Risk Of Hypospadias In Offspring Research Articles

Maternal exposure to sulfur dioxide before and after conception and the risk of hypospadias in offspring

As far as we know, there have been no studies exploring the association between maternal sulfur dioxide (SO2 ) exposure and the risk of hypospadias in offspring. We aimed to evaluate this association during the 3 months before conception and the first trimester. A population-based case-control study was conducted in male infants, consisting of 348 cases of hypospadias and 4023 controls. Maternal exposure to SO2 , particulate matter with aerodynamic diameters ≤10 μm (PM10 ), and nitrogen dioxide (NO2 ) was assessed by averaging the concentrations recorded at all stations in the mother's city of residence. Air pollutants were tested for multicollinearity using variance inflation factor analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multivariable logistic regression models. SO2 exposure during the 3 months before conception was significantly associated with the risk of hypospadias (highest tertile: OR=7.40, 95% CI:3.54-15.62). When focusing on shorter exposure windows, similar associations were observed for SO2 exposure in the first and second month before and the first month after conception. In conclusion, maternal exposure to SO2 during the 3 months before and the first and second months after conception may increase the risk of hypospadias in offspring.

Association between prenatal air pollution exposure and risk of hypospadias in offspring: a systematic review and meta-analysis of observational studies.

Background: The findings of associations between prenatal air pollution exposure and hypospadias risk in offspring are inconsistent. No systematic review or meta-analysis has yet summarized the present knowledge on the aforementioned topic.Methods: Relevant manuscripts were identified by searching PubMed and Web of Science databases through January 31, 2020. Summary odds ratios (ORs) with 95% confidence intervals (CIs) in meta-analyses were estimated based on a random effects model. Publication bias was evaluated by funnel plots, Begg’s test, and Egger’s test.Results: The search identified 3,032 relevant studies. Sixteen studies cumulatively involving 21,701 hypospadias cases and 1,465,364 participants were included. All of these studies were classified as having a low risk of bias. We classified pollutants as nitrogen oxides, particulate matter (PM), ozone, and other exposures. The exposure window to pollutants varied from three months before conception to seven days after delivery. In the meta-analyses, only PM2.5 exposure in the first trimester was related to increased risk of hypospadias (per 10 μg/m3 OR = 1.34; 95% CI: 1.06–1.68).Conclusion: We found evidence for an effect of PM2.5 exposure on hypospadias risk. Improvements in the areas of study design, exposure assessment, and specific exposure window are needed to advance this field.

Association between prenatal exposure to ambient particulate matter and risk of hypospadias in offspring: A systematic review and meta-analysis

BackgroundEpidemiological studies on whether prenatal exposure to PM2.5, PM2.5-10, and PM10 increases the risk of hypospadias are limited and the results are inconsistent. ObjectivesWe conducted this systematic review and meta-analysis to evaluate these associations. MethodsRelevant studies were identified by searching the PubMed and Embase databases up to the end of February 2020. Observational studies that investigated the relationships between prenatal exposure to PM10, PM2.5, and PM2.5-10 and the risk of hypospadias in offspring were eligible for the review. The risk of bias was evaluated using the Newcastle-Ottawa scale. Random-effects models were used to estimate pooled relative risks (RRs) and 95% confidence intervals (CIs) for the associations. ResultsNine studies (two cohort and seven case-control studies) with a total of 2806 hypospadias cases were included. Eight studies were at low risk of bias and only one study was at high risk of bias. Five studies reported the association between per interquartile range increase in PM2.5 exposure within the first trimester and the risk of hypospadias. The pooled RR was 1.17 (95% CI: 1.00, 1.36). Two studies reported the per interquartile range increase in PM2.5 exposure during 1 month before pregnancy associated with the risk of hypospadias, with a pooled RR of 1.25 (95% CI: 1.03, 1.51). No association was observed between PM2.5-10 and PM10 exposure during pregnancy and the risk of hypospadias in offspring. ConclusionThis study suggested a modest association between prenatal PM2.5 exposure during 1 month before pregnancy or within the first trimester and the risk of hypospadias in offspring. Further large-scale cohort studies are required to verify this association.

Risk of Hypospadias in Offspring of Women Using Loratadine during Pregnancy

Loratadine, a second-generation antihistamine, is commonly used to treat seasonal allergies. Some studies have suggested that use of loratadine by pregnant women increases the risk of hypospadias in male offspring. This meta-analysis was designed to assess the strength of the association between loratadine and hypospadias. To locate pertinent articles published in any language from January 1989 until August 2007, we searched electronic databases (MEDLINE, OVID, EMBASE, SCOPUS, TOXLINE Special, ReproTox, TERIS, CINAHL and others), conference proceedings and bibliographies. Studies were eligible for this analysis if they were cohort, case-control or case series studies that reported the incidence of hypospadias in the offspring of women who were or were not exposed to loratadine during pregnancy. Two authors independently extracted information on study design, participant characteristics, measures of outcome, control for potential confounding factors and risk estimates using a standardized data collection form. The Newcastle-Ottawa Scale was then used to assess the quality of each study. We used a random-effects meta-analysis model to combine the risk data. In 1402 potentially relevant titles, we found three case-control studies and seven cohort studies that reported the incidence of hypospadias or other congenital malformations in offspring of women who did or did not use loratadine during pregnancy. Together the studies in our meta-analysis provided information about 453 053 male births in Brazil, Canada, Denmark, Israel, Italy, Sweden, the UK and the US.Of 2694 male infants born to women using loratadine, 39 (1.4%) had hypospadias. Of 450 413 male infants born to women not using loratadine, 4231 (0.9%) had hypospadias. Women who used loratadine during pregnancy were not significantly more likely to have a son with hypospadias (unadjusted odds ratio [OR] 1.27, 95% CI 0.73, 2.23; adjusted OR 1.28, 95% CI 0.69, 2.39). The results of our systematic review and meta-analysis of controlled observational studies indicate that the use of loratadine during pregnancy does not significantly increase the risk of hypospadias in male offspring.

Maternal use of Loratadine during pregnancy and risk of hypospadias in offspring

To examine the risk of hypospadias after exposure to loratadine and other antihistamines during pregnancy, we conducted a population-based case-control study in four Danish counties, which account for 30% of the Danish population (approximately 1.6 M). We obtained data on maternal use of antihistamines from prescription databases, and data on birth outcomes from the Danish Medical Birth Registry (MBR) and the Hospital Discharge Registry (HDR). A total of 65,383 male births with a full prescription history of the mother in the study period from 1989-2002 were available for analysis. Within this cohort, we identified cases with a diagnosis of hypospadias, and 10 selected controls per case without such a diagnosis (matched on birth month, gender and year of birth). We identified 227 cases of hypospadias recorded in the HDR within six months postpartum and 2270 controls. One case (0.4%) and eight (0.4%) controls were exposed to loratadine in the first trimester and up to 30 days before the time of conception. The adjusted odds ratio (OR) for hypospadias among users of loratadine relative to non-users was 1.4 (95% CI: 0.2-11.2) and the corresponding OR for other antihistamines was 1.9 (95% CI: 0.7-5.7). In this study, maternal exposure to loratadine did not appear to be associated with an increased risk of hypospadias when compared with other antihistamines, although it should be noted that the statistical precision of the risk estimates might be limited.

Abnormal sperm morphology and function in the fathers of hypospadiacs

A lower motility of spermatozoa and a higher incidence of abnormal sperm morphology were found in 25 fathers of hypospadiacs compared with those of 50 fathers who produced children who were not hypospadiacs. Subfertility of fathers may result in a higher risk of hypospadias in offspring and as subfertile males now represent a higher proportion among fathers, owing to the improved efficacy of infertility treatment, this may explain the increased occurrence of hypospadias. Our relaxed-selection hypothesis, which states that there is a redistribution in the number of children born to fertile and infertile (subfertile) couples, may account for the increasing number of other defects and cancers of male genitalia observed today and the fall in sperm counts.