Paracetamol use in pregnancy

The BNF states that use of paracetamol as analgesia in pregnancy is 'not known to be harmful'

• the Avon Longitudinal Study of Parents and Children (ALSPAC) study followed 14,000 pregnancies through birth and beyond
  • in this population-based study women were asked twice during pregnancy (at 18-20 weeks and 32 weeks) about their usage of paracetamol and aspirin. Six months after birth, and at yearly intervals thereafter, mothers were asked about wheezing and eczema symptoms in their child
• paracetamol was taken frequently (most days/daily) by only 1% of women
  • after controlling for potential confounders, frequent paracetamol use in late pregnancy (20-32 weeks), but not in early pregnancy (<18-20 weeks), was associated with an increased risk of wheezing in the offspring at 30-42 months (adjusted odds ratio (OR) compared with no use 2.10 (95% CI 1.30 to 3.41); p=0.003), particularly if wheezing started before 6 months (OR 2.34 (95% CI 1.24 to 4.40); p=0.008)
• assuming a causal relation, only about 1% of wheezing at 30-42 months was attributable to this exposure. Frequent paracetamol use in pregnancy was not associated with an increased risk of eczema. Frequent aspirin use in pregnancy was associated with an increased risk of wheezing only at <6 months
• the authors concluded that frequent use of paracetamol in late pregnancy may increase the risk of wheezing in the offspring, although such an effect could explain only about 1% of the population prevalence of wheezing in early childhood
• this study should be taken in the context that it is a cohort study and that frequent use of paracetamol may be a surrogate marker for some other, as yet unidentified, factor

Paracetamol and breastfeeding (3):

• paracetamol is the painkiller of choice whilst breastfeeding
• very small amounts of paracetamol pass into the breast milk, and these amounts are far below the doses that would normally be given to infants directly
• the properties of paracetamol are such that there is no risk of it building up in the infant’s system
• there have been no adverse effects reported in infants exposed to paracetamol through breastmilk, except for one isolated case report of a hypersensitivity reaction. However, given the length of time that paracetamol has been available on the market, and its widespread use, the risk of such a reaction happening is extremely rare

A further review states (4):

• is very little published evidence for its use during breastfeeding
• properties of paracetamol are such that at therapeutic doses, there is no risk of it accumulating in the infant’s system
  • is potential for liver toxicity if there has been a maternal overdose, however management of this scenario would require specialist advice
• have been no side effects reported in infants exposed to paracetamol through breast milk, except for one isolated case report of a hypersensitivity reaction
  • given the length of time that paracetamol has been available, and its widespread use, the risk of such a reaction happening is extremely rare

Prenatal and postnatal exposure to paracetamol (acetaminophen) in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood (5,6)

• meta-analysis (n=73,881 mother-child pairs) showed that children prenatally exposed to paracetamol were 19% more likely to subsequently have autism spectrum conditions (OR 1.19, 95% CI 1.07-1.33) and 21% more likely to have ADHD symptoms (1.21; 1.07-1.36) vs. non-exposed children (5):
  • study authors concluded that "considering all evidences on acetaminophen use and neurodevelopment, we agree with previous recommendations indicating that while acetaminophen should not be suppressed in pregnant women or children, it should be used only when necessary..."
• Swedish study (185,909 children exposed to paracetamol during pregnancy from database of 2 480 797 births), using sibling control analysis, found no evidence of association with autism (HR 0.98, 95%CI 0.93-1.04), ADHD (0.98, 0.94-1.02) & intellectual disability (1.01, 0.92-1.10) (6):
  • was also no evidence of a dose-response pattern
  • authors state that associations observed in other models may have been attributable to familial confounding

Reference:

1. British National Formulary (accessed 28/12/2013)
2. Shaheen SO et al. Paracetamol use in pregnancy and wheezing in early childhood. Thorax 2002;57:958-963
3. NHS Specialist Pharmacy Service (April 2020). Can breastfeeding mothers take paracetamol or combination paracetamol products?
4. NHS Specialist Pharmacy Service (November 2023). Using paracetamol during breastfeeding.
5. Alemany S et al. Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts. Eur J Epidemiol (2021). https://doi.org/10.1007/s10654-021-00754-4
6. Ahlqvist VH, Sjöqvist H, Dalman C, et al. Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability. JAMA. 2024;331(14):1205–1214. doi:10.1001/jama.2024.3172