Parental Subfertility, Fertility Treatment, and the Risk of Congenital Anorectal Malformations

Wijers, Charlotte H. W.; Rooij, Iris A. L. M. van; Rassouli, Roxana; Wijnen, Marc H. W. A.; Broens, Paul M. A.; Sloots, Cornelius E. J.; Brunner, Han G.; Blaauw, Ivo de; Roeleveld, Nel

doi:10.1097/ede.0000000000000226

Cited by 15 publications

(15 citation statements)

References 16 publications

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“…Contrary to the latest studies, we did not find an increased risk of ARM following sterility treatment, hormone intake or in-vitro fertilization. 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.…”

Section: Evaluation Of Prenatal Risk Factors and Rising Incidencesupporting

confidence: 91%

“…As in previous studies, we found significantly more frequent problems during pregnancy in ARM mothers, such as infections of the urogenital tract and vagina as well as symptoms of gestosis like nausea and vomiting. 21 In contrast, Wijers et al 13 described an association of fever in the first trimester of pregnancy with ARM, which we could not confirm. It remains to be verified whether taking antisickness medication or treating vaginal infections early in the pregnancy influence ARM occurrence or not.…”

Section: Abnormal Pregnancy Historycontrasting

confidence: 74%

“…19 Other drugs in our study and those of others seem to have little if any association with ARM, although the evidence is still limited. 13 Nicotine consumption or increased exposure to nicotine during the first trimester of pregnancy is a known risk factor for ARM and our data can corroborate these findings, 20 but we did not find an increased risk for ARM with alcohol intake or illegal drug abuse.…”

Section: Evaluation Of Prenatal Risk Factors and Rising Incidencesupporting

confidence: 73%

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

Kapapa

Becker

Serra

2021

Pediatrics & Neonatology

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Background: Incidences of anorectal malformations (ARM) occur in 1 of 2000e5000 live births and up to 64% have associated malformations (ARMa). The aim of the study was to evaluate possible prenatal risk factors for ARM in a tertiary hospital. Methods: A caseecontrol design was used to compare risk factors in ARM (n Z 44) to a control group (CG; n Z 26). We used modified prenatal questionnaires, analyzed mothers' prenatal records and participants completed a structured interview. Endpoints were medical history, drug consumption, occupational risk factors, and time point of diagnosis, associated malformations and sensitivity of radiological imaging. Results: Our results showed that ARM couples had a significantly higher age difference (p Z 0.028) compared to CG. ARM mothers had more abnormalities during pregnancy (p Z 0.002), more positive vaginal smears of group B streptococci (p Z 0.024), urogenital infections (p Z 0.005), gestosis (p Z 0.03), emesis (p Z 0.025) and higher numbers of chronic diseases (p Z 0.018). ARM mothers took less medication during pregnancy (p Z 0.013) than CG mothers including folic acid (p Z 0.041); their intake of iodine tablets was significantly higher (p Z 0.035) and they continued smoking for longer (p Z 0.036) than CG mothers, and they had more stillbirths (p Z 0.035). In using illegal drug and alcohol use, the groups did not show significant differences. ARMa was present in 68.1% (n Z 30), of which 45.5% were of urogenital origin (n Z 20). ARM diagnosis was made on the first day of life in 72.7% (n Z 32), while diagnosis was delayed in 12 patients (27.3%). Conclusion: A combination of different risk factors seem to be associated with the development of ARM, which takes place at an early stage (<7th week) of pregnancy. Therefore, risk factors influencing fetal development must be critically considered. We advocate an

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Section: Evaluation Of Prenatal Risk Factors and Rising Incidencesupporting

confidence: 91%

Section: Abnormal Pregnancy Historycontrasting

confidence: 74%

Section: Evaluation Of Prenatal Risk Factors and Rising Incidencesupporting

confidence: 73%

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

Kapapa

Becker

Serra

2021

Pediatrics & Neonatology

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“…In recent years, our etiologic studies have been focused on anorectal malformations, the VACTERL association, and CAKUT. We found several nongenetic factors that were associated with anorectal malformations, but no association was observed with the use of folic acid supplements (van Rooij et al, ; Wijers et al, ). In a small study on patients affected with both an anorectal malformation and hypospadias, we identified a potentially interesting nonsynonymous variant in the DKK1 gene (van de Putte et al, ).…”

Section: Resultsmentioning

confidence: 79%

AGORA, a data‐ and biobank for birth defects and childhood cancer

Rooij¹,

Zanden²,

Bongers

et al. 2016

Birth Defects Research

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“…In addition, a relationship between a single umbilical artery and ARM is suspected [ 31 ]. Assisted reproductive techniques also pose a strongly increased risk for ARM [ 32 – 38 ], but it remains unclear whether the procedure itself or underlying parental infertility cause the defects. Besides these non-genetic factors, the influence of maternal drug intake before and during pregnancy, such as vitamin A overdose [ 39 ] or deficiency [ 40 ], multivitamin [ 27 ], folic acid [ 27 , 41 ], anti-asthmatic drugs [ 42 ] or benzodiazepine lorazepam [ 43 ], is subject to ongoing debate.…”

Section: Introductionmentioning

confidence: 99%

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

Zwink

Jenetzky

2018

Orphanet J Rare Dis

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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.

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Parental Subfertility, Fertility Treatment, and the Risk of Congenital Anorectal Malformations

Abstract: We found evidence of a role of ICSI and IVF treatments in the etiology of anorectal malformations. However, subfertility without treatment increased only the risk of anorectal malformations with additional congenital malformations.

Cited by 15 publications

References 16 publications

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

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

AGORA, a data‐ and biobank for birth defects and childhood cancer

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

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