Neurodevelopmental Outcomes at 42 Months After Thyroxine Supplementation in Infants Below 28 Weeks' Gestation: A Randomized Controlled Trial

Ng, Sze May; Turner, Mark A.; Weindling, A M

doi:10.1089/thy.2019.0293

Cited by 18 publications

(19 citation statements)

References 32 publications

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“…Testing at 36 months of age did not find any differences in neurodevelopmental index scores among the eight groups ( Table 2 ). Finally, in a double-blind, randomized, placebo-controlled trial in preterm babies <28 weeks gestation from the United Kingdom, evaluation at 42 months by the Bayley III Mental and Psychomotor Developmental Indices showed statistically better motor, language, and cognitive domains in the group treated with thyroid hormone ( 46 ). In summary, the randomized, placebo-controlled trials show mixed results, with potentially some benefit of T4 treatment in infants <28 weeks but potential harm in infants >28 weeks gestation.…”

Section: Unique Patterns Of Thyroid Dysfunction In Preterm/low Birth Weight Infantsmentioning

confidence: 99%

“…While it is difficult to separate out the effects of co-morbidities from hypothyroxinemia on neurodevelopmental outcome, there are now two randomized, placebo controlled trials in preterm infants <28 weeks gestation that report higher scores in the T4-treated group ( 42 , 46 ). As noted above, there may be some “physiological” support for this finding, as thyroid function in infants born <28 weeks gestation may be too immature to quickly replace the lost maternal thyroid hormone contribution.…”

Section: Conclusion: Unresolved Questions and Areas Of Controversymentioning

confidence: 99%

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Thyroid Function in Preterm/Low Birth Weight Infants: Impact on Diagnosis and Management of Thyroid Dysfunction

LaFranchi

2021

Front. Endocrinol.

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Maternal thyroid hormone crosses the placenta to the fetus beginning in the first trimester, likely playing an important role in fetal development. The fetal thyroid gland begins to produce thyroid hormone in the second trimester, with fetal serum T4 levels gradually rising to term. Full maturation of the hypothalamic-pituitary-thyroid (HPT) axis does not occur until term gestation or the early neonatal period. Postnatal thyroid function in preterm babies is qualitatively similar to term infants, but the TSH surge is reduced, with a corresponding decrease in the rise in T4 and T3 levels. Serum T4 levels are reduced in proportion to the degree of prematurity, representing both loss of the maternal contribution and immaturity of the HPT axis. Other factors, such as neonatal drugs, e.g., dopamine, and non-thyroidal illness syndrome (NTIS) related to co-morbidities contribute to the “hypothyroxinemia of prematurity”. Iodine, both deficiency and excess, may impact thyroid function in infants born preterm. Overall, the incidence of permanent congenital hypothyroidism in preterm infants appears to be similar to term infants. However, in newborn screening (NBS) that employ a total T4-reflex TSH test approach, a higher proportion of preterm babies will have a T4 below the cutoff, associated with a non-elevated TSH level. In NBS programs with a primary TSH test combined with serial testing, there is a relatively high incidence of “delayed TSH elevation” in preterm neonates. On follow-up, the majority of these cases have transient hypothyroidism. Preterm/LBW infants have many clinical manifestations that might be ascribed to hypothyroidism. The question then arises whether the hypothyroxinemia of prematurity, with thyroid function tests compatible with either non-thyroidal illness syndrome or central hypothyroidism, is a physiologic or pathologic process. In particular, does hypothyroxinemia contribute to the neurodevelopmental impairment common to preterm infants? Results from multiple studies are mixed, with some randomized controlled trials in the most preterm infants born <28 weeks gestation appearing to show benefit. This review will summarize fetal and neonatal thyroid physiology, thyroid disorders specific to preterm/LBW infants and their impact on NBS for congenital hypothyroidism, examine treatment studies, and finish with comments on unresolved questions and areas of controversy.

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Section: Unique Patterns Of Thyroid Dysfunction In Preterm/low Birth Weight Infantsmentioning

confidence: 99%

Section: Conclusion: Unresolved Questions and Areas Of Controversymentioning

confidence: 99%

Thyroid Function in Preterm/Low Birth Weight Infants: Impact on Diagnosis and Management of Thyroid Dysfunction

LaFranchi

2021

Front. Endocrinol.

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“…Hormones have numerous physiological impacts on development, so it should be considered whether supplementation of infant feeding regimens with selected hormones might offer benefits to infant nutrition and health. Ng and coworkers recently published a study investigating the effect of early thyroxine supplementation and found that it improves neurodevelopment at age 3–4 years in infants born below 28 weeks’ gestation [ 50 ]. This observation highlights the importance of studies focusing on early supplementation, especially in donor milk-fed or formula-fed preterm infants.…”

Section: Discussionmentioning

confidence: 99%

Breast Milk for Term and Preterm Infants—Own Mother’s Milk or Donor Milk?

et al. 2021

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Hormones are important biological regulators, controlling development and physiological processes throughout life. We investigated pituitary hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and total protein levels during the first 6 months of lactation. Breast milk samples were collected every fourth week of lactation from mothers who gave birth to preterm (n = 14) or term (n = 16) infants. Donor milk is suggested when own mother’s milk is not available; therefore, we collected breast milk samples before and after Holder pasteurization (HoP) from the Breast Milk Collection Center of Pécs, Hungary. Three infant formulas prepared in the Neonatal Intensive Care Unit of the University of Pécs were tested at three different time points. Our aim was to examine the hormone content of own mother’s milk and donor milk. There were no significant changes over time in the concentrations of any hormone. Preterm milk had higher PRL (28.2 ± 2.5 vs. 19.3 ± 2.3 ng/mL) and LH (36.3 ± 8.8 vs. 15.9 ± 4.1 mIU/L) concentrations than term milk during the first 6 months of lactation. Total protein and FSH concentrations did not differ between preterm and term breast milk. Holder pasteurization decreased the PRL concentration (30.4 ± 1.8 vs. 14.4 ± 0.6 ng/mL) and did not affect gonadotropin levels of donor milk. Infant formulas have higher total protein content than breast milk but do not contain detectable levels of pituitary hormones. Differences were detected in the content of pituitary hormones produced for preterm and term infants. Divergence between feeding options offers opportunities for improvement of nutritional guidelines for both hospital and home feeding practices.

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“…were divided into two groups and one group was given thyroxine from the first days, and the control group was not given any treatment. Motor, language, and cognitive functions were found to be significantly higher in Bayley III development tests performed at 42 months in the group that received the thyroxine treatment [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

The factors associated with transient hypothyroxinemia of prematurity

et al. 2021

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Background Hypothyroxinemia is defined by low levels of thyroxine (T4) despite low or normal levels of thyroid-stimulating hormone (TSH). This study aimed to evaluate the factors associated with transient hypothyroxinemia of prematurity (THOP) in newborns admitted to the neonatal intensive care unit (NICU). Method This is a single center, retrospective, case-control study. Premature newborns, between 24 and 34 weeks of gestation, hospitalised between January 2014–December 2019 in Istanbul University-Cerrahpasa Faculty of Medicine NICU were analyzed through their medical records. Thyroid function tests were routinely performed between the 10th and 20th days of postnatal life and were evaluated according to the gestational age references. Thirty six possible associated factors (prenatal and postnatal parameters, medical treatments, clinical diagnoses and applications in NICU) were searched in the patient group with THOP (n = 71) and the control group with euthyroid prematures (n = 73). The factors for THOP were identified by univariate analysis, followed by multivariate analysis. Results Mean gestational ages of the study and the control groups were 29.7 ± 2.48 and 30.5 ± 2.30 weeks, respectively (p = 0.606). The birth weight, small for gestational age (SGA), intraventricular hemorrhage (IVH), congenital heart disease (CHD) were found to be the possible associated factors for THOP in the univariate analysis and CHD (p = 0.007, odds ratio [OR]:4.9, 95% confidence interval [CI]: 1.5–15.8), BW (p = 0.004, OR:0.999, 95% CI: 0.9–1.0) and SGA (p = 0.010, OR:4.6, 95% CI: 1.4–14.7) were found to be factors associated with THOP determined by univariate logistic regression analysis. Conclusıons Although some treatment practices might have had direct effects on pituitary–thyroid axis, related with the severity of the newborn clinical conditions, non of them was found to be a associated factor for THOP. However, CHD and SGA may be considered as associated factors with THOP detected in preterm infants.

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Neurodevelopmental Outcomes at 42 Months After Thyroxine Supplementation in Infants Below 28 Weeks' Gestation: A Randomized Controlled Trial

Cited by 18 publications

References 32 publications

Thyroid Function in Preterm/Low Birth Weight Infants: Impact on Diagnosis and Management of Thyroid Dysfunction

Thyroid Function in Preterm/Low Birth Weight Infants: Impact on Diagnosis and Management of Thyroid Dysfunction

Breast Milk for Term and Preterm Infants—Own Mother’s Milk or Donor Milk?

The factors associated with transient hypothyroxinemia of prematurity

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