The association between human chorionic gonadotropin and adverse pregnancy outcomes: a systematic review and meta-analysis

OBJECTIVE: This study aimed to evaluate the association between human chorionic gonadotropin and adverse pregnancy outcomes. DATA SOURCES: Medline, Embase, PubMed, and Cochrane were searched in November 2021 using Medical Subject Headings (MeSH) and relevant key words. STUDY ELIGIBILITY CRITERIA: This analysis included published full-text studies of pregnant women with serum human chorionic gonadotropin testing between 8 and 28 weeks of gestation, investigating fetal outcomes (fetal death in utero, small for gestational age, preterm birth) or maternal factors (hypertension in pregnancy: preeclampsia, pregnancy-induced hypertension, placental abruption, HELLP syndrome, gestational diabetes mellitus). METHODS: Studies were extracted using REDCap software. The Newcastle-Ottawa scale was used to assess for risk of bias. Final meta-analyses underwent further quality assessment using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method. RESULTS: A total of 185 studies were included in the final review, including the outcomes of fetal death in utero (45), small for gestational age (79), preterm delivery (62), hypertension in pregnancy (107), gestational diabetes mellitus (29), placental abruption (17), and HELLP syndrome (2). Data were analyzed separately on the basis of categorical measurement of human chorionic gonadotropin and human chorionic gonadotropin measured on a continuous scale. Eligible studies underwent meta-analysis to generate a pooled odds ratio (categorical human chorionic gonadotropin level) or difference in medians (human chorionic gonadotropin continuous scale) between outcome groups. First-trimester low human chorionic gonadotropin levels were associated with preeclampsia and fetal death in utero, whereas high human chorionic gonadotropin levels were associated with preeclampsia. Second-trimester high human chorionic gonadotropin levels were associated with fetal death in utero and preeclampsia. CONCLUSION: Human chorionic gonadotropin levels are associated with placenta- mediated adverse pregnancy outcomes. Both high and low human chorionic gonadotropin levels in the first trimester of pregnancy can be early warning signs of adverse outcomes. Further analysis of human chorionic gonadotropin subtypes and pregnancy outcomes is required to determine the diagnostic utility of these findings in reference to specific cutoff values.