Unexplained elevations of maternal serum alpha-fetoprotein in women with antiphospholipid antibodies: a harbinger of fetal death

Abstract

Objective: To determine whether unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) in women with antiphospholipid antibodies are associated with adverse pregnancy outcomes.

Methods: A retrospective cohort study was used to compare pregnancy outcomes between women with second-trimester MSAFP values equal to or greater than 2.5 multiples of the median (MoM) and less than 2.5 MoM. The cohort included 60 pregnancies in 47 women with medium to high positive levels of immunoglobulin (Ig) G anticardiolipin antibodies, lupus anticoagulant, or both.

Results: Thirteen pregnancies (22%) had elevated MSAFP values (median 3.6 MoM, range 2.5-12.6). Of these, amniotic fluid AFP was normal in seven and elevated in one. None of the elevated MSAFP levels were explained by fetal anomalies, current fetal death, multiple gestation, incorrect dates, or vaginal bleeding. Pregnancies with elevated MSAFP values had a significantly higher incidence of fetal death (eight of 13, 62%, versus three of 47, 6%) and perinatal loss (ten of 13, 77%, versus seven of 47, 15%) than those with normal MSAFP (P < .001, Fisher exact test). In these women, the sensitivity and specificity of an unexplained elevated MSAFP level in ascertaining fetal death were 73 and 90%, respectively. For perinatal loss, the sensitivity was 59% and the specificity was 93%. Of the placentas studied, infarction occurred in eight of nine (89%) among the women with elevated MSAFP.

Conclusions: Unexplained second-trimester elevations of MSAFP are common in women with antiphospholipid antibodies and are significantly associated with fetal loss. Abnormalities in the fetoplacental barrier are implicated as part of the pathophysiology of antiphospholipid antibody-mediated pregnancy loss.