Down syndrome screening in an Asian population using alpha-fetoprotein and free beta-hCG: a report of the Taiwan Down Syndrome Screening Group

OBJECTIVE: To evaluate whether the strategy of maternal serum screening for Down syndrome, using alpha-fetoprotein (AFP) and free beta-hCG in combination with maternal age, a technique developed in western countries, is applicable to an Asian population. METHODS: Alpha-fetoprotein and beta-hCG were measured in serum samples from 23 Down syndrome pregnancies and 1748 unaffected singleton Taiwanese (ethnically Chinese) pregnancies at 14-22 weeks' gestation. Gestational age-specific medians and a maternal weight correction formula were established for our own population. Likelihood ratio for Down syndrome pregnancies in relation to multiples of the median (MoM) levels of these analytes were derived from the overlapping gaussian frequency distribution curves for Down syndrome and unaffected pregnancies. RESULTS: The serum AFP and free beta-hCG median MoM values of Down syndrome pregnancies were significantly abnormal in Asian subjects (0.77 and 2.91, respectively), and similar to those of affected pregnancies in white women. The median value of free beta-hCG:AFP MoM ratio (2.97) in Down syndrome pregnancies was significantly higher than that of unaffected pregnancies (1.09). The mean maternal weight during the second trimester in pregnant Asian women (55.2 kg) was markedly lighter than that of white women. At a 5.8% false-positive rate, free beta-hCG identified 47.8% of Down syndrome pregnancies (likelihood ratio 8.2), AFP detected only 13% of the cases (likelihood ratio 2.2), and free beta-hCG:AFP MoM ratio detected 43.5% of the cases (likelihood ratio 7.4). By using a multivariate risk algorithm involving the combination of AFP, free beta-hCG, and maternal age, 56.5% of Down syndrome cases could be detected with a 5.3% false-positive rate (likelihood ratio 10.7). CONCLUSION: Maternal serum screening strategy using AFP and free beta-hCG in combination with maternal age is feasible in the detection of fetal Down syndrome among Asian women.

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