This report has shown that during the period from 1996 to 2002 women in the United States with LMPs in April–July (i.e. the time of conception) were significantly more likely to have a live birth with a birth defect than in other months. The report further demonstrates, using NAWQA surface water samples that concentrations of atrazine, nitrates and other pesticides also were higher in the months of April–July. The correlation between birth defects, pesticides and nitrates was statistically significant.
Pesticides and nitrates, separately and in combination, have been linked to embryo toxicity and to untoward outcomes of pregnancy (12
). Women's pesticide exposures through household gardening, professional application or living in close proximity to agricultural crops were associated with increased risks of offspring having neural tube defects and limb anomalies (14
). Garry et al. found that in western Minnesota the rate of specific birth defects was elevated in pesticide applicators as well as the general population of western Minnesotans and that this risk was most pronounced for infants conceived in the spring (15
). Specific birth defect categories showing significant increased risk in Garry's study were circulatory/respiratory, urogenital and musculoskeletal/integumental which are similar to the categories found in our study. Schreinemachers et al. found that infants in four wheat-producing states conceived in April–June, the time of herbicide application, were more likely to have circulatory/respiratory (excluding heart) malformations compared with births conceived during other months. She also found that counties with high wheat acreage had higher rates of heart malformations, musculoskeletal/integumental anomalies and infant death from congenital anomalies in males (16
In Missouri men, high urine levels of atrazine, alachlor and diazinon were associated with abnormal sperm (9
). The same study found that spring or summer samples were more likely to be abnormal than winter samples and that exposed men were frequently exposed to more than one pesticide causing many of the pesticide metabolites to be correlated. Thus, paternal as well as maternal exposures to pesticides might potentiate birth defects.
A causal link between birth defects and environmental nitrates/pesticides is plausible but not proven from this present ecological study. Nevertheless a statistically significant increased risk was found for any birth defect and for spina bifida, circulatory, tracheal, gastrointestinal, urogenital, musculoskeletal anomalies, cleft lip, adactyly, clubfoot and Down's syndrome in women with LMPs between April and July in the United Sates (). This period of increased risk is an important reproductive demographic.
Nitrates and pesticides occur as mixtures in most water samples (17
). Recent observations in frogs, rats and other animals have demonstrated that individual chemicals at environmentally relevant concentrations may show little or no toxicity but when added together the effects are significantly more toxic or disruptive of vital endocrine functions (12
). It is likely that other contaminants not specifically measured by the NAWQA study could also peak in April–July including air pollutants (20
). Thus, the period of increased risk might not be associated solely with pesticides and nitrates.
This study has many limitations. Vital records have limited reliability and validity and should be used with caution (21
). As of May 2001, 13 states plus the District of Columbia had only passive birth defects surveillance programmes (22
Using NAWQA water data as a proxy for human exposure have significant limitations as well. Drinking water sources vary from surface to ground water and varied mixtures at different times of the year are common. Mean levels of nitrates and pesticides in NAWQA test sites are significantly higher than drinking water means would be in most locations. Nevertheless, in an EPA drinking water data sample from the same time period, peak frequency of pesticide detections were found in June, and correlated qualitatively with NAWQA surface water data. Atrazine was found in 57.9% of drinking water samples in Maryland (23
) and 87% of drinking water samples in a sample of 12 Corn Belt states (17
). A Canadian study of the northern Great Plains reported pesticides in numerous drinking water reservoirs, and depending upon location despite water treatment, 3 to 15 herbicides remained in drinking water (24
Several studies in children and pregnant women using urine, amnionic fluid and meconium have demonstrated that from 89% to 100% of fetuses in the United States are exposed to pesticide in utero
and most are exposed to mixtures of several pesticides (25
). The importance of interactions between genetic susceptibility and in utero
pesticide exposure has also been reported (26
The National Health and Nutrition Examination Survey (NHANES) found that 95% of the United States population has measurable pesticide metabolites in urine samples (27
). Although the atrazine mercapturate (AM) metabolite of atrazine was found in <5% of NHANES participants, Barr et al. have recently found that population-based atrazine exposures have been significantly underestimated for samples collected in the 1990's (28
). The National Human Exposure Assessment Study in Maryland (NHEXAS-MD) demonstrated that over 80% of sampled individuals had at least one of three pesticide metabolites in their urine. The study found atrazine peaks occur in late summer and fall in the Baltimore area whereas the Midwest peaks occur in May and June (29