Extremely high prevalence of neural tube defects in a 4-county area in Shanxi Province, China

BACKGROUND: In the past, northern China's Shanxi Province has reported the highest incidence of neural tube defects (NTDs) in the world. However, little is known about the epidemiology of NTDs in this area in recent years. METHODS: Data were collected from a population-based birth defects surveillance system in 4 counties that captures information on all live births, stillbirths of at least 20 weeks' gestation, and pregnancy terminations at any gestational age resulting from prenatal diagnosis of a birth defect. We also surveyed mothers of NTD case patients to determine their use of folic acid before and during early pregnancy. RESULTS: During 2003, 160 NTD cases were identified among 11,534 births (NTD birth prevalence = 138.7/10,000 births). The rates of anencephaly, spina bifida and encephalocele were 65.9, 58.1, and 14.7 per 10,000, respectively, and a female predominance was observed among anencephaly cases (male-to-female relative risk [RR], 0.49; 95% confidence interval [CI], 0.30-0.79), but not among spina bifida (RR, 0.90; 95% CI, 0.55-1.45) and encephalocele (RR, 1.03; 95% CI, 0.40-2.69) cases. The percentages of pregnancy termination following prenatal diagnosis of anencephaly, spina bifida, and encephalocele were 50%, 41.8%, and 35.3%, respectively. NTD birth prevalence tended to be higher among mothers aged <20 or > or =30 years (P = .06) and was markedly associated with lower levels of maternal education (P < .001). Among 143 NTD mothers, only 6 (4.2%) used folic acid supplements during the periconceptional period. CONCLUSIONS: The NTD birth prevalence rate in the study area is among the highest worldwide. Folic acid deficiency may be one important risk factor.     

Neural tube defects among twin births.

To obtain accurate, unbiased rates of neural tube defects (NTDs) in twins, we conducted a population-based study that included live births and fetal deaths in Los Angeles County, California, ascertaining cases by multiple methods. Twenty-eight twin cases yielded a prevalence-at-birth of 1.6/1,000 twin births, which is significantly higher than the singleton prevalence of 1.1/1,000 births. In twins compared with singletons, the prevalences of both encephalocele and anencephaly are increased, whereas spina bifida is decreased. The twin case male/female sex ratio (.55) is lower than the singleton case sex ratio (.77). Concordance is relatively low at 3.7%, but appears to be higher than recently reported recurrence risks in other low prevalence areas. Stillbirths were most common among female cases and like-sex twins. Our study tends to support proposed etiologic theories associating NTDs with females or monozygotic twins, or both. There is increasing evidence that the etiology of NTDs may differ in high and low prevalence areas. We suggest also that twins and singletons may differ in their response to etiologic factors. The variations among anencephaly, spina bifida, and encephalocele in their association with twinning suggest that there may be different factors that influence the development of each specific NTD. The noted differences among the malformations also indicate that some of the variation among results of other studies of NTDs and twinning may be due to case ascertainment. Including spina bifida cases would decrease the proportion of twins in a study population, while including anencephalics would increase the proportion. Importantly, ascertaining fetal deaths would increase the proportion of anencephalics and case females, so studies of NTDs that do not include fetal deaths will show fewer twins than expected. On the basis of our findings and those of Layde et al., excluding encephaloceles will also decrease the number of twins among NTD cases. When investigating etiologic hypotheses for NTDs, these potential biases must be recognized.     

Clinical, genetic, and epidemiological factors in neural tube defects.

We examined clinical, genetic, and epidemiologic factors among 512 probands with nonsyndromal neural tube defects (NTDs). Data were analyzed after grouping the probands in four different ways with respect to pathological features and putative pathogenic mechanisms. Apparently unrelated congenital anomalies occurred more frequently among probands with craniorachischisis (62%), encephalocele (30%), or multiple NTDs (25%) than among probands with anencephaly (14.7%) or spina bifida (10.1%) (P much less than .0001). Unrelated congenital anomalies occurred less often among probands with low spina bifida (6.7%) than among probands with high spina bifida (19.5%). NTDs were seen in 7.8% of the siblings of probands with high spina bifida but in only 0.7% of the siblings of probands with low spina bifida, in 2.2% of the siblings of anencephalic probands, and in none of the siblings of probands with craniorachischisis, encephalocele, or multiple NTDS (P less than .001). In all 16 families in which two siblings had NTDs, both had either defects of the type associated with abnormal primary neurulation or defects of the type associated with abnormal canalization. High spina bifida and multiple NTDs were found more frequently than expected among the Sikh probands (P less than .02). The frequency of non-NTD congenital anomalies was higher among siblings of Sikh probands (8.8%) than among siblings of other probands (2.4%) (P less than .05). This excess was due to the occurrence of hydrocephalus without spina bifida in four of 68 siblings of Sikh probands.     

The sex ratio in anencephaly

It is shown that the well known excess of females in anencephalic births is statistically significant when compared with (a) the general population and (b) their normal sibs.There is also a statistically significant difference between the sex ratio of anencephalic births and that of spina bifida births which suggests that there is a definite difference in the genetic component of their aetiology.These results are discussed with reference to the genetics of anencephaly and spina bifida and a genetic model of the inheritance of the genetic component of anencephaly is given. The significance of a possible cytoplasmic factor is also considered.     

Proctalgia fugax: a cause of marital dysharmony.

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.     

Associated malformations in cases with neural tube defects

Infants with neural tube defects (NTDs) may have other associated congenital defects. The reported incidence and the types of associated malformations vary between different studies. The purpose of this investigation was to assess the prevalence of associated malformations in a geographically defined population. The prevalences at birth of associated malformations in infants with NTDs were collected between 1979 and 2003 on all infants born in the area covered by the registry of congenital anomalies of Northeastern France in 334,262 consecutive births. Of the 360 infants with NTDs born during this period, 20.5 % had associated malformations. Associated malformations were more frequent in infants who had encephalocele (37.5 %) than in infants with anencephaly (11.8 %) or infants with spina bifida (23.7 %). Malformations in the face (oral clefts), in the musculoskeletal system, in the renal system, and in the cardiovascular system were the most common other anomalies. In conclusion the overall prevalence of malformations, which was one in five infants, emphasizes the need for a thorough investigation of infants with NTDs. A routine screening for other malformations especially facial clefts, musculoskeletal, renal and cardiac anomalies may need to be considered in infants with NTDs, and genetic counseling seems warranted in most of these complicated cases.     

Genetic heterogeneity in neural tube defects.

In 1985-1987, the authors attempted to ascertain all cases of confirmed neural tube defects (NTD) in California and Illinois, not only among live-born infants (postnatal) but also cases ascertained during pregnancy (prenatal). Mothers of both prenatal and postnatal NTD cases were interviewed within 5 months. Among postnatal NTD cases, 14.9% (45/303) had anomalies not ordinarily associated with NTD. The frequency of non-NTD related anomalies was 9.4% (5/53) in anencephaly, 0/3 in craniorachischisis, 22.9% (8/35) in encephalocele, 14.5% (27/186) in spina bifida, 20% (1/5) in multiple NTD cases and 19% (4/21) in other NTDs. However, relatively few postnatal NTD cases had known multiple malformation patterns; Meckel-Gruber syndrome was the most common, with 2 postnatal cases, and 3 additional prenatal cases. Maternal age, paternal age and birth order in postnatal cases were 26.7 +/- 5.4 SD, 28.9 +/- 5.8 and 2.8 +/- 1.8, respectively. These characteristics were similar in prenatal NTD cases (27.9 +/- 6.0, 30.1 +/- 6.3, 2.5 +/- 1.5, respectively). We also found no differences in parental ages among different types of NTD. Frequency of prior spontaneous abortion differed neither between postnatal NTD (9.3%) and postnatal controls (8.1%), nor between prenatal NTD (10.7%) and prenatal control (8.7%). Loss rates in the pregnancy immediately prior to the index NTD cases were not significantly higher than in control subjects. The high frequency of non-NTD associated malformations (14.9%) indicates the caution must be exercised before assuming that a given NTD case is polygenic-multifactorial in etiology, especially cases of encephalocele.     

Prevalence of neural tube defects in South Australia, 1966-91: effectiveness and impact of prenatal diagnosis.

OBJECTIVE--To determine trends in total prevalence of neural tube defects in South Australia during 1966-91, the impact of prenatal diagnosis on birth prevalence, and the effectiveness of prenatal screening for neural tube defects in 1986-91. DESIGN--All births and terminations of pregnancy affected by neural tube defects and information on prenatal screening were ascertained from multiple sources including the South Australian perinatal and abortion statistics collections, birth defects register, and state maternal serum alpha fetoprotein screening programme. SETTING--Southern Australia. SUBJECTS--All 1058 births and terminations of pregnancy affected by neural tube defects in 1966-91. MAIN OUTCOME MEASURES--Total prevalence and birth prevalence of individual and all neural tube defects. The proportion of screened cases detected prenatally. RESULTS--Total prevalence of neural tube defects during 1966-91 was 2.01/1000 births with no upward or downward trend. However, birth prevalence fell significantly (by 5.1% a year), with an 84% reduction from 2.29/1000 births in 1966 to 0.35/1000 in 1991 (relative risk = 0.16, 95% confidence interval 0.07 to 0.34). The fall was 96% for anencephaly and 82% for spina bifida. 85% of defects, both open and closed, were detected before 28 weeks'' gestation in women screened by serum alpha fetoprotein or mid-trimester ultrasonography, or both, in 1986-91 (99.0% for anencephaly and 75.7% for spina bifida). CONCLUSIONS--While the total prevalence of neural tube defects in South Australia remained stable, prenatal diagnosis and termination of pregnancy resulted in an 84% fall in birth prevalence during 1966-91. Screening detected over four fifths of cases in 1986-91.     

Prevalence of spina bifida and anencephaly during the transition to mandatory folic acid fortification in the United States

BACKGROUND: In 1992, the United States Public Health Service recommended that all women of childbearing age consume 400 microg of folic acid daily. The Food and Drug Administration authorized the addition of synthetic folic acid to grain products in March 1996 with mandatory compliance by January 1998. The impact of these public health policies on the prevalence of neural tube defects needs to be evaluated. We sought to determine the prevalences of spina bifida and anencephaly during the transition to mandatory folic acid fortification. METHODS: Twenty-four population-based surveillance systems were used to identify 5,630 cases of spina bifida and anencephaly from 1995-99. Cases were divided into three temporal categories depending on whether neural tube development occurred before folic acid fortification (January 1995 to December 1996), during optional fortification (January 1997 to September 1998), or during mandatory fortification (October 1998 to December 1999). Prevalences for each defect were calculated for each time period. Data were also stratified by programs that did and did not ascertain prenatally diagnosed cases. RESULTS: The prevalence of spina bifida decreased 31% (prevalence ratio [PR] = 0.69, 95% confidence interval [CI] = 0.63-0.74) from the pre- to the mandatory fortification period and the prevalence of anencephaly decreased 16% (PR = 0.84, 95% CI = 0.75-0.95). Stratification by prenatal ascertainment did not alter results for spina bifida but did impact anencephaly trends. CONCLUSIONS: The decline in the prevalence of spina bifida was temporally associated with folic acid fortification of US grain supplies. The temporal association between fortification and the prevalence of anencephaly is unclear.     

Spina bifida and anencephaly in Scotland.

Data obtained from routine sources showed that from 1971 to 1982 the birth prevalences of spina bifida and anencephaly in Scotland fell. When known terminations after routine alpha fetoprotein screening were added to total births the adjusted birth prevalence could be calculated. In 1974-82 this fell by 40% for spina bifida (3 X 0-1 X 8) and 36% for anencephaly (2 X 2-1 X 4). These findings were compared with data on birth prevalences in England and Wales, Northern Ireland, and Glasgow. The fall in birth prevalences of spina bifida and anencephaly over the past decade appears to have been due both to a true fall in incidence as well as to increased screening and termination for these conditions.     

与神经管畸形相关的基因学研究进展

神经管畸形（neural tube defects,NTDs）是指由于在胚胎发育过程中,神经管闭合不全所引起的一组出生缺陷,包括无脑儿、脊柱裂、脑积水、脑或脑脊膜膨出等,其危害极大,严重影响患儿的生理发育和生活质量,给家庭和社会带来沉重的精神压力和经济负担。大多数研究认为神经管畸形是多因素多基因的遗传疾病,是遗传、环境、营养因素共同作用、交互影响的结果,目前还不能用一种单一原因解释该疾病的发生。本文主要从导致神经管畸形发生的叶酸代谢酶基因多态性、神经管形态学方面的相关基因研究等做一综述。     

Epidemiology and genetics of neural tube defects: an application of the Utah Genealogical Data Base

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%.     

Trends in the postfortification prevalence of spina bifida and anencephaly in the United States

BACKGROUND: The prevalence of NTDs in the US declined significantly after mandatory folic acid fortification; however, it is not known if the prevalence of NTDs has continued to decrease in recent years relative to the period immediately following the fortification mandate. METHODS: Population‐based data from 21 birth defects surveillance systems were used to examine trends in the birth prevalence of spina bifida and anencephaly during 1999–2000, 2001–2002, and 2003–2004. Prevalence data were stratified by non‐Hispanic White, non‐Hispanic Black, and Hispanic race or ethnicity. Prevalence ratios were calculated by dividing the birth prevalences during the later time periods (2001–2002 and 2003–2004) by the birth prevalences during 1999–2000. RESULTS: During 1999–2004, 3,311 cases of spina bifida and 2,116 cases of anencephaly were reported. Hispanic infants had the highest prevalences of NTDs for all years. For all infants, the combined birth prevalences of spina bifida and anencephaly decreased 10% from the 1999–2000 period to the 2003–2004 period. The decline in spina bifida (3%) was not significant; however the decline in anencephaly (20%) was statistically significant. CONCLUSIONS: While the prevalences of spina bifida and anencephaly in the United States have declined since folic acid fortification in the food supply began, these data suggest that reductions in the prevalence of anencephaly continued during 2001–2004 and that racial and ethnic and other disparities remain. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Area Differences in Spontaneous Abortion Rates in South Wales and Their Relation to Neural Tube Defect Incidence

Data are presented from the South Wales Congenital Malformation Survey (92,982 births 1964-6 inclusive) showing that within areas in South Wales there exists an inverse relation between previous spontaneous abortion rate and the prevalence at birth of neural tube defect (anencephaly or spina bifida cystica or both). This relation is independent of social class, parity, and maternal age, and is not likely to be explained by area differences in accuracy of reporting previous spontaneous abortions.On the basis of these findings a hypothesis is advanced which proposes that the incidence of neural tube defects is uniform throughout South Wales and that the present substantial and relatively stable differences in area prevalence are controlled by small area differences in mortality of malformed embryos. This would seem to suggest that factors initiating the malformation are genetic and that any related environmental factors exert their effect on already abnormal fetuses by influencing, in one way or another, their capacity to survive.     

Neural-tube defects: importance of a history of abortion in aetiology.

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.     

Spina bifida and so-called asplenia syndrome occurring separately in sibs.

Attention is drawn to the possibility that neural-tube defects may sometimes be associted with the so-called asplenia syndrome (Ivemark syndrome). This hypothesis is based upon a family in which one child had spina bifida and hydrocephaly and another had cardiovascular and other fissural anomalies, similar to Ivemark syndrome. The family history, moreover, revealed several cases of anencephaly and/or spina bifida, both on the paternal and maternal sides.     

Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects

BACKGROUND: The number of mouse mutants and strains with neural tube closure defects (NTDs) now exceeds 190, including 155 involving known genes, 33 with unidentified genes, and eight "multifactorial" strains. METHODS: The emerging patterns of mouse NTDs are considered in relation to the unknown genetics of the common human NTDs, anencephaly, and spina bifida aperta. RESULTS: Of the 150 mouse mutants that survive past midgestation, 20% have risk of either exencephaly and spina bifida aperta or both, parallel to the majority of human NTDs, whereas 70% have only exencephaly, 5% have only spina bifida, and 5% have craniorachischisis. The primary defect in most mouse NTDs is failure of neural fold elevation. Most null mutations (>90%) produce syndromes of multiple affected structures with high penetrance in homozygotes, whereas the "multifactorial" strains and several null-mutant heterozygotes and mutants with partial gene function (hypomorphs) have low-penetrance nonsyndromic NTDs, like the majority of human NTDs. The normal functions of the mutated genes are diverse, with clusters in pathways of actin function, apoptosis, and chromatin methylation and structure. The female excess observed in human anencephaly is found in all mouse exencephaly mutants for which gender has been studied. Maternal agents, including folate, methionine, inositol, or alternative commercial diets, have specific preventative effects in eight mutants and strains. CONCLUSIONS: If the human homologs of the mouse NTD mutants contribute to risk of common human NTDs, it seems likely to be in multifactorial combinations of hypomorphs and low-penetrance heterozygotes, as exemplified by mouse digenic mutants and the oligogenic SELH/Bc strain.     

Spina bifida phenotypes in infants or fetuses of obese mothers

BACKGROUND: A twofold or greater risk of neural tube defect (NTD)-affected pregnancy has been associated with prepregnant obesity, where obesity was defined as body mass index (BMI) of >29 kg/m(2). Risks have been more elevated for spina bifida than for anencephaly. METHODS: We investigated whether finer phenotypic classifications of spina bifida, in combination with other factors, were associated with a BMI of >29 kg/m(2). Data were derived from a case-control study of fetuses and infants with NTDs among 1989-1991 California births. Interviews were conducted with mothers of 277 spina bifida cases and 517 nonmalformed controls. RESULTS: Women with a BMI of >29 kg/m(2) compared with those 29 kg/m(2) compared with males whose mothers were 相似文献   

Birth defects in Arkansas: Is folic acid fortification making a difference?

BACKGROUND: Since 1998, fortification of grain products with folic acid has been mandated in the United States, in an effort to reduce the prevalence of neural tube defects (NTDs). Published reports have shown a reduction in the prevalence of spina bifida since fortification was mandated, but no published studies have reported a reduction in birth defects, other than NTDs, that are postulated to be associated with folic acid deficiency. This study was performed to determine if fortification has reduced the prevalence of NTDs and other birth defects in Arkansas. METHODS: Using data from the Arkansas Reproductive Health Monitoring System, prevalences were computed for thirteen specific birth defects with prior evidence supporting a protective effect of folic acid or multivitamins. Prevalences were calculated using data for live births to Arkansas residents for 1993-2000. Exposure to folic acid fortification was classified by birth year as "pre-fortification" (1993-1995), "transition" (1996-1998) or "post-fortification" (1999-2000). Logistic regression analysis was used to compute crude and adjusted prevalence odds ratios comparing the identified time periods. RESULTS: Prevalences decreased between the pre- and post-fortification periods for spina bifida, orofacial clefts, limb reduction defects, omphalocele, and Down syndrome, but only the decrease in spina bifida was statistically significant (prevalence odds ratio 0.56; 95% confidence interval, 0.37, 0.83). CONCLUSION: In Arkansas, the prevalence of spina bifida has decreased since folic acid fortification of foods was implemented. Similar studies by other birth defects surveillance systems are needed to confirm a preventive effect of fortification for malformations other than spina bifida.     

Feasibility of using the national hospital discharge survey to estimate the prevalence of selected birth defects

BACKGROUND: Nationally representative data on the prevalence of certain birth defects are largely unavailable. We evaluated the feasibility of using data from the National Hospital Discharge Survey (NHDS) to describe the prevalence of selected birth defects. METHODS: All live births recorded in the NHDS during 1999-2001 were included. The prevalence for selected birth defects was calculated using weighted ratio estimators. Prevalence ratios comparing the NHDS estimates to published national estimates from the National Birth Defects Prevention Network (NBDPN) were calculated. RESULTS: With the exception of common truncus, the NHDS prevalence for the selected defects was consistently lower than the NBDPN estimates. The prevalence ratios ranged from 0.38 for trisomy 18 and anopthalmia/micropthalmia to 1.16 for common truncus. The NHDS prevalence estimates for spina bifida without anencephaly (PR 0.89, 95% CI: 0.57-1.22) and gastroschisis/omphalocele (PR 0.94, 95% CF: 0.48-1.40) most closely approximated the NBDPN estimates. CONCLUSIONS: NHDS data underestimate the prevalence of most birth defects. Additional research is needed to determine whether NHDS estimates may be useful for evaluating trends in certain conditions. Surveillance systems employing active case-finding continue to provide more accurate estimates of birth defects prevalence.