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

OBJECTIVESTo identify any associations between in utero exposure to five over-the-counter (non-prescription) analgesics (paracetamol, ibuprofen, aspirin, diclofenac, naproxen) and adverse neonatal outcomes. DESIGNRetrospective cohort study using the Aberdeen Maternity and Neonatal Databank. PARTICIPANTS151,141 singleton pregnancies between 1985 and 2015. MAIN OUTCOME MEASURESPremature delivery (<37 weeks), stillbirth, neonatal death, birthweight, standardised birthweight score, neonatal unit admission, APGAR score at 1 and 5 minutes, neural tube and amniotic band defects, gastroschisis and, in males, cryptorchidism, and hypospadias. RESULTS83.7% of women taking over-the-counter analgesics reported first trimester use when specifically asked about use at their first antenatal clinic visit. Pregnancies exposed to at least one of the five analgesics were significantly independently associated with increased risks 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 <2,500g (aOR=1.28, 95%CI 1.20-1.37), birthweight >4,000g (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). The overall prevalence of over-the-counter analgesics use during pregnancy was 29.1%, however it rapidly increased over the 30-year study period, to include over 60% of women in the last seven years of the study. This makes our findings highly relevant to the wider pregnant population. CONCLUSIONSOver-the-counter (non-prescription) analgesics consumption during pregnancy was associated with a substantially higher risk for adverse perinatal health outcomes in the offspring. The use of paracetamol in combination with other non-steroidal anti-inflammatory drugs conferred the highest risk. The increased risks of adverse neonatal outcomes associated with non-prescribed, over-the-counter, analgesics use during pregnancy indicate that healthcare guidance for pregnant women regarding analgesic use need urgent updating. FundingBiotechnology and Biological Sciences Research council (BBSRC) funding under the EASTBIO doctoral training programme (grant number 1942576) to AZ and EU Horizon 2020 project FREIA (Grant Number 825100) to PAF. RTM is supported by MRC Centre for Reproductive Health Grant MR/N022556/1.