A potential outcomes approach to defining and estimating gestational age-specific exposure effects during pregnancy

Many studies seek to evaluate the effects of potentially harmful pregnancy exposures during specific gestational periods. We consider an observational pregnancy cohort where pregnant individuals can initiate medication usage or become exposed to a drug at various times during their pregnancy. An imp...

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Bibliographic Details
Published in:Statistical methods in medical research 2022-02, Vol.31 (2), p.300-314
Main Authors: Schnitzer, Mireille E, Guerra, Steve Ferreira, Longo, Cristina, Blais, Lucie, Platt, Robert W
Format: Article
Language:English
Subjects:
Age differences
Asthma
Bias
Birth weight
Causality
Cohort Studies
Corticosteroids
Drugs
Exposure
Female
Gestational Age
Humans
Maximum likelihood estimates
Maximum likelihood estimation
Maximum likelihood method
Original s
Perinatal mortality
Pregnancy
Probability
Selection bias
Statistical analysis
Time dependence
Weighting
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Summary:Many studies seek to evaluate the effects of potentially harmful pregnancy exposures during specific gestational periods. We consider an observational pregnancy cohort where pregnant individuals can initiate medication usage or become exposed to a drug at various times during their pregnancy. An important statistical challenge involves how to define and estimate exposure effects when pregnancy loss or delivery can occur over time. Without proper consideration, the results of standard analysis may be vulnerable to selection bias, immortal time-bias, and time-dependent confounding. In this study, we apply the “target trials” framework of Hernán and Robins in order to define effects based on the counterfactual approach often used in causal inference. This effect is defined relative to a hypothetical randomized trial of timed pregnancy exposures where delivery may precede and thus potentially interrupt exposure initiation. We describe specific implementations of inverse probability weighting, G-computation, and Targeted Maximum Likelihood Estimation to estimate the effects of interest. We demonstrate the performance of all estimators using simulated data and show that a standard implementation of inverse probability weighting is biased. We then apply our proposed methods to a pharmacoepidemiology study to evaluate the potentially time-dependent effect of exposure to inhaled corticosteroids on birthweight in pregnant people with mild asthma.
ISSN:0962-2802
1477-0334
DOI:10.1177/09622802211065158