Maternal and placental responses before preterm birth: adaptations to increase fetal thyroid hormone availability?

Background: During pregnancy, maternal thyroid hormone supply is crucial for fetal development. Preterm infants often present with hypothyroxinemia. Preterm birth, either spontaneous or medically indicated, is always the result of a complicated pregnancy. We hypothesized that in preterm birth, the maternal transplacental thyroid hormone supply is influenced by the pregnancy complication and we questioned whether maternal and placental compensatory mechanisms are activated to increase thyroid hormone transfer. Methods: Observational case-control study in mother-infant-dyads with complicated pregnancies ending in spontaneous preterm birth (n = 31) or indicated preterm birth due to vascular complications (n = 45) and normal pregnancies (healthy term controls; n = 41). At delivery, maternal and cord blood and placenta samples were collected. Cord and maternal plasma concentrations of thyroid stimulating hormone (TSH), total T4, fT4/FTI, total T3, and T4 binding globulin (TBG), and maternal serum concentrations of thyroid peroxidase (TPO)-antibodies were measured. Placental maturity was evaluated histologically and mRNA and/or protein levels of thyroid hormone deiodinases (DiO) 1, 2 and 3, and transporters (MCT8, MCT10, and OATP1c1) were quantified. Results: In indicated and spontaneous preterm births, cord plasma T4 concentrations were lower than in healthy term controls (p <= .001), whereas T3 was only decreased in spontaneous preterm birth (p <= .001). Compared with spontaneous preterm births and healthy term controls, indicated preterm birth was characterized by higher maternal plasma TSH (p <= .05), earlier placental maturation, higher placental DiO2 gene and MCT10 protein levels and lower DiO3 gene levels (all p <= .01). Conclusions: Low T4 was observed in preterm infants irrespective of the cause of preterm birth, while maternal (TSH) and placental (DiO2, DiO3, and MCT10) compensatory responses were only activated in indicated preterm birth due to vascular complications. This may have mediated the normal fetal T3 availability in preterm infants born after indicated preterm birth but not after spontaneous preterm birth.