The Problem of Confounding in Studies of the Effect of Maternal Drug Use on Pregnancy Outcome

Abstract

In most epidemilogical studies, the problem of confounding adds to the uncertainty in conclusions drawn. This is also true for studies on the effect of maternal drug use on birth defect risks. This paper describes various types of such confounders and discusses methods to identify and adjust for them. Such confounders can be found in maternal characteristics like age, parity, smoking, use of alcohol, and body mass index, subfertility, and previous pregnancies including previous birth of a malformed child, socioeconomy, race/ethnicity, or country of birth. Confounding by concomitant maternal drug use may occur. A geographical or seasonal confounding can exist. In rare instances, infant sex and multiple birth can appear as confounders. The most difficult problem to solve is often confounding by indication. The problem of confounding is less important for congenital malformations than for many other pregnancy outcomes.

Risk of Preterm or Small-for-Gestational-Age Birth After Influenza Vaccination During Pregnancy: Caveats When Conducting Retrospective Observational Studies

“…Seasonal confounding has been identified as a potential source of bias in studies of the associations of exposures with birth outcomes, with the rate of prematurity and birth weight being dependent on season of conception (36, 37), although this potential bias may be only an artifact of the cohort truncation bias. Therefore, grouping pregnancies by pregnancy start date, care date, or trimester of vaccination may account for the 2 potential biases simultaneously.…”

The association between the regular use of risk-based term IOL and improved birth outcomes in an Italian hospital: A retrospective cohort study

“…Furthermore, even for women having a "non-indicated" IOL, there usually exist one or more risk factors that underlie the recommendation, or the request, for the IOL [51]. If women delivering after the spontaneous onset of labour are less likely to have risk factors than women having a "non-indicated" IOL, then the observational studies comparing the outcomes following IOL to the outcomes following spontaneous labour probably contain significant "confounding by indication" [52,53]. Finally, most of the observational studies that compared "non-indicated" IOL to spontaneous labour failed to correctly model the actual impact of ni_IOL on the flow of term pregnancy.…”

Sex-Gender Variable: Methodological Recommendations for Increasing Scientific Value of Clinical Studies

“…Even after the dramatic examples of diethylstilbestrol and thalidomide, in our opinion, it is urgent to increase the knowledge on drug effects in pregnant women through the use of multi-disciplinary research teams (obstetrics, pharmacologists, and so on); furthermore, it should be considered relative to the sex–gender of fetus. As sustained by the FDA, the inclusion of pregnant women in RCT is necessary to keep in mind that are many maternal and infant confounders [154]. Among infant confounders, it is necessary to recall the sex–gender of the fetus [155].…”