Discussion We found that maternal exposure to OP insec- ticides, assessed by measuring urinary OP pesticide metabolites, was inversely associated with gestational age and birth weight. The esti- mated effects of OP exposure differed by race: Gestational age was inversely associated with DAP concentrations in white, but not black mothers. In contrast, we observed a stronger inverse association between maternal DAP concentrations and birth weight among black newborns than white newborns. The same pat- tern persisted when we restricted the analysis to full-term newborns, although the associa- tions were attenuated. Although we chose not to adjust for gestational age in the primary analysis because it is may be on the causal path- way, our results in white mothers are consistent with those of Eskenazi et al. (2004), who found that higher urinary ΣDMAP concentrations were associated with shortened gestation and small increases in gestational age–adjusted birth weight in a primarily Latina cohort. The results for the association of OP insecticides and birth weight for gestational age z-scores closely mir- rored our results for birth weight adjusted for gestational age. Again, we found an association for black, but not white, infants. In addition, at 39 weeks gestation (the study population mean) the estimated z-score decrease of 0.4 associated with a 10-fold increase in ΣDAPs corresponds to a decrease of about 160 g (Oken et al. 2003). Although others have reported effect modification by child sex (Marks et al. 2010), we found no evidence of an interaction. It is possible that different levels of exposure could affect the results; however, we observed ΣDAP concentrations (median = 81.3 nmol/L) comparable to the urban population in the Mount Sinai birth cohort in New York City (median = 75.9 nmol/L) (Wolff et al. 2007) and lower than those in the agricultural popu- lation of the CHAMACOS cohort (median = 136 nmol/L) (Eskenazi et al. 2004). The Columbia University birth cohort used serum chlorpyrifos to categorize OP exposure, and was not directly comparable (Whyatt et al. 2004). It is unclear why OP insecticides would be associated with shorter gestation in white newborns, but not black newborns. Although Organophosphate pesticides and perinatal outcomes black mothers had higher levels of urinary OP pesticide metabolites than white mothers, these metabolites are a nonspecific measure of exposure to various OP insecticides; different OP pesticides may act through a variety of mechanisms, some affecting length of gestation and others affecting fetal growth. Blacks and whites might differentially be exposed to these different formulations of pesticides. Maternal race/ethnicity may also be acting as a proxy for a combination of conditions—socioeconomic factors, genetic susceptibility, psychological stressors, and environmental toxicants—only some of which were measured in our study. We examined several possible confounders, including income, education, maternal depres- sive symptoms, maternal IQ, insurance sta- tus, area of residence, prenatal care, PON1 genotype, and gestational exposure to alcohol, lead, and tobacco; however there may be other factors we did not measure. Like Davis et al. (2009), we found racial differences in the dis- tribution of PON1 genotypes; however, the race/ethnicity interactions were not affected when we adjusted for PON1 genotype (data not shown). Excluding mothers with specific medical conditions, especially those who had placental abnormalities or chorioamnionitis, attenu- ated the association of urinary DAP concen- trations and perinatal outcomes. Excluding women with hypertensive conditions, which were more common in black mothers than in white mothers, strengthened the associations to a negligible extent. For both PON1 polymorphisms we exam- ined, the heterozygous groups (PON1192QR and PON1–108CT) generally showed the largest estimated decreases in birth weight and gesta- tional length associated with log10-transformed ΣDAP concentrations. These results were unex- pected, but > 200 polymorphisms of PON1 have been identified, and it may be unreason- able to expect two PON1 polymorphisms to explain the amount of PON produced or its efficiency in detoxifying certain chemicals (Costa et al. 2005, 2011). Several studies look- ing for OP–PON1 interactions have measured not only genotype, but PON enzyme activity as well (Harley et al. 2011; Wolff et al. 2007). We did not measure serum levels of PON and other OP-detoxifying enzymes, or maternal PON1 genotype, which may be more relevant during gestation and fetal development. It is also worth noting that studies on PON1 have focused on pesticides such as chlorpyrifos, diaz- inon, and parathion, which metabolize into DEP and DETP, whereas other OPs such as malathion, azinphos methyl, and dimethoate metabolize into DMP and DMTP (Maroni et al. 2000). DMAP metabolites were much more abundant in our study samples, and their associations were typically stronger than the DEAP metabolite associations. It is possible that PON1 polymorphisms act differently on DEAP- and DMAP-producing OPs. This study has several strengths and limita- tions, primarily related to using urinary DAP metabolites as a marker of OP insecticide expo- sure. Urinary DAP measurements reflect expo- sure to nontoxic preformed metabolites as well as the parent (toxic) OP pesticides, particularly for dietary exposures (Lu et al. 2005). Urinary DAPs have a half-life < 24 hr in humans, so their urinary concentrations reflect only recent exposure (Barr and Angerer 2006). The combi- nation of the short elimination half-life and the episodic nature of exposures to OP pesticides results in a high degree of variability in uri- nary DAP concentrations. We were also unable to rule out the possibility that differences in DAP concentrations partially reflect individual variation in metabolism. One strength of this study, however, is that we were able to account for some of the temporal variation in urinary DAP concentrations by combining the con- centrations of two samples taken months apart. Although there may still have been some degree of exposure misclassification, it was most likely nondifferential, and would tend to bias our results towards the null. Another limitation is that, unlike serum measures of the OP pes- ticide, which are often undetectable, urinary DAP concentrations cannot quantify exposure to a particular parent pesticide, although the class of metabolites (DEAP vs. DMAP) can suggest exposure to certain groups of OP pesti- cides. The ability to identify specific OP expo- sures would improve etiological studies because OPs differ widely in their uses and relative Table 3. Median ΣDAP concentration in mothers with and without selected medical conditions and mean change in gestational length and birth weight associ- ated with a 10-fold increase in average urinary ΣDAP concentrations after exclusion based on medical conditions. Condition None Placental/chorio Hypertensive Placental/chorio and hypertensive n 306 296 288 282 Median ΣDAP concentration (nmol/L) (25th–75th) With condition 133.3 (82.7–192.7) 110.3 (63.8–190.9) 128.3 (64.8–237.1) Without condition 77.9 (41.6–207.4) 76.1 (41.2–210.6) 76.2 (41.4–210.5) 75.7 (41.1–207.4) Gestational age (weeks)a Birth weight (g)a Birth weight, adjusted for gestational age (g)b β (95% CI) –0.5 (–0.8, –0.1) –0.3 (–0.6, 0.0) –0.6 (–0.9, –0.2) –0.3 (–0.7, 0.0) p-value 0.01 0.08 < 0.01 0.06 β (95% CI) –151 (–287, –16) –115 (–245, 15) –168 (–307, –28) –111 (–248, 26) p-value 0.03 0.08 0.02 0.11 β (95% CI) –40 (–146, 65) –48 (–154, 59) –30 (–143, 83) –33 (–145, 79) p-value 0.45 0.38 0.60 0.56 NA, not applicable. 25th and 75th are percentiles. Excludes 15 mothers in “other race” category and 23 with missing covariate information. “Placental/chorio” (n = 10) includes 8 mothers with abruptio placenta, 1 with abruption placenta and placenta previa, and 1 with chorioamnionitis. “Hypertensive” (n = 18) includes 9 mothers with preeclampsia, 3 mothers with pregnancy-induced hypertension, and 6 mothers with preeclampsia and pregnancy-induced hypertension. Four mothers had preeclampsia and hypertensive conditions. aAdjusted for mother’s age, race, household income, marital status, parity category, and log10-transformed blood lead and log10-transformed cotinine. bAdditional adjustment for gestational age. Environmental Health Perspectives • volume 120 | number 7 | July 2012 1059