Maternal thyroid dysfunction and neonatal cardiac disorders

The normal levels of thyroid hormones (THs; thyroxine, T4 & 3,5,3′-triiodo-L-thyronine, T3) are necessary for the normal development [1-48], particularly the fetal and neonatal cardiac growth and development [49]. The actions of THs are facilitated genomically by thyroid receptors (TRs, α and β) and non-genomically at the plasma membrane, in the cytoplasm and in cellular organelles [4,49-55], by stimulation of Na+, K+, Ca2+ and glucose transport, activation of protein kinase C (PKC), protein kinase A (PKA) and mitogen activated and protein kinase (ERK/MAPK) [4]. In addition, the transport of T4 and T3 in and out of cells is controlled by several classes of transmembrane TH-transporters (THTs) [56], including members of the organic anion transporter family (OATP), L-type amino acid transporters (LATs), Na+/Taurocholate cotransporting polypeptide (NTCP), and monocarboxylate transporters (MCTs) [4,49,57,58]. Adding additional complexity, the metabolism of T4 and T3 is regulated by 3 selenoenzyme iodothyronine deiodinases (Ds: D1, D2 and D3) [59-61]. On the other hand, the congenital hypothyroidism can cause the following [49,62-64], (1) congenital heart diseases; (2) diastolic hypertension; (3) reduced cardiac output, stroke volume and a narrow pulse pressure; (4) dilatation and overt heart failure; (5) elevation in the systemic vascular resistance [65-68]. Similarly, the chronic hyperthyroidism can cause the following [49,64]: (1) cardiac hypertrophy; (2) increase in the cardiomyocyte (CM) length rather than width; (3) noticeable diminution in systemic vascular resistance; (4) elevation in the cardiac contractility; (5) systolic hypertension; (6) increase in the cardiac output, venous volume return, blood volume and pulse pressure; and (7) reduction in the systemic vascular resistance [49,69]. T3-therapy can induce DNA synthesis and cardiomyocyte proliferation, and improve the cardiac contractility; though, this action is as still unidentified [49,70-74]