollution and select birth defects (Dadvand et al, 2011a(Dadvand et al, , 2011bDolk et al, 2010;Gilboa et al, 2005;Hansen et al, 2009;Hwang and Jaakkola, 2008;Rankin et al, 2009;Ritz et al, 2002;Stingone et al, 2014;Strickland et al, 2009); however, only until recently have studies included PM 2.5 and benzene as pollutants of interest (Agay-Shay et al, 2013;Lupo et al, 2011;Marshall et al, 2010;Padula et al, 2013aPadula et al, , 2013bPadula et al, , 2013cRamakrishnan et al, 2013;Schembari et al, 2014;Vinikoor-Imler et al, 2013).…”

Congenital Malformations, Deformations and Chromosomal Abnormalities in Cyprus

“…In contrast, a number of studies have shown no correlation between PM10 and fetal cardiovascular malformations [17]. An inverse correlation between PM10 and abdominal diaphragmatic defects has also been reported [18] between fine particles (PM2,5 with aerodynamic diameter ≤ 2,5 μm) and vaginal diaphragmatic defects [13,19] and isolated arterial patency [15]. This work studies the congenital malformations, deformations and chromosomal abnormalities related to the gender and age of occurrence in Cyprus and their relation to atmospheric pollution.…”

Preventing birth defects: The value of the NBDPS case–control approach

“…These studies may also be subject to confounding from the potential correlation of high ascertainment of birth defects in urban centers and high pollution measurements (Armstrong et al, 2007). Stingone et al (2014) have made a recent contribution to this literature with NBDPS data, with maternal address during early pregnancy linked to data from the nearest air pollution monitor. As usual, multiple testing across 6 criteria air pollutants, and 17 CHD types, make for complex interpretation that requires looking for patterns, particularly doseresponse trends, rather than individually significant results, and correlations between pollutants must also be taken into account.…”

“…As usual, multiple testing across 6 criteria air pollutants, and 17 CHD types, make for complex interpretation that requires looking for patterns, particularly doseresponse trends, rather than individually significant results, and correlations between pollutants must also be taken into account. Examination by week of pregnancy showed how sensitive the results can be to the specification of the critical exposure window (Stingone et al, 2014). The case-control study design has the advantage in environmental pollution studies of providing early pregnancy residence (the availability of which is a great strength of NBDPS), and rich data on confounding variables.…”