Open neural tube defects

Treated pregnant rats produce offspring with major birth defects including open neural tubes, abnormal flexure rotation and proencephalic defects, among others. In experimental animals, PAHs such as 3-MC and metabolites have been noted to produce... 

Amniotic fluid is analyzed for AFP for detection of open neural tube or abdominal wall defects in tlie fetus. Saliva is tested for secretory IgA in infantile hypogammaglobulinemia and for BMG in Sjogren s syndrome. Assay of feces for AAT is sometimes used in the diagnosis of exudative enteropathy, because AAT is not significantly hydrolyzed in the gut. However, intravenous injection of Cr-labeled albumin, followed by measurement of the radioactive label in feces, is a more reliable test. 

Open neural tube defects, Down syndrome, and trisomy 18 (discussed separately below) are fetal anomalies that are partially detectable by maternal serum screening. However, because of the large number of pregnancies screened, and the interest in other fetal conditions and their possible association with abnormal maternal serum analyte concentrations, a wealth of associations between rarer conditions and screening results has been pubhshed. These findings are never diagnostic and are reported rarely by the screening laboratory. In certain circumstances, however, the healthcare provider may determine a need for more extensive medical evaluation. 

The birth prevalence of open neural tube defects varies with factors such as geographic location (higher in the Eastern United States, lower in the West), race (lower in African-Americans), ethnicity (higher in Scotch-Irish), family history (higher with prior births of affected individuals), and maternal weight (higher in obese women)... 

An average figure for the United States is 1 open neural tube defect per 1000 pregnancies (about 1 in 2000 for each indi-... 

Women who have a positive screening test result for open neural tube defects are usually referred for genetic counsel-... 

Compared with maternal serum, amniotic fluid AFP concentrations in pregnancies affected with open neural tube defects are far more separated from unaffected pregnan-cies. However, amniotic fluid AFP measurements are not by themselves diagnostic because of false-positive results. If the amniotic fluid is contaminated with even a small amount of fetal blood, as many as 2% to 3% of the results can be falsely positive. All abnormal amniotic fluid AFP results must be confirmed by measurement of amniotic fluid AChE. The combination of amniotic fluid AFP and AChE is virtually diagnostic for an open neural tube defect. 

There is no compelling evidence that the rate of Down syndrome births in women with IDD is substantially different from that in the general population. However, there is evidence that birth prevalence of open neural tube defects is higher by up to a factor of 5. Thus at a given AFP MoM concentration, women with IDD are at a substantially higher risk of open neural tube defects than the general population. This can be taken into account by lowering the AFP MoM cutoff from, for example, 2.0 to 1.5. 

Epidemiologic Monitoring of Open Neural Tube Defect Screening... 

Amniotic fluid AFP has been measured as early as 8 weeks. It rapidly decreases to its lowest point at 11 weeks, then increases to reach a second maximum at 13 weeks. The concentration then falls in a log-linear fashion until 25 weeks, when the decline steepens. Several studies have shown that AChE used in combination with amniotic fluid AFP can aid in the detection of open neural tube defects from 13 to 25 weeks of pregnancy. ... 

Maternal serum and amniotic fluid AFP are useful tests for detecting some serious fetal anomalies. Maternal serum AFP is elevated in 85% to 95% of cases of fetal open neural tube defect and is low in about 30% of cases of fetal Down syn-drome. Because maternal serum screening for fetal... 

AChE is an essential confirmatory test for all fluids with elevated amniotic fluid AFP. Normal amniotic fluid contains a group of nonspecific cholinesterases referred to as pseudocholinesterase (PChE). Cerebrospinal fluid contains high concentrations of the neural enzyme AChE, and in cases of fetal open neural tube defects (and in about 80% of cases with defects of the abdominal wall), fluid leaks from the open lesion and allows AChE to enter the amniotic fluid. 

Rasmussen-Loff AG, Nanchahal K, Cuckle HS, Wald NJ> Hulten M, Leedham P, et al. Amniotic fluid acetylcholinesterase m the prenatal diagnosis of open neural tube defects and abdominal wall defects a comparison of gel electrophoresis and a monoclonal antibody immunoassay. Prenat Diagn 1990 10 449-59. 

Open neural tube defects (not spina bifida occulta) lead to increased alfa-fetoprotein during pregnancy, which, in conjunction with ultrasound, allows prenatal diagnosis. 

Determination of AFP levels in amnio tic fluid or maternal serum is used for antenatal screening for certain birth defects and chromosomal abnormafities in the fetus (see Chapter 54). Elevated maternal serum AFP indicates the possibility of a neural tube or open abdominal wall defect in the fetus. The levels may also be elevated with multiple fetuses, low birth weight, fetal demise, and incorrect estimation of gestational age. Trisomy 21 (Down syndrome) and trisomy 18 are associated with low maternal serum AFP levels. AFP is also used as a marker for hepatocellular and germ cell carcinomas. For a discussion of the role of AFP as a tumor marker, see Chapter 23. 

Neural tube defect Birth defects that involve an incomplete development of the brain and spinal cord, and their protective coverings. There are three types of neural tube defects anencephaly (underdeveloped brain), encephalocele (hole in the skull through which brain tissues protrude), and spina bifida (spinal column remains open). The supplementation of folic acid to women prior to conception and during the first month of pregnancy reduces the risk of neural tube defects. 

---