Parents handing a feverish infant a dose of acetaminophen have spent years absorbing warnings drawn from observational research linking early exposure to eczema, wheezing, and asthma. A randomized trial of nearly 4,000 babies has now directly tested that concern, and at age one, it found no meaningful difference between acetaminophen and ibuprofen on either outcome.
The trial, called PIPPA Tamariki, enrolled 3,923 New Zealand infants younger than eight weeks and assigned each family to give only acetaminophen, known there as paracetamol, or only ibuprofen whenever their baby needed medication for fever or pain during the first year. At regular points, parents were asked whether their child had experienced eczema, asthma symptoms, or bronchiolitis, and the team also reviewed prescription and hospital records.
About 16 percent of babies in the acetaminophen group developed eczema, compared with about 15 percent in the ibuprofen group. Roughly 5 percent of children in each group were hospitalized for bronchiolitis, viral-induced wheeze, or asthma, the trial's second key outcome. Neither difference was statistically significant. Serious adverse events were uncommon, and none were attributed to either medication.
The Design Is What Makes This Different
Most of the worry about infant acetaminophen came from observational studies, which compare children whose parents happened to give the medicine with children whose parents did not. That design carries a well-known problem called confounding by indication, a point emphasized in a linked commentary published alongside the results. Babies who receive more fever medicine are babies who get sick more often, and frequent early respiratory illness is itself associated with later wheezing and asthma.
Sorting the drug from the illness that prompted it is nearly impossible without randomization. PIPPA Tamariki assigned the medication by chance, which distributes the underlying illness risk evenly between the groups. The results were published in The Lancet Child and Adolescent Health and were from a multicentre, open-label, parallel-group, superiority randomized controlled trial conducted at three sites in Auckland and Wellington, with enrollment from April 2018 to July 2023.
"Our study found that paracetamol and ibuprofen are incredibly safe to use in young children," said Professor Stuart Dalziel of the University of Auckland, a pediatrician at Starship Children's Hospital and the lead researcher on the trial, who added that the medicines must be given at the correct doses. Lead author Dr. Eunicia Tan, a senior lecturer at the university and an emergency physician at Middlemore Hospital, said the broader study is designed to test links between paracetamol and asthma, eczema, hay fever, and developmental disorders including autism and ADHD.
The Limits Parents Should Understand
This result covers hospitalizations for eczema and bronchiolitis at age one. It does not yet answer the asthma question, and it does not address autism or attention-deficit hyperactivity disorder.
That gap is deliberate rather than an oversight. Asthma cannot be diagnosed reliably in a one-year-old. Dalziel has noted that two-thirds of children who are wheezy at age three do not develop asthma by age six, which is why the team is following participants to age six before drawing conclusions about the primary question the trial was built to answer. Developmental conditions are likewise identified more accurately as children get older. Results at age three are expected first, followed by the age six analysis.
Other limits apply. The trial was open-label, meaning families knew which medication they were administering, and the eczema outcome was assessed using standardized diagnostic criteria applied to parent-reported information alongside hospitalization records. It was conducted in New Zealand, and while the biology of infant fever does not change at a border, healthcare patterns and background illness rates do differ. Dosing followed the New Zealand Formulary for Children, with acetaminophen at 15 mg per kilogram and ibuprofen at 5 mg per kilogram under three months and 10 mg per kilogram from three months, rather than whatever a household happened to have in the cupboard.
The finding is that neither drug proved superior on these outcomes. It is not a finding that either drug is risk-free at any dose.
Dosing Errors Remain the Larger Practical Danger
Both medicines are safe when given correctly, and the more common household hazard is not the choice between them but the arithmetic. Infant dosing is weight-based, and the errors that send babies to emergency departments involve incorrect amounts, confusion between concentrations, or two caregivers unknowingly dosing within the same window.
Parents can reduce that risk with steps that require no medical judgment. Use the dosing device that came with the bottle. Write down the time and amount of each dose so that every caregiver can see it. Check the concentration on each new bottle, since formulations differ. Confirm the current weight rather than a figure from a past appointment.
Ibuprofen is not recommended for infants under six months without clinician direction, and acetaminophen dosing for newborns should be confirmed with a pediatrician. Any fever in an infant younger than three months warrants prompt medical evaluation regardless of what medication is available at home.
Fever itself is not the enemy. It is a normal immune response, and the reason to treat is to make an uncomfortable baby more comfortable, not to force a number down.
The Question Behind the Question
The reason this trial exists is the hypothesis that early acetaminophen exposure might contribute to childhood asthma. The Medical Research Institute of New Zealand, which collaborated on the work with the University of Auckland, describes it as the largest children's trial ever conducted in the country.
If the age-six results show no difference, a hypothesis that has shaped parental anxiety for two decades will have been tested and found not to be supported. If they show a difference, the finding will carry weight precisely because it came from a randomized trial rather than an observational association.
For now, the practical guidance remains unchanged. Parents managing a feverish infant can use either medication as directed by their pediatrician, with attention to weight-based dosing and the age restrictions on ibuprofen. Parents avoiding acetaminophen out of concern about eczema or bronchiolitis now have randomized evidence suggesting that specific worry is not supported.
Anyone whose child has a chronic condition, takes other medications, or was born prematurely should confirm dosing with their clinician. The research was funded by the Health Research Council and Cure Kids.
Key Questions Answered
What did the trial find? Among 3,923 infants randomly assigned to receive either acetaminophen or ibuprofen for fever and pain during their first year, there was no statistically significant difference in eczema or bronchiolitis hospitalization at age one, and no serious adverse events were attributed to either drug.
Does this prove acetaminophen does not cause asthma? No. Asthma cannot be diagnosed reliably at age one. The trial is following the same children to age six, which is when the asthma question will be answered.
Does it say anything about autism or ADHD? Not yet. Those conditions are diagnosed more accurately in older children, and the research team has said later analyses will address them.
Which medicine should parents give? Either can be appropriate depending on the child's age and situation. Ibuprofen is generally not given to infants under 6 months without a clinician's direction. Parents should confirm dosing with their pediatrician.
What is the biggest safety risk with these medicines? Dosing errors. Incorrect amounts, confusion between product concentrations, and duplicate doses given by different caregivers are more common problems than the drugs themselves.
When should a feverish baby see a doctor? Any fever in an infant under three months requires prompt evaluation. Older infants should be seen for a persistent fever, poor feeding, unusual sleepiness, difficulty breathing, or a rash that does not fade with pressure.
Where was the study done and who paid for it? It was conducted in Auckland and Wellington, New Zealand, by the University of Auckland and the Medical Research Institute of New Zealand, with funding from the Health Research Council of New Zealand and Cure Kids.
