Alpha-fetoprotein: a biomarker for pregnancy outcome

Area of Science:

• Obstetrics and Gynecology
• Prenatal Diagnostics
• Perinatal Epidemiology

Background:

• Since 1977, studies have indicated a correlation between elevated maternal serum alpha-fetoprotein (MSAFP) levels in early pregnancy and adverse outcomes like low birthweight and perinatal death.
• Concerns regarding potential biases influencing these observed associations have been raised in the scientific community.

Purpose of the Study:

• To systematically review existing literature and critically evaluate the association between maternal serum alpha-fetoprotein levels and pregnancy outcomes.
• To determine if proposed biases could account for the reported association between high MSAFP and adverse pregnancy outcomes.

Main Methods:

• A comprehensive review of 21 independent studies investigating maternal serum alpha-fetoprotein levels and pregnancy outcomes.
• Statistical analysis to assess the relative risk of fetal death and low birthweight in relation to MSAFP levels, specifically comparing women with levels ≥ 2.5 times the median to all other women.

Main Results:

• All 21 reviewed studies consistently reported a significant association between high maternal serum alpha-fetoprotein and both low birthweight and perinatal death.
• The proposed biases were found to be insufficient to explain the observed association.
• Relative risks for fetal death ranged from 4.4 to 21.0 (95% CI: 2.8–7.0 to 8.4–52.2), and for low birthweight (<2,500 grams), risks ranged from 1.9 to 6.4 (95% CI: 1.5–2.5 to 3.1–13.1).

Conclusions:

• The association between elevated maternal serum alpha-fetoprotein in early pregnancy and increased risk of fetal death and low birthweight is a genuine phenomenon.
• This association is not attributable to confounding factors or biases, underscoring its clinical significance in prenatal risk assessment.