Research expertise gained and pilot studies to inform current programme of research

Ontogeny of human enzyme systems

The role of the deiodinases D1, D2 and D3 and reversible sulfation in the tissue specific and time dependent regulation of thyroid hormone bioactivity during fetal development has been investigated in animals but comparatively little is known about the ontogeny of these enzymes in humans.  We have investigated the ontogeny of iodothyronine deiodinases in human liver and brain, and the sulfotransferases and sulfatases in various developing human tissues.

Human fetal and infant serum thyroid hormone levels and development

Understanding the development of serum thyroid hormone levels in the fetus and infant is a necessary pre-requisite for the successful design of therapeutic interventions.  We have measured cord thyroid hormones (T4, T3, FT4, rT3, T4S), TBG and TSH of almost 1000 infants across the gestational age range 23-42 weeks; and described factors which influence their levels.

Confounders of human fetal and infant serum thyroid hormone levels

Many factors alter serum thyroid hormone levels, TSH and TBG, from withdrawal of the maternal-placental thyroxine transfer, hypothalamic-pituitary-thyroid immaturity, developmental constraints on the synthesis and peripheral metabolism of iodothyronines, iodine deficiency and non-thyroidal illness.  We have measured serum thyroid hormone levels (T4, FT4, T3, rT3 and T4S), TSH and TBG in almost 1000 infants on postnatal days 7, 14 and 28 within the gestational age range 23-36 weeks.  We have linked this dataset to an extensive bank of epidemiological data on these infants.

Neurodevelopmental Follow up of preterm and term infants

The transient hypothyroxinaemia of prematurity has been associated in many studies with adverse neurodevelopmental outcome.  However defining transient transient hypothyroxinaemia is not with out difficulty.  Typically transient hypothyroxinaemia has been characterised by low levels of plasma T4 and T3, but normal levels of TSH.  Clarification of what constitutes transient hypothyroxinaemia is important, so that the association between it and subsequent neurodevelopmental outcome may be elucidated.

Iodine metabolism in extreme preterm infants

The potential reserves of iodine in preterm infants are extremely low and current commercial formula appear, on the basis of balance studies, to be adequate for low birth weight infants.  In contrast, infants who are parenterally fed are at risk of iodine deficiency as the recommended iodine content in infant parenteral nutrition regimens is limited to 1 microgram/kg/day.  The recommended daily enteral intake for preterm infants for iodine is currently 30 microgram/kg/day.