Bias from conditioning on live birth in pregnancy cohorts: an illustration based on neurodevelopment in children after prenatal exposure to organic pollutants

Zeyan Liew; Jørn Olsen; Xin Cui; Beate Ritz; Onyebuchi A Arah

doi:10.1093/ije/dyu249

Bias from conditioning on live birth in pregnancy cohorts: an illustration based on neurodevelopment in children after prenatal exposure to organic pollutants

Int J Epidemiol. 2015 Feb;44(1):345-54. doi: 10.1093/ije/dyu249. Epub 2015 Jan 19.

Authors

Zeyan Liew¹, Jørn Olsen², Xin Cui³, Beate Ritz², Onyebuchi A Arah⁴

Affiliations

¹ Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA zeyanliew@ucla.edu.
² Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA.
³ Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA.
⁴ Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA.

Abstract

Only 60-70% of fertilized eggs may result in a live birth, and very early fetal loss mainly goes unnoticed. Outcomes that can only be ascertained in live-born children will be missing for those who do not survive till birth. In this article, we illustrate a common bias structure (leading to 'live-birth bias') that arises from studying the effects of prenatal exposure to environmental factors on long-term health outcomes among live births only in pregnancy cohorts. To illustrate this we used prenatal exposure to perfluoroalkyl substances (PFAS) and attention-deficit/hyperactivity disorder (ADHD) in school-aged children as an example. PFAS are persistent organic pollutants that may impact human fecundity and be toxic for neurodevelopment. We simulated several hypothetical scenarios based on characteristics from the Danish National Birth Cohort and found that a weak inverse association may appear even if PFAS do not cause ADHD but have a considerable effect on fetal survival. The magnitude of the negative bias was generally small, and adjusting for common causes of the outcome and fetal loss can reduce the bias. Our example highlights the need to identify the determinants of pregnancy loss and the importance of quantifying bias arising from conditioning on live birth in observational studies.

Keywords: Bias analysis; attention-deficit/hyperactivity disorder; birth cohort; live-birth bias; perfluoroalkyl substances; prenatal exposure; reproductive epidemiology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Attention Deficit Disorder with Hyperactivity / epidemiology*
Bias
Denmark
Environmental Pollutants / toxicity*
Female
Fetal Death
Fluorocarbons / toxicity*
Humans
Live Birth
Monte Carlo Method
Pregnancy
Pregnancy Outcome / epidemiology*
Prenatal Exposure Delayed Effects / epidemiology*

Substances

Environmental Pollutants
Fluorocarbons

Abstract

Publication types

MeSH terms

Substances

Grants and funding