Study protocol

TIPIT: A randomised controlled trial of thyroxine in preterm infants under 28 weeks gestation: Magnetic Resonance Imaging and Magnetic Resonance Angiography protocol

Sze M Ng¹ , Mark A Turner¹ , Carrol Gamble² , Mohammed Didi³ , Suresh Victor⁴ , Christina Malamateniou⁵ , Laura M Parkes⁶ , Anna Tietze⁸ , Lloyd Gregory⁷ , Vanessa Sluming⁵ , Laurence Abernethy⁸ and Alan M Weindling¹

¹School of Reproductive and Developmental Medicine, University of Liverpool, Liverpool, UK

²Centre for Medical Statistics and Health Evaluation, University of Liverpool, Liverpool, UK

³Department of Endocrinology, Royal Liverpool Children's Hospital, Liverpool, UK

⁴Maternal and Fetal Health Research Group, School of Clinical and Laboratory Sciences, Faculty of Medical and Human Sciences, University of Manchester, UK

⁵School of Health Sciences, University of Liverpool, Liverpool, UK

⁶Magnetic Resonance Imaging and Analysis Research Center (MARIARC), University of Liverpool, Liverpool, UK

⁷Wellcome Trust Clinical Research Facility, Manchester, UK

⁸Department of Radiology, Royal Liverpool Children's Hospital, Liverpool, UK

author email corresponding author email

BMC Pediatrics 2008, 8:26doi:10.1186/1471-2431-8-26

Published:	30 June 2008

Abstract

Background

Infants born at extreme prematurity are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone described as hypothyroxinaemia, which is recognised to be a frequent phenomenon in these infants. Derangements of critical thyroid function during the sensitive window in prematurity when early development occurs, may have a range of long term effects for brain development. Further research in preterm infants using neuroimaging techniques will increase our understanding of the specificity of the effects of hypothyroxinaemia on the developing foetal brain. This is an explanatory double blinded randomised controlled trial which is aimed to assess the effect of thyroid hormone supplementation on brain size, key brain structures, extent of myelination, white matter integrity and vessel morphology, somatic growth and the hypothalamic-pituitary-adrenal axis.

Methods

The study is a multi-centred double blinded randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks corrected gestational age. The primary outcomes will be width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks corrected gestational age. The secondary outcomes will be thyroid hormone concentrations, the hypothalamic pituitary axis status and auxological data between birth and expected date of delivery; thyroid gland volume, brain size, volumes of key brain structures, extent of myelination and brain vessel morphology at expected date of delivery and markers of morbidity which include duration of mechanical ventilation and/or oxygen requirement and chronic lung disease.

Trial registration

Current Controlled Trials ISRCTN89493983