SAT-229 HCG Alpha Might Supplant TSH during the Fetal Period to Promote Brain Development

Abstract

It is widely agreed that adequate maternal thyroid hormone is necessary for proper brain development. The role of the fetal placenta in ensuring the production and delivery of thyroid hormone during fetal brain development is less well understood. We hypothesized that the placenta ‘hijacks’ the maternal thyroid in early pregnancy to ensure adequate thyroid hormone, and either or both endocrine systems are vulnerable to perturbation by phthalate exposure. We did a pilot study to examine this theory. 50 subjects were recruited in Memphis, TN into the CANDLE birth cohort study, and were were: 68% African-American, 32% White, 50% female babies, mean maternal age of 27.5 years, 28% nulliparous, 50% had greater than a high school education. Blood and urine samples were collected between 17-28 wks gestation. Infant cognition was measured by the Bayley’s Scales at 1 and 3 years of age, and combined into one measure. hCG-alpha, hCG-beta, hyperglycosylated hCG, intact hCG, thyroid stimulating hormone and free thyroxine were analyzed in maternal serum by immunofluorometric assays. Phthalate metabolites were measured in maternal urine by HPLC tandem mass spectrometry. Linear regression models, with quadratic terms, were used to estimate sex-specific associations, and then decomposed to evaluate direct vs. indirect effects of phthalates on infant cognition: phthalates > placental hormone > thyroid hormone > infant cognition. Consistent with previous knowledge, TSH was negatively associated with FT4 (-0.23 pmol/l per log TSH, 95% CI -0.4, -0.1) and both hormones were related to infant cognition, but without statistical significance. hCG-alpha was significantly associated with infant cognition (u-shaped), positively associated with TSH (0.38 log units TSH, 95% CI -0.1, 0.8), negatively associated with FT4 in females (-0.84 pmol/l FT4, 95% CI -1.8, 0.1). Of the phthalates, only mono-n-butyl phthalate (MnBP) was associated with lower hCG-alpha (-0.14 log units, 95% CI -0.3, 0.1), higher FT4 (1.11 pmol/l, 95% CI 0.5, 1.8) in females, and infant cognition to year 3 (-0.11 log units in females, 95% CI -0.2, 0.0). The MnBP indirect effect on cognition, through the hormones, was null. Pilot data were underpowered to generate robust findings, but provided insights: 1) hCG-alpha has a distinct correlation structure, different from the other forms of hCG, in relation to MnBP, thyroid hormone, and infant cognition; 2) these data offer support for the theory that hCG-alpha supplants TSH during this critical period of brain development. Endocrine pathways in pregnancy are related to fetal brain development and vulnerable to phthalate exposure. These types of effects can be studied by the measurement of relevant hormones. Funding was provided by The Department of Epidemiology at the University of Pittsburgh, NIEHS, Vanderbuilt University CTSA, and the Urban Child Institute.