Human chorionic gonadotropin alpha and beta levels are associated with maternal demographic characteristics and psychosocial measures of stress and discrimination

Human chorionic gonadotropin (hCG) is a heterodimeric hormone regulated in part by the maternal neuroendocrine-placenta axis. Serum levels of the beta subunit (hCGβ) are higher in Black vs. White pregnancies. The underlying causes of the difference remain unclear. The objective of the study was to measure associations of maternal demographic and anthropometric characteristics, and self-reported measures of stress and discrimination with hCG and its subunits in a racially diverse sample. Serum samples were provided by longitudinal birth cohorts in Rochester, NY and in Pittsburgh, PA. Research participants were enrolled in early pregnancy from 2015-2019. Serum hCG levels in the first and second trimesters, measured by immunofluorometric assays (IFMA) as intact hCG, its hyperglycosylated form (h-hCG) and free alpha and beta subunits (hCGα and hCGβ), were normalized for gestational day of blood draw as the multiple of the median (MoM). Minimally adjusted generalized linear models were fit to explore associations of exposures, including maternal demographic characteristics, pregnancy characteristics, perceived stress, depression, stressful life events, experiences of discrimination and everyday discrimination, with serum levels of hCGs. Research subjects (n=451) identified as Black (24%) and White (59%). hCGα was lower (-0.35 log MoM; 95% CI -0.45, -0.24) in Black vs. White participants and intact hCG and hCGβ were higher (0.19 log MoM; 95% CI 0.02, 0.36). Body mass index, weight, gravidity and smoking were negatively associated with hCGα. Maternal age, education, income, and partnered (vs. single) status were positively associated with hCGα. Number of stressful life events and experiences of discrimination were negatively associated with hCGα. Everyday discrimination was positively associated with hCGβ. An hCG-subunit specific pattern of association was described with maternal social and psychosocial experience in early pregnancy. More work is needed to understand these differences and their applicability to interventions to reduce stress and its long-term impacts on maternal and child health. • This is the first report of association of long-term and short-term experience of social and psychosocial stress and serum levels of pregnancy hormone human chorionic gonadotropin (hCG) in the first and second trimesters of pregnancy, in a combined sample of two US urban birth cohorts. • The alpha subunit of hCG, produced by the pituitary and the placenta, was inversely associated with income, education, age, smoking status, stress, and discrimination. • The beta subunit of hCG, produced by the placenta, was positively associated with reports of discrimination. • Results support the efforts to measure maternal environmental and social influences directly to understand and address the effects of stress on maternal and child health.