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A survey was carried out to determine the effect of prenatal screening and therapeutic abortion on births in 1985 with anencephaly and spina bifida in England and Wales. Maternal serum alpha-fetoprotein tests were done on 399,288 women (60 per cent of pregnant women): 4 per cent were reported as being screen-positive and 1 per cent had an amniocentesis. An estimated 534 pregnancies associated with anencephaly were terminated and an estimated 445 pregnancies associated with spina bifida (but without anencephaly) were terminated. Most (63 per cent) of the anencephalic pregnancies were first suspected from an ultrasound examination; 57 per cent of the spina bifida pregnancies were first suspected from a positive maternal serum alpha-fetoprotein test, 35 per cent by ultrasound, and the remaining 8 per cent by other means. The birth prevalence of anencephaly declined by 94 per cent between 1964-1972 and 1985, but when the terminations of pregnancy on account of having a fetus with anencephaly are added to the births the decline in prevalence was only 50 per cent. The birth prevalence of spina bifida declined by 68 per cent over the same period but when the terminations were added to the births the decline in prevalence was only 32 per cent. Among births with anencephaly 66 per cent had had no screening or diagnostic tests in early pregnancy, but in those that did nearly all were positive--usually in twin pregnancies where one fetus was affected but not the other. Among births with spina bifida, 48 per cent had no tests and in those that did the results were mainly negative.(ABSTRACT TRUNCATED AT 250 WORDS)

The overall incidence of anencephaly and spina bifida (ASB) in 69,056 pregnancies was 4.7/1000 births. ASB was more common (8.4/1000 births) among children of mothers who had had two or more abortions, but the increased risk was confined to spina bifida. A history of abortion was more common in older women and women of higher parity, but this was not matched by a similar increase in the incidence of ASB. The incidence of ASB was related to social class, but the prevalence of previous abortions was similar in all classes. The results suggest that expectant mothers with a history of two or more abortions have an increased risk of producing a child with spina bifida. The abortions are considered to be a manifestation of previous abnormal conceptions rather than the primary cause.

This study suggests that social class has an effect on the incidence of anencephalus and spina bifida, the malformations being more frequent in the lower socio-economic groups. A family study of 226 patients with a CNS malformation suggests that social class also may be important in determining the recurrence risk of such malformations: there are higher risks in social classes III, IV and V than in social classes I and II.

A 9-year survey of neural tube defects in Newfoundland showed (1) evidence for secular variation, with a peak in 1980, but no general downward trend as seen in some other populations; (2) significant geographic variation which did not correlate with hardness or nitrate content of the lake water; (3) a tendency for the proportion of females among anencephalic births to increase with increasing frequency of anencephaly among geographic regions. This supports previous evidence for a female-specific contribution to the causes of increased liability to neural tube defect.

Brittany is celtic, like Ireland and Wales where the incidence of neural tube defects is raised. We searched the hospital files in Brittany for all live and still births, and terminations of pregnancy after prenatal diagnosis for the years 1975-1984. 225 cases of spina bifida and 210 cases of anencephaly were identified; giving an incidence of 0.60 per 1000 births for spina bifida and 0.56 per 1000 births for anencephaly. No seasonality was found for both malformations. Analysis of the sex ratio for anencephaly indicated significantly higher proportion of females to males. Maternal age in the affected group was similar to the normal population. Casual heterogeneity among neural tube defects patients was presumed because 14% of our cases had other congenital anomalies.

In the homozygous state, the splotch (Sp) gene causes spina bifida and exencephaly. Close to 25% of the embryos from Sp/ + X Sp/+ litters are affected. The frequency of these defects is significantly reduced by maternal treatment with 5 mg/kg retinoic acid on day 9 of gestation. There is no significant increase in the resorption frequency with this treatment, indicating that the fall in the frequency of neural tube defects is not due to differential mortality of the affected fetuses. The effects of retinoic acid are time specific, with treatment at different times on day 9 having the greatest influence on either the anterior or posterior neuropore. Treatment on day 8 with the same dose of retinoic acid causes an increase in both resorptions and neural tube defects, although only the increase in the former was significant.

For the period 1973 to 1977, a total of 536 cases of anencephalus and spina bifida were ascertained in Los Angeles County, California, a low-risk area, and compared with a 2 per cent random sample of all live births in the county. Women with Spanish surnames had an elevated risk for anencephalus and to a lesser extent for spina bifida; Blacks were at lowest risk, especially for spina bifida. The occurrence of a previous fetal death was a strong risk factor for anencephalus but there was no association between socio-economic status and either of the defects. Advanced maternal age was a stronger risk factor for spina bifida than for anencephalus but, as in other studies in low-risk areas, no increased risk was observed among teenage mothers. Paternal age did not show any independent association after controlling for mother's age. Finally, the association of high birth-order with the birth defects was weakened greatly after simultaneous adjustment for age and ethnicity.

The amniotic fluid alpha-fetoprotein assay (AF-AFP) is the single most valuable method of detecting anencephaly--spina bifida (ASB) in utero. A raised AF-AFP, however, is a more reliable indicator of a fetus with ASB in the pregnancy at high risk for ASB. Most women undergoing fetal chromosomal analysis are at low risk for ASB. Consequently, gravid patients who have an AF-AFP incidental to chromosomal studies, and elect abortion because of a raised AF-AFP, will more frequently abort a normal fetus than the gravida who has previously had an infant with ASB. For the obstetrician utilizing this assay, the predictive value positive (PVP) concept, a guide for the interpretation of a positive result, is introduced and then applied to examples of patients at varying risk for ASB in their offspring.

The parents of 226 of the 360 patients with anencephalus or spinal bifida or both, born in Belfast 1964 to 1968, were visited to document the occurrence of these malformations among other relatives. The proportions of sibs with anencephalus and spina bifida were 10.41% for spina bifida index patients and 6.4% for anencephalus. For patients born after the index patients, the proportions were 12.19% and 6.35%, respectively. The overall incidence of either malformation among sibs was 8.87%. This estimate is higher than the 4 to 5% commonly reported and is probably related to the specific background of the Northern Ireland population, which is known to have the highest incidence of CNS malformations in the United Kingdom. The substantial size of this risk indicates the importance of amniocentesis for monitoring subsequent pregnancies of women who have had one child with a CNS malformation.

Given the observed variation in birth prevalence and recurrence rates of neural tube defects, it is important to obtain such data specific to a given locality for research and genetic counseling purposes. A review of hospital medical charts, the patient lists of the Medical Genetics and Myelomeningocele clinics at Alberta Children's Hospital and data from the Canadian Congenital Anomalies Surveillance System revealed the annual birth prevalence rate of neural tube defects in southern Alberta in 1970-81 to be 1.62/1000 total births. This figure suggests southern Alberta to be a low-frequency area. There was no significant variation in the annual rates of spina bifida, encephalocele or all neural tube defects combined over the study period. A significant linear decline in the frequency of births of anencephalic infants, however, was noted (p = 0.025). Information on the total reproductive history of the mothers revealed that the empiric risk of recurrence of a neural tube defect was 2.2%, and the risk to all siblings was estimated to be 2.3%. In future prevalence studies multiple sources of case ascertainment should be used, including data on pregnancies terminated because of a fetal neural tube defect.

During the period 1975-1980, 105 infants out of a total of 116 859 delivered at selected hospitals in the Cape Town area had a neural tube defect. The combined incidence of spina bifida and anencephaly in Whites was approximately 1/300 births, which is similar to that generally encountered in the UK. However, the incidence in other ethnic groups was appreciably lower at 1/1250 and 1/2000 births for the Coloured (mixed ancestry) and Black groups respectively.

We report a clinical analysis of 327 cases of Spina Bifida and 102 cases of Anencephaly in Brittany. Maternal age, parity, birth weight are not different from random population. Male rate is 0.40 for Anencephaly and 0.50 for Spina Bifida. The study of pregnancies shows an increased frequency of hydramnios during anencephaly pregnancies (0.34) and high rate of abnormalities during the pregnancy of Spina Bifida (0.34) or Anencephaly (0.86). Four mothers of Spina Bifida were taking valproic acid. Thirty children (0.07) had other malformations.

The Vietnam Experience Study was a multidimensional assessment of the health of Vietnam veterans. From a random sample of enlisted men who entered the US Army from 1965 through 1971, 7924 Vietnam and 7364 non-Vietnam veterans participated in a telephone interview; a random subsample of 2490 Vietnam and 1972 non-Vietnam veterans also underwent a comprehensive medical examination. During the telephone interview, Vietnam veterans reported more adverse reproductive and child health outcomes than did non-Vietnam veterans. However, children of Vietnam veterans were not more likely to have birth defects recorded on hospital birth records than were children of non-Vietnam veterans. The rates of total, major, minor, and suspected defects were similar among children of Vietnam and non-Vietnam veterans (odds ratios, 1.0, 1.1, 1.0, and 0.9, respectively). These results are consistent with the findings of three epidemiologic studies conducted since 1981 on the relationship of Vietnam service and birth defects in children of male veterans.

Geographical variation in the incidence of an Anencephaly and Spina-Bifida is well documented. The highest rates for these malformations were found in Ireland, Wales, Scotland and in Western regions of England. These rates decrease progressively towards eastern Europe. In France the highest rates were found in some regions of Brittany. The geographical correlations between the mortality rates of Spina-Bifida and incidence of Spina-Bifida and Anencephaly and the HLA antigen frequencies are studied. There is a positive correlation with A1 and B8 and a negative one with B5 and BW35. The role of the HLA system in these associations is discussed.

In the NIH Collaborative Perinatal Project, a prospective study of over 53,000 pregnant women and their offspring, 71 single-born children (13.33/10,000) were found to have a non-syndromal neural tube defect (NTD). A family history was present in only one case. The group of individuals with NTD was compared to a group of 400 randomly selected non-malformed control infants. Of over 50 maternal factors studied the following showed significant association with NTD in the offspring: diabetes mellitus; organic heart disease; lung disease; and diuretic, antihistamine, and sulfonamide use. The interval between the termination of the immediately previous pregnancy and the start of the proband pregnancy was significantly shorter in mothers of NTD children than in mothers of control infants. The risk for NTD was also significantly increased if the immediately previous pregnancy was a spontaneous abortion. There was no increased risk for NTDs among sibs of children with major malformations such as tracheo-esophageal "dysraphism," cleft lip/palate, or renal agenesis. NTDs are apparently etiologically heterogeneous.

A survey of the records of all hospitals with obstetric services in Nova Scotia revealed that during 1980-84 there were 122 pregnancies involving a neural tube defect. The mean rate was 2/1000 births. Of the affected fetuses or infants 54% had spina bifida, 35% had anencephaly and 11% had encephalocele. The records showed that in the early part of the period studied at least one prenatal ultrasonographic examination had been performed in 60% of the pregnancies; in 1984 the rate was 74%. When examinations done before 16 weeks' gestation were excluded, the overall detection rates at the first ultrasonographic examination were 100% for anencephaly and 73% for spina bifida and encephalocele; the rates improved toward the end of the study period.

Screening of 11 585 pregnant women between 16 and 20 completed weeks' gestation for raised serum-alphafetoprotein (A.F.P.) levels showed that the birth of 81.4% of babies with open neural-tube defects could be avoided. The screening test was sensitive enough to detect 93% of those affected and serum-A.F.P. levels above the point at which intervention shouldbe considered were found in 1.7% of pregnancies. After 75.2% of false-positives had been excluded by ultrasonography or by a repeat of the serum test, only 0.63% of pregnancies proceeded to amniocentesis, 46.6% of amniocenteses showed raised amniotic A.F.P. levels due to fetal abnormality. Fetal loss by abortion or perinatal death after amniocentesis occurred in 0.034% of pregnancies screeded, 75% being associated with threatened abortion before amniocentesis. There were no terminations of normal pregnancies due to false-positive amniotic A.F.P. results. It is concluded that voluntary maternal serum-A.F.P. screening has a valuable role in antenatal care.

A survey was made of the upper cervical vertebrae in children with cleft lip and palate in order to determine the prevalence of cervical vertebral anomalies. The cleft sample consisted of 105 patients attending for orthodontic treatment. It was subdivided into cleft lip (CL), cleft palate (CP), unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) subgroups. A control was comprised of 120 orthodontic patients. The cervical vertebral anomalies were classified into two types, posterior arch deficiency (PAD) and fusion anomalies (FUS). The results confirmed that the cervical vertebral anomalies occurred significantly more often in the cleft sample (13%) than in the controls (0.8%), p less than 0.001. The total prevalence of cervical vertebral anomalies was similar in the four cleft sub-samples, but the occurrence of each of the two types of cervical vertebral anomalies showed a more differentiated pattern. Posterior arch deficiency occurred significantly more often in cleft palate (CP), (16%) than in controls p less than 0.001, but fusions did not occur more frequently in any cleft groups than in controls.

Neural tube defects, anencephaly and spina bifida (including encephalocele) have been the major malformation problem in South Wales. Births of affected offspring of residents of Mid and South Glamorgan between 1956 and June 1985 were ascertained from various sources. To these were added terminations following prenatal diagnosis and affected spontaneous abortions of 16 weeks gestation or more since 1973. Variable fluctuation in prevalence occurred between 1956 and 1965. Since then there has been an accelerating decline in the birth prevalence of NTD but especially of anencephaly in both counties. When abortions and terminations are taken into consideration the decline until 1984, though still present, is much slower and is virtually non-existent now. The need for continuing NTD pregnancy screening and prenatal diagnosis followed by selective abortion is stressed. It is suggested that genetic counselling health education to improve maternal nutrition preconceptional counselling and population folic acid supplementation should be extended to prevent these defects.

The distribution and prevalence of births with neural tube defects in Utah from 1940 to 1979 are analyzed with regard to prevalence rates, secondary sex ratios, seasonality, yearly rates, and time-space clustering. The overall prevalence rate of 1.00 per thousand live births is comparable to that of other populations in the western United States. Analysis of sex ratios indicates a substantially higher proportion of females than males. No significant secular trends or time-space clustering are observed. No seasonality is seen for spina bifida; however, the anencephaly cases are delivered more frequently in the early spring and fall months. Following linkage of the neural tube defect cases to the Utah Genealogical Data Base, application of the genealogical index method shows substantial familial clustering of the disease. The average inbreeding coefficient of the neural tube defect cases is not elevated over that of matched controls. The empirical recurrence risk for the disease is calculated to be 3%, and the heritability estimate is 70%. Likelihood analysis of pedigrees containing spina bifida occulta and spina bifida cystica indicates that they may segregate as an autosomal dominant trait with a penetrance of 75%.

Data from birth certificates (BC), death certificates (DC) and medical rehabilitation files (MR) were analyzed to estimate the livebirth prevalence of spina bifida in upstate New York in 1969-1974 and the completeness of the data sources. Birth certificates listed about 68% of cases, death certificates about 27% and medical rehabilitation files about 25%. The three sources together, it is estimated, included only about 80% of cases in the population. For each source, comparisons of estimates of completeness derived using each of the other two as reference sources were found to be useful for evaluating the likelihood of source dependence. The estimated livebirth prevalence rate, adjusting for incomplete reporting and the observed negative dependence of MR and DC sources, was 0.85 per 1000 livebirths by both Bernoulli census and log-linear methods. Taking into account in addition evidence for a BC-DC positive dependence, the resulting prevalence rate estimates were slightly higher, 0.88 per 1000 by log-linear methods and 0.90 per 1000 by the Bernoulli census approach. In view of the likely BC-DC positive dependence, it is suggested that Bernoulli census estimates derived using only these two sources without some ancillary third data source are likely to be biased to a false low figure. Nevertheless, estimates from BC and DC alone may still be useful in establishing that the prevalence rate is above some minimum figure, for example a "breakeven" prevalence rate, in cost-benefit analyses of a possible prevention program.

We studied the survival of a population-based cohort of 154 infants with spina bifida who were born during the eight-year period from 1972 through 1979 to residents of Atlanta. Our objectives were to describe the cohort's survival experience and to explore relationships between clinical characteristics and survival. Overall, 57% of the cohort survived one year or more. This figure is misleading, however, because it conceals important differences in survival among subgroups of affected infants. From univariate analyses, we observed significant differences in survival among infants categorized by year of birth, birth weight, the open-closed status of the defect, the highest level of the defect on the spine, the presence of multiple major birth defects, and the presence of hydrocephalus at birth. More infants born in the late 1970s survived their first year of life than infants born in the early 1970s; infants with open defects had lower survival than those with closed defects; and infants whose defects were low on the spine had better survival than those whose defects were higher. When comparing the survival experience of this cohort with that of other groups from other areas or from more recent years, health workers must consider referral biases and differences in the distribution of clinical characteristics.

We have reviewed the family histories of children with neural tube defects to determine which relatives are at sufficient risk to be offered amniocentesis for prenatal diagnosis. The recurrence risks for sibs was 6%; therefore, women with one affected child should be made aware of the availability of this test for monitoring subsequent pregnancies. The empiric recurrence risks for various groups of second and third degree relative exceeds 1% only for mothers' sisters' children. The lower values for the other groups may reflect either true biologic differences of reporting biases. Unit the matter is clarified, all sibs of affected children and all sibs of the parents of affected children should be informed of the availability of amniocentesis for monitoring their (or their spouse's) pregnancies.

The birth rates for all neural tube defects and the mortality rates from spina bifida and encephalocele have been obtained for Sheffield children by examining the congenital anomalies register and death certificates during the period from 1963-1978. The introduction of atenatal alpha foetoprotein screening of all pregnant women in 1977 is associated in time with a sharp fall in the birth rate of neural tube defects. The mortality rate for spina bifida with encephalocele rose gradually from 1967 to 1976, apparently unaffected by the introduction of clinical selection prior to surgery in 1971. The antenatal screening of previously affected families (since 1973) did not affect the mortality rate, but screening the total pregnant population since 1977 has been associated with a sharp reduction in the mortality rate. The mortality rate curve for spina bifida with encephalocele is markedly different from the birth rate curve which makes the common practice of inferring birth rates from mortality rates invalid. There was a gradual increase from 1967 to 1978 in the proportion of children born with spina bifida in any given year who died before their second birthday. This increase appears to have been uninfluenced by the introduction of selection or antenatal screening. The changes in mortality rate and survival may be as much due to unknown factors as to changes in medical management.

Published reports on the sex ratio of spina bifida have been reviewed. With one exception, there seems to be no evidence of variation in the sex ratio of spina bifida. In particular, unlike anencephaly, the sex ratio of spina bifida seems to be unrelated to the prevalence of the malformation: this (M/(M+F)) is of the order of 0.44 in respect of all spina bifida births (liveborn and stillborn). The sex ratio of spina bifida in Negroes does not seem to differ from that in whites (though the data on this point are not numerous). The exception noted above concerns spina bifida occurrring in twins: these cases are disproportionately often female. The point stands in need of explanation.

The prevalence and time trends of spina bifida and anencephaly in the central area of Israel have been studied using data derived from four hospitals affiliated with the International Clearinghouse for Birth Defects Monitoring Systems. Spina bifida rates show a continuous increase from 1978 (1.1/10,000) to 1986 (7.4/10,000) with a peak in 1984 (7-fold increase compared with 1978). The logistic regression analysis of proportion of cases revealed a significant linear trend over time (P less than 0.005). Anencephaly rates increased from 1978 to 1981 but later decreased continuously until 1986 when the prevalence returned to the initial level of 1978. This time trend of spina bifida may represent a real alarm; the implications of this observation are discussed.

Detailed analysis is presented on the dramatic decline in spina bifida births and other congenital central nervous system defects in the past 12 years, in both Sheffield and the rest of Great Britain. In Sheffield, there was an average of 20 spina bifida births per year up to 1972, but since then there has been a progressive fall to only one in 1984. This decrease may be partly attributable to antenatal diagnosis and terminations of affected pregnancies, but there is no known explanation for the rest of the fall, which has also been experienced throughout Great Britain. The virtual elimination of spina bifida is now possible, as long as the existing methods of prevention and antenatal diagnostic facilities are used even more fully. Relaxation of our effort and a reverse in the 'natural' trend could bring the incidence of spina bifida back to where it was 15 years ago.

Within the framework of a retrospective epidemiological investigation concerning the incidence of CNS-malformations in the city of Cologne during the period 1971-80, 76 749 hospital births assessed from records in six hospitals were considered. This represents 88% of all hospital births. The incidence varied between 0.79-1.80 with a mean of 1.37/1000 total births. This figure was primarily influenced by the values obtained from Spina bifida (0,59/1000). If the dates for the period 1961-70 are included, a marginal increment is exhibited (from 1.13 up to 1.37/1000) for the total occurrence of CNS-births, as opposed to a slight decrease for the Sb-group (0,65 down to 0.59/1000). A seasonal variation was not revealed for the total number of births. Contrary to worldwide literature, the male rates were significantly higher (113 : 100). The stillbirth-rate was 23,8% compared to 0,63% of total births, whereby hydrocephalus cases with 52% were heavily represented. A relationship between mother's age and incidence of occurrence was, as in the previous decade, not substantiated. Since the dates presented are obtained on the basis of hospital obstetrics records, it is unlikely that similar figures will arise in future studies, due to improved prenatal diagnosis (sonography and amniocentesis), which influence decisions relating to the possibilities of interruption of pregnancy.

Reports of an apparent decline in the incidence of neural tube defects (NTDs) have come from various parts of the world. If these findings are consistent they would have an important impact on prenatal diagnosis and on screening programs. The incidence of NTDs over a 10-year period was examined in British Columbia, a province that has a population-based health surveillance registry through which there is virtually complete ascertainment of liveborn infants with NTDs. The results showed a significant decrease in incidence only for stillborn infants with anencephaly. The increased use of ultrasonography and the subsequent termination of pregnancies in which the fetus has been found to have anencephaly may explain this observation.

Data from the Finnish Register of Congenital Malformations for the years 1965-73 were used in a search for associations between environmental influences and defects of the central nervous system (CNS). The material consisted of 710 cases of CNS defects and their matched-pair controls. Moreover, and 'internal' control group of 259 cases of polydactyly and their matched-pair controls were used. The first report gives information on variations in time and space, sex distribution, and parental age. A higher incidence of anencephaly was noted in the eastern part of the country, but no significant secular or seasonal variations were found. The sex ratio (M/F) was lower than expected in the groups of anencephaly and CNS defects as a whole. High parental age turned out to be a risk factor in the group of all CNS defects, mainly owing to the subgroup of hydrocephaly. The dangers of observational studies due to confounding factors are discussed.

An evaluation was made of all cases of neural tube defects born in seven gynaecological hospitals and obstetric centres of Havana, between 1970 and 1980. Neural tube defects were recordable from 492 infants out of 319,228 births. The families concerned were briefed in human genetics and informed about the possibility of prenatal diagnosis of anencephaly and bifid spine (spina bifida aperta). Some of them had a record of this defect. Amniocentesis was applied to 30 women with an empirical risk of 1:20, and alphafoetoprotein was analysed in their amniotic fluid. Anencephaly was diagnosed in one case and confirmed by termination of pregnancy. The occurrence of neural tube defects usually is of spontaneous nature, and incidence is relatively high. Therefore efforts are now being made to introduce a scheme of prenatal screening based on alphafoetoprotein assessment in the serum of pregnant women.

Plain radiographs of the urinary tract on 2707 normal volunteers were reviewed to establish the prevalence and patterns of spina bifida occulta in the normal population. Abnormalities in the formation of the posterior arch were identified in 23%, and four different patterns are described. In this group of subjects the condition was twice as common in males as in females (P less than 0.001) and commoner in younger adults. The commonest defects were either in S1 alone or involved S1 and S2 together. Isolated defects at L5 or S2 were rare. The level of opening of the posterior sacral arcs was assessed and a high level of opening was shown to correlate with the presence of spina bifida occulta.

This paper reports the results of a study of families in the Eastern Ontario/Western Quebec region who had a child born with a neural tube defect during the years 1969-1981. As in several other geographic areas, the prevalence of neural tube defects at birth has fallen from previous levels. However, there was no evidence of further decline during the period of study. Socioeconomic and ethnic influences were noted, but there was no evidence of seasonal variation or any correlation with maternal age or parity. There was support for a causative role of maternal fever in some cases. The rates of miscarriage varied between pregnancies before and those after the proband, and there was an excess of males born prior to the proband. Family studies showed a 2.4% risk for sibs born after the proband and an excess of affected relatives on the maternal side. Knowledge of rates of occurrence in relatives is useful for counseling and the interpretation of the results of alpha-fetoprotein screening.