Does unexplained second-trimester (15 to 20 weeks' gestation) maternal serum alpha-fetoprotein elevation presage adverse perinatal outcome? Pitfalls and preliminary studies with late second- and third-trimester maternal serum alpha-fetoprotein.

Several reports have suggested that persons with an unexplained maternal serum alpha-fetoprotein elevation at 15 to 20 weeks' gestation are at an increased risk for a variety of other pregnancy complications (e.g., preeclampsia) and adverse perinatal outcomes (e.g., fetal death, low-birth-weight infants). However, ascertainment biases could explain some of these reported findings, and predictive value of unexplained elevated maternal serum alpha-fetoprotein levels in the prediction of pregnancy complications seems limited. If elevated second-trimester levels were truly predictive of pregnancy complications, we reason that third-trimester levels could prove even more useful. We thus studied late second-trimester and early third-trimester (24 to 36 weeks' gestation) maternal serum alpha-fetoprotein levels with the same enzyme immunoassay we use to evaluate routine second-trimester (15 to 20 weeks' gestation) levels. Values rose up to 32 weeks and fell slightly thereafter. Variance was greater than at 15 to 20 weeks but not so great as to preclude clinical usefulness in the third trimester. Of 279 women with a normal (0.4 to 2.49 multiples of the median) maternal serum alpha-fetoprotein value at 15 to 20 weeks' gestation, 270 (96.8%) showed levels in the same range later in gestation; however, none of six singleton pregnancies with unexplained maternal serum alpha-fetoprotein levels greater than 2.50 multiples of the median at 15 to 20 weeks' gestation showed maternal serum alpha-fetoprotein levels in this range at 24 to 36 weeks' gestation. The relationship between second- and third-trimester maternal serum alpha-fetoprotein levels in abnormal pregnancies remains to be elucidated in a large sample. Thus we are conducting not only cohort but also cross-sectional studies. Preliminary findings suggest that women with preterm premature rupture of membranes or with premature labor show elevated late second-trimester and early third-trimester maternal serum alpha-fetoprotein levels; however, larger sample sizes are necessary.