The estimated prevalence of hypospadias in Hokkaido, Japan

BACKGROUND: Hypospadias is one of the most common congenital anomalies in the world. Recently, increases in the prevalence of hypospadias have been reported in various countries including Japan. In this study, we examined whether the prevalence of hypospadias in Hokkaido, Japan, increased or not, using standardized diagnostic criteria. We also investigated the degree of its severity. METHODS: We calculated prevalence of hypospadias using hospital records of hypospadias repair in Hokkaido. The prevalence from 1985 through 1997 by dividing the number of patients obtained from hospital records by the number of births. RESULTS: The average prevalence of hypospadias in Hokkaido was 3.9 per 10,000 births, and did not significantly change (p=0.7). The average proportions of distal, proximal and chordee alone were 56.7%, 39.6% and 3.7%, respectively. The decrease in the proportion of the proximal type was statistically significant (p=0.05) for the entire time period, whereas the proportion of the distal type did not have a significant upward trend for the observed 13 years (p=0.1). CONCLUSION: No significant changes in the prevalence of hypospadias existed in Hokkaido.     

Hypospadias in sons of women exposed to diethylstilbestrol in utero

BACKGROUND: Diethylstilbestrol (DES) is a synthetic estrogen that was widely prescribed to pregnant women before 1971. DES increases the risk of breast cancer in women who took the drug and the risk of reproductive tract abnormalities in their offspring. Dutch investigators have reported a 20-fold increase in risk of hypospadias among sons of women who were exposed to DES in utero. We assessed this relation in data from an ongoing study of DES-exposed persons. METHODS: Several U.S. cohorts of women with documented exposure in utero to DES have been followed by mailed questionnaires since the 1970s. Comparison subjects are unexposed women of the same ages. In 1997, participants were asked about congenital abnormalities in their children. We calculated prevalence odds ratios for the risk of hypospadias in sons of exposed mothers relative to sons of unexposed mothers using generalized estimating equations to adjust for multiple sons per mother and controlling for maternal age at the son's birth. RESULTS: We obtained data from 3916 exposed and 1746 unexposed women. These women reported a total of 13 liveborn sons with hypospadias (10 exposed, 3 unexposed). The prevalence odds ratio for risk of hypospadias among the exposed was 1.7 (95% confidence interval = 0.4-6.8). CONCLUSIONS: Our findings do not support a greatly increased risk of hypospadias among the sons of women exposed to DES in utero, as has been previously reported.     

Maternal and gestational risk factors for hypospadias

BACKGROUND: An increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown. OBJECTIVES: Our 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. METHODS: We 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. RESULTS: A 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) > or = 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). CONCLUSIONS: A 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.     

Maternal use of oral contraceptives and risk of hypospadias – a population-based case-control study

The aim of this population-based case-control study was to examine the risk of isolated hypospadias in boys born to mothers who have used oral contraceptives in early pregnancy. The study was based on data from the Hungarian Case-Control Surveillance of Congenital Abnormalities from 1980 to 1996, and included 3,038 boys with hypospadias (cases), 24,799 boys without congenital abnormalities (CA-free controls), and 11,881 boys with abnormalities other than hypospadias. We used unconditional logistic regression to adjust for birth order, maternal age, maternal employment status, maternal diabetes, and pre-eclampsia. When comparing cases with CA-free controls the OR for maternal use of OC was 1.21 (95% CI: 0.67–2.17). When comparing cases with boys with other abnormalities, the OR for maternal use of OC was 0.83 (95% CI: 0.46–1.50). Our data showed that self-reported maternal use of oral contraceptives during pregnancy was not associated with an increased risk of hypospadias in the offspring.     

Agricultural pesticide use and hypospadias in eastern Arkansas

INTRODUCTION: We assessed the relationship between hypospadias and proximity to agricultural pesticide applications using a GIS-based exposure method. METHODS: We obtained information for 354 cases of hypospadias born between 1998 and 2002 in eastern Arkansas; 727 controls were selected from birth certificates. We classified exposure on pounds of pesticides (estimated by crop type) applied or persisting within 500 m of each subject's home during gestational weeks 6 to 16. We restricted our analyses to 38 pesticides with some evidence of reproductive, developmental, estrogenic, and/or antiandrogenic effects. We estimated timing of pesticide applications using crop phenology and published records. RESULTS: Gestational age at birth [odds ratio (OR) = 0.91; 95% confidence interval (CI), 0.83-0.99], parity (OR = 0.79; 95% CI, 0.65-0.95), and delaying prenatal care until the third trimester (OR = 4.04; 95% CI, 1.46-11.23) were significantly associated with hypospadias. Risk of hypospadias increased by 8% for every 0.05-pound increase in estimated exposure to diclofop-methyl use (OR = 1.08; 95% CI, 1.01-1.15). Pesticide applications in aggregate (OR = 0.82; 95% CI, 0.70-0.96) and applications of alachlor (OR = 0.56; 95% CI, 0.35-0.89) and permethrin (OR = 0.37; 95% CI, 0.16-0.86) were negatively associated with hypospadias. CONCLUSIONS: Except for diclofop-methyl, we did not find evidence that estimated exposure to pesticides known to have reproductive, developmental, or endocrine-disrupting effects increases risk of hypospadias. Further research on the potential effects of exposure to diclofop-methyl is recommended.     

Is the incidence of hypospadias increasing? Analysis of Finnish hospital discharge data 1970-1994

Reports suggesting an increasing incidence of male genitourinary anomalies such as hypospadias, possibly related to environmental factors such as environmental estrogen-like compounds, have recently received considerable publicity. These reports are based on birth defects registry data, and there may be variation in the completeness of the registries used. We analyzed temporal trends in the prevalence of hypospadias in Finland to assess the previously reported low overall prevalence and to detect any possible increasing tendencies during the past decade. We identified all patients who were surgically treated for hypospadias before the age of 9 years among boys born 1970-1986 in the national hospital discharge registry. We calculated the cumulative prevalence by dividing the number of patients by the number of male births, and we used Poisson regression analysis. Out of 549,176 boys born in Finland in 1970-1986, 1,543 were treated for hypospadias by the age of 8 years (28.1 surgically treated patients per 10,000 male live births; 95% confidence interval, 26.7-29.5). The prevalence of hypospadias in Finland remained constant throughout the study period and appears to have been approximately three times higher than previously reported. Changes in completeness of registration may account for a substantial proportion of the reported increases in the prevalence of hypospadias in Finland and possibly also elsewhere.     

Distribution of hemoglobinopathy variants by ethnicity in a multiethnic state

It has been well known for many years that Black Americans are at increased risk for sickle cell disease and that individuals of Mediterranean ancestry are at increased risk for thalassemias. Beyond this, however, complete assessments of the epidemiology of hemoglobinopathies in Americans have been constrained by lack of large enough sample size, incomplete diagnostic work or testing inadequacies, or missing or misleading ethnicity data. California began universal, mandatory screening of all infants born in the state in 1990, and by January 1996, had screened over 3.3 million infants of various ethnic backgrounds. New information is now available on groups at increased risk for disease, as well as carrier status. The overall prevalence of sickle cell disease (all types) remains high in Blacks at 1 per 396 births, but is lower than expected (from east coast/Caribbean published data) for Hispanics at 1 in 36,000 births or from previously published data on other higher risk groups such as Middle Eastern (no cases in over 22,000 screens) or Asian Indian (1 case in 16,000 screens). The distribution of different types of sickle cell disease has also changed, with increased numbers of Hb SE disease resulting from multiethnic partnerships. Demographic trends in California have led to a major sift in the at-risk groups for major beta thalassemias, with the majority of cases detected in families of Asian. Southeast Asian, and Asian Indian ancestry. The “new” hemoglobinopathy condition in California, Hb E/Beta Thalassemia, is found almost exclusively in Southeast Asians with a prevalence of 1 in every 2,600 births. Carrier conditions are found in virtually every ethnic category, with higher than expected rates in non-Hispanic Whites (1 per 600 births). © 1996 Wiley-Liss, Inc.     

Hypospadias and maternal exposures to cigarette smoke

The few previous studies of hypospadias and smoking have suggested either no association or a reduced risk. This study, which uses data from the National Birth Defects Prevention Study, a multi-state, population-based case-control study, includes data on males born with severe hypospadias (i.e. the urethra opens at the penile shaft, scrotum or perineum) from 1997 to 2000. Non-malformed, liveborn male controls were selected randomly from birth certificates or from birth hospitals. Maternal interviews were completed by telephone with 453 case mothers and 1267 control mothers. Maternal smoking was not associated with hypospadias risk. For example, during the third month of pregnancy, smoking < 0.5 pack/day had an odds ratio (OR) of 1.1 [95% CI 0.6, 1.9]; 0.5 pack/day, 0.6 [0.4, 1.1]; and > or = 1 pack/day, 0.8 [0.4, 1.6]. Exposure to any secondhand smoke at home during the third month of pregnancy showed an OR of 0.6 [95% CI 0.4, 1.0], and exposure at work or school, an OR of 0.7 [0.5, 1.1]. Similar risks were observed for other months during the periconceptional period, and adjustment for several potential confounders did not substantially alter results. This analysis does not confirm a recent report suggesting that maternal smoking is associated with a reduced risk of having offspring with hypospadias.     

Role of structural birth defects in preterm delivery

The proportion of preterm births associated with structural birth defects has not been adequately quantified. We explored the proportion of preterm infants with structural birth defects diagnosed in the first year of life, as well as the specific phenotypes of birth defects occurring among preterm infants. The data used were from the California Birth Defects Monitoring Program, a population-based registry, as well as data from California vital records corresponding to births and fetal deaths in the period 1984-96. The prevalence of structural birth defects exceeded 8% among deliveries with gestational ages < or = 30 weeks, and prevalence decreased to 2% as gestational age increased to > or = 37 weeks gestation. The decreasing prevalence pattern with increasing gestational age was observed for a variety of anatomically defined birth defect groups suggesting that certain birth defects were not the sole contributors to the elevated prevalences among preterm births. Decreasing prevalence with increasing gestational age was also observed across strata of maternal race/ethnicities, ages, infant's sex and each year studied. These data indicate that structural birth defects may contribute significantly to the proportion of infants who are delivered before 37 weeks gestation.     

Neural tube defects in Victoria, Australia: potential contributing factors and public health implications

OBJECTIVES: To measure population prevalence and determine potential predictors of neural tube defects. METHOD: Analysis of all births reported to a mandated collection of perinatal data, and terminations prior to 20 weeks' gestation that have been reported to a data collection of birth defects in Victoria from 1983 to 1997. Prevalence at birth and risk ratios of infant and maternal characteristics associated with neural tube defects were calculated. RESULTS: Prevalence of spina bifida has remained steady for 15 years and was 8.8/10,000 in 1997. Anencephaly increased to 7.9/10,000 in 1997. After exclusion of pregnancy terminations, the 1997 birth prevalence was 4.5/10,000 for spina bifida and 2.4/10,000 for anencephaly. Neural tube defects are identified in 1 in 1600 fetuses, the risk being significantly higher for epileptic women (Adjusted Odds Ratio (AOR) = 3.70, 95% CI 2.25-6.07), multiple births (AOR = 4.56, 95% CI 3.46-6.02), teenage mothers (AOR = 1.47, 95% CI 1.09-2.00) compared with those aged 25-29, and women with three or more previous pregnancies (AOR = 1.40, 95% CI 1.10-1.78). The risk was lower for women of East Asian (AOR = 0.70, 95% CI 0.49-1.00) and Middle Eastern origin (AOR = 0.60, 95% CI 0.35-1.02) and these differences were approaching statistical significance. CONCLUSION: Total prevalence of neural tube defects did not decline up to 1997. IMPLICATIONS: It is unlikely that targeting 'at risk' groups identified in this study would make a difference to neural tube defect incidence. However, consideration could be given to identifying larger 'at risk' groups such as those with homocysteine metabolism defects.     

Trisomy 18 in Kuwait.

BACKGROUND: Trisomy 18 (Edwards' syndrome, T18) is the second most common trisomy in man. We describe 118 children with regular T18 who were ascertained clinically and cytogenetically in the Kuwait Medical Genetics Centre during 1980-1997. METHODS: Ascertainment of T18 cases was performed shortly after birth. Chromosomal studies were carried out in addition to other relevant investigations. To investigate the factors associated with T18, a case-control study was carried out with 131 normal healthy newborns. Studied factors included maternal and paternal age, birth order, abortion, associated malformation, and survival. Multiple logistic regression analysis was used to adjust for confounding between variables. RESULTS: There was a preponderance of females among T18 cases (female:male ratio 2.1:1). The majority of T18 cases (53%) died before the second week of life. The most common associated anomalies were: congenital heart (38.1%) and gastrointestinal (25.4%). Multiplicity of malformations was also observed. Significant seasonal variation in T18 cases was detected with a peak in spring. Of the 118 T18 cases, 59 were delivered during 1994-1997 (average overall T18 birth prevalence rate 8.95 per 10 000 live births [95% CI: 6.66-11.23]). Concerning maternal age, 30.5% of the T18 cases' mothers were > or =35 years compared to 10.7% in the control group. The difference was statistically significant, P = 0.002. Logistic regression analysis showed that maternal age >30 years was a significant risk factor for T18, after adjusting for confounding with paternal age. Paternal age and abortion were not found to be significant risk factors. CONCLUSION: Trisomy 18 birth prevalence rate is high in Kuwait with advanced maternal age as a significant risk factor.     

Evaluation of an association between loratadine and hypospadias--United States, 1997-2001

Hypospadias is a birth defect that affects approximately seven in 1,000 male infants in the United States. In affected infants, the urethral opening is located along the underside of the penis, scrotum, or perineum; the condition usually is corrected by surgery. Hypospadias is classified in order of increasing severity as first, second, or third degree. In 2002, a study in Sweden noted that among male infants born to women who while pregnant had taken loratadine (Claritin), a nonsedating antihistamine commonly used for seasonal allergies, hypospadias prevalence was twice that of the general population. However, insufficient data were available to determine the severity of the hypospadias cases, and the study did not control for confounding variables (e.g., family history of hypospadias or maternal age). In 2003, a prospective study using data from four countries indicated that five of 142 pregnancies in women exposed to loratadine resulted in infants with major malformations, a prevalence consistent with that of the general population; none had hypospadias. To further assess any potential association between loratadine and hypospadias, CDC analyzed data from the National Birth Defects Prevention Study (NBDPS). This report summarizes the results of that analysis, which determined that no increased risk for second- or third-degree hypospadias existed among women who used loratadine in early pregnancy. These results might be useful for women and health-care providers to address concerns about loratadine use and hypospadias.     

Maternal reproductive and demographic characteristics as risk factors for hypospadias

This study examined the association of hypospadias risk with several maternal reproductive and demographic characteristics: age, parity, body mass index (BMI), nausea and vomiting of pregnancy (NVP), multiple pregnancy, fertility treatments and procedures, education and race-ethnicity. The study included data on deliveries with estimated due dates from October 1997 to December 2000 that were part of the National Birth Defects Prevention Study, a multi-state case-control study of many birth defects. The analysis included 502 cases with second or third degree hypospadias (i.e. the urethra opened at the penile shaft, scrotum or perineum) and 1286 male, liveborn, non-malformed controls. Risks were estimated from a multivariable logistic regression model that included all exposures of interest. Results indicated particularly elevated risks among births to women who were primiparae, aged >or=35 years and had a BMI of >26, compared with women who were multiparae, aged <30 years and had a BMI of 相似文献   

Hypospadias and endocrine disruption: is there a connection?

Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 250 newborns or roughly 1 in 125 live male births. It is the result of arrested development of the urethra, foreskin, and ventral surface of the penis where the urethral opening may be anywhere along the shaft, within the scrotum, or in the perineum. The only treatment is surgery. Thus, prevention is imperative. To accomplish this, it is necessary to determine the etiology of hypospadias, the majority of which have been classified as idiopathic. In this paper we briefly describe the normal development of the male external genitalia and review the prevalence, etiology, risk factors, and epidemiology of hypospadias. The majority of hypospadias are believed to have a multifactorial etiology, although a small percentage do result from single gene mutations. Recent findings suggest that some hypospadias could be the result of disrupted gene expression. Discoveries about the antiandrogenic mechanisms of action of some contemporary-use chemicals have provided new knowledge about the organization and development of the urogenital system and may provide additional insight into the etiology of hypospadias and direction for prevention.     

Talipes equinovarus in Western Australia

In Western Australia (WA), talipes equinovarus is a notifiable birth defect and, since 1980, has been ascertained by the population-based Birth Defects Registry (BDR). Talipes equinovarus deformities were classified as two distinct and distinguishable types, viz. isolated talipes equinovarus (no other birth defects present) and associated talipes equinovarus (other birth defects present). The birth prevalence of associated talipes in WA between 1980 and 1994 was 0.90 per 1000 births, and of isolated talipes was 1.25 per 1000 births. The rate of the isolated deformity was higher in Aboriginal infants (3.49 per 1000 births) than in Caucasian infants (1.11 per 1000 births) and non-Aboriginal non-Caucasian infants (0.73 per 1000 births). The sex differential in the rate of the isolated deformity was greatest among Aboriginal infants, with the rate in males being almost four times that in females. The birth prevalence of both types of the deformity remained stable over the 15-year study period. The rate of caesarean and breech deliveries and the proportion of bilaterally affected feet was greater among infants with associated talipes equinovarus deformity. An accurate and complete identification of cases of isolated talipes equinovarus in the 1980-94 WA birth cohort provides a basis for furthering the understanding of the epidemiology and hence the aetiology of the deformity.     

Epidemiology and outcome of congenital diaphragmatic hernia: a 9-year experience

The aim of this study was to report the birth prevalence and short-term outcome of congenital diaphragmatic hernia (CDH) in a large geographically defined population, and to assess the feasibility of performing a randomised control trial (RCT) in this population. Data were collected on all cases of CDH reported to the East Midlands and South Yorkshire Congenital Anomalies Register between 1997 and 2005. A total of 194 cases of CDH were identified from 547,025 births; a birth prevalence of 3.5/10,000. Overall 1-year survival was 42%. In total, 69% of cases resulted in a live birth, of these 61% survived to 1 year; 73% were diagnosed antenatally and 22% postnatally, with 1-year survivals 30% and 71%, respectively. A total of 54% were isolated cases and 46% associated with another anomaly, with more live births (80% vs. 56%) and better 1-year survival (62% vs. 19%) with isolated CDH. Overall, only 83 babies were born alive with an isolated CDH: the only group suitable for inclusion in a RCT. In conclusion, given the small numbers of live isolated CDH cases it is impossible that any network alone would be able to perform a valid RCT of treatments, highlighting the need for collaborative international trials to address this complex condition.     

Evidence of an environmental contribution to the aetiology of cryptorchidism and hypospadias?

Objectives Evidence suggests that there is geographical variation in the birth prevalence of both cryptorchidism and hypospadias. The aim was to determine if there is evidence of spatial heterogeneity in the prevalence of these conditions and to test the hypothesis that environmental factors may contribute to aetiology. Methods A population-based dataset of cryptorchidism and hypospadias cases was constructed from the hospital episodes statistics that covered the Northern Region of England and assigned to a small area based on the residential address at time of admission. Expected numbers of cases for each small area were computed. The ratio of observed to expected cases was determined for each small area and analysed with respect to both geographical heterogeneity and small area level socio-economic deprivation. The Potthoff–Whittinghill method was used to determine if there was localized spatial clustering of cases. Results There was statistically significant spatial clustering for cases of both cryptorchidism [estimated Extra-Poisson Variation (EPV) = 0.14; 95% CI, 0.03–0.25] and hypospadias (EPV = 0.17; 95% CI, 0.05–0.28). In addition, increased prevalence was associated with lower levels of deprivation for hypospadias (P = 0.06), but there was no such relationship for cryptorchidism (P = 0.61). Conclusions The finding of localized spatial heterogeneity in the prevalence of cryptorchidism and hypospadias is consistent with the involvement of a spatially varying environmental risk factor. The apparent social patterning of hypospadias is likely to reflect an association with lifestyle and other factors which underpin social variation in health. However, there also remains a possibility that these findings may be due to variability in ascertainment of cases.     

Spatial and temporal clustering of isolated cleft lip with or without cleft palate in Poland

Background: Geographic variation in the prevalence of isolated cleft lip with or without cleft palate may be due to exogenous environmental factors or genetic variation. In this study, we aim to evaluate the prevalence of isolated cleft lip with or without cleft palate in Polish urban and rural environments in order to identify geographic areas with high prevalence (defect clusters). Methods: We use all cases of congenital malformations reported to the Polish Registry of Congenital Malformations in the years 1998–2008 from the total population of 2,362,502 births. Results: We detect a strong signal of increased prevalence of isolated cleft lip with or without cleft palate in a single region of Poland, the Dolno?l?skie voivodeship. Furthermore, we demonstrate a statistically significant prevalence differences between the urban and rural areas within this region. Through our comprehensive spatiotemporal analysis, we precisely define the cluster of the highest risk that comprises the eastern part of this voivodeship.