The Effect of Serum β-Human Chorionic Gonadotropin on Pregnancy Complications and Adverse Pregnancy Outcomes: A Systematic Review and Meta-Analysis

BACKGROUND: The relationship among elevated serum β-human chorionic gonadotropin (β-hCG), the incidence of pregnancy complications, and adverse pregnancy outcomes has been controversial. Differences in study design, subject bias due to demographic characteristics, and differences in local medical levels could contribute to inconsistent results. METHODS: Literature searches were performed in PubMed, EMBASE, Medline, Central, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science Digital Library (CSDL) databases. Inclusion criteria were as follows: (1) research subjects were singleton pregnant women; (2) the study is identified as cohort study; (3) the subjects were assigned to the high β-hCG group and control group according to whether the exposure factors increased β-hCG in the second trimester; (4) the observed outcomes include at least pregnancy-induced hypertension (PIH), diabetes (gestational diabetes mellitus, GMD), preterm delivery (PD), and intrauterine growth restriction (IUGR); and (5) the odds ratio (OR) and 95% confidence interval (CI) of exposure factors are calculated based on literature dataset. To determine the risk bias of selected literatures, Newcastle-Ottawa scale was applied. The chi-square test was further used for heterogeneity analysis. If heterogeneity was identified, subgroup analyses were then performed for source investigation. RESULTS: A total of 13 literatures were included and analyzed, including 67,355 pregnant women and 5980 pregnant women assigned to the high β-HCG group and 61,375 pregnant women to the control group. The incidence of PIH in the high β-HCG group was higher than that in the control group (OR = 2.11, 95% CI [1.90, 2.35], Z = 13.85, P < 0.00001). There was no heterogeneity among literatures (χ(2) = 8.53, P = 0.38, I(2) = 6%), and thus there is no identified publication bias (P > 0.05). The incidence of preterm birth in the high β-HCG group was higher than that in the control group (OR = 2.11, 95% CI [1.90, 2.35], Z = 13.85, P < 0.00001). The analysis suggested no heterogeneity among included literatures (χ(2) = 11.78, P = 0.11, I(2) = 41%) and no publication bias (P > 0.05). Higher incidence of abortion was observed in the high β-HCG group compared with the control group (OR = 2.80, 95% CI [1.92, 4.09], Z = 5.32, P < 0.00001). There was no heterogeneity among literatures (χ(2) = 3.43, P = 0.33, I(2) = 13%) and no publication bias (P > 0.05). The incidence of gestational diabetes was higher in the high β-HCG group than in the control group (OR = 2.15, 95% CI [1.05, 4.40], Z = 2.09, P = 0.04). Heterogeneity was identified among literatures (χ(2) = 47.01, P < 0.00001, I(2) = 87%). Sensitivity analysis showed that the results were not robust, and there was no publication bias (P > 0.05). Compared with control, the incidence of IGUR was higher in the high β-HCG group (OR = 2.70, 95% CI [1.75, 4.19], Z = 4.45, P < 0.0001) with no heterogeneity among literatures (χ(2) = 3.92, P = 0.14, I(2) = 49%) and no publication bias (P > 0.05). CONCLUSION: High levels of β-hCG during pregnancy in singleton women are associated with a high incidence of pregnancy complications and adverse pregnancy outcomes. Pregnant women with high levels of β-hCG should be monitored more closely, followed up, and given timely medical interventions to reduce the incidence of pregnancy complications and adverse outcomes.