Maternal drug use and the risk of anorectal malformations: systematic review and meta-analysis

Abstract

BackgroundOrigin of anorectal malformations (ARM) are considered multifactorial. Several genetic and non-genetic risk factors are discussed in literature. Maternal periconceptional medical drug use as possible risk factor, however, has not been reviewed systematically.MethodsStudies published between 1977 and April 2017 were reviewed through systematic search in PubMed, ISI Web of Knowledge and Scopus databases. Furthermore, related and cross-referencing publications were reviewed. Pooled odds ratios (95% confidence intervals) were determined to quantify associations of maternal periconceptional use of folic acid, multivitamins, anti-asthma medication (separated in any anti-asthma medication, inhaled corticosteroids and salbutamol), thyroid hormone supplements, psychiatric drugs (separated in antidepressants, any selective serotonin reuptake inhibitors [SSRI], sertraline, citalopram, fluoxetine, paroxetine, hypnotics and benzodiazepine) and aspirin with ARM using meta-analyses.ResultsThirty-seven studies that reported on the association between maternal periconceptional drug intake and infants born with ARM were included in this review. These were conducted in the United States of America (n = 14), Sweden (n = 6), Hungary (n = 5), Germany (n = 3), the Netherlands (n = 3), Denmark (n = 2), France (n = 2), Norway (n = 1) and the UK (n = 1). However, only few of these studies reported on the same risk factors. Studies were heterogeneous with respect to case numbers, period ingestion of medical drug use, control selection and adjustment for covariates. Consistently increased risks were observed for any anti-asthma medication, and hypnotics and benzodiazepine, but not for folic acid, multivitamins, inhaled corticosteroids, salbutamol, thyroid hormone supplements, antidepressants, any SSRI, sertraline, citalopram, fluoxetine, paroxetine and aspirin. In meta-analyses, pooled odds ratios (95% confidence intervals) for any anti-asthma medication, and hypnotics and benzodiazepine were 1.64 (1.22–2.21), and 2.43 (1.03–5.73), respectively.ConclusionEvidence on maternal drug use before conception and during pregnancy as risk factor for ARM from epidemiological studies is still very limited. Nevertheless, the few available studies indicate any anti-asthma medication, and hypnotics and benzodiazepine to be associated with increased risks. Further, ideally large-scale multicenter and register-based studies are needed to clarify the role of maternal drug intake for the development of ARM.

Risk factors for anorectal and associated malformations in German children: A 10-year analysis

“…8,13 Another significant risk factor was the presence of chronic maternal diseases, often from lung or gastrointestinal origin; however, we did not observe an increased ARM incidence in maternal diabetes mellitus like Correa et al, 14 In terms of medication intake at the onset of pregnancy, ARM mothers took the recommended folic acid prophylaxis significantly less than controls, which is in accordance with recent data showing folic acid depletion as a risk factor for ARM. 14 Our data do not corroborate asthma medications, 15 benzodiazepines or proton-pump inhibitors 16 intakes as being associated with the development of ARM. However our study is the first to report a significant correlation between increased intake of iodine tablets during pregnancy and ARM.…”

Comparison of Maternal Histories and Exposures in Children With Isolated Anorectal Malformation Versus Anorectal Malformation With Genitourinary Anomalies

“…While the etiology of ARM likely has a genetic component, factors such as environmental and parental also play a role [1][2][3][4]. The non-genetic associations that have been reported include maternal overweight/obesity, prematurity, small for gestational age, parental smoking, family history of ARM, fever during pregnancy, maternal occupational chemical exposures, use of assisted reproductive technology, multiple pregnancies, maternal diabetes, previous miscarriages, and maternal medication exposure during pregnancy including anti-asthma medications, hypnotics, and benzodiazepines [3,[5][6][7][8][9][10][11].…”

Association of Rs2435357 and Rs1800858 Polymorphisms in Ret Proto-Oncogene With Hirschsprung Disease: Systematic Review and Meta-Analysis

“…Furthermore, it is associated with other congenital malformations in 5%-32% of cases including gastrointestinal tract, by CNS anomalies, hearing impairment and congenital anomalies of the kidney and urinary tract 28 , 31 . Perinatal and environmental risk factors for HSCR, such as vitamin A, maternal age, obesity, parity, hypothyroidism during pregnancy, medical drug use have been sparsely studied; however, the results have not been consistent 15 , 22 , 43 .…”