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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020469-03
Application #
3318573
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1985-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
de la Monte, S M; Wands, J R (1994) Diagnostic utility of quantitating neurofilament-immunoreactive Alzheimer's disease lesions. J Histochem Cytochem 42:1625-34
Marcillac, I; Troalen, F; Bidart, J M et al. (1992) Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms. Cancer Res 52:3901-7
Nebiolo, L; Ozturk, M; Brambati, B et al. (1990) First-trimester maternal serum alpha-fetoprotein and human chorionic gonadotropin screening for chromosome defects. Prenat Diagn 10:575-81
Ozturk, M; Milunsky, A; Brambati, B et al. (1990) Abnormal maternal serum levels of human chorionic gonadotropin free subunits in trisomy 18. Am J Med Genet 36:480-3
Berkowitz, R; Ozturk, M; Goldstein, D et al. (1989) Human chorionic gonadotropin and free subunits' serum levels in patients with partial and complete hydatidiform moles. Obstet Gynecol 74:212-6
Ozturk, M; Motte, P; Takahashi, H et al. (1989) Identification and characterization of a Mr 50,000 adrenal protein in human hepatocellular carcinoma. Cancer Res 49:6764-73
Takahashi, H; Ozturk, M; Wilson, B et al. (1989) In vivo expression of two novel tumor-associated antigens and their use in immunolocalization of human hepatocellular carcinoma. Hepatology 9:625-34
Ozturk, M; de la Monte, S M; Gross, J et al. (1989) Elevated levels of an exocrine pancreatic secretory protein in Alzheimer disease brain. Proc Natl Acad Sci U S A 86:419-23
Takahashi, H; Carlson, R; Ozturk, M et al. (1989) Radioimmunolocation of hepatic and pulmonary metastasis of human colon adenocarcinoma. Gastroenterology 96:1317-29
Motte, P; Takahashi, H; Ozturk, M et al. (1989) Characterization of a malignant phenotype-associated cell surface glycoprotein common to various human tumor cells and preferentially expressed on adenocarcinoma of the lung. Cancer Res 49:1349-56

Showing the most recent 10 out of 28 publications