American Journal of Medical Genetics 39:64-67 (1991)

Risks Associated With an Elevated Amniotic Fluid a-Fetoprotein Level Barbara F. Crandall and Myles Matsumoto Departments of Psychiatry (B.F.C., M.M.) and Pediatrics (B.F.C.), University of California, Los Angeles Two and two-tenthspercent of 85,000 consecutive amniotic fluid (AF) samples had a-fetoprotein (AFP)levels 22.0 MOM.Half measured 2.0-2.4 MOM,and 93%had a normal outcome. Sixty-seven percent of those with higher levels had abnormalities. A positive acetylcholinesterase (AChE) increased the risk from 67% for levels between 2.0 and 2.4 MOM to 99% at 25.0 MOMS. After a normal ultrasound and chromosome studies, the risk for a fetal abnormality was 1% for AF AFP measuring 2.0-2.4 MOM and 3% for higher levels.

pregnancy (>23 weeks) because of a n abnormal US are excluded. These samples were submitted from 17 prenatal diagnosis centers in California.

MATERIALS AND METHODS AFP levels were measured by radioimmunoassay (RIA) in the first 30,000 cases and by enzyme-linked immunosorbent assay (ELISA) in the remainder. All samples were assayed in duplicate. Interassay variation was less than 10% (4.2-9.6%). AChE gel electrophoresis has been described previously and was included if there was a n increased risk of open NTD [family history, elevated maternal serum (MS) AFP, or US abnormality] or if AFP levels measured 21.75 MOM [Crandall et al., 19821. KEY WORDS: neural tube defect, AFP, aceAChE was interpreted as positive if a clear band was tylcholinesterase, ultrasound present in the position of the specific cholinesterase and disappeared with the specific inhibitor (BW284C51). The selected cut-off for AF AFP was 2.0 MOMand AFP INTRODUCTION was called elevated if above this level, indicating the The purpose of this paper is to assess the risk of a n need for further studies. Bloody samples were tested for abnormality after a n elevated amniotic fluid (AF) fetal red cells by Betke-Kleihauer test. Gestational ages a-fetoprotein (AFP),negative and positive acetylcholin- were usually determined by menstrual dates and conesterase (AChE), and normal results of ultrasound (US) firmed by US. examination. Previous large studies have reported the risk for an open neural tube defect (NTD) and other RESULTS abnormalities with different degrees of AF AFP elevation [Secondreport of the U.K. collaborative study, 1979; The indications for the amniocenteses are shown in Milunsky, 1980; Crandall and Matsumoto, 19861. Im- Table I. Since the inception of the MS AFP screening provements in both US equipment and operator experi- program in California in April, 1986, an increasing ence have resulted in fewer missed open NTDs and other number of amniocenteses is performed because of a high serious abnormalities, but these still occasionally occur. or low MS AFP. Suspected US abnormalities now acIn addition, a number of serious abnormalities are un- count for about 1%of cases. Of the AF samples, 1,849 likely to be detected by US and yet may have a major (2.2%) showed AFP levels 22.0 MOM.This number varimpact on the survival, health, and development of the ied slightly in different prenatal diagnosis centers. For infant. purposes of risk determination, elevated AFPs were diWe have performed routine AFP assays on 85,000 AF vided into 3 groups by the degree of elevation (2.0-2.4, samples over the past 15 years. Consecutive samples 2.5-4.9, and ?5.0), and these are shown in Table 11. only are included in this analysis; samples sent to con- Fifty percent of the elevated samples measured between firm a n elevated AFP or those obtained later in the 2.0 and 2.4 MOM,and 92.6% of these had normal outcomes. Twenty-six percent measured 2 5 . 0 MOM, and only 5.6% had a normal outcome. The overall chance of a normal outcome was 63% after a n elevated AFP and Received for publication March 26,1990; revision received July 58% if bloody samples were excluded. Six of the normal 3, 1990. outcomes occurred in 3 families who had elevated AFAddress reprint requests to Dr. Barbara F. Crandall, NeuroAFPs in 2 succeeding pregnancies: No abnormalities psychiatric Institute 48-233, Department of Psychiatry and Pediwere detected and renal function was normal. We beatrics, University of California, Los Angeles, CA 90024. 0 1991 Wiley-Liss, Inc.

Risks Associated With Elevated AF AFP TABLE I. Indication for Amniocentesis Percent

Indication Maternal age" Anxietyb Low MS AFP High MS AFP US abnormality Previous chromosome abnormality Previous congenital abnormality Metabolic disorder Parent with chromosome abnormality Family history Down syndrome Family history mental retardation Family history NTD Previous NTD Other (radiation. drugs. bleeding)

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65

TABLE 11. Risk of Abnormality or Demise After Elevated AF AFP [85,000 tested, levels in MOM (%)I

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69.0 9.0 10.0 5.0 1.0 1.0 1.0 0.3 0.4 1.0 1.0 0.5 0.5 0.5

Maternal age >34 years. age

Risks associated with an elevated amniotic fluid alpha-fetoprotein level.

Two and two-tenths percent of 85,000 consecutive amniotic fluid (AF) samples had alpha-fetoprotein (AFP) levels greater than or equal to 2.0 MoM. Half...
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