Prenatal ONTD Screening
Open Neural Tube Defects
The most common serious birth defects in the U.S. involve openings of the skull and spine called open neural tube defects (ONTDs). These ONTDs are related in that they all involve defects of the formation of the skull and spine. They occur at about one month after conception, when the tissue which is to become the brain and spinal cord is represented by a flat tissue running down the back of the embryo. This tape-like tissue must form a closed tube (the neural tube). If the tube fails to seal at the skull, the resulting defect is an open skull (anencephalus or encephalocele). If the tube fails to seal along the spine, the resulting defect is an open spine (meningomyelocele or spina bifida).
SPINAL DYSRAPHISM is the association of spina bifida occulta with scoliosis and/or pilonidal cysts or other skin changes on the spine. Spinal dysraphism is an ONTD with the same cause and recurrence risk as other ONTDs. Spina bifida occulta alone is not an ONTD and does not have the same cause or recurrence risks.
Heredity and, in many cases, environment, play a role in causing these birth defects. About 95% of couples who have a fetus affected with ONTD have a negative family history. Most ONTDs are caused by multifactorial inheritance.
Multifactorial inheritance refers to the phenomenon in which a combination of genes from either or both parents with or without influence of environmental factors causes a birth defect. About 10% of ONTDs are caused by chromosome disorders, other genetic disorders, or environmental teratogen.
A fetus with anencephalus (open skull) may be miscarried, stillborn, or die shortly after birth. A fetus with an open spine may live longer, but usually have additional serious problems such as paralysis from the waist down and hydrocephalus. Some babies may have urinary tract problems, other anomalies, and mental retardation. Only rarely will a baby with an open spine have mild or moderate defects. Medical treatment usually cannot completely resolve these problems.
PRENATAL ONTD SCREENING
The fetus synthesizes alpha-fetoprotein (AFP) in the liver and gastro-intestinal tract. The AFP is excreted into amniotic fluid and diffuses into the maternal circulation. AFP levels in amniotic fluid (AFAFP) and maternal serum (MSAFP) are usually elevated when the fetus has an open neural tube defect. Many other fetal anomalies may be associated with an elevated MSAFP or AFAFP.
MSAFP screening is recommended for low risk patients. Screening can detect most anencephallic pregnancies, about 98% of open spina bifida, and about 60% of ventral wall defects.
Patients with a high ONTD risk (greater than 0.5% based on family or pregnancy history) should be referred for genetic counseling, ultrasound and amniocentesis, rather than have MSAFP screening. Targeted fetal ultrasound and MSAFP screening may be substituted in some cases if the patient declines amniocentesis; however, amniocentesis detects 99% of ONTDs and should be recommended because:
- Many ONTDs, ventral wall defects, and the majority of chromosome abnormalities are not detectable by ultrasound.
- Analysis of amniotic fluid alpha-fetoprotein (AFAFP) and acetylcholinesterase (AChE) can detect ONTDs and other fetal anomalies not detectable by ultrasound.
- About 5-7% of ONTDs are caused by chromosome disorders. Therefore, the recurrence risk of a fetal chromosome abnormality is increased for some ONTD family history patients.
- Patients with an elevated MSAFP have a fetal chromosome abnormality risk equal to or greater than a 35 year old woman.
- Patients taking the epilepsy medications valporic acid and/or carbamezepine have a 1.5% risk of having a fetus with spina bifida.
ONTD RISK TABLE
The live birth incidence of an ONTD is approximately 1 to 2 per 1000 pregnancies. The table below identifies high risk patients for whom genetic counseling and prenatal diagnosis are recommended.
| PATIENT'S RISK OF HAVING A BABY WITH AN ONTD | ||
| Family History or Age | Percent | Ratio |
|---|---|---|
| One child with an ONTD | 2% | 1/50 |
| Two children with an ONTD | 5% | 1/20 |
| Three children with an ONTD | 10% | 1/10 |
| Patient has an ONTD | 2% | 1/50 |
| Patient and child with ONTD | 6.5% | 1/15 |
| Patient's sib with an ONTD | 2% | 1/50 |
| One child with multiple vertebral or spinal dysraphism | 2% | 1/50 |
| Maternal aunt of child with an ONTD | 1% | 1/100 |
| Epilepsy medication - valproic acid and/or carbamezepine | 1.5% | 1/66 |
| Other parents who have 1st or 2nd degree relative with an ONTD | 0.3% | 1/333 |
| Maternal age 35 years and over | 0.33% | 1/300 |
| Maternal age less than 35 years | 0.14% | 1/700 |
Information provided on this site is for information purposes ONLY. This should not be used as a substitute for professional medical advice, treatment or diagnosis.