No significant differences were demonstrated for median baseline pesticides/metabolites concentrations or other study covariates by critical window (). The median interval between the collection of the two serum specimens varied by critical window: 151 days (interquartile range (IQR)=180.5) between baseline and prenatal specimens among women giving birth, and then 240 days (IQR = 21) between prenatal and postnatal specimens among those women; 63 days (IQR= 4) between baseline and early pregnancy loss specimens; 79 days (IQR=76) between baseline and clinical pregnancy loss specimens; and 446 days (IQR=127) between baseline and infertility specimens.
Description of study cohort at baseline by critical window. New York State Angler Cohort Prospective Pregnancy Study.
The vast majority of values for DDE (89–100%), mirex (89–100%), oxychlordane (100%), and HCB (89–100%) were measured above the LODs regardless of critical window (); considerable variation for aldrin (30–89%), β-HCH (0–43%), and trans-nonachlor (60–100%) was observed. The majority (57–100%) of β-HCH values, including all early loss and infertile specimens, were measured below the LOD, precluding assessment of changes in these critical windows for this compound. Baseline concentrations across pesticides/metabolites concentrations (n=67) were positively correlated at low to moderate strength (i.e. r= 0.17–0.45; P<0.05 to P<0.10). However, a single inverse correlation was measured between concentrations of the dieldrin metabolite aldrin and the chlordane metabolite trans-nonachlor (rSp=−0.25, P=0.038).
Mean limit of detection (LOD) values and percentage of concentrations above for organochlorine pesticides/metabolites (ng/g serum), by critical windows. New York State Angler Cohort Prospective Pregnancy Study.
Non-parametric correlations for pesticides/metabolites, and total serum lipids, across critical windows are presented in . No significant correlations were measured between concentrations for aldrin or β-HCH regardless of critical window. The chlorinated insecticide metabolite DDE demonstrated strong positive correlations between measures, regardless of critical window (baseline-prenatal r=0.85, P<0.0000, n=48; baseline-early loss r=0.92, P=0.000, n=10; baseline-infertile r=0.80, P=0.010, n=9; and prenatal-postnatal r=0.76, P<0.0000, n=47), as did the cylodiene pesticide mirex (baseline-prenatal r=0.78, P<0.0001; baseline-early loss r=0.92, P=0.000; baseline-infertile rSp=0.70, P=0.035; and prenatal-postnatal rSp=0.40, P=0.005) For HCB, only concentrations for baseline and prenatal measures demonstrated a significant correlation (r=0.29, P=0.043). Oxychlordane (baseline-infertile r=0.87, P=0.002 and prenatal-postnatal r=0.52, P=0.000) and trans-nonachlor (baseline-infertile r=0.79, P=0.012) also each demonstrated significant correlations only for specific critical windows. For each pesticide/metabolite, correlations across critical windows were statistically similar except those for oxychlordane between baseline-infertility, and each baseline-prenatal (P=0.005) and baseline-early loss (P=0.010). Serum total lipids demonstrated moderate to strong positive correlations across critical windows however statistical significance was shown for only the baseline-prenatal measures (r=0.48, P=0.002) and the prenatal-postnatal measures (r=0.58, P<0.0001). Following division of pesticides/metabolites by serum total lipids point estimates varied somewhat from those generated using serum wet weight values. However no substantial differences were noted between correlation coefficients expressed on a wet weight basis and those expressed on a lipid weight basis (data not shown).
Spearman correlation coefficients among paired sera specimens (ng/g serum) by organochlorine pesticides/metabolites and critical windows. New York State Angler Cohort Prospective Pregnancy Study.
Median values were considered for the overall (i.e., ng/g serum) and daily (i.e., ng/g serum per day) rates of change in pesticides/metabolites across critical windows (data not shown). Between baseline and prenatal specimens (n=48), statistically significant decreases were demonstrated for the overall and daily rate of change in HCB (−0.035 and −0.001, respectively) and trans-nonachlor (−0.050 and −0.002, respectively). Conversely, increases were measured for oxychlordane (0.032 and 0.001, respectively). Between baseline and early loss specimens (n=10), significant decreases were observed for the overall and daily rate of change in HCB (−0.061 and −0.003, respectively) and for the overall change in trans-nonachlor (−0.054). No significant crude changes were observed for DDE or mirex among women who conceived, regardless of outcome. Significant overall and daily rates of change were demonstrated for DDE (−0.069 and −8.00 × 10−5, respectively), HCB (−0.088 and −0.000, respectively), and for trans-nonachlor (0.045 and 1.90 × 10−4, respectively) between baseline and infertility specimens (n=9). Excluding β-HCH, all measured pesticides/metabolites demonstrated significant overall and daily rates of change between prenatal and postnatal concentrations (n=47). These latter changes reflected decreases (aldrin, DDE, HCB, and oxychlordane) and increases (mirex and trans-nonachlor) between the prenatal and postnatal measurement. Expressed as mg/dL, total serum lipids showed median overall and daily rates of decrease from baseline to prenatal for women whose pregnancies ended in a live birth (−15.965 and −0.627, respectively) and for women experiencing early losses (−1.571 and −0.030, respectively), but an increase for infertile women (18.969 and 0.033, respectively). None of these results achieved significance (data not shown). However, statistically significant increases (P<0.0001) were demonstrated for the overall and daily rates of change in total serum lipids between the prenatal and postnatal specimens (169.016 and 0.705, respectively).
Multiple linear regression models, describing the adjusted mean overall and daily rate of change for pesticides/metabolites by critical window are presented in . Means were adjusted for the overall or daily rate of change in serum total lipids and baseline pesticides/metabolites concentrations. Women who conceived during the study, those with live births (n=48) and those with early pregnancy losses (n=10), demonstrated significant reductions in the overall and daily rate of change in serum HCB (−0.032 and −0.001; −0.069 and −0.003, respectively), and trans-nonachlor (−0.050 and −0.002; −0.045 and −0.002, respectively) concentrations similar to the aforementioned unadjusted median values. Statistically significant increases in oxychlordane (0.029 and 0.001, respectively; 0.015 for overall change only) were observed, though somewhat more moderate than those observed in the aforementioned unadjusted medians analysis.
Mean adjusted overall and daily rates of change in serum pesticides/metabolites concentrations by critical windows. New York State Angler Cohort Prospective Pregnancy Study.
In contrast to women giving birth, women experiencing early pregnancy losses were observed to have significant adjusted changes in both the overall and daily rates of change in sera concentrations of aldrin (−0.002 and −1.47 × 10−4, respectively) and mirex (0.006 and 3.32 × 10−4, respectively). These pesticides/metabolites did not demonstrate significant changes in the unadjusted medians analysis. Changes in HCB (−0.069 and −0.003, respectively) as well as trans-nonachlor (−0.045 and −0.002, respectively) were significant with the former slightly greater and the latter slightly smaller than those demonstrated during the unadjusted medians analysis.
As presented in , significant decreases in the adjusted overall and daily rate of change between baseline and infertility measures (n=9), were demonstrated for aldrin (−0.003 and −3.52 × 10−6, respectively), DDE (−0.210 and −4.29 × 10−4 respectively), and HCB (−0.096 and −2.03 × 10−4, respectively). In contrast, significant increases were demonstrated for the overall and daily rate of change in trans-nonachlor (0.034 and 7.59 × 10−5, respectively). Baseline pesticides/metabolites concentrations were generally strong and significant inverse predictors of the overall and daily rates of change in pesticides/metabolites concentrations among infertile women (data not shown). In general, as the baseline concentration for pesticides/metabolites increased, the rate of decrease in concentration between time points increased, or conversely, the rate of increase between time points decreased. Total serum lipids were a significant predictor for only the overall and daily rate of change in oxychlordane (7.02 × 10−5, 7.67 × 10−5, respectively).
Baseline pesticides/metabolites concentrations were frequently significant and strong inverse predictors for both overall and daily rates of change (data not shown). However, the change in total serum lipids concentration was infrequent and generally weakly positive (data not shown). Serum lipids had little importance for pesticides/metabolites concentrations between the baseline and prenatal measures among the 48 women who went on to a live delivery; significant lipids coefficients were observed for only the overall and daily rate of change in DDE (0.001 and 0.002, respectively) and (daily) trans-nonachlor (1.11 × 10−4).Among women with early losses significant lipids coefficients were observed for both the overall and daily rate of change in aldrin (4.68 × 10−5, 7.59 × 10−5, respectively) as well as (daily) trans-nonachlor (2.60 × 10−4).
also presents the overall and daily rates of change in pesticides/metabolites concentrations between the pre- and postnatal measures (n=47) adjusted for the change in serum total lipids, prenatal pesticides/metabolites concentrations, and the reported duration of breastfeeding between the delivery and the postnatal serum specimen. Significant decreases were demonstrated for the overall and daily rates of change in aldrin (−0.004 and −1.14 × 10−5, respectively), β-HCH (−0.004 and −1.46 × 10−5, respectively), DDE (−0.141 and −0.001, respectively), HCB (−0.027 and −1.16 × 10−4, respectively), and oxychlordane (−0.032 and −1.38 × 10−4, respectively). In contrast, significant increases were demonstrated for the overall and daily rate of change in trans-nonachlor (0.110 and 4.64 × 10−4, respectively) concentrations. Total serum lipids were generally weak positive predictors of change except for the daily rate of change in aldrin for which the lipids coefficient was negative (data not shown). Baseline pesticides/metabolites concentrations were significant and strong inverse predictors for all measures (data not shown).
illustrates the overall () and daily rate of change () in DDE by critical window, as a function of women’s baseline concentrations. These figures illustrate the dependence of daily rate of change on baseline concentration using DDE as an example, especially for women becoming pregnant or experiencing early losses. A general pattern of a greater decrease in concentrations from baseline to the next critical window is observed for an increasing baseline concentration, supporting adjustment for baseline concentration when estimating rates of change.
Neither age nor BMI at baseline were significantly associated with any of the measured changes in pesticides/metabolites (data not shown) regardless of critical window nor was self reported duration of breastfeeding among women with a live birth. However, among women with a prior pregnancy (n=38), the overall (r=0.38, P=0.020) and daily (r=0.38, P=0.017) rates of change for mirex concentrations from baseline to prenatal collection were significantly associated with parity as was the daily rate of change in oxychlordane (r=−0.45, P=0.005).