Background: Early identification of pregnant women at risk of delivering small-for-gestational-age (SGA) infants is required to reduce the rates of mortality and morbidity in their whole life. This meta-analysis was performed to determine whether women with higher blood alpha-fetoprotein (AFP) levels are at increased risk of SGA.
Methods: Studies identified by searching 11 databases, including PubMed, were assessed using the Newcastle-Ottawa Scale. Subgroup and meta-regression analyses and sensitivity analysis removing a potential outlier were performed. Publication bias was assessed using Egger's test.
Results: A total of 39 good-quality cohort studies involving 93,968 women and their newborn infants or fetuses ensured both internal and external validity. Relative risk of SGA among women with higher in comparison to lower blood AFP levels was 2.021 (95% CI: 1.751-2.334). Maternal blood AFP levels showed a dose-response relationship with risk of SGA. Relative risk was higher with diagnosis of SGA by ultrasound than actual birth weight (P = 0.004). Sources of heterogeneity, subgroups, confounding factors, or potential outliers did not alter the interpretations without publication bias (P = 0.320).
Conclusions: Pregnant women with higher blood AFP levels are at increased risk of SGA compared to those with lower blood AFP levels.
Impact: Pregnant women with higher blood alpha-fetoprotein levels (AFP) levels are at increased risk of small for gestational age (SGA) compared to those with lower blood AFP levels. High-quality evidence showed a dose-response relationship of maternal blood AFP levels with risk of delivering SGA and was robust to sources of heterogeneity, subgroups, confounding factors, potential outliers, or publication bias. Politically and practically, monitoring of maternal blood AFP level is strongly recommended to identify women at risk of delivering SGA.