Live Male Births Research Articles

P02-210 - Klinefelter's Syndrome and psychiatric pathology: a case report

IntroductionThe presence of an extra X-chromosome, also known as Klinefelter's Syndrome, occurs in approximately 1 in 500 live male births. Epidemiological studies have reported an increased vulnerability to psychiatric disturbances in this group of patients and suggest that the X chromosome may be involved in the aetiology.Material and MethodsComprehensive review of the scientific literature (Medline, Ovid) on Psychiatric pathology in Klinefelter's Syndrome published over the last 20 years.ResultsThis is a case report of a 27 year-old-male with Klinefelter's Syndrome confirmed by karyotyping (XXY), suffering from different neuropsychiatric disorders, such as mental retardation, dyslexia, ADHD and social dysfunctioning. Since the age of 16 he has required multiple psychiatric hospitalizations due to his impulse control difficulties and exaggerated mood swings.This case raises the question of whether Klinefelter's syndrome patients are predisposed to psychiatric pathology (including Schizophrenia, Bipolar Disorder, Anorexia Nervosa or social-emotional processing) at a genetic level.ConclusionsReviews of the neuropsychiatric problems associated with Klinefelter's Syndrome confirm an association between disorders in this area and the chromosomal abnormality. Further studies are needed to identify involvement of X-linked epigenetic influence and susceptibility to several psychiatric diseases.

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.

Distribution of Birth Weight for Gestational Age in Japanese Infants Delivered by Cesarean Section

BackgroundNeonatal anthropometric charts of the distribution of measurements, mainly birth weight, taken at different gestational ages are widely used by obstetricians and pediatricians. However, the relationship between delivery mode and neonatal anthropometric data has not been investigated in Japan or other countries.MethodsThe subjects were selected from the registration database of the Japan Society of Obstetrics and Gynecology (2003–2005). Tenth centile, median, and 90th centile of birth weight by sex, birth order, and delivery mode were observed by gestational age from 22 to 42 weeks among eligible singleton births.ResultsAfter excluding 248 outliers and 5243 births that did not satisfy the inclusion criteria, 144 980 births were included in the analysis. The distribution of 10th centile curves was skewed toward lower birth weights during the preterm period among both first live births and second and later live births delivered by cesarean section. More than 40% of both male and female live births were delivered by cesarean section at 37 weeks or earlier.ConclusionsThe large proportion of cesarean sections influenced the skewness of the birth weight distribution in the preterm period.

Human sex ratio at birth and related factors

Sir, The ‘‘sex ratio at birth’’ (SRB) is defined as the number of male live births per every 100 female births. Within any population, the determination of sex at birth is understood to be the result of complex paternal and maternal factors. For any single pregnancy, the sex-determining region Y (SRY) gene which is located on the Y chromosome determines the sex of a fertilized egg. There is a normalized rate of the proportion of male and female births. Based on the United Nations report in 2004, for every 100 female births, 105 male births occur typically, which can also be explained as the male proportion of 0.515 w23x. Neonatal gender bears significant social and psychological impact on societies. Many families tend to have sex preferences. As a result, many studies evaluated the effects of various factors on sex ratio. Even long before the advent of modern reproductive technologies, people have been interested in giving birth specifically to a boy or a girl, trying every technique ranging from herbal treatments to sexual positions that have been claimed to yield a male or female baby. Maternal stress and balanced diets (N-6 enriched in corn oil) increase probability of female birth w9x. Maternal eating disorders may also influence the offspring sex and the direction of the effect may vary according to the eating disorder subtype w3x.

Fecundidad de la chinchilla (Chinchilla laniger gray) macho de criadero.

In male chinchillas of commercial flocks fertility demographic indexes were studied in order to asses its reproduction capacity. The data were obtained from the registries of two commercial flocks of the Metropolitan region of Chile. These flocks were very similar in their management. The mean general rase fertility was 3.06 live births by male in a year. The greatest speciflc fertility rase was observed in animals aged from 1.5 to 5.5 years. The total fertility rate showed that the mean offspring of a mate chinchilla was 51 live births during his life, 27 of them were male live births. The sex rase at birth was 111 males by 100 females and the sex rate during the reproduction age was 59 males by 100 females.

Review of Duchenne Muscular Dystrophy (DMD) for the Pediatricians in the Community

Duchenne muscular dystrophy (DMD), an inherited X-linked recessive disorder, is characterized by progressive symmetric muscle weakness and gait disturbance, with onset in early childhood. DMD is the most common muscular dystrophy in children, and incidence ranges from 1 in 3600 to 4700 live male births. Early diagnosis (screening, confirmation, and genetic counseling), treatment, and long-term follow-up of affected individuals in routine pediatric practice can be challenging and are the focus of this review.

Targeting Fibrosis in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is the most common genetic muscle disease affecting 1 in 3,500 live male births. It is an X-linked recessive disease caused by a defective dystrophin gene. The disease is characterized by progressive limb weakness, respiratory and cardiac failure, and premature death. Fibrosis is a prominent pathological feature of muscle biopsies from patients with DMD. It directly causes muscle dysfunction and contributes to the lethal DMD phenotype. Although gene therapy and cell therapy may ultimately provide a cure for DMD, currently the disease is devastating, with no effective therapies. Recent studies have demonstrated that ameliorating muscle fibrosis may represent a viable therapeutic approach for DMD. By reducing scar formation, antifibrotic therapies may not only improve muscle function but also enhance muscle regeneration and promote gene and stem cell engraftment. Antifibrotic therapy may serve as a necessary addition to gene and cell therapies to treat DMD in the future. Therefore, understanding cellular and molecular mechanisms underlying muscle fibrogenesis associated with dystrophin deficiency is key to the development of effective antifibrotic therapies for DMD.

Contemporary Epidemiology and Characterization of Newborn Males with Prune Belly Syndrome

Prune belly syndrome (PBS) is a rare condition characterized by the congenital absence or deficiency of the abdominal wall musculature, with associated abnormalities of the genitourinary tract, including hydronephrosis and cryptorchidism. Few population-based epidemiology or mortality data are available. We retrospectively reviewed the Kids' Inpatient Database to evaluate PBS among newborn infants during their initial hospitalization in 2000, 2003, and 2006. The International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients and to determine the comorbidity status. The PBS incidence, demographics, comorbid conditions, and disposition were assessed. A total of 133 newborn male infants diagnosed with PBS were identified of 1,420,991 live male births, for a weighted incidence estimate of 3.8 cases/100,000 live births. Of the newborns with PBS, 50% were white, 31% black, and 10% were Hispanic. In-hospital mortality was high (39 of 133, 29%). Of the 133 patients with PBS, 55 (41%) were discharged home and 39 (29%) required inpatient transfer or home nursing care. Fifty-seven patients (43%) were born premature; 56% of the PBS deaths occurred in premature infants. Mechanical ventilation was required in 64 newborns (48%), and 33 (24%) had coexisting congenital cardiovascular anomalies. Renal failure was uncommon, occurring in only 5 newborns (4%); none required dialysis. Only 13 patients (10%) underwent urinary diversion (vesicostomy or ureterostomy). The incidence of PBS was 3.8 cases/100,000 live births. Despite advances in care for children with PBS, this condition continues to be associated with high perinatal mortality, likely related to the associated prematurity and pulmonary complications. Renal failure was rare, as was immediate urinary diversion.

Klinefelter's syndrome and psychoneurologic function

Klinefelter's syndrome (KS) is due to the presence of one or more supernumerary X chromosomes. Aneuploidy 47,XXY is the most common abnormality of sex chromosomes in humans, with an incidence of 1/500 male live births. Only one-third of subjects with KS is, however, diagnosed. The aim of this work is to present a review of current literature about neurogenetic functions in KS, referring to both clinical and therapeutics aspects. If it is well known that the majority of subjects with 47,XXY karyotype have a normal intellectual level, the identification of strengths and weaknesses of their intellectual functioning is important for the purpose of planning early psycho-educational interventions. Language difficulties are one of the more distinctive traits in cognitive functioning of people with KS. It has also been suggested that the limitations in communication markedly affect social adaptation and behavioral aspects, as well as the development of personality. Moreover, difficulties in learning language appear to be related to an altered functional lateralization; therefore, KS subjects are a suitable model for studying genetic abnormalities of lateralization. In this, perspective psychopathological risk is analyzed. Early recognition of this aspect is needed to address the educational and therapeutic perspectives for KS subjects.

Proteomic analysis of amniotic fluid in pregnancies with Klinefelter syndrome foetuses

Klinefelter syndrome is a sex chromosomal abnormality (47, XXY karyotype), occurring approximately in 1 in 1000 male live births. In the present study proteomic analysis was performed in twelve 2nd trimester amniotic fluid samples, eight coming from pregnancies with normal males and four with Klinefelter syndrome foetuses, as shown by routine prenatal cytogenetic analysis. Samples were analysed by 2-DE, coupled with MALDI-TOF-MS analysis. Three proteins (Ceruloplasmin, Alpha-1-antitrypsin and Zinc-alpha-2-glycoprotein) were found to be up-regulated in samples obtained from pregnancies with Klinefelter syndrome foetuses, whereas four proteins (Apolipoprotein A-I, Plasma retinol-binding protein, Gelsolin, and Vitamin D-binding protein) were down regulated when compared to proteins detected in samples from normal foetuses. The differential expression of Ceruloplasmin, Apolipoprotein A-I and Plasma retinol-binding protein was further confirmed by immunoblotting. Since these proteins are likely to cross the placenta barrier and be detected in maternal plasma they could be used as biomarkers for the non-invasive prenatal diagnosis of Klinefelter syndrome.

Gene changes in Duchenne muscular dystrophy: Comparison of multiplex PCR and multiplex ligation-dependent probe amplification techniques

Duchenne muscular dystrophy (DMD) is a common X-linked recessive neuromuscular disorder, affecting 1 in 3,500 live male births. About 65% of cases are caused by deletions; ~5% to 8%, by duplication; and the remaining, by point mutations of the dystrophin gene. The frequency of complex rearrangements (double-deletion and non-contiguous duplications) is reported to be 4%. In this study, we examined the usefulness of multiplex ligation-dependent probe amplification (MLPA) for screening of deletion and duplication mutations in a group of DMD/ BMD (Becker muscular dystrophy) patients from India. We analyzed 180 patients referred from all over India, by both multiplex PCR technique (22 exons) and MLPA (all 79 exons). By multiplex PCR, deletions were detected in 90 (50%) patients. MLPA studies in these cases detected 3 additional deletions, 16 (8.9%) duplications and 2 point mutations. MLPA is useful to verify absence of deletions/ duplications in all 79 exons. This sets the stage to look for point mutations using RNA- or DNA-based tests because of the availability of the drug PTC124. Also, the extent of the deletions and duplications could be more accurately defined by MLPA. The delineation of the precise extent of deletion helps in deciding whether exon-skipping technique would be useful as therapy.

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.

Hemophagocytic lymphohistiocytosis in a patient with x-linked lymphoproliferative disease

X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency affecting approximately 1 to 3 per million live male births. Patients are generally healthy until facing a viral infection such as Epstein-Barr Virus and then may develop fulminant infectious mononucleosis and die. XLP patients are also at increased risk of hemophagocytic lymphohistiocytosis (HLH), which may be triggered by assorted viruses. Here we report a novel case of HLH in a patient with XLP. Significant to his presentation is a paradoxical increase in natural killer (NK) cell activity. We hypothesize that this indicates that Parvovirus B19 activates NK cells via a signaling lymphocytic activation molecule-associated protein (SAP)-independent mechanism. Our case demonstrates an important etiology to consider in the differential diagnosis of XLP patients with nonfocal findings and febrile illnesses.

Incidence of the mucopolysaccharidoses in Taiwan, 1984–2004

Previous studies on the incidence of the various types of mucopolysaccharidoses (MPS) in different populations have shown considerable variation. However, information regarding the incidence of MPS in the Asian population is lacking. An epidemiological study of the MPS disorders in Taiwan using multiple ascertainment sources was undertaken, and incidences of different types of MPS during the period of 1984-2004 were estimated. We compared our data with previous reports in different populations. The combined birth incidence for all MPS cases was 2.04 per 100,000 live births. MPS II (Hunter syndrome) had the highest calculated birth incidence of 1.07 per 100,000 live births (2.05 per 100,000 male live births), comprising 52% of all MPS cases diagnosed. The birth incidences of MPS I (Hurler syndrome), III (Sanfilippo syndrome), IV (Morquio syndrome), and VI (Maroteaux-Lamy syndrome) were 0.11, 0.39, 0.33, and 0.14 per 100,000 live births, respectively, which accounted for 6%, 19%, 16%, and 7% of all MPS, respectively. No cases of MPS III D (Sanfilippo syndrome type D), MPS IV B (Morquio syndrome type B), MPS VII (Sly syndrome) or MPS IX were ascertained during the study period. Overall incidence of MPS in Taiwan was consistent with that reported in Western populations. However, in contrast to the higher incidence of MPS I in most Western populations, this study showed a higher incidence of MPS II in Taiwan. It remains to be investigated whether this discrepancy is attributed to the under-diagnosis of MPS I in Taiwan or to ethnic differences.

Clinical and Molecular Characteristics of 35 Chinese Children with Wiskott–Aldrich Syndrome

Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency disease, with an incidence of 4/1,000,000 live male births. In China, an estimated number of 35 babies with WAS are born each year, but likely many remain undiagnosed. The objectives of study were to review the clinical and molecular characteristics of a cohort of Chinese children with WAS and to describe the long-term outcome of those who underwent hematopoietic stem cell transplant (HSCT). Records of 35 patients diagnosed with WAS during 1991-2008 were reviewed. Genetic diagnosis was established by direct gene sequencing. All patients had classical WAS phenotype. WASP mutations were identified in 33 patients from 29 families. Nine patients underwent HSCT at a mean age of 22.1 months (match-unrelated donor, n = 5; mismatched related donor, n = 2; matched-sibling donor, n = 2). Post-transplant immune hemolytic anemia and thrombocytopenia occurred in three patients with complete resolution. All patients survived without significant long-term complications and had full platelet, T and B lymphocyte recovery within 2 years post-transplant. In the past decade, there has been significant improvement in clinical and genetic diagnosis of WAS in Chinese. We demonstrated excellent long-term survival in patients who underwent HSCT. Early workup for transplant should be advocated for children with classical WAS before they suffer from major disease complications and morbidities.

A Pregnant Pause to Consider Teratogenicity of Topiramate

Topiramate in Pregnancy: Preliminary Experience from the UK Epilepsy and Pregnancy Register. Hunt S, Russell A, Smithson WH, Parsons L, Robertson I, Waddell R, Irwin B, Morrison PJ, Morrow J, Craig J, UK Epilepsy and Pregnancy Register. Neurology 2008;71(4):272–276. Objectives Topiramate (Topamax®) is licensed to be used, either in monotherapy or as adjunctive treatment, for generalized tonic-clonic seizures or partial seizures with or without secondary generalization and for prevention of migraine. The safety of topiramate in human pregnancy is largely unknown. Here we report on our experience of pregnancies exposed to topiramate. Methods This study is part of a prospective, observational registration and follow-up study. Suitable cases are women with epilepsy who become pregnant while taking topiramate either singly or along with other antiepileptic drugs (AEDs), and who are referred before outcome of the pregnancy is known. The main outcome measure is the major congenital malformation (MCM) rate. Secondary outcomes include risk of specific MCM, minor malformation rate, birthweight, and gestational age at delivery. Results Full outcome data are available on 203 pregnancies. Of these, 178 resulted in live birth; 16 had an MCM (9.0%; 95% CI 5.6–14.1%). Three MCMs were observed in 70 monotherapy exposures (4.8%; 95% CI 1.7–13.3%) and 13 in cases exposed to topiramate as part of a polytherapy regimen (11.2%; 95% CI 6.7–18.2%). Four of the MCMs were oral clefts (2.2%; 95% CI 0.9–5.6%). Four cases of hypospadias were reported (5.1%; 95% CI 0.2–10.1%) among 78 known live male births, of which two were classified as major malformations. Conclusions The number of outcomes of human pregnancies exposed to topiramate is low, but the MCM rate for topiramate polytherapy raises some concerns. Overall, the rate of oral clefts observed was 11 times the background rate. Although the present data provide new information, they should be interpreted with caution due to the sample size and wide confidence intervals.

Maternal Eating Disorders Influence Sex Ratio at Birth

Previous studies have shown that low maternal weight, a diet low in certain fats, higher stress levels, and lower androgen levels are associated with fewer male births, but no association has been reported between maternal eating disorders and sex ratio at birth (defined as the proportion of male live births). This prospective, population-based, cohort study was conducted as part of the Norwegian Mother and Child Cohort Study. A total of 38,340 pregnant women at a median of 18.6 weeks gestation completed a questionnaire on eating behavior that reflected DSM IV criteria for four eating disorders: anorexia nervosa, binge eating disorder, bulimia nervosa, and eating disorders not otherwise specified-purging type (EDNOS-P). Estimates of the sex ratio at birth were determined for women with singleton live births and eating disorder diagnoses. Poisson regression analyses were used to estimate unadjusted and adjusted proportions and ratios for factors known to affect the sex ratio at birth, including mother's age, marital status, prepregnancy body mass index (BMI), maternal education, lifetime smoking status, income, gestational age, and parity. Compared to a reference group, unadjusted analyses showed that proportions of male live births were 10% lower for mothers with anorexia nervosa and 8% lower for mothers with bulimia nervosa. A higher proportion of male births was found among mothers with maternal binge eating disorder (4%) and EDNOS-P (28%). Adjustment for covariates did not affect the results. These data suggest an association between the sex of offspring and maternal eating disorders. The specific eating disorder subtype appears to influence the direction of the effect.

Early detection of cardiomyopathy in Duchenne muscular dystrophy, is there a role for MRI?

Muscular dystrophies are progressive myopathic disorders resulting from defects in a number of genes required for normal muscle function [1]. Duchenne muscular dystrophy is caused by a defective gene located on the X chromosome, that is responsible for the production of dystrophin [2] and is related to other inherited myopathies like Emery–Dreifuss muscular dystrophy, Becker muscular dystrophy, limb-girdle muscular dystrophies, fascioscapulohumeral muscular dystrophy and myotonic dystrophy. Duchenne muscular dystrophy has a recessive inheritance. The disease is clinically associated with muscle fiber degeneration. The incidence is one in 3,500 live male births, with a prevalence of 3 per 100,000 [3]. The clinical onset of weakness usually occurs between 2 and 3 years of age [4]. One of the major complications of Duchenne muscular dystrophy is a dilated cardiomyopathy. The main cardiac expression of the disease is extensive fibrosis of the posterobasal and lateral left ventricular wall. In patients with Duchenne muscular dystrophy, the incidence of the cardiomyopathy increases from zero under the age of 10, to one-third at the age of 14 years to one half at the age of 18 years and nearly 98% in patients over 18 years [5]. The incidence of cardiac failure in female carriers is reported to be 10% even in the absence of skeletal muscle involvement [6]. However, in these females carriers, life expectancy is not affected by the presence of the abnormal gen [7]. The cardiomyopathy can be detected by an abnormal ECG characterized by tall right precordial R waves with an increased R/S ratio and deep Q waves in the lateral leads and by echocardiography showing localised lateral thinning and akinesia and noncompaction of the endocardium ultimately progressing in a dilated cardiomyopathy [8–10]. For early and appropriate detection of cardiac involvement of muscular dystrophy, a recent workshop on the management of cardiac involvement in muscular dystrophy gave the following recommendations:

How can economic schemes curtail the increasing sex ratio at birth in China?

Fertility decline, driven by the one-child policy, and son preference have contributed to an alarming difference in the number of live male and female births in China. We present a quantitative model where people choose to sex-select because they perceive that married sons are more valuable than married daughters. Due to the predominant patrilocal kinship system in China, daughters-in-law provide valuable emotional and financial support, enhancing the perceived present value of married sons. We argue that inter-generational transfer data will help ascertain the extent to which economic schemes (such as pension plans for families with no sons) can curtail the increasing sex ratio at birth.

Consumo de agrotóxicos e distribuição temporal da proporção de nascimentos masculinos no Estado do Paraná, Brasil

To determine the trend in male birth rates from 1994-2004 in the state of Paraná, Brazil, and whether a correlation exists between this trend and the state's agricultural toxic sales in 1985. This ecological study employed data from the Brazilian Institute for Geography and Statistics (agricultural toxic sales) and the Unified Health System's database "DATASUS" (sex ratio at birth). Three hundred and eight (308) municipalities were analyzed, divided into quartiles by pesticide usage. Each of the four resulting quartiles included 77 municipalities, with the fourth quartile representing the highest consumption. The male birth rate was obtained for each year for each municipality. Then the median rate was calculated for the entire period (1994-2004) for each municipality. A bivariate analysis was carried out. Pearson coefficients were calculated for each quartile. An exploratory and comparative analysis of quartiles was performed, and the mean per capita consumption was calculated for each quartile. Ten municipalities with intense agricultural activity were then selected and analyzed individually in terms of their agricultural profile and male birth rate trend during the study period. A discrete decline was observed in the rate of live male births for the entire state. The magnitude of this decline was more evident when the group of 10 municipalities was analyzed: in this group, the rates observed at the end of the study period were much lower than those usually described in the literature (male birth rate < 50%). Pearson's correlation was negative for all quartiles, although without statistical significance. The statistically significant trend towards a decline in male births in some of the Paraná municipalities suggests that this phenomenon may be a result of a high level of environmental exposure to pesticides. Future studies should confirm and measure the impact of environmental pesticide contamination on reproductive health, expressed in this study as sex ratio at birth.