Is the Relationship between Prenatal Exposure to PCB-153 and Decreased Birth Weight Attributable to Pharmacokinetics?

Abstract

Background: A recent meta-analysis based on data from > 7,000 pregnancies reported an association between prenatal polychlorinated biphenyl (PCB)–153 exposure and reduced birth weight. Gestational weight gain, which is associated negatively with PCB levels in maternal and cord blood, and positively with birth weight, could substantially confound this association.Objective: We sought to estimate the influence of gestational weight gain on the association between PCB-153 exposure and birth weight using a pharmacokinetic model.Methods: We modified a recently published pharmacokinetic model and ran Monte Carlo simulations accounting for variability in physiologic parameters and their correlations. We evaluated the pharmacokinetic model by comparing simulated plasma PCB-153 levels during pregnancy to serial measurements in 10 pregnant women from another study population. We estimated the association between simulated plasma PCB-153 levels and birth weight using linear regression models.Results: The plasma PCB-153 level profiles generated with the pharmacokinetic model were comparable to measured levels in 10 pregnant women. We estimated a 118-g decrease in birth weight (95% CI: –129, –106 g) for each 1-μg/L increase in simulated cord plasma PCB-153, compared with the 150-g decrease estimated based on the previous meta-analysis. The estimated decrease in birth weight was reduced to –6 g (95% CI: –18, 6 g) when adjusted for simulated gestational weight gain.Conclusion: Our findings suggest that associations previously noted between PCB levels and birth weight may be attributable to confounding by maternal weight gain during pregnancy.Citation: Verner MA, McDougall R, Glynn A, Andersen ME, Clewell HJ III, Longnecker MP. 2013. Is the relationship between prenatal exposure to PCB-153 and decreased birth weight attributable to pharmacokinetics? Environ Health Perspect 121:1219–1224; http://dx.doi.org/10.1289/ehp.1206457

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis

“…Most studies measured the contaminants late in pregnancy, at birth or during lactation and not precisely at the time of differentiation of the male gonads, that based upon animal studies in the rat, is assumed to take place in gestational week 8–14 (Welsh et al ., 2008; Macleod et al ., 2010). Considering the long half-lives of the persistent chemicals with little expected fluctuation of tissue levels across a few months, measurements around the time of birth seems a reasonable proxy for exposure levels during early pregnancy although distribution kinetics during pregnancy may be an issue (Verner et al ., 2013). This is entirely different for compounds with a rapid metabolism and excretion such as phthalates and bisphenol A, which fluctuate markedly within individuals as shown in studies with repeated sampling.…”

“…All studies seemed to provide data on all measured substances regardless of association. Finally, only a few studies corrected for weight gain during pregnancy which may cause false positive associations due to dilution of the distribution volume for biopersistent chemicals (Verner et al ., 2013), an issue if the outcome is related to lower birthweight or congenital malformations.…”

Overview of ongoing cohort and dietary studies in the Arctic

“…These results were included in a large European meta-analysis of birth weight in relation to PCB and DDE exposure, confirming the negative association between PCB exposure and birth weight (43). However, it has been questioned whether the results could have been biased by maternal weight gain during pregnancy (44). …”

Challenges and Future Directions to Evaluating the Association Between Prenatal Exposure to Endocrine-Disrupting Chemicals and Childhood Obesity

“…Inverse associations between lipophilic compounds, like polychlorinated biphenyls (PCBs), measured in maternal blood, and offspring body weight or BMI may be explained by a weight-gain induced dilution of serum PCB levels during pregnancy[69, 70]. Normal physiological changes during pregnancy are one potential source of bias, but sub-clinical/clinical disease may alter both fetal growth and the metabolism or excretion of environmental chemicals.…”