The role of confounding in the association between pregnancy complications and subsequent preterm birth: a cohort study

Abstract

Objective: To estimate the degree of confounding necessary to explain the associations between complications in a first pregnancy and the subsequent risk of preterm birth.

Design: Population-based cohort study.

Setting: Western Australia.

Population: Women (n = 125 473) who gave birth to their first and second singleton children between 1998 and 2015.

Main outcome measures: Relative risk (RR) of a subsequent preterm birth (<37 weeks of gestation) with complications of pre-eclampsia, placental abruption, small-for-gestational age and perinatal death (stillbirth and neonatal death within 28 days of birth). We derived e-values to determine the minimum strength of association for an unmeasured confounding factor to explain away an observed association.

Results: Complications in a first pregnancy were associated with an increased risk of a subsequent preterm birth. Relative risks were significantly higher when the complication was recurrent, with the exception of first-term perinatal death. The association with subsequent preterm birth was strongest when pre-eclampsia was recurrent. The risk of subsequent preterm birth with pre-eclampsia was 11.87 (95% CI 9.52-14.79) times higher after a first term birth with pre-eclampsia, and 64.04 (95% CI 53.58-76.55) times higher after a preterm first birth with pre-eclampsia, than an uncomplicated term birth. The e-values were 23.22 and 127.58, respectively.

Conclusions: The strong associations between recurrent pre-eclampsia, placental abruption and small-for-gestational age with preterm birth supports the hypothesis of shared underlying causes that persist from pregnancy to pregnancy. High e-values suggest that recurrent confounding is unlikely, as any such unmeasured confounding factor would have to be uncharacteristically large.

Tweetable abstract: First pregnancy complications are associated with a higher risk of subsequent preterm birth, with evidence strongest for pregnancies complicated by pre-eclampsia.

Keywords: Confounding; e-values; placental abruption; pre-eclampsia; preterm birth; small-for-gestational age.