Fetal Neural Tube Defects Research Articles

Health literacy and patient understanding of screening tests for aneuploidy and neural tube defects

To determine if health literacy is associated with patient understanding of prenatal screening tests for fetal aneuploidy and neural tube defects. We performed a prospective observational study on a cohort of English-speaking patients receiving prenatal care in two resident-staffed ambulatory clinics. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine-7. Understanding of the prenatal screening tests was assessed using a modified Maternal Serum Screening Knowledge Questionnaire. Over an 8-month period, 125 patients were approached, and 101 (81%) consented to the study. Thirty-eight (38%) women demonstrated low health literacy. Patients with low health literacy were more likely to demonstrate inadequate understanding when compared to those with adequate health literacy (97% versus 11%, respectively; P < 0.01). Similarly, patients with < 12th grade education were more likely to have inadequate understanding when compared to patients with > 12th grade education (53% versus 30%, respectively; P = 0.02). Health literacy is a more sensitive and specific predictor of inadequate understanding than education (sensitivity 84% versus 70%, respectively, P < 0.05; specificity 98% versus 47%, respectively, P < 0.05). Patients with low health literacy are more likely to demonstrate inadequate understanding of these prenatal screening tests than women with adequate health literacy.

Prenatal screening and diagnosis—An introduction

Prenatal screening and diagnosis—An introduction

Routine assessment of amniotic fluid alpha‐Fetoprotein in early second‐trimester amniocentesis is no longer justified

Open fetal neural tube defects are often followed by an increase in alpha-Fetoprotein concentration in amniotic fluid. For over 25 years there has been a routine to measure amniotic fluid alpha-Fetoprotein in conjunction with early genetic amniocentesis. The efficacy of such a screening test in a low-risk population has been questioned but never evaluated in a Swedish population. Data were reviewed retrospectively from all consecutive early second-trimester genetic amniocenteses from two hospitals during the years 1993-2003. Indications for the genetic amniocenteses were maternal age > or = 35 years, maternal anxiety or a history of fetal aneuploidy. A questionnaire was sent to all obstetric clinics in Sweden regarding current common policy and experience of routine amniotic fluid alpha-Fetoprotein measurements, in the detection of open fetal neural tube defects. A total of 1,813 samples were included. In eight cases (0.4%) the amniotic fluid alpha-Fetoprotein concentrations were > or = 3 multiples of median, but five of them were false positive (63%). Out of the three true positive cases, one had clinical relevance. In the other two cases the detection of open fetal neural tube defects was of subordinate importance. In Sweden, during 2004, 91% of the obstetric clinics performed routine assessment of amniotic fluid alpha-Fetoprotein at second-trimester genetic amniocentesis, but only 9% regarded the analysis useful in clinical practice. According to our results, routine measurement of amniotic fluid alpha-Fetoprotein in early second-trimester genetic amniocentesis, to rule out a risk of open fetal neural tube defects, does not seem justified. The clinical usefulness seems to be limited.

Expression of p53/hgf/c-met/STAT3 signal in fetuses with neural tube defects

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

Fetal anomaly scan potentially will replace routine AFAFP assays for the detection of neural tube defects

Introduction of the second-trimester fetal anomaly scan and the decision to offer this scan to every woman in the 18th-22nd week of pregnancy necessitates a re-evaluation of the diagnostic value of the measurement of alpha-fetoprotein (AFP) concentrations in the amniotic fluid (AF) for the detection of neural tube defects (NTDs). In this study of 6501 women who underwent amniocentesis, amniotic fluid AFP (AFAFP) concentrations were measured. The women were divided into three categories: group I, without any increased risk of fetal NTD (N = 6188); group II, with an increased risk of fetal NTD (N = 258); and group III, with a clinically diagnosed fetal NTD with known AFAFP concentrations (N = 55). In 27 women of group I (0.4%), the MoM (multiple of the median) level was > 2.5 times the median AFP concentration for the corresponding gestational age, and in two fetuses this was related to NTD. In two pregnancies of group II (0.8%), an increased AFAFP was related to NTD. In group III, 44 of the 55 (80%) samples had an increased AFAFP. In the near future, it is likely that imaging will replace AFAFP assays for the detection of fetal NTDs because high quality ultrasound imaging will detect NTDs accurately.

P-912: Elevated Homocysteine levels in women with recurrent pregnancy loss (RPL) are associated with A1298C mutations of methylenetetrahydrofolate reductase (MTHFR) in the absence of C677T mutations

Hyperhomocystenemia has emerged as a risk factor for arterial and venous thrombosis. Folic acid is an important factor in the metabolism of homocysteine. MTHFR is one of three enzymes that are responsible for the circulating form of folic acid. Recently, pregnancy complications such as RPL and fetal neural tube defects have been reported in association with hyperhomocysteinemia. Two frequent polymorphisms have been identified in the gene for MTHFR. The first, C677T, occurs in 10 to 15% of the white population and has been associated with hyperhomocysteinemia. The second, A1298C, is also found frequently but, to date, has not been associated with hyperhomocysteinemia. The purpose of this study was to identify the frequency of elevated homocysteine in a populataion of women with a history of RPL, and to determine the association with the mutations C677T and A1298C. Folate deficiency is also a common cause of hyperhomocysteinemia. Single-center, prospective study. Women with RPL were included in this study if they had at least two consecutive pregnancy losses by the same partner. All women had a complete evaluation including karyotypes, assessment of the uterine cavity, hormonal tests for TSH, prolactin, midluteal progesterone, fasting insulin and glucose, autoimmune tests for lupus anticoagulant and anticardiolipin antibodies, a thrombophilia panel, and cervical cultures. Homocysteine levels were determined by immunoassay on a fasting sample. Levels were considered abnormal if values were greater than 10.4 umol/L. All patients with elevated levels of homocysteine had blood drawn for DNA analysis of the MTHFR gene by PCR amplification followed by restriction analysis.The diaganostic sensitivity is > 99%. Thirty-six of two humdred and seven (17.4%) of women with RPL were found to have and elevated homocysteine. The following MTHFR polymorphisms were identified: MTHFR A1298C heterozygous 9/36 25.0%, MTHFR A1298C homozygous 3/36 8.3%, MTHFR C677T heterozygous 7/36 19.4%, MTHFR C677T/A1298C 8/36 22.2%, MTHFR wild type, normal 9/36 25.0% Elevated homocysteine is found frequently in women with RPL. This is probably an underestimate because virtually all of these women were taking prenatal vitamins with folate, vitamin B6, and vitamin B12 at the time of the assay. Approximately one-third of the women had hyperhomocysteinemia associated with the A1298C polymorphism in contrast to what is routinely reported in the literature. Another one-third of patients had polymorphisms at C677T or combinations of C677T and A1298C while one-third of women had no mutations identified. Fasting homocysteine is easy to test for and is easily treated with supplemental B vitamins (folate, B6, B12). When elevations of homocysteine are found associated with MTHFR mutations, women should be advised that they have an increased lifetime risk of thrombosis, that her parents and siblings should be screened, and that she should stay on lifelong B vitamin supplementation.

P03.05: 10‐year (1995–2004) outcome of fetal neural tube defects

P03.05: 10‐year (1995–2004) outcome of fetal neural tube defects

Teratology study of derivatives of tetramethylcyclopropyl amide analogues of valproic acid in mice

Although valproic acid (VPA) is used extensively for treating various kinds of epilepsies, it is well known that it causes neural tube and skeletal defects in both humans and animals. The amide and urea derivatives of the tetramethylcylcopropyl VPA analogue, N-methoxy-2,2,3,3-tetramethylcyclopropanecarboxamide (N-methoxy-TMCD) and 2,2,3,3-tetramethylcyclopropanecarbonylurea (TMC-urea), were synthesized and shown to have a more potent anticonvulsant activity than VPA. The objective of this study was to investigate the teratogenic effects of these compounds in NMRI mice. Pregnant NMRI mice were given a single subcutaneous injection of either VPA, N-methoxy-TMCD, or TMC-urea at 1.8 and 3.6 mmol/kg on gestation day (GD) 8. Cesarean section was performed on GD 18. First, the live fetuses were examined to detect any external malformations, then their skeletons were double-stained for bone and cartilage and subsequently examined. Significant increases in fetal losses and neural tube defects were observed with administration of VPA at 3.6 mmol/kg when compared to the vehicle control. In contrast, upon cesarean section, there were no significant differences between either N-methoxy-TMCD or TMC-urea and the control groups for any parameter. Skeletal examination revealed that a number of the abnormalities were induced by VPA dose-dependently at high rates of incidence. These abnormalities were mainly at the axial skeletal level. However, lower frequencies of skeletal abnormality were observed with N-methoxy-TMCD and TMC-urea than with VPA. In addition to their more potent antiepileptic activity, these findings clearly indicate that N-methoxy-TMCD and TMC-urea are distinctly less teratogenic than VPA in NMRI mice.

Effect of maternal exposure to homocystine on sodium valproate-induced neural tube defects in the mouse embryos

Neural tube defects (NTD) are mainly of multifactorial origin. Maternal treatment with valproic acid (VPA) during pregnancy induces NTD in susceptible fetuses. Elevated levels of homocysteine are observed in pregnancies with NTD. The mechanism by which homocysteine might cause NTD is unknown. The aim of this study was to determine if homocystine would augment VPA-induced exencephaly in an experimental model. Groups of mice were injected (IP) on gestational day 8 (GD) with a single dose of 75 mg/kg of L: -Homocystine (HC) or a proportionate volume of saline, followed by a single dose of 600 mg/kg of VPA or an equal volume of saline. In a second experiment, mice were treated with a daily dose of 75 mg/kg of HC or an equal volume of saline (IP) from GD 5 and continued through GD 10. These animals had a single exposure to 600 mg/kg of VPA or saline (IP) on GD 8. All animals were killed by cervical dislocation on GD 18. Plasma homocysteine, folate and vitamin B12 were determined on GD 8 and GD 10 from single and multiple dose groups of mice, respectively, from additional experiments. The VPA and HC+VPA induced significantly higher rates of embryonic resorption and intrauterine growth retardation (IUGR) than HC or saline alone. HC + VPA groups had significantly more numerous fetuses with severe IUGR than HC alone or VPA alone groups. Both single and multiple doses of HC augmented VPA-induced reduction in fetal body weight. Successive doses of HC did not augment the rate of IUGR more significantly than a single dose of HC. Incidence of exencephaly was significantly enhanced in the HC + VPA groups compared to that in the HC or VPA alone groups. HC alone was not teratogenic. Plasma homocysteine levels increased several fold both in HC and HC + VPA groups and the increase was not particularly more marked in multiple dose groups than in the single dose groups. VPA did not elevate homocysteine concentration. Both FA and vitamin B12 concentrations were reduced by VPA, HC and HC + VPA, but HC and VPA when combined did not produce an additive effect on vitamin levels. These data indicate that HC and VPA interact in neurulation stage embryos, affect fundamental processes of closure of the neural tube and lead to enhanced incidence of NTD.

Antiepileptic Drugs: A Case Report in a Pregnancy With a Neural Tube Defect

While receiving lamotrigine, a patient pregnant with triplets suffered a double fetal neural tube defect. Plasma homocysteine, folate, vitamins B12 and B6 (pyridoxal phosphate), and red cell folate levels were measured in samples while she was receiving folic acid therapy for 1 month during the second trimester of pregnancy. Some mutations were sought, involved in homocysteine metabolism and linked with the folate metabolism. Her results were compared with those of a pregnant woman with normal triplets and with those of 58 pregnant women, with a normal pregnancy. Results indicated a decrease in vitamin B12 and B6 values in plasma in the patient, and a genotype AG (polymorphism A66G) was observed, but was not found in the pregnant woman with normal triplets. Even if lamotrigine therapy is not known to be associated with significant changes in red cells or in serum folate, periconceptional folic acid supplementation is counseled for women, along with periconceptional B12 and B6 vitamin supplementation when their plasma values are decreased.

The effects of analytical factors on second trimester risk estimations

Objective: Triple test with measured maternal serum α-fetoprotein, human chorionic gonadotropin, and unconjugated estriol combination as a routine procedure for fetal Down's syndrome, trisomy 18 and neural tube defect screening has some intrinsic problems, such as precision. The aim of this study was to evaluate the effect of analytical variation of triple test on prenatal risk estimation. Method: Five different serum pools were prepared and triple test was performed seven times for within run and five times for between run precision determination. Result: Within run and between run, precision values of risk estimations by measuring the same sample for Triple test were calculated to be 7.9–21.4% and 14.1–31.0% for trisomy 21, 13.2–23.7% and 14.2–15.1% for trisomy 18, 47.2 and 42.0 % for neural tube defect, respectively. Conclusion: These results demonstrated that analytical variations have great impact on second trimester risk estimation procedures; therefore, triple test analyses should be carried out in laboratories using strict internal and external quality control programs. Moreover, triple test results should always be interpreted by considering analytical and biological variations.

OV-A-1Methylenetetrahydrofolate reductase (MTHFR) molecular pharmacogenetics: Isoform characterization and human liver expression

BACKGROUND MTHFR genetic variation is a risk factor for cardiovascular disease and fetal neural tube defects. In fetal liver, MTHFR exists as 70 and 77 kDa isoforms. Gene resequencing studies revealed a nonsynonymous cSNP in the 77 kDa isoform, an isoform which has never been successfully expressed or characterized. We expressed the 77kDa isoform with the E2 and V222 polymorphisms and performed functional genomic studies. We also studied patterns of isoform expression during fetal growth and development. METHODS The two isoforms and the variant allozymes were expressed using bacterial and mammalian systems and their biochemical properties were studied. Expression of both isoforms in 73 human fetal livers was measured using Western blots. RESULTS Recombinant wild-type (WT) 77 kDa isoform and the D2E allozyme showed no significant differences in activity or substrate kinetics as compared to the recombinant 70 kDa isoform. However, the V222 77 kDa allozyme had 26% of WT activity. 77 kDa isoform expression decreased during fetal development, while this trend was less evident for the 70 kDa isoform. Both isoforms showed large individual variation in expression at comparable gestational age. CONCLUSIONS These studies represent the first successful expression and characterization of the 77 kDa MTHFR isoform and variant allozymes and provide insight into MTHFR pharmacogenetics as well as variation in expression during fetal growth and development. Clinical Pharmacology & Therapeutics (2005) 79, P34–P34; doi: 10.1016/j.clpt.2005.12.122

Contamination accidentelle du liquide amniotique par du milieu de culture cellulaire. Conséquences biochimiques et mise en évidence

Prenatal diagnosis of neural tube defect is based on ultrasound findings and maternal serum AFP. Because of the good performance of ultrasound scan, amniotic fluid cholinesterase electrophoresis is performed in the most difficult cases. However, fortuitous contamination of amniotic fluid by culture medium used for amniotic fluid karyotyping will lead to false positive results. We studied two culture mediums, Amniomax ® and Amniochrome Plus ®. A 1/100 dilution is enough to induce a false positive result. To prove such a contamination is difficult. Insulin assay, with a low value in the amniotic fluid (1 UI/l) and a high value in culture medium (60000 UI/l), will allow proving such a contamination. Therefore, an unexpected positive aspect at amniotic fluid cholinesterase electrophoresis in cases with no patent sign of fetal neural tube defect at ultrasound scan must lead to insulin assay in order to avoid a prenatal diagnosis error.

Second trimester maternal serum screening for fetal open neural tube defects and aneuploidy

Maternal serum screening has been modified during the past 25 years and is now widely utilized during the second trimester to identify women at risk for fetal open neural tube defects (ONTDs), anencephaly, and trisomies 21 and 18. This statement replaces the 1994 and 1996 ACMG position statements on serum screening and discusses clinical guidelines for screening that complement the sections of ACMG’s Standards and Guidelines for Clinical Genetics Laboratories entitled “Prenatal screening for open neural tube defects” and “Prenatal screening for Down syndrome” (http://www.acmg.net).

P14.70: Routine assessment of amniotic fluid alpha‐fetoprotein in second trimester genetic amniocentesis to detect fetal neural tube defects

The main aim of the study was to evaluate the clinical usefulness of routine assessment of amniotic fluid alpha-fetoprotein (AF-AFP) in second trimester genetic amniocentesis, to detect fetal neural tube defects (NTD). A secondary aim was to survey the routine for analyses of AF-AFP in obstetric clinics in Sweden today. This is a retrospective study. The studied population included all 1919 pregnant women, from the county hospitals of Norrköping and Jönköping, who underwent second trimester genetic amniocentesis, during the years 1993–2003. Indications for the genetic amniocentesis were elevated maternal age (> 35 years old) or increased anxiety for chromosomal defects of the expected baby. A questionnaire concerning policy and experience of AF-AFP analyses was sent to all obstetric clinics in Sweden who performed genetic amniocentesis in 2003. Of the 1811 analysis of AF-AFP, eight cases had increased values (0.4%) and five of them were false positive (63%). Of the three true positive cases, one had clinical relevance. In the other two cases the detection of NTD was of subordinate importance; one fetus had trisomy 18 and the other pregnancy was a missed abortion at the ultrasound check-up. In Sweden 91% (39/43) of the obstetric clinics perform routine assessment of AF-AFP at second trimester genetic amniocentesis, but according to the answers in the questionnaire only 8% of the clinics regarded the analyses useful in clinical practice. During 2003 about 8000 genetic amniocentesis were made in Sweden. We concluded that routine assessment of AF-AFP in second trimester genetic amniocentesis does not appear to be justified. The clinical usefulness seems to be limited, and the result of AF-AFP more often creates parental anxiety.

Sonographic Signs of Fetal Neural Tube and Central Nervous System Defects

Sonography may provide prenatal diagnosis of neural tube defects and has become a routine part of prenatal care. Neural tube defects include malformations of the brain and spine. Among congenital anomalies, neural tube defects are second in incidence following cardiac defects. Laboratory tests combined with sonography are often able to diagnose the failure of the neural tube to fuse. Specific sonographic signs provide direct or indirect evidence of a neural tube defect.

Vitamin B12 insufficiency and the risk of fetal neural tube defects.

Although maternal folate insufficiency is a risk factor for fetal neural tube defects (NTDs), there is controversy about whether vitamin B12 (B12) insufficiency is also associated with an increased risk of NTDs. To investigate whether low maternal B12 is associated with an increased risk of fetal NTDs. Systematic review. A systematic search of Medline between 1980 and October 2002, with an examination of the citations of all retrieved studies. Studies were included that: (i) used a cohort or case-control design; (ii) included case mothers with a prior or current NTD-affected pregnancy; (iii) assessed a group of unaffected 'controls'; and (iv) measured the vitamin B12 status of all participants. Overall, 17 case-control studies were included, mean sample size 33 cases and 93 controls. In 5/6, mean amniotic fluid B12 concentration was significantly lower in case mothers than in controls. Of 11 that measured maternal serum or plasma B12, three observed a significantly lower mean concentration in case mothers vs. controls, while five others found a non-significant lower trend in the case group. One study observed a significantly higher mean concentration of maternal serum methylmalonic acid among the maternal cases, while another found a non-significant lower mean concentration of plasma holo-transcobalamin. Five studies estimated the risk of NTDs in relation to low B12 or B12-related metabolic markers: it was significantly increased in three studies, with a non-significant trend in the fourth. There seems to be a moderate association between low maternal B12 status and the risk of fetal NTDs. However, several design limitations, and the inclusion of few study participants, may have under-represented this. A large observational study, using reliable and valid indicators of B12 status in early pregnancy, could best assess the association between B12 insufficiency and the risk of fetal NTDs.

Diagnosis of fetal acrania during the first trimester nuchal translucency screening for Down syndrome

Objectives: Prenatal screening during the first-trimester using fetal nuchal translucency (NT) measurement and maternal serum levels of free β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) has become an established method for the detection of fetal Down syndrome. Increasing evidence has shown that some of the fetal structural abnormalities could be identified during NT scanning. Second trimester maternal serum alpha-fetoprotein (MSAFP) measurements and ultrasound scans have been widely used in clinical practice to identify fetal neural tube defects (NTDs). In this study, we evaluated the effectiveness of early diagnosis of fetal acrania during NT scanning. Methods: We reviewed the medical records of 5890 pregnancies that were delivered in our hospital between January 1, 1999 and January 31, 2001. Among them, 3600 pregnant women received NT-based Down syndrome screening at 10–13 weeks’ gestation. Pregnancies with fetal NTDs were evaluated and their maternal serum levels of free β-hCG and PAPP-A were compared with those of the normal control pregnancies. Results: Seven of the 3600 pregnancies were identified with fetal acrania and all of them were detected during first-trimester NT scanning. Among the seven cases, five had measurements of maternal serum concentration free β-hCG and PAPP-A concentration, yet there were not significant difference between the pregnancies with fetal acrania and those of the control pregnancies (PAPP-A, 1.13 vs. 0.96; free β-hCG, 1.10 vs. 1.06; P>0.05). Two of the seven affected patients did not have maternal serum biochemical measurements due to the immediate termination of pregnancies. Conclusions: We demonstrated that pregnancies with fetal acrania could be easily identified at the time of NT scanning. Careful ultrasound inspection of fetal structure during NT measurements at 10–13 weeks of gestation provides an encouraging advantage for early diagnosis of fetal acrania.

Hyperhomocyst(e)inemia and Hemostatic Factors: The Atherosclerosis Risk in Communities Study

PURPOSE: To determine whether homocyst(e)ine (H(e)) is related to hemostatic factors in a population-based sample without evidence of cardiovascular disease. METHODS: A subsample of 660 participants—67 African-American women, 53 African-American men, 201 white women, and 339 white men—was selected from the Atherosclerosis Risk in Communities Study baseline cohort. This was based on carotid intimal-medial wall thickness above the 90th percentile or below the 75th percentile of the population distribution, assessed by B-mode ultrasonography. Unadjusted and multivariable-adjusted associations between fasting plasma H(e) and the hemostatic factors fibrinogen, factor VII:c, factor VIII:c, protein C antigen, hematocrit, platelet count, β-thromboglobulin (β-TG), tissue plasminogen activator (tPA), PAI-1, D-dimer, and lipoprotein[a] were examined. RESULTS: Mean age-adjusted H(e) was positively, albeit weakly, correlated with β-TG, tPA, hematocrit, D-dimer and PAI-1; inversely correlated with protein C; and was higher in smokers, men and African-Americans. In multivariable regression, β-TG, tPA, and factor VII:c were positively associated with H(e), as well as age, black race, male sex, and current cigarette smoking. CONCLUSIONS: These cross-sectional data for a biracial group of middle-aged individuals suggest that H(e) levels falling below values consistent with homocyst(e)inemia are associated with several prothrombotic factors after adjustment for sociodemographic factors. If H(e) change is antecedent to altered hemostasis, FDA-mandated fortification of grain products with folic acid for prevention of fetal neural tube defects may lead to both reduced plasma H(e) levels and improved hemostatic profiles.

Chronology of neurological manifestations of prenatally diagnosed open neural tube defects

Objective: To evaluate the incidence and chronology of sonographic markers of neurological compromise in prenatally diagnosed neural tube defects.Methods: We reviewed our ultrasounddatabase from 1988 to 1999 to identify all cases of prenatally diagnosed neural tube defects. All patients received an initial detailed targeted ultrasound evaluation with subsequent evaluations every 4-6weeks. Cases involving multiple congenital anomalies, aneuploidy, or inadequate follow-up were excluded. Specific ultrasound markers assessed included the presence of ventriculomegaly (> 10 mm) and clubfoot.Results: Forty-seven cases of neural tube defects were identified over the study interval. After exclusions, 42 cases were available for evaluation. The overall incidence of ventriculomegalyand clubfoot in the study cohort was 86% and 38%, respectively. In the 33 patients with initial ultrasound examination performed at < 24 weeks' gestation, 76% (25/33) had evidence of ventriculomegalyand 30% (10/33) and clubfoot. Only 9% (1/11) of the patients managed expectantly developed evidence of ventriculomegaly and 3/11 (27%) developed clubfoot from the time of the initial ultrasound examinationto delivery.Conclusions: Ultrasound markers of neurological compromise are early and frequent findings associated with fetal neural tube defects. Development of ventriculomegaly is an uncommonoccurrence later in gestation, while the risk for developing clubfoot appears to increase as gestation progresses.