Elevated maternal serum alpha-fetoprotein with low unconjugated estriol and the risk for lethal perinatal outcome

Objective: To determine whether a combination of elevated maternal serum alpha-fetoprotein (MSAFP) and low unconjugated estriol (E3) concentration identifies pregnancies at particularly high risk for fetal abnormality or poor outcome. Methods: Pregnancy outcomes were reviewed for women with elevated MSAFP (≥2.0 MoM) from our database of 50,315 women who had received triple marker testing from 1993-1998. Outcomes for those with low E3 (≤ 0.7 MoM) were compared with those with normal E3 (> 0.7 MoM). The incidences of fetal death, neural tube defects, chromosome abnormalities, congenital abnormalities, preterm birth, small-for-gestational age (SGA), twins, and inaccurate dates were compared in the two groups using Fisher's exact test with P < 0.05 considered significant. Results: Of the 50,315 women screened, 1,435 (2.85%) had an elevated MSAFP. Pregnancy outcomes were obtained in 94% of those with elevated MSAFP and 70% of all patients screened. Neural tube defects were present in 57 fetuses/infants (21 anencephalic, 29 spina bifida, 7 encephalocele) of which 46 (81%) had an elevated MSAFP. Of the 1,435 women with an elevated MSAFP, 199 (14%) had a low E3. Compared to those women with elevated MSAFP but normal E3, women with elevated MSAFP and low E3 were at significantly increased risk for fetal death (20.6% vs. 2.8%, relative risk (RR) 8.9), anencephaly (9.0% vs. 0.1%, RR 122.8) and chromosome abnormality (2.5% vs. 0.6%, RR 4.0). Conclusions: Pregnancies complicated by elevated second trimester MSAFP and low E3 are at a particularly high risk (32%) for lethal perinatal outcomes. Twins, while a common cause of elevated MSAFP, are rarely found when an elevated MSAFP is associated with low E3.