21-Hydroxylase deficiency: screening and incidence in Israel

BACKGROUND: Neonatal screening for congenital adrenal hyperplasia was introduced in 1977. However, even today only a few national screening programs exist and their cost effectiveness is still debatable. This study was conducted in order to evaluate the advisability of a national or regional screening program in Israel. METHODS: From June 1987 until December 1992 we screened a countrywide random sample of 113,846 newborns for 21-hydroxylase (21-OH) deficiency measuring 17alpha-OH progesterone (17-OHP) from blood spotted on filter paper. Between January 1993 and August 1995 we continued the screening program concentrating on the population of northern Israel. A total of 56,958 newborns were screened. We compared these findings with the incidence of 21-OH deficiency in the total population born in Israel during the years 1986-1991. RESULTS: In the countrywide screening program, 4 newborns (2 Arabs and 2 Jews) were found to have levels of 17-OHP between 409 and 2,049 nmol/l (2 males and 2 females). This constitutes a low incidence of 1 in 28,462 live births. In the north-Israel screening program 4 newborns (all Arabs) were detected (2 males and 2 females) constituting a much higher incidence of 1 in 14,240 live births. The data obtained from the archives revealed that the incidence of 21-OH deficiency nationwide during the years 1986-1991 was 1:19,000 live births, 1:30,000 for Jews and 1:8,000 for Arabs. The incidence of 21-OH deficiency among Arab newborns in the northern part of the country was as high as 1:5,000 (14:71,130). The female to male (F:M) ratio was 2.6:1 and the ratio of the salt-losing to the simple virilizing variant was 5:1. Two male patients were diagnosed prenatally, 21 patients (17 F and 4 M) during the first month after birth and 6 others subsequently. CONCLUSIONS: The high F:M ratio of 21-OH deficiency in the total population compared to a 1:1 ratio in our random screening programs suggests that 21-OH-deficient male patients in the general population might have been missed or died early due to a salt-losing crisis. The high incidence of this disease in the northern part of the country and especially among the Arabs, suggests that screening in this part of the country, especially among the Arab population, is warranted and might save the lives of some male patients.     

Long-term data on the reproduction and maintenance of a colony of common marmosets (Callithrix jacchus jacchus) 1972-1983

We have used our laboratory records to compare data on the reproduction and maintenance of common marmosets in different colonies and to provide additional information on the species in captivity. Data are presented for a period of 12 years. This was long enough to allow information on longevity, mortality, aggression and incest. In addition 543 infants were born from a total of 202 births. No seasonality was found and the highest proportion of births overall was that of triplets. A significantly greater proportion of males was born, but perinatal mortality reduced this to a proportion of 52.2% surviving males. The interbirth interval for all normal births ranged from 145 to 382 days, with a median of 158 days. There was no evidence that interbirth intervals increased with age. The proportion of non-breeding pairs was small (4 out of 28) and progesterone assays showed that these females were ovulating.     

Congenital and hereditary anomalies in the rhesus monkeys (Macaca mulatta) of Cayo Santiago

During seven annual birth seasons, from January 1976 to July 1982, 963 infants were born in the Cayo Santiago, Puerto Rico, colony of free-ranging rhesus monkeys (Macaca mulatta). The reproductive rate for mature females, 4 years of age and older, ranged between 74.1% and 84.7%, with a cumulative mean of 80.8% over 7 years. Live births comprised 95.3% of the total and the secondary sex ratio was 109 male to 100 female births. No twinning was observed. Aborted and stillborn monkeys represented 4.7% of all births. The percentage of stillborn females was greater than that of males (4.0% vs. 3.1%). Neonatal death, defined as mortality within 48 hours postpartum, occurred in 0.8% of the live births. Two cases of congenital abnormalities were observed. The first was an anencephalic, acranial female and the second a congenitally blind male. Both infants were born to matrilineally unrelated 7-and 8-year-old multiparous females with no prior history of delivering malformed offspring. The incidence of each defect, based on 963 births, was 0.10%, with a cumulative incidence of 0.20% for all teratisms seen during the study. Multiple occurrences of a rare, nonpathological and nonlethal hereditary anomaly were also seen. Five "golden" macaques were born into two genetically distinct social groups within the last 2 years of observation. The incidence of this phenotype, based on five cases, was 0.52%, 52 times the expected rate (.01%).     

Population structure of Hylobates concolor in Bawanglin Nature Reserve,Hainan, China

The Hainan gibbon continues to survive in Bawanglin Nature Reserve in four social groups totalling 21 individuals. Twelve births have occurred since 1982, and 11 of these individuals survive in 1989. Only three of these 12 births have been females, however. The total female population consists of 6 adult females, two of which are at least 19 years old, and three juvenile females born since 1985. Two of the four social groups have only one adult female each and no juvenile females. All four groups are well protected, but their survival is precarious.     

The incidence and gene frequency of ataxia-telangiectasia in the United States.

Ataxia-telangiectasia (A-T) is an autosomal recessive neurological syndrome of considerable interest because homozygotes are highly predisposed to cancer. Vigorous casefinding in the United States in 1970-72 and 1980-84 identified 231 white, 29 black, and three Oriental A-T cases that provide information about the incidence and gene frequency of A-T. White patients identified in this study were born at the rate of 3.0 per million live births in the U.S. in the years 1965-69. The highest observed incidence was in the state of Michigan for 1965-69, where identified white A-T patients were born at the rate of 11.3 per million births. Based on the incidence data, the minimum frequency of a single hypothetical A-T gene in the U.S. white population was estimated to be .0017. Pedigree analysis, which estimates the gene frequency from the proportion of affected close blood relatives of homozygous probands, estimated the most likely gene frequency to be .007 on the assumption that A-T is a single homogeneous genetic syndrome, with 95% confidence limits of .0012-.02. Given that complementation analysis has demonstrated the genetic heterogeneity of A-T, the A-T heterozygote frequency will probably fall between 0.68% and 7.7%, with 2.8% being the most likely estimate.     

Marriage and mortality: a life table analysis

This paper examines the effects of age at marriage and differential mortality of males and females on the incidence of widowhood between the sexes. Abridged life tables constructed from marital status and death registration data of a rural area of Bangladesh for the period 1974-79 were used. The difference in life expectancy between males and females varies from 0.4 to 2.2 years at the ages 0 to 65 years and over. The mortality differentials show that the probabilities of a male or a female surviving the other spouse would be approximately the same, were there no other influence. But the incidence of widows is about ten times that of widowers. Other relevant factors, under a given regime of mortality, are age at marriage and age difference between husband and wife.     

Estimates of Incidence and Prevalence of Mongolism and of Congenital Heart Disease in British Columbia

There is a need for accurate ascertainment of incidence and prevalence rates of congenital anomalies. In British Columbia the Registry for Handicapped Children and Adults used in conjunction with vital records has proved a valuable source of information. Birth notifications alone cannot be relied upon for incidence data. It was found that seven times as many cases of congenital heart disease were registered subsequently as were reported at birth. The estimated minimal incidence rates of mongolism and congenital heart disease per 1000 live births were 1.46 and 4.75, respectively. The well-known association of maternal age with mongolism was confirmed. Twice as many babies with congenital heart disease (without mongolism) were born to mothers over 39 years of age as would be expected on the basis of the maternal age distribution for all live births in the population. Prevalence estimates of these two diseases compared favourably with other published estimates.     

Epidemiology of Down syndrome in South Australia, 1960-89.

During 1960-89 687 Down syndrome live births and 46 Down syndrome pregnancy terminations were identified in South Australia. Ascertainment was estimated to be virtually complete. The sex distribution of Down syndrome live births was found to be statistically different from the non-Down syndrome live-birth sex distribution (P less than .01). Smoothed maternal age-specific incidence was derived using both maternal age calculated to the nearest month and a discontinuous-slope regression model. The incidence of Down syndrome at birth for the study period was estimated to be 1.186 Down syndrome births/1,000 live births. Annual population incidence was shown to be correlated with trends in the maternal age distribution of confinements. If current trends in the maternal age distribution of confinements continue, the population incidence of Down syndrome in South Australia is predicted to exceed 1.5 Down syndrome births/1,000 live births during the 1990-94 quinquennium.     

An analysis for paternal-age effect in Ohio's Down syndrome births, 1970-1980.

The purpose of this study was to analyze Down syndrome (DS) births during 1970-1980 in the State of Ohio for a paternal-age effect independent of maternal age. Birth certificates and chromosome analysis records were used to ascertain 1,244 white DS births, which by capture-recapture methodology were estimated to comprise two-thirds of all white DS births in Ohio for this period. The control data consisted of 1,667,210 white live births in Ohio during the same period. One method of statistical analysis was a case-control comparison, which for each single-year maternal age compares the mean paternal age for controls with each observed DS paternal age. No statistically significant paternal-age effect was found in nine of the 11 years. For two of the years, and for all years combined, the DS fathers were significantly younger than the fathers of controls. When the data were subdivided according to ascertainment, one subpopulation--those DS individuals obtained from birth certificates alone--also showed a statistically significant negative paternal-age effect. The Mantel-Haenszel test was also applied to these data. Assuming no paternal-age effect, a lower rate of DS births than expected was found at paternal ages greater than or equal to 40, but not at greater than or equal to 45, greater than or equal to 50, or greater than or equal to 55. These same methods were used to test for a maternal-age effect. In each of the 11 years and over all 11 years combined, a strong and statistically significant positive maternal-age effect was detected.     

Demography of the human sex ratio in some Latin American countries, 1967-1986.

A sample based on hospital births recorded for the Latin American Collaborative Study on Congenital Malformations (ECLAMC) program was used in the present study to determine sex ratios for live births and for stillbirths. Sixty-four cities and 147 hospitals in 11 countries (Uruguay, Chile, Argentina, Brazil, Bolivia, Peru, Paraguay, Ecuador, Venezuela, Colombia, and Costa Rica) were included in the present analyses. The number of live births was 1,886,653 in the period 1967-1986, and the number of stillbirths was 24,818 in the period 1978-1986. The sex ratio for the total sample was 0.5112 for live births and 0.5477 for stillbirths. The sex ratio as a whole is decreasing with time in a parabolic fashion. Each country in our study behaved differently. Except for Peru and Uruguay, the countries experienced a significant decrease in the sex ratio after 1978 for live births; only Brazil did not show a temporal trend for the sex ratio for stillbirths.     

Sources of variability in numbers of live births in wild golden lion tamarins (Leontopithecus rosalia)

We examined the effects of several variables on the number of live births in multiparous females in a wild population of golden lion tamarins (Leontopithecus rosalia). Independent variables included the number of infants born to a female the previous breeding season, the number of infants weaned the previous breeding season, the female's age and body mass, the number of adult males and helpers in the group, and the inbreeding coefficient of the offspring. We also tested the hypothesis that trapping and chemical immobilization during pregnancy affected the number of live births. Female body mass was the only statistically significant predictor of the number of live-born infants in the current season when both first and second peaks were included. Characteristics that predicted higher numbers of infants in the first peak of a season were the number of infants born the previous season and the body mass of the female. The greater the number of infants born the previous season, the greater the number of infants born in the first peak of the current season. Factors positively correlated with the number of live births in the second peak within a season included the number of infants born the previous season, as well as the number of available helpers. Due to sample size constraints, the analysis of litters in the second peak did not include body mass of the female as a variable. Inbreeding and handling did not affect the number of live births. We found no evidence that current reproduction negatively impacts future reproduction in this species. We also found no evidence for an age-related reduction in fertility.     

An analysis for temporal variation in Down syndrome births in Ohio, 1970–1979

Our study investigates the epidemiology of Down syndrome (DS) in the state of Ohio during the 1970s. The occurrence of DS births was examined to learn if statistically significant temporal variation was present among these data. Both monthly and annual numbers of DS births, adjusted for changing numbers of live births, were tested for such variation; furthermore, the data were analyzed for cyclic variation by attempting to fit simple trigonometric functions to the data.

Individuals with DS were ascertained using the records of cytogenetics laboratories and birth certificate records. Demographic data such as race, date of birth, and maternal age were collected on these individuals using their birth certificates as the data source. Appropriate parallel live-birth data were obtained from the Ohio Department of Health. The total number of affected individuals ascertained was 1,364, 66.7% of the total estimated population size. The data analysis was restricted to whites only (1,203 individuals) because they represented a more homogeneous sample than the total.

Monthly and annual variation in the numbers of live births was removed by producing single-year maternal-age adjusted numbers of DS births using the total Ohio white live births as the reference population. Analysis of covariance using single-year maternal ages ≤ 16 and ≥ 45 as the covariate was used to analyze the adjusted numbers of DS births for temporal variation.

No significant differences were detected among the annual adjusted numbers of DS births (P = .24), nor were there differences among the monthly adjusted numbers of DS (P = .37). The modes of ascertainment were tested to learn if there were annual or monthly differences in the method of ascertainment. No significant differences were detected for these data (P = .82 and P = .85, respectively). Furthermore, the data were separated into the maternal-age categories < 35 and ≥ 35, and annual and monthly adjusted DS births to these two maternal-age categories were examined for temporal variation. No significant differences were found among these data, P > .10 for all four of the tests. No simple cyclic functions were found to fit either the annual or monthly data.

The Ohio study reported here showed that through the use of a large sample, controlling for variation in the numbers of live births, and the use of detailed statistical tests, no significant temporal variation in the occurrence of DS births existed during the 1970s.

     

Isolated oral cleft malformations: associations with maternal and infant characteristics in a California population

Data on isolated oral cleft malformations from a birth defects registry covering a large population base were examined to describe potential associations with maternal and infant characteristics. Infants with cleft palate (CP) were analyzed separately from infants with cleft lip with or without cleft palate (CLP). The prevalence of isolated CLP per 1,000 births was 0.741, approximately twice the prevalence of isolated CP, which was 0.383. Male infants were more likely to be born with CLP (OR = 1.9) but less likely to be born with CP (OR = 0.56) than were females. Women 39 years or more of age were twice as likely as 25-29 year olds to have a child with either type of cleft. Black, nonhispanic infants had a lowered risk for CLP compared to white, nonhispanics (OR = 0.40). These risks were found to be independent of each other based on multivariate analyses. Associations with either type of cleft malformation were not observed for plurality, number of previous live births, and maternal birthplace.     

Captive breeding of cheetahs in North American Zoos: 1987–1991

From 1987 to 1991, the North American captive cheetah population increased by 38% (to 266 animals), due to importation and captive breeding. This population constitutes 26% of the world's captive cheetahs and 36% of all reproductively successful animals. Since 1956, 33% of all cubs born in North America occurred during this 5-year period. Because of importation of animals from breeding programs abroad, East African (A. jubatus raineyi) genes have been introduced into the North American cheetah population, and 39% of all cubs born during 1987--1991 were South African/East African hybrids. Also during this time, the breeding population and effective breeding population increased by 86% and 72.6%, respectively. The incidence of infant mortality decreased from 37% (last recorded for the years 1956 to 1986) to 28% (averaged over 5 years), although infant mortality during the latter period ranged from 15% (for unrelated parents) to 41% (for related parents). Management recommendations implemented to increase fecundity and population size appear to be successful, although the founder base of the population still has only been increased from 52 cheetahs in 1986 to 72 animals in 1991. © 1993 Wiley-Liss, Inc.     

Lipid metabolism and diet: possible mechanisms of slow aging

The ability to survive to an extremely old age is a consequence of complex interactions among genes, environment, lifestyle and luck. In the last two centuries, life expectancy in western countries has doubled, increasing from 40 to 81 years (79 for males and 82 for females). The candidate factors to determine such mortality reduction are reduced exposure to infections and the subsequent reduction in inflammatory responses, and to some extent, improvement in diet and nutrition. Among the people born at the beginning of the previous century, a small portion of individuals (1 in 10,000 born) have reached 100 years, surviving approximately 20 years more than the general population. The successful longevity of these individuals shows a familial component, possibly genetic, as underlined by the centenarian sibling's increased chance of reaching 100 years of age compared to the general population. Genetic studies on long living individuals have led to the discovery of potential genetic causes of extreme longevity. These discoveries have highlighted the role of lipid metabolism as a potential key player in the ability to survive to extreme old age. Additional studies on the longevity phenotype have confirmed the role of lipids and lipid-associated cell activities in the predisposition to longevity, from lower eukaryotes to humans. The main focus of this review is the appreciation of demographic survival data and changes in recent diet with the above mentioned genetic and phenotypic biomarkers of longevity, in order to elucidate hypotheses on mechanisms of slow aging and disease resistance.     

Population dynamics of a group of lion-tailed macaques (Macaca silenus) inhabiting a rainforest fragment in the Western Ghats, India

We observed the overall population dynamics and number of births and deaths in identified individuals between January 2002 and October 2005, in a large group of lion-tailed macaques in the Anaimalai Hills of the Western Ghats in the south Indian state of Tamilnadu. The group inhabited an isolated rainforest fragment located inside a private tea/coffee garden. The group size increased from 56 in January 2002 to 84 in October 2005. All females reproduced, and the interbirth interval was 23.18 months. Of the 37 infants born between 2002 and 2005, only 1 died providing an infant survivorship rate of about 97.3%. Although births occurred in all months, most of the infants were born between February and March, and this pattern of births was consistent over the years, indicating a major birth peak in this species. The population growth rate in this unusually large group was found to be higher than even in those groups of lion-tailed macaques that inhabit large and relatively undisturbed rainforest complexes. This high growth rate could be attributed to the availability of abundant cultivated fruit plants including commercial crops such as coffee seeds. The observations provide a perspective for the management of other groups of this endangered species inhabiting rainforest fragments.     

Thyroid cancer incidence in Ukraine: trends with reference to the Chernobyl accident

For the first time, a comparative analysis of thyroid cancer incidence in Ukraine after the Chernobyl accident was done in a cohort that is almost as large as the general population. On the basis of thyroid doses from radioactive iodine in individuals aged 1-18 years at the time of accident, geographic regions of Ukraine with low and high average accumulated thyroid doses were established and designated "low-exposure" and "high-exposure" territories, respectively. A significant difference of thyroid cancer incidence rates as a function of time between the two territories was found. That is, the increase in the incidence was higher in high-exposure regions than in low-exposure regions. The incidence rates varied substantially among the different attained age-groups, especially in the youngest one (up to 19 years old). The analysis that was adjusted for screening and technological effects also indicated that in the high-exposure regions, thyroid cancer incidence rates at the age of diagnosis of 5-9, 10-14 and 15-19 years were significantly higher in those born in 1982-1986 compared to those born in 1987-1991, while in the low-exposure regions, no significant difference was observed. The observed probable excess of radiation-induced thyroid cancer cases in adults exposed to radioactive iodine from the Chernobyl accident, especially in females, may be due to the high power of the present study. However, it should be noted that our investigation was not essentially free from ecological biases.     

The accident at Chernobyl and outcome of pregnancy in Finland.

OBJECTIVE--To evaluate the outcome of pregnancy in Finnish women after the accident at the Chernobyl nuclear power plant on 26 April 1986. DESIGN--Geographic and temporal cohort study. SETTING--Finland divided into three zones according to amount of radioactive fallout. SUBJECTS--All children who were exposed to radiation during their fetal development. Children born before any effects of the accident could be postulated--that is, between 1 January 1984 and 30 June 1986--served as controls. INTERVENTIONS--Children were divided into three temporal groups: controls, children who were expected to be born in August to December 1986, and children who were expected to be born in February to December 1987. They were also divided, separately, into three groups according to the three geographic zones. END POINT--Incidence of congenital malformations, preterm births, and perinatal deaths. MEASUREMENTS AND MAIN RESULTS--There were no significant differences in the incidence of malformations or perinatal deaths among the three temporal and three geographic groups. A significant increase in preterm births occurred among children who were exposed to radiation during the first trimester whose mothers lived in zones 2 and 3, where the external dose rate and estimated surface activity of caesium-137 were highest. CONCLUSIONS--The results suggest that the amount of radioactive fallout that Finnish people were exposed to after the accident at Chernobyl was not high enough to cause fetal damage in children born at term. The higher incidence of premature births among malformed children in the most heavily polluted areas, however, remains unexplained.     

Reproductive Coordination in a Nonseasonally Breeding Primate Species,Macaca silenus

Varying types of reproductive coordination among females have been described for several mammals. Among nonhuman primates, female reproductive coordination has usually been described as breeding seasonality, or in few cases, closer synchrony within the breeding or birth season. We examined birth records from a large captive colony of lion-tailed macaques, Macaca silenus, a nonseasonally breeding species, in order to determine the degree of female reproductive synchrony in this population. Births were nonrandomly distributed over the 10-year study period. Of the total of 28 births, the majority (21 or 75 %) of births occurred in cohorts, in spite of wide variations in interbirth intervals among cohort birth mothers. Cohorts consisted of two to five infants born within a 90-d period or less. Of the remaining 7 “isolated” births, four were in the three years in which only one or two births occurred. The pattern of cohort births was nonrandomly distributed according to mother's parity: three of the isolated births were to primiparous mothers, whereas only one of the 21 cohort births was to a primiparous mother. Estrous synchrony results showed that females in the longer-established of two groups exhibited greater synchrony, suggesting social facilitation of reproductive coordination. It is thus suggested that synchrony in this sample was the result of social rather than ecological mechanisms, as has been hypothesized for some other mammalian species.     

Graduated change of life expectancy in mice in ontogenesis

Life expectancy of descendants of a normal female mouse and a male with an inherited growth inhibition mutation discovered in a laboratory population was investigated. The hereditability of the characteristic allows us to consider it a result of mutation. It was shown that, in mice, the curve of dependence of life expectancy on their serial number in a row of increase in life expectancy (curve of rank distribution) has step-like shape for mutant males and females, as well as for males with normal development. The first grade of mice death on the curve of rank distribution was observed at one month after their birth and was characteristic only of males and females with a mutation during the period of maximum lag in weight as compared with their normal relatives. The surviving mutants catch up to the normally developing individuals within two months and externally become indistinguishable from them. The subsequent grades of death in mutants and normal males coincide on the time axis. The steps are absent on the rank curves of life expectancy of normally developing females. The time intervals between the steps are reproduced in parallel groups of mice and, hence, are not casual deviations from theoretical curves and are of a regular nature. The discovered phenomenon is interpreted within the scope of a hypothesis about the realization of the genetic program of ontogenesis, which provides periodic change of vitality stages with stages of sensitivity to external risk factors, which increase the probability of death, by mice. Absence of such stages in the group of normally developing females can be explained by shifts in development, which are produced by the irregular performance of reproductive functions.