Neural Tube Defects In Offspring Research Articles

Maternal Lactase Polymorphism (rs4988235) Is Associated with Neural Tube Defects in Offspring in the National Birth Defects Prevention Study

The risk of neural tube defect (NTD)-affected pregnancies is reduced with adequate folic acid intake during early pregnancy. However, NTDs have been observed among offspring of women with adequate folic acid intake. Some of these women are possibly not absorbing enough folic acid. Because lactase deficiency can lead to poor nutrient absorption, we hypothesized that lactase-deficient women will be at increased risk of having offspring with NTDs. We examined the association between maternal rs4988235 (a lactase deficiency genetic marker) and NTDs in offspring. We conducted a case-control study using data from the National Birth Defects Prevention Study, United States, 1997-2009, restricting to non-Hispanic white (NHW) and Hispanic women. Cases were women with an offspring with an NTD (n = 378 NHW, 207 Hispanic), and controls were women with an offspring without a birth defect (n = 461 NHW, 165 Hispanic). Analyses were conducted separately by race/ethnicity, using logistic regression. Women with the CC genotype were categorized as being lactase deficient. To assess potential effect modification, analyses were stratified by lactose intake, folic acid supplementation, dietary folate, and diet quality. Among NHW women, the odds of being lactase deficient were greater among cases compared with controls (OR: 1.37; 95% CI: 1.02, 1.82). Among Hispanic women, the odds of being lactase deficient were significantly lower among cases compared with controls (OR: 0.50, 95% CI: 0.33, 0.77). The association differed when stratified by lactose intake in NHW women (higher odds among women who consumed ≥12 g lactose/1000 kcal) and by dietary folate in Hispanic women (opposite direction of associations). The association did not differ when stratified by folic acid supplementation or diet quality. Our findings suggest that maternal lactase deficiency is associated with NTDs in offspring. However, we observed opposite directions of effect by race/ethnicity that could not be definitively explained.

Prepregnancy asthma and the subsequent risk of central nervous system defects in offspring.

The relationship between childhood asthma and central nervous system defects in offspring is poorly understood. We assessed if childhood asthma was associated with the risk of having an infant with neural tube or other nervous system defects compared with asthma during pregnancy. We analyzed a longitudinal cohort of 128,060 women who were 5 years or less at study entry and later delivered an infant in Quebec, Canada (1989-2014). We identified women hospitalized for asthma before pregnancy, including childhood and adolescence, and determined if asthma was present during pregnancy based on obstetric records. Main outcomes were neural tube and non-neural tube defects in pregnancy. We used log-binomial regression models to determine risk ratios (RR) and 95% confidence intervals (CI) for the association between asthma and risk of nervous system defects, adjusting for patient characteristics. Asthma was associated with a greater risk of neural tube defects in offspring (RR 2.39, 95% CI 1.03-5.53) compared with no asthma, but not non-neural tube defects (RR 1.10, 95% CI 0.71-1.71). Women whose asthma resolved before pregnancy had a greater risk of neural tube defects (RR 3.43, 95% CI 1.35-8.69), while women with asthma during pregnancy were at greater risk of non-neural tube defects, especially microcephaly (RR 2.80, 95% CI 1.23-6.40). Asthma that resolved before pregnancy was associated with an increased risk of neural tube defects in offspring but not non-neural tube defects. Further investigation is needed to determine the pathophysiology connecting childhood asthma with nervous system defects in offspring.

Maternal oversupplementation with folic acid and its impact on neurodevelopment of offspring.

Folic acid, a B vitamin, is vital for early neurodevelopment and is well known for its protective effect against neural tube defects. Various national health agencies worldwide recommend that women of childbearing age take approximately 0.4 to 1 mg of supplemental folic acid daily to reduce the risk of neural tube defects in offspring. Several countries have tried to promote folic acid intake through mandatory fortification programs to reduce neural tube defects. Supplementation combined with mandatory fortification of foods has led to high levels of folic acid and related metabolites in women of childbearing age. Recent studies have reported that oversupplementation, defined as exceeding either the recommended dietary allowance or the upper limit of the daily reference intake of folic acid, may have negative effects on human health. This review examines whether maternal oversupplementation with folic acid affects the neurodevelopment of offspring. Data from animal studies suggest there are behavioral, morphological, and molecular changes in the brain of offspring. Additional studies are required to determine both the dosage of folic acid and the timing of folic acid intake needed for optimal neurodevelopment in humans.

Preconception folic acid supplementation use and the occurrence of neural tube defects in Japan: A nationwide birth cohort study of the Japan Environment and Children's Study.

We evaluated the relationship between preconception folic acid supplementation and the occurrence of neural tube defects (NTDs) in offspring, using data from the Japan Environment and Children's Study (a nationwide prospective birth cohort study) database. Of 92 269 participants with single pregnancies, 74 cases (offspring or fetuses) had NTDs, including 32 cases of spina bifida, 24 cases of anencephaly, and 19 cases of encephalocele. A total of 7634 participants (8.27%) used preconception folic acid supplementation, and of these, 621 (0.67%) also took in dietary folic acid at ≥480 μg/day. Multivariate logistic regression analyses demonstrated no association between preconception folic acid supplementation and NTDs in offspring or fetuses (odds ratio [OR] 0.622; 95% confidence interval [CI]: 0.226-1.713). Moreover, the participants who combined preconception folic acid supplement use with dietary folic acid intake ≥480 μg/day demonstrated no incidence of NTDs in offspring or fetuses. Our analysis is limited by the absence of the data on the daily amount of supplementary folic acid intake, requiring careful attention to the interpretation. Additional surveys are required in Japan to resolve those limitations for further comprehensive assessment.

NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects.

Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that NMDA receptors are important for the formation of the neural tube and that the loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation.SIGNIFICANCE STATEMENT Neural tube defects are one of the most common birth defects. Clinical investigations have determined that the use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that they are side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy.

Low maternal folate concentrations and maternal MTHFR C677T polymorphism are associated with an increased risk for neural tube defects in offspring: a case-control study among Pakistani case and control mothers.

There is considerable evidence that periconceptional maternal folate deficiency and coding variants in maternal genes coding for critical enzymes in the folate pathway are associated with neural tube defects (NTDs) in offspring. In a case-control study we investigated C677T polymorphism in the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene in case and control mothers of Pakistani origin, and compared these with the respective maternal folate concentrations measured at the time of delivery. A case-control study was conducted among 109 case and 100 control mothers identified through the Holy Family Hospital Rawalpindi, Quaid-i-Azam University, Islamabad, Pakistan. Red blood cell (RBC) and serum folate concentrations and MTHFRC677T polymorphism were compared between case and control mothers. Mean RBC folate and serum folate concentrations were significantly lower in cases compared with control mothers (p<0.0001). Maternal MTHFR 677CT and 677TT genotypes were more common among cases compared with control mothers (CC vs TT p<0.0393 and CC/CT vs TT p<0.021). T-allele frequency was higher in cases compared with control mothers (C vs T p<0.017). Case mothers with 677CT or 677TT genotypes had significantly lower serum (p<0.0001) and RBC folate concentrations (p<0.0001) compared with control mothers. The present study provides further evidence that maternal folate deficiency and MTHFRC677T polymorphism might be associated with an increased risk for NTDs in offspring. Our results are limited by the fact that maternal folate concentrations were not obtained during the periconceptional period, but at delivery. Further analyses, including maternal folate levels during the periconceptional period, are warranted.

Maternal Use of Weight Loss Products and the Risk of Neural Tube Defects in Offspring: A Systematic Literature Review.

Several studies have assessed potential associations between use of weight loss products in the periconceptional period and neural tube defects (NTDs). However, the individual studies are inconclusive and there has not been a systematic review of this literature. We conducted a systematic search, using Ovid MEDLINE and PubMed, to identify studies that evaluated the association between products used for weight loss and the risk of NTDs. Because many studies of birth defects only evaluate a composite birth defect outcome, we evaluated studies that defined the outcome as "any major birth defect" or as NTDs. We abstracted data on study design, exposure definition, outcome definition, covariates and effect size estimates from each article that met our inclusion criteria. For studies that evaluated a composite birth defect outcome, we also abstracted the number of NTD cases included in the composite outcome. We used a modified version of the Newcastle-Ottawa Scale to assess the quality of each article. We screened 865 citations and identified nine articles that met our inclusion criteria. The majority of studies reported positive associations between maternal use of weight loss products and birth defects (overall and NTDs). However, there were few significant associations and there was considerable heterogeneity in the specific exposures assessed across the nine studies. Our systematic review of weight loss products and NTDs indicates that the literature on this topic is sparse. Because several studies reported modest, positive associations between risk and use of weight loss products, additional studies are warranted. Birth Defects Research 110:48-55, 2018. © 2017 Wiley Periodicals, Inc.

Maternal occupation and the risk of neural tube defects in offspring

ABSTRACTWe evaluated the association between maternal occupation and the risk of neural tube defects (NTDs) in offspring. Data for 491 nonsyndromic cases were obtained from the Texas Birth Defects Registry for deliveries between 1999 and 2009. We randomly selected 2,291 controls among all live births in Texas during this time. Maternal occupations were classified using automated software and manual assignment. Multivariable logistic regression analyses were used to examine the relationship between maternal occupation and risk for any NTD, adjusting for maternal race/ethnicity, any diabetes, and maternal body mass index. These analyses were repeated for spina bifida specifically. Some maternal occupations, particularly those related to business/finance, health care practice, and cleaning/maintenance, were significantly associated with increased risk of spina bifida and/or any NTD. Further research is needed to identify the specific occupational exposures related to NTD risk.

Folate receptors and neural tube closure

Neural tube defects (NTD) are among the most common human congenital malformations, affecting 0.5-8.0/1000 of live births. Human clinical trials have shown that periconceptional folate supplementation significantly decreases the occurrence of NTD in offspring. However, the mechanism by which folate acts on NTD remains largely unknown. Folate receptor (Folr) is one of the three membrane proteins that mediate cellular uptake of folates. Recent studies suggest that mouse Folr1 (formerly referred to as Fbp1) is essential for neural tube closure. Therefore, we examined spatial and temporal expression patterns of Folr1 in developing mouse embryos, showing a close association between Folr1 and anterior neural tube closure. Transient transgenic analysis was performed using lacZ as a reporter; we identified a 1.1-kb enhancer that directs lacZ expression in the neural tube and optic vesicle in a manner that is similar to endogenous Folr1. The 1.1-kb enhancer sequences were highly conserved between humans and mice, suggesting that human FOLR1 is associated with anterior neural tube closure in humans. Several experimental studies in mice and human epidemiological and genetics studies have suggested that folate receptor abnormalities are involved in a portion of human NTDs, although the solo defect of FOLR1 did not cause NTD.

Association of essential trace metals in maternal hair with the risk of neural tube defects in offspring.

The relationship between essential trace metals (ETMs) and the risk of neural tube defects (NTDs) is still unclear. One of the challenges is to evaluate the intake of ETMs of women during their early period of pregnancy. We proposed the hypothesis that an ETM deficiency in women during their early period of pregnancy is associated with an elevated risk of NTDs in offspring. We recruited 191 women with NTD-affected pregnancies (case group) and 261 women who delivered healthy infants (control group). Nine ETMs in hair sections grown during maternal early pregnancy were analyzed: iron (Fe), zinc (Zn), copper (Cu), cobalt (Co), manganese (Mn), chromium (Cr), nickel (Ni), molybdenum (Mo), and stannum (Sn). Information on maternal dietary habits were collected by questionnaire. We observed a significant decreasing trend in the dose-response relationships between the Ni and Mo concentrations in hair and NTD risks. A Zn deficiency was only associated with an elevated risk of spina bifida, and a Sn deficiency was only associated with anencephaly. The Ni and Zn concentrations in hair were positively correlated with the frequency of consumption of fresh green vegetables and fresh fruits, while the Zn concentration was also associated with fish or meat consumption. We concluded that maternal intakes of the four ETMs (Ni, Mo, Zn, and Sn) played an important role in the formation of NTDs in our study population, and that this intake is related to maternal dietary habits.Birth Defects Research 109:234-243, 2017.© 2016 Wiley Periodicals, Inc.

Association between titanium and silver concentrations in maternal hair and risk of neural tube defects in offspring: A case-control study in north China

Increasing uses of titanium and silver in various products raise concerns for their potential adverse effects on pregnancy outcomes. We aimed to examine the associations between titanium and silver concentrations in maternal hair growing during the periconception period and the risk of neural tube defects (NTDs) in offspring. Our case–control study recruited 191 women with NTD-affected pregnancies and 261 women delivering healthy infants. Metal concentrations in maternal hair were measured by inductively coupled plasma-mass spectrometry. The adjusted odds ratios (AOR) of titanium concentration above the median were 1.46 (95% confidence interval (CI), 0.99–2.13) for total NTDs and 2.10 (95% CI, 1.12–3.94) for anencephaly, while OR of silver wasn't statistically significant. Titanium concentration was positively correlated with consumptions of vegetables and fruits. Maternal exposure to titanium during the periconception period was associated with an increased NTD risk in offspring, which may be partly mediated through maternal dietary habits.

Maternal Antenatal Bereavement and Neural Tube Defect in Live-Born Offspring: A Cohort Study.

BackgroundMaternal emotional stress during pregnancy has previously been associated with congenital neural malformations, but most studies are based on data collected retrospectively. The objective of our study was to investigate associations between antenatal maternal bereavement due to death of a close relative and neural tube defects (NTDs) in the offspring.MethodsWe performed a register-based cohort study including all live-born children (N = 1,734,190) from 1978–2008. Exposure was bereavement due to loss of a close relative from one year before conception to the end of the first trimester of pregnancy. The outcome was NTDs in the offspring according to the International Classification of Disease. We used multivariate logistic regression to estimate prevalence odds ratios (ORs).ResultsA total of 2% children were born to mothers who lost a close relative prenatally. During 30 years of follow-up, 1,115 children were diagnosed with any NTDs: spina bifida (n = 889), anencephaly (n = 85) and encephalocele (n = 164). And 23 children were diagnosed with two types of NTDs. Overall, when comparing bereaved mothers to non-bereaved mothers, no significant increased prevalence of NTDs in the offspring was seen (OR = 0.84; 95% confidence interval: 0.52–1.33).ConclusionOverall maternal bereavement in the antenatal period was not related to NTDs in liveborn offspring.

Maternal obesity and the risk of neural tube defects in offspring: A meta-analysis

The aim of this was to access maternal obesity and the risk of neural tube defects (NTDs) in offspring, and establishes a nonlinear dose-response relationship between maternal body mass index (BMI) and risk of NTDs in offspring. PubMed and Web of Science were systematically searched. We compared NTDs risk difference in maternal obesity group vs. normal weight group+overweight group, and maternal obesity group vs. normal weight group. We also examined the dose-response relationship between maternal body mass index and the risk of NTDs in offspring. A total of 22 studies with 1,758,832 patients included in the meta-analysis. The results showed obesity maternal obesity is an important risk factor for NTDs in offspring. When maternal obesity group compared with normal weight group+overweight group, the summary OR of NTDs was 1.632 (95% CI 1.473-1.808; Z=9.37, P<0.00001); when maternal obesity group compared with normal weight group, the summary OR was 1.682 (95% CI 1.510-1.873; Z=9.44, P<0.00001). No publication biases were found. Dose-response meta-analysis showed statistically significant association between maternal BMI and risk of NTDs in offspring (model χ2=41.49, <0.00001). In linear model, the OR of NTDs in offspring was 1.040 (95% CI 1.027-1.051) for every 1kg/m2 BMI increase in mother. In spline model, the OR of NTDs in offspring risk increased rapidly along with maternal BMI, especially when BMI >30kg/m2. Sensitivity analyses by only included the studies reported adjusted OR showed the result was robust. Our meta-analysis indicated that maternal obesity is an important risk factor for neural tube defects in offspring.

Maternal plasma folate, vitamin B12 levels and multivitamin supplementation during pregnancy and risk of Autism Spectrum Disorder in the Boston Birth Cohort

BackgroundThe role of preconception/prenatal nutrition in the development of Autism Spectrum Disorder (ASD) is under-studied. Maternal adequate folate intake is important in protecting against neural tube defects in offspring, but uncertainty remains on its role in ASD. ObjectiveTo understand the relationship between maternal multivitamin supplementation during pregnancy and maternal plasma biomarkers of folate and vitamin B12 measured 24–72 hours after delivery and risk of later Autism Spectrum Disorder in children. MethodsData are from the Boston Birth Cohort, an ongoing longitudinal prospective birth cohort study that recruited low-income urban, primarily minority mother-offspring pairs (n=1,391) at the Boston Medical Center and followed them from birth through childhood between 1998–2013. Based on electronic medical records, children were diagnosed as having ASD (n=107) or categorized as ‘typical’ (n=1284). Prenatal multivitamin supplement intake data and maternal blood samples were collected 24–72 ho...

The green tea polyphenol EGCG alleviates maternal diabetes–induced neural tube defects by inhibiting DNA hypermethylation

Maternal diabetes increases the risk of neural tube defects in offspring. Our previous study demonstrated that the green tea polyphenol, Epigallocatechin gallate, inhibits high glucose-induced neural tube defects in cultured embryos. However, the therapeutic effect of Epigallocatechin gallate on maternal diabetes-induced neural tube defects is still unclear. We aimed to examine whether Epigallocatechin gallate treatment can reduce maternal diabetes-induced DNA methylation and neural tube defects. Nondiabetic and diabetic pregnant mice at embryonic day 5.5 were given drinking water with or without 1 or 10 μM Epigallocatechin gallate. At embryonic day 8.75, embryos were dissected from the visceral yolk sac for the measurement of the levels and activity of DNA methyltransferases, the levels of global DNA methylation, and methylation in the CpG islands of neural tube closure essential gene promoters. embryonic day 10.5 embryos were examined for neural tube defect incidence. Epigallocatechin gallate treatment did not affect embryonic development because embryos from nondiabetic dams treated with Epigallocatechin gallate did not exhibit any neural tube defects. Treatment with 1 μM Epigallocatechin gallate did not reduce maternal diabetes-induced neural tube defects significantly. Embryos from diabetic dams treated with 10 μM Epigallocatechin gallate had a significantly lower neural tube defect incidence compared with that of embryos without Epigallocatechin gallate treatment. Epigallocatechin gallate reduced neural tube defect rates from 29.5% to 2%, an incidence that is comparable with that of embryos from nondiabetic dams. Ten micromoles of Epigallocatechin gallate treatment blocked maternal diabetes-increased DNA methyltransferases 3a and 3b expression and their activities, leading to the suppression of global DNA hypermethylation. Additionally, 10 μM Epigallocatechin gallate abrogated maternal diabetes-increased DNA methylation in the CpG islands of neural tube closure essential genes, including Grhl3, Pax3, and Tulp3. Epigallocatechin gallate reduces maternal diabetes-induced neural tube defects formation and blocks the enhanced expression and activity of DNA methyltransferases, leading to the suppression of DNA hypermethylation and the restoration of neural tube closure essential gene expression. These observations suggest that Epigallocatechin gallate supplements could mitigate the teratogenic effects of hyperglycemia on the developing embryo and prevent diabetes-induced neural tube defects.

Maternal Coffee Consumption During Pregnancy and Neural Tube Defects in Offspring: A Meta-Analysis

ABSTRACTPurpose To examine the association between maternal coffee consumption during pregnancy and the occurrence of neural tube defects (NTDs) in offspring. Methods PubMed, Springer Link and Elsevier databases were searched up to August, 2014. Case-control and cohort studies published on the association between maternal coffee consumption during pregnancy and the occurrence of NTDs in offspring were included. Meta-analysis was applied to calculate the pooled effect estimates and their 95% confidence intervals (CIs) using a random-effects model. Results A total of six case-control studies and one cohort study were included. The pooled effect estimate of maternal coffee consumption during pregnancy was 0.86 for total NTDs (95% CI: 0.51– 1.45) and 1.30 (95% CI: 0.67– 2.52) for NTDs subtype of spina bifida. Conclusions Our findings suggested that maternal coffee consumption during pregnancy was not significantly associated with the occurrence of total NTD or the spina bifida subtype of NTD.

Maternal periconceptional alcohol consumption and the risk of neural tube defects in offspring: a meta-analysis

Objective: Several studies have been conducted to examine the association between alcohol consumption during pregnancy and risk of neural tube defects (NTDs), while the results are inconsistent. In the present study, we aimed to clarify the relationship between maternal periconceptional alcohol consumption and NTDs risk in offspring.Methods: PubMed, Springer Link, and Elsevier databases were searched up to November, 2014. All case–control and cohort studies of maternal alcohol consumption during pregnancy with risk of NTDs were included. The pooled odds ratios (ORs) and their 95% confidence intervals (CIs) for highest versus lowest category of alcohol consumption were calculated using a fixed- or random-effects model.Results: The pooled ORs of maternal periconceptional alcohol consumption were 1.01 (95% CI: 0.71–1.45) for total NTDs and 1.03 (95% CI: 0.65–1.64) for NTDs subtype of spina bifida. Specifically, the pooled ORs of maternal alcohol consumption in the first trimester and binge drinking were 1.01 (95% CI: 0.71–1.43), and 1.07 (95% CI: 0.81–1.41), respectively.Conclusions: Our findings suggested no association between maternal periconceptional alcohol consumption and NTDs risk in offspring.

Poor sleep during the periconceptional period increases risk for neural tube defects in offspring.

Poor sleep has been studied in relation to various diseases. Few studies have investigated the effect of poor sleep on birth defects. We examined the association of maternal poor sleep during periconceptional period and the risk of neural tube defects (NTDs) in offspring based on a large case-control study in northern China. The subjects included 629 NTD cases and 858 normal controls investigated between 2002 and 2007. Maternal sleep status was collected by health workers within first week after delivery. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of NTDs in association with poor sleep. The proportion of mothers with frequent poor sleep (≥4 days/week on average) was markedly higher in NTDs group (5.9%) than in control group (1.2%). In the multivariate analysis, frequent poor sleep was significantly associated with an increased risk of total NTDs (adjusted OR, 4.1; 95% CI, 1.9-8.8) and spina bifida subtype (adjusted OR, 6.4; 95% CI, 2.8-14.5). Frequent poor sleep showed a significant interaction with body mass index (BMI). Relative to women who reported poor sleep <4 days/week and with BMI < 24, frequent poor sleep showed a markedly higher increased risk of NTDs among overweight or obese women (adjusted OR, 11.8; 95% CI, 1.4-97.6) than women with BMI < 24 (adjusted OR, 2.5; 95% CI,1.1-5.9). Maternal frequent poor sleep during the periconceptional period may increase the risk for all NTDs and spina bifida. The association appears to be independent of some lifestyle factors that are closely associated with sleep quality.

Maternal consumption of non-staple food in the first trimester and risk of neural tube defects in offspring.

To study the associations between maternal consumption of non-staple food in the first trimester and risk of neural tube defects (NTDs) in offspring. Data collected from a hospital-based case-control study conducted between 2006 and 2008 in Shandong/Shanxi provinces including 459 mothers with NTDs-affected births and 459 mothers without NTDs-affected births. Logistic regression models were used to examine the associations between maternal consumption of non-staple food in the first trimester and risk of NTDs in offspring. The effects were evaluated by odds ratio (OR) and 95% confidence intervals (95% CIs) with SAS9.1.3.software. Maternal consumption of milk, fresh fruits and nuts in the first trimester were protective factors for total NTDs. Compared with consumption frequency of ˂1 meal/week, the ORs for milk consumption frequency of 1–2, 3–6, ≥7 meals/week were 0.50 (95% CI: 0.28–0.88), 0.56 (0.32–0.99), and 0.59 (0.38–0.90), respectively; the ORs for fresh fruits consumption frequency of 1–2, 3–6, ≥7 meals/week were 0.29 (95% CI: 0.12–0.72), 0.22 (0.09–0.53), and 0.32 (0.14–0.71), respectively; the ORs for nuts consumption frequency of 1–2, 3–6, ≥7 meals/week were 0.60 (95% CI: 0.38–0.94), 0.49 (0.31–0.79), and 0.63 (0.36–1.08), respectively. Different effects of above factors on NTDs were found for subtypes of anencephaly and spina bifida. Maternal non-staple food consumption of milk, fresh fruits and nuts in the first trimester was associated with reducing NTDs risk in offspring.

Markers of macromolecular oxidative damage in maternal serum and risk of neural tube defects in offspring

Neural tube defects (NTDs) are among the most common and severe congenital malformations. To examine the association between markers of macromolecular oxidative damage and risk of NTDs, we measured levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), protein carbonyl (PC), and 8-iso-prostaglandin F2α (8-iso-PGF2α) in maternal serum samples of 117 women with NTD-affected pregnancies and 121 women with healthy term newborns. We found higher levels of 8-OHdG and PC in the NTD group than in the control group; however, we did not observe a statistically significant difference in 8-iso-PGF2α levels between the NTD and the control groups. NTD risk increased with increasing quartiles of 8-OHdG [odds ratio (OR)=1.17; 95% confidence interval (CI) 0.39–3.51; OR=2.19; 95% CI, 0.68–7.01; OR=3.70; 95% CI, 1.30–10.51, for the second, third, and fourth quartile relative to the lowest quartile, respectively; P=0.009], and with increasing quartiles of PC (OR=2.26; 95% CI, 0.66–7.69; OR=3.86; 95% CI, 1.17–12.80; OR=5.98; 95% CI, 1.82–19.66, for the second, third, and fourth quartile relative to the lowest quartile, respectively; P=0.002]. Serum levels of 8-OHdG were higher in women who did not take folic acid supplements during the periconceptional period. These results suggest that oxidative stress is present in women carrying pregnancies affected by NTDs.