Unveiling the impact of hCG on pregnancy outcomes


Delve into the intricate correlation between human chorionic gonadotropin levels during pregnancy and various adverse outcomes, shedding light on its multifaceted role in maternal-fetal health.

Unveiling the impact of hCG on pregnancy outcomes | Image Credit: © Wedding photography - © Wedding photography - stock.adobe.com.

Unveiling the impact of hCG on pregnancy outcomes | Image Credit: © Wedding photography - © Wedding photography - stock.adobe.com.

There is a correlation between human chorionic gonadotropin (hCG) levels and placenta-mediated adverse pregnancy outcomes, according to a recent study published in the American Journal of Obstetrics & Gynecology.


  1. The study reveals a significant correlation between human chorionic gonadotropin (hCG) levels during pregnancy and various adverse outcomes such as spontaneous abortion, stillbirth, small for gestational age (SGA), preeclampsia (PE), gestational diabetes mellitus (GDM), preterm delivery, and placental abruption.
  2. The association between hCG levels and adverse outcomes varied between the first and second trimesters. For instance, while first-trimester hCG levels were strongly associated with spontaneous abortion, second-trimester levels were more linked to conditions such as SGA and PE.
  3. The impact of hCG levels on different adverse outcomes varied. For example, low hCG levels in the first trimester were associated with an increased risk of spontaneous abortion and SGA, while high hCG levels were linked to risks such as PE and GDM.
  4. The study employed rigorous methodologies, including comprehensive searches of multiple databases, strict inclusion and exclusion criteria, and independent screening of articles. This approach enhances the reliability and validity of the findings.
  5. The findings underscore the importance of monitoring hCG levels during pregnancy as a potential indicator for adverse outcomes. This may aid in early identification and management of high-risk pregnancies, potentially improving maternal and fetal outcomes.

HCG is responsible for maternal–fetal circulation, making it vital for early fetal development. Chromosomal and congenital anomaly risks during pregnancy are often determined using hCG and other biomarkers. Additionally, hCG is involved in preparing the uterine wall for corpus luteum implantation and maintenance.

Adverse pregnancy outcomes including hypertension in pregnancy, small for gestational age (SGA), fetal death in utero (FDIU), gestational diabetes mellitus (GDM), prematurity, and placental abruption have been linked to placental inflammation, poor placentation, and abnormal formation of maternal–fetal vasculature. However, there is little data on how abnormal hCG levels during pregnancy impact other hCG functions.

Investigators conducted a study to evaluate the association between hCG levels in the first and second trimesters of pregnancy and adverse pregnancy outcomes. Data was collected from full-text studies including unselected pregnant women with serum hCG measured between 8- and 28-weeks’ gestation. Results were reported as multiples of the population median (MoMs).

Studies with high-risk pregnancies and multiple fetuses, focusing on pregnant women with a specific medical condition, or solely screening for an obstetric condition were excluded from the analysis. Additional exclusion criteria included being a duplicate, not published in English, not having a comparison group, and being an abstract or case report.

Articles were found through comprehensive searches of the Embase, Medline, Cochrane, and PubMed databases in November 2018 and November 2021. Outcomes included SGA, FDIU, hypertension in pregnancy, GDM, preterm birth, placental abruption, perinatal asphyxia, and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome.

Titles and abstracts, then full texts, were screened by 2 independent reviewers, with a third consulted to resolve disagreements. The Research Electronic Data Capture tool was used to collect and manage demographic and relevant study data.

There were 185 observational studies with 1,648,627 pregnancies included in the analysis. Most participants were women receiving routine prenatal screening, and 80% of studies only included singleton pregnancies.

FDIU was evaluated in 45 studies, SGA in 79, preterm delivery in 62, hypertension in pregnancy in 107, GDM in 29, placental abruption in 17, HELLP syndrome in 2, and perinatal asphyxia in 1. β-hCG was the primary hCG type used to assess the exposure in the first trimester, while hCG type wasn’t specified during the second trimester.

FIDU was assessed in 45 studies, 25 of which reported first-trimester hCG levels and 23 reported second-trimester levels. An association was found between first trimester hCG levels and spontaneous abortion risk, with an odds ratio (OR) of 3.03. For stillbirth, the OR was 1.45. In the second trimester, the OR for spontaneous abortion was 3.06.

SGA was evaluated in 79 studies, 49 of which reported first trimester hCG levels and 34 reported second-trimester levels. Little association was found between first trimester hCG levels and SGA. The strongest evidence with an OR of 1.71 was reported for low hCG levels and a birth weight below the fifth centile.

In the second trimester, hCG with MoM over 2 had an OR of 1.64 for SGA. For hCG with MoM over 3, the OR was 2.05.

Hypertension in pregnancy was evaluated in 107 studies. An association was reported between first trimester hCG and preeclampsia (PE) risk, with an OR of 1.11 for hCG with over 2 MoM and 3.13 for hCG with over 3 MoM. In the second trimester, high hCG had an OR of 2.18 for PE.

Preterm delivery was evaluated in 62 studies, 34 of which reported first trimester hCG and 31 reported second trimester hCG. The OR for spontaneous preterm delivery in the first trimester was 1.76, vs 1.36 in the second trimester.

Low first trimester hCG was also associated with GDM, with an OR of 1.36 for MoM under 0.5 vs an OR of 0.73 for MoM over 2. In the second trimester, these ORs were 1.18 and 1.36, respectively, indicating a greater association with increased hCG.

Placenta abruption was assessed in 17 studies, 9 in the first trimester and 11 in the second trimester. Minimal association was reported in the first trimester, with an OR of 1.12. Similar results were found for second trimester hCG.

These results indicated an association between hCG and pregnancy outcomes. Investigators concluded hCG may play a role in placental dysfunction as well as its established roles in other adverse outcomes.


Peris M, Crompton K, Shepherd DA, Amor DJ. The association between human chorionic gonadotropin and adverse pregnancy outcomes: a systematic review and meta-analysis. American Journal of Obstetircs & Gynecology. 2024;230(2):118-184. doi:10.1016/j.ajog.2023.08.007

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