A recent systematic review and meta-analysis published in The Lancet Obstetrics, Gynaecology & Women’s Health found no evidence of a significant association between prenatal paracetamol exposure and an increased risk for autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), or intellectual disability in children. These reassuring findings, based on rigorous analyses, include sibling comparisons to minimize confounding and reinforce the current clinical guidance that paracetamol remains the first-line option for managing pain and fever during pregnancy when used as indicated and for the shortest duration necessary.

The association between paracetamol use during pregnancy and neurodevelopmental disorders in children has been the subject of intense debate in recent years. This newly published meta-analysis provides reassurance, finding no significant association between ASD, ADHD, and intellectual disability.

Paracetamol is recommended, including in Germany, as the first-line treatment for pain and fever during pregnancy. Concerns escalated last autumn when claims emerged from the US administration under President Donald Trump, suggesting a probable link between prenatal paracetamol exposure and autism. These assertions have been widely criticized for their lack of scientific rigor and have contributed to confusion among pregnant individuals and clinicians.

Public Anxiety

Misleading statements by Trump and others have caused considerable uncertainty.

“The poorly substantiated claims by US President Trump and his administration that paracetamol use during pregnancy was responsible for the increase in children with ASD caused considerable public concern last September,” said Wolfgang Paulus , MD, senior physician and head of the counseling center for reproductive toxicology, University Women’s Clinic Ulm, Ulm, Germany, in response to an inquiry from the Science Media Center (SMC).

He noted that many pregnant women subsequently inquired more frequently about safer alternatives. However, nonsteroidal anti-inflammatory drugs such as ibuprofen, diclofenac, and opioids are only usable during pregnancy under substantial restrictions and do not represent safer options.

The hypothesis that maternal paracetamol use might be associated with neurodevelopmental disorders in offspring is largely based on older observational studies that lack adequate control for confounding factors.

A large cohort study published in JAMA in April 2024 helped ease concerns, showing no evidence of a causal association between prenatal paracetamol exposure and ASD, ADHD, or intellectual disability when sibling comparisons were used.

No Risk Increase

The new meta-analysis reinforces these findings. The research team, led by Francesco D’Antonio, MD, from the Center for Fetal Care and High-Risk Pregnancy, University of Chieti-Pescara, Chieti, Italy, evaluated 17 studies for the primary meta-analysis. In the primary analysis focusing on sibling comparison studies, no significant increase in the risk for neurodevelopmental disorders was observed.

This applied to ASD, with an odds ratio (OR) of 0.98 (95% CI, 0.93-1.03); ADHD, with an OR of 0.95 (95% CI, 0.86-1.05); and intellectual disability, with an OR of 0.93 (95% CI, 0.69-1.24).

“This approach substantially increases the strength of the evidence compared with many older analyses,” said Paulus. Sibling comparison studies reduce potential confounding factors by accounting for shared familial influences, such as genetics, socioeconomic status, and home environment.

The results remained consistent in a broader analysis that included all studies with adjusted estimates, regardless of the sibling design. The authors concluded that the associations reported in earlier conventional studies were likely attributable to confounding factors, such as maternal illness, fever, or genetic predisposition, rather than the causal effects of paracetamol.

Dose Data Lacking

One limitation of the meta-analysis was the inability to differentiate by the dosage or duration of paracetamol use. This point was highlighted by Ursula von Mandach , PhD, head of the Office of the Swiss Academy of Perinatal Pharmacology, University Hospital Zurich, Zürich, Switzerland, in a statement to the SMC.

In clinical practice, she continues to recommend relying on data distinguished by treatment duration. “Paracetamol is an important aid for pregnant women in the case of pain and fever during infections, as long as we are in short-term use of a maximum of 2 weeks and not in continuous use,” she said.

Paulus described the publication as confirming the current safety recommendations for the use of paracetamol during pregnancy. He emphasized that, similar to any medication during pregnancy, its use should remain strictly indicated and as brief as possible. Given the lack of detailed dose and duration data, clinicians should recommend moderate dosing and avoid unnecessary use.

Politically motivated claims lacking robust evidence remain problematic; Paulus added that they suggest medical risks without scientific support and primarily fuel uncertainty.

The potential consequences were outlined by Anne Reinhardt, PhD, research associate at the Chair of Health Communication at the Ludwig Maximilian University of Munich, Munich, Germany. She believes that the current meta-analysis remains valuable: “Such evidence can be a key tool for correcting false narratives and supporting people in making informed health decisions,” Reinhardt said.

This story was translated from Medscape’s German edition.