Breakthrough Insights from New Zealand's Largest Paediatric Trial

In a landmark development for paediatric care, the PIPPA Tamariki study has delivered compelling evidence that both paracetamol (commonly known as acetaminophen) and ibuprofen are safe for infants during their first year of life when used as directed for fever or pain relief. This multicentre randomised controlled trial (RCT), the largest ever conducted in children in New Zealand, directly addresses longstanding concerns raised by observational research suggesting potential links between early-life paracetamol exposure and conditions like eczema, wheeze, and asthma.

Led by Professor Stuart Dalziel from the University of Auckland's Department of Paediatrics, Child and Youth Health, the trial randomised nearly 4,000 newborns across multiple New Zealand sites. Half received paracetamol exclusively, while the other half used ibuprofen as needed. Parents reported symptoms at regular intervals, with data cross-verified against prescribing and hospital records. At one year, no significant differences emerged in rates of eczema or bronchiolitis between groups, and serious adverse events were exceedingly rare with none attributed to the medications.

This gold-standard RCT provides reassurance to parents and clinicians alike, potentially reshaping how infant pain is managed in New Zealand and beyond. As Dalziel notes, "Our study found that paracetamol and ibuprofen are incredibly safe to use in young children." The findings, published in The Lancet Child & Adolescent Health on 27 January 2026, mark a pivotal moment in paediatric pharmacology research.Read the full study here.

The Backdrop: Why These Medications Sparked Debate

Paracetamol and ibuprofen rank among the most widely used analgesics globally for infant fever and pain, with paracetamol often first-line due to its long safety record. In New Zealand, guidelines from bodies like Starship Children's Hospital recommend paracetamol for neonates and ibuprofen from one month of age, with caution under three months. Yet, observational studies over the past two decades fuelled apprehension. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three, analysing data from over 200,000 children, found paracetamol use in the first year associated with a 46% higher odds of asthma symptoms, rhinoconjunctivitis, and eczema at ages 6-7.

Subsequent cohort studies echoed this, reporting odds ratios up to 2.0 for wheeze and eczema with frequent exposure. Critics argued confounding factors—sicker children receive more medication—might explain associations, but the signal persisted, prompting calls for RCTs. Ibuprofen faced separate scrutiny for potential renal and gastrointestinal risks in very young infants, with some guidelines advising avoidance under six months due to sparse data. Systematic reviews, however, found no significant increase in adverse events for short-term use in hydrated infants.

In New Zealand, where infant fever consultations are common—over 20% of under-ones present annually—these uncertainties influenced prescribing habits. The PIPPA Tamariki trial was conceived to deliver definitive answers through rigorous randomisation.

Unpacking the PIPPA Tamariki Study Design

Launched in 2023, PIPPA Tamariki (Paracetamol and Ibuprofen in the Primary Prevention of Asthma in Tamariki) is a prospective, multicentre, open-label, parallel-group superiority RCT. Eligibility: healthy infants under eight weeks born in New Zealand. Exclusion: known allergies, contraindications, or conditions precluding trial drugs. Randomisation (1:1) allocated groups to paracetamol (15 mg/kg every 6 hours under one month, every 4-6 hours thereafter) or ibuprofen (5-10 mg/kg every 6-8 hours).

Parents dispensed medication PRN for fever (>38°C) or pain, following standard dosing. Follow-up questionnaires at 3, 6, 9, and 12 months assessed eczema (via UK Working Party criteria), bronchiolitis (wheeze/doctor-diagnosed), and usage. Primary outcomes: cumulative incidence of eczema and bronchiolitis at 12 months. Secondary: wheeze/asthma symptoms, hospitalisations, adverse events. Power calculation targeted 4,000 for 80% power to detect 3% absolute difference.

Conducted across 20 sites including Starship Children's Hospital, Middlemore, and Wellington, with oversight from University of Auckland and Medical Research Institute of New Zealand (MRINZ). Funded by Health Research Council of New Zealand and Cure Kids, no pharma conflicts declared. Participant retention exceeded 95%, minimising bias.

Key Results: No Elevated Risks Emerge

Of 3,908 infants analysed (1,985 paracetamol, 1,923 ibuprofen), baseline characteristics were balanced: 51% male, mean gestation 39.5 weeks. Medication exposure was similar—median 3 days in first year for both.

Eczema incidence: 16.2% (322/1,985) paracetamol vs 15.4% (296/1,923) ibuprofen; adjusted odds ratio (aOR) 1.07 (95% CI 0.91-1.27, p=0.41). Bronchiolitis: 5.1% vs 4.9%; aOR 1.04 (0.81-1.33, p=0.77). No differences in wheeze or doctor-diagnosed asthma at one year.

Usage patterns mirrored real-world: 85% received at least one dose, primarily for fever post-immunisation or teething. Hospitalisations for respiratory issues were comparable (2.8% vs 2.6%). These null findings persist after adjustments for confounders like family atopy history.

Longer-term data (ages 3 and 6) pending, but early signals challenge causal links from prior epidemiology.

Safety Profile: Reassuring Even in Young Infants

Serious adverse events (SAEs) occurred in 17 infants (0.4%), with 19 total reports—eight in paracetamol, nine in ibuprofen groups. None deemed drug-related; most viral illnesses or unrelated. No excess renal impairment, GI bleeds, or hypersensitivity.

This aligns with meta-analyses showing short-term ibuprofen safe under six months, with renal risks <1% in euvolemic infants. Paracetamol's hepatic profile remained unremarkable, consistent with global data where overdoses, not therapeutic use, pose risks. Co-author Dr Eunicia Tan emphasises, "These results give parents and health professionals high confidence."

In NZ context, where ibuprofen prescriptions rose 20% post-2020 amid paracetamol shortages, this validates flexible options. Guidelines may evolve, but core advice—accurate dosing, hydration—endures. For details, see Starship's analgesia protocols.Starship Paediatric Analgesia Guidelines.

Expert Perspectives and Stakeholder Reactions

Professor Richard Beasley, MRINZ Director, hails it as "essential evidence guiding parents, clinicians, and policymakers." Paediatricians welcome closure on debates dogging practice for 15 years. The Royal New Zealand College of General Practitioners notes alignment with pragmatic use, urging education on dosing errors (common in 10% of cases).

Internationally, US and UK experts anticipate guideline updates; FDA labels ibuprofen from 6 months, but evidence supports earlier. Parents' forums buzz with relief, though some await asthma data. Cure Kids CEO praises community recruitment success, reflecting Kiwi health research engagement.

Implications for New Zealand Families and Clinicians

New Zealand sees ~60,000 births yearly; fever/pain affects 70% of under-ones. This empowers confident management: paracetamol for neonates, ibuprofen as effective alternative reducing fever faster in some. Teething, immunisations, minor illnesses—tools now evidence-backed.

Equity lens: Māori/Pasifika infants face higher bronchiolitis rates (15% vs 5% European); no disparities in trial outcomes. Pharmacists, via Minor Ailments Service, can reinforce safety. Public health campaigns may pivot from fear to proper use, cutting unnecessary GP visits (saving $50m annually).

Challenges persist: overdose risks (NZ Poisons Centre logs 2,000 infant calls/year), formulation confusion. Digital apps for dosing could help.

Global Context and Future Directions

Globally, paracetamol dominates (80% infant analgesic use), ibuprofen 40% in older babies. Observational biases confounded prior signals; RCTs like this illuminate truth. Upcoming PIPPA data on asthma (true diagnosis at school-age), ADHD, autism will inform further.

Research frontiers: combination therapy efficacy, long-acting formulations, non-pharma adjuncts like sucrose for neonates. NZ's trial prowess—bolstered by unis like Auckland, Otago—positions it as paediatric research hub. For careers, explore roles at these institutions.

Timeline: Age 3 results 2028, final 2030. Watch University of Auckland updates.

Practical Advice: Safe Infant Pain Relief Step-by-Step

• Assess need: Fever >38°C rectally or pain impacting feeding/sleep.
• Choose agent: Paracetamol first; ibuprofen if faster antipyresis needed (>3 months).
• Dose accurately: Weight-based, use syringe/oral measure. Max 4 doses/24h.
• Monitor: Hydrate, non-pharma (cuddles, tepid sponge). Seek GP if >48h fever, lethargy.
• Red flags: Rash, breathing distress, dehydration.

Empowerment through evidence: NZ parents can trust these staples.

Photo by Daniel Romero on Unsplash

Addressing Limitations and Next Research Horizons

Open-label design risks bias, but objective outcomes mitigate. High retention, intention-to-treat analysis strengthen validity. Underrepresentation of high-risk groups (preterms excluded) noted; subgroup analyses pending.

Future: Head-to-head vs placebo? Precision dosing via apps? Cultural tailoring for Māori whānau. This study catalyses, but vigilance endures.