First trimester maternal serum alpha fetoprotein is associated with ischemic placental disease

Abstract Background While elevated second trimester maternal serum alpha fetoprotein (msAFP) has been associated with adverse pregnancy outcomes, the utility of first trimester msAFP in predicting these outcomes is limited. Some laboratories have been including msAFP as part of the first trimester analyte screening for aneuploidy and preeclampsia, offering its potential utility in predicting pregnancy outcomes. Objective Our primary objective was to determine the association between elevated first trimester msAFP and preeclampsia, as well as ischemic placental disease (a composite of preeclampsia, fetal growth restriction and/or placental abruption). Secondary outcomes included early onset preeclampsia requiring delivery at Study Design An IRB-approved multi-site retrospective cohort study was performed including all patients with first trimester msAFP as part of routine first trimester aneuploidy screening from April 2015-January 2017. Pregnancies with multiple gestations, known structural or chromosomal abnormalities, known malignancy, and incomplete delivery records were excluded. Delivery records were reviewed for baseline characteristics and adverse pregnancy outcomes. The optimal cut-off point for first trimester msAFP to predict these outcomes was assessed and an elevated msAFP was considered > 2.0 MoM. Fisher exact test and odds ratios were used to determine the association between elevated first trimester msAFP and adverse pregnancy outcomes. Spearman correlation coefficient assessed the relationship between first and second trimester msAFP. Results Of 1478 patients with first trimester msAFP, 1280 had complete records available for review (86.6%). There was no association demonstrated between elevated first trimester msAFP (> 2.0 MoM) and the primary outcome, overall preeclampsia (5.8% vs. 4.6%, OR 1.29, 95% CI 0.58, 2.91). However, there was an increased incidence of ischemic placental disease, 15.8% vs 7.7% (OR 2.26, 95% CI 1.33-3.87) in those with an elevated AFP. Also, elevated first trimester msAFP was associated with a higher incidence of fetal growth restriction (7.5% vs 2.3%, OR 3.40, 95% CI 1.56-7.42) and preterm birth (18.3% vs 10.3%, OR 1.95, 95% CI 1.18-3.21). Also, a positive correlation between first and second trimester msAFP was demonstrated (rho = 0.46, P Conclusions Elevated first trimester msAFP is associated with ischemic placental disease, fetal growth restriction, and preterm birth. This suggests that elevated msAFP may help to identify high risk pregnancies as early as the first trimester of pregnancy. Future studies are necessary to determine if addition of first trimester msAFP to existing algorithms can improve the early detection of ischemic placental disease.