OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

Objective To investigate the multiple correspondence of genetic and environmental risk factors with abnormal birth history and provide a scientific basis for improving the birth defects surveillance system and reducing the incidence of birth defects. Methods Data were collected from all the perinatal infants from 28-week-old fetuses to 7-day-old infants born in all the hospitals with obstetrical department in Xi'an from 2003 to 2015. Results A total of 1 236 937 perinatal infants were surveyed,including 10 619 with birth defects.The average incidence rate of birth defects was 0.86% (0.70%-1.15%).Multiple correspondence analysis showed that the women who had had 1 or 2 children with birth defects were associated with the history of spontaneous abortion,family history of birth defects,and history of exposure to toxic and harmful substances.The women who had had 3 or more children with birth defects showed stronger association with family history of birth defects.The birth defects in women with history of spontaneous abortion (257/10 619) was ranked in the order of congenital heart disease,polydactyly,neural tube defects,congenital hydrocephalus,cleft lip with cleft palate,and simple cleft lip.The birth defects in women who had given birth to children with birth defects (135/10 619) followed the order of cleft lip with cleft palate,anencephaly,hydrocephalus,neural tube defects,cleft lip,and talipes equinovarus. Conclusions Abnormal birth history is associated with family history of birth defects and history of exposure to environmental risk factors.Giving birth to three or more children with birth defects is highly correlated with the family history of birth defects.
Child ; Pregnancy ; Female ; Humans ; Cleft Lip/etiology* ; Cleft Palate/complications* ; Reproductive History ; Abortion, Spontaneous ; Neural Tube Defects/epidemiology* ; Risk Factors

OBJECTIVE: To find out the status of folic acid supplementation among women, to evaluate the prevention effects on neural tube defects (NTDs), and to explore the factors impact on folic acid supplementation compliance. METHODS: Based on the routine data of 92 121 women in prenatal health care and birth defect surveillance system in Tongzhou District of Beijing from 2013 to 2018, we described the prevalence of periconceptional folic acid supplementation, pre-pregnancy folic acid supplementation and regularly folic acid supplementation (compliance supplementation). Trend χ² tests were used to evaluate the change of folic acid supplementation prevalence. The prevalence difference among the women with folic acid supplementation and without supplementation were tested with Fisher's exact test. Factors asso-ciated with folic acid supplementation compliance rate were analyzed with univariate and multivariate Logistic regression model. RESULTS: The prevalence of periconceptional folic acid supplementation during the six years was 90.08% and it was increased from 2013 to 2018, but the rate of pre-pregnancy and regular supplementation was only 41.5% and declined from 2013 to 2018, especially 2013 to 2015. The prevalence of NTDs among the fetuses whose mothers took folic acid during periconceptional period was 5.5/10 000, while the prevalence for the fetuses whose mothers did not take folic acid was 19.7/10 000 (P < 0.001), the rates ratio was 27.9% (χ²=23.74, P < 0.001). The difference between the prevalence of NTDs among the fetuses whose mothers took folic acid only and multiple micronutrients was not statistically significant. After controlling the confounding factors, it was found that the compliant folic acid supplementation rates in women, whose household registrations were outside Beijing and whose education levels were junior high school or below, and who were younger than 25 years old, and who were multiparas and who were pre-pregnancy underweight or obese, were lower than those of the corresponding control groups (P < 0.05). CONCLUSION The rate of folic acid supplementation among women in Tongzhou District of Beijing was relatively high, but their compliance was poor. Women who did not take folic acid during periconception seriously affected the prevention effect of NTDs. We should focus on women who are younger than 25 years old, lower educated, pre-pregnancy underweight or obese, multiparas and nonlocal household registers, in order to improve the periconceptional folic acid supplementation compliance and improve the effects of NTDs prevention.
Adult ; Beijing ; Dietary Supplements ; Female ; Fetus ; Folic Acid ; Humans ; Neural Tube Defects/epidemiology* ; Pregnancy ; Prevalence

BACKGROUNDTo investigate the surveillance trend of birth defects, incidence, distribution, occurrence regularity, and their relevant factors in Xi'an City in the last 10 years for proposing control measures.

METHODSThe birth defects monitoring data of infants during perinatal period (28 weeks of gestation to 7 days after birth) were collected from obstetrics departments of all hospitals during 2003-2012. Microsoft Excel 2003 was used for data input, and Statistical Package for the Social Sciences version 16.0 (International Business Machines Corporation, New York, NY, USA) was used for descriptive analysis. χ2 test, Spearman correlation and linear-by-linear association trend test were used for statistical analyses.

RESULTSThe birth defect rate declined from 9.18% in 2003 to 7.00% in 2012 (χ2 = 45.001, P < 0.01) with a mean value of 7.85%, which is below the Chinese national average level (χ2 = 20.451, P < 0.01). The order of five most common birth defects has changed. The incidence of congenital heart disease (CHD) increased with time, particularly after 2012, it became the most frequent type (r s = 0.808, P < 0.001). Till then, the number of neural tube defects (NTDs) declined significantly (χ2 = 76.254, P < 0.01). The average birth defects rate of 8.11% in rural areas was higher than that in urban areas (7.56%, χ2 = 7.919, P < 0.01) and much higher in males (8.28%) than that in females (7.18%, χ2 = 32.397, P < 0.01). Maternal age older than 35 years (χ2 = 35.298, P < 0.01) is the most dangerous age bracket of birth defects than maternal age younger than 20 years (χ2 = 7.128, P < 0.01).

CONCLUSIONSA downward trend of birth defects was observed in Xi'an City from 2003 to 2012. NTDs significantly decreased after large-scale supplemental folic acid intervention, while the incidence rate of CHD significantly increased.

Congenital Abnormalities ; epidemiology ; Data Collection ; Female ; Humans ; Infant, Newborn ; Neural Tube Defects ; epidemiology ; Pregnancy ; Quality Control ; Vital Statistics

BACKGROUNDThe 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are attractive candidates for screening for risk of neural tube defects (NTDs). The aim of the current study was to investigate maternal MTHFR and MS polymorphisms and the interaction between them and their influence on children with NTDs in the Shanxi Province of northern China.

METHODSFifty-one mothers who previously had children with NTDs constituted the case group and 51 age-matched mothers with children that were unaffected by any birth defects constituted the control group. All subjects were genotyped for MTHFR C677T and MS A2756G polymorphisms. SPSS 11.5 software package was used for all analyses.

RESULTSThere was a significant difference for MTHFR genotype distribution for one site (C677T) between the case and control groups. The T allele frequencies were significantly higher in the case group than in the control group (55.9% vs. 35.3%, P < 0.05). A lack of association was observed for the MS A2756G polymorphism. There was an interaction between the maternal MTHFR C677T genotype and MS A2756G genotype.

CONCLUSIONGenetic interaction between MTHFR and MS genes raises the probability of neural tube defects.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; China ; Female ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Neural Tube Defects ; epidemiology ; genetics ; Polymorphism, Genetic ; genetics

INTRODUCTIONAnorectal malformations (ARMs) and low-lying spinal cord (LLC) are commonly associated owing to their common embryonic origin. LLC may lead to tethered cord syndromes (TCS), requiring surgery. This study aimed to review the incidence of LLC in children with ARMs using ultrasonography (US) and magnetic resonance (MR) imaging, the incidence of TCS and the surgical outcomes of these patients after detethering.

METHODSWe conducted a retrospective study of children who underwent surgery for ARMs in 2002-2009 at KK Women's and Children's Hospital, Singapore.

RESULTSOut of 101 (16.8%) ARM patients, 17 had LLC, of which 12 (70.6%) were high ARMs. 12 of the 17 (70.6%) patients had abnormal US and MR imaging findings. Five (29.4%) had normal US but abnormal MR imaging results; in these five patients, MR imaging was performed due to new symptoms and equivocal US findings. These 17 patients subsequently underwent surgical detethering. Three out of seven patients with TCS improved after surgery. None of the 17 patients had any complications.

CONCLUSIONLLC appeared to be associated with high ARMs, although this was not statistically significant. LLC should be investigated for whenever ARM is diagnosed, regardless of its type. Lumbar US is useful for first-line screening for LLC. Abnormal US or onset of new symptoms should subsequently be investigated with MR imaging. Equivocal US findings are also likely to benefit from further MR imaging. Surgery to detether LLC can improve outcome in TCS, while prophylactic detethering for asymptomatic patients with lipoma of the filum terminale has very low surgical risk.

Anorectal Malformations ; Anus, Imperforate ; epidemiology ; surgery ; Female ; Humans ; Incidence ; Infant ; Lumbar Vertebrae ; Magnetic Resonance Imaging ; Male ; Neural Tube Defects ; diagnosis ; diagnostic imaging ; epidemiology ; surgery ; Neurosurgical Procedures ; adverse effects ; Retrospective Studies ; Sensitivity and Specificity ; Singapore ; epidemiology ; Treatment Outcome ; Ultrasonography

OBJECTIVETo develop a new technique for assessing the risk of birth defects, which are a major cause of infant mortality and disability in many parts of the world.

METHODSThe region of interest in this study was Heshun County, the county in China with the highest rate of neural tube defects (NTDs). A hybrid particle swarm optimization/ant colony optimization (PSO/ACO) algorithm was used to quantify the probability of NTDs occurring at villages with no births. The hybrid PSO/ACO algorithm is a form of artificial intelligence adapted for hierarchical classification. It is a powerful technique for modeling complex problems involving impacts of causes.

RESULTSThe algorithm was easy to apply, with the accuracy of the results being 69.5%±7.02% at the 95% confidence level.

CONCLUSIONThe proposed method is simple to apply, has acceptable fault tolerance, and greatly enhances the accuracy of calculations.

Algorithms ; Artificial Intelligence ; China ; epidemiology ; Environmental Exposure ; adverse effects ; Humans ; Infant, Newborn ; Models, Biological ; Neural Tube Defects ; epidemiology ; Risk Factors

OBJECTIVEOur objective is to build a model that explains the association between the exposure to trace elements in the soil and the risk of neural tube defects.

METHODSWe built a function with different parameters to describe the effects of trace elements on neural tube defects. The association between neural tube defects and trace element levels was transformed into an optimization problem using the maximum likelihood method.

RESULTSTin, lead, nickel, iron, copper, and aluminum had typical layered effects (dosage effects) on the prevalence of neural tube defects. Arsenic, selenium, zinc, strontium, and vanadium had no effect, and molybdenum had one threshold value that affected the prevalence of birth defects.

CONCLUSIONAs an exploratory research work, our model can be used to determine the direction of the effect of the trace element content of cultivated soil on the risk of neural tube defects, which shows the clues by the dosage effect of their toxicological characteristics. Based on our findings, future biogeochemical research should focus on the direct effects of trace elements on human health.

China ; epidemiology ; Dose-Response Relationship, Drug ; Environmental Exposure ; Female ; Humans ; Metals ; chemistry ; toxicity ; Models, Biological ; Neural Tube Defects ; chemically induced ; epidemiology ; Pregnancy ; Prevalence ; Soil Pollutants ; chemistry ; toxicity ; Trace Elements ; chemistry ; toxicity

BACKGROUNDNeural tube defects are the most common human birth defects. The causes are multifactorial with complex genetic and environmental factors, although the exact genetic causes are unknown. This research was conducted to study the frequency of Msx2 gene polymorphisms in 59 women with a history of pregnancy with a neural tube defect and in 73 healthy controls. We aimed to determine the effect of this genetic polymorphism on the incidence of neural tube defects in the Han Chinese population.

METHODSWe studied 59 mothers with at least one previous child with a neural tube defect (the case group) and 73 case-control subjects during the same period, from Shanxi Province, China. We analyzed the genotypic distributions and allele frequencies of Msx2 C386T polymorphisms in DNA samples from the case and control groups. A three-dimensional protein model was predicted using Swiss-Pdb Viewer software version 4.0. Disease association was analyzed using chi-square tests.

RESULTSSignificant differences were observed in the genotypes and allele frequencies of the Msx2 C386T allele between the case and control groups (CT: 32% vs. 15%, P = 0.0073 and TT 15% vs. 4%, P = 0.013, respectively). Logistic regression analysis showed that the C386T mutation is a potential risk factor for neural tube defects (P < 0.05; OR: 3.466; 95%CI: 1.831 - 6.560). Three-dimensional structure prediction revealed that the Msx2 C386T mutation results in a threonine substitution for methionine at position 129 of exon 2, which might lead to structural mutations or dysfunctions in the protein encoded by Msx2.

CONCLUSIONMaternal Msx2 C386T gene polymorphisms were associated with fetal neural tube defects in Han Chinese women in Shanxi Province.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Homeodomain Proteins ; chemistry ; genetics ; metabolism ; Humans ; Neural Tube Defects ; epidemiology ; genetics ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; genetics ; Pregnancy ; Protein Structure, Secondary ; Young Adult

OBJECTIVETo predict neural tube birth defect (NTD) using support vector machine (SVM).

METHODThe dataset in the pilot area was divided into non overlaid training set and testing set. SVM was trained using the training set and the trained SVM was then used to predict the classification of NTD.

RESULTNTD rate was predicted at village level in the pilot area. The accuracy of the prediction was 71.50% for the training dataset and 68.57% for the test dataset respectively.

CONCLUSIONResults from this study have shown that SVM is applicable to the prediction of NTD.

China ; epidemiology ; Humans ; Neural Tube Defects ; epidemiology ; Pilot Projects