Maternal First-Trimester Alpha-Fetoprotein and Placenta-Mediated Pregnancy Complications

BACKGROUND: Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional first-trimester screening (FTS) that included PAPP-A (pregnancy-associated plasma protein-A) and beta-hCG (human chorionic gonadotropin), to the enhanced FTS test, which added first-trimester AFP (alpha-fetoprotein) and PlGF (placental growth factor). However, whether elevated first-trimester AFP has a similar association with placenta-mediated complications to that observed for elevated second-trimester AFP remains unclear. Our objective was to estimate the association of first-trimester AFP with placenta-mediated complications and compare it with the corresponding associations of second-trimester AFP and other first-trimester serum markers. METHODS: Retrospective population-based cohort study of women who underwent trisomy 21 screening in Ontario, Canada (2013-2019). The association of first-trimester AFP with placenta-mediated complications was estimated and compared with that of the traditional serum markers. The primary outcome was a composite of stillbirth or preterm placental complications (preeclampsia, birthweight less than third centile, or placental abruption). RESULTS: A total of 244 990 and 96 167 women underwent FTS and enhanced FTS test screening, respectively. All markers were associated with the primary outcome, but the association for elevated first-trimester AFP (adjusted relative risk [aRR], 1.57 [95% CI, 1.37-1.81]) was weaker than that observed for low PAPP-A (aRR, 2.48 [95% CI, 2.2-2.8]), low PlGF (aRR, 2.28 [95% CI, 1.97-2.64]), and elevated second-trimester AFP (aRR, 1.97 [95% CI, 1.81-2.15]). When the models were adjusted for all 4 enhanced FTS test markers, elevated first-trimester AFP was no longer associated with the primary outcome (aRR, 0.77 [95% CI, 0.58-1.02]). CONCLUSIONS: Unlike second-trimester AFP, elevated first-trimester AFP is not an independent risk factor for placenta-mediated complications.