Short interpregnancy interval and pregnancy outcomes: How important is the timing of confounding variable ascertainment?

Abstract

Estimation of causal effects of short interpregnancy interval on pregnancy outcomes may be confounded by time-varying factors. These confounders should be ascertained at or before delivery of the first ("index") pregnancy, but are often only measured at the subsequent pregnancy. To quantify bias induced by adjusting for time-varying confounders ascertained at the subsequent (rather than the index) pregnancy in estimated effects of short interpregnancy interval on pregnancy outcomes. We analysed linked records for births in British Columbia, Canada, 2004-2014, to women with ≥2 singleton pregnancies (n=121151). We used log binomial regression to compare short (<6, 6-11, 12-17months) to 18-23-month reference intervals for 5 outcomes: perinatal mortality (stillbirth and neonatal death); small for gestational age (SGA) birth and preterm delivery (all, early, spontaneous). We calculated per cent differences between adjusted risk ratios (aRR) from two models with maternal age, low socio-economic status, body mass index, and smoking ascertained in the index pregnancy and the subsequent pregnancy. We considered relative per cent differences <5% minimal, 5%-9% modest, and ≥10% substantial. Adjustment for confounders measured at the subsequent pregnancy introduced modest bias towards the null for perinatal mortality aRRs for <6-month interpregnancy intervals [-9.7%, 95% confidence interval [CI] -15.3, -6.2). SGA aRRs were minimally biased towards the null (-1.1%, 95% CI -2.6, 0.8) for <6-month intervals. While early preterm delivery aRRs were substantially biased towards the null (-10.4%, 95% CI -14.0, -6.6) for <6-month interpregnancy intervals, bias was minimal for <6-month intervals for all preterm deliveries (-0.6%, 95% CI -2.0, 0.8) and spontaneous preterm deliveries (-1.3%, 95% CI -3.1, 0.1). For all outcomes, bias was attenuated and minimal for 6-11-month and 12-17-month interpregnancy intervals. These findings suggest that maternally linked pregnancy data may not be needed for appropriate confounder adjustment when studying the effects of short interpregnancy interval on pregnancy outcomes.