The Landmark University of Auckland Study on Infant Pain Relief

New research from the University of Auckland has provided reassuring evidence on the safety of paracetamol and ibuprofen for infants. This randomised controlled trial, known as PIPPA Tamariki, involved nearly 4,000 New Zealand babies and found no increased risk of eczema or bronchiolitis associated with either medication when used as directed for fever or pain in the first year of life.

Paracetamol, also known as acetaminophen outside New Zealand and Australia, and ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), are the most commonly used over-the-counter medications for managing fever and discomfort in babies worldwide. For New Zealand parents, these findings align closely with everyday health practices recommended by organisations like Plunket, the country's leading child health service.

Background: Resolving Decades of Uncertainty

Prior observational studies had raised alarms about potential links between early-life paracetamol exposure and conditions such as eczema, wheezing, and even asthma later in childhood. For instance, large international surveys like ISAAC Phase Three, involving over 200,000 children, reported adjusted odds ratios suggesting higher risks. However, these associations were correlational, often confounded by the fact that sicker infants receive more medication.

The PIPPA Tamariki trial addresses this by using a gold-standard randomised controlled design, eliminating confounding factors and providing causal evidence. Conducted across Auckland and Wellington, it reflects New Zealand's diverse population, including Māori (15.6%), Pacific (15.5%), Asian (23.7%), and New Zealand European or other (44.9%) participants.

Study Design: A Model of Rigorous Paediatric Research

Infants under 8 weeks old, born at 32 weeks gestation or more, were randomised 1:1 to receive either paracetamol (15 mg/kg every 6 hours under 1 month, every 4 hours after) or ibuprofen (5 mg/kg every 6 hours under 3 months, 10 mg/kg after), dosed orally as required per the New Zealand Formulary for Children. Randomisation was stratified by site, maternal asthma, and multiple births to ensure balance.

• Recruitment: April 2018 to July 2023, 3,923 enrolled, 3,908 analysed (1,985 paracetamol, 1,923 ibuprofen).
• Outcomes: Primary - eczema (UK Working Party's Diagnostic Criteria or hospitalisation); bronchiolitis (hospitalisation for bronchiolitis, viral wheeze, or asthma).
• Follow-up: Parental questionnaires, hospital records checked regularly.

This open-label, multicentre approach at University of Auckland and Wellington sites exemplifies collaborative academic research in New Zealand.

Key Results: Comparable Risks Across Groups

Eczema developed in 16.2% (322/1,985) of the paracetamol group versus 15.4% (296/1,923) in ibuprofen (absolute risk difference 0.8%, 95% CI -1.5 to 3.1; adjusted OR 1.10, 95% CI 0.92-1.32). Bronchiolitis rates were 4.9% (98/1,985) versus 4.3% (82/1,923) (risk difference 0.7%, 95% CI -0.6 to 2.0; adjusted OR 1.23, 95% CI 0.82-1.71). No statistically significant differences emerged, reassuringly dispelling concerns for these early outcomes.

These figures underscore the trial's power, with narrow confidence intervals indicating reliable precision.

Safety Data: Minimal Adverse Events

Serious adverse events were rare, affecting 17 participants (19 events total): 0.4% in paracetamol (8/1,985) and 0.5% in ibuprofen (9/1,923). None were linked to the study medications, including no cases of renal issues or gastrointestinal bleeding typically monitored with NSAIDs in infants. This aligns with global pharmacovigilance data, affirming both drugs' profiles when dosed correctly.

Insights from Principal Investigators

Professor Stuart Dalziel, Cure Kids Chair of Child Health Research at the University of Auckland and paediatrician at Starship Children’s Hospital, stated: “Our study found that paracetamol and ibuprofen are incredibly safe to use in young children. These results give parents and health professionals high confidence to continue to use these important medications.” Co-lead Dr Eunicia Tan, senior lecturer and emergency physician, added that the ongoing follow-up to age six will clarify links to asthma, hay fever, and neurodevelopmental conditions like autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).

The publication in The Lancet Child & Adolescent Health (read full study) marks a pinnacle for New Zealand paediatrics.

Implications for Kiwi Families and Clinicians

In New Zealand, where respiratory infections peak in winter and eczema affects up to 20% of children, these findings empower confident use of first-line analgesics. Pharmacists and Plunket nurses can reassure whānau (families), emphasising precise dosing to avoid under- or overdosing. For Māori and Pacific communities, disproportionately affected by childhood asthma, this reduces unwarranted medication avoidance.

Explore university jobs in New Zealand for health sciences roles supporting such impactful research.

University of Auckland's Paediatric Research Excellence

The University of Auckland's Faculty of Medical and Health Sciences, including collaborators from the Liggins Institute and Medical Research Institute of New Zealand (Wellington), spearheaded this Health Research Council-funded effort. Professor Dalziel's team exemplifies translational research, bridging lab insights to policy. Aspiring researchers can find opportunities in higher ed research jobs, contributing to child health advancements.

Contrasting with Global Observational Data

Meta-analyses previously pooled odds ratios around 1.2-1.5 for paracetamol and eczema/asthma, but RCTs like this one clarify no causation. Smaller trials in asthmatic or preterm children showed mixed results, but PIPPA Tamariki's scale in healthy term infants fills a critical gap. Visit the PIPPA Tamariki site for more.

Looking Ahead: Age 3 and 6 Outcomes

With children tracked to school age, forthcoming data will assess persistent wheeze evolving to asthma (only one-third do) and allergies. Funded by Cure Kids, this positions New Zealand at the forefront of paediatric epidemiology. Health sciences students at NZ universities gain from such models.

Career Pathways in New Zealand Paediatric Research

This study highlights demand for experts in clinical trials, epidemiology, and child health. Roles like research assistants or lecturers abound; check research assistant jobs or career advice adaptable to NZ. Rate professors like Dalziel on Rate My Professor.

Photo by Amanda Jones on Unsplash

Practical Guidance for Safe Use

• Always use age/weight-appropriate dosing from NZ Formulary.
• Consult GP if fever persists >48 hours or other symptoms.
• Alternate if needed, but prioritise paracetamol for under 3 months.
• Monitor for rare allergies.

For more, explore higher ed career advice in health fields.