Effects of Thyroxine Supplementation on Neurologic Development in Infants Born at Less Than 30 Weeks' Gestation

Wassenaer, Aleid G. van; Kok, Joke H.; Vijlder, J. J. M. De; Briët, Judy M.; Smit, Bert; Tamminga, Pieter; Baar, Anneloes L. van; Dekker, Friedo W.; Vulsma, Thomas

doi:10.1056/nejm199701023360104

Cited by 275 publications

(194 citation statements)

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“…This is progressively replaced by fetal thyroid hormone after midgestation. Neonates with congenital hypothyroidism have detectable levels of T4 in cord blood (30% to 50% of normal values) which is of maternal origin and drops sharply after birth (98). D2 is also present in the decidual membranes, and increases during pregnancy (99), and is a potential source of T3 to the embryo.…”

Section: Deiodinases and Maternal-fetal Physiologymentioning

confidence: 99%

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

Marsili

Zavacki

Harney

et al. 2011

J Endocrinol Invest

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Thyroxine (T4) is a prohormone secreted by the thyroid. T4 has a long half life in circulation and it is tightly regulated to remain constant in a variety of circumstances. However, the availability of iodothyronine selenodeiodinases allow both the initiation or the cessation of thyroid hormone action and can result in surprisingly acute changes in the intracellular concentration of the active hormone T3, in a tissue-specific and chronologically-determined fashion, in spite of the constant circulating levels of the prohormone. This fine-tuning of thyroid hormone signaling is becoming widely appreciated in the context of situations where the rapid modifications in intracellular T3 concentrations are necessary for developmental changes or tissue repair. Given the increasing availability of genetic models of deiodinase deficiency, new insights into the role of these important enzymes are being recognized. In this review, we have incorporated new information regarding the special role played by these enzymes into our current knowledge of thyroid physiology, emphasizing the clinical significance of these new insights.

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Section: Deiodinases and Maternal-fetal Physiologymentioning

confidence: 99%

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

Marsili

Zavacki

Harney

et al. 2011

J Endocrinol Invest

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“…11,[18][19][20] Moreover, most of these trials have focused on clinical, instead of neurodevelopmental, outcomes. [18][19][20] Our trial was aimed primarily at improvement of neurodevelopmental outcome at 2 years of age.…”

Section: Discussionmentioning

confidence: 99%

“…11 Two-hundred infants of 25 to 29 6 ⁄7 weeks' gestation were included in this study before the 24th hour of life between January 1991 and July 1993. Details of the randomization process and study design are described elsewhere.…”

Section: Patientsmentioning

confidence: 99%

“…However, at both ages T4 supplementation was associated with clinically and statistically improved outcomes in the subgroup of infants born at Ͻ28 weeks' gestation, especially in those Ͻ27 weeks' gestation. 11,12 These infants have the lowest concentrations of (free) T4, accompanied by the above-mentioned immature metabolic pathways. On the other hand, T4 supplementation was associated with a worse outcome for infants born at 29 weeks' gestation.…”

mentioning

confidence: 99%

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Ten-Year Follow-up of Children Born at <30 Weeks’ Gestational Age Supplemented With Thyroxine in the Neonatal Period in a Randomized, Controlled Trial

et al. 2005

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ABSTRACT. Background. Thyroid hormones are essential for brain development. We conducted a randomized, controlled trial with thyroxine (T4) supplementation in infants <30 weeks' gestation and with the last neurodevelopmental follow-up moment at the age of 5.5 years. T4 supplementation was associated with improved outcome of infants <28 weeks' gestation and worse outcome of infants of 29 weeks' gestation. We studied gestational age-dependent effects of T4 supplementation at the mean age of 10.5 years in children participating in our randomized, controlled trial.Methods. Questionnaires regarding school outcome, behavior, quality of life, motor problems, and parental stress were sent to the parents and children and their teachers at the same time point for all surviving children (9 -12 years of age).Results. Seventy-two percent of the families responded to our questionnaires. Nonrespondents had more sociodemographic risk factors and worse development until 5.5 years. At the mean age of 10.5 years, T4 supplementation was associated with better school outcome in those who were <27 weeks' gestation and better motor outcome in those who were <28 weeks' gestation, whereas the reverse was true for those who were born at 29 weeks' gestation. No other gestational age-dependent outcomes were found.Conclusions. Gestation-dependent effects of T4 supplementation remain stable over time. These effects do not prove beneficial effects of T4 in infants <28 weeks but should be the background for a new randomized, controlled trial with thyroid hormone in this age group.

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“…35 At age 2 years, T 4 -treated infants born ,27 weeks' gestation scored 18 points higher on a general development examination than those in the placebo group. However, for those in the T 4 -treated group born at 27 weeks' gestation or later, a detrimental effect of the supplementation was found, with the T 4 -treated group scoring 10 points lower than their placebo counterparts.…”

Section: Free Thyroxine Concentrations Over the First 6 Weeks Of Lifementioning

confidence: 93%

Free Thyroxine Levels After Very Preterm Birth and Neurodevelopmental Outcomes at Age 7 Years

2014

PEDIATRICS

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WHAT'S KNOWN ON THIS SUBJECT: Preterm infants have transiently lowered thyroid hormone levels during the early postnatal period. Past research suggests that low thyroid hormone levels are related to cognitive and developmental deficits in children born preterm. WHAT THIS STUDY ADDS:Contrary to expectations, in this study of children born ,30 weeks' gestation, higher concentrations of free thyroxine over the first 6 weeks of life were associated with poorer cognitive function at 7 years of age. abstract BACKGROUND AND OBJECTIVES: Preterm infants commonly have transient hypothyroxinemia of prematurity after birth, which has been associated with deficits in general intellectual functioning, memory, attention, and academic achievement. However, research has predominantly focused on thyroxine levels in the first 2 weeks of life and outcomes are limited to the preschool period. Our objective was to evaluate the relationships between free thyroxine (fT 4 ) levels over the first 6 weeks after very preterm (VPT) birth with cognitive functioning and brain development at age 7 years. METHODS:A total of 83 infants born VPT (,30 weeks' gestation) had fT 4 concentrations measured postnatally and 2-and 6-week area under the curve (AUC) summary measures were calculated. Follow-up at age 7 years included a neuropsychological assessment and brain MRI. Univariable and multivariable regression modeling was used where AUC for fT 4 was the main predictor of neurodevelopmental outcome at age 7 years.RESULTS: Multivariable modeling revealed that higher, not lower, postnatal fT 4 levels (2-week AUC) were associated with poorer cognitive performances at age 7 years on tasks of verbal learning (P = .02), verbal memory (P = .03), and simple reaction time (P , .001). A similar pattern of results was found when the 6-week AUC was examined. No significant associations between postnatal fT 4 levels and brain volumes at age 7 years were identified. CONCLUSIONS:Results are contradictory to previous observations and suggest that after adjustment for confounders, higher postnatal fT 4 levels in VPT infants, rather than lower levels, may be a marker of adverse neuropsychological development in childhood. Pediatrics 2014;133:e955-e963 AUTHORS:

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Effects of Thyroxine Supplementation on Neurologic Development in Infants Born at Less Than 30 Weeks' Gestation

Cited by 275 publications

References 23 publications

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

Ten-Year Follow-up of Children Born at <30 Weeks’ Gestational Age Supplemented With Thyroxine in the Neonatal Period in a Randomized, Controlled Trial

Free Thyroxine Levels After Very Preterm Birth and Neurodevelopmental Outcomes at Age 7 Years

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Effects of Thyroxine Supplementation on Neurologic Development in Infants Born at Less Than 30 Weeks' Gestation

Cited by 275 publications

References 23 publications

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

Ten-Year Follow-up of Children Born at &lt;30 Weeks’ Gestational Age Supplemented With Thyroxine in the Neonatal Period in a Randomized, Controlled Trial

Free Thyroxine Levels After Very Preterm Birth and Neurodevelopmental Outcomes at Age 7 Years

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Ten-Year Follow-up of Children Born at <30 Weeks’ Gestational Age Supplemented With Thyroxine in the Neonatal Period in a Randomized, Controlled Trial