Paracetamol safe to use during pregnancy: study

The use of paracetamol during pregnancy does not appear to increase the likelihood of autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), or intellectual disability in children, according to the results of a systematic review and meta-analysis.

“This finding supports the recommendations made by major medical organizations regarding its use,” said the investigators, who searched Medline, Embase, ClinicalTrials.gov, and the Cochrane Library from inception to 30 September 2025 for cohort studies reporting adjusted estimates of the risk of ASD, ADHD, and intellectual disability. Unadjusted studies were excluded.

The research team calculated odds ratios (ORs) and restricted analyses to sibling-comparison studies with adjusted estimates. They used the generic inverse variance method for the random-effects meta-analyses and performed subgroup analyses when possible (trimester, duration of use, offspring sex, and follow-up length. [Lancet 2026;doi:10.1016/S3050-5038(25)00211-0]

Forty-three studies were included in the systematic review and 17 in the meta-analyses. In sibling comparison studies, maternal exposure to paracetamol did not increase the odds of ASH (OR, 0.98, 95 percent confidence interval [CI], 0.93‒1.03; p=0.45), ADHD (OR, 0.95, 95 percent CI, 0.86‒1.05; p=0.31), or intellectual disability (OR, 0.93, 95 percent CI, 0.69‒1.24; p=0.63) in the offspring.

Likewise, when considering only studies at low risk of bias according to the Quality In Prognosis Studies tool, paracetamol use during pregnancy showed no significant association with ASD (OR, 1.03, 95 percent CI, 0.86‒1.23; p=0.78), ADHD (OR, 0.97, 95 percent CI, 0.89‒1.05; p=0.49), or intellectual disability (OR, 1.11, 95 percent CI, 0.92‒1.34; p=0.28).

These findings were consistent in all studies with adjusted estimates and those with more than 5 years of follow-up.

Mechanisms

Several studies have tried to explain the connection between paracetamol use and neurodevelopmental outcomes. Biological mechanisms proposed include endocrine disruption and oxidative stress mediated by the metabolite N-acetyl-p-benzoquinone imine, altered prostaglandin signalling, and epigenetic modifications. [N Engl J Med 2003; 349:1157-1167; Int J Clin Pharmacol Ther 2006;44:57-63]

“The immature foetal liver has limited detoxification capacity, potentially increasing susceptibility to these pathways,” the investigators said. [Am J Perinatol 2017;34:541-543]

“Although these mechanisms are plausible, most supporting evidence has been obtained from animal or in-vitro studies, and no human data have established causality,” they added.

Maternal fever

Paracetamol, commonly used for fever or pain, is one of the most widely taken medicines in pregnancy and is included on the WHO List of Essential Medicines. [https://list.essentialmeds.org/medicines/15]

To avoid the use of paracetamol based on inconclusive evidence may expose pregnant women and their offspring to risks associated with untreated fever or severe pain. For instance, untreated maternal fever could result in miscarriage, congenital anomalies, preterm birth, and difference in neurodevelopment. [Epidemiology 2005;16:216-219; Pediatrics 2014;133:e674-e688; Mol Autism 2021;12:60]

“For this reason, discouraging the appropriate use of paracetamol has the potential to cause greater harm than the drug itself,” the investigators said.

“Future studies should employ designs that minimize confounding by indication, such as sibling or other quasi-experimental approaches, and, where feasible, incorporate biomarker-based exposure assessment to improve the precision of exposure measurement and strengthen causal inference,” they added.