Associations of periconceptional oral contraceptive use with pregnancy complications and adverse birth outcomes

Int J Epidemiol. 2023 Oct 5;52(5):1388-1399. doi: 10.1093/ije/dyad045.

Abstract

Background: Periconceptional use of oral contraceptives (OCs) has been reported to increase risks of pregnancy complications and adverse birth outcomes, but risks are suggested to differ depending on the timing of discontinuation, amount of oestrogen and progestin content.

Methods: Prospective cohort study among 6470 pregnancies included in the PRegnancy and Infant DEvelopment (PRIDE) Study in 2012-19. Exposure was defined as any reported use of OCs within 12 months pre-pregnancy or after conception. Outcomes of interest were gestational diabetes, gestational hypertension, pre-eclampsia, pre-term birth, low birthweight and small for gestational age (SGA). Multivariable Poisson regression using stabilized inverse probability weighting estimated relative risks (RRs) with 95% CIs.

Results: Any periconceptional OC use was associated with increased risks of pre-eclampsia (RR 1.38, 95% CI 0.99-1.93), pre-term birth (RR 1.38, 95% CI 1.09-1.75) and low birthweight (RR 1.45, 95% CI 1.10-1.92), but not with gestational hypertension (RR 1.09, 95% CI 0.91-1.31), gestational diabetes (RR 1.02, 95% CI 0.77-1.36) and SGA (RR 0.96, 95% CI 0.75-1.21). Associations with pre-eclampsia were strongest for discontinuation 0-3 months pre-pregnancy, for OCs containing ≥30 µg oestrogen and for first- or second-generation OCs. Pre-term birth and low birthweight were more likely to occur when OCs were discontinued 0-3 months pre-pregnancy, when using OCs containing <30 µg oestrogen and when using third-generation OCs. Associations with SGA were observed for OCs containing <30 µg oestrogen and for third- or fourth-generation OCs.

Conclusions: Periconceptional OC use, particularly those containing oestrogen, was associated with increased risks of pre-eclampsia, pre-term birth, low birthweight and SGA.

Keywords: Birthweight; PRIDE Study; gestational hypertension; oral contraceptives; pre-eclampsia; pre-term birth.

MeSH terms

  • Birth Weight
  • Child
  • Contraceptives, Oral* / adverse effects
  • Diabetes, Gestational*
  • Estrogens
  • Female
  • Humans
  • Hypertension, Pregnancy-Induced* / chemically induced
  • Hypertension, Pregnancy-Induced* / epidemiology
  • Pre-Eclampsia* / epidemiology
  • Pregnancy
  • Pregnancy Complications / epidemiology
  • Premature Birth* / epidemiology
  • Progestins
  • Prospective Studies

Substances

  • Contraceptives, Oral
  • Estrogens
  • Progestins