Association between human chorionic gonadotropin (hCG) levels and adverse pregnancy outcomes: A systematic review and meta-analysis.

Human chorionic gonadotropin (hCG), a glycoprotein produced in the placenta, is crucial for a healthy pregnancy. We investigated the relationship between hCG levels and adverse pregnancy outcomes. We conducted a systematic review including studies measuring hCG blood levels in the first or second trimester, reporting on any of the 12 predefined adverse pregnancy outcomes with logistic regression-adjusted association estimates. The primary outcomes were placenta-associated complications, such as miscarriage, preeclampsia, intrauterine growth restriction, and preterm delivery. We searched PubMed, Embase and CINAHL Complete. The hCG levels were analysed as multiple of the median (MoM). Odds ratio (OR) and 95% confidence interval (CI) were used. Risk of bias and the certainty of evidence were assessed using ROBINS-I and GRADE, respectively. Meta-analysis also showed that hCG levels, reported as MoM ≥2/2.31/2.5, might be associated with an increased risk of preeclampsia (OR 2.08, 95% CI 1.26 to 3.44) and preterm delivery (OR 1.29, 95% CI 1.12 to 1.47), but the evidence is very uncertain. High second trimester hCG levels may be associated with preeclampsia and preterm delivery but confidence in evidence is low.

Placenta-associated adverse pregnancy outcomes in women experiencing mild or severe hyperemesis gravidarum - a systematic review and meta-analysis.

BACKGROUND: Nausea and vomiting in pregnancy (NVP) affects 50-80% of pregnant women and is correlated to the level of human chorionic gonadotropin (hCG). Hyperemesis gravidarum (HG) is a severe condition, with an incidence of 0.2-1.5%, characterized by consistent nausea, vomiting, weight loss and dehydration continuing after the second trimester. AIM: The aim of this systematic review was to investigate a potential correlation between NVP or HG with adverse pregnancy outcomes and hCG levels. METHOD: A systematic search in PubMed, Embase and CINAHL Complete was conducted. Studies on pregnant women with nausea in the first or second trimester, reporting either pregnancy outcomes or levels of hCG were included. The primary outcomes were preterm delivery (PTD), preeclampsia, miscarriage, and fetal growth restriction. Risk of bias was assessed using ROBINS-I. The overall certainty of evidence was assessed using GRADE. RESULTS: The search resulted in 2023 potentially relevant studies; 23 were included. The evidence was uncertain for all outcomes, however women with HG had a tendency to have an increased risk for preeclampsia [odds ratio (OR) 1.18, 95% confidence of interval (CI) 1.03 to 1.35], PTD [OR 1.35, 95% CI 1.13 to 1.61], small for gestational age (SGA) [OR 1.24, 95% CI 1.13 to 1.35], and low birth weight (LBW) [OR 1.35, 95% CI 1.26 to 1.44]. Further, a higher fetal female/male ratio was observed [OR 1.36, 95% CI 1.15 to 1.60]. Meta-analyses were not performed for women with NVP; however, most of these studies indicated that women with NVP have a lower risk for PTD and LBW and a higher risk for SGA, and a higher fetal female/male ratio. CONCLUSION: There may be an increased risk in women with HG and a decreased risk in women with NVP for adverse placenta-associated pregnancy outcomes, however the evidence is very uncertain. TRIAL REGISTRATION: PROSPERO: CRD42021281218.