British Columbia Health Surveillance Registry Research Articles

Excess of congenital abnormalities in French-Canadian children with neuroblastoma: a case series study from Montréal.

Neuroblastoma is one of the most common cancers of childhood. Some studies have shown an excess of congenital abnormalities in children who have been diagnosed with neuroblastoma. In this study we examined the medical records of all children with neuroblastoma seen at St. Justine Children's Hospital between the years 1977 and 1993. A total of 141 children (131 of French-Canadian ancestry) were included in this study. Twelve children (8.5%) had 21 defined congenital abnormalities (1,490 per 10,000 children). This compared with a rate of 444.3 children with abnormalities per 10,000 live births (4.44%) for all congenital abnormalities in the British Columbia Health Surveillance Registry, 1979-1988 (relative risk = 1.91, P = 0.03). Six of the 12 children had cardiovascular malformations. These and previous results suggest that there may be a common developmental origin to neuroblastoma and to some congenital malformations. Genes that control development may be worthy of further study in these children.

PATERNAL AGE AND THE RISK OF BIRTH DEFECTS IN OFFSPRING

Previous studies have shown that advanced paternal age is associated with an increase in new dominant mutations that may result in some rare congenital anomalies or syndromes in the offspring. Nevertheless, few epidemiologic studies have evaluated the effect of paternal age on the risk of more common birth defects. We examined data from the British Columbia Health Surveillance Registry, which included a total of 9,660 cases of birth defects (22 specific defect groups). We chose matched controls from the birth files of British Columbia (1952-1973). With the exception of an unusual change in direction in the 45-49 years age category, we found a general pattern of increasing relative risk estimates (adjusted for maternal age and other factors) with increasing paternal age for neural tube defects, congenital cataracts, reduction defects of the upper limb, and Down syndrome. For example, the adjusted relative risk estimates for neural tube defects in the offspring were 1.2 (for fathers age 30-34 years relative to 25-29 years); 1.3 (35-39); 1.6 (40-44); 0.6 (45-49); and 2.3 (men 50 years and older). Men under 20 years of age were also at increased risk for fathering children with birth defects such as neural tube defects, hypospadias, cystic kidney, and Down syndrome. We hypothesize that among certain commonly observed birth defects a subgroup of cases may be due to new, unrecognized dominant mutations.

Paternal age and the risk of congenital heart defects

The effect of paternal age on the risk of birth defects among offspring is less well studied than the effect of maternal age, with few comprehensive epidemiologic studies having been conducted. Advanced paternal age has been shown to be associated with an increase in new dominant mutations that result in particular congenital anomalies. The relationship between paternal age and more common birth defects, for example, cardiac defects, has not been as extensively evaluated. Therefore, a total of 4,110 cases of congenital heart defects was identified from the British Columbia Health Surveillance Registry. Matched controls were obtained from the birth files of British Columbia for the years 1952-1973. Prevalence odds ratios for paternal age, adjusted for maternal age and other factors, were estimated for 8 cardiac defect groups. A suggestive general pattern of increasing risk with increasing age among cases (excluding chromosomal anomalies) relative to controls was found for ventricular septal defects (VSD), atrial septal defects (ASD), and patent ductus arteriosus (PDA). In addition, an increased risk among men younger than 20 yr was found for VSD and ASD. These findings are consistent with the results of some previous epidemiologic studies. Based on the results of this study it is estimated that for cardiac defects such as VSD, approximately 5% of cases may be due to advanced paternal age (> 35 yr), possibly through dominant mutations.

Retinopathy of Prematurity-Induced Blindness: Birth Weight-Specific Survival and the New Epidemic

A recent population-based study in the Canadian province of British Columbia showed that, since the mid-1960s, there has been a significant increase in the incidence of retinopathy of prematurity-induced blindness in infants weighing 750 to 999 g at birth. To determine the impact of changing birth weight-specific survival on this new epidemic, all infants born in the province in the period 1952 through 1986 and known to the British Columbia Health Surveillance Registry as having retinopathy of prematurity-induced blindness were identified. In addition, the birth registration records for the 1,299 740 infants born in British Columbia in the same period and the death records of the 22,940 British Columbia-born infants who died in the province before the end of their first year of life were linked using a combination of probabilistic and manual record linkage techniques. These linked records and the records from the Health Surveillance Registry were used to calculate birth weight-specific incidence rates of retinopathy of prematurity-induced blindness in liveborn infants and first-year-of-life survivors. The rates, in 5-year intervals, showed that, in both liveborn infants and first-year survivors, the highest birth weight-specific rates occurred during the first epidemic of retinopathy of prematurity, which ended in British Columbia in 1954. Since the mid-to late-1960s, the incidence of retinopathy of prematurity-induced blindness in liveborn infants weighing less than 1000 g increased steadily whereas in infants weighting 1000 to 1499 g, incidence decreased slightly since the original epidemic ended. However, the experience of first-year-of-life survivors is substantially different.(ABSTRACT TRUNCATED AT 250 WORDS)

Life expectancy in Down syndrome

This study is part of a collaborative effort between the Division of Vital Statistics, Ministry of Health, Province of British Columbia and the Department of Medical Genetics, University of British Columbia. Permission to use the provincial vital and health records was conditional on the strict observance of the oath of secrecy regarding the nonstatistical information contained in the records. To develop life expectancy data for Down syndrome, we studied 1341 patients with Down syndrome identified by the British Columbia Health Surveillance Registry from more than one million consecutive live births from 1952-1981 inclusive. Our results indicate that life expectancy is much better than generally believed. For patients with Down syndrome with congenital heart anomalies, survival to age 1 year is 76.3%; to age 5, 61.8%; to age 10, 57.1%; to age 20, 53.1%; and to age 30, 49.9%. For patients with Down syndrome without congenital heart anomalies, survival to the same ages is 90.7%; 87.2%, 84.9%, 81.9%, and 79.2%, respectively. Survival for these patients without congenital heart defects is still significantly lower than that for a comparison group of mentally retarded persons without congenital heart defects.

Congenital anomalies in American Indians of British Columbia.

Birth prevalences of congenital anomalies in the American Indians of British Columbia are compared with those of the total British Columbia population. This study is based on data from the British Columbia Health Surveillance Registry for a 16-year period (1966-1981) judged to be the most reliable reporting period in the 35-year history of the registry. The overall congenital anomaly frequency is lower in Indians than in the general population (45 versus 60 per 1,000 livebirths). The Indian rates for individual anomalies are lower than the corresponding general population rates with the exception of orofacial clefting and congenital heart defects. Defects of the central nervous system in both populations are comparable. There is a striking paucity of hypospadias, other anomalies of the genital organs and foot deformities in Indian males. It is suggested that the differences in the congenital anomaly rates between the American Indians and the non-Indians of British Columbia may reflect genetic differences between the two groups, but differences in ascertainment and infant mortality probably also play a role.

Congenital malformations associated with anencephaly in liveborn and stillborn infants.

Records from the population-based British Columbia Health Surveillance Registry were examined, and a total of 456 infants with anencephaly (181 liveborns, 275 stillborns) were identified. Registry records list up to four congenital malformations per individual, and the records of the study cohort were reviewed for the presence of additional malformations. A total of 12.7% of infants (14.4% liveborns, 11.6% stillborns) had congenital malformations in addition to anencephaly. The frequencies of specific congenital malformations (e.g., talipes, cleft lip and/or palate, omphalocele) in infants with anencephaly were compared with the frequencies of these malformations in the general population of liveborns. In addition, the types of additional congenital malformations in liveborn anencephalics compared to stillborns were looked at. The similarity suggests that it is not just the presence of these additional congenital malformations that leads to death in utero. The data provide further evidence for etiological heterogeneity in neural tube defects.

Hypospadias in British Columbia.

The British Columbia Health Surveillance Registry (BCHSR) records the frequency, incidence, and distribution of congenital malformations and other disabilities among individuals within the province using multiple sources of ascertainment. The most important sources of ascertainment for this study were Physician's Notice of Birth forms and discharge diagnosis from all hospitals in the province on children 7 years old or younger. These data were used to determine the minimal incidence of hypospadias with and without other congenital anomalies in order to provide information useful in management and to establish baseline prevalence data on a common genital malformation. In addition, incidence over time was evaluated. The study found the minimal incidence of hypospadias in British Columbia to be 4.44 per 1,000 male live births (1,314 cases out of 295,656 male live births) during 1966-1981. This is in the previously reported range of the incidence of hypospadias (2-8.2 per 1,000 male live births). Hypospadias was the only malformation in almost 80% of all individuals identified. The most frequent additional anomalies involved the genital and inguinal regions (7.2% of all cases or 36% of cases with additional anomalies). Cardiac lesions were the next most common anomalies, representing 14% of those cases with additional anomalies. Limb malformations and gastrointestinal anomalies were also quite common, representing 12.1% and 9.1% of cases of hypospadias with additional anomalies, respectively. Thus, 1 in 225 males born in British Columbia has some degree of hypospadias, and 20% of these infants also have at least one other anomaly.

Sib risks for nonspecific mental retardation in British Columbia.

Cases of nonspecific mental retardation (MR) born in British Columbia between 1952 and 1970 ascertained through the British Columbia Health Surveillance Registry were linked by birth registration number to family sibships from computer-linked groupings of birth and marriage records in British Columbia. It was possible to retrieve family information for 97% of the cases by this method. Because of good ascertainment and relatively large sample size, the 1952-1965 birth cohort comprising 2,209 index cases was selected for calculations of overall risks and recurrence risks to sibs categorized by sex, MR level, associated neurological disability, and singleton versus multiple birth. The overall risk of affected individuals among all sibs was 4.4 +/- 0.6%, which was about ten times greater than the minimum population incidence of nonspecific MR. The risk among subsequent sibs of the first affected case in a family was 3.7 +/- 0.8%. These risks varied depending on sex, MR level, and whether the mental retardation was associated with hydrocephalus, microcephalus, cerebral palsy, or epilepsy. The recurrence risk after two affected individuals was 12 +/- 7%--about three times greater than after one affected individual. Even though the frequency of MR is greater among twins than in the overall population, the recurrence risk of nonspecific MR was not significantly different for index cases from either singleton or multiple births.

Nonspecific X-linked mental retardation II: the frequency in British Columbia.

Data on nonspecific mental retardation in two or more sibs ascertained from the British Columbia Health Surveillance Registry are utilized to calculate the frequency of X-linked mental retardation in the population of British Columbia (B.C.). In the 1950-1969 birth cohort there are 107 sibships with only males affected and 35 sibships with only females affected giving an excess of 72 male-affected sibships. Family histories of the sibships with two more more mentally retarded males provide evidence that the mothers of the excess of male-affected sibships are carriers of X-linked mental retardation. Thus, a frequency of 1.83 per 1,000 males for X-linked mental retardation and carrier frequency of 2.44 per 1,000 females are calculated. This frequency can account for all the excess of males in the population who are affected with nonspecific mental retardation. We estimate that seven to 19 X-linked genes exist to cause nonspecific mental retardation, and that the frequency of the marker-X chromosome, associated with X-linked mental retardation in some families, may be 0.92 per 1,000 male births.

Maternal age and down syndrome: Age‐specific incidence rates by single‐year intervals

Maternal age-specific risks of giving birth to a child with the Down syndrome (DS) are given by single-year age intervals. Such data are of value for more precise genetic counseling and in cost-benefit analyses of prenatal diagnosis programs. The data were obtained by linking records of children with DS at the British Columbia Health Surveillance Registry ( BCHSR ) to the appropriate birth registrations to derive maternal ages. The data related to 519 affected children out of a total of 354,880 live births in British Columbia between 1961 and 1970. The results, which are based on a high level of ascertainment, are compared to those reported in the only other published study relating to risks by single-year maternal age groupings, where completeness of ascertainment was estimated to be only 38%.

Poland syndrome in British Columbia: Incidence and reproductive experience of affected persons

Patients with Poland syndrome were ascertained through the British Columbia Health Surveillance Registry, through hospital records, and through practicing plastic and orthopedic surgeons. Of 44 patients who were ascertained, 28 had family histories taken and were examined. Physical findings were: absence of the sternal head of the pectoralis major in all patients, symbrachydactyly in most patients, and infrequent other associations such as ipsilateral undescended testis, Möbius syndrome, clubfoot, and submucous cleft palate. Family histories were "negative" in all cases. The 8 affected adults had 24 reportedly normal children. Mean paternal age was significantly higher than the paternal age in the population. The incidence was 1/32,000 livebirths in British Columbia. It was concluded that in the British Columbia population the syndrome is usually a sporadic event.

Longevity in Down's syndrome in British Columbia.

Life Tables to age twenty for Down's syndrome cases born in British Columbia from 1952 through 1971 were constructed using data from the British Columbia Health Surveillance Registry. No significant difference in survival to age twenty between males and females was found either in the presence or in the absence of congenital heart anomalies. Data from the life Tables show that Down's syndrome patients with congenital heart anomalies experience higher mortality to age twenty than cases without congenital heart anomalies.