Prevalence Of Hypospadias Research Articles

Time trends and geographic variations in the prevalence of hypospadias in China

Little is known about the main epidemiologic characteristics of hypospadias prevalence in China. We investigated the time trends and geographic variations in the prevalence of hypospadias in China from 1996 to 2008. Data were retrieved from the hospital-based birth defects monitoring system in China from 1996 to 2008. We used prevalence ratios (PRs) to describe the difference in prevalence of hypospadias between urban and rural areas, as well as among different regions. Poisson regression was used to explore the long time trend for the prevalence of hypospadias and its regional disparity. The prevalences of hypospadias for isolated anomalies, multiple anomalies, and overall cases were 7.64, 1.39, and 9.03 per 10,000 births, respectively. The national PRs (urban vs. rural) of hypospadias for overall and isolated cases were 1.25 (95% confidence interval [CI], 1.16-1.35) and 1.27 (95% CI, 1.17-1.38), respectively. The highest prevalence (12.10 per 10,000 births) was observed in the eastern region. A positive correlation was found between the prevalence of hypospadias and maternal age (p < 0.01). The average annual increase of 7.43% (95% CI, 5.52-9.38%) was observed in the overall prevalence of hypospadias in China; it was 5.28% (95% CI, 4.16-6.43%) in urban areas, 9.79% (95% CI, 7.72-11.90%) in rural areas, 9.08% (95% CI, 6.36-11.86%) in the eastern region, 4.76% (95% CI, 2.93-6.62%) in the central region, and 6.57% (95% CI, 4.44-8.74%) in the western region. The increasing trends and differences of hypospadias prevalence by urban-rural classification and geographical location suggest that environmental exposure and maternal age might have a critical role in the development of hypospadias.

A NESTED CASE-CONTROL STUDY OF INTRAUTERINE EXPOSURE TO PERSISTENT ORGANOCHLORINE POLLUTANTS IN RELATION TO RISK OF HYPOSPADIA

Background and aims: In western countries the prevalence of hypospadias varies from two to eight cases per 1,000 live births. Knowledge about risk factors for hypospadias is still scarce. However, environmental exposures to so called endocrine disrupting chemicals (EDCs) have been suggested as a risk factor. An important group of EDCs is persistent organochlorine pollutants (POPs). Due to the unique personal identification number present in the biobank databases and the national health registries in Sweden we have the possibility to investigate the association between POPs and hypospadias in relatively large studies. Methods: The Malmö Microbiology Biobank (MMB) contains about 200 000 deep-frozen serum samples, stored after population-based serological screening for virus infections and rubella immunity during pregnancy week 14. Linkages between the Medical Birth Register, the Malformation Register and the In-patient Register resulted in 390 boys with hypospadia. For 237 (61 %) of them, sufficient amount of serum samples were found in the biobank. For each case a control boy was randomly selected from the MMB. 2,2’,4,4’,5,5’-hexachlorobiphenyl (PCB-153), the major DDT metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p´-DDE) and hexachlorbenzene (HCB) were used as biomarkers of POP exposure. Results: A 65 percent statistically significantly increased risk in the highest maternal exposure quartile of HCB as compared to the three lowest HCB exposure categories was observed. The pattern was, although not statistically significant, similar for maternal exposure for p,p´-DDE. Conclusion: The present study indicates that in utero exposure to HCB and perhaps exposure to p,p´-DDE is a risk factor for hypospadia. The fact that HCB and p,p´-DDE may affect the androgen-signalling pathway should reinforce the concept that ECDs, though present at low doses, may affect human health negatively.

Maternal Pregnancy Levels of trans -Nonachlor and Oxychlordane and Prevalence of Cryptorchidism and Hypospadias in Boys

Background: The etiologies of the male urogenital anomalies—cryptorchidism and hypospadias—are poorly understood. Given positive associations between chlordane isomers and testicular germ cell tumors, it is reasonable to assume that chlordanes might also be associated with other testicular dysgenesis syndrome disorders, namely cryptorchidism and hypospadias.Objective: To examine whether exposure to in utero chlordane is related to cryptorchidism and hypospadias, we evaluated levels of chlordane derivatives, trans-nonachlor and oxychlordane, among pregnant women enrolled in the Collaborative Perinatal Project (CPP).Methods: From 1959 to 1965, the CPP enrolled pregnant women at 12 U.S. medical centers. We analyzed serum trans-nonachlor and oxychlordane levels measured in third-trimester serum from the mothers of 217 sons with cryptorchidism, 197 sons with hypospadias, and 557 sons with neither condition. Adjusted odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression.Results: The quartile-specific ORs for cryptorchidism or hypospadias show no notable associations with trans-nonachlor or oxychlordane. Further, there were no significant trends with increasing quartile of maternal trans-nonachlor or oxychlordane level in either cryptorchidism or hypospadias (p-trend all > 0.45).Conclusions: The results do not support an association between chlordane levels and cryptorchidism or hypospadias. It is unlikely that current chlordane exposure is related to the development of either anomaly, given that serum chlordane levels at the time of sample collection, the early 1960s, were considerably higher than levels at present.

Documenting the prevalence of cryptorchidism and hypospadias

I was impressed by the efforts the authors made to document the prevalence of cryptorchidism and hypospadias over such a long period of time.1 Although there are small fluctuations during the period studied, there seems to be a diminution of cryptorchidism in recent years. This change occurs in spite of the fact that the age of surgery has now shifted from over the age of 5 to under the age of 2 (or less than a year). Due to referral patterns and surgical practice, cryptochidism was certainly underreported in the registry in its early years. The real difference is most probably higher. It is also interesting to note that regional differences exist, and that some regions have a combined hypospadias and cryptorchidism prevalence that are higher than others. This may in fact be associated with environmental exposures as the authors have hypothesized, but may also be related to genetic determinants. Further studies may help define these differences, especially for the province of Quebec, where there seems to be a higher prevalence than reported in the literature.

Outcomes of Hypospadias Repair in Older Children: A Prospective Study

The American Academy of Pediatrics recommendation is to perform hypospadias repair at age 6 to 12 months. However, our patient population included a significant proportion of patients in adolescence and beyond undergoing primary repair. We report a comparison of outcomes in patients in different age groups. We prospectively report on patients with distal hypospadias who underwent primary repair at our institution during 7 months. Study parameters included age, degree of hypospadias, surgical technique and the complications rate. A total of 61 patients were included in analysis. All cases underwent repair using the tubularized incised plate technique. More proximal hypospadias and different repair techniques were excluded from study. Patients were classified by age, including group 1-25 (40%) 6 months to 2 years old, group 2-17 (28%) 2.2 to 3.7 years old and group 3-19 (32%) 4 years old or older. Only 6 patients (9.8%) had postoperative complications and all were in groups 2 and 3. In group 2 there were 3 complications (17.6%), including loss of repair, meatal stenosis and hematoma in 1 case each. In group 3 there were 3 cases (15.8%) of postoperative fistula. The fistula incidence was higher in group 3 (p = 0.032). Despite previous reports suggesting a much higher incidence of complications in older children the complication rate is within the acceptable range for infant hypospadias repair in some series. However, these complications were statistically significantly different between the older groups when compared with the recommended age group under American Academy of Pediatrics guidelines.

Prevalence of hypospadias in grandsons of women exposed to diethylstilbestrol during pregnancy: a multigenerational national cohort study

Prenatal diethylstilbestrol (DES)-exposed mice have raised the suspicion of a transgenerational effect in the occurrence of genital malformation in males. This nationwide cohort study in collaboration with a French association of DES-exposed women studied 529 families and showed that a significant proportion of boys born to DES daughters exhibited hypospadias with no other molecular defects identified.

Epidemiology of Hypospadias and Treatment Trends in Taiwan: A Nationwide Study

We investigated the rate of diagnosis and treatment trends of hypospadias in Taiwan within the first 3 years of life. We used a subset of the Taiwan National Health Insurance Research Database, which contains data on all inpatient and outpatient medical benefit claims, for the period 1997 through 2008 for a sample of 1 million individuals randomly drawn from the population of 25.68 million who held membership in the National Health Insurance program during any part of the calendar year 2005. We analyzed claims data for all subjects who were diagnosed with hypospadias through age 3 years. Among 52,705 newborns (individuals whose claims included live birth) 178 were diagnosed with hypospadias within 3 years of birth. Thus, mean incidence was 33.8 per 10,000 live male births. The hypospadias repair rate was 14.3 per 10,000 live male births. There was no significant tendency toward increase or decrease in rates of diagnoses or repairs, or proportion of severe hypospadias. There were significant associations between rates of hypospadias diagnoses and urbanization level of the community where the diagnosis was made. Approximately 54% of patients who underwent surgical repair did so after age 18 months. The nationwide incidence of hypospadias in children younger than 3 years in Taiwan is similar to that reported in previous studies. Delayed diagnosis and treatment of hypospadias are important clinical concerns that warrant further investigation.

Letter to the Editor

We appreciate the comments concerning our manuscript, Rising hypospadias rates: disproving a myth (J Pediatr Urol 2010;6:37–39). We agree that uniformity, among population study groups, would provide more consistent data. However, the data set analyzed for our study is more than 20 years in length and represents one of the longest databases available. This data accrued over a long study period would appear to be more robust than data collected over a 2-year period by Peirik et al. (A high hypospadias rate in the Netherlands. Hum Reprod 2002;17:1112–1115). Re: Harry Fisch et al.: Rising hypospadia rates: Disproving a myth. (Journal of Pediatric Urology 2010; 6: 37–39)Journal of Pediatric UrologyVol. 6Issue 5PreviewWe read with interest the report by Fisch, Hyun and Hensle in the January issue of the Journal of Pediatric Urology[1]. The authors have reviewed the data from the birth registries of New York State, California, Washington, Scotland, and the European registries, and have concluded that the prevalence of hypospadias did not rise significantly during 1982–83 to 2002–05. In addition, based on this data, they have refuted the hypothesis suggesting an increase in the incidence of hypospadias due to the potential effects of ‘endocrine disruptors’ such as phthalates and bisphenol-A on male reproductive health. Full-Text PDF

Secular trends of hypospadias prevalence and factors associated with it in southeast China during 1993–2005

The aim of this study is to describe the prevalence of hypospadias and its time trends during 1993-2005 in southeast China, and to explore the potential risk factors. The study population included all male live and still births (at least 20 weeks of gestation) in 11 cities and counties in Jiangsu and Zhejiang Provinces in Southeast China born during January 1, 1993, through December 31, 2005. Overall prevalence of hypospadias was 5.8 per 10,000 male births and presented an increasing trend during 1993-2005 (with chi(for trend) (2) of 3.94, p = 0.047). Prevalence of coronal hypospadias and those with unknown sites increased from 1.7 and 0.3 per 10,000 male births in 1993 to 3.6 and 1.4 per 10,000 male births in 2005, respectively (with chi(for trend) (2) of 7.29 and 9.05, p = 0.007 and p = 0.002, respectively), but prevalence of perineal hypospadias decreased (with chi(for trend) (2) of 7.13, p = 0.008). Maternal fever during first trimester, birth of twins or more children, and year of birth were independent risk factors for hypospadias, with odds ratios of 4.14 (95% CI, 1.32-12.83), 3.37 (95% CI, 1.73-6.58), and 1.04 (95% CI, 1.00-1.08), respectively, after adjusting for confounding factors with multivariable logistic regression analysis. Prevalence of hypospadias increased during 1993-2005 in the two provinces in southeast China. Maternal fever in the first trimester and birth of twins or more children are associated with the risk for hypospadias.

Low testosterone levels in pre-term newborns born small for gestational age

Previous studies showed that small for gestational age (SGA) newborns have an increased prevalence of hypospadias and other congenital defects of external genitalia. We observed that in the first days of life, SGA male pre-term newborns have reduced testosterone levels compared with adequate for gestational age pre-term newborns, independently from the presence of abnormalities of the external genitalia.

Rising hypospadias rates: Disproving a myth

Hypospadias is one of the most common congenital abnormalities occurring in males. In recent years, the prevalence of hypospadias and whether that prevalence is rising or stable has become part of a larger debate over the potential effects of so-called 'endocrine disruptors', such as phthalates and bisphenol-A, on male reproductive health. This commentary critically examines allegations suggesting a worldwide increase in hypospadias rates. Despite the lack of scientific support for this hypothesis and for related claims that the disorders of male reproductive health are related to endocrine disruptors, these constructs remain firmly entrenched in popular literature, and are being used in part to justify litigation banning suspected endocrine disruptors such as phthalates and bisphenol-A. A review of the epidemiologic data on this issue amassed to date clearly demonstrates that the bulk of evidence refutes claims for an increase in hypospadias rates. This suggests that two of the three components of alleged testicular dysfunction syndrome, i.e. decline in sperm counts and rise in urogenital anomalies, lack clinical support. It further suggests that extrapolations from data derived in laboratory animal studies about alleged occult risks to humans of various candidate compounds are unwarranted at this time.

Prevalence of Hypospadias in New York State 1992–2005

Prevalence of Hypospadias in New York State 1992–2005

Maternal Use of Oral Contraceptives During Early Pregnancy and Risk of Hypospadias in Male Offspring

To examine the association between maternal use of oral contraceptives in early pregnancy and increased prevalence of hypospadias in male offspring. We conducted a nationwide population-based case-control study using data from nationwide medical databases. Among live male births between January 1, 1996, and December 31, 2005, we identified all cases of hypospadias recorded anytime postpartum (n = 1683) and randomly selected 10 controls per case without such a diagnosis (n = 15 650), matched by year and hospital of birth. We used conditional logistic regression to estimate prevalence ratios stratified according to time of diagnosis (within 6 months postpartum, >6 months postpartum), controlling for potential confounding factors including maternal age, birth order, maternal smoking, prescriptions for ovulation-inducing drugs, antiepileptics, and antidiabetics, and a maternal diagnosis of pre-eclampsia. We included 1683 cases of hypospadias and 15,650 population controls during 1996-2005. Among the 1186 boys who had their hypospadias diagnosis recorded within 6 months postpartum, 28 (2.4%) had been exposed to oral contraceptives between 30 days before conception until the end of the first trimester. Among the controls, 307 (2.8%) were similarly exposed, corresponding to a prevalence ratio of 0.85 (95% CI: 0.57-1.27) after adjusting for possible confounders. For a diagnosis registered >6 months postpartum, the adjusted prevalence ratio was 1.12 (95% CI: 0.61-2.06). Our data do not support the hypothesis that maternal use of oral contraceptives around conception is associated with an increased prevalence of hypospadias in the offspring.

Reply

Hypospadias is a common congenital malformation of the genitourinary system in male infants. Infants with hypospadias can also have difficulty with sexuality and developing normal relationships as adults. Previous reports of an increase in prevalence have been mainly from North America, Europe, and Australia, with an incidence of ≤3 per 1000 births or even greater. However, an epidemiologic survey of the prevalence of hypospadias in a large sample of Chinese newborns was deficient. Zhejiang Province is one of the provinces with a rapidly developing economy in southeast China.

Hypospadias Rates in New York State are Not Increasing

The testicular dysgenesis syndrome describes urogenital abnormalities associated with exposure to environmental endocrine disruptors such as phthalates, specifically decreased semen quality, and increased rates of testis cancer and hypospadias. Recently there has been concern that these abnormalities described in animal studies may also be present in humans. To determine if hypospadias rates are increasing, we retrospectively reviewed the total prevalence of hypospadias in New York State from 1992 to 2005, categorized by maternal age younger than 35 years and 35 years or older. Hypospadias rates were obtained from the New York State Congenital Malformations Registry from 1992 to 2005. An analysis was also performed on the rates of children with hypospadias who had mothers younger than 35 years and mothers 35 years or older. This investigation was approved by the Columbia University internal review board. There was no statistical change in hypospadias rates in New York State from 1992 to 2005 (r = 0.127, p = 0.6). Overall the mean +/- SE prevalence rate was 34.9 +/- 0.36 per 10,000 live births. However, mean +/- SE hypospadias rates in children of mothers 35 years old or older (38.7 +/- 0.7) were significantly greater than those in children of mothers younger than 35 years (34.1 +/- 0.386, t test p <0.01). Hypospadias rates have not changed in New York State from 1992 to 2005. Additionally advanced maternal age continues to be a risk factor for hypospadias. Combined with previous studies that demonstrate sperm counts are not declining, these data suggest that the testicular dysgenesis syndrome described in animal models may not be evident in humans.

Prevalence of Hypospadias in Danish Boys: A Longitudinal Study, 1977–2005

BackgroundHypospadias is a relatively common congenital malformation. Data on temporal trends in prevalence of hypospadias are conflicting. It is unclear whether changes of maternal age distribution over time are associated with changes in hypospadias prevalence. ObjectiveTo study changes in prevalence of hypospadias in Denmark during a 29-yr period and to investigate whether maternal age was associated with the prevalence of hypospadias. Design, setting, and participantsThrough Denmark's National Patient Registry, covering all Danish hospitals, we identified all boys diagnosed with hypospadias in Denmark. From the Danish Medical Birth Registry, we obtained information on maternal age and on the annual total number of live-born boys from 1977 to 2005. MeasurementsPrevalence of hypospadias at birth. Results and limitationsAmong 921745 boys born alive from 1977 to 2005, we identified 3490 boys with hypospadias. The prevalence increased from 0.24% in 1977 to 0.52% in 2005, corresponding with an annual increase in prevalence of 2.40% (95% confidence interval: 1.94–2.86). The prevalence of hypospadias did not differ according to maternal age. The mean annual prevalence was 0.38% in sons of mothers aged ≤25 yr, 0.37% in sons of mothers aged 26–30 yr, 0.39% in sons of mothers aged 31–35 yr, and 0.39% in sons of mothers >35 yr. ConclusionsThe hypospadias prevalence was increasing in Denmark from 1977 to 2005. Increased maternal age did not explain this trend.

Prevalence of hypospadias in Italy according to severity, gestational age and birthweight: an epidemiological study

BackgroundHypospadias is a congenital displacement of the urethral meatus in male newborns, being either an isolated defect at birth or a sign of sexual development disorders. The aim of this study was to assess the prevalence rate of hypospadias in different Districts of Italy, in order to make a comparison with other countries all over the world.MethodsWe reviewed all the newborns file records (years 2001–2004) in 15 Italian Hospitals.ResultsWe found an overall hypospadias prevalence rate of 3.066 ± 0.99 per 1000 live births (82.48% mild hypospadias, 17.52% moderate-severe). In newborns Small for Gestational Age (birthweight < 10th percentile) of any gestational age the prevalence rate of hypospadias was 6.25 per 1000 live births. Performing multivariate logistic regression analysis for different degrees of hypospadias according to severity, being born SGA remained the only risk factor for moderate-severe hypospadias (p = 0.00898) but not for mild forms (p > 0.1).ConclusionIn our sample the prevalence of hypospadias results as high as reported in previous European and American studies (3–4 per 1000 live births). Pathogenesis of isolated hypospadias is multifactorial (genetic, endocrine and environmental factors): however, the prevalence rate of hypospadias is higher in infants born small for gestational age than in newborns with normal birth weight.

Increase in hypospadias prevalence and the role of endocrine disrupting chemicals

Increase in hypospadias prevalence and the role of endocrine disrupting chemicals

Maternal and Gestational Risk Factors for Hypospadias

BackgroundAn increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown.ObjectivesOur goal was to assess the association between risk of hypospadias and indicators of placental function and endogenous hormone levels, exposure to exogenous hormones, maternal diet during pregnancy, and other environmental factors.MethodsWe conducted a case–control study in Sweden and Denmark from 2000 through 2005 using self-administered questionnaires completed by mothers of hypospadias cases and matched controls. The response rate was 88% and 81% among mothers of cases and controls, respectively. The analyses included 292 cases and 427 controls.ResultsA diet during pregnancy lacking both fish and meat was associated with a more than 4-fold increased risk of hypospadias [odds ratio (OR) = 4.6; 95% confidence interval (CI), 1.6–13.3]. Boys born to obese [body mass index (BMI) ≥ 30] women had a more than 2-fold increased risk of hypospadias (OR = 2.6; 95% CI, 1.2–5.7) compared with boys born to mothers with a normal weight (BMI = 20–24). Maternal hypertension during pregnancy and absence of maternal nausea increased a boy’s risk of hypospadias 2.0-fold (95% CI, 1.1–3.7) and 1.8-fold (95% CI, 1.2–2.8), respectively. Nausea in late pregnancy also appeared to be positively associated with hypospadias risk (OR = 7.6; 95% CI, 1.1–53).ConclusionsA pregnancy diet lacking meat and fish appears to increase the risk of hypospadias in the offspring. Other risk associations were compatible with a role for placental insufficiency in the etiology of hypospadias.

Loratadine During Pregnancy and Hypospadias

To the Editor: In November 2001, 2780 infants exposed to loratadine in utero were identified in The Swedish Medical Birth Registry. Among those infants were 15 cases of hypospadias, compared with 5.6 cases expected (based on a population rate of 1 case per 500 in the general population). The adjusted odds ratio for hypospadias and loratadine exposure was 2.4 (95% confidence interval = 1.4–3.4).1 Continued monitoring suggested that the association was not readily consistent with occurrence by chance. Recently, the Swedish group2 repeated the analysis for the period 2002–2004 and reported a prevalence ratio of 0.47 (0.06–1.65), a value considerably lower than their earlier report. This new analysis was based on 1911 infants exposed to loratadine in early pregnancy. Other attempts to study this relationship have been hampered by insufficient data and inconsistent results.3–5 To examine this association, we conducted a large nationwide case-control study in Denmark, based on administrative medical health databases and linkage to the Danish nationwide prescription database. We identified all boys with hypospadias in Denmark born in the period 1996–2004 from the nationwide Hospital Discharge Registry covering all Danish hospitals. The codes for hypospadias in ICD-10 are Q54.0 (n = 640), Q54.1 (n = 173), Q54.2 (n = 41), Q54.3 (n = 9), Q54.4 (n = 48), Q54.8 (n = 10), Q54.9 (n = 654). Using these codes, a total of 1575 cases of hypospadias were identified anytime after delivery. For each case we randomly selected from the Danish Medical Birth Registry up to 10 controls (live male births) without a diagnosis of hypospadias, matched by birth year and mother's residence. Through the nationwide prescription database, maintained by The Danish Medicines Agency, we identified all prescriptions to the mothers of cases and controls before the date of birth. We used conditional logistic regression to estimate prevalence ratios, controlling for potential confounding factors obtained from the databases, including maternal age, smoking status, birth order, preeclampsia, and prescriptions for ovulation-inducing drugs, antidiabetics, and antiepileptics (Table).TABLE: Characteristics of 1575 Cases of Hypospadias Recorded Anytime Postdelivery and 14,660 Control SubjectsWe found a negative association between maternal exposure to loratadine and prevalence of hypospadias. Among 1575 cases of hypospadias, 7 cases (0.4%) and 88 controls (0.6%) were exposed to loratadine in the 30 days before conception and during the first trimester. The adjusted prevalence ratio for hypospadias among users of loratadine relative to nonusers was 0.6 (95% CI = 0.3–1.4) and the corresponding prevalence ratio for other antihistamines was 1.3 (0.9–1.9). The adjusted prevalence ratio for hypospadias among users of loratadine during the entire pregnancy relative to nonusers was 0.9 (0.5–1.6) and the corresponding prevalence ratio for other antihistamines was 1.0 (0.7–1.5). Thus, in this large population-based nationwide study, we found strong evidence that maternal exposure to loratadine does not substantially increase the risk of hypospadias. Our findings do not corroborate the first Swedish study1 that initiated the hypospadias debate, but they are consistent with the other small studies that have reported on this topic.3–5 Several factors should be taken into account when interpreting this study. The full and independent nationwide registration of births, malformations, and prescriptions prevented several types of bias. Any noncompliance with the use of antihistamines and inaccurate data in the databases might bias the estimates of risk towards the null, since this imperfect specificity in routinely recorded data is most likely independent of prescription information. Lars Pedersen Mette Nørgaard Department of Clinical Epidemiology Aarhus University Hospital Aarhus C, Denmark [email protected] Kenneth J. Rothman RTI Health Solutions Research Triangle Park, NC Henrik Toft Sørensen Department of Clinical Epidemiology Aarhus University Hospital Aarhus C, Denmark