Background: Acetaminophen use during pregnancy has been associated with a reduced risk of stillbirth and preterm birth, but findings are based on few studies with small numbers of exposed women.
Methods: To examine whether prenatal exposure to acetaminophen reduces the risk of adverse pregnancy outcomes, we used data from the Danish National Birth Cohort. We also examined the combined potential effects of acetaminophen, coffee and tobacco use on pre-eclampsia and preterm birth. The study population consisted of women who provided information on acetaminophen use during pregnancy and gave birth to singletons (n = 98 140). The cohort was linked to the Danish National Hospital Registry and the Medical Birth Registry, which covers all Danish hospitals, miscarriages and births in Denmark.
Results: Women using acetaminophen during the third trimester of pregnancy had an increased risk of preterm birth [adjusted hazard ratio (HR) = 1.14, 95% CI: 1.03-1.26]. The risk of preterm birth was increased in mothers with pre-eclampsia (HR = 1.55, 95% CI: 1.16-2.07) but not in women without pre-eclampsia (HR = 1.08, 95% CI: 0.97-1.20). Tobacco smoking and coffee consumption did not modify the effect of acetaminophen in any consistent pattern. No association was found between acetaminophen use and risk of preterm complications, miscarriages, stillbirths, low birth weight or small size for gestational age.
Conclusion: Findings do not provide strong support for a change in clinical practice regarding use of acetaminophen during pregnancy, but the increased risk of preterm birth among women with pre-eclampsia should be further investigated.