Paracetamol in pregnancy and the risk of wheezing in offspring: a systematic review and meta-analysis.

BACKGROUND There is evidence to suggest that the risk of asthma might be increased with exposure to paracetamol in the intrauterine environment, infancy, later childhood and adult life. OBJECTIVE To review the evidence from studies investigating the association between paracetamol use in pregnancy and childhood asthma. METHODS A systematic review and meta-analysis was undertaken of studies reporting the association between paracetamol use in pregnancy and subsequent asthma in childhood. The primary outcome variable was wheeze in the last 12 months. For tabulated raw data, not adjusted for confounders, random effects odds ratios (OR) were pooled by the inverse variance weighted method. RESULTS There were six studies identified that were included in the meta-analysis. The age of children studied ranged from 30 to 84 months. The pooled random effects OR 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). Features of the studies variably included an association with paracetamol use during all trimesters of pregnancy and an association with persistent asthma, severe asthma, and with atopy. CONCLUSION AND CLINICAL RELEVANCE The use of paracetamol during pregnancy is associated with an increased risk of childhood asthma. More research is urgently required to determine the impact of paracetamol during pregnancy on the risk of wheezing in offspring so that appropriate public health recommendations can be made.