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Serum Perfluorooctanoic Acid and Birthweight: An Updated Meta-analysis With Bias Analysis
Kyle Steenland1, Vaughn Barry1, David Savitz2
1From the Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA.
Insights
Per- and polyfluoroalkyl substances (PFAS) like perfluorooctanoic acid (PFOA) show a modest association with decreased birthweight. Studies with early pregnancy blood sampling revealed little PFOA-birthweight link, unlike late-pregnancy samples.
Area of Science:
- Environmental Health
- Reproductive Toxicology
- Epidemiology
Background:
- Perfluorooctanoic acid (PFOA) is a persistent environmental contaminant.
- Previous meta-analyses suggest a link between PFOA exposure and reduced birthweight.
- Newer studies have expanded the dataset for more robust analysis.
Purpose of the Study:
- To conduct a comprehensive meta-analysis on the association between PFOA and birthweight.
- To evaluate the impact of exposure timing and population characteristics on the PFOA-birthweight relationship.
Main Methods:
- Meta-analysis of 24 studies, incorporating nine new studies and one previously excluded large study.
- Approximation of untransformed PFOA results from log-transformed data.
- Sensitivity analysis including the large, previously excluded study.
Main Results:
- A meta-analysis of 24 studies found a decrease of 10.5 g in birthweight per ng/ml PFOA.
- Excluding a large study or restricting to early pregnancy samples showed minimal association.
- Studies with late pregnancy blood sampling indicated a significant association: -17.8 g per ng/ml PFOA.
Conclusions:
- Human evidence suggests a modest association between PFOA and decreased birthweight.
- Little to no association was observed in studies with wide exposure ranges or early pregnancy blood sampling, where confounding is less likely.
- The timing of blood sampling significantly influences the observed PFOA-birthweight association.
Background:
A recent meta-analysis of 15 studies found a change in birthweight of -12.8 g (95% CI = -23.1, -2.38) per ng/ml PFOA in maternal or cord blood and -27.1 g (-50.6, -3.6) per log ng/ml PFOA. Almost all studies were done in low-exposed populations. There are nine new studies, adding 6,019 births to the previous 6,937 births.
Methods:
We conducted a meta-analysis of 24 studies. To combine all results, we approximated results for untransformed PFOA from nine studies using log-transformed PFOA. We also included another large study, excluded from previous analyses, in a sensitivity analysis.
Results:
We found a change of birthweight of -10.5 g (-16.7, -4.4) for every ng/ml PFOA in maternal or cord blood. After adding one previously excluded large study, we found little evidence of an association (-1.0 g; 95% CI = -2.4, 0.4). Restricting to studies where blood was sampled from mothers early in the pregnancy or shortly before conception (5,393 births), we found little association of PFOA with birthweight (-3.3 g [-9.6, 3.0]). In studies where blood was sampled late in the pregnancy (7563 pregnancies), lower birthweight was associated with higher PFOA (-17.8 [-25.0, -10.6]).
Conclusion:
Present human evidence provides only modest support for decreased birthweight with increasing PFOA. Studies with a wide range of exposure, and studies with blood sampled early in pregnancy, showed little or no association of PFOA with birthweight. These are studies in which confounding and reverse causality would be of less concern.
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