Statistical Challenges in the Analysis of Biomarkers of Environmental Chemical Exposures for Perinatal Epidemiology
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Purpose of Review
Biomarkers are widely used in perinatal epidemiology to examine the health effects of environmental chemical exposures during pregnancy. These measurements take the form of chemical concentrations measured in blood, urine, or other biospecimens. Biomarkers have the advantage of providing objective estimates of chemical exposures from multiple sources. However, they are difficult to handle at the data analysis stage. We review recent trends and developments in the statistical analysis of biomarkers with particular emphasis on exposure assessment and multivariable modeling.
Six statistical challenges are presented in the recent literature: (1) the analysis of biomarkers that fall below the limit of detection, (2) adjustment for dilution-dependent sample variation, (3) handling repeated biomarker measurements within a single pregnancy, (4) accounting for heterogeneity in biomarker levels between chemicals within the same chemical class, (5) variable selection and shrinkage for biomarkers in the same class, and finally, (6) dimension reduction strategies including the sum-of-chemical approach.
The analysis of biomarkers of environmental chemical exposures remains immensely difficult, and the proper application of emerging statistical techniques requires input from experts in diverse disciplines. We highlight specific gaps in the literature where innovation in statistical methods is required.
KeywordsBiomarkers Environmental exposures Epidemiology Biostatistics Children’s health
The authors gratefully acknowledge input and thoughtful comments from Tim Takaro and Ryan Allen on an earlier version of the manuscript.
JH and LM drafted the manuscript with input from HZ and BB. All authors approved the final version of the manuscript.
This project was funded by a Catalyst Grant from the Canadian Institutes for Health Research (L-CIP-150736).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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