Lack of association between hypothyroxinemia of prematurity and transient thyroid abnormalities with adverse long term neurodevelopmental outcome in very low birth weight infants

Tan, Lay Ong; Tan, Mary Grace; Poon, Woei Bing

doi:10.1371/journal.pone.0222018

Cited by 19 publications

(16 citation statements)

References 42 publications

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“…In our study, TT4 concentration was not an important cause of long-term neurodevelopmental impairment. Our findings are consistent with previous research [ 28 , 37 , 38 ].…”

Section: Discussionsupporting

confidence: 94%

Postnatal Serum Total Thyroxine of Very Preterm Infants and Long-Term Neurodevelopmental Outcome

et al. 2021

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Primary congenital hypothyroidism is a disease associated with low serum thyroxine and elevated thyroid-stimulating hormone (TSH) levels. The processes of screening and treating congenital hypothyroidism, in order to prevent neurodevelopmental impairment (NDI) in newborns, have been well investigated. Unlike term infants, very preterm infants (VPIs) may experience low thyroxine with normal TSH levels (<10.0 μIU/mL) during long-stay hospitalization. In the current literature, thyroxine treatment has been evaluated only for TSH-elevated VPIs. However, the long-term impact of low thyroxine levels in certain VPIs with normal TSH levels deserves more research. Since July 2007, VPIs of this study unit received screenings at 1 month postnatal age (PNA) for serum TSH levels and total thyroxine (TT4), in addition to two national TSH screenings scheduled at 3–5 days PNA and at term equivalent age. This study aimed to establish the correlation between postnatal 1-month-old TT4 concentration and long-term NDI at 24 months corrected age among VPIs with serial normal TSH levels. VPIs born in August 2007–July 2016 were enrolled. Perinatal demography, hospitalization morbidities, and thyroid function profiles were analyzed, and we excluded those with congenital anomalies, brain injuries, elevated TSH levels, or a history of thyroxine treatments. In total, 334 VPIs were analyzed and 302 (90.4%) VPIs were followed-up. The postnatal TT4 concentration was not associated with NDI after multivariate adjustment (odd ratios 1.131, 95% confidence interval 0.969–1.32). To attribute the NDI of TSH-normal VPIs to a single postnatal TT4 concentration measurement may require more research.

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“…In our study, TT4 concentration was not an important cause of long-term neurodevelopmental impairment. Our findings are consistent with previous research [ 28 , 37 , 38 ].…”

Section: Discussionsupporting

confidence: 94%

Postnatal Serum Total Thyroxine of Very Preterm Infants and Long-Term Neurodevelopmental Outcome

et al. 2021

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“…However, owing to “confounding variables” common to preterm infants, it is difficult to establish a causal relationship with the hypothyroxinemia alone. In a study of preterm infants <1500 g, a comparison of outcome in infants with and without hypothyroxinemia did not find any significant differences in neurodevelopmental, vision or hearing impairment at 5 years of age ( 40 ).…”

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

confidence: 93%

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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“…Many studies have found adverse effects in the later life of these newborns, such as cerebral palsy and impaired cognitive functions (3,22). On the contrary, other studies did not find any association between THOP and neurodevelopmental outcome (23,24). Scratch and cols.…”

Section: Discussionmentioning

confidence: 99%

Transient hypothyroxinemia of prematurity and its risk factors in an extramural neonatal intensive care unit

Rai¹,

Singh²,

Bhakhri³

2021

Archives of Endocrinology and Metabolism

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Objective: Thyroid functions in preterm newborns may be altered in the first week of life. Hypothyroxinemia has been commonly reported in these babies, which could be due to the immaturity of the hypothalamic pituitary thyroid axis or acute illness. It could have a long-term impact on the developing brain of these babies. We conducted this study to estimate the incidence of transient hypothyroxinemia of prematurity (THOP) and to determine its risk factors. Materials and methods: We analyzed thyroid stimulating hormone (TSH) and free T4 levels of 64 preterm neonates admitted in the neonatal intensive care unit. TSH and free T4 levels were measured in the first week and then at 14-21 days of life to estimate the incidence of THOP and determine its risk factors. We also estimated the incidence of congenital hypothyroidism (CH) and delayed TSH elevation in CH. Risk analysis was conducted using simple and multiple logistic regression, and numerical data was compared using the Mann Whitney U test and t test. Results: THOP was seen in 25% of the preterm babies. Caesarean delivery, presence of one or more morbidities, mechanical ventilation, birth weight ≥ 1,500 g, and gestational age ≥ 32 weeks were identified as risk factors for THOP based on simple logistic regression. In multiple regression, mechanical ventilation and gestational age ≥ 32 weeks were significantly associated with THOP. CH was seen in 2 (3.1%) babies, and 1 of these cases had delayed TSH elevation. Conclusion: Thyroid abnormalities are common in preterm admitted neonates. Mechanical ventilation is an independent risk factor for development of THOP.

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Lack of association between hypothyroxinemia of prematurity and transient thyroid abnormalities with adverse long term neurodevelopmental outcome in very low birth weight infants

Cited by 19 publications

References 42 publications

Postnatal Serum Total Thyroxine of Very Preterm Infants and Long-Term Neurodevelopmental Outcome

Postnatal Serum Total Thyroxine of Very Preterm Infants and Long-Term Neurodevelopmental Outcome

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

Transient hypothyroxinemia of prematurity and its risk factors in an extramural neonatal intensive care unit

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