Maternal Gestational Smoking, Diabetes, Alcohol Drinking, Pre-Pregnancy Obesity and the Risk of Cryptorchidism: A Systematic Review and Meta-Analysis of Observational Studies

Abstract

BackgroundMaternal gestational smoking, diabetes, alcohol drinking, and pre-pregnancy obesity are thought to increase the risk of cryptorchidism in newborn males, but the evidence is inconsistent.MethodWe conducted a systematic review and meta-analysis of studies on the association between maternal gestational smoking, diabetes, alcohol drinking, and pre-pregnancy obesity and the risk of cryptorchidism. Articles were retrieved by searching PubMed and ScienceDirect, and the meta-analysis was conducted using Stata/SE 12.0 software. Sensitivity analysis was used to evaluate the influence of confounding variables.ResultsWe selected 32 articles, including 12 case—control, five nested case—control, and 15 cohort studies. The meta-analysis showed that maternal smoking (OR = 1.17, 95% CI: 1.11–1.23) or diabetes (OR = 1.21, 95%CI: 1.00–1.46) during pregnancy were associated with increased risk of cryptorchidism. Overall, the association between maternal alcohol drinking (OR = 0.97, 95% CI: 0.87–1.07), pre-pregnancy body mass index (OR = 1.02, 95% CI: 0.95–1.09) and risk of cryptorchidism were not statistically significant. Additional analysis showed reduced risk (OR = 0.89, 95% CI: 0.82–0.96) of cryptorchidism with moderate alcohol drinking during pregnancy. No dose—response relationship was observed for increments in body mass index in the risk of cryptorchidism. Sensitivity analysis revealed an unstable result for the association between maternal diabetes, alcohol drinking and cryptorchidism. Moderate heterogeneity was detected in studies of the effect of maternal alcohol drinking and diabetes. No publication bias was detected.ConclusionMaternal gestational smoking, but not maternal pre-pregnancy overweight or obesity, was associated with increased cryptorchidism risk in the offspring. Moderate alcohol drinking may reduce the risk of cryptorchidism while gestational diabetes may be a risk factor, but further studies are needed to verify this.

A retrospective population-based cohort study to evaluate the impact of an older sibling with undescended testis and hypospadias on the known maternal and fetal risk factors for undescended testis and hypospadias in Ontario, Canada, 1997–2007

“…Associated HYP was identified as an independent risk factor in the study by Biggs et al and in this study. Zhang et al in a systematic review suggested that maternal gestational diabetes may be a risk factor for UDT (pooled OR, 1.21; 95% CI, 1.0e1.5), unlike shown in this study, but the authors acknowledge the heterogeneity of studies included in their analysis [29].…”

Risk factors for cryptorchidism

“…9446589758092824076104105 Two separate meta-analyses have confirmed this association, 100,106 with the most recent including information from 25 studies and observing a 17% increased risk of cryptorchidism among boys born to mothers who smoked tobacco during pregnancy (pooled OR: 1.17, 95% CI: 1.11–1.23). 100 To put this into perspective, the association between maternal smoking and the development of cryptorchidism is comparable to that observed for smoking and cleft lip defect (OR range 1.2–1.6). 101 …”

“…A recent meta-analysis reported a null association (adjusted pooled odds ratio: 0.97, 95% CI 0.87–1.07). 100 …”

Maternal Overweight and Obesity and Genital Anomalies in Male Offspring: A Population‐Based Swedish Cohort Study

“…There are only few studies focusing on associations between maternal overweight and obesity and these specific genital anomalies in boys, and results remain conflicting. A recent meta‐analysis showed that maternal pre‐pregnancy overweight was not associated with the occurrence of cryptorchidism in offspring, and results from the original observational studies pointed in different directions. The current literature on hypospadias is also conflicting: some studies demonstrated no association while others reported an increased risk of hypospadias in sons of overweight women .…”