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PubMed2003

Folate intake and the risk of neural tube defects: an estimation of dose-response.

BACKGROUND: Studies have shown that folic acid supplementation in early pregnancy markedly reduces the risk of neural tube defects (NTDs). Investigation of the relation between relative dose of supplemental folic acid or total folate intake and NTD risk is limited. METHODS: We used data from 23,228 women, predominantly from the northeastern United States, enrolled between October 1984 and June 1987 in a prospective study of early prenatal exposures and pregnancy outcomes. Diet and vitamin intake data were gathered in the early second trimester. NTDs were ascertained through prenatal testing and by report of the delivering physician. Data analyses included multiple logistic regression and restricted spline regression modeling. RESULTS: For each additional 500 dietary folate equivalents consumed per day, the prevalence of NTDs decreased by 0.78 cases (95% confidence interval [CI] = 0.47-1.09) per 1,000 pregnancies. Compared with women having the lowest total folate intakes (0-149 folate equivalents per day), the prevalence of NTDs declined by 34%, 30%, 56% and 77% among the offspring of those women consuming 150-399, 400-799, 800-1199 and > or = 1200 folate equivalents per day, respectively (P-value for linear trend = 0.016). CONCLUSIONS: Our results suggest that NTD risk declines markedly with modest increases of total folate in early pregnancy. Total folate dose, rather than supplemental folate alone, should be considered in formulating public health guidelines for NTD prevention.

Adult↗
PubMed1995

Periconceptional vitamin use, dietary folate, and the occurrence of neural tube defects.

With a case-control study, we investigated whether periconceptional intake of supplemental or dietary folate reduced the risk of having a neural tube defect (NTD)-affected pregnancy. Mothers of 549 (88% of eligible) cases and 540 (88%) controls were interviewed in person about vitamin supplements used in either the 3 months before or the 3 months after conception and also about usual diet in the 3 months before conception. Women with any use of a folic acid-containing vitamin in the 3 months before conception had a lower risk of having an NTD-affected pregnancy [odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.45-0.94]. ORs were similar for 3 levels (< 0.4, 0.4-0.9, and > 0.9 mg per day) of average daily intake of folic acid. Any level of use in the first 3 months after conception resulted in a lowered risk as well (OR = 0.60; 95% CI = 0.46-0.79). Reduced risks were less marked for Hispanics and were not observed among women who graduated from college. Modest reduced risks were noted among non-vitamin users whose estimated daily dietary intake of folate was more than 0.227 mg. We observed decreasing risk with increasing folate intake from combined dietary sources and vitamin supplements. A reduction in NTD risk associated with folate intake is consistent with other studies; however, the reduced risk may be particular to subsets of the population, primarily non-Hispanic women and women whose education does not exceed high school.

Adult↗
PubMed1979

Antenatal screening in Oxford for fetal neural tube defects.

Between May 1975 and the end of 1977, 6443 antenatal patients were screened mainly between 16 and 22 weeks of pregnancy for neural tube defects (NTDs) at the John Radcliffe Hospital, Oxford, by maternal serum alpha-fetoprotein (AFP) measurement; a take-up of 72 per cent. Seventeen out of 18 (94 per cent) patients with open NTD pregnancies (9 out of 9 with anencephaly and 8 out of 9 with open spina bifida) had positive screening tests, and all except one were offered and accepted a termination of pregnancy. Two hundred and forty-five (3.8 per cent) patients with unaffected pregnancies also had positive screening tests, although only 1.4 per cent had an amniocentesis. Following ultrasonography, about 50 per cent of patients with unaffected pregnancies with positive screening tests were not offered an amniocentesis because they had a multiple pregnancy or their gestational age had been underestimated. The odds of having a fetus with an NTD among the women who had an amniocentesis was about 1 to 6 (1 to 11 for open spina bifida alone). Two apparently normal pregnancies were terminated. A survey of the acceptability of the screening programme among a consecutive sample of 73 patients who knew that they had a positive screening test revealed that all except one had no objection to screening in general, and 68 (93 per cent) wanted to be tested again in a future pregnancy. The approximate direct cost of the programme was 2 pounds to 3 pounds per patient screened, or about 1000 pounds per NTD detected (about 2200 pounds per open spina bifida detected).

Amniocentesis↗
PubMed1999

[Folic acid protects against neural tube defects. But how many women of reproductive age have been informed about this fact?].

The involvement of folic acid in the aetiology of neural tube defects (NTDs) has been discussed for decades. Both observational and controlled intervention trials have shown periconceptional folic acid supplementation (PFAS) to significantly reduce the incidence both of first-time and recurrent NTDs. PFAS may also be associated with reduction in the incidence of certain other congenital malformations, preterm delivery, and intra-uterine growth retardation. However, the mechanism whereby folic acid exerts its protective effect remains unclear. Thermolabile 5,10-methyl-enetetrahydrofolate reductase was the first folate-related enzyme to be associated with an increased risk of NTDs. This genetic variant may result in increased plasma homocysteine levels, which have been linked to an increased risk of NTDs. The folate-dependent genetic variants known today can explain no more than 30-50 per cent of the observed protective effect of folate. However, available evidence suggests low maternal folate status itself to be the major determinant of NTD risk. Since the vast majority of NTDs are first occurrences, and in Sweden a large proportion of fetuses with spina bifida remain undetected at routine ultrasonography during pregnancy, primary prevention by means of PFAS represents a major potential public health asset, capable of reducing both mortality and morbidity due to NTDs. Accordingly, implementation of a national strategy to reduce the incidence of NTDs, and promote awareness among health care providers and women of reproductive age of the benefits of PFAS is strongly to be recommended. Although supplemental folic acid tablets are the best proven means of improving folate status, compliance may be a problem, which emphasises the importance of considering a nutrient fortification programme as a complementary strategy for reducing the incidence of NTDs.

Female↗
PubMedDate not supplied

'Dual positivity' for neural tube defects and down syndrome at maternal serum screening: gestational outcome.

OBJECTIVE: To evaluate the gestational outcome of pregnancies screen-positive for both neural tube defects (NTD) and Down syndrome (DS) ('dual positivity'). METHODS: Among 10,667 mid-trimester women screened for DS and NTD with alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG), delivered up to July 1996, we have selected cases with both an unexplained AFP value > or = 2.5 multiples of median (MoM) and a DS risk > or = 1:250. All these pregnant women were managed with amniocentesis and/or CVS, ultrasound scans, and Doppler velocimetry. We have collected all data about the gestations with 'dual positivity' and no obvious explanation for these findings (cases with fetal malformations related to raised AFP). RESULTS: Twelve women (1.1:1,000) showed unexplained 'dual positivity'. Abnormal karyotypes were found in 3 fetuses, and pregnancies were terminated: there were 2 triploidies with partial hydatiform mola, and 1 DS. In 9 cases the fetal karyotype was normal, but a confined placental trisomy 16 was found in 4. Of the 9 continuing gestations, 8 displayed fetal growth retardation (FGR). One gestation ended with fetal death at 27 weeks. All 9 fetuses were morphologically normal, and 8 were small for gestational age. CONCLUSIONS: 'Dual positivity' at NTD/DS screening may anticipate pregnancy complications. The finding of trisomy 16 confined to the placenta and FGR in 4 cases suggests that at least some fetuses with growth restriction may suffer from a distinct placental disease. Maternal serum screening may have implications different from DS and NTD, as demonstrated by the 2 cases with triploidy and incomplete hydatiform mola, the 4 cases with placental trisomy 16, and the 4 cases of FGR of the 5 fetuses without chromosome abnormalities. As the pathologic outcome of these pregnancies is more important than the mere serum screening results, we feel that these cases need a strict work-up, including CVS, amniocentesis and ultrasound studies to better address the obstetrical management.

Adult↗
PubMed1983

Rapid acetylcholinesterase screening test for neural tube defect.

A 5-min optimized automated assay for measuring acetylcholinesterase (AChE) and total cholinesterase (ChE) in amniotic fluids is described in which a centrifugal analyzer is used. Total ChE was measured by using acetylthiocholine iodide and monitoring the color developed after 5,5'-dithiobis(2-nitrobenzoic acid) is added. We evaluated four direct and indirect procedures for measuring AChE in which thiocholine is generated. These methods involve either the specific enzyme inhibitors ethopropazine and BW284C51 or the specific substrates S-butyrylthiocholine and acetyl-beta-methylthiocholine. We found the last method distinguishes normal pregnancies most efficiently from those with neural tube defect. Filtering samples through 0.22-micron membrane filters before analysis decreased the incidence of false positives. Significantly increased AChE concentrations were noted in all abnormal pregnancies (n = 45) and in 4.8% of normal pregnancies (n = 310). The rapid AChE assay involving acetyl-beta-methylthiocholine, when applied alongside a rapid alpha-fetoprotein assay, increases the efficiency of screening programs for pregnancies with neural tube defect to 99.4%. It also identifies samples with negative results for alpha-fetoprotein that require further examination by the sensitive gel-electrophoretic test for AChE.

Acetylcholinesterase↗
PubMed2006

Postmortem evaluation of 220 prenatally diagnosed fetuses with neural tube defects: detection of associated anomalies in a Turkish population.

OBJECTIVES: The aim of this study is to represent the distribution of disorders resulting from neural tube defects (NTDs). MATERIALS AND METHODS: This study was conducted on 220 prenatally diagnosed cases with NTDs. Fetuses were evaluated by physical examination, anthropometric measurements, X-rays, and photographs after termination of pregnancy. Chromosome analysis and autopsy were performed for 37 fetuses (16.8%) with additional malformations. RESULTS: In 29 out of 37 fetuses (78.4%), additional malformations were detected by prenatal ultrasonography, whereas in eight cases postmortem evaluation produced additional findings that were not detected prenatally. Fourteen of 37 (37.8%) and 65 of 220 (29.5%) fetuses had clubfoot, which was mostly secondary to NTDs. There was no difference in sex distribution between isolated NTDs and the group with additional abnormalities and among the groups anencephaly and anencephaly + anomaly, encephalocele and encephalocele + anomaly, spina bifida and spina bifida + anomaly. There was only one case, a female fetus, with iniencephaly in this group. Anencephaly was more frequent in cases with isolated NTDs (48.1%) than in those with additional anomalies (27%). There was no difference for other groups of NTDs. The most frequent disorder was vertebral segmentation defects, which were detected in 11 out of 37 cases (29.7%). CONCLUSIONS: Evaluation of associated malformations and confirmation of ultrasound findings can be performed by postmortem examination and simple X-ray studies for exact diagnosis, which strongly affects decisions on further pregnancies as well as genetic counseling. This method is straightforward, inexpensive and effective.

Autopsy↗
PubMed2000

Expression of the sonic hedgehog gene in human embryos with neural tube defects.

BACKGROUND: To estimate the rate of malformations observed during early human development, a series of 38,913 first-trimester abortions were studied. Neural tube defects (NTD) were found in 57 cases. METHODS: A histological study of serial sections performed in 25 embryos revealed a spectrum of axial structure abnormalities. Expression of the SHH gene was studied by in situ hybridization in one case of CRS and in two cases of SB. RESULTS: A cervical notochord duplication was always found in craniorachischisis (CRS, n = 8), but not in spina bifida (SB, n = 10) or diplomyelia (split cord malformation, n = 3). In the embryo with CRS, expression of SHH was found in both domains, corresponding to the duplicated part of the notochord, whereas a single signal was observed in the nonduplicated part. This expression was associated at the cervical level of the open neural tube with a broad SHH expression domain and with two or even three domains in its lumbar region, suggesting multiple functional floor plates. Similarly, in two embryos with SB, two domains of SHH expression were found in the ventral neural tube. CONCLUSIONS: Our findings suggest that notochord splitting in the cervical region might be involved in the pathogenesis of CRS. Interestingly, similar notochord abnormality and altered expression of the shh gene are observed in Lp mice with NTD. This suggests that the Lp gene could be a candidate gene for human CRS. Further studies are needed to establish the primary event responsible for the notochord splitting and for the abnormal expression of the SHH gene in the floor plate in embryos with CRS and SB.

Abortion, Induced↗
PubMed1997

Dietary intake of myo-inositol and neural tube defects in offspring of diabetic rats.

OBJECTIVE: Embryopathy in diabetic mothers occurs at a rate four to five times higher than that observed in the general population. The current investigation was undertaken to assess the use of dietary myo-inositol supplementation as a pharmacologic prophylaxis to obviate the teratogenic effects of hyperglycemia in an in vivo study. STUDY DESIGN: Seventy Sprague-Dawley rats were mated and after conception were randomly divided into five groups: one group was nondiabetic normal controls and four groups had diabetes experimentally induced with streptozotocin. Of the diabetic groups, one received the usual diet, whereas the others received, respectively, 0.08, 0.16, and 0.5 mg/day supplemental myo-inositol orally. RESULTS: With the myo-inositol supplementation (0.08 mg/day), the incidence of neural tube defects was significantly reduced from 20.4% to 9.5% (p < 0.01). The most effective dosage of myo-inositol was 0.08 mg/day. Increasing the dose of myo-inositol beyond that level did not significantly reduce the rate of neural tube defects. However, the resorption rate was increased to 29.8%. CONCLUSION: These data demonstrate that myo-inositol supplementation reduces the incidence of diabetic embryopathy and may serve as a pharmacologic prophylaxis against diabetes-induced congenital malformations.

Animals↗
PubMed2003

Reduced folate carrier polymorphism (80A-->G) and neural tube defects.

Transport of folates in mammalian cells occurs by a carrier-mediated mechanism. The human folate carrier (RFC-1) gene has been isolated and characterized. Within this gene, a common polymorphism, 80A-->G, changing a histidine to an arginine in exon 2 (H27R), was recently identified. Defects in folate metabolism, such as defective carrier molecules, could be implicated in the etiology of neural tube defects (NTDs). In the present case-control study, we recruited 174 Italian probands with nonsyndromic NTD, 43 mothers, 53 fathers and 156 control individuals and evaluated the impact of RFC-1 variant on NTD risk. A statistically significant risk was calculated for the 80GG genotype of the NTD cases (OR=2.35; 95% CI 1.21-4.58) and mothers (OR=2.74; 95% CI 0.92-8.38). On the contrary, the heterozygous genotype of the mothers and both heterozygous and homozygous genotypes of the fathers did not seem to be significant NTD risk factors. Furthemore, according to the multifactorial inheritance of NTDs, we demonstrated that the combined genotypes for MTHFR 1298A-->C and RFC-1 80A-->G polymorphisms of cases resulted in greater NTD risk than heterozygosity or homozygosity for RFC-1 80A-->G variant alone. Conversely, our data provide no evidence for an association between NTD phenotype and combined MTHFR C677T/RFC-1 A80G genotypes. Moreover, here we describe the combinations of the two MTHFR polymorphic sites (677CT and 1298AC) with RFC-1 genotypes. We found that both patients and controls could have at most quadruple-mutation combinations. Interestingly, 27% (7/26) of the mothers and 18.75% (30/160) of the cases genotyped presented four mutant alleles in comparison with 8.5% (11/129) of the controls. Finally, the frequency of NTD cases and mothers carrying combined heterozygosity for the two MTHFR polymorphisms and RFC-1 80GG homozygosity (677CT/1298AC/80GG) (cases=11.3%; mothers 11.5%) was increased compared with controls (1.6%). Altogether, our findings support the hypothesis that RFC-1 A80G variant may contribute to NTD susceptibility in the Italian population.

Adult↗
PubMed2006

[Pre-administration of Ganoderma lucidum spore reduces incidence of neural tube defects induced by retinoic acid in pregnant mice].

OBJECTIVE: To explore whether pre-administration of Ganoderma lucidum spore (GASP) can reduce incidence of neural tube defects (NTDs) induced by all-trans retinoic acid (ATRA) in pregnant mice. METHODS: Twenty pregnant mice were randomly divided into four groups: normal control group, solvent-treated group, ATRA-induced group, and GASP-treated plus ATRA-induced group. GASP solution, which was prepared with solvent (sodium carboxymethyl cellulose), was fed to the pregnant mice in the GASP-treated plus ATRA-induced group twice a day from embryo (E) 0 d to E10.5 d. The same dose of solvent was given to the pregnant mice in the solvent-treated group. At E7.75 d, ATRA (50 mg/kg) was given to the pregnant mice in both ATRA-induced group and GASP-treated plus ATRA-induced group for single time. Embryos were sampled from pregnant mice at E10.5 d. Then the incidence rate of NTDs in mouse embryo was calculated and the crown-rump length of mouse embryo was measured. The positive rate of nestin expression and the distribution of cell cycle of embryonic neural tube neuroepithelial cells were detected by histochemical staining technique and flow cytometry respectively. Reverse transcription-polymerase chain reaction method was used to detect the gene expressions of cyclin-dependent protein kinase 2 (Cdk2) and Cdk4 mRNAs. RESULTS: The incidence rates of NTDs in mouse embryos in the ATRA-induced group and the GASP-treated plus ATRA-induced group were 79.41% and 21.67% respectively, while the crown-rump length of mouse embryos in these two groups were (3.62+/-1.27) mm and (5.84+/-0.92) mm respectively. The positive rate of nestin expression in embryonic neural tube neuroepithelial cells of mouse embryo at E10.5 d in the ATRA-induced group was 32.44%, while that in the GASP-treated plus ATRA-induced group was 77.65%. The cell cycle of embryonic neural tube neuroepithelial cells was obviously arrested at G(0)/G(1) phase in the ATRA-induced group as compared with that in the GASP-treated plus ATRA-induced group. The Cdk4 mRNA was transcripted at a high level in embryonic neural tube in the GASP-treated plus ATRA-induced group, but the Cdk2 mRNA was not detected in this group. CONCLUSION: Pre-administration of GASP can reduce the incidence of NTDs induced by ATRA in pregnant mice.

Animals↗
PubMed1992

Neural tube defect etiology: new evidence concerning maternal hyperthermia, health and diet.

The authors conducted a retrospective case-control study to determine risk factors for neural tube defects (NTD). 88 Louisiana women (44 matched pairs) were interviewed. Previous evidence suggested that maternal health and/or nutrition may be involved in the etiology of NTD. The findings substantiate the importance of maternal risk factors, including the apparent elevation of body temperature from taking hot baths during the first gestational month. Maternal health, as measured by reported illness and use of medications during pregnancy, was also significant. Several dietary factors, including intake of foods high in beta carotene, appeared to confer a protective effect. These findings suggest that some risk factors, particularly those involving maternal nutrition, may be population-specific.

Anencephaly↗
PubMed2003

[Sex distribution of neural tube defects and their birth outcome in high- and low-prevalence areas of China].

OBJECTIVE: To describe and analyze epidemiological characteristics of babies with neural tube defects (NTD) by sex and birth outcome in a high-prevalence and a low-prevalence areas of China. METHODS: Birth defects surveillance data collected from 1992 through 1994, as a part of the Sino-American cooperative project on NTD prevention, were used to classify NTD as four categories, i.e., anencephaly, encephalocele, high-level and low-level spina bifida according to the sites of lesion (high vs. low level lesion were cervicothoracic and lumbosacral, respectively). Each category was sub-classified, according to single or compound defect, as isolated external defects (including those with NTD only) or multiple external defects (including those with NTD and another major external birth defects that is not the sequence of a defect such as cleft lip with or without cleft palate). The rates of anencephalus, encephalocele, high- and low-level spina bifida (SB) in males and females and their sex ratios were calculated, adjusted for urban and rural areas, season, category and birth outcome by sex and sites of lesions (high vs. low). RESULTS: Totally, 784 NTD cases were identified from 326 874 recorded births (including live births, stillbirths and fetal deaths with a gestation age of at least 20 weeks). The prevalence rates of anencephalus (1.30 per 1 000 female births) and high-level SB (3.99) in females were higher than those (0.66 and 1.66 per 1 000 male births) in males in the high-prevalence northern regions; with adjusted prevalence rates of females 1.8 - 2.1 times greater than those of males. In the low-prevalence southern regions, the prevalence of high- (0.32 per 1 000 female births) and low-level SB (0.21) in female were higher than those in males, with high- and low-level SB rate of 0.10 and 0.09 per 1 000 male births), with adjusted rates for females of 1.3 - 1.6 times higher than in males. Isolated NTD accounted for more than 80% of all NTD cases, and the prevalence of isolated NTD in females (2.57) was higher than that in males (1.40). CONCLUSIONS: The sex differences in NTD existed between north and south, in accordance with the phenotype of NTD. It suggested that proportion of high level SB and anencephalus in females could increase as the prevalence of NTD going up, anencephaly, high- and low-level SB had the different genetic and environmental background.

China↗
PubMed1989

[Prenatal diagnosis of neural tube defects and clinical consequences].

Today, ultrasound is the most important method for antenatal recognition of defects of the central nervous system. This article reports our 17 years experience in antenatal diagnosis and management of neural tube malformations. A total of 103 neural tube defects were diagnosed, including anencephaly (36), rachischisis (31), encephalocele (13), microcephaly (11), and hydrocephalus (35). Ultrasonic findings, clinical histories, and management are reviewed.

Anencephaly↗
PubMed1990

Maternal serum alpha-fetoprotein screening for open neural tube defects in twin pregnancies.

Data on maternal serum alpha-fetoprotein (AFP) levels at 13-24 weeks' gestation in 46 twin pregnancies with open neural tube defects (22 with anencephaly, 24 with open spina bifida) and 169 unaffected twins were used to estimate the detection and false-positive rates associated with different cut-off levels. Using the conventional cut-off level of 2.5 multiples of the median (MoM) for unaffected singleton pregnancies of the same gestation and laboratory, the detection rate in twins was 99 per cent for anencephaly and 89 per cent for open spina bifida, with a false-positive rate of 30 per cent. Using a 5.0 MoM cut-off level to maintain a similar false-positive rate to that found among singleton pregnancies at 16-18 weeks' gestation (about 3 per cent), the detection rate was 83 per cent for anencephaly and 39 per cent for open spina bifida. Estimates are provided of the odds of having an affected twin pregnancy given a positive AFP result as well as the odds for individual women with a raised AFP level.

Anencephaly↗
PubMed1995

Genetic basis of neural tube defects: the mouse gene loop-tail maps to a region of chromosome 1 syntenic with human 1q21-q23.

A genetic basis for neural tube defects (NTD) is rarely doubted, but the genes involved have not yet been identified. This is partly due to a lack of suitable families on which to perform linkage analysis. An alternative approach is to use the many mouse genes that cause NTD as a means of isolating their human homologues. Loop-tail (Lp) is a semidominant mouse gene that, in homozygous mutants, causes the severe NTD phenotype cranio-rachischisis. As a first step toward cloning Lp, we have performed linkage analysis on an intraspecific backcross, using microsatellite and RFLP DNA markers. This study has localized Lp to a region of approximately 1.46 cM on mouse chromosome 1, flanked by the gene for the alpha chain of high-affinity Fc receptor for IgE (Fcer1 alpha) and a microsatellite repeat D1Mit113. Physical mapping data in the region suggest that the interval is likely to be no more than 1.8 Mb in size. The localization is several centimorgans distal to that previously assigned by linkage studies with biochemical and visible markers and suggests that the human homologue of Lp is likely to reside in a region of conserved homology on 1q21-q23.

Animals↗
PubMed2002

Paternal occupational group and risk of offspring with neural tube defects.

Selected paternal occupations as well as specific occupational exposures to chemicals such as organic solvents have been suggested as possible risk factors for neural tube defects (NTD). We investigated data from a population-based, case-control study of fetuses and liveborn infants with NTDs among 1989-91 California births and fetal deaths. Interviews were conducted with mothers of 538 NTD cases and 539 non- malformed controls. Mothers were asked to report the occupations that the fathers had in the period 3 months before and 3 months after conception. Each job title and industry reported was coded in accordance with the 1990 US Census. Considering those fathers who worked in managerial and professional occupations as the reference group, elevated odds ratios (OR) for NTDs were observed for the categories: technical, sales and administrative, OR = 1.5 [95% confidence interval 1.0, 2.4]; service, OR = 2.0 [1.2, 3.1]; farming, forestry and fishing, OR = 2.1 [1.3, 3.3]; operators, fabricators and labourers, OR = 1.8 [1.2, 2.7]; and military, OR = 1.9 [0.7, 5.0]. Stratification by NTD phenotype revealed that these elevated ORs were primarily observed for spina bifida phenotypes. Analyses adjusted for maternal body mass index, maternal periconceptional use of multivitamins containing folic acid, paternal race/ethnicity, maternal race/ethnicity and maternal education revealed attenuated risk estimates for most of the occupational groups. Analyses of 182 more specific occupational groups defined by aggregating fathers on similar job titles, when compared with fathers who worked in managerial and professional occupations, revealed that four job title groups were associated with fairly precise effect estimates of >or=1.5. These groups were: cooks; janitors and cleaners; farm workers; and groundsmen/gardeners. Using occupational titles as defined in previous investigations, we did not observe an elevated OR associated with paternal occupational solvent exposures, OR = 0.8 [0.5, 1.3]. These analyses generated potential clues regarding paternal occupational exposures as NTD risk factors. Risk variation observed by spina bifida phenotype is interesting and will need to be investigated further.

Anencephaly↗