Fetal Neural Tube Defects Research Articles

Diagnosis of fetal neural tube defects by MRI

Objective To explore the diagnostic value of MRI on fetal neural tube defects.Methods Ten pregnant women,aged from 25 to 35 years(average 28 years)and with gestation from 20-39 weeks(average 33 weeks)were studied with a 1.5 T superconductive MR unit within 24 to 48 hours after ultrasound(US)studies.The imaging protocol included fast-imaging employing steady-state acquisition,single-shot FSE and T_1-weighted fast inversion recovery motion insensitive sequences in the axial,frontal,and sagittal planes relative to the fetal brain,thorax,abdomen,and spines.Prenatal US and MRI findings were compared with postnatal MRI diagnoses(3 fetuses)or autopsy(7 fetuses).Results Ten pregnant women(9 with a single fetus and 1 with twin fetuses)were examined.For all cases,the diagnoses established by MRI were correct when compared with postnatal diagnosis or autopsy.In 7 cases,US and MRI findings were in complete agreement with postnatal diagnoses.US missed the diagnosis in 1 case and misdiagnosed in 2 cases.Ten neural tube defects in this study included anencephaly(1 case),exencephaly (1 case),meningoencephalocele associated with amniotic band sequence(1 case),meningocele(1 case),thoracic myelomeningocele(1 case),lumbar spinal bifida(1 case),sacroiliac myelomeningocele(2 cases),sacroiliac large cystic spinal meningocele(1 case),sacroiliac spinal bifida(1 case).Conclusions Prenatal MRI is effective in the assessment of fetal neural tube defects.It can exactly discriminate herniated contents and locate the spinal lesion level. Key words: Fetus; Neural tube defects; Magnetic resonance imaging; Ultrasonography

Effects of maternal hyperhomocysteinemia induced by methionine intake on oxidative stress and apoptosis in pup rat brain

Maternal hyperhomocysteinemia is associated with a number of complications such as preeclampsia syndrome, thromboembolic events, repeated miscarriages, abruptio placentae, in utero fetal death, intrauterine fetal growth restriction and fetal neural tube defects. However, little is known about the mechanism of homocysteine on the degeneration of fetal brain. Thus, our study is aimed to investigate the effects of maternal hyperhomocysteinemia on oxidative stress and apoptosis in pup brain. Hyperhomocysteinemia was induced in female rats by way of administrating methionine dissolved in water at a dose of 1g/kg body weight throughout the pregnancy. After delivery, level of lipid peroxidation (LPO; as malondialdehyde+4-hydroxyalkenals) was determined in various fractions of pub brains. Furthermore, DNA fragmentation, levels of Bcl-2 protein and p53 mRNA expression were determined to evaluate apoptosis. Significant elevation was found in the levels of LPO in subcellular fractions of pup brains delivered from hyperhomocysteinemic mothers. DNA fragmentation, a hallmark of apoptosis was observed in the brain of pups of homocysteine group while significant reduction was seen in the levels of anti-apoptotic Bcl-2 levels. In addition, maternal hyperhomocysteinemia increased cerebral p53 mRNA expression above the control value. As a conclusion, we demonstrate and suggest that the pups of hyperhomocysteinemic mothers have an increased oxidative stress in brain tissues. The increased oxidative stress appears to cause apoptosis and cell death. These results may be significant to understand chronic pathology of the complications of hyperhomocysteinemia and congenital malformations of fetuses.

Gender‐dependent differences in the incidence of ochratoxin A‐induced neural tube defects in the Pdn/Pdn mouse

Genetic polydactyly/arhinencephaly mouse embryo, Pdn/Pdn, exhibits suppression of Gli3 gene expression. Ochratoxin A (OTA) is a teratogen that causes neural tube defects (NTD) in mice. We investigated gender-dependent differences in the incidence of NTD induced by OTA in the Pdn/Pdn mouse. After administering 2 mg/kg OTA to Pdn/+ female mice, mated with Pdn/+ males, on day 7.5 of gestation, we examined the genotypes, sex and NTD of fetuses on day 18. Non-treated Pdn/Pdn had a 15.8% risk of NTD, and all NTD fetuses were female. When Pdn/Pdn embryos were exposed to OTA, the incidence of NTD increased to 16 (51.6%) of 31 Pdn/Pdn fetuses, and 10 (71.4%) of 14 male Pdn/Pdn fetuses exhibited NTD. From these results, it was speculated that NTD in OTA-treated male Pdn/Pdn were due to the synergistic effect between depressed Gli3 and altered sex-correlated gene expression from OTA treatment. After treatment with OTA, the embryos were recovered on day 9 and gene expressions, which were correlated with Gli3, telencephalic morphogenesis, formation of gonadal anlage, and gender-dependent differentiation were investigated. From real-time polymerase chain reaction analysis results, it was suggested that the manifestation of NTD in the male OTA-treated Pdn/Pdn might be due to the complicated altered gene expressions among Gli3, Wnt7b, Wnt8b, Fez1, Barx1, Lim1, Dmrt1, Igf1, Fog2, Dax1 and Sox9, and in particular, upregulation and gender-dependent difference in Barx1 and gender-dependent difference in Sox9 gene expressions might be noteworthy findings.

S100-beta protein is increased in fetuses with neural tube defect

We investigated the levels of S100 beta protein (S100B) in the serum of fetuses with neural tube defects (NTD), and their mother. Samples from 20 fetuses with NTD and 30 controls at the same gestational age, and their mothers, were studied. S100B protein levels were determined using Lia-mat Sangtec. kit. S100B concentrations were significantly higher in NTD fetuses (median 2.71 microg/L) than in control subjects (median 0.98 microg/L). Increased S100B levels were also found in mothers carrying fetuses with NTD compared to control and uncomplicated pregnancies. This study indicates that NTD is associated with increased serum concentration of S100B in fetuses and mothers. Moreover, it gives information on S100B levels in the fetal circulation in early-mid gestation.

Polycomb group proteins are essential for spinal cord development

Birth defects are the leading cause of infantile mortality, followed by neural tube defects (NTD) and congenital heart defects. Spina bifida and anencephaly are among the most common forms of NTD. NTD etiologies are complex, and are associated with both genetic and environmental factors. Polycomb group proteins are essential for vertebrate development; therefore, the purpose of this study was to determine the role of PcGs in spinal cord morphogenesis in normal and all-trans-retinoic acid (RA)-treated fetal rat models of spina bifida. Pregnant rats were gavage-fed RA, resulting in fetal NTD, and embryos were obtained on day 15.5, 17.5, and 19.5. Western blot and immunohistochemistry were used to reveal PcGs expression in the normal and RA-treated E15.5-19.5 rat sacral cords. Western blot and immunohistochemistry revealed decreased EED, RNF2, SUZ12, and H3K27me3 expression in the normal, E15.5-19.5, rat sacral cords. In addition, the spinal cord of RA-treated rats during embryonic development exhibited altered PcGs protein expression. Administration of excess RA results in NTD. Our results suggest that the Polycomb proteins may be involved in spinal cord development.

Lack of Association Between Folate-Receptor Autoantibodies and Neural-Tube Defects

In a previous pilot study, autoantibodies against folate receptors were found in 75% of serum samples collected from pregnancies affected by a fetal neural-tube defect, compared to only 10% of samples collected from controls. Although these findings have been difficult to confirm, primarily due to the lack of suitable assays for folate-receptor autoantibodies, improved assays are now available. This case-control study investigated whether the presence of folate-receptor autoantibodies increased the maternal risk of having a pregnancy complicated by a neural-tube defect. The study subjects included pregnant women in an Irish population with a high prevalence of neural tube defects. This report is comprised of 2 studies. In study 1, the presence of autoantibodies against folate-receptors was determined through analysis of stored blood specimens obtained between 1993 and 1994 from 103 case mothers with a pregnancy complicated by a fetal neural-tube defect, 103 matched-control mothers without normal pregnancies, 58 women with no history of pregnancy, and 36 men. Study 2 used fresh blood samples to rule out the possibility that any differences found between cases and controls in study 1 could be due to protein degradation occurring during storage of the frozen specimens. Blood samples in study 2 were collected from 37 case mothers, 22 control mothers, 10 women who had never been pregnant, and 9 men. Assays for both blocking and binding autoantibodies against folate receptors were carried out. In study 1, there was no significant difference between the cases and controls in the frequency of blocking or binding autoantibodies against folate receptors. Blocking antibodies were present in 17% of case and 13% of control women (odds ratio [OR], 1.54; 95% confidence interval [CI], 0.70–3.39) and binding autoantibodies were found in 29% of case and 32% of control women (OR, 0.82; 95% CI, 0.44–1.50). In study 2, similar results were obtained with fresh samples, indicating that there was little or no degradation of the stored samples. These findings do not confirm the results of the pilot study and show no association between the presence of folate-receptor autoantibodies and a history of pregnancy affected by neural-tube defects in an Irish population.

Screening for fetal aneuploidy and neural tube defects

Maternal serum screening for neural tube defects and fetal aneuploidy in the second trimester has been incorporated into obstetrical practice over the past two decades. Now, as a result of several multicenter trials, first trimester screening between 11 and 14 weeks has been shown to be an effective and reliable screening test for Down syndrome and trisomy 18. This policy updates the American College of Medical Genetics policy statement entitled Second Trimester Maternal Serum Screening for Fetal Open Neural Tube Defects and Aneuploidy (2004), incorporates First trimester diagnosis and screening for fetal aneuploidy (2008) and complements the sections of American College of Medical Genetic's Standards and Guidelines for Clinical Genetics Laboratories entitled Prenatal Screening for Down syndrome (2005) and Prenatal Screening for Open Neural Tube Defects (2005).

Dyslipidemia in pregnancy may contribute to increased risk of neural tube defects -a pilot study in north Indian population.

Neural tube defects are congenital structural abnormalities of the brain and vertebral column resulting from improper or non-timely closure of the neural tube. Prevalence of neural tube defects is reported to be higher among women with diabetes mellitus and obesity. This study was designed to investigate the relation between the presence of dyslipidemia in antenatal patients and the risk of fetal neural tube defects. The present study was an observational, cross-sectional study involving 129 pregnant women in 16 to 18 weeks gestation period. Of these, 80 women had normal pregnancies and 49 were clinically high-risk cases for neural tube defects. Fasting blood samples were analyzed for blood sugar and lipid profile by enzymatic assay and alpha-fetoprotein levels using Enzyme Immunoassay. Alpha-fetoprotein (AFP) values were converted to Multiples of Median (MoM) appropriate for the gestational age. Based on AFP values, women were labeled as screen negative (AFP <2 MoM, n= 102) and screen positive (AFP > 2 MoM, n =27). Screen positive women were further evaluated by ultrasound and 21 women were found to carry a neural tube defects positive pregnancy. Statistical analysis was done on SPSS software. Body weight of the women showed a significant positive correlation with serum triglycerides, plasma sugar and AFP MoM values. A significant difference was observed in serum cholesterol levels (p= 0.038), triglycerides (p=0.001) and plasma sugar levels (p=0.002) between normal women and those with neural tube defects positive pregnancy. The Odds ratio for neural tube defects risk in dyslipidemic cases was 24.23 (CI 4.73 - 148.60) with a relative risk of 12.12. Dyslipidemia especially hypertriglyceridemia was found to be significantly associated with fetal neural tube defects.

Fetal Neural Tube Defects: Diagnosis, Management, and Treatment

Fetal Neural Tube Defects: Diagnosis, Management, and Treatment

US obstetrician-gynaecologist's prevention and management of obesity in pregnancy

SummaryA survey regarding management of obesity in pregnancy was mailed to 787 practising members of the American College of Obstetricians and Gynecologists (ACOG); 433 responded of whom 353 practised obstetrics. Most (79.2%) had read ACOG Committee Opinion, ‘Obesity in Pregnancy,’ and rated it helpful (68.6%) or very helpful (17.2%). Most responding physicians (91.2%) use BMI to assess their patients weight status; fewer (63.4%) use pre-pregnancy BMI to modify their pregnancy weight gain recommendation. Having read the Committee Opinion and being a woman were independent factors associated with using pre-pregnancy BMI. Responding physicians that had read the Committee Opinion were more knowledgeable about obesity-related pregnancy complications; but even among those physicians, only 32.2% were aware that maternal obesity is a risk factor for fetal neural tube defects. The responding physicians appeared well-versed on appropriate practice for caesarean delivery for obese patients whether they had read the Committee Opinion or not.

The role of C5a in reproductive impairment in the mouse and human

Adequate dietary folate is essential for a healthy pregnancy. Folate deficiency during pregnancy has been shown to contribute to foetal demise, growth retardation, craniofacial, cardiovascular, and neural tube defects, and numerous other congenital abnormalities. The present study aimed to determine whether the complement factor C5a contributes to folate-deficiency induced reproductive impairment, given that recent investigations have demonstrated that C5a can contribute to pathology in both antibody-dependent and -independent models of pregnancy loss. Administration of a folate-deficient diet (FDD) to wildtype mice resulted in poor fertility, reduced birth weights, and a high incidence of foetal loss. In contrast, C5a receptor knockout (C5aR KO) mice were resistant to foetal loss induced by a FDD, with a comparable incidence of resorption to mice administered a folate replete diet. C5aR-deficient mice on a FDD had significantly reduced birth weights and a very high prevalence of neural tube defects (40%)—a much higher frequency than FDD-fed wildtype mice. This observation suggests that in the presence of C5a, otherwise non-viable embryos from folate-deficient dams are rescued, resulting in an increased frequency of major birth defects. We also studied the expression of complement in human placenta. Placentas from growth restricted babies exhibited significant placental deposition of the upstream complement factor C3 compared to healthy controls. Intriguingly, when foetal growth restriction was associated with preeclampsia, an upregulation of placental C5aRs was additionally observed. These results suggest a complex role for the complement system and for C5a in foetal health and survival.

RETIRED: Obstetrical Complications Associated With Abnormal Maternal Serum Markers Analytes

RETIRED: Obstetrical Complications Associated With Abnormal Maternal Serum Markers Analytes

Importance of accurate diagnosis in counseling for neural tube defects diagnosed prenatally

In cases of fetal neural tube defects (NTD), termination of pregnancy without ascertainment of specific etiology may lead to provision of incorrect recurrence risks and erroneous diagnosis in future pregnancies. Four patients are presented who illustrate the etiologic diversity of neural tube defects. The patients were referred for prenatal diagnosis because of elevated maternal serum alphafetoprotein (AFP). All four chose pregnancy termination. Diagnostic methods included fetal ultrasound, amniocentesis for fetal karyotyping and amniotic fluid AFP/acetylcholinesterase (AChE) and/or fetal karyotyping after delivery, and dysmorphology evaluation of the fetus after intact delivery. These cases highlight the benefits of fetal karyotype analysis and of an intact delivery and thorough clinical examination of the fetus when patients choose to terminate pregnancies with fetal anomalies.

Thrombophilia-associated gene mutations in women with pregnancies complicated by fetal neural tube defects

Neural tube defects (NTDs) are one of the most common fetal defects. The causes of these defects are considered to have multiple factors involving nutritional deficiencies, genetic predisposition, and environmental factors such as drug exposure [1]. The aim of our study was to investigate the frequencies of thrombophilia-associated gene factor V Leiden mutations and prothrombin gene G20210A mutations, as well as methylenetetrahydrofolate reductase MTHFR C677T mutation which has a substantial role in the folate mechanism of women experiencing pregnancies with NTDs. This study consisted of 2 groups: group 1 consisted of 29 women whose previous pregnancies were complicated with NTDs, and group 2 was the control group consisting of 35 women who experienced uncomplicated pregnancies. The ages of patients in the control group matched with those in the NTD group. Case characteristics are displayed in Table 1. The frequency of theMTHFRC677Tmutationwas found to be significantly higher in women who experienced pregnancies withNTDs,while occurrence of factor V Leiden andprothrombin gene G20210A mutations were not significantly different between the study and control groups. The frequency of both homozygous and heterozygous MTHFR C677T mutation was 69.0% inwomenwho experienced pregnancies with NTDs (42.9% in the control group). Thepresence ofMTHFRC677Thad an odds ratio of 2.96 (95.0%CI, 1.05–8.32) for the development of NTDs. The frequencies of factor V Leiden, prothrombin geneG20210A, and MTHFR C677T mutations and allele frequencies with statistical comparisons are shown in Table 1. A study by Akar et al. [2] showed no relationship between MTHFR C677T mutation and spina bifida. However, they suggested that coexpression of MTHFR A1298C and MTHFR C677T mutations increased the risk of spina bifida. A similar association for NTD cases was reported in another study [3]. ⁎ Corresponding author. Department of Obstetrics and Gynecology, Gulhane Military Medical Academy, Etlik, 06010 Ankara, Turkey. Tel.: +90 312 3045818; fax: +90 312 3045800. E-mail address: temelceyhan@yahoo.com (S.T. Ceyhan).

Prenatal screening and diagnosis of fetal abnormal chromosome and nervous tube defect: report of 7698 cases

This study was to explore the value of maternal serum screen in identification of fetal abnormal chromosome and neural tube defect(NTD). By using time-distinguished fluorescence immunoassay, serum levels of free-β-HCG and alpha fetal protein(AFP)were obtained in 7698 pregnant women at 15～20 +6weeks. and 483 were found at a higher risk of fetal abnormal chromosome. Based on amniotic fluid examination or cord blood testing on 344 high. Risk participants. Fetal abnormal chromosome was found in 18 women with a positive rate of 5. 2%. Twenty-five pregnant women were NTD high-risk, and their positive rate was 0. 3%. B-mode ultrasound identified 6 fetal malformations and 2 fetal deaths ( positive rate of 32. 0%). In high-risk or low-risk group, there were 25. 6%and 7. 7%subjects developed adverse outcome, respectively(P＜0. 05). Our findings suggested that maternal serum screen is an effective prediction factor for fetal abnormal chromosome and NTD. Key words: Prenatal diagnosis; Pregnancy outcome

Chromosomal Abnormalities Associated with Neural Tube Defects (I): Full Aneuploidy

Fetuses with neural tube defects (NTDs) carry a risk of chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with other structural abnormalities, and family history of chromosome aberrations. This article provides an overview of chromosomal abnormalities associated with NTDs in embryos, fetuses, and newborn patients, and a comprehensive review of numerical chromosomal abnormalities associated with NTDs, such as trisomy 18, trisomy 13, triploidy, trisomy 9, trisomy 2, trisomy 21, trisomy 7, trisomy 8, trisomy 14, trisomy 15, trisomy 16, trisomy 5 mosaicism, trisomy 11 mosaicism, trisomy 20 mosaicism, monosomy X, and tetraploidy. NTDs may be associated with aneuploidy. Perinatal identification of NTDs should alert one to the possibility of chromosomal abnormalities and prompt a thorough cytogenetic investigation and genetic counseling.

Fewer Neural-Tube Defects in Canada After Folic Acid Fortification

Daily consumption of 400 μg of folic acid before conception reduces the risk for fetal neural-tube defects, but many women do not consume the

Metabolic syndrome and risk of fetal neural tube defects

complicated versus 21.2% uncomplicated pregnancies (Pb0.001). Thirty-seven (10.5%) placentas showed more than 1 abnormality. Pathology was more likely to be documented in the presence of more than 1 obstetric complication. In such situations, the possibility of detecting more than 1 pathologic diagnosis increased (Table 1). Pathological chorioamnionitis was more common in cases of abruptio placentae compared to those with an uncomplicated clinical course (19.0% versus 3.0%, P=0.031), even when chorioamnionitis was not suspected clinically. Pathologies were noted in 62.2% IUFD, 61.9% abruption, 57.5% chorioamnionitis, 54.2% IUGR, 52.4% HT, and 51.7% MS cases. The highest pathology yield was from placentas submitted for abruption with IUFD (6/8, 75%) and chorioamnionitis with high grade fever (11/14, 78.6%). In IUFD, the result was similar in those less than 500 g (11/19, 57.9%) and those more than 500 g (22/34, 64.7%). Placentas were normal in 5/13 (38.5%) cases with the clinical diagnosis of abruptio placentae and chorioamnionitis. Factors for this suboptimal yield should be sought and amended. Residency training programs that stress the importance of placental pathology, recruitment of pathologists experienced in placental pathology with appropriate technical support, utilization of adequate staining techniques and sensitive markers, adherence to guidelines for placental pathologic examination, and adequate communication between obstetricians and pathologists are needed [2]. Such a plan might initially increase costs but improve the long-term outcome and hence compliance with recommendations.

Maternal nutrition in pregnancy: of importance in The Netherlands?

The importance of maternal nutrition during pregnancy is increasingly emphasized and several recommendations are given to pregnant women. This article will review the evidence on which such recommendations are based, with a particular focus on The Netherlands. In well-nourished populations, the evidence is generally insufficient and results are relatively poor. Aside from the benefits of stopping smoking, alcohol and substance abuse, the only evidence-based nutritional recommendation in The Netherlands is the periconceptional use of folic acid for the prevention of fetal neural tube defects. However, only approximately a third of all pregnant Dutch women actually do take folic acid. This implies that other strategies need to be explored in order to reach more of these women. In addition, there is a need for more high-quality research on the benefits of good nutrition during pregnancy in well-nourished populations, both for mother and child. In developing countries, the health benefits of supplementing the...

Assessment of neural tube defects in fetuses: accuracy of imaging and correlation of findings with neuro-urologic outcomes

Purpose In order to provide accurate information to parents whose fetus has a neural tube defect (NTD) we evaluated the accuracy of the assigned lesion level by prenatal ultrasound (US) and magnetic resonance (MRI) with postnatal imaging, neuro-motor assessment and urodynamic studies (UDS). Material and methods The retrospective review involved all pregnant women whose fetus had a NTD who were counselled at our fetal center between August 1999 and January 2006. Prenatal imaging (US/MRI) defined a lesion level in 38 of 55. Findings were compared with available postnatal imaging (N = 9) neuro-motor level (N = 15) and urodynamic findings (N = 17). Results US and MRI were equally accurate in demonstrating the anatomic level in 23 of 24 (95.8%) fetuses prenatally. Twenty of 38 women delivered a live-born infant. Lesion levels from prenatal and postnatal imaging correlated within one vertebral level in 9 of 9. The postnatal neuro-motor level was similar or caudad to the anatomic prenatal imaging level in 12 of 15 (80%) and > 2 vertebral levels (either cephalad or caudad) in only 4 of these 15 (26.6%). Prenatal imaging levels did not correlate with postnatal urodynamic function. Conclusions US and MRI are equally accurate in demonstrating the anatomic NTD level in utero. Postnatal neuro-motor level is often more caudad than the identified anatomic level. The relationship between estimated anatomic level and urodynamic function is not predictable by prenatal imaging. Caution should be exercised in predicting functional outcomes during prenatal counseling based on the prenatal anatomic level of the NTD.