Handling unobserved confounding in the relation between prenatal risk factors and child outcomes: a latent variable strategy

BACKGROUND: Several studies have examined maternal health behavior during pregnancy and child outcomes. Negative control variables have been used to address unobserved confounding in such studies. This approach assumes that confounders affect the exposure and the negative control to the same degree. The current study introduces a novel latent variable approach that relaxes this assumption by accommodating repeated measures of maternal health behavior during pregnancy. METHODS: Monte Carlo simulations were used to examine the performance of the latent variable approach. A real-life example is also provided, using data from the Norwegian Mother, Father, and Child Study (MoBa). RESULTS: Simulations: Regular regression analyses without a negative control variable worked poorly in the presence of unobserved confounding. Including a negative control variable improved result substantially. The latent variable approach provided unbiased results in several situations where the other analysis models worked poorly. Real-life data: Maternal alcohol use in the first trimester was associated with increased ADHD symptoms in the child in the standard regression model. This association was not present in the latent variable approach. CONCLUSION: The current study showed that a latent variable approach with a negative control provided unbiased estimates of causal associations between repeated measures of maternal health behavior during pregnancy and child outcomes, even when the effect of the confounder differed in magnitude between the negative control and the exposures. The real-life example showed that inferences from the latent variable approach were incompatible with those from the standard regression approach. Limitations of the approach are discussed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00857-6.