Somatosensory evoked potentials in very preterm infants in relation to L-thyroxine supplementation. Thyroid Function in Very Preterm Infants: Influences of Gestational Age and Disease Thyroid function in very low birth weight infants: effects on neonatal hypothyroidism screening. A Randomized, Masked Study of Triiodothyronine Plus Thyroxine Administration in Preterm Infants Less Than 28 Weeks of Gestational Age: Hormonal and Clinical Effects Treatment for congenital hypothyroidism: thyroxine alone or thyroxine plus triiodothyronine? Free thyroxine levels during the first weeks of life and neurodevelopmental outcome until the age of 5 years in very preterm infants. Motor nerve conduction velocity in very preterm infants in relation to L-thyroxine supplementation. Tri-iodothyronine treatment in children after cardiac surgery: a double-blind, randomised, placebo-controlled study Evaluation of the effect of thyroxine supplementation on behavioural outcome in very preterm infants. Thyroid function in preterm newborns; is T4 treatment required in infants < 27 weeks' gestational age? Initial treatment dose of L-thyroxine in congenital hypothyroidism. Effects of thyroxine supplementation on neurologic development in infants born at less than 30 weeks' gestation. Results of controlled double-blind study of thyroid replacement in very low-birth-weight premature infants with hypothyroxinemia. The Relation between Neonatal Thyroxine Levels and Neurodevelopmental Outcome at Age 5 and 9 Years in a National Cohort of Very Preterm and/or Very Low Birth Weight Infants Reduction of mortality rate in premature infants by substitution of thyroid hormones Dopamine infusion and hypothyroxinaemia in very low birth weight preterm infants L-Thyroxine Treatment of Preterm Newborns: Clinical and Endocrine Effects Topical iodine-containing antiseptics and subclinical hypothyroidism in preterm infants. Thyroid function in very preterm newborns: possible implications. Postnatal Thyroxine Supplementation in Infants Less Than 32 Weeks' Gestation: Effects on Pulmonary Morbidity The thyroid-system function in preterm infants of postmenstrual ages of 31 weeks or less: evidence for a "transient lazy thyroid system". Neonatal Thyroxine Supplementation in Very Preterm Children: Developmental Outcome Evaluated at Early School Age A longitudinal assessment of thyroid hormone concentrations in preterm infants younger than 30 weeks' gestation during the first 2 weeks of life and their relationship to outcome. Postnatal triiodothyronine replacement and respiratory distress syndrome of the preterm infant.
OBJECTIVE To study the effect of L-thyroxine supplementation on neurologic maturation in very preterm infants with transient hypothyroxinemia . DESIGN R and omized , double-blind , placebo-controlled , L-thyroxine supplementation trial . SETTING Level III neonatal intensive care unit . SUBJECTS A total of 200 infants < 30 weeks ' gestational age . INTERVENTION Subjects were r and omly assigned to receive L-thyroxine ( 8 microg/kg birth weight per day ) or a placebo during the first 6 weeks of life . METHODS Median nerve somatosensory evoked potentials were recorded , measuring cortical N1 peak latency at 2 weeks of age , at term , and at 6 months ( corrected ) age . RESULTS Cortical N1 peak latency was not decreased significantly in the L-thyroxine group compared with the placebo group throughout the study period . CONCLUSION L-Thyroxine supplementation during the first 6 weeks of life did not decrease cortical N1 peak latency in infants of < 30 weeks ' gestational age It is not known how immaturity and disease influence postnatal thyroid function in infants < 30 wk of gestational age . We performed serial measurements of  plasma thyroxine ( T4 ) , free T4 ( FT4 ) , triiodothyronine ( T3 ) , reverse T3 ( rT3 ) , TSH , and T4-binding globulin ( TBG ) in 100 infants of < 30 wk of gestation , during the first 8 postnatal weeks , to investigate the influences of disease and gestational age on the time course of thyroid hormones . One hundred infants were divided twice into two groups : 1 ) in a group of 25 - 28 and of 28 - 30 wk of gestation ; and 2 ) in a sick and a healthy group , with similar gestational ages . The time course of T4 , FT4 , T3 , TSH , and TBG , but not rT3 differed significantly ( p < 0.005 ) between the gestational age groups . T4 and FT4 decreased to levels below the cord blood value with a deeper FT4 nadir on d 7 in the youngest group . Disease decreased T4 , FT4 , T3 , TSH , and TBG concentrations especially during the 1st wk after birth ( p < 0.005 ) . However , the FT4 nadir on d 7 was similar in sick and healthy infants . After 3 wk , T4 , FT4 , T3 , and TBG were higher in the sick group compared with the healthy group . rT3 levels were not increased in sick infants . We conclude that the extent of the FT4 decrease after birth in infants of < 30 wk gestation is mainly influenced by gestational age and probably reflects a transient depletion of thyroidal hormone reserves . rT3 can not be used as a marker of nonthyroidal illness in very preterm infants OBJECTIVES To supply normative data for screening thyroxine ( T4 ) and thyrotropin concentrations correlated with birth weight and age at screening of infants with birth weights ranging from 400 to 5500 gm , and to document the effects of screening of very low birth weight ( VLBW ) infants , because VLBW infants comprise 0.86 % of surviving newborn infants and have very low total T4 concentrations with normal or elevated free T4 concentrations as a result of deficient protein binding of thyroid hormones . STUDY DESIGN Both retrospective and prospect i ve studies were used . We conducted retrospective analyses of screening of T4 and thyrotropin concentrations in 9,324 term , 18,946 low birth weight , and 3,450 VLBW infants in Massachusetts , and a prospect i ve study of T4 and thyrotropin concentrations in 48 VLBW infants at 2 weeks of age . Forty of the infants also had hormone measurements at 4 weeks , 29 at 8 weeks of age , and 24 had analysis of cord blood sample s. RESULTS Median T4 concentrations for each weight group ( in 250 gm increments ) increased progressively and significantly up to 2500 gm . Of the surviving VLBW infants , 1.5 % had screening T4 concentrations that were unmeasurably low ( < 3.9 nmol/L ( 0.3 microgram/dl ) ) . The mean T4 concentration varied with age at screening , increasing from cord blood concentrations to a peak at 1 to 3 days of age and thereafter decreasing to a nadir at about 2 weeks in both low birth weight and VLBW infants . In VLBW infants the mean concentrations return to the level of 1 to 3 days by 4 to 8 weeks of age . The incidence of screening thyrotropin concentrations > or = 40 mU/L correlates inversely with weight . The incidence of early , transient hypothyroidism in VLBW infants defined by this thyrotropin concentration was eight times that in term infants . Two infants had late-onset , transient hypothyroidism at 2 and 7 weeks , respectively . CONCLUSIONS The normative data related to birth weight and age at screening allow proper interpretation of VLBW results for primary T4 and primary thyrotropin screening programs . Screening of the concentrations of T4 and thyrotropin in VLBW increases the number of secondary measurements of T4 in a primary thyrotropin screening program and the number of secondary thyrotropin measurements in a primary T4 screening program by 6 % and 9 % , respectively . We recommend screening analyses for VLBW infants in the latter part of the first week of life and again at 2 and 4 to 6 weeks of age . This protocol would increase the number of screening analyses by 1.6 % A r and omized , placebo-controlled , masked study was conducted of the responses of thyroid parameters , cortisol , and the cardiovascular system to a single dose of triiodothyronine ( T3 ) 24 h after birth , followed by a daily dose of thyroxine ( T4 ) during 6 wk to infants < 28 wk gestational age . Thirty-one infants were assigned to three groups:1 ) group A : T3 24 h after birth plus daily T4 during 6 wk ; 2 ) group B : placebo T3 and T4 during 6 wk ; and 3 ) group C : placebo T3 and placebo T4  . T4 , free T4 , T3 , free T3 , reverse T3 , thyroid-stimulating hormone , and cortisol were measured in cord blood and on days 1 , 3 , 7 , 14 , 21 , 42 , and 56 . Data on pulse rate , blood pressure , and cumulative dose of inotropic agents were collected . T3 ( 0.5 μg/kg ) result ed in a plasma increase until day 3 . Thereafter , plasma T3 levels were comparable between the groups . T4 , free T4 , and reverse T3 were increased in groups A and B during the period of T4 administration . Thyroid-stimulating hormone suppression was of shorter duration in group A. T3 and T4 administration did not have any effect on cortisol levels . We did not find any effects of T3 or of T4 administration on the cardiovascular system . A single injection of T3 ( 0.5 μg/kg ) given 22–26 h after birth only leads to a 2-d increase of T3 levels and does not have effects on the cardiovascular system . This study does not support the use of T3 according to our regimen in preterm infants OBJECTIVE To compare the effects of therapy with thyroxine ( T4 ) plus triiodothyronine ( T3 ) versus T4 alone from the first days of life in screened congenital hypothyroid ( CH ) infants . METHODS We examined 14 CH infants diagnosed by neonatal screening and a group of control infants . CH patients were divided r and omly into 2 groups , 1 treated with T4 alone ( group 1 ) and the other treated with T4 plus T3 ( liothyronine ; group 2 ) . In all patients  electrocardiography and thyroid hormone evaluations  were performed before and 15 and 30 days and 3 , 6 , and 12 months after the beginning of therapy . Psychological tests were also performed at 6 and 12 months of age in CH patients and in other matched controls . RESULTS After 15 days of treatment , serum thyrotropin ( TSH ) levels become normal in 5 of 7 cases of group 1 ( median TSH level 10.7 micro U/ml ) and in 1 of 7 cases of group 2 ( median TSH level 72.5 micro U/ml ) . At the same period , serum-free thyroid hormone levels were within the normal range in both groups , but free T4 values were significantly higher in group 1 than in group 2 and in controls . At the subsequent examinations , free T4 values were within the upper normal limit in group 1 , whereas they remained within the normal range in group 2 . No clinical or electrocardiographic signs of heart disease were found in any of the patients . The psychometric quotient in CH infants was significantly lower than in controls , but similar in patients of group 1 and group 2 . CONCLUSIONS The combined treatment with T4 plus T3 seems not to show significant advantages , at least in our experimental conditions , compared with the traditional treatment with T4 alone in early treated CH infants . A further longer and more extensive follow-up is m and atory BACKGROUND We have conducted a r and omized trial with thyroxine ( T4 ) in 200 infants < 30 weeks ' gestation .  T4 treatment was associated with better 5-year outcome in infants < 29 weeks ' gestation , but with worse outcome in infants of 29 weeks . These effects could be related to low , respectively high free thyroxine ( FT4 ) levels METHODS For each infant , the average FT4 of 5 scheduled measurements was calculated between day 3 and day 28 . Infants of the  placebo and the  T4 group separately were divided in 2 groups . The placebo group consisted of a group of infants with average FT4 in the lowest quartile and a group in the upper 75 % . The T4 group consisted of a group of infants with average FT4 in the upper quartile and a group in the lower 75 % . Developmental outcome ( mental/cognitive , motor , and neurologic ) at 2 and 5.7 years was compared between high and low FT4 groups , and then compared separately for the T4 and placebo group . RESULTS In the placebo group , low FT4 was associated with worse outcome on all domains at both time points . After correction for confounding variables , mental and neurologic outcome remained significantly different at 2 years , and motor outcome at 5 years . In the T4 group , high FT4 was not associated with worse outcome , neither at 2 nor at 5 years . CONCLUSIONS In untreated infants , low FT4 values during the first 4 weeks after birth in infants born at < 30 weeks ' gestation are associated with worse neurodevelopmental outcome at 2 and 5 years . In  T4-treated infants , high FT4 is not associated with worse outcome . Other factors than high FT4 concentrations must play a role in the worse outcome of the T4-treated group of 29 weeks ' gestational age BACKGROUND Transient hypothyroxinemia is common in preterm infants and has been associated with neurodevelopmental dysfunction and slow nerve conduction velocity . It is still unknown whether L-thyroxine supplementation is required . During an L-thyroxine supplementation trial , motor nerve conduction velocity was measured to answer the question whether L-thyroxine supplementation improves motor nerve conduction velocity . METHODS Two hundred infants < 30 weeks ' gestational age were enrolled in a r and omized , double-blind , placebo-controlled L-thyroxine supplementation trial . L-Thyroxine ( 8 micrograms/kg birthweight per day ) or a placebo was administered during the first 6 weeks of life . Motor nerve conduction velocity was measured in the ulnar and posterior tibial nerve shortly after birth , at 2 weeks , at 40 weeks , and at 66 weeks postmenstrual age . RESULTS At 2 weeks , the ulnar motor nerve conduction velocity had improved in the L-thyroxine group compared with the placebo group , although the difference was not statistically significant ( difference between means : 0.8 msec ; 95 % CI : -0.13 to 1.80 ; p = 0.06 ) . Later on , no effect of L-thyroxine supplementation on motor nerve conduction velocity was found . CONCLUSION This study shows that in infants < 30 weeks ' gestational age  L-thyroxine supplementation during the first 6 weeks of life does not clearly improve motor nerve conduction velocity BACKGROUND Serum thyroid hormone concentrations decline transiently during critical illness and after surgical procedures . We investigated prospect ively the endocrine and haemodynamic effects of tri-iodothyronine treatment after cardiopulmonary bypass operations in children with congenital cardiac malformations . METHODS We did a r and omised , double-blind , placebo-controlled trial , in which 40 children ( median age 0.6 years ; range 2 days to 10.4 years ) were r and omly assigned placebo ( saline ) or one daily infusion of tri-iodothyronine ( 2 microg/kg bodyweight on day 1 after surgery and 1 microg/kg bodyweight on subsequent postoperative days up to 12 days after surgery . Before and 2 h , 24 h , and 72 h after the first infusion , plasma concentrations of thyroid hormones were measured by RIA , and systolic cardiac function was evaluated by echocardiography . During the postoperative course intensive-care measures were assessed by use of the therapeutic intervention scoring system . FINDINGS In all patients , postoperative plasma concentrations of thyrotropin , thyroxine , free thyroxine , tri-iodothyronine were abnormally low and plasma concentrations of reverse tri-iodothyronine were raised . After start of treatment , tri-iodothyronine was significantly higher in patients given tri-iodothyronine than in those receiving placebo , whereas thyrotropin , thyroxine , free thyroxine , and reverse tri-iodothyronine remained similar in the two groups . At discharge , thyroid hormones of all patients were within the normal range , but thyrotropin secretion increased to plasma concentrations higher than those seen before treatment . The mean change of cardiac index was significantly higher in children given tri-iodothyronine ( 20.4 % [ SD 19.6 ] vs 10.0 % [ 15.2 ] ; p=0.004 ) . Systolic cardiac function improved most in patients given tri-iodothyronine after longer cardiopulmonary bypass operations . Overall , patients given tri-iodothyronine had significantly lower mean treatment scores . INTERPRETATION Treatment of children with tri-iodothyronine after cardiopulmonary bypass operations raises tri-iodothyronine plasma concentrations and improves myocardial function especially in patients with low postoperative cardiac output without adverse events , and without delaying postoperative recovery of thyroid function . Furthermore , tri-iodothyronine reduces the need for postoperative intensive care Two-hundred infants of < 30 weeks gestational age were included in a r and omized double-blind controlled trial to study the effect of thyroxine administration on  neurodevelopmental outcome in very preterm children . The infants were given either a fixed dose of thyroxine ( 8 microg/kg birthweight/day ) or placebo for the first 6 weeks of life . This paper evaluates the effect of thyroxine administration on behavioural outcome at the age of 2 years . More externalizing , especially destructive , behaviours were found in the group given thyroxine than in the placebo group . This difference was more pronounced in boys and in children born after 27 weeks ' gestation . The thyroxine-treated children with behavioural problems had lower plasma-free thyroxine levels than the thyroxine-treated children without behavioural problems . This finding suggests that the presence of more behavioural problems in the group given thyroxine was not an immediate consequence of the treatment Thyroid hormones are essential for brain maturation . Very preterm infants , who are at risk of neurodevelopmental disabilities also have low T4 and FT4 values in the first weeks after birth . This transient hypothyroxinemia may in part be causal to the neurodevelopmental problems . We have carried out a r and omised , double-blind , placebo-controlled trial with T4 in 200 infants < 30 weeks ' gestation . In the study groups as a whole ( n = 100 in the  T4 group , n = 100 in the Placebo group ) , no clear effect of T4 administration was found . In this study we examined whether gestational age influenced the effect of T4 administration . The T4- and placebo groups were subdivided into 4 groups according to gestational age . FT4-values during the first weeks after birth were lowest in the youngest gestational age group in the T4 as well as in the placebo group . In this group with infants < 27 weeks ' gestation mental developmental outcome at 2 years of age was significantly better than in the placebo group of the same gestational age . There was also a trend towards a better psychomotor and neurological outcome . Beyond 27 weeks ' gestation , no clear effect of T4 could be found ; on the contrary , a possible harmful effect on mental developmental outcome might be the result . In conclusion . T4 treatment possibly improves developmental outcome in infants < 27 weeks ' gestation , but seems not necessary beyond this gestational age OBJECTIVES To determine the optimal initial treatment dose of L-thyroxine in congenital hypothyroidism ( CH ) by evaluating the time course of rise of thyroxine ( T(4 ) ) and free T(4 ) concentrations into an established " target range " and normalization of thyroid-stimulating hormone ( TSH ) and to reevaluate the " target range " for T(4 ) and free T(4 ) concentrations during the first 2 weeks of CH treatment . STUDY DESIGN Infants of birth weight 3 to 4 kg with CH ( n = 47 ) detected by newborn screening were r and omly assigned into three L-thyroxine treatment dose arms : 37.5 microg/day ( group 1 ) ; 62.5 microg/day for 3 days , then 37.5 microg/day ( group 2 ) ; and 50 microg/day ( group 3 ) .  Serum T(4 ) , free T(4 ) , triiodothyronine ( T(3 ) ) , free T(3 ) , and TSH were measured before treatment and at 3 days and 1 , 2 , 4 , 8 , and 12 weeks after treatment . RESULTS T(4 ) and free T(4 ) concentrations increased into the target range ( 10 to 16 microg/dL ) by 3 days of therapy in infants in groups 2 and 3 and by 1 week in group 1 ; 50 microg/day ( average 14.5 microg/kg/day ) provided the most rapid normalization of TSH by 2 weeks . With the use of linear regression analysis of T(4 ) versus TSH or free T(4 ) versus TSH plots , the intercept at the lower range of normal for TSH ( 1.7 mU/L ) showed T(4 ) = 19.5 microg/dL and free T(4 ) = 5.23 ng/dL. CONCLUSIONS Initial dosing of 50 microg/day ( 12 - 17 microg/kg per day ) raised serum T(4 ) and free T(4 ) concentrations to target range by 3 days and normalized TSH by 2 weeks of therapy . We recommend consideration of a somewhat higher " target range " of 10 to 18 microg/dL for T(4 ) and 2 to 5.0 ng/dL for free T(4 ) during the first 2 weeks of L-thyroxine treatment . After 2 weeks of treatment , the target range drops to 10 to 16 microg/dL for T(4 ) and 1.6 to 2.2 for free T(4 ) BACKGROUND Premature infants who have transient hypothyroxinemia in the first weeks of life may have developmental delay and neurologic dysfunction . Whether thyroxine treatment during this period results in improved developmental outcomes is not known . METHODS We carried out a r and omized , placebo-controlled , double-blind trial of thyroxine supplementation in 200 infants born at less than 30 weeks ' gestation .  Thyroxine ( 8 microg per kilogram of birth weight ) or placebo was administered daily , starting 12 to 24 hours after birth , for six weeks . Plasma free thyroxine concentrations were measured weekly for the first eight weeks after birth . Scores on the Bayley Mental and Psychomotor Development Indexes and neurologic function were assessed at 6 , 12 , and 24 months of age ( corrected for prematurity ) . RESULTS Mortality and morbidity up to the time of discharge from the hospital were similar in the study groups . At 24 months of age , 157 infants were evaluated . Overall , neither mental nor psychomotor scores differed significantly between the study groups at any time , nor was the frequency of abnormal neurologic outcome significantly different . In thyroxine-treated infants born at gestational ages of less than 27 weeks , the score on the Bayley Mental Development Index at 24 months of age was 18 points higher than the score for the infants with similar gestational ages at birth in the placebo group ( P=0.01 ) ; for thyroxine-treated infants born at 27 weeks or later , the mental-development score was 10 points lower than that of their counterparts in the placebo group ( P=0.03 ) . There was no relation between the initial plasma free thyroxine concentration and the effect of treatment . CONCLUSIONS In infants born before 30 weeks ' gestation , thyroxine supplementation does not improve the developmental outcome at 24 months The nature of hypothyroxinemia in sick very low-birth-weight ( VLBW ) infants was evaluated by assessment of the hypothalamic-pituitary axis and by the clinical response to thyroxine ( T4 ) therapy .  Twenty-three very low-birth-weight infants of gestational age 26 to 28 weeks , whose serum T4 concentrations were 4 micrograms/dL on two occasions , and thyrotropin less than 20 microU/mL , were included in a double-blind study . Following a thyrotropin-releasing hormone stimulation test , babies were given either T4 or placebo . Nine babies were thyrotropin-releasing hormone tested prior to therapy ; four babies , two from each group , were tested 1 to 2 weeks after therapy . In 11 untreated babies , mean base line serum thyrotropin of 7.0 + /- 1.4 rose to 23.7 + /- 4.1 microU/mL in 30 minutes . This response was not significantly greater than the observed response in full-term babies , 23.7 + /- 4.1 v 16.6 + /- 0.97 microU/mL , respectively , P greater than .05 . In two babies treated with T4 the thyrotropin response to thyrotropin-releasing hormone was completely suppressed . Serial serum T4 determinations showed normalization in both groups after a similar time interval . There was no beneficial effect of T4 therapy on growth of head circumference , length , or weight . Developmental data revealed no significant differences in the mental , motor , or gross neurologic outcome in the treated and nontreated infants after 1 year of follow-up . These observations imply that hypothyroxinemia in sick preterm infants is not a direct consequence of hypothyroidism . Despite the lack of demonstrable short-term beneficial effects of T4 therapy , follow-up studies are necessary to resolve the question of long-term benefits Transient neonatal hypothyroxinemia is very common in preterm infants . The literature on the effect of this hypothyroxinemia is , however , controversial , and large or long-term follow-up studies are not available . In a nationwide prospect i ve follow-up study on very preterm and ( or ) very low birth weight infants ( n = 717 ) , we studied the relationship between thyroxine levels in the 1st wk of life and neurodevelopmental outcome at 5 y of age and school performance at 9 y of age .  Thyroxine concentrations from filter paper eluates were determined in 717 infants : 32 % had levels of more than 3 SD below the mean ( < 60 nmol/L ) . The percentage of infants with such low levels increased with decreasing gestational age . At the age of 5 y , 96 % of survivors(n = 640 ) were available for extensive neurodevelopmental examination : 85 ( 13.3 % ) had a disability and 92 ( 14.3 % ) a h and icap . At the age of 9 y , 83 % of survivors ( n = 552 ) answered a question naire on school performance : 300 ( 54.3 % ) were in mainstream education in a grade appropriate for age , 151 ( 27 % ) were in mainstream education with grade retention , and 101 ( 18.3 % ) were in special education . Both neurologic dysfunction at age 5 y and school failure at age 9 y were significantly related to lower neonatal thyroxine levels even after adjustment for other perinatal factors ( odds ratio , 1.3 ) . Whether this relationship is causal should be investigated . If a causal relationship exists , substitution therapy may at least partially prevent neurologic dysfunction and learning disabilities , both common sequelae of very preterm birth Our previous examinations had shown that 9 of 13 premature infants with severe respiratory distress  had hypothyroid T4-values . On the basis of these results a prospect i ve study was initiated . Every second neonate born after less than 37 weeks gestation or weighing less than 2200 g and admitted to our intensive care unit since Janary 1979 received a prophylactic dose of 25 μg l-Thyroxine and 5 μg Tri-iodothyronine daily . Five of the patients inadvertently did not receive the drug and were included in the non-treated group which thus numbered 55 . Both groups were nearly identical with regard to gestational age , birth weight and Apgar score . In the treated group of 45 infants three ( = 6.6 % ) died . In the untreated group of 55 infants 16 ( = 29 % ) died . The probability that the different mortality in the two groups was due to chance alone is less than 0.5 % ( χ2-test : P<0.005 ) . In 14 of the 55 non-treated patients transient hypothyroidism developed . Five patients with transient hypothyroidism and 2 patients with low T4-values without a TSH-increase were treated with thyroid hormone after ascertainment of their serum thyroxine levels and six survived . The analysis of the prophylactically treated cases showed that the dosage of 25 μg l-Thyroxine and 5 μg Tri-iodothyronine in critically ill infants ( i.e. , those who were mechanically ventilated or had sepsis ) was rarely sufficient to produce normal serum thyroxine levels . In these children thyroxine usually rose to normal levels only when they had passed the acute stage of the disease . It therefore seems advisable to double the dose of thyroid hormone during the acute stage of the disease The purpose of this study was to assess the relationship between transient hypothyroxinaemia of prematurity ( THOP ) in very low birth weight newborns and dopamine administration . A total of 172 newborns was enrolled in a prospect i ve observational study and divided into three groups : group A included newborns who were never treated with dopamine ; group B were infants in whom dopamine treatment was discontinued for at least 6 h before the congenital hypothyroidism screening and group C included infants who were given dopamine during the screening . Among those newborns given dopamine , the THOP incidence was higher ( 11.6 % in group A ; 53.8 % in group B ; 89.3 % in group C ) , and the vales of TSH ( 1.67±2.32 µU/ml in group A ; 1.29±1.74 µU/ml in group B ; 0.89±1.34 µU/ml in group C ) and thyroxine ( 6.1±2.2 µg/dl in group A ; 3.9±1.9 µg/dl in group B ; 2.4±1.4 µg/dl in group C ) were significantly lower . These differences were further confirmed even after gestational age stratification and mathematical correction for differences in clinical conditions . The effects of dopamine appear to be dose-dependant . Conclusion : even if it can not be excluded that reduced thyroid stimulating hormone and thyroxine concentrations are caused by non-thyroidal illness , the results suggest that the infusion of dopamine reduces the thyroid stimulating hormone and thyroxine levels in very low birth weight newborns Preterm newborns have low serum thyroxine ( T4 ) levels compared with late-gestational fetuses . Low thyroid hormone levels are associated with increased severity of neonatal illness and neurodevelopmental dysfunction . We assessed the endocrine and clinical effects of increasing serum T4 levels in preterm newborns with a gestational age < 31 wk . Forty newborns were r and omized in a double blind protocol : 20 infants received a daily dose of 20 μg/kg l-T4 for 2 wk , whereas 20 control infants received saline .  Serum concentrations of T4 , triiodothyronine ( T3 ) , reverse T3 ( rT3 ) , thyroglobulin ( TG ) , and TSH were measured weekly as well as serum levels of GH , prolactin , and IGF-I. After 2 wk , a TSH-releasing hormone ( TRH ) test was performed . Neonatal illness and outcome was evaluated by noting heart rate , oxygen requirement , duration of ventilation , development of chronic lung disease , oral fluid intake , and weight gain ; a Bayley score was done at the corrected age of 7 mo . l-T4 administration induced a marked increase in serum T4 without apparent change in T3 levels , whereas the postnatal decline in serum rT3 was more gradual . l-T4 treatment was associated with a decrease in serum TG and TSH levels . TRH injection induced a definite rise in serum TSH and T3 in controls , but not in L-T4 treated newborns . Neither l-T4 treatment , nor TRH administration appeared to alter circulating levels of prolactin , GH , or IGF-I. In contrast to the pronounced endocrine effects , no clinical effects of l-T4 administration were detected The influence of topical iodine-containing antiseptics on thyroid function test results of premature infants was determined in two separate studies . Thyroxine and thyrotropin levels were measured on blood-spotted filter paper . Sample s were obtained from 128 premature infants on their tenth day of life ; the infants were treated in two neonatal intensive care units . Both units used similar treatment protocol s ; however , one routinely used topical iodinated antiseptic agents ( n = 73 ) , whereas the other used chlorhexidine-containing antiseptics ( n = 55 ) . There was no difference in the mean T4 levels between the two groups . The mean thyrotropin levels were elevated in preterm babies exposed to iodine ( 15.4 vs 7.8 mIU/L , p < 0.01 ) . Among the iodine-exposed infants , elevated thyrotropin levels ( > 30 mIU/L ) were found in 13.7 % of infants , compared with none in the chlorhexidine-treated group ( p < 0.01 ) . We then studied an additional 46 premature infants who were treated in one neonatal intensive care unit .  Iodine-containing solutions were used in 24 infants and chlorhexidine was used in 22 infants . T4 and thyrotropin levels were measured weekly during the first 28 days , one every 2 weeks until the age of 60 days , and at the age of 90 days . Among iodine-exposed infants , 20.8 % had thyrotropin values > 30 mIU/L , whereas none of the infants in the chlorhexidine group had elevated thyrotropin values ( p < 0.05 ) . The elevated thyrotropin levels correlated positively with the area of disinfection . Elevated urine iodine levels were present reflecting an abnormally high iodine absorption . This study suggests that iodine absorption from topical iodine-containing antiseptics may cause disturbances in thyroid function test results in premature infants . We recommend that caution be exercised in the use of iodine-containing antiseptics in premature infants Thyroid hormones are essential for brain maturation . Very preterm infants , who are at risk of neurodevelopmental disabilities also have low thyroxine ( T4 ) and free thyroxine ( FT4 ) values in the first weeks after birth . This transient hypothyroxinemia may in part be causal to the neurodevelopmental problems . We have carried out a r and omized , double-blind , placebo-controlled trial with T4 in 200 infants less than 30 weeks gestation .  T4 ( or placebo ) was given in fixed dose of 8 microg/kg birth weight per day during the first 6 weeks after birth . It result ed in a significant increase of T4 , FT4 , and reverse triiodothyronine ( rT3 ) . Thyrotropin ( TSH ) secretion was suppressed , and , probably as a result of TSH suppression , triodothyronine ( T3 ) levels were decreased in the T4 group . Mortality was 14 % in the T4 group and 21 % in the placebo group ( NS ) . No effect was found on morbidity . Heart rate was significantly higher in T4-treated infants less than 28 weeks gestation , but not in T4-treated infants 28 weeks or more , who had the highest FT4 levels . In the study groups as a whole , no clear effect of T4 administration was found on neurodevelopmental outcome . However , there was a strong trend toward improvement of adverse outcome , defined as death or abnormal developmental outcome at 2 years of age . In addition , mental outcome in a subgroup of T4-treated infants less than 27 weeks ' gestation was significantly better than in placebo infants of the same age group . In conclusion , this trial does not clearly have conclusive results . New trials of thyroid hormone treatment should be carried out in preterm infants , in order to investigate whether indeed T4 supplementation is required in preterm infants less than 27 or 28 weeks gestation . Addition of T3 to the treatment schedule needs to be considered OBJECTIVE : Transient hypothyroxinemia in premature newborns has been linked with poor neonatal outcomes . We design ed this study to evaluate the effects of early thyroxine ( T4 ) administration in the premature infant . STUDY DESIGN : A total of 49 newborns less than 32 weeks ' gestation , were r and omized in a double-blind , placebo-controlled trial . Within the first 48 hours of life , T4 ( 10 or 20 μg/kg ; intravenous or through nasogastric tube , respectively ) was administered for a total of 21 days . Chronic lung disease , the primary outcome variable , was defined by oxygen dependency at 28 days of life . RESULTS : The incidence of chronic lung disease , death , grade III or IV intraventicular hemorrhage , periventicular leukomalacia , and sepsis was not different in the placebo and treated groups . CONCLUSION : Early T4 supplementation in preterm newborns less than 32 weeks ' gestation does not decrease the incidence of chronic lung disease or other complications of prematurity A prospect i ve study was conducted in order to evaluate thyroid function in 20 healthy and 18 sick preterm infants with postmenstrual ages of 31 weeks or less . The clinical condition of both groups was compared using a " Neonatal Special Care Evolution Score " . The effect of thyroid hormone treatment , given from D10 on to the sick infants , was also studied . TSH , thyroid hormone levels ( TG , T4 , T3 , rT3 , FT4 and FT3 ) and TBG were measured by radioimmunoassays at D0 , D10 , D20 , D30 and D40 . Healthy preterm infants on D0 have a median TSH level of 22 microU/ml and a high TG level of 200 ng/ml ; thereafter , median serum levels decrease to 6 microU/ml and 35 ng/ml respectively . During the same period , median serum T4 is maintained at a low level of about 6 - 8 micrograms/dl , median serum T3 gradually increases from 80 ng/dl on D0 to 150 ng/dl on D40 , and median serum rT3 decreases beyond D10 from a plateau of 200 ng/dl to about 100 ng/dl . In the sick preterm infants before treatment , serum TSH is as in the control group but serum T4 , T3 and rT3 on D10 are well below the control values ( P = 0.005 ) . In all conditions , there is a significant correlation between serum T4 and FT4 , and between serum T3 and FT3 .  Thyroxine , given to the sick preterm infants from D10 on , brings median serum T4 values closely to the ones of the control group whereas serum levels of TSH and TG are unaffected and similar to those of the healthy preterm infants . Furthermore , thyroxine brings serum rT3 within the range of the control group but leaves median serum T3 at a low level of about 50 ng/dl . On T3 treatment , serum T3 normalizes but rT3 and particularly T4 tend to decline further . In the conditions of this study a significant difference in TBG level is not proven . Although an untreated sick group was not enrolled in the study , thyroid hormone treatment brought the " Neonatal Special Care Evolution Score " of the treated sick infants closer to that of the healthy preterm infants . In the sick preterm infant with failure to thrive on D10 , there is an impaired thyroid discharge of T4 in spite of serum TSH values not different from those of the control group . ( ABSTRACT TRUNCATED AT 400 WORDS Objective . Transient hypothyroxinemia in very premature infants is associated with developmental problems . A r and omized , placebo-controlled trial of thyroxine ( T4 ) supplementation was conducted in a group of 200 infants < 30 weeks ' gestation .  T4 supplementation improved mental outcome at 2 years old in children of 25/26 weeks ' gestation only . The effect of T4 supplementation beyond 2 years of age is unknown . We present the effects of neonatal T4 supplementation on outcome at early school age . Methods . St and ardized measurements were used to assess cognitive , behavioral , and motor outcome , as well as a qualitative assessment of neurologic functioning .  Survivors of the T4trial were assessed at the age of 5.7 years . Results . Ninety-nine percent of the 157 survivors participated . Outcome on all domains was comparable between the T4 group and placebo group . In children < 27 weeks ' gestation , a 10 IQ point difference was found in favor of the T4 group , whereas in children of 29 weeks ' gestation , a difference of 15 IQ points was found in favor of the placebo group . Teachers ' reports showed less behavioral problems in the T4-treated children of 25/26 weeks ' gestation , but more behavioral problems in the T4-treated children of 27 weeks ' gestation . Differences in motor outcome and neurologic outcome were in favor of the T4-treated children < 29 weeks ' gestation , but not of the T4-treated children of 29 weeks ' gestation . Conclusions . We found benefits of T4supplementation for children < 29 weeks ' gestation , and especially in children of 25/26 weeks ' gestation . However , in children of 29 weeks ' gestation T4 supplementation is associated with more developmental problems OBJECTIVE This trial examined the effects of triiodothyronine ( T3 ) and hydrocortisone on  lung disease .  We present here the placebo data as this provides a natural history of thyroid hormone changes in this group of very preterm infants . We also examined the relationship between thyroid hormone levels and the outcome death and ventilator dependence at 2 weeks . METHODS Plasma-free T3 ( FT3 ) , free thyroxine ( FT4 ) , total T3 , total T4 , and thyroid-stimulating hormone were measured prospect ively in preterm infants who were < 30 weeks ' gestation during the first 14 days of life . The data were obtained from the placebo arm of a multicenter , r and omized , double-blind , clinical trial of T3 and hydrocortisone , called the THORN Trial . RESULTS A total of 128 infants were recruited into the placebo group . The mean FT3 level at < 5 hours of age was 4.9 pmol/L and remained below this level . FT4 levels decreased from 15 pmol/L to 9.7 pmol/L at 7 days and then increased to 11.0 pmol/L by day 14 . Total T3 and total T4 levels fell after 5 hours of age and reached a minimum on day 3 . Thyroid-stimulating hormone levels fell markedly from 9.2 mU/L to 1.8 mU/L at 72 hours and then increased to approximately 4 mU/L. We found that all thyroid hormones but particularly FT3 and FT4 hormones were highly significantly related to outcome . The lower the hormone levels , the worse the outcome ( death or ventilator dependence at 2 weeks of age ) . CONCLUSION 1 ) Thyroid hormone levels in preterm infants < 30 weeks were much lower than in term infants , 2 ) the postnatal surge of thyroid hormones normally seen at 24 to 48 hours of age in term infants did not occur in our group of preterm infant , and 3 ) low FT3 and FT4 levels are associated with higher mortality and severity of lung disease Improvements in the management of respiratory distress syndrome ( RDS ) include pre- and postnatal stimulation of pulmonary maturity , and triiodothyronine ( T3 ) is believed to influence directly surfactant production . Its circulating levels are low in premature infants with RDS probably due to a low thyroxine T4-T3 hepatic conversion mechanism . While a state of hypotriiodothyroninemia exists at birth , we studied the influence of postnatal intravenous T3 administration on the course of RDS in preterm infants of less than 32 weeks ' gestation . Fifty preterm infants with RDS were studied ( mean gestational age 30.4 + /- 1.2 weeks and birth weight 1,180 + /- 220 g ) . They were at r and om assigned to treatment with 50 micrograms L-T3 ( Thyrotardin ) or to the control group .  Mortality rate , peak oxygen concentrations , duration of artificial ventilation and development of major complications of RDS were the criteria to estimate the influence of T3 treatment on RDS . We failed to detect a statistically significant difference between the two groups in all of the mentioned criteria except for FiO2 concentrations required to maintain PaO2 between 50 and 60 mm Hg ( p less than 0.05 ) . These observations suggest a relative beneficial effect of T3 replacement on the course of RDS in preterm infants of less than 32 weeks of gestation
BACKGROUND Extremely premature infants are at risk of transient hypothyroxinaemia in the first weeks after birth .
These low thyroid hormone levels are associated with an increased incidence of neonatal morbidity , mortality and longer term developmental impairments .
Thyroid hormone therapy might prevent these problems .
OBJECTIVES To determine the evidence for thyroid hormone therapy in preterm infants with transient hypothyroxinaemia ( low thyroid hormone level , normal TSH ) for improvement of neonatal outcomes and neurodevelopment .