Risk Of Hypospadias Research Articles

The Association between Maternal Endocrine-Disrupting Chemical Exposure during Pregnancy and the Incidence of Male Urogenital Defects: A Systematic Review and Meta-Analysis.

The increasing incidence of hypospadias and cryptorchidism, coupled with the widespread presence of endocrine-disrupting chemicals (EDCs), has raised concerns about the potential impact of these environmental factors on male urogenital development. This systematic review and meta-analysis aims to evaluate the association between maternal exposure to various EDCs and the risk of hypospadias and cryptorchidism. We conducted a comprehensive search of PubMed, Scopus, Web of Science, and Cochrane databases from inception until May 2024. We included case-control and cohort studies that examined the association between maternal EDC exposure and hypospadias or cryptorchidism, reporting adjusted odds ratios (aOR) or crude odds ratios (cOR). Data were extracted and pooled using a random effects model, and heterogeneity was assessed using the Q test and I-square statistics. The risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS). A total of 48 studies were included in the systematic review, with 46 studies included in the meta-analysis. The pooled analysis revealed a significant association between maternal EDC exposure and an increased risk of hypospadias (aOR = 1.26, 95% CI: 1.18-1.35, p < 0.0001) and cryptorchidism (aOR = 1.37, 95% CI: 1.19-1.57, p < 0.001). Subgroup analyses showed that exposure to pesticides, phthalates, alkyl phenolic compounds (ALKs), and heavy metals significantly increased the risk of hypospadias. In contrast, polychlorinated biphenyls (PCBs) did not show a significant association. Significant associations were found with pesticide and PCB exposure for cryptorchidism, but not with phthalate, ALK, or heavy metal exposure. Maternal exposure to certain EDCs is associated with an increased risk of hypospadias and cryptorchidism in male children. These findings underscore the importance of addressing environmental and occupational exposures during pregnancy to mitigate potential risks. Further research is needed to elucidate the mechanisms by which EDCs affect urogenital development and to develop effective interventions to reduce exposure among vulnerable populations.

Association between maternal peri-conceptional exposures and risk of hypospadias and cryptorchidism in offspring

Objective: To investigate the relationship between maternal exposures to peri-conceptional risk factors and the risk of hypospadias and cryptorchidism in offspring. Methods: Pregnant women who delivered male newborns and participated in the China birth cohort study between February 2018 and December 2020 at the research center of Beijing Obstetrics and Gynecology Hospital, Capital Medical University were selected for the study. All were enrolled at 6-13+6 weeks of their gestation. Baseline risk factor information was collected by questionnaire survey. Information on the outcome of hypospadias and cryptorchidism was obtained by clinical examination at birth and ultrasonography. Logistic regression was used to analyze the Odds Ratio (OR) and 95% Confidence Interval (95%CI) of each factor with respect to the onset of the outcome. Results: A total of 15, 833 pregnant women with an average age of (31.81±3.84) years were included. Among their offsprings, 113 were diagnosed as hypospadias or cryptorchidism (42 hypospadias, 69 cryptorchidism, and 2 both hypospadias and crypterchidism), with an incidence of 7.14‰. The results of multivariate logistic regression analysis showed that mothers with pregnancy history of birth defects (OR=3.01, 95%CI: 1.09-8.35), with preconception Hepatitis B infection (OR=4.74, 95%CI: 1.10-20.42), fetal growth restriction (OR=4.02, 95%CI: 2.10-7.68), multivitamin use since preconception (OR=1.98, 95%CI: 1.12-3.52), and never cook and eat at home (OR=2.17, 95%CI: 1.23-3.82) were risk factors for hypospadias and cryptorchidism (all P<0.05). Conclusions: Obesity in early pregnancy, preconception Hepatitis B infection, pregnancy history of birth defects, fetal growth restriction, multivitamin use before pregnancy, and rarely cook and eat at home were associated with an increased risk of hypospadias or cryptorchidism in their offsprings.

Research progress on the association between prenatal exposure to air pollutants and hypospadias in the offspring

Recent epidemiological studies have increasingly found that pregnant women who are exposed to air pollutants (for example airborne particulate matter, nitrogen oxides, ozone, and sulfur dioxide) increase the risk of various birth defects in their offspring, such as congenital heart disease, neural tube defects, cleft lip and palate, and hypospadias. Hypospadias not only impairs the sexual function of infants but also causes major social and psychological problems during their growth period, therefore, the prevention and treatment of hypospadias infant carry substantial public health importance. However, the association between prenatal exposure to air pollution and hypospadias remains controversial. The study reviews the epidemiological research progress and potential biological mechanisms of prenatal maternal exposure to air pollutants such as particulate matter, nitrogen oxides, ozone, sulfur dioxide, and the risk of hypospadias in offspring. The study also summarizes the limitations of previous research and looks forward to future research directions, to provide scientific evidence for creating a healthy living environment for pregnant women, and reducing the risk of hypospadias in offspring.

A Potential Pathogenic SRD5A2 Mutation and rs632148, rs523349 and rs522638 Polymorphisms in Increasing the Risk of Syndromic Hypospadias in Indonesian Population

BACKGROUND: Hypospadias, a congenital birth defect in male, is the opening of the urethra located on the ventral side of the penis. Several mutations in SRD5A2 encoding steroid 5 alpha-reductase type 2 protein have been identified in hypospadias and polymorphisms in this gene have been known to be associated with an increased risk of hypospadias. In this study, several crucial molecular analyses of the SRD5A2 gene and the association of the identified variants to the risk of syndromic hypospadias in Indonesian population were conducted.METHODS: Thirty-two isolated and 29 syndromic hypospadias patients were enrolled in this study. DNA was isolated from whole blood for the amplification of all exons and exon-intron boundaries of SRD5A2 by polymerase chain reaction (PCR), followed by Sanger sequencing. In silico analysis was performed using PolyPhen-2, Sorting Intolerant from Tolerant (SIFT) and Align GVGD. Statistical analysis was performed using Chi-squared test.RESULTS: A novel missense mutation c.32T&gt;C/p.Leu11Pro was identified in one isolated hypospadias patient and the in silico analysis predicted the mutation to be pathogenic. Three polymorphisms were identified, two in the non-coding region (c.-62G&gt;C/rs632148 and c.281+15T&gt;C/rs522638) and one in exon-1 (c.265C&gt;G/p.Val89Leu/rs523349). Mutant alleles of these polymorphisms were significantly associated with syndromic hypospadias with odds ratios (OR) of 3.4, 3.13 and 2.54 respectively.CONCLUSION: This study suggests that SRD5A2 mutation is one of the causes of hypospadias in Indonesian population and rs632148, rs523349 and rs522638 polymorphisms are significantly associated with an increased risk of syndromic hypospadias.KEYWORDS: mutation, polymorphism, SRD5A2, syndromic hypospadias

Maternal PM2.5 exposure and hypospadias risk in Chinese offspring: Insights from a nationwide surveillance-based study

Research on the association between maternal PM2.5 exposure and hypospadias risk in male offspring, particularly in highly polluted areas, has been limited and inconsistent. This study leveraged data from China’s National Population-based Birth Defects Surveillance System spanning the years 2013 to 2019, and employed sophisticated machine learning models to estimate daily PM2.5 levels and other pollutants for mothers at a 1-km resolution and a 6-km buffer surrounding maternal residences. Multivariate logistic regression analyses were performed to evaluate the relationship between PM2.5 exposure and hypospadias risk. For sensitivity analyses, stratification analysis was conducted, and models for one-pollutant and two-pollutants, as well as distributed lag nonlinear models, were constructed. Of the 1194,431 boys studied, 1153 cases of hypospadias were identified. A 10 μg/m3 increase in maternal PM2.5 exposure during preconception and the first trimester was associated with an elevated risk of isolated hypospadias, with Odds Ratios (ORs) of 1.102 (95% CI: 1.023–1.188) and 1.089 (95% CI: 1.007–1.177) at the 1-km grid, and 1.122 (95% CI: 1.034–1.218) and 1.143 (95% CI: 1.048–1.246) within the 6-km buffer. Higher quartiles of PM2.5 exposure were associated with increased odds ratios compared to the lowest quartile. These findings highlight a significant association between PM2.5 exposure during the critical conception period and an elevated risk of isolated hypospadias in children, emphasizing the need for targeted interventions to reduce PM2.5 exposure among expectant mothers.

Temporal analysis of the prevalence of congenital hypospadias in the municipality of Gela

to evaluate the risk profile of hypospadias in Gela, an Italian National Priority Contaminated Site (NPCS) located in Sicily Region (Southern Italy), characterized by a significant excess of hypospadias in newborn residents compared to data from reference on regional, national, and international basis and, until 2014, by the presence of a petrochemical plant. geographical analyses were conducted by comparing the prevalence of the Gela municipality to prevalence found in Sicily, in a territorial area bordering Gela (ALG), and in the NPCSs of Milazzo and Priolo. The geographical comparisons were conducted for the period 2010-2020, the trend within the Gela NPCS was evaluated by comparing two subperiods (2010-2014 and 2015-2020). children up to 1 year of age with hypospadias resident in the municipality of Gela in the period 2010-2020. crude odds ratios (OR) and respective 95% confidence intervals (95%CI) were used to compare the prevalence observed in Gela and that detected in the comparison areas. excess risk for hypospadias was highlighted in 2010-2020 in Gela vs Sicily (OR 4.45; 95%CI 3.45-5.75), vs ALG (OR 4.29; 95%CI 3.02-6.10), and vs the NPCSs of Milazzo (OR 2.32; 95%CI 1.32-4.07) and Priolo (OR 2.37; 95%CI 1.55-3.62). The between-period comparisons in Gela did not show an important difference between 2010-2014 and 2015-2020 (OR 1.37; 95%CI 0.83-2.24), with a prevalence of 98.9 and 72.4 per 10,000, respectively. the prevalence of hypospadias in 2015-2020 remains very high, although decreasing when compared to 2010-2014 period. The Gela data, despite the refinery being closed after 2014, suggest a complex situation in which multiple risk factors may play a role.

Meconium Concentrations of Pesticides and Risk of Hypospadias: A Case-Control Study in Brittany, France.

Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role for environmental risk factors is suspected, including prenatal exposure to pesticides. To study the risk of hypospadias in association with multiple pesticide measurements in meconium samples. The Brittany Registry of Congenital Anomalies (France) conducted a case-control study between 2012 and 2018. Cases were hypospadias, ascertained by a pediatrician and a pediatric surgeon, excluding genetic conditions, following European Surveillance of Congenital Anomalies guidelines (N = 69). Controls (N = 135) were two male infants without congenital anomaly born after each case in the same maternity unit. Mothers in the maternity units completed a self-administered questionnaire, we collected medical data from hospital records, and medical staff collected meconium samples. We performed chemical analysis of 38 pesticides (parent compound and/or metabolite) by UHPLC/MS/MS following strict quality assurance/quality control criteria and blind to case-control status. We carried out logistic regression accounting for frequency-matching variables and major risk factors. Among the 38 pesticides measured, 16 (42%) were never detected in the meconium samples, 18 (47%) were in <5% of samples, and 4 (11%) in ≥5% of the samples. We observed an association between the detection of fenitrothion in meconium and the risk of hypospadias (OR = 2.6 [1.0-6.3] with n cases = 13, n controls = 21), but not the other pesticides. Our small study provides a robust assessment of fetal exposure. Fenitrothion's established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.

Maternal periconceptional folic acid supplementation and risk for fetal congenital genitourinary system defects.

Taking folic acid supplementation could reduce the risk of neural tube defects for offspring in the maternal periconceptional period, but the relationship between folic acid use and other birth defects remains unclear, such as genitourinary system birth defects. The data from a Prenatal Health Care System and Birth Defects Surveillance System in Tongzhou, Beijing, China, were collected from 2013 to 2018. We adjusted for differences in characteristics between comparison groups using propensity score inverse probability weighting and assessed associations with Poisson regression modeling. A total of 65,418 live births and stillbirths were included, and there were 194 cases with congenital genitourinary defects among them. The prevalence of genitourinary system birth defects was 29.2 (34.9) per 10,000 for FA/MMFA users (nonusers). Compared to nonusers, FA/MMFA users had a lower risk for genitourinary system birth defects (adjusted risk ratio [aRR] 0.81, 95% confidence interval [CI] 0.67, 0.98), and for hypospadias (aRR 0.55, 95% CI 0.40, 0.76). FA or MMFA supplementation during the maternal periconceptional period could reduce the risk for genitourinary system birth defects in offspring. More mechanisms should be explored for the protective effect. Folic acid (FA) or multiple micronutrients containing folic acid (MMFA) supplementation during the maternal periconceptional period could reduce the risk for genitourinary system birth defects in offspring. Maternal FA/MMFA supplementation during the periconceptional period may reduce the risk for hypospadias.

Risk of congenital malformations in live-born singletons conceived after intracytoplasmic sperm injection: a Nordic study from the CoNARTaS group

To investigate whether the risk of major congenital malformations is higher in live-born singletons conceived with intracytoplasmic sperm injection (ICSI) compared with invitro fertilization (IVF)? Nordic register-based cohort study. Cross-linked data from Medical Birth Registers and National ART and Patient Registers in Denmark, Norway and Sweden. Data were included from the year the first child conceived using ICSI was born: Sweden, 1992; Denmark, 1994; and Norway, 1996. Data were included until 2014 for Denmark and 2015 for Norway and Sweden. All live-born singletons conceived using fresh ICSI (n = 32,484); fresh IVF (n = 47,178); without medical assistance (n = 4,804,844); and cryo-ICSI (n = 7,200) during the study period. Different invitro conception methods, and cryopreservation of embryos. Risk of major congenital malformations on the basis of International Classification of Diseases codes. The European Concerted Action on Congenital Anomalies and Twins was used to differentiate between major and minor malformations. Among singletons conceived using fresh ICSI, 6.0% had a major malformation, compared with 5.3% of children conceived using fresh IVF; 4.2% of children conceived without medical assistance; and 4.9% of children conceived using cryo-ICSI; adjusted odds ratio (AOR) 1.07 (95% confidence interval [CI] 1.01-1.14) in ICSI vs. IVF; and AOR 1.28 (95% CI, 1.23-1.35) in ICSI vs. no medical assistance; and AOR 1.11 (95% CI, 0.99-1.26) in ICSI fresh vs. cryo-ICSI. When malformations were grouped by different organ systems, children conceived using ICSI had a higher risk of respiratory and chromosomal malformations compared with children conceived using IVF, but there were very few cases in each group. When categorizing children conceived using ICSI according to treatment indication (male factor infertility only vs. other indications), we found a higher risk of hypospadias when ICSI was performed because of male factor infertility only (AOR 1.85 [95% CI 1.03-332]). The indications for ICSI changed over time, as male factor infertility did not remain the primary indication for ICSI throughout the study period. In this large cohort study, we found the risk of major malformations in live-born singletons to be slightly higher after fresh ICSI compared with fresh IVF. These findings should be considered when choosing the assisted reproductive technology method for couples without male factor infertility.

Trends and predictors of incidence of hypospadias in a tertiary hospital in South Africa

BackgroundHypospadias is a penile congenital abnormality characterized by an ectopic urethral opening, ventral curvature and incomplete foreskin closure with a dorsal hooded prepuce. Management of the outcome demands high cost. The aim of this study was to determine the trends and predictors of hypospadias among babies born at Charlotte Maxeke Johannesburg Academic Hospital between 01 January 2014 and 31 December 2016.MethodsMothers’ files from the transfer unit of the labour ward were reviewed. A case–control study compared boys with hypospadias and those without born approximately at the same time. Data were retrospectively collected on data collection forms. EpiData version 3.1 and STATA version 15.1 were used for statistical analysis. The Mantel Haenszel method determined combined odds ratios for hypospadias outcome on boys whose mothers were exposed to certain conditions versus boys of unexposed mothers. Woolf’s method was used to compute confidence intervals of the odds ratios. Logistic regression analysis was used to assess the independent contributing maternal factors to the risk of hypospadias.ResultsRecords of 221 male babies were collected of which 73 were cases and 148 controls in the ratio of 1:2. Hypospadias was more frequent in boys born by Caesarean Section (p < 0.001), those with low birth weight (p < 0.001) and those small for gestational age (p < 0.002). Alcohol use (odds ratio 3.1), smoking (odds ratio 1.54), herbal use (odds ratio 2.05), medical history (odds ratio 2.8), multiple pregnancies (odds ratio 1.69) and maternal congenital abnormalities (odds ratio 3.03) indicated an increased risk of hypospadias. Surgical history (odds ratio 1.29), pre-natal vaccination (odds ratio 0.92), employment (odds ratio 0.85), and education (odds ratio 0.48) were not associated with the risk of hypospadias.ConclusionsMothers older than 36 years presented a stratifying effect on disease outcome. Our findings did not indicate major changes in trends of incidence of hypospadias. The years assessed did not have a significant effect on the number of cases.

Parental smoking and risk of hypospadias: An updated meta-analysis of observational studies.

Inconsistent relationships have been shown between cigarette smoking and hypospadias in offspring. The purpose of this study was to summarize epidemiological evidence to evaluate the relationship between parental smoking and the risk of hypospadias. Up until October 2022, PubMed, EMBASE, Web of Science, and the Cochrane Library were systematically searched for qualified research. The summary RRs and 95% CIs were calculated using either a fixed-effects or a random-effects model. There were subgroup analyses undertaken to identify potential sources of heterogeneity. 44 studies with 16,637,830 participants were included in our meta-analysis. Overall, maternal active smoking [risk ratio (RR) = 0.94; 95% confidence interval (CI): 0.90-0.99; P < 0.01] was significantly associated with the risk of hypospadias. And neither paternal smoking (RR = 1.00; 95% CI: 0.86-1.15) nor maternal passive smoking (RR = 0.91; 95% CI: 0.60-1.23) was associated with the risk of hypospadias. Our study discovered an association between maternal active smoking and a decreased risk of hypospadias, which may be due to the effect of smoking on androgen. However, as numerous studies have proved that cigarette smoking during pregnancy increases the risk of overall birth abnormalities in offspring, quitting cigarettes before pregnancy positively influences the health of offspring and should be advocated worldwide. [www.crd.york.ac.uk/prospero], identifier [CRD42022319378].

Risk of hypospadias due to use of Pesticides among the rural families of Haryana, Uttar Pradesh and Bihar in India: An AIIMS-Delhi study highlighting the risk on agriculture produce in Pregnant Mothers &amp; the importance of regulatory controls in the prevention of Birth Defects in Children

Risk of hypospadias due to use of Pesticides among the rural families of Haryana, Uttar Pradesh and Bihar in India: An AIIMS-Delhi study highlighting the risk on agriculture produce in Pregnant Mothers &amp; the importance of regulatory controls in the prevention of Birth Defects in Children

Levels of persistent organic pollutants in breast milk samples representing Finnish and Danish boys with and without hypospadias

Hypospadias is a congenital malformation of penile urethra with unknown etiology in most cases. Persistent organic pollutant (POP) exposure may disrupt endocrine function during a critical window of development of male genitalia. In animal studies, POPs have been associated with male reproductive disorders, including hypospadias, but only few studies have assessed this relationship in humans. The aim of this study is to investigate the association between hypospadias and POP concentration levels in breast milk, as a proxy for prenatal exposure. This is a nested case-control study of Danish and Finnish mother-son pairs. Maternal breast milk samples were collected between 1997 and 2002, and they represent infant boys born with hypospadias [n = 33 (n = 22 Danish and n = 11 Finnish)] and their 1:1 matched controls. Breast milk samples were analyzed for six classes of POPs [including dioxins, polychlorinated biphenyls, flame retardants and perfluorinated alkylated substances (PFAS)]. We estimated odds ratios (ORs) and 95% confidence intervals (CI) for each chemical class using conditional logistic regression. In addition, a composite exposure score system was used to explore the effect of a POP mixture (four chemical classes): The composite score was categorized as low, moderate, or high exposure, and differences between cases and controls were tested with conditional logistic regression. No statistically significant associations were observed between the sums of the chemical classes and hypospadias in either country. The composite score was unable to detect differences in the risk of hypospadias between the tertiles of POP exposure. Levels of PFAS were significantly higher in Danish than in Finnish breast milk samples. This small study does not provide evidence for an association between hypospadias and exposure to POPs but adds information on quantitative exposures. Further development of multi-exposure models is needed for assessing the potential mixture effect associated with multiple chemical exposures.

Effects of Elevated Maternal Adiposity on Offspring Reproductive Health: A Perspective From Epidemiologic Studies.

One in seven couples in developed countries suffers from infertility. Maternal overweight or obesity have detrimental and lasting effects on offspring cardiometabolic health, and although substantially more data are needed, hormonal imbalances in utero resulting from excessive maternal adiposity could also disrupt reproductive programming and affect the future reproductive health of offspring. Therefore, this mini-review evaluates the human epidemiologic evidence that maternal overweight/obesity could be associated with poor reproductive health outcomes in offspring. We searched PubMed for relevant studies using terms such as "maternal obesity" and "reproductive development." While the human epidemiologic literature is limited, studies have thus far observed that maternal obesity is associated with disrupted external genital development and several other markers of reproductive health across the lifespan. Specifically, maternal obesity is associated with higher risks of hypospadias and cryptorchidism in males and disrupted anogenital distance both in males and females. Maternal obesity has also been linked to earlier age at menarche in daughters, and precocious puberty in both sons and daughters. Finally, daughters of women with overweight or obesity have higher risks of developing polycystic ovarian syndrome, which has implications for fertility. This body of research suggests that in utero exposure to maternal obesity could disrupt reproductive system development, but substantially more evidence is needed, as almost no human epidemiologic studies have evaluated the long-term consequences of maternal obesity with regard to offspring fertility/fecundity.

Retraction: Associations of TGFBR1 and TGFBR2 gene polymorphisms with the risk of hypospadias: a case-control study in a Chinese population.

This article is being retracted from Bioscience Reports at the request of several listed co-authors who claim to have had no involvement in the paper and that they were unaware of its submission and publication. The corresponding author has been contacted with regards to the retraction and has not responded to the Journal's queries or the concerns raised. Several listed co-authors wish to retract the article and the Editorial Board agree with the Retraction.

Maternal exposure to DDT, DDE, and pyrethroid insecticides for malaria vector control and hypospadias in the VHEMBE birth cohort study, Limpopo, South Africa

Hypospadias is the ectopic opening of the urethra on the penis or scrotum. Exposure to estrogenic and/or anti-androgenic chemicals in utero may play an etiologic role. DDT and the pyrethroids cypermethrin and deltamethrin, are used to control malaria. DDT is estrogenic and its breakdown product DDE is anti-androgenic; cypermethrin and deltamethrin can also disrupt androgen pathways. We examined the relationship between maternal exposure to these insecticides during pregnancy and hypospadias among boys participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) in Limpopo Province, South Africa. We measured peripartum levels of p,p'-DDT and p,p'-DDE in maternal serum and urinary pyrethroid metabolites. We conducted urogenital examination on 359 one-year-old boys. A total of 291 (81.0 %) had phimosis, which prevented full urogenital examination, leaving a final sample of 68 boys for determination of the presence of hypospadias. Diagnosis was based on concordance of two independent physicians. We identified hypospadias in 23 of the 68 boys (34 %). Maternal urinary concentrations of cis-DCCA and trans-DCCA metabolites of cypermethrin and other pyrethroids, were associated with an increased risk for hypospadias, but the other metabolite 3-PBA was not (adjusted relative risk per 10-fold increase = 1.58, 95 % CI 1.07–2.34; 1.61, 95 % CI 1.09–2.36; and 1.48, 95 % CI 0.78–2.78, respectively). No associations were found between p,p'-DDT, p,p'-DDE, 3-PBA or cis-DBCA and hypospadias. We observed a high prevalence of hypospadias among boys without phymosis. Boys with higher prenatal exposure to pyrethroid insecticides were at higher risk of hypospadias. Our findings may have global implications given that pyrethroid insecticides are widely used for malaria control, in agriculture and for home use.

Maternal Cigarette Smoking During Pregnancy and Genital Anomalies in Boys: A Register-Based Cohort and Sibling-Matched Design Study.

PurposeCryptorchidism and hypospadias share several prenatal risk factors. However, in published studies, boys exposed to cigarette smoking during pregnancy have a higher risk of cryptorchidism and a lower risk of hypospadias. Using Danish register-based data, we revisited these findings with a cohort and sibling-matched design to investigate the potential effect of shared time-stable factors.Patients and MethodsFor the cohort study, we included 823,670 live-born, singleton boys born from 1991 to 2016. Crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression models for each genital anomaly according to maternal cigarette smoking during pregnancy. For the sibling-matched design, we included 399,258 brothers and used a stratified Cox regression model creating family-adjusted results.ResultsIn the cohort study, we found a higher risk of cryptorchidism (aHR = 1.18, 95% CI: 1.12, 1.24) and a lower risk of hypospadias (aHR = 0.84, 95% CI: 0.76, 0.93) when comparing boys exposed to cigarette smoking with non-exposed, and for increasing numbers of cigarettes smoked. In comparison, the sibling-matched analyses suggested a slightly weaker association for cryptorchidism and an association of similar magnitude for hypospadias, both in the same direction as in the cohort study.ConclusionShared, familial confounding does not seem to explain earlier findings of higher risk of cryptorchidism and lower risk of hypospadias.

Exposure to corticosteroids in the first trimester is associated with an increased risk of urogenital congenital anomalies.

Does maternal exposure to first trimester corticosteroids in IVF/ICSI treatment result in an increased risk of congenital anomalies? Children born with the aid of IVF/ICSI whose mothers were treated with adjuvant corticosteroids during the first trimester had an increased risk of cryptorchidism, hypospadias and talipes. Maternal exposure to corticosteroids may increase the risk of congenital anomalies such as cleft palate and neural tube defects. However, the existing studies have conflicting outcomes, are underpowered, and do not study a population undergoing IVF/ICSI, a group known to be at increased risk of abnormalities. This retrospective cohort analysis covering Monash IVF fertility clinics in Melbourne, Australia assessed the outcomes of 12 426 live births from both fresh and frozen embryo transfers between 2010 and 2016. There were 618 live births included in our study group of mothers exposed to corticosteroids (oral prednisolone or dexamethasone) during their IVF/ICSI treatment, with the remainder of births not exposed to steroids (control, n = 11 808). The primary outcome measured was the presence of congenital anomalies and secondary outcomes were birth weight and gestation length. Multivariate binary logistic regression was used to assess the independent effects of corticosteroid exposure and the freezing of embryos, with adjustment for maternal age at oocyte retrieval, smoking status, number of cycles taken, BMI, etiology of the infertility and the use of ICSI. Results are presented as incidence rate ratios (IRRs) with 95% CIs. Amongst 12 426 live births, and 597 birth defects, multivariate logistic regression demonstrated there was an increased incidence in talipes equinovarus (1.33% vs 0.32%, adjusted IRR = 4.30, 95% CI = 1.93, 9.58; P < 0.001), hypospadias (0.66% vs 0.18%, adjusted IRR = 5.90, 95% CI = 2.09, 16.69; P = 0.001) and cryptorchidism (0.83% vs 0.19%, adjusted IRR = 5.53, 95% CI = 1.91, 15.42; P = 0.001) in the offspring of mothers exposed to corticosteroids compared to those who were unexposed. The incidence of neither neural tube defects nor cleft palate were significantly increased in babies exposed to corticosteroids. The sex ratio of infants exposed to corticosteroids during a fresh embryo transfer cycle significantly favored males but reverted to the normal sex ratio in infants conceived in frozen embryo transfer cycles. This was a retrospective observational cohort study using administrative datasets with the potential for measurement error and unobserved confounding. Missing outcome data were obtained from patients using self-report leading to possible ascertainment bias. Given the rare incidence of some of the anomalies assessed, the study was underpowered to identify differences in abnormality rates for some specific anomalies. The findings of this study, the largest of its kind, suggest that caution should be heeded when prescribing corticosteroids to women undergoing IVF/ICSI, given that this study has now identified three previously unassociated serious neonatal complications (talipes, hypospadias and cryptorchidism), plus a potential alteration in sex ratio. Physicians should be careful in using corticosteroids in the critical first trimester and should counsel patients regarding the potential risks of this treatment. There was no funding sought or obtained for this study. K.T., V.T., B.V. and D.Z.-F. are employees or contractors to Monash IVF and hold a minority stock position in Monash IVF. R.J.W. reports no conflict of interest. N/A.

Maternal, environmental and demographic factors in hypospadias: Jordan tertiary center results

Highlights

CORRELATION BETWEEN MATERNAL AGE, LOW BIRTH WEIGHT, PREMATURITY AND HORMONAL DRUGS USING WITH THE OCCURRENCE OF HYPOSPADIAS (CASE STUDY AT BINA SEHAT JEMBER HOSPITAL, PARU JEMBER HOSPITAL, AND BHAYANGKARA BONDOWOSO HOSPITAL)

Objective: This research aims to determine the correlation between maternal age during pregnancy, low birth weight (LBW), prematurity, and history of hormonal drugs used in the first trimester of pregnancy with the occurrence of hypospadias. Material &amp; Methods: This research is an observational analytic research with case control design. The sample in this study were 50 samples that consisting of 25 patients with hypospadias and 25 patients without hypospadias at Bina Sehat Jember Hospital, Paru Jember Hospital, and Bhayangkara Bondowoso Hospital. After determined every case and control group, data acquired retrospectively by traced the hypospadias risk factors (maternal age at pregnancy, LBW, prematurity, and history of hormonal drugs using in the first trimester of pregnancy) by interviewing the patient's mother. The data of this research were analyzed by bivariate and multivariate using SPSS 16.0. Bivariate analysis in this study used chi-square Yates correction (chi-square with continuity correction) and fisher's exact test, whereas multivariate analysis used logistic regression techniques with significance p-value&lt;0.05. Results: The result of bivariate analysis in this study showed that variable maternal age during pregnancy more than 35 years (p = 0.667) has no correlation with occurrence of hypospadias, while variable of LBW (p = 0.027), prematurity (p = 0.041), and the history of hormonal drug use in the first trimester of pregnancy (p = 0.049) have a correlation with the occurrence of hypospadias. Conclusion: In this study, there was a significant correlation between LBW, prematurity, and history of hormonal drugs using in the first trimester of pregnancy with the occurrence of hypospadias. This study did not show a significant correlation between maternal age during pregnancy with the occurrence of hypospadias.&#x0D;