Abstract

BackgroundChronic respiratory diseases and use of antiasthmatic medication during pregnancy may both play a role in the etiology of congenital anorectal malformations (ARM). However, it is unclear, whether the medication use or the underlying condition would be responsible. Therefore, our aim was to unravel the role of maternal chronic respiratory diseases from that of antiasthmatic medication in the etiology of ARM.MethodsWe obtained 412 ARM patients and 2,137 population‐based controls from the Dutch AGORA data‐ and biobank. We used maternal questionnaires and follow‐up telephone interviews to obtain information on chronic respiratory diseases, antiasthmatic medication use, and potential confounders. Multivariable logistic regression analyses were performed to estimate odds ratios (ORs) with 95% confidence intervals (95% CI).RESULTSWe observed higher risk estimates among women with chronic respiratory diseases with and without medication use (1.4 [0.8–2.7] and 2.0 [0.8–5.0]), both in comparison to women without a chronic respiratory disease and without medication use. Furthermore, increased ORs of ARM were found for women using rescue medication (2.4 [0.8–7.3]) or a combination of maintenance and rescue medication (2.5 [0.9–6.7]). In addition, increased risk estimates were observed for women having nonallergic triggers (2.5 [1.0–6.3]) or experiencing exacerbations during the periconceptional period (3.5 [1.4–8.6]).CONCLUSIONSAlthough the 95% CIs of most associations include the null value, the risk estimates all point towards an association between uncontrolled chronic respiratory disease, instead of antiasthmatic medication use, with ARM in offspring. Further in‐depth studies towards mechanisms of this newly identified risk factor are warranted.

Highlights

  • Anorectal malformations (ARM) are one of the most frequently observed birth defects of the digestive system and are characterized by a disturbed embryonic hindgut development during weeks 4–8 after conception

  • We considered year of birth, maternal age at delivery, maternal education, primiparity, previous miscarriage, assisted reproductive techniques (ART), recommended use of folic acid supplements, periconceptional smoking, and pre-pregnancy body mass index (BMI) as potential confounders in the analyses, as these factors were previously identified as risk factors for anorectal malformations (ARM) or were found to be associated with ARM in this study

  • We studied the chronic respiratory diseases and antiasthmatic medication use more in detail

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Summary

Introduction

Anorectal malformations (ARM) are one of the most frequently observed birth defects of the digestive system and are characterized by a disturbed embryonic hindgut development during weeks 4–8 after conception. Several nongenetic factors have been associated with ARM, such as assisted reproductive techniques (ART), twin pregnancies, maternal overweight, preexisting diabetes, and previous miscarriage (van de Putte et al, 2017; Wijers, van Rooij, et al, 2014). As these factors do not explain ARM in the majority of patients (Wijers, van Rooij, et al, 2014), the knowledge about the etiology of ARM is still far from complete. Chronic respiratory diseases and use of antiasthmatic medication during pregnancy may both play a role in the etiology of congenital anorectal malformations (ARM). It is unclear, whether the medication use or the underlying condition would be responsible. Further in-depth studies towards mechanisms of this newly identified risk factor are warranted

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