Is the relationship between prenatal exposure to PCB-153 and decreased birth weight attributable to pharmacokinetics?
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.


CONCLUSIONS
Our findings suggest that associations previously noted between PCB levels and birth weight may be attributable to confounding by maternal weight gain during pregnancy.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Marc-André
MA
Verner
Robin
R
McDougall
Anders
A
Glynn
Melvin E
ME
Andersen
Harvey J
HJ
Clewell
Matthew P
MP
Longnecker
D001724:Birth Weight / Q000187:drug effects*; D003198:Computer Simulation; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure; D009010:Monte Carlo Method; D011078:Polychlorinated Biphenyls / Q000097:blood* / Q000633:toxicity*; D011247:Pregnancy; D015430:Weight Gain / Q000187:drug effects
D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl