Infants given acetaminophen (also called paracetamol; brand name, Tylenol) for pain or fever relief in their first year were no more likely to develop eczema or bronchiolitis by age 1 than those given ibuprofen (eg, Advil), according to a randomized controlled trial published last week in The Lancet Child & Adolescent Health.
Previous observational research had suggested a possible link between acetaminophen use in the first year of life and the development of eczema and asthma later on.
The current study, led by researchers from the University of Auckland in New Zealand, enrolled 3,908 infants younger than 8 weeks old at three sites in Auckland and Wellington from April 2018 to July 2023. Of the participants, 1,985 were randomized to the acetaminophen group and 1,923 to the ibuprofen group. The cohort was diverse, with 15.6% identifying as Maori, 15.5% as Pacific, 23.7% as Asian, and 44.9% as New Zealand European or other.
Infants received either acetaminophen alone (15 milligrams per kilogram [mg/kg] at specified intervals) or ibuprofen alone (5 to 10 mg/kg, depending on age), as required for fever or pain, according to age-based dosing from the New Zealand Formulary for Children.
At age 1 year, eczema was reported in 322 (16.2%) of infants in the acetaminophen group and 296 (15.4%) in the ibuprofen group. Bronchiolitis occurred in 98 participants (4.9%) in the acetaminophen group and 82 participants (4·3%) in the ibuprofen group. These numbers correspond to absolute risk differences of 0.8% (95% confidence interval [CI], –1.5 to 3.1) and 0.7% (95% CI, –0.6 to 2.0), respectively, indicating low risk with no significant statistical significance between the two drugs.
‘Incredibly safe to use in young children’
These findings may reassure caregivers and clinicians who rely on acetaminophen and ibuprofen for managing fever or pain in infancy. “Our study found that paracetamol and ibuprofen are incredibly safe to use in young children,” senior author Stuart Dalziel, PhD, chair of child health research at Waipapa Taumata Rau, University of Auckland, and pediatrician at Starship Children’s Hospital, said in a press release.
The current research stands in contrast to earlier observational study findings that suggested an association between early acetaminophen use and later development of atopic diseases such as eczema and asthma. But Alan R Smyth, MBBS, a professor in the School of Medicine, Dentistry and Biomedical Sciences at Queen’s University Belfast, notes in an accompanying commentary that “associations seen in observational studies do not prove causation—in this case, because of the potential for confounding by the indication for paracetamol use.”
While ongoing research will follow children through age 6 years to explore any increased risk of asthma and acetaminophen use, the study authors conclude that their randomized trial “provides high-quality reassurance about the safety of paracetamol and ibuprofen use in infancy. Because paracetamol and ibuprofen are the most common medications used globally in the first year of life, this evidence is highly relevant to all parents and health-care providers who care for infants.”
