Congenital malformations, mental retardation and genetic disorders together constitute a major source of morbidity and mortality in childhood and beyond. Some 25 to 30% of all admissions to Children's Hospitals in the western world are for these categories of disease. The two most common major congenital defects in western society are neural tube defects (NTD's) and Down's syndrome. For NTD's maternal serum alpha-fetoprotein (MSAFP) screening by conventional radioimmunoassays (C-RIAs) has been available for 10 years. The clear benefit of second trimester MSAFP include detection of unexpected serious congenital defects and serve as a non-specific signal of pregnancies at risk. We have developed a highly sensitive, reproducible and specific monoclonal RIA (M-RIA) for measurement of MSAFP and amniotic fluid AFP levels. Preliminary studies have demonstrated that MSAFP levels may be accurately measured in the first trimester and we have found AFP elevations not detected by C-RIA in fetal developmental abnormalities such as closed neural tube defects, nuchal cysts and hydrocephalus. We will assess the value of MSAFP elevations by M-RIA in the early detection of NTD's and chromosome abnormalities as well as other birth defects in a prospective study. Comparisons will be made to a standard polyvalent C-RIA. In addition, we will compare high as well as low amniotic fluid AFP values as measured by M-RIA to a conventional technique in the diagnosis of birth defects. Our goals, therefore, are to determine the value of elevated first trimester MSAFP levels in the identification of open and closed NTD's and assess its importance as a non-specific predictor of fetal wastage, pregnancy complications and low birth weight. Finally, we will explore the implication of first and second trimester MSAFP levels in Down's syndrome and other chromosomal abnormalities by M-RIA. Any screening test which could reliably detect pregnancies in which the fetus had a NTD or other serious chromosome abnormality in the first trimester would be of considerable value and represent a major advance in the early detection of such conditions. We are optimistic that new data of biologic and clinical significance will be forthcoming and the evolution of a new standard of care for MSAFP screening may be possible.
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