Unexplained elevated maternal serum alpha-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes

OBJECTIVE: The study was undertaken to determine the risks of adverse obstetric outcomes in pregnant women with unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) and/or human chorionic gonadotropin (hCG) and to determine whether these risks vary by prepregnancy risk status. STUDY DESIGN: All women who underwent double-marker screening (MSAFP+hCG) between 1994 and 2000 and were delivered of an infant in Nova Scotia, Canada, during this period were identified from a hospital serum screening database and a provincial perinatal database. Patients with inaccurate dating, major structural anomalies, or chromosomal abnormalities were excluded. The primary outcomes studied were preeclampsia, abruptio placentae, fetal growth restriction, fetal death, and preterm birth. Women with medical or previous obstetric complications were designated high risk. Logistic regression, controlling for confounding factors, was used to estimate the relative risks (RRs) and 95% CI for elevated levels of MSAFP and/or hCG and each of the outcomes. RESULTS: Among the 14,374 women who met the study criteria, 5,789 were designated high risk. Except for abruptio placentae, unexplained elevated MSAFP or elevated hCG levels were independently associated with all the outcomes in both high- and low-risk women. Elevated screening values were associated with increased risk of abruptio placentae among low-risk women only. Particularly large RRs were seen for fetal death in both high- and low-risk women (RR=4.9, 95% CI 2.7-8.7 for elevated MSAFP or hCG in high- and low-risk women combined). CONCLUSION: Unexplained elevated levels of MSAFP and/or hCG are associated with an increased risk of most pregnancy complications. Increased antenatal surveillance of these patients is important regardless of prepregnancy risk status.