Lower neonatal screening thyroxine concentrations in Down syndrome newborns

There is an unexplained higher incidence of congenital hypothyroidism (CH) detected by T-4-based neonatal screening programs and a very high prevalence of (mild) plasma TSH elevation in young children with Down syndrome (DS). To determine whether newborns with DS have decreased blood T-4 concentrations at the time of the neonatal screening, we conducted an observational study in a large and representative cohort of Dutch children with DS born in 1996 and 1997. CH screening results (T-4, TSH, and T-4-binding globulin concentrations) were analyzed in comparison with clinical information obtained by interviewing the parents and data from the general newborn population and a large control group. The mean T-4 concentration of the studied children with DS (n = 284) was significantly decreased. The individual T-4 concentrations were normally (Gaussian) distributed but shifted to lower concentrations. This could not be explained by prematurity, nonthyroidal illness, or iodine exposure. Mean TSH and T-4-binding globulin concentrations were significantly increased and normal, respectively. The decreased T-4 concentration, left-shifted normal distribution, and mildly elevated TSH concentrations point to a mild hypothyroid state in newborns with DS and support the existence of a DS-specific thyroid (regulation) disorder. The question remains whether this contributes to the brain maldevelopment.