Family History Of Neural Tube Defects Research Articles

Incidence and Risk Factors of Neural Tube Defects in Kashan, Central Iran.

Neural tube defects (NTDs) are the most common congenital defects of central nervous system due to neural tube closure deficit during the third and fourth weeks of gestational age. Our study was performed to detect the incidence and risk factors of NTDs in Kashan, center of Iran. This case-control study was done on all pregnancies with NTD affected neonates (n=91) and 209 pregnancies with normal neonates from February 2007 to December 2012 in three hospitals in Kashan, center of Iran. Annual and the mean incidence of NTDs were calculated. Risk factors including neonatal gender, maternal age, gravidity, maternal abortion history, maternal gestational diabetes (GDM), folic acid use, familial marriage, maternal body mass index (BMI), birth season and family history of NTDs were evaluated by interview with mothers. Univariate and multivariate logistic regression were used to analyze the risk factors. The mean incidence of NTDs was 2.33 per 1000 births. The multivariate analysis indicated that maternal history of abortion (OR: 4.9, CI: 1.9-12.8), and maternal obesity (OR: 5.4, CI: 1.3-21.8) were significantly associated with NTDs. Maternal history of abortion and BMI were the major risk factors of NTDs.

A Case of Dichorionic Twin Pregnancy Concordant for Bilateral Cleft Lip and Palate and Discordant for Spina Bifida; Schisis Association

Backround: The schisis theory suggests that neural tube defect (NTD), cleft lip and palate (CL/P), omphalocele and diaphragmatic hernia are associated to each other more frequently than at the expected random combination rates in a given fetus. However, it is unusual to see schisis-associated defects concordantly in dichorionic twin pregnancy with other schisis-associated and non-associated defects. In addition, the association of lower limb oligodactly with oral cleft and spina bifida has not been reported before. Case: A 24-year-old woman with twin gestation at 21 weeks was referred to our unit. At ultrasound examination, bilateral CL/P and single umbilical artery in male fetus, and bilateral CL/P and open lumbar spina bifida in female fetus were revealed. At autopsy, oligodactyly of both lower limbs was demonstrated in the female fetus. The parents had no family history of NTD and CL/P. There was no consanguinity, nor was the mother exposed to teratogens.

Proportion of neural tube defects attributable to known risk factors

Recognized risk factors for neural tube defects (NTDs) poorly predict population-level NTD risk. However, the proportion of NTDs that can be attributed to these risk factors is uncertain. To determine the proportion of NTD cases that is attributable to known or suspected risk factors (i.e., female infant sex, family history of NTDs, and maternal Hispanic ethnicity, obesity, pregestational diabetes, gestational diabetes, low dietary folate intake, lack of folic acid supplementation, anticonvulsant use, and hot tub or sauna use), we estimated the adjusted population attributable fraction (aAF) for each factor, using the method of Eide and Geffler and data from the National Birth Defects Prevention Study. Our analyses of these data indicate that the proportion of cases of spina bifida and anencephaly that can be attributed to known risk factors is 28% and 44%, respectively. For spina bifida, the factor with the greatest attributable fraction was maternal obesity (aAF, 10%), whereas for anencephaly it was Hispanic ethnicity (aAF, 15%). Our analyses indicate that known risk factors account for <50% of NTD cases. Hence, the majority of NTD cases are attributable to, as yet, unidentified factors. These findings highlight the need for continued research to identify genetic and additional nongenetic risk factors for NTDs. Further, these findings suggest that strategies that aim to reduce the risk of NTDs associated with maternal Hispanic ethnicity and obesity may have the greatest impact on the population prevalence of these conditions.

Periconceptional Folic Acid Supplementation: A New Indication for Therapeutic Drug Monitoring

The role of periconceptional folic acid supplementation in the prevention of neural tube defects (NTDs) has been well established. Maternal red blood cell (RBC) folate concentration is inversely associated with NTD risk, and concentrations above 906 nmol/L are associated with a low risk of NTDs. Current guidelines call for a minimum of 0.4 mg of folic acid per day for all women who could become pregnant and higher levels of supplementation for women with a family history of NTDs or risk factors associated with NTDs. However, there is variability in supplement adherence and lack of knowledge of conditions that may elevate folate requirements or NTD risk. Therefore, guidance provided to the population as a whole may be inappropriate for individual women. Current data show that a significant proportion of women of childbearing age have RBC folate concentrations below 906 nmol/L, rendering a higher-than-baseline risk for NTDs. Therapeutic drug monitoring (TDM) of RBC folate could be used to identify these women and to help them improve their folate status, thus reducing their risk for having a child with an NTD.This review describes the evolution of the evidence for TDM of RBC folate and preliminary experience with TDM in a population of 12 women who were planning a pregnancy and who were being treated with an atypical antipsychotic.

Technical standards and guidelines: Prenatal screening for open neural tube defects: This new section on “Prenatal Screening for Open Neural Tube Defects,” together with the new section on “Prenatal Screening for Down Syndrome,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories

Technical standards and guidelines: Prenatal screening for open neural tube defects: This new section on “Prenatal Screening for Open Neural Tube Defects,” together with the new section on “Prenatal Screening for Down Syndrome,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories *

Folate Intake and the Risk of Neural Tube Defects: An Estimation of Dose-Response

Folic acid supplements in the form of multivitamins, taken in the periconceptional period, lower the risk of neural tube defects (NTDs), but few studies have demonstrated a clear dose-response relationship. This prospective study analyzed data from 23,228 women, chiefly from the northeastern United States, who enrolled from 1984 through 1987. Diet and vitamin intake were assessed by telephone interviews early in the second trimester of pregnancy. Dietary folate was estimated using a 50-item food frequency questionnaire. Women using the highest-dose supplements in the first 5 weeks of pregnancy tended to be older and college-educated, and to have used multivitamins before becoming pregnant. They also were likelier than others to have a history of diabetes or a family history of NTDs. No dose-response relationship was noted when analyzing folic acid intake from supplements alone. The estimated reduction in NTD risk ranged froth 44% to 71%. Women with the lowest dietary folate intake had the highest risk of having an infant with an NTD (4 cases per 1000). There were indications that a higher intake of folate from foods is protective, but any protective effect was not linear. Women taking the least folate had a prevalence of NTDs of 3.4 cases per 1000. The risk declined as total folate increased, and the risk for those taking the most folate was 0.8 cases per 1000, a 77% reduction in risk. The prevalence of NTDs declined by 0.78 cases for every additional 500 dietary folate equivalents consumed per day. It appears that the NTD risk decreases substantially with a modest increase in total folate, from both food and supplements, in early pregnancy. Total folate intake is the critical parameter when formulating public health guidelines.

Neural Tube Defects and Chromosome Deletions

Patients with neural tube defects (NTDs) complicated by congenital heart defects, facial anomalies, thymic hypoplasia, cleft lip or palate, or hypocalcemia and a family history of NTDs and other anomalies were tested for 22qll deletions at the Departments of Pediatrics and Molecular Genetics, Oregon Health Sciences University, Eugene, Oregon.

Antenatal detection of neural tube defects: Comparison of biochemical and immunofluorescence methods

The aim of this study was to determine whether identification of glial cells in amniotic fluid samples could form a useful supplementary test in the antenatal diagnosis of neural tube defects (NTDs). In a 5-year study, 1452 samples of middle trimester amniotic fluid were examined blind to the results of other antenatal diagnostic tests and to the outcome of pregnancy. Reason of amniocentesis included raised serum alpha-fetoprotein (329), previous NTD (73), and a family history of NTDs (71). Duplicate cytospin preparations were stained with Giemsa and an antibody to glial fibrillary acidic protein (GFAP), and on this basis a prediction of fetal NTD status was made which was not communicated to clinicians. Subsequent management of pregnancies was influenced only by the results of routine antenatal testing for NTDs. Twenty cases of NTDs occurred among the 1406 cases in which the outcome was subsequently known. Of these 20 cases, only five (four anencephalic, one spina bifida) were correctly predicated by immunofluorescent identification of GFAP-positive cells in the amniotic fluid. The remaining 15 cases (two anencephalic, 13 spina bifida) were not so identified. In a further 18 cases, apparently GFAP-positive cells were identified in the absence of NTDs. We conclude that GFAP immunofluorescence examination of routine amniocentesis samples of amniotic fluid is not a useful predictive test for NTDs.

Maternal Heat Exposure and Neural Tube Defects

MILUNSKY, AUBREY; ULCICKAS, MARIANNE; ROTHMAN, KENNETH J.; WILLETT, WALTER; JICK, SUSAN S.; JICK, HERSHEL Author Information

Maternal zinc and fetal neural tube defects.

Among the factors implicated in the heterogeneous etiology of neural tube defects (NTDs) is the trace element zinc (Zn). In a case-control study, we collected midtrimester maternal toenail samples for multiple trace element analyses, including Zn, which were assayed by neutron activation analysis. We studied 17 women with NTD offspring and 1,787 controls. The crude OR for NTD comparing Zn values greater than normal range to normal Zn values was 3.2 (95% CI 1.1,9.7). These results were not materially affected when adjustment was made for folic acid supplementation. An overall increased risk for NTD associated with increasing toenail Zn was also evident. A matched subset of 17 cases and 73 controls yielded a crude OR of 3.1 (95% CI 0.9,10.3) when cases with elevated Zn (greater than or equal to 120 ppm) were compared to those with normal Zn. Matched analyses controlling for folic acid supplements, family history of NTD, assay batch, age of mother and year of delivery yielded an OR of 5.0 (95% CI 1.1,21.6). This study reveals an association between increased toenail Zn in the second trimester of pregnancy and the risk of having a child with an NTD. Whether Zn sequestration has resulted in relative Zn deficiency at the site of neural tube closure remains uncertain.

Maternal Heat Exposure and Neural Tube Defects

To determine if exposure to hot tub, sauna, fever, or electric blanket during early pregnancy was associated with an increased risk for neural tube defects (NTDs). Prospective follow-up study. Mostly private obstetric practices, primarily in New England. A cohort of 23,491 women having serum alpha-fetoprotein screening or an amniocentesis were identified. Complete exposure and outcome information was available for 97% of these women. Relative risks (RRs) were used to compare incidence of NTD in those exposed to heat with those who were not exposed to any heat. Crude RRs were calculated directly from the data. Unconfounded RRs were calculated using logistic regression. Women reporting any heat exposure (sauna, hot tub, fever, or electric blanket) in early pregnancy had a crude risk of their fetuses developing NTD of 1.6 (95% CI [confidence interval], 0.9 to 2.9). Women reporting exposure to sauna, hot tub, or fever in early pregnancy had a crude risk of their fetuses developing NTD 2.2 times that of women without heat exposure (95% CI, 1.2 to 4.1). For hot tub use, the crude RR was 2.9 (95% CI, 1.4 to 6.3); for sauna, 2.6 (95% CI, 0.7 to 10.1); for fever, 1.9 (95% CI, 0.8 to 4.1); and for electric blanket, 1.2 (95% CI, 0.5 to 2.6). Multivariate adjusted RRs for individual heat sources, after controlling for maternal age, folic acid supplements, family history of NTD, and exposure to other heat sources, were for hot tub use, 2.8 (95% CI, 1.2 to 6.5); sauna, 1.8 (95% CI, 0.4 to 7.9); fever, 1.8 (95% CI, 0.8 to 4.1); and electric blanket, 1.2 (95% CI, 0.5 to 2.6). When only hot tub, sauna, and fever were considered and the women's exposure to each tallied, compared with no heat exposure, the RR for NTDs increased from 1.9 (95% CI, 0.9 to 3.7) after one type of heat exposure to 6.2 (95% CI, 2.2 to 17.2) after two types of heat exposure. Exposure to heat in the form of hot tub, sauna, or fever in the first trimester of pregnancy was associated with an increased risk for NTDs. Hot tub exposure appeared to have the strongest effect of any single heat exposure. Exposure to electric blanket was not materially associated with increased risk for NTDs.