Parental risk factors and anorectal malformations: systematic review and meta-analysis

Abstract

BackgroundAnorectal malformations (ARM) are rare forms of congenital uro-rectal anomalies with largely unknown causes. Besides genetic factors, prenatal exposures of the parents to nicotine, alcohol, caffeine, illicit drugs, occupational hazards, overweight/obesity and diabetes mellitus are suspected as environmental risk factors.MethodsRelevant studies published until August 2010 were identified through systematic search in PubMed, EMBASE, ISI Web of Knowledge and the Cochrane Library databases. Furthermore, related and cross-referencing publications were reviewed. Pooled odds ratios (95% confidence intervals) were determined to quantify associations of maternal and paternal smoking, maternal alcohol consumption, underweight (body mass index [BMI] < 18.5), overweight (BMI 25-29.9), obesity (BMI ≥30) and maternal diabetes mellitus with ARM using meta-analyses.Results22 studies that reported on the association between prenatal environmental risk factors and infants born with ARM were included in this review. These were conducted in the United States of America (n = 12), Spain (n = 2), Sweden (n = 2), the Netherlands (n = 2), Japan (n = 1), France (n = 1), Germany (n = 1) and Hungary (n = 1). However, only few of these studies reported on the same risk factors. Studies were heterogeneous with respect to case numbers, control types and adjustment for covariates. Consistently increased risks were observed for paternal smoking and maternal overweight, obesity and diabetes, but not for maternal smoking and alcohol consumption. In meta-analyses, pooled odds ratios (95% confidence intervals) for paternal smoking, maternal overweight, obesity, pre-gestational and gestational diabetes were 1.53 (1.04-2.26), 1.25 (1.07-1.47), 1.64 (1.35-2.00), 4.51 (2.55-7.97) and 1.81 (1.23-2.65), respectively.ConclusionEvidence on risk factors for ARM from epidemiological studies is still very limited. Nevertheless, the few available studies indicate paternal smoking and maternal overweight, obesity and diabetes to be associated with increased risks. Further, ideally large-scale multicentre and register-based studies are needed to clarify the role of key risk factors for the development of ARM.

Comparison in the incidence of anorectal malformations between a first- and third-world referral center

“…The exact genetics, perhaps in combination with environmental facts, remain ill defined [19]. Environmental studies have implicated paternal cigarette smoking and exhaust fume exposure as well as maternal obesity and diabetes as possible risk factors [20][21][22]. In addition, maternal exposure to industrial cleaning agents, multivitamin use and first trimester pyrexia have been implicated, although some of these findings could not be replicated in follow-up studies [21,22].…”

Cigarette smoking significantly alters sperm DNA methylation patterns

“…M. Lee et al, 2009; Pang et al, 2003; Vine, 1996) suggesting smoke-induced genetic or epigenetic changes occur in sperm that are transmitted to offspring. Additionally, children of men who smoke are at increased risk for childhood cancers, asthma (Svanes et al, 2016) and birth defects including cleft palate, urethral stenosis, hydrocephalus (Savitz et al, 1991), congenital heart disease, cardiovascular anomalies (Cresci et al, 2011) anorectal malformations (Zwink et al, 2011), spina bifida (Zhang et al, 1992), and reduced kidney volume (Kooijman et al, 2015). …”

The Impact of Paternal and Maternal Smoking on Semen Quality of Adolescent Men

“…However, smoking has damaging effect on DNA [14]–[16], and the DNA of spermatozoa has been reported to be much more sensitive to damage than DNA of oocytes [17], [18]. Paternal smoking has been reported to cause DNA adducts in embryos [19] of the same type found in sperm of smoking men [20], DNA breaks in cord blood of the offspring [21], and also seems associated with; lower pregnancy rates at assisted reproduction [22], pregnancy loss [23], [24], malformations [25]–[30] and cancer [31]–[36] as well as with reduced birth weight [37] in the offspring. Further, DNA mutations in mice, caused by general air pollution is reported to be inherited with predominance through the paternal germ line [38].…”