Abstract
Disclosure: J.J. Adibi: None. H. Liang: None. X. Xun: None. K. Carpio: None. A. Layden: None. T.G. O'Connor: None. N.K. Moog: None. H. Koistinen: None. E.S. Barrett: None. Background: Human chorionic gonadotropin (hCG) is a heterodimer placental hormone that is regulated in part by the maternal neuroendocrine-placenta axis and is essential to successful human reproduction. It has utility in maternal-fetal medicine as a predictor of Down's Syndrome, preeclampsia, and growth restriction. Additionally, serum levels of hCGβ are systematically higher in Black vs. White subjects, however the causes of this persistent race different are not understood. Race as a variable is often used as a proxy for social determinants of health, including racism, which are unmeasured. To evaluate this assumption empirically, associations of serum hCG subunits and direct measures of social disadvantage, psychosocial stress, mental health, and discrimination were explored to identify patterns consistent with the race difference. Methods: Intact heterodimeric hCG and its hyperglycosylated form (h-hCG) and free subunits (hCGα and hCGβ) were measured in first and second trimester maternal serum in subjects enrolled in 2 urban cohorts. hCG was normalized for gestational day of blood draw and analyzed as multiples of the median (MoM). Unadjusted and adjusted linear models were fit with and without effect measure modification by race. Findings: The sample (N=451) included 24% Black and 59% White pregnant people. hCGα was lower (-0.35 log ga-MoM units 95% CI -0.45, -0.24) and hCGβ was higher (0.19 log units 95% CI 0.02, 0.36) in Black vs. White participants. We postulated that negative associations with hCGα and positive associations with hCGβ indicate an 'hCG signature' of physiologic and/or psychosocial stressors. Following this pattern, body mass index, weight, and smoking were inversely associated with hCGα, whereas positive associations were observed for maternal age, education, income, and partnered (vs. single) status. Psychosocial stress measures that negatively associated with hCGα were: stressful life events (SLEs), life experience survey (LES) and summary measures of experiences of discrimination (EOD). Psychosocial stress measures that were positively associated with hCGβ were: SLEs and everyday discrimination total score. Eight specific items in the discrimination scale followed the same pattern. Social determinants of health and psychosocial stress were associated widely with hCGα and measures of individual level discrimination were associated with hCGβ. Interpretation: Our results suggest a basis to understand the widely reported race difference in hCG in the context of social determinants of health, and structural and individual level measures of racism. The maternal-placental neuroendocrine axis may be important in generating new ideas and paradigms to screen for and modify social and psychosocial exposures and risks. Presentation: 6/3/2024