Clinical Information

Neural tube defects (NTD) are a type of birth defect involving openings along the brain and spine. They develop in the early embryonic period when the neural tube fails to close completely. NTD can vary widely in severity. Anencephaly represents the most severe type of NTD, which occurs when the cranial end fails to develop properly, resulting in an absence of the forebrain, the area of the skull that covers the brain, and the skin. Most infants with anencephaly are stillborn or die shortly after birth. NTD along the spine are referred to as spina bifida. Individuals with spina bifida may experience hydrocephalus, urinary and bowel dysfunction, club foot, lower body weakness, and loss of feeling or paralysis. Severity varies depending upon whether the NTD is covered by skin, whether herniation of the meninges and spinal cord are present, and the location of the lesion. NTD not covered by skin are referred to as open NTD and are typically more severe than closed NTD. Likewise, those presenting with herniation and higher on the spinal column are typically more severe.

Most NTD occur as isolated birth defects with an incidence of approximately 1 to 2 in 1000 live births in the United States. Rates vary by geographic region with lower rates being observed in the North and West than in the South and East. A fetus is at higher risk when the pregnancy is complicated by maternal diabetes, exposed to certain anticonvulsants, or there is a family history of NTD. Studies have shown a dramatic decrease in risk as a result of maternal dietary supplementation with folic acid. The March of Dimes currently recommends all women of childbearing age take 400 mcg of folic acid daily, increasing the amount to 600 mcg/day during pregnancy. For women who have had a prior pregnancy affected by an NTD, the recommended dose is at least 4000 mcg/day starting at least 1-month preconception and continuing through the first trimester.

When an NTD is suspected based upon maternal serum alpha-fetoprotein (AFP) screening results or diagnosed via ultrasound, analysis of AFP and acetylcholinesterase (AChE) in amniotic fluid are useful diagnostic tools. AChE is primarily active in the central nervous system with small amounts of enzyme found in red blood cells, skeletal muscle, and fetal serum. Normal amniotic fluid does not contain AChE, unless contributed by the fetus as a result of an open NTD.