Alpha-fetoprotein and poor pregnancy outcomes: Observed patterns, pathophysiology, and clinical utility

During pregnancy, maternal serum alpha-fetoprotein (MSAFP) is commonly used as a second trimester prenatal screening biomarker for chromosomal and structural birth defects. In the absence of birth defects, abnormal levels of mid-pregnancy MSAFP are associated with adverse pregnancy outcomes including fetal demise and preterm birth. Pregnancies ending in fetal demise or preterm birth often have unusually lower or higher mid-pregnancy MSAFP levels than pregnancies that do not. The same is true for pregnancies with specific conditions that are closely related to fetal demise and preterm birth including preeclampsia, conditions of abnormal placentation (e.g., previa, abruption, accreta), and pregnancies carrying a fetus with intrauterine growth restriction. In this chapter, we review specific studies looking at the relationship between MSAFP and fetal demise or preterm birth. In addition, we will review associations between MSAFP and conditions with close links to fetal demise and preterm birth including preeclampsia, placenta previa, placental abruption, placenta accreta, and intrauterine growth restriction. We also provide a brief review of the pathophysiological literature that underscores these relationships and we suggest next steps with respect to research and clinical use of MSAFP data.