Alpha-fetoprotein: a biomarker for pregnancy outcome.

Beginning in 1977, numerous studies have reported an association between high levels of maternal serum alpha-fetoprotein, measured in early pregnancy, and low birthweight and perinatal death. It has been suggested, however, that these findings may be explained by bias. We reviewed 21 studies and found that they were unanimous in reporting this association and that the association cannot be explained by any of the proposed biases. Comparing women whose alpha-fetoprotein levels were 2.5 times the median or more with all other women, the highest relative risk of fetal death was 21.0, with a 95% confidence interval of 8.4-52.2, and the lowest relative risk of fetal death was 4.4, with a 95% confidence interval of 2.8-7.0. For low birthweight (< 2,500 grams), the highest relative risk was 6.4 (95% confidence interval = 3.1-13.1) and the lowest relative risk was 1.9 (95% confidence interval = 1.5-2.5).