ELEVATED MATERNAL SERUM MIDTRIMESTER ALPHA-FETOPROTEIN LEVELS ARE ASSOCIATED WITH FETOPLACENTAL ISCHEMIA

OBJECTIVE: Elevation of maternal serum alpha-fetoprotein in the second trimester is associated with poor pregnancy outcome, including fetal death, preterm delivery, and fetal growth restriction. We hypothesized that placental ischemia may be the common underlying pathogenesis of these outcomes. Thus we tested angiogenin, a potent inducer of neovasc ularization, in midtrimester amniotic fluid of patients with elevated maternal serum alpha-fetoprotein values to determine whether alpha-fet oprotein elevation is due to ischemia with subsequent stimulation of a ngiogenesis. STUDY DESIGN: In this case-control study, patients with e levated maternal serum a-fetoprotein levels (greater than or equal to 2.0 multiples of the median, n = 9) at triple screen were matched with two controls (n = 18) on the basis of year of amniocentesis and mater nal age, race, and parity. The median elevation of maternal serum alph a-fetoprotein in the study population was 4.01 multiples of the median (range 2.65 to 7.24 multiples of the median). inclusion criteria were (1) singleton gestation, (2) no evidence of fetal structural or chrom osomal anomalies, and (3) genetic amniocentesis. Amniotic fluid was im munoassayed for angiogenin (Quantikine, R&D Systems; sensitivity 0.026 ng/ml, interassay and intraassay coefficients of variation 4.6% and 2 .9%, respectively). Statistical analysis included one-way analysis of variance and regression with p < 0.05 significant. Angiogenin and mate rnal serum alpha-fetoprotein values were normalized with use of natura l log transformation for statistical analysis. RESULTS: Angiogenin val ues were significantly elevated in patients with high maternal serum a lpha-fetoprotein levels (median 31.1 [range 9.2 to 54.6] vs 17.1 [rang e 9.0 to 29.2] ng/ml, p = 0.02). Mean gestational age at sampling, mat ernal age, and year of amniocentesis were not significantly different between the study and control groups (each p 0.05). As anticipated, th ere was, a significant increase in preterm deliveries and small-for-ge stational-age neonates in the patients with elevated maternal serum al pha-fetoprotein levels (each p < 0.01). CONCLUSIONS: Midtrimester amni otic fluid angiogenin levels are significantly elevated in patients wi th elevated midtrimester maternal serum alpha-fetoprotein levels. Beca use angiogenin is a known marker of tissue ischemia, resulting in neov ascularization, we hypothesize that elevation of maternal serum alpha- fetoprotein levels at triple screen is due to placental ischemia.