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

<p>Abstract </p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p><b>Trial registration</b></p> <p>Current Controlled Trials ISRCTN89493983</p

Serotonin, genetic variability, behaviour, and psychiatric disorders - a review

Brain monoamines, and serotonin in particular, have repeatedly been shown to be linked to different psychiatric conditions such as depression, anxiety, antisocial behaviour, and dependence. Many studies have implicated genetic variability in the genes encoding monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) in modulating susceptibility to these conditions. Paradoxically, the risk variants of these genes have been shown, in vitro, to increase levels of serotonin, although many of the conditions are associated with decreased levels of serotonin. Furthermore, in adult humans, and monkeys with orthologous genetic polymorphisms, there is no observable correlation between these functional genetic variants and the amount or activity of the corresponding proteins in the brain. These seemingly contradictory data might be explained if the association between serotonin and these behavioural and psychiatric conditions were mainly a consequence of events taking place during foetal and neonatal brain development. In this review we explore, based on recent research, the hypothesis that the dual role of serotonin as a neurotransmitter and a neurotrophic factor has a significant impact on behaviour and risk for neuropsychiatric disorders through altered development of limbic neurocircuitry involved in emotional processing, and development of the serotonergic neurons, during early brain development

The prevalence of insufficient iodine intake in pregnancy in Africa: Protocol for a systematic review and meta-analysis

Background: Insufficient iodine intake in pregnancy is associated with many adverse pregnancy outcomes. About 90% of African countries are at risk of iodine deficiency due to poor soils and dietary goitrogens. Pregnancy predisposes to insufficient iodine nutrition secondary to increased physiological demand and increased renal loss. Iodine deficiency is re-emerging in countries thought to be replete with pregnant women being the most affected. This review seeks to identify the degree of iodine nutrition in pregnancy on the entire African continent before and after the implementation of national iodization programmes. Methods: A systematic search of published literature will be conducted for observational studies that directly determined the prevalence of insufficient iodine intake among pregnant women in Africa. Electronic databases and grey literature will be searched for baseline data before the implementation of population-based iodine supplementation and for follow-up data up to December 2018. Screening of identified articles and data extraction will be conducted independently by two investigators. Risk of bias and methodological quality of the included studies will be assessed using a risk of bias tool. Appropriate meta-analytic techniques will be used to pool prevalence estimates from studies with similar features, overall and by major characteristics including the region of the study, time period (before and after implementation of iodization programmes), sample size and age. Heterogeneity of the estimates across studies will be quantified and publication bias investigated. This protocol is reported according to Preferred Reporting Items for Systematic reviews and Meta-Analysis protocols (PRISMA-P) 2015 guidelines. Discussion This review will help ascertain the impact of national iodization programmes on the iodine nutrition status in pregnancy in Africa and advise policy on the necessity for monitoring and mitigating iodine deficiency in pregnancy in Africa. This review is part of a thesis that will be submitted to the Faculty of Health Sciences, University of Cape Town, for the award of a PhD in Medicine whose protocol has been granted ethics approval (UCT HREC 135/2018). In addition, the results will be published in a peer-reviewed journal