Use of prescription paracetamol during pregnancy and risk of asthma in children: a population-based Danish cohort study

Abstract

PurposeUse of paracetamol during pregnancy may increase the risk of asthma in offspring. The association between prenatal exposure to maternal use of paracetamol and risk of asthma was investigated.MethodsA cohort study of 197,060 singletons born in northern Denmark in 1996–2008 was conducted, with follow-up until the end of 2009. Maternal paracetamol use during pregnancy was defined as a redeemed prescription. Asthma in offspring was defined as at least two prescriptions of both a β-agonist and an inhaled glucocorticoid and/or a hospital diagnosis of asthma during follow-up. Absolute risk of asthma in offspring was estimated using the Kaplan–Meier method and incidence rate ratios adjusted for known risk factors were estimated using Cox proportional-hazards regression.ResultsOverall, 976 (0.5%) children were exposed prenatally to maternal use of prescription paracetamol. During follow-up, 24,506 (12.4%) children developed asthma. Absolute risk of asthma was 7.5% after 2 years and 14.4% after 10 years among the unexposed children. Corresponding risks were 12.7% and 21.6% among the exposed children. The adjusted incidence rate ratio was 1.35 (95% confidence interval: 1.17–1.57) for exposure in any trimester of pregnancy. A similar association was present for paracetamol exposure in each of the trimesters and for maternal use of prescription nonsteroidal anti-inflammatory drugs. Furthermore, maternal prescription use in the year following the relevant delivery also showed similar associations.ConclusionA robust association was found between prenatal exposure to maternal use of prescription paracetamol and the risk of asthma; however, noncausal explanations could not be ruled out for such association.

Paracetamol exposure in pregnancy and early childhood and development of childhood asthma: a systematic review and meta-analysis

“…Five cohort studies,23 32–35 that measured wheeze outcomes before the age of 5 years, two cohort studies that measured paracetamol exposure during adulthood,36 37 and three RCTs,38–40 that did not measure incident asthma were subsequently excluded. Of the remaining 11 studies (representing 10 cohorts) included in the meta-analysis, all were observational cohort studies, five measured paracetamol exposure during pregnancy,13 41–44 one measured exposure during both pregnancy and infancy,14 and five measured exposure during infancy15 30 45–47 (table 1). The age at which outcome of asthma was measured ranged from 5 to 10 years.…”

“…A weak association between paracetamol exposure during the third trimester of pregnancy and childhood asthma was shown by two studies (pooled OR=1.17, 95% CI 1.04 to 1.31, figure 2), while the three other studies that examined paracetamol exposure during the second and third trimester showed a stronger association (pooled OR=1.49, 95% CI 1.37 to 1.63, figure 2). There was significant heterogeneity among the three studies that assessed associations with paracetamol use through the entire pregnancy (Andersen et al ,13 OR=1.65, 95% CI 1.17 to 2.32; Rebordosa et al ,43 OR=1.22, 95% CI 1.11 to 1.34; Kang et al ,42 OR=0.74, 95% CI 0.5 to 1.09; I 2 =89%), so results were not pooled (figure 3). …”

“…The review by Etminan et al 51 combined the findings of the cohort studies with cross sectional studies, with the latter dominating the overall findings, whereas in this review we only included cohort studies. In addition, our review also included three studies13 41 45 that had not been published at the time of previous reviews by Etminan et al 51 and Eyers et al ,50 or were missed30 due to a lack of a systematic review by Garcia-Marcos et al 49. Furthermore, we focused on asthma measured after the age of 5 years rather than wheeze symptoms.…”

Maternal drug use during pregnancy and asthma risk among children

“…Preterm birth has been associated with increased childhood morbidity, among other things like childhood asthma . Some studies have found an association between maternal use of paracetamol (acetaminophen) with an increased risk of asthma , and one study described a link between maternal use of gastric acid–suppressive drugs and childhood asthma.…”

Prenatal exposure to H2blockers and to proton pump inhibitors and asthma development in offspring

“…Andersen et al showed that exposure to paracetamol within 30 days prior to the first menstrual period increased the risk of childhood asthma. This association was also found for 1 year after birth, and the authors could not rule out the noncausal explanations of their findings …”