PURPOSE OF THE STUDY.
To review the evidence from studies that investigated the association between paracetamol (acetaminophen) use in pregnancy and childhood asthma.
The meta-analysis included randomized controlled trials (RCTs) and observational studies published before October 2010 that compared women who used paracetamol during pregnancy with a placebo (RCT) or control (observational) group and evaluated the effect of paracetamol use during pregnancy on offspring using wheeze or asthma as a primary outcome. Only studies that presented raw data, or from which raw data were available from the authors on request, were used.
Articles were searched for in health research databases, in previous meta-analyses, and in the reference lists of relevant studies. Articles were examined, and raw data were extracted. If appropriate data were not included in the studies, the lead author was contacted in an attempt to obtain the raw data. The primary outcome variable was wheeze in the 12 months before the last interview, defined as “current wheeze.” For tabulated raw data, not adjusted for confounders, random-effects odds ratios were pooled by the inverse variance weighted method.
Six studies were included: 5 prospective cohort studies and 1 cross-sectional study. The age range of the children in these studies was 30 to 84 months. The pooled random-effects odds ratio for the risk of current wheeze in the children of women who were exposed to any paracetamol during any stage of pregnancy was 1.21 (95% confidence interval: 1.02–1.44).
The use of paracetamol during pregnancy is associated with an increased risk of childhood asthma.
The results of this meta-analysis confirm the association seen in individual studies over recent years between early paracetamol (acetaminophen) exposure and wheeze. In contrast with studies of the association between paracetamol use in early postnatal life and wheeze, studying paracetamol exposure in utero vastly decreases the potential for confounding by indication. The authors' decision to use the unadjusted odds ratio is well justified but leaves open the possibility that the effect seen might be a result of confounding to some extent. Given the almost ubiquitous use of paracetamol, and the recent increase in rates of atopy, untangling the true association between paracetamol and atopy is a topic that should, and undoubtedly will, have significant attention devoted to it in the coming years.
- Copyright © 2011 by the American Academy of Pediatrics