Live Male Births Research Articles

Occurrence of hemophilia in the United States

An active surveillance system was used to identify all residents with hemophilia in six U.S. states (Colorado, Georgia, Louisiana, Massachusetts, New York, and Oklahoma). A hemophilia case was defined as a person with physician-diagnosed hemophilia A or B and/or a measured baseline factor VIII or IX activity (FA) of 30% or less. Case-finding methods included patient reports from physicians, clinical laboratories, hospitals, and hemophilia treatment centers. Once identified, trained data abstractors collected clinical and outcome data retrospectively from medical records. Among cases identified in 1993-1995, 2,743 were residents of the six states in 1994, of whom 2,156 (79%) had hemophilia A. Of those with available FA measurements, 1,140 (43%) had severe (FA < 1%), 684 (26%) had moderate (FA 1%-5%), and 848 (31%) had mild (FA 6%-30%) disease. The mean and median age was 25.4 and 23 years, respectively. The age-adjusted prevalence of hemophilia in all six states in 1994 was 13.4 cases/100,000 males (10.5 for hemophilia A and 2.9 for B). The prevalence by race/ethnicity was 13.2 cases/100,000 among white, 11.0 among African American, and 11.5 among Hispanic males. Application of age-specific prevalence rates from the six surveillance states to the U.S. population resulted in an estimated national population of 13,320 cases of hemophilia A and 3,640 cases of hemophilia B. For the 10-year period 1982-1991, the average incidence of hemophilia A and B in the hemophilia surveillance system (HSS) states was estimated to be 1 in 5,032 live male births.

Incidence of the mucopolysaccharidoses in Northern Ireland.

An epidemiological study of the mucopolysaccharidoses (MPS) in Northern Ireland using multiple ascertainment sources was carried out and the incidence rate for the period 1958-1985 was estimated. An incidence of approximately 1 in 76,000 live births was obtained for MPS 1H (Hurler phenotype); 1 in 280,000 for MPS 1 H/S (Hurler/Scheie phenotype); 1 in 140,000 live births (1 in 72,000 male live births) for MPS II (Hunter syndrome); 1 in 280,000 for MPS III (Sanfilippo syndrome) and 1 in 76,000 for MPS IV A (Morquio syndrome type A). No cases of MPS IS (Scheie phenotype), MPS IV B (Morquio syndrome type B) or MPS VI (Maroteaux-Lamy syndrome) were ascertained during the study period. Three cases of non-immune hydrops fetalis born to consanguineous parents were thought to be due to beta-glucuronidase deficiency (MPS VII) on the basis of placental histology and enzyme studies on both parents but no living cases of MPS VII were ascertained. The overall incidence for all types of mucopolysaccharidosis was approximately 1 in 25,000 live births. A comparison is made with incidence estimates obtained from other published studies.

Albanian paradox, another example of protective effect of Mediterranean lifestyle?

Low mortality in Mediterranean populations has stimulated much interest, a possible explanation being diet. We have analysed data from Albania, the poorest country in Europe, to see if they corroborate findings from elsewhere in the region. Data on mortality routinely collected in Albania, corrected for incompleteness, were analysed. Demographic and food consumption data from United Nations agency sources were used to identify potential explanations for the mortality pattern. Consistent with its economic situation, Albania has one of the highest infant mortality rates in Europe (45.4 per 1000 live births for males and 38.0 for females in 1990). By contrast, adult mortality, including mortality from cardiovascular diseases, is similar to that in other Mediterranean countries. For example, age-standardised mortality for coronary heart disease in males aged 0-64 was 41 per 100,000 in Albania in 1990, less than half the rate in the UK but similar to that in Italy. Analysis of the geographical distribution of mortality within Albania (1978) showed that mortality was lowest in the southwest where most of the olive oil, fruits, and vegetables are produced and consumed. This paradox of high adult life expectancy in very-low-income country can be most plausibly explained by diet--namely, low consumption of total energy, meat, and milk products but high consumption of fruit, vegetables, and carbohydrates. If this hypothesis is confirmed by future research, Albanian experience can contribute to formulation of preventive policy in high mortality countries.

4. Gene Therapy of Duchenne Muscular Dystrophy

This chapter reviews the gene therapy of Duchenne muscular dystrophy (DMD). DMD is an X-linked disorder affecting about 1:3500 live male births. It is a more complex disease involving the heart and the central nervous system (CNS), as well as peripheral nerves and smooth muscle; it is generally noticed between the ages of 2 and 5 years. Skeletal muscle is the tissue with the most striking pathology in patients lacking dystrophin, but heart and central nervous system (CNS) may also be affected. More recent studies using magnetic resonance spectroscopy indicate that DMD patients have significant higher values than controls in the brain ratios of inorganic phosphate to ATP to phosphomonoesters, and to phosphocreatine. Animal models are becoming increasingly important in testing potential therapeutic approaches for DMD. Histopathologic analysis of skeletal muscle appears to be the easiest and most reliable way of assessing the efficacy of dystrophin gene replacement, particularly if the analysis is carried out in the diaphragm.

Gender differences in postneonatal infant mortality in Taiwan

Numerous studies have indicated that gender discrimination influencing child survival is widespread in Asia. Therefore, we have investigated gender and cause-specific postneonatal mortality in Taiwan. Mortality data derived from death certificates and demographic statistics in Taiwan between 1981 and 1990 were analyzed. Postneonatal mortality decreased from 9.4 per 1000 live births to 5.5 per 1000 live births for males, and from 8.3 to 5.0 for females. The trends for cause-specific mortality for male and female infants were similar during the study period. The male-to-female ratio of overall death rates was 1.11. It was slightly higher in cities and lower in rural areas, and lowest in the least developed eastern region of Taiwan. Mortality from congenital diseases had the lowest male-to-female ratio, specifically in the North, the cities and areas of indigenous people. Infectious disease mortality showed low male-to-female ratios in the rural areas and in the eastern region. The place of death from infectious diseases as a measure for the use of sophisticated medical care showed that more female than male deaths occurred at home in the rural areas, cities, and central regions. It was concluded that a high level of socio-economic development created conditions of gender equality, whereas in situations of low socio-economic development males were favoured. The tendency to discriminate according to gender is very subtle in Taiwan, much less so than in other regions of Asia, including Thailand and India.

The recognition and investigation of X-linked learning disability syndromes

X-linked learning disability syndromes occur in approximately one per 600 live male births and account for 20-30% of all learning disability. Fragile-X syndrome comprises some 40% of all X-linked learning disability, and there are currently about 95 recognized syndromes comprising the rest. Clinicians should be alert to these other forms of X-linked learning disability: families should be offered genetic counselling, including dysmorphology opinion and cytogenetic testing. Gene mapping on the X chromosome is advancing very rapidly and some causative genes for X-linked learning disability are now known. Clinicians involved in the care of patients with X-linked learning disability are encouraged to investigate all families, report new syndromes and those with cytogenetic abnormalities, and collaborate with clinical geneticists and laboratory scientists working on X chromosome gene mapping.

Muscular Dystrophy

Several varieties of muscular dystrophy can be distinguished on clinical, genetic, morphologic, and physiologic grounds. The classification includes Duchenne and Becker muscular dystrophies, both X-linked disorders; facioscapulohumeral muscular dystrophy, which is autosomal dominant; and limb-girdle muscular dystrophy, generally autosomal recessive. Duchenne muscular dystrophy (DMD), which occurs in approximately 1 in 3500 live male births, has no recognizable signs or symptoms at birth. However, markedly elevated serum creatine kinase always is demonstrable, even at birth. A molecular diagnosis can be made at any time in the patient's lifetime by demonstrating the defect in the dystrophin gene, the absence of dystrophin in a muscle biopsy, and the characteristic morphologic abnormalities.

Birth Complications Combined With Early Maternal Rejection at Age 1 Year Predispose to Violent Crime at Age 18 Years

Background: This study tests the biosocial interaction hypothesis that birth complications when combined with early maternal rejection of the infant predispose to adult violent crime. Methods: This hypothesis was tested using a cohort of 4269 consecutive live male births on whom measures of birth complications (age 0), early maternal rejection (age 1 year), and violent crime (age 18 years) were collected. Results: A significant interaction (P Conclusions: To our knowledge, this is the first study to show that birth complications in combination with early child rejection predispose to violent crime. The findings illustrate the critical importance of integrating biological with social measures to fully understand how violence develops and also suggest that prenatal, perinatal, and early postnatal health care interventions could significantly reduce violence.

High Sex Ratios in China's Future

In China in recent years, male live births have exceeded those of females by amounts far greater than those that occur naturally in human populations, a trend with significant demographic consequences. The resulting imbalance in the first-marriage market is estimated to be about 1 million males per year after 2010. These "excess" males were not easily accommodated in models with substantial changes in first-marriage patterns. The current sex ratio at birth has little effect on a couple's probability of having at least one son, so future increases in the sex ratio may well occur, especially given increasing access to sex-selective abortion.

Duchenne muscular dystrophy.

Duchenne and Becker muscular dystrophy are X-linked muscle-wasting disorders that arise from mutations in the gene coding for dystrophin. The incidence of Duchenne muscular dystrophy (DMD) is approximately 1 in 3500 live male births, one-third of which are sporadic with no previous family history. In the absence of dystrophin, patients with DMD exhibit progressive muscle fiber necrosis which, despite the regenerative capacity of the muscle during the early stages, leads to the gradual deposition of fibrotic and fat tissues and the loss of ambulation around 11 years of age. Death due to respiratory failure usually occurs by the third decade (Emery, 1993). Becker muscular dystrophy (BMD), the incidence of which is approximately 10-fold less than DMD, follows a generally much milder course due to the presence of a partially functional form of dystrophin. Generally the BMD phenotype tends to be much more varied, both with regard to the age of onset and clinical presentation, and some patients never lose the ability to walk.

Duchenne muscular dystrophy: present and future therapy

Duchenne muscular dystrophy (DMD) is the second commonest genetic disease in Western populations, occurring in 1 in 4000 live male births/ It is an X-linked disorder, characterized by progressive loss of muscle power and development of joint contractures, which may be associated with intellectual impairment and cardiomyopathy. Progressive respiratory muscle weakness and occasionally cardiomyopathy lead to death in affected boys by their late teens or early twenties. While a relatively small part of paediatric workload, the importance of the condition is two-fold: first, while at present there is no curative treatment, the quality of life of affected boys can be improved considerably by vigorous appropriate management; secondly, the explosion of interest in molecular genetics and possible gene therapy has featured DMD and its milder allelic disorder Becker muscular dystrophy (BMD) as one of the inherited conditions in which the gene has been cloned and has offered itself for manipulation. wide range of tissues including muscle, brain and cardiac muscle. It is absent from DMD muscle, leading to muscle cell necrosis. This forms the basis of the diagnostic features on muscle biopsy: in DMD, dystrophin cannot be identified whereas in BMD, dystrophin is present although in reduced amount or of altered molecular weight. The molecular abnormalities in DMD and BMD are usually intragenic deletions, which can be identified with current laboratory techniques in about 65% of boys. Other abnormalities identified include point mutations and duplications. The position of the deletion with reference to the DNA triplet eodon sequence of bases has been suggested to explain severity of phenotype; for those deletions which leave the reading frame out of frame, a severe phenotype occurs as the genetic message is a nonsense, while an in-frame deletion leads to a milder phenotype such as BMD as dystrophin, albeit a truncated form, is synthesized)

Birth Complications Combined With Early Maternal Rejection at Age 1 Year Predispose to Violent Crime at Age 18 Years

This study tests the bisocial interaction hypothesis that birth complications when combined with early maternal rejection of the infant predispose to adult violent crime. This hypothesis was tested using a cohort of 4269 consecutive live male births on whom measures of birth complications (age 0), early maternal rejection (age 1 year), and violent crime (age 18 years) were collected. A significant interaction (P < .0001) between birth complications and early maternal rejection indicated that those who suffered both birth complications and early child rejection were most likely to become violent offenders in adulthood. While only 4.5% of the subjects had both risk factors, this small group accounted for 18% of all violent crimes. The effect was specific to violence and was not observed for nonviolent criminal offending. To our knowledge, this is the first study to show that birth complications in combination with early child rejection predispose to violent crime. The findings illustrate the critical importance of integrating biological with social measures to fully understand how violence develops and also suggest that prenatal, perinatal, and early postnatal health care interventions could significantly reduce violence.

Reappraisal of the incidence rate of Duchenne and Becker muscular dystrophies on the basis of molecular diagnosis.

The incidence rates of Duchenne and Becker muscular dystrophies (X-linked recessive) in a given sample of the Italian population were recalculated using the results of DNA and dystrophin analysis. While the incidence rate of Duchenne muscular dystrophy remained unchanged, the new figure for the incidence of Becker muscular dystrophy (7.2 per 100,000 male live births) was much higher than previously reported, since molecular diagnosis revealed additional cryptic cases, but this incidence is still an underestimate.

Cell transplantation and gene therapy in muscular dystrophy.

Duchenne's muscular dystrophy (DMD), which affects 1/3500 live male births, involves a progressive degeneration of skeletal and cardiac muscle, leading to early death. The protein dystrophin is lacking in DMD and present, but defective, in the allelic, less severe, Becker muscular dystrophy and is also missing in the mdx mouse. Experiments on the mdx mouse have suggested two possible therapies for these myopathies. Implantation of normal muscle precursor cells (mpc) into mdx skeletal muscle leads to the conversion of dystrophin-negative fibres to -positive, with consequent improvement in muscle histology. Direct injection of dystrophin cDNA into skeletal or cardiac muscle also gives rise to dystrophin-positive fibres. Although both appear promising, there are a number of questions to be answered and refinements to be made before either technique could be considered possible as treatments for myopathies in man.

Neonatal tetanus estimates of mortality derived from a cluster survey in Northern Nigeria

A two-stage cluster survey of deaths from neonatal tetanus (NNT) was carried out in Kano metropolis, Northern Nigeria in order to estimate the mortality from the disease. Estimates of mortality were obtained by three different methods which were compared. According to clinical diagnosis, mortality was 20.6/1000 live-births while reports of 4-14 day deaths gave a figure of 11.4/1000 live-births. From information volunteered by informants, it appeared to be only 4.6/1000 live-births. NNT accounted for 68% neonatal deaths. The sex-specific mortality rates were 23.4 and 17.9 per 1000 live-births for males and females respectively. There was, however, no significant association between sex and death from neonatal tetanus. The mortality for the first 6 months of recall period was 15.2/1000 live-births and 24.2/1000 live-births for the last 6 months. There was also no significant association between recall period and death. In view of the markedly different estimates by the various methods of diagnosis, retrospective clinical diagnosis is suggested for community-based surveys of mortality related to neonatal tetanus.

Increasing incidence of early onset type 1 (insulin-dependent) diabetes mellitus: a study of Danish male birth cohorts.

To provide information of the incidence trends of Type 1 (insulin-dependent) diabetes mellitus we performed a cohort study of a series of Danish male birth cohorts. All male livebirths in Denmark between 1 January 1949 and 31 December 1964, were investigated regarding the development of Type 1 diabetes during the first 20 years of life using the files of the Danish Conscript Board, supplemented by a search in the Danish National Registry of Deaths. Diagnosis was verified and clinical information obtained from medical records. The material is estimated to be more than 95% complete. A total of 1705 diabetic subjects were identified of whom 23 were not representative of idiopathic Type 1 diabetes. The cumulative rate of Type 1 diabetes development during the first 20 years of life increased from 2.37 to 2.90 per 1000 for the first eight and last eight birth cohorts, respectively. A log-linear analysis of the incidence revealed significantly increasing incidence rates, independent of age effects, with a maximum in the late 1970's. About 75% of the cases presented short duration of symptoms prior to diagnosis, and only very few cases were diagnosed incidentally. Cases were diagnosed relatively less frequently during summer months than during winter months.

Birth and population prevalence of Duchenne muscular dystrophy in the Netherlands

Mutations causing Duchenne muscular dystrophy (DMD) have a short survival. Therefore, birth and population prevalence are maintained by new mutations. The present inventory was made to estimate the birth and population prevalence rates of DMD in the Netherlands. Seven methods of case identification were used. Data on 496 definite, probable or possible DMD patients born since 1961, or alive on January 1, 1983, were obtained. Several methods gave an estimated ascertainment of more than 95%. The prevalence rate at birth of DMD was estimated at 23.7 x 10(-5) (1:4215) male live births (MLB) yearly. The prevalence rate in the male population on January 1, 1983 was 5.4 x 10(-5) (1:18496). About 1% of the males in this study may have autosomal recessive Duchenne-like muscular dystrophy. Until now there has been no convincing evidence for geographic differences in DMD prevalence at birth. A list of frequency studies of Duchenne muscular dystrophy is included. The DMD mutation rate calculated by the indirect method is 7.9 x 10(-5) genes per generation. However, this may well be an over-estimate, as this method does not account for germline mosaicism. Using a modified sex ratio method the proportion of sporadic DMD among all cases was estimated to be 0.106 (range 0-0.332). High frequency of germline mosaicism in DMD is a likely cause for the apparent lack of sporadic cases as found in previous studies, if mutation rates in male and female gametes are equal. Therefore, methods for estimating the proportion of new mutants in DMD should take germline mosaicism into account. The modified sex ratio method allows incorporation of data on germline mosaicism if available.

Prevalence of intellectual handicap in Western Australia: a community study

To produce comprehensive community based data on individuals with intellectual handicap, the level of retardation, associated handicaps and demographic data. Multiple sources of ascertainment were used to identify all children in birth cohorts, 1967-1976 inclusive, who had an IQ less than 70. The majority of cases were ascertained through Western Australian government agencies that provide services for the intellectually handicapped. Other sources included the support branch of the education department, private schools and the children's hospital. In all, 1602 children, aged between 6 and 16 years, fitted the study criteria. The prevalence of intellectual handicap was found to be 8.9 per 1000 live male births and 6.3 per 1000 live female births with an overall rate of 7.6. The figures for mild, moderate, severe and profound retardation were 3.0, 2.4, 1.0 and 0.6 per 1000, respectively, with 0.8 per 1000 with an unknown IQ. Cerebral palsy occurred in 20% and epilepsy in 13% in addition to intellectual handicap. There was a significantly higher rate among those from rural compared with urban areas: 9.9 v. 6.5 per 1000 live births, respectively. This comprehensive epidemiological data on intellectual handicap in Western Australia will be of value in the planning of services, including screening and genetic counselling, and for the evaluation of care. The rural preponderance, in particular, is worthy of further evaluation.

Prevalence and incidence of Becker muscular dystrophy

We measured the prevalence and incidence of Becker muscular dystrophy in the Northern Health Region of England, UK. Patients were identified from the records of the Regional Neurological Centre and Muscular Dystrophy Group laboratories, Newcastle upon Tyne, and by writing to local doctors. We used cDNA probes and/or dystrophin immunolabelling of muscle-biopsy samples to prove the diagnosis of all cases. Results were compared with the known prevalence and incidence of Duchenne muscular dystrophy. 73 patients alive and resident in the Northern Health Region were identified, giving a prevalence rate of 2·38/100 000. This compares with a prevalence of Duchenne muscular dystrophy of 2·48/100 000. The cumulative birth incidence of Becker muscular dystrophy (at least 1 in 18 450 male live births) was about one third that of Duchenne muscular dystrophy (1 in 5618 male live births), suggesting that the disorder is more common than previously thought.

Child neuromuscular disease in southern Norway. The prevalence and incidence of Duchenne muscular dystrophy.

In a survey carried out to determine the incidence of Duchenne muscular dystrophy in South East Norway, 38 cases were ascertained among 149,975 live male births during the years 1968-1978. The overall incidence is 1:3,917 in live male births (25.33 x 10(-5). This incidence is compared with those in other studies. There is an apparent drop in incidence in the last cohort studied, and the possible role of genetic counselling and antenatal sexing are discussed.