Randomized controlled trial of asthma risk with paracetamol use in infancy – a feasibility study

Riley, Judith; Braithwaite, Irene; Shirtcliffe, Philippa; Caswell-Smith, Rachel; Hunt, Anna; Bowden, Victoria; Power, Sharon; Stanley, Thorsten; Crane, Julian; Ingham, Tristram; Weatherall, Mark; Mitchell, Edwin A.; Beasley, Richard

doi:10.1111/cea.12433

Cited by 11 publications

(7 citation statements)

References 40 publications

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“… 59 Focussed pharmacovigilance may be needed to further unveil the complex, potentially causal association between paracetamol exposure and subsequent increase risk to develop atopy. 60 …”

Section: General Discussion and New Aspects Of An Old Drugmentioning

confidence: 99%

Clinical Pharmacology of Paracetamol in Neonates: A Review

Pacifici

Allegaert

2015

Current Therapeutic Research

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Paracetamol is commonly used to control mild-to-moderate pain or to reduce opioid exposure as part of multimodal analgesia, and is the only compound recommended to treat fever in neonates.Paracetamol clearance is lower in neonates than in children and adults. After metabolic conversion, paracetamol is subsequently eliminated by the renal route. The main metabolic conversions are conjugation with glucuronic acid and with sulphate. In the urine of neonates sulphated paracetamol concentration is higher than the glucuronidated paracetamol level, suggesting that sulfation prevails over glucuronidation in neonates. A loading dose of 20 mg/kg followed by 10 mg/kg every 6 hours of intravenous paracetamol is suggested to achieve a compartment concentration of 11 mg/L in late preterm and term neonates. Aiming for the same target concentration, oral doses are similar with rectal administration of 25 to 30 mg/kg/d in preterm neonates of 30 weeks’ gestation, 45 mg/kg/d in preterm infants of 34 weeks’ gestation, and 60 mg/kg/d in term neonates are suggested. The above-mentioned paracetamol doses for these indications (pain, fever) are well tolerated in neonates, but do not result in a significant increase in liver enzymes, and do not affect blood pressure and have limited effects on heart rate. In contrast, the higher doses suggested in extreme preterm neonates to induce closure of the patent ductus arteriosus have not yet been sufficiently evaluated regarding efficacy or safety. Moreover, focussed pharmacovigilance to explore the potential causal association between paracetamol exposure during perinatal life and infancy and subsequent atopy is warranted.

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“… 59 Focussed pharmacovigilance may be needed to further unveil the complex, potentially causal association between paracetamol exposure and subsequent increase risk to develop atopy. 60 …”

Section: General Discussion and New Aspects Of An Old Drugmentioning

confidence: 99%

Clinical Pharmacology of Paracetamol in Neonates: A Review

Pacifici

Allegaert

2015

Current Therapeutic Research

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“…The feasibility of an acetaminophen withdrawal study was previously examined for the purpose of evaluating the connection between acetaminophen and asthma. 186 However, that feasibility study involved only 120 infants admitted to hospital after birth, at a time when some acetaminophen exposure may have already happened (e.g. during circumcision).…”

Section: Conducting An “Acetaminophen Withdrawal Study”: Practical Comentioning

confidence: 99%

The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism

et al. 2017

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The wide range of factors associated with the induction of autism is invariably linked with either inflammation or oxidative stress, and sometimes both. The use of acetaminophen in babies and young children may be much more strongly associated with autism than its use during pregnancy, perhaps because of well-known deficiencies in the metabolic breakdown of pharmaceuticals during early development. Thus, one explanation for the increased prevalence of autism is that increased exposure to acetaminophen, exacerbated by inflammation and oxidative stress, is neurotoxic in babies and small children. This view mandates extreme urgency in probing the long-term effects of acetaminophen use in babies and the possibility that many cases of infantile autism may actually be induced by acetaminophen exposure shortly after birth.

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“…Paracetamol in particular has been hypothesized to increase risk of asthma when used during early life, perhaps by depleting glutathione levels and thereby rendering the host airway vulnerable to oxidant‐induced inflammation. An association between paracetamol and asthma has been reported in observational studies including the ISAAC survey and an interesting pilot randomized controlled trial showed that it is possible to randomize infants aged 6–24 months to receive paracetamol more or less frequently, with parents’ preferred alternative treatment for randomization being ibuprofen. These encouraging findings should now allow a definitive randomized controlled trial to be designed, which can confirm or refute the paracetamol/asthma hypothesis.…”

Section: Clinical Allergymentioning

confidence: 95%

Developments in the field of clinical allergy in 2015 through the eyes of Clinical and Experimental Allergy

Roberts

Boyle

Bryce

et al. 2016

Clin Experimental Allergy

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SummaryIn the second of two papers, we describe developments in the field of clinical allergy as documented by Clinical and Experimental Allergy in 2015. Epidemiology, clinical allergy, asthma and rhinitis are all covered.In this second of two reviews, we discuss the new findings in the field of allergy in 2015 focusing on clinical aspects. These highlight the contribution published in Clinical and Experimental Allergy. We focus on epidemiology, clinical allergy, asthma and rhinitis. Epidemiology GeneralThe research field of allergy-related diseases is complex since we often lack firm data on exposure, and outcome is not easy to estimate as diagnosis is often more subjective compared to other disease areas. Additionally we lack high-quality registries. Such registries are based on a doctor's willingness to enter patient data. Such registers give us a good description of entered patients although we do not know what data are excluded. However, the situation is improving with i-technology. In some EU countries, there are now inpatient, outpatient and national registers including registers for twins. However, a lot of information for epidemiological research in the field of allergy related diseases is still based on questionnaire data, where the quality of the collected information is not always known.

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Randomized controlled trial of asthma risk with paracetamol use in infancy – a feasibility study

Abstract: Although separation in paracetamol dosing is likely to be achieved with a liberal vs. restricted paracetamol regime, ibuprofen is the preferred comparator treatment in the proposed RCT of paracetamol use and risk of asthma in childhood.

Cited by 11 publications

References 40 publications

Clinical Pharmacology of Paracetamol in Neonates: A Review

Clinical Pharmacology of Paracetamol in Neonates: A Review

The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism

Developments in the field of clinical allergy in 2015 through the eyes of Clinical and Experimental Allergy

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