Maternal over-the-counter analgesics use during pregnancy and adverse perinatal outcomes: Cohort study of 151,141 singleton pregnancies

Aikaterini Zafeiri, Edwin Amalraj Raja, Rod T Mitchell, David C Hay, Sohinee Bhattacharya, Paul Fowler

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Abstract

OBJECTIVES
To identify any associations between in utero exposure to five over-the-counter (non prescription) analgesics (paracetamol, ibuprofen, aspirin, diclofenac, naproxen) and adverse neonatal outcomes.
DESIGN
Retrospective cohort study using the Aberdeen Maternity and Neonatal Databank.
PARTICIPANTS
51,141 singleton pregnancies between 1985 and 2015.
MAIN OUTCOME MEASURES
Premature 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.

RESULTS
83.7% 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.
CONCLUSIONS
Over-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.
Original languageEnglish
Article numbere048092
Number of pages27
JournalBMJ Open
Volume12
Issue number5
Early online date3 May 2022
DOIs
Publication statusPublished - 3 May 2022

Keywords

  • acetaminophen
  • aspirin
  • diclofenac
  • ibuprofen
  • in utero exposure
  • naproxen
  • offspring outcomes
  • over-the-counter analgesics
  • paracetamol
  • Pregnancy
  • epidemiology
  • clinical pharmacology
  • obstetrics
  • Humans
  • Hypospadias
  • Male
  • Pregnancy Outcome/epidemiology
  • Female
  • Stillbirth/epidemiology
  • Retrospective Studies
  • Infant, Newborn
  • Perinatal Death
  • Birth Weight
  • Acetaminophen
  • Premature Birth/epidemiology
  • Analgesics/adverse effects
  • Cohort Studies
  • POPULATION
  • MILD ANALGESICS
  • ACETAMINOPHEN
  • BIRTH-DEFECTS PREVENTION
  • INTRAUTERINE EXPOSURE
  • 1ST TRIMESTER
  • RISK-FACTORS
  • NEURAL-TUBE DEFECTS
  • ASPIRIN CONSUMPTION
  • MEDICATION USE

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