In this well-educated population of women living on farms, we found that out of 27 individual pesticides examined, only a history of carbaryl use, a cholinesterase-inhibiting insecticide, was associated with lower birth weight. Previous studies on carbamates or carbaryl in particular are limited. Among pregnant women in NY, residential prenatal exposures to the carbamate pesticide, proxopur, was not associated with changes in birth weight 8
. One animal study examining pre-conception and post-conception carbaryl and malathion exposures in rats and mice found a significant decrease in birth weight in relation to high dose exposures 22
Birth weight was slightly lower among women who reported agricultural exposures during pregnancy in our analysis, but the exposed group was small and the exposure measure was not pesticide-specific. While limited information exists on carbamates, more data are available on organophosphate insecticide exposures during pregnancy. In a cohort of inner city women, Whyatt et al. found that chlorpyrifos concentrations in cord blood were inversely related to birth weight 8
. In another cohort of New York women whose homes were sprayed with insecticides, organophosphate exposure during pregnancy (as measured by urine metabolites) was associated with decreased head circumference only among women with slow activity of paraoxonase 1, an enzyme involved in the metabolism of organophosphate pesticides 9
. This finding suggests that this group women may have longer time periods of detoxification and thus potentially higher organophosphate concentrations in the body over a long period of time, which could impact fetal growth 9
. However, in the CHAMACOS (the Center for the Health Assessment of Mothers and Children of Salinas) birth cohort, Eskenazi and colleagues did not find a significant relationship between prenatal organophosphate exposure as measured with biological markers and fetal growth 6
Studies examining pre-conceptional exposure to cholinesterase-inhibiting pesticides and potential long term impacts on reproduction are lacking Organochlorine insecticides can persist in the body over long periods of time, and some may have genotoxic effects leading to long term health impact. The organochlorine endosulfan, is known to be genotoxic with mutagenic effects leading to decreased apoptosis and potential for mutant cell growth 23
. In a study of medaka fish, early life endosulfan exposure had long term impacts on growth and reproduction 16
. In addition, DDT, a persistent organochlorine pesticide, has long term, generational effects on female reproduction and development 24
. Because the half-life of cholinesterase-inhibiting pesticides is usually much shorter, their long term toxic effects are more difficult to study in humans. Future animal and human research should focus on such impacts of these chemicals.
We relied on self-reported information on exposures and outcomes in this analysis. Because our analysis was cross-sectional, it is possible that exposure misclassification and recall bias may have influenced our results. However, the quality of self-reported birth weight and pesticide data are generally regarded as accurate. Two studies examining the validity of self-reported birth weight in relation to medical records document excellent correlations between the two among cases with cancer and age/year matched controls (correlation coefficients of 0.84 – 0.99) 25,26
. Rates of preterm delivery and low birth weight in our study population (primarily white) were lower than that of the non-Hispanic white US population in 2005 (12% and 5%, respectively) according to the Centers for Disease Control and Prevention National Vital Statistics Report 27
. These low rates may indicate that this is an overall healthier population compared with the US white population as a whole.
In utero pesticide exposure may be related to preterm birth, itself a major cause of low birth weight, and thus inclusion of preterm birth in the regression models may mask an effect. However, we saw no indication that pesticide exposure was associated with preterm birth, and we included preterm birth in the model to increase the precision of the estimates. For the pregnancy-related exposures, point estimates showed a greater effect for indirect and residential exposures, but confidence intervals remained large when preterm birth was not controlled for in the model. The point estimates for several individual pesticides showed approximately a 10% change when preterm birth was taken out of the model, and some results became statistically significant. For example, the point estimate for terbufos changed from 150g (95% CI= −5, 319) to 180g (95% CI= 5, 355). For malathion, the point estimate changed from −59g (95% CI= −118, 0.5) to −67g (95%CI= −131, −3). Among term births only (93% of the cohort), the results are very similar to those for the entire cohort. For carbaryl, the point estimate for birth weight was slightly attenuated but with a similar confidence interval, −65g (95% CI −113, −17). The only other association that was statistically significant in this subset was for the use of terbufos, 163g (95% Confidence Interval 10, 317).
Other studies within the US report an association between high rates of farm work and pesticide use among farmer’s wives 28,29
. In the AHS, an analysis examining the reliability of self-reported pesticide use by applicators showed 70–90% agreement between repeated self-administered questionnaires 30
. For pregnancy-related exposures, we aggregated questions based on potential magnitude of exposure and created a hierarchical structure for these data. Exposures may have differed within each level, but we believe that the exposures within each group are of the same relative magnitude. We could not account for other pesticide exposure pathways, including diet, which may depend on residential use as well as take-home exposures from the spouse (such as contaminated clothes, shoes, etc). Our analysis of pesticide exposure during pregnancy was limited by small numbers of women reporting agricultural exposures, the estimated highest exposure category. This may have limited our ability to see an effect if one existed. In addition, we only had data on first trimester exposures. While the velocity of weight gain is highest in the third trimester, the fetus is growing throughout pregnancy. It is unclear when the primary window of susceptibility might be for a potential impact of pesticides on fetal weight gain but current studies point to the third trimester as the most important time period. Recently, the first trimester has been recognized as an important period of vulnerability in relation to adverse birth outcomes including low birth weight 31
. The entire pregnancy may present different windows of susceptibility for environmental exposures to impact growth. There is little evidence suggesting that paternal pesticide use may be related to changes in birth weight. We conducted an analysis examining paternal individual pesticide use in relation to birth weight which resulted in null findings for all exposures examined. Given the lack of evidence in the scientific literature and the lack of temporal specificity of paternal exposures we did not proceed further with this analysis.
While we did not see an association between birth weight and pesticide-exposure related activities during pregnancy, we did observe an inverse association with the women’s use of carbaryl. Temporality of exposure in relation to outcome is a major limitation of our study. We restricted our analysis to the most recent birth that occurred within five years of enrollment to maximize the probability that the exposure occurred before the birth of the child, although we have no data to verify that this was indeed the case. However, a previous analysis from the AHS suggested that women with small children were less involved with farm work 32
, and it is thus likely that, in the time window examined, the pesticide exposure preceded birth. As an additional analysis, we included all pregnancies (not restricting to those within five years of enrollment) and saw similar results: maternal report of carbaryl use was inversely associated with birth weight, even though in this case the temporal relation between exposure and birth may be more likely to go in either direction. Our exposure data are unfortunately limited in that we do not have measures on either intensity or duration and timing of exposure. Other studies have generally relied upon biological markers of exposure, which provide a better measure of dose, but with the trade-off of a smaller sample size compared to our study. We explored 27 individual pesticide compounds, and this resulted in 27 comparisons, and the one significant finding for carbaryl may well be a result of chance. With a Bonferroni correction, this result would not achieve statistical significance.
While the overall response rate for spouses was high (75%), only 61% of these women returned the female and family health questionnaire. Among all enrolled women younger than 50 years whose husband reported having at least one child in the home the response rate to the FFH questionnaire was 57%. Women who did not complete the questionnaire did not differ by age, race, BMI, education level, or the number of children in the home compared with those who returned the FFH questionnaire. Current smokers were less likely to return the FFH. Women who reported use of any individual pesticide were slightly more likely to have completed the FFH compared to women who did not complete FFH (56% vs. 53%) and women who reported carbaryl use were slightly more likely to return the FFH compared to women who did not report carbaryl use (27% vs. 25%). While the differences in proportions are not large, we did see that more exposed women were likely to be included in this analysis, potentially giving us more power to detect an association. Given the small proportion of low birth weight babies in this group, it is unlikely that women who completed the FFH had worse outcomes than those who did not return the questionnaire.
Our results provide information regarding pesticide exposure as a modulator of birth weight. Only one pesticide, carbaryl, use was associated with reduced birth weight among children of farm women in the AHS. Carbaryl is widely used for agricultural and residential purposes in the US, and was used by 21% of the women in the AHS. Our limited findings support the possibility that carbaryl use may affect birth weight. Additional research is needed, with biomarker and temporal characterization of exposure, to examine maternal pesticide exposure in relation to later health outcomes.