Birth ranks of spontaneous abortions in sibships of children affected by anencephaly or spina bifida.

Data on the birth ranks of miscarriages within sibships in which a case of anencephaly or spina bifida (ASB) had occurred were analysed by the Haldane-Smith statistical test. This showed that miscarriages in ASB sibships tend to have a negative birth order effect--that is, they occur in earlier rather than later pregnancies within the sibship. The strongest source of bias in this analysis--the fact that mothers tend to forget early spontaneous abortions--worked against this finding, so the negative birth order effect is probably genuine. Because ASB itself shows a negative birth order effect and because spontaneous abortions in normal sibships do not show such an effect, the additional spontaneous abortions in ASB sibships are probably of fetuses affected by ASB.     

Spina bifida and anencephaly: miscarriage as possible cause.

In two retrospective Liverpool surveys the domestic, family, dietary, and medical environments of the mothers of children affected by anencephaly or spina bifida, or both (ASB) were examined. None seemed to be of more than minor importance and the findings of others were therefore examined to see if they suggested a major factor. The most promising lead came from the hypothesis that ASB is usually due to an interaction between twin fetuses or between a fetus and residual trophoblastic material from the previous normal pregnancy, particularly when this is of the opposite sex to the propositus. The sex finding was not confirmed. It was noted that hydatidiform moles, like children with ASB, were usually female and that moles and choriocarcinomas on the one hand and children with ASB on the other occurred in mothers of similar ages, but were to some extent reciprocal in geographical incidence. This suggested that trophoblastic disease might be a factor common to all three and if so then one would expect the frequency of miscarriages to be higher immediately before than immediately after the birth of an ASB child, since mole and choriocarcinoma seldom follow a normal pregnancy. An analysis of published data confirmed that this was almost certainly so. Hence residual pathological trophoblastic material from either a previous miscarriage or a co-twin may interact unfavourably with another fetus to produce ASB and this may be the primary cause of the condition. The hypothesis is consistent with the observed lack of concordance in twins, the high incidence in females, the maternal age effect, and the greater prevalence in social classes IV and V.     

Maternal fever and neural tube defects

It has been proposed that hyperthermia in the pregnant woman is associated with neural tube defects in her offspring. We analyzed retrospective interview data for a maternal history of probable febrile illness during the first trimester of pregnancy among mothers of infants with anencephaly or spina bifida. There were two control groups--mothers of infants with Down syndrome and mothers of infants with cleft lip or palate. With the Down syndrome group serving as controls, the incidence of febrile illness among mothers of all infants with neural tube defects was significantly elevated. With the cleft group as controls, the fever incidence was not significantly increased in the neural tube defect groups. When the combined cleft and Down syndrome controls were used, only mothers of the spina bifida group had an elevated fever incidence. Epidemiology data suggest an association of maternal fever during pregnancy with neural tube defects in the offspring.     

Heterogeneity of neural tube defects in Europe: the significance of site of defect and presence of other major anomalies in relation to geographic differences in prevalence.

In the period 1980-1987, neural tube defects were two to three times more prevalent in populations covered by EUROCAT registries in the United Kingdom and Ireland (UKI) than in Continental Europe and Malta (CEM). 1864 NTD cases in a total population of 580,000 births in UKI and 455 cases in a population of 380,000 births in CEM were analysed to find if there were differences in the ratio of prevalence rates between UKI and CEM according to site of the defect and association with non-central nervous system (CNS) anomalies. The prevalence rate ratio was high for anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida, and low for encephalocele, lower spina bifida, and anencephaly without other neural tube defects. There was a greater female excess for anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida than for other defects in both geographic areas. There was a female excess for encephalocele in UKI but a male excess in CEM. Certain sites (anencephaly with accompanying spina bifida, iniencephaly, and encephalocele) were more likely to have accompanying non-CNS anomalies. The prevalence rate ratio of multiply malformed NTD was in general lower than for isolated NTD but showed the same pattern by site. The prevalence rate ratio was high for multiply malformed anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida. The sex ratio was similar between isolated and multiply malformed cases when site of the defect is taken into account. It is concluded that the geographic prevalence pattern and sex ratio differ according to site of NTD but do not differ substantially according to whether NTD is isolated or associated with non-CNS anomalies.     

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.     

Orofacial clefts and spina bifida: N-acetyltransferase phenotype,maternal smoking,and medication use

BACKGROUND: Orofacial clefts and spina bifida are midline defects with a multifactorial etiology. Maternal smoking and medication use periconceptionally have been studied as risk factors for these malformations. The biotransformation enzyme N-acetyltransferase 2 (NAT2), plays a part in the inactivation of toxic compounds in cigarette smoke and medication. We investigated maternal NAT2 phenotype and the interaction with smoking and medication use periconceptionally on orofacial cleft and spina bifida risk in offspring. METHODS: In this case-control study of 45 mothers of orofacial cleft children, 39 mothers of spina bifida children and 73 control mothers, NAT2 acetylator status was determined by measuring urinary caffeine metabolites. RESULTS: Slow NAT2 acetylators showed no increased risk for orofacial cleft (OR = 1.0, 95% CI: 0.4-2.3) or spina bifida offspring (OR = 0.7, 95% CI: 0.3-1.7) compared to fast NAT2 acetylators. More mothers with orofacial cleft and spina bifida offspring smoked cigarettes (36% and 23% respectively) and used medication periconceptionally (38% and 44% respectively) compared to control mothers (smoking:18%, medication use:19%). No interaction between maternal NAT2 acetylator status and smoking or medication use was observed for orofacial cleft and spina bifida risk. CONCLUSIONS: Maternal smoking and medication use is associated with orofacial cleft risk as well as medication use is with spina bifida. The maternal NAT2 acetylator status, however, was not associated with an increased risk for orofacial cleft or spina bifida offspring, nor in combination with periconceptional smoking or medication use.     

Prevalence of spina bifida occulta in patients with functional disorders of the lower urinary tract and its relation to urodynamic and neurophysiological measurements.

OBJECTIVE--To determine the relation between neurophysiological abnormalities and the radiological detection of spina bifida occulta in patients with dysfunction of the lower urinary tract. DESIGN--Blind assessment and subsequent decoding of mixed batch of abdominal radiographs from patients with and without urological symptoms for evidence of spina bifida occulta and comparison of results with those of previous control series. SETTING--Review study among tertiary referrals to an incontinence clinic of a city hospital. PATIENTS--One hundred and thirty eight adults with proved urodynamic abnormalities in whom neurophysiological measurements were available. INTERVENTIONS--None. END POINT--Correlation of neurophysiological abnormalities in lower urinary tract dysfunction with presence and type of spina bifida occulta and level of opening of posterior sacral arcs. MEASUREMENTS AND MAIN RESULTS--On decoding radiographs those from patients without urological symptoms showed a similar prevalence of spina bifida occulta to that in the control series (631/2707 controls; 23%). By contrast, patients with urological symptoms had a significantly increased prevalence of spina bifida occulta at S1 and S2 and a higher level of opening of posterior sacral arcs. The increased prevalence of the bony defect was particularly striking in men with urgency and instability and in women with stress incontinence. No significant correlation was found between any particular neurophysiological abnormality and the presence of spina bifida. CONCLUSIONS--In patients with dysfunction of the lower urinary tract neurophysiological abnormalities may be associated with congenital dysraphic lesions in the lower lumbar spine and sacrum. There appears to be no direct causal relation between the radiological and neurophysiological abnormalities but the findings suggest a common aetiological factor.     

Risk factors in the prevalence of anencephalus and spina bifida in New Zealand

This paper presents results from an epidemiological study on the 51 anencephalus and 53 spina bifida cases in the 1978 New Zealand birth cohort. Multiple sources were used in the ascertainment, and the prevalence rates were 0.98 and 1.02 per 1,000 total births, respectively. No association was found with the traditional indicators of the effect of environmental factors: maternal age, social class, nuptiality, month of birth, or estimated month of conception. Males comprised 41% of anencephalus and 36% of spina bifida cases; the prevalence was higher in the non-Maori than in the Maori population. New Zealand-born mothers appear to have a much lower risk of spina bifida, but not anencephaly, than those born in England/Scotland. The rate for the latter population was within the range of a number of UK-based studies. As the bloodstock of New Zealand whites has been predominantly derived from the UK population, and as New Zealand is a low prevalence area, this suggests that the higher risk for these women is likely to be attributable to factors present in their birthplace but absent in New Zealand. These findings provide further evidence that the epidemiologic patterns of anencephalus and spina bifida in low-prevalence areas are at variance with those in high-prevalence areas, such as the United Kingdom. They also support the hypothesis that the contrast in rates between high- and low-prevalence areas is a reflection of the impact of environmental factors in high-prevalence areas on the "background" or baseline frequency of anencephalus and spina bifida found in low-prevalence areas.     

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   

Anencephaly and spina bifida among Hispanics: Maternal,sociodemographic, and acculturation factors in the National Birth Defects Prevention Study

BACKGROUND : We used data from the multisite National Birth Defects Prevention Study for expected delivery dates from October 1997 through 2003, to determine whether the increased risk in anencephaly and spina bifida (neural tube defects (NTDs)) in Hispanics was explained by selected sociodemographic, acculturation, and other maternal characteristics. METHODS : For each type of defect, we examined the association with selected maternal characteristics stratified by race/ethnicity and the association with Hispanic parents' acculturation level, relative to non‐Hispanic whites. We used logistic regression and calculated crude odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS : Hispanic mothers who reported the highest level of income were 80% less likely to deliver babies with spina bifida. In addition, highly educated Hispanic and white mothers had 76 and 35% lower risk, respectively. Other factors showing differing effects for spina bifida in Hispanics included maternal age, parity, and gestational diabetes. For spina bifida there was no significant elevated risk for U.S.–born Hispanics, relative to whites, but for anencephaly, corresponding ORs ranged from 1.9 to 2.3. The highest risk for spina bifida was observed for recent Hispanic immigrant parents from Mexico or Central America residing in the United States <5 years (OR = 3.28, 95% CI = 1.46–7.37). CONCLUSIONS : Less acculturated Hispanic parents seemed to be at highest risk of NTDs. For anencephaly, U.S.–born and English‐speaking Hispanic parents were also at increased risk. Finally, from an etiologic standpoint, spina bifida and anencephaly appeared to be etiologically heterogeneous from these analyses. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

An intervention study to increase knowledge and use of folic acid among relatives in neural tube defect-affected families in Washington, D.C

BACKGROUND: Little is known about the level of knowledge and use of folic acid among near relatives in U.S. families of a child with spina bifida. We hypothesized that relatives would be more knowledgeable than the general population and more likely to take folic acid. Further, we hypothesized that relatives would be more motivated by an intervention to increase their use of folic acid. METHODS: We conducted an intervention study among females in families attending a hospital spina bifida clinic in Washington, DC. RESULTS: The 231 subjects consisted of the affected individuals, mothers, sisters, and aunts. The average age was 34 years. At baseline, most (87.4%) reported that they had heard of folic acid; 37.6% were currently taking multivitamins with folic acid and 6.9% were taking folic acid tablets. The intervention significantly increased both knowledge (to 99%) and intake of folic acid from 41.9 to 48.5%. Folic acid intake increased significantly among African-American women and women with less education, women who were older, married, with children, and nonsmokers. CONCLUSIONS: This intervention was successful in increasing folic acid intake among female relatives in spina bifida-affected families. By the end of the study, almost all women had heard of folic acid and folic acid use had increased by 16%. Among these women at higher than expected risk for having an affected child, this rate of intake, while more than the general population, still falls short of optimum. Fortification of food with folic acid may be the only way to ensure increased folic acid intake.     

Anthropological study on spina bifida in the Community of Madrid

The incidence of spina bifida in the Community of Madrid (Spain) has been assessed during an eleven-year period, since 1970 to 1980: 0.37 per 1,000 newborns over a total of 272,332 newborns, dead and alive, of simple births. The sex ratio at birth was 94. Maternal variables have been studied (maternal age, menarche, parity, etc.), obstetric variables (number of abortions, medication during pregnancy, etc.) and also neonatal variables (weight, gestational age, state at birth, etc.). Seasonal variations were observed.     

Spina Bifida and Potatoes

The results of a retrospective survey of the dietetic and other habits of the mothers of 83 children with spina bifida (mostly schoolchildren with meningomyelocele) were compared with 85 carefully matched controls. The survey was particularly concerned with the consumption of or contact with potatoes by the mothers. No significant differences were found in the amount of potatoes eaten as reported by the mothers (mean for spina bifida group 3·60 1b (1630 g), and for controls 3·98 1b (1800 g) per week). Of the seven other comparisons associated with potatoes only one (obtaining them from the chip shop or restaurant) was significant, the mothers of the children with spina bifida being more likely to obtain some of them from this source.When examining other aspects of diet it was found that the mothers of spina bifida children reported a lower consumption of a number of important foods, though the deficiency was not significant in any instance. These mothers were also significantly more likely to have been prescribed drugs other than iron and vitamins early in pregnancy and to have reported a wider variety of illnesses.The results in general do not support the hypothesis that the quantity of potatoes taken is important. They do lend support to the view that poor dietary habits are associated with a higher incidence of spina bifida irrespective of social class. Furthermore, general ill health in the mother may be implicated.     

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.     

Incidence of anencephalus and spina bifida in Greece

A cross-sectional national survey of 11,048 births in the whole of Greece in April 1984 identified 7 cases of anencephalus and 9 of spina bifida. There was thus an incidence of 1.45 neural tube defects per 1,000 total births. This is the first geographically defined population study from southern Europe. In comparison with hospital-based data from the 2 countries on its borders, the Greek rates are rather similar to those of Yugoslavia but much lower than reports from Turkey.     

Birth prevalence and recurrence rates of neural tube defects in southern Alberta in 1970-81.

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.     

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.     

Perinatal mortality and adverse pregnancy outcomes in a low-income rural population of women who smoke

We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low-income, rural mothers who participated in two randomized smoking cessation trials. In the Baby BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women's pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women who had a live infant after November 2004 were recruited again into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population and perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than 20 weeks' gestation, 23% were premature births, and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1000 births (BB study) compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births (United States). The postneonatal infant mortality rate was 13.4 per 1000 live births (BBK) compared with 2.1 per 1000 live births (United States). The health disparity in this population of impoverished, rural, pregnant women who smoke, particularly in regard to perinatal and infant deaths, warrants attention.     

Interaction of PDGFRA promoter haplotypes and maternal environmental exposures in the risk of spina bifida

BACKGROUND: Neural tube defects are multifactorial malformations involving both environmental exposures, such as maternal nutrition, and genetic factors. Aberrant expression of the platelet‐derived growth factor alpha‐receptor (PDGFRA) gene has been implicated in neural‐tube‐defect etiology in both mice and humans. METHODS: We investigated possible interactions between the PDGFRA promoter haplotype of mother and child, as well as maternal glucose, myo‐inositol, and zinc levels, in relation to spina bifida offspring. Distributions were determined of the PDGFRA promoter haplotypes H1 and H2 in a Dutch cohort, consisting of 88 spina bifida children with 56 of their mothers, and 74 control children with 72 of their mothers, as well as maternal plasma glucose, myo‐inositol, and red blood cell zinc concentrations. RESULTS: A significantly higher frequency of H1 was observed in children with spina bifida than in controls (30.1 vs. 20.3%; OR = 1.69, 95% CI 1.02–2.83). High maternal body mass index (BMI) and glucose were significant risk factors for both H1 and H2 children, whereas low myo‐inositol and zinc were risk factors for H2 but not for H1 children. Stepwise multiple logistic regression analysis showed that high maternal glucose and low myo‐inositol are the main risk factors for H2 spina bifida children, whereas for H1 spina bifida children, maternal BMI was the main risk factor. Interestingly, H1 mothers (median 165.5 cm) showed a significantly lower body height than H2 mothers (median 169.1 cm; p = 0.003). CONCLUSIONS: These data suggest that the child's PDGFRA promoter haplotype is differentially sensitive for periconceptional exposure to glucose, myo‐inositol, and zinc in the risk of spina bifida. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.