Current Epidemiology Reports

, Volume 5, Issue 3, pp 284–292 | Cite as

Statistical Challenges in the Analysis of Biomarkers of Environmental Chemical Exposures for Perinatal Epidemiology

  • Janice M.Y. Hu
  • Liheng Harry Zhuang
  • Brendan A. Bernardo
  • Lawrence C. McCandlessEmail author
Reproductive and Perinatal Epidemiology (R Platt, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Reproductive and Perinatal Epidemiology


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.

Recent Findings

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.


Biomarkers 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.

Author’s Contributions

JH and LM drafted the manuscript with input from HZ and BB. All authors approved the final version of the manuscript.

Funding Information

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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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Janice M.Y. Hu
    • 1
  • Liheng Harry Zhuang
    • 1
  • Brendan A. Bernardo
    • 1
  • Lawrence C. McCandless
    • 1
    Email author
  1. 1.Faculty of Health SciencesSimon Fraser UniversityBurnabyCanada

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