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Serum Thyroid Hormones in Preterm Infants: Associations with Postnatal Illnesses and Drug Usage

Community Health Sciences (F.L.R.W., S.A.O.) and Maternal and Child Health Sciences (R.H.), University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom; and Department of Internal Medicine (H.v.T., T.J.V.), Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Professor Robert Hume, Maternal and Child Health Sciences, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, United Kingdom. E-mail: r.hume{at}dundee.ac.uk.

Context: Transient hypothyroxinemia is common in infants less than 30 wk gestation and is associated with neurodevelopmental deficits. Reductions in T₄ and T₃ levels with TSH unchanged are the key features of severe illness using surrogate indices of overall severity of illness, but these do not inform the impact of individual disease conditions or drug use.

Objective: Our objective was to investigate the contribution of postnatal factors to the variations in serum levels of iodothyronines, thyroid-binding globulin, and TSH.

Design: We recruited a cohort of infants (23–34 wk gestation; n = 780) between January 1998 and September 2001.

Setting and Patients: The study involved 11 level III Scottish neonatal intensive care units and included cohorts of infants delivered at 23–34 wk gestation.

Main Outcome: We assessed serum levels of iodothyronines, thyroid-binding globulin, and TSH at 7, 14, and 28 d adjusted for the potentially significant postnatal influences (n = 31).

Results: Serum levels of TSH, free T₄, T₃, and T₄ are variably but significantly associated with bacteremia, endotracheal bacterial cultures, persistent ductus arteriosus, necrotizing enterocolitis, cerebral ultrasonography changes, oxygen dependence at 28 d, and the use of aminophylline, caffeine, dexamethasone, diamorphine, and dopamine.

Conclusions: There are many more associations of postnatal factors with transient hypothyroxinemia than had previously been considered in preterm infants. Alternative strategies should be considered for correction of hypothyroxinemia rather than sole reliance on the direct therapy of hormone replacement. A more oblique preventative approach may be necessary through reduction in the incidence or severity of individual illness(es). Similarly, alternatives to those drugs that interfere with the hypothalamic-pituitary-thyroid axis should be evaluated (e.g. other inotropics instead of dopamine).