Over-the-counter Analgesics in Pregnancy and Offspring Neonatal Outcomes: A Retrospective Cohort Study

Objective To identify associations between in utero exposure to 5 over-the-counter (OTC) analgesics and adverse neonatal outcomes. Design Retrospective cohort study Setting Aberdeen UK Population 151,141 singleton deliveries, 1985 to 2015 Methods Self-reported, non-prescription, consumption of paracetamol, aspirin, ibuprofen, diclofenac and naproxen during pregnancy and neonatal outcomes were obtained from the Aberdeen Maternity and Neonatal Databank (AMND). Univariable and multivariable regression analyses were performed to investigate associations between analgesic use and offspring neonatal outcomes. Crude (cORs) and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were reported, indicating the strength of association. Main Outcome Measures Premature delivery (<37 weeks), stillbirth, neonatal death, birthweight, standardised birthweight score, neonatal unit admission, APGAR score at 1 and 5 minutes, cryptorchidism, neural tube and amniotic band defects, hypospadias and gastroschisis. Results Pregnancies exposed to at least one of the 5 analgesics were significantly independently associated with increased odds for premature delivery <37 weeks (aOR=1.50, 95%CI 1.43-1.58), stillbirth (aOR=1.33, 95%CI 1.15-1.54), neonatal death (aOR=1.56, 95%CI 1.27-1.93), birthweight 4000g (aOR=1.09, 95%CI 1.05-1.13), admission to neonatal unit (aOR=1.57, 95%CI 1.51-1.64), APGAR score <7 at 1 minute (aOR=1.18, 95%CI 1.13-1.23) and 5 minutes (aOR=1.48, 95%CI 1.35-1.62), neural tube defects (aOR=1.64, 95%CI 1.08-2.47) and hypospadias (aOR=1.27, 95%CI 1.05-1.54 males only). Conclusions There was a high prevalence of OTC analgesics use during pregnancy, which steeply increased during the 30-year study period. Analgesic consumption was independently associated with multiple adverse neonatal offspring outcomes. The use of paracetamol in combination with other NSAIDs conferred the highest risk. Funding Biotechnology and Biological Sciences Research council (BBSRC) funding under the EASTBIO doctoral training programme.