Paracetamol as analgesic and risk of bronchopulmonary dysplasia in extremely preterm infants: a secondary analysis of the BeNeDuctus trial.

BACKGROUND

Paracetamol is increasingly used as analgesic and to treat patent ductus arteriosus (PDA) in preterm infants, though preclinical data suggest it may potentially harm the developing lung. The BeNeDuctus trial compared expectant PDA management versus ibuprofen in infants with gestational age <28 weeks, allowing paracetamol for analgesia. In this secondary analysis of the trial, we investigated the potential association between paracetamol and the risk of bronchopulmonary dysplasia (BPD).

METHODS

The 273 infants enrolled in the BeNeDuctus were classified into four subgroups based on their exposure to paracetamol (n = 30), ibuprofen (n = 87), paracetamol and ibuprofen (n = 49), or no exposure (control, n = 107). Multivariable logistic regression was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Confounders were selected based on a Directed Acyclic Graph.

RESULTS

Compared with the control group, exposure to paracetamol alone (aOR 3.22, CI 1.05-9.89), ibuprofen alone (aOR 2.90, CI 1.40-6.03), or paracetamol and ibuprofen (aOR 3.88, CI 1.57-9.57) was associated with an increased odds of moderate-to-severe BPD.

CONCLUSION

Our data suggest that paracetamol, used for pain management, increased the risk of moderate-to-severe BPD. This finding supports the calls for a thorough evaluation of the safety of paracetamol on the developing lungs of extremely preterm infants.

IMPACT: Paracetamol is gaining interest as pharmacological treatment for patent ductus arteriosus (PDA) in extremely preterm infants. Safety is assumed, based on data from studies evaluating the effects of paracetamol exposure on liver function, although recently concerns on lung development are emerging. This study supports the urgent need for additional research on the safety of paracetamol as treatment option for PDA, but also for other indications in extremely preterm infants, with regard to lung development.