Intrauterine Exposure To Acetaminophen (paracetamol) And Childhood Asthma: Systematic Review And Meta-Analysis

Background: Past studies have reported conflicting results regarding the association between acetaminophen use during pregnancy and the risk of developing childhood asthma. Objectives: To perform an updated review on past studies investigating the association between prenatal acetaminophen use and the risk of developing asthma within the first ten years of life. Methods: A systematic review and meta-analysis was conducted using PubMed search (1950-December 1, 2011) to identify studies that investigated the association between intrauterine exposure to acetaminophen and childhood asthma. Inclusion criteria consisted of a study design restricted to prospective cohort studies, primary exposure of acetaminophen intake during pregnancy, and primary outcome of physician-diagnosed asthma or a combination of two of the following indicators of asthma (use of asthma medication, hospitalization due to asthmatic symptoms, wheezing, and ER visits due to wheezing). Study quality was assessed and data was extracted by one reviewer. An inverse variance fixed-effects model was used, and adjusted odds ratio was calculated to compare effect sizes of studies. Results: The review comprised of six studies: two studies assessed physician-diagnosed asthma among children under the age of 2 years and four studies ascertained asthma outcome between the ages 2 and 10 years. The overall pooled estimate calculated from all six studies was 1.12 (95%CI: 1.03, 1.22). Children whose asthma status was recorded before the age of 2 had an overall pooled aOR of 1.18 [95%CI:1.13,1.23] while children between the ages of 2 and 10 years had a pooled aOR of 1.13[95%CI:1.01, 1.26]. For studies that did a follow-up among children under the age of 2 years, subgroup analyses of acetaminophen exposure during different stages of pregnancy displayed consistent statistically significant associations between prenatal acetaminophen use and childhood asthma. The subgroup analysis of different stages of pregnancy for studies that reported asthma outcome among children older than 2 years of age showed that risk of childhood asthma was only associated with intrauterine exposure to acetaminophen during the later stages of pregnancy (aOR[95%CI]: 1.23[1.08, 1.42]). There was not enough information to verify a dose-response relationship. Conclusions: The findings support a modest association of exposure to prenatal acetaminophen use with childhood asthma development. By reviewing only prospective studies, we established temporality, thus further strengthening our hypothesis that acetaminophen use during pregnancy causes an increased risk of childhood asthma. Further studies need to be conducted to confirm this association, and specify the dose, frequency and trimester use of acetaminophen. (Word count 398