A matched case control study with propensity score balancing examining the protective effect of paracetamol against parentally reported apnoea in infants

Background

Central apnoea occurs in infants and if not detected leads to death. Central apnoea is a prostaglandin E₂ (PGE2) mediated effect that is susceptible to pharmacologic manipulation in animal models. Paracetamol and ibuprofen are centrally and peripherally acting PGE2 inhibitors, respectively.

Aim

To determine if infants who had received paracetamol or ibuprofen are relatively protected from apnoea.

Methods

We performed a matched case control study using propensity score balancing to adjust for non-random drug assignment. We included infants from prospective studies of central apnoea and bronchiolitis. We matched on age, prematurity and fever to adjust for the infants’ underlying risk of apnoea. The primary outcome measure was odds of exposure to paracetamol or ibuprofen by apneic infants compared to their controls.

Results

Forty-two apneic and 729 non-apneic infants were identified. Infants with apnoea were younger than those without, median age 6.5 versus 12.2 weeks and were more likely to be premature. These differences were balanced using matching. Differences between those who did and did not receive paracetamol were satisfactorily balanced using the propensity score. Ibuprofen was used too infrequently to analyse it further. In the unadjusted analysis fewer apneic infants had had prior paracetamol use 5/42 (12%) versus 211/729 (29%) or prior ibuprofen use 1/42 (2%) versus 51/729 (7%). In the adjusted analysis paracetamol was protective against apnoea; OR 0.30 (95% CI 0.11, 0.78).

Conclusions

Prior paracetamol use was protective against apnoea in infants. We could not demonstrate an effect for ibuprofen.