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Published on: August 7, 2017
A matched case control study with propensity score balancing examining the protective effect of paracetamol against
Paul Walsh1, Lucas Shanholtzer, Mark Loewen
1Kern Medical Center, Bakersfield, CA, USA. yousentwhohome@gmail.com
Insights
Paracetamol use in infants may protect against central apnoea, a potentially fatal condition. This study found prior paracetamol use was protective, while ibuprofen showed no significant effect in preventing infant apnoea.
Area of Science:
- Neonatal medicine
- Pharmacology
- Pediatric critical care
Background:
- Central apnoea in infants can be fatal if undetected.
- Central apnoea is mediated by prostaglandin E(2) (PGE2) and can be pharmacologically manipulated.
- Paracetamol and ibuprofen are PGE2 inhibitors with central and peripheral actions, respectively.
Purpose of the Study:
- To investigate whether paracetamol or ibuprofen administration offers protection against central apnoea in infants.
- To determine the relative risk of apnoea in infants exposed to paracetamol or ibuprofen.
Main Methods:
- A matched case-control study design was employed.
- Propensity score balancing was used to adjust for non-random drug assignment and infant risk factors (age, prematurity, fever).
- The primary outcome was the odds of exposure to paracetamol or ibuprofen in apneic infants compared to controls.
Main Results:
- The study identified 42 apneic and 729 non-apneic infants.
- Infants with apnoea were younger and more likely to be premature, but these differences were balanced by matching.
- Adjusted analysis revealed that prior paracetamol use was protective against apnoea (OR 0.30, 95% CI 0.11, 0.78). Ibuprofen data was insufficient for analysis.
Conclusions:
- Prior use of paracetamol demonstrated a protective effect against central apnoea in infants.
- No significant protective effect of ibuprofen against infant apnoea was observed in this study.
Background:
Central apnoea occurs in infants and if not detected leads to death. Central apnoea is a prostaglandin E(2) (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.
