Reduction of mortality rate in premature infants by substitution of thyroid hormones

Schönberger, W; Grimm, W.; Emmrich, P; Gempp, W.

doi:10.1007/bf00442098

Cited by 59 publications

(20 citation statements)

References 37 publications

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“…In addition, T 3 enhances expression of the type I deiodinase gene (27), and T 3 treatment thus could increase endogenous T 3 production. It may, however, be difficult to find an appropriate T 4 /T 3 regimen, because a middle course must be found between a T 3 dose by which maturation is enhanced and morbidity is decreased (33,34), and a T 3 dose that does not increase protein catabolism (35). Treatment with T 3 alone is not advisable, as it will result in lower plasma T 4 concentrations by negative feedback (19), and thus will increase the risk of depletion of cerebral thyroid hormone supply.…”

Section: European Journal Of Endocrinology (1998) 139mentioning

confidence: 99%

Thyroxine administration to infants of less than 30 weeks gestational age decreases plasma tri-iodothyronine concentrations

Wassenaer¹,

Kok²,

Dekker³

et al. 1998

European Journal of Endocrinology

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Objective: To investigate the effect on thyroid hormone metabolism of the administration of thyroxine to very preterm infants. Design and methods: Two hundred infants of less than 30 weeks gestation were enrolled into a randomized, double-blind, placebo-controlled trial. Thyroxine (T 4 ) (at a fixed daily dose of 8 mg/kg birthweight) or placebo was started 12-24 h after birth and discontinued 6 weeks later. Plasma concentrations of T 4 , tri-idothyronine (T 3 ), reverse T 3 (rT 3 ), TSH, and thyroxine-binding globulin were measured weekly during trial medication and 2 weeks thereafter. Results: The T 4 and the placebo group each comprised 100 infants. Antenatal, perinatal, and postnatal clinical characteristics were comparable in both groups. T 4 and rT 3 were significantly increased in the T 4 group. TSH concentrations were depressed in the T 4 group and T 3 was significantly decreased, probably as a result of TSH depression. The T 4 /T 3 and T 4 /rT 3 ratios differed significantly between the two study groups. Conclusions: Daily T 4 administration during the first 6 weeks after birth to infants of less than 30 weeks gestation prevents hypothyroxinemia, but decreases plasma T 3 concentrations. Our finding possibly implies that very preterm infants should receive supplements of both T 4 and T 3 .

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Section: European Journal Of Endocrinology (1998) 139mentioning

confidence: 99%

Thyroxine administration to infants of less than 30 weeks gestational age decreases plasma tri-iodothyronine concentrations

Wassenaer¹,

Kok²,

Dekker³

et al. 1998

European Journal of Endocrinology

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“…In a case control study Eggermont et al treated 10 premature infants with a mean GA of 28.7 weeks with 5 mg/kg/d of T 3 during 6 weeks (29). Scho Ènberger et al (30) studied the effect of the combined treatment with T 4 (25 mg) and T 3 (5 mg) in 45 premature infants in a quasi-randomized manner. Both studies used much higher doses of T 3 , and administered T 3 on a daily basis during a period of time.…”

Section: Discussionmentioning

confidence: 99%

Changes in plasma thyroid hormone levels after a single dose of triiodothyronine in premature infants of less than 30 weeks gestational age

Cools

Wassenaer²,

Kok³

et al. 2000

European Journal of Endocrinology

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Objective: Evaluation of thyroid hormone response to a single administration of triiodothyronine (T 3 ) early postnatally to premature infants of ,30 weeks gestational age. Design: A prospective clinical trial with historical control. Methods: Ten infants born ,28 weeks gestational age and ten infants born between 28 and 30 weeks gestational age were given 0.5 mg/kg T 3 intravenously at 12 h after birth. The infants ,28 weeks gestational age were also treated with thyroxine (T 4 ; 8 mg/kg, once daily) during the first 6 weeks of life. Premature infants from a previous trial served as a matched historical control group. Analysis of variance for repeated measurements was performed. Results: For the infants 28±30 weeks gestational age mean plasma T 3 concentrations were significantly higher in the T 3 -treated group P 0X027 for at least 2 weeks, whereas mean plasma levels of T 4 , free T 4 and TSH were comparable. For the infants ,28 weeks gestational age plasma T 3 levels were also significantly different after correction for gestational age P 0X0002Y with either comparable or higher values in the T 3 -treated infants up to 56 days after injection of T 3 . Mean plasma free T 4 levels were lower during the first 3 days and higher or comparable thereafter P 0X0014Y and TSH suppression was more evident in the T 3 -treated infants P 0X003X Conclusion: A single administration of T 3 to premature infants ,30 weeks gestational age early postnatally results in a sustained increase of plasma T 3 levels during the first weeks of life. In infants of 28±30 weeks gestational age this occurs without change in plasma free T 4 levels, whereas in infants ,28 weeks gestational age a transient decrease of plasma free T 4 was present. The increase in plasma T 3 is possibly caused by a T 3 -induced increase of type I deiodinase activity.

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“…The sample sizes in the subgroups are too small to draw definite conclusions. The only trial to have shown any overall benefit is one in which both T 4 and T 3 were given together (38). In this trial the mortality was reduced from 29% to 6.6%, but the results must be interpreted with caution because the study population included any baby less than 37 wk gestation and only 11% of the treated group and 16% of the untreated group were Ͻ 31 wk.…”

Section: Table 3 Adverse Effectsmentioning

confidence: 95%

Pulmonary Effects of Triiodothyronine (T3) and Hydrocortisone (HC) Supplementation in Preterm Infants less than 30 Weeks Gestation: Results of the THORN Trial—Thyroid Hormone Replacement in Neonates

et al. 2003

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The THORN trial was a multicenter, randomized, doubleblind, placebo-controlled clinical trial to test the hypothesis that administration of triiodothyronine (T 3 ) and hydrocortisone would decrease mortality and respiratory morbidity in preterm infants of less than 30 wk gestation. Two hundred fifty-three infants were randomized to receive either 6 g·kg Ϫ1 ·d Ϫ1 of T 3 with 1 mg·kg Ϫ1 ·d Ϫ1 of hydrocortisone or 5% dextrose (placebo) as a continuous i.v. infusion for 7 d. The dose was halved on d 5. Our first primary outcome was death or ventilator dependence at 1 wk, and the second was death or oxygen dependence at 2 wk. The overall mortality rate for both groups was 11.4%. Relative risk of death or ventilator dependence at 1 wk, treated versus placebo, was 0.87, p ϭ 0.2, and death or oxygen dependence at 2 wk, 1.00, p ϭ 0.9. We examined the relationship between free T 3 (FT 3 ) and free thyroxine (FT 4 ) levels in the first 7 d and the primary outcome death or ventilator dependence at 1 wk in all 253 babies. We found significant positive correlations of p ϭ 0.05 for FT 3 and p ϭ 0.002 for FT 4 . Thus the higher the FT 3 and FT 4 levels, the better the outcome. No beneficial effects of T 3 and hydrocortisone were shown. In this study, although FT 3 levels were doubled by the treatment infusion, FT 4 levels were significantly suppressed. The lack of any beneficial effect of T 3 in our study may be explained by suppression of A number of studies have demonstrated that premature babies have low levels of T 3 and T 4 (1-5) and that hypothyroxinemia has been associated with developmental problems (6 -8) and increased respiratory morbidity (9, 10). Consequently, several studies have examined thyroid hormone substitution in preterm infants, but most of these have involved small numbers of subjects. One large study of T 4 given to babies of less than 30 wk gestation assessed neurodevelopmental outcome and found no overall beneficial effect (11). However mental outcome in a subgroup of T 4 -treated infants less than 27 wk gestation was significantly better than in the placebo infants when tested at 2 y of age. Two studies examining respiratory factors as end points, one giving T 4 (12) and another T 3 (13), have not shown any clear-cut benefit.In spite of improvements in neonatal care during the past few decades (14), most tertiary level neonatal units have seen an increase in the incidence (15) of bronchopulmonary dysplasia (chronic lung disease) defined as an oxygen requirement at the age of 4 wk or beyond 36 wk conceptual age. Much of the increase can be attributed to the increasing survival of very premature babies born before 30 wk gestational age, which in turn raises the question of why these infants develop chronic lung disease when pulmonary surfactants are readily available.

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Reduction of mortality rate in premature infants by substitution of thyroid hormones

Cited by 59 publications

References 37 publications

Thyroxine administration to infants of less than 30 weeks gestational age decreases plasma tri-iodothyronine concentrations

Thyroxine administration to infants of less than 30 weeks gestational age decreases plasma tri-iodothyronine concentrations

Changes in plasma thyroid hormone levels after a single dose of triiodothyronine in premature infants of less than 30 weeks gestational age

Pulmonary Effects of Triiodothyronine (T3) and Hydrocortisone (HC) Supplementation in Preterm Infants less than 30 Weeks Gestation: Results of the THORN Trial—Thyroid Hormone Replacement in Neonates

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