Comparisons between serum concentrations of thyroxine and thyroxine-binding proteins in samples simultaneously obtained from capillary, peripheral vein, central vein and aorta in newborn infants.

A total number of 40 newborn infants with various maturity were studied: 13 babies without perinatal events, 19 infants recovered from transient diseases, 6 infants with idiopathic respiratory distress syndrome and 2 infants with asphyxia indicating artificial ventilation. Comparisons were performed between serum concentrations of thyroxine (T4), thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) in capillary versus peripheral vein, aorta versus central vein and, finally, in peripheral versus central veins. In healthy infants serum T4 concentrations in capillary blood and peripheral vein did not differ significantly. Although serum concentrations of thyroid hormone-binding proteins tended to be increased in aortic compared to central venous specimens no statistically significant differences appeared. In infants in good clinical conditions serum T4, TBG, TBPA, and Alb levels were 6--8% higher in peripheral than in central veins, possibly primarily due to a hemo-concentrating effect of venous stasis. Therefore, in evaluation of the thyroid variables in newborn infants the technique of blood sampling must be considered. In most infants with idiopathic respiratory distress syndrome and in one asphyxiated baby a remarkable tendency to a low serum TBG and T4 concentration in peripheral compared to central vein samples were observed.     

CHANGES IN SERUM CONCENTRATIONS OF THYROID HORMONES AND THYROID HORMONE-BINDING PROTEINS DURING EARLY INFANCY Studies in Healthy Fullterm, Small-for-gestational Age and Preterm Infants Aged 7 to 240 Days

Abstract. Serum concentrations of thyrotropin (TSH), thyroxine (T₄), triiodothyronine (T₃), thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were determined in 492 blood samples from 127 fullterm (FT), 91 small-for-gestational age (SGA) and 88 preterm (PT) healthy infants aged 7 to 240 days. Serum T ₄ decreased about 20% during the first month of life. In infants aged 7–49 days, serum T₄ concentrations were significantly lower in SGA than in FT infants, and even lower values were found in PT infants. Serum T ₃ increased 50–70% reaching maximal values by 50–79 days of life. Serum T₃ levels were higher in FT than in SGA infants throughout the observation period. In PT infants serum T₃ increased from low values to levels which exceeded those of SGA and FT infants by 120–240 days of life. Serum TSH level did not change with age and was 5 mU/1 in all infants. Serum TBG values were high compared to normal adult values and did not change significantly with age. Comparable serum TBG values were found in FT, SGA and PT infants. Serum TBPA increased with age. Serum TBPA increased gradually in FT infants. In SGA infants serum TBPA increased from low values to levels which by 120–240 days of life exceeded those of PT and FT infants. In PT infants a decrease in serum TBPA appeared before the rise commenced. Serum Alb increased gradually in FT, SGA and PT infants during the observation period. Serum Alb in PT infants aged 30–119 days was lower than those in FT infants with similar ages. These physiological changes in serum concentrations of thyroid hormones and hormone-binding proteins during early infancy should be considered when interpreting thyroid function tests in infants with various maturity.     

SERUM CONCENTRATIONS OF THYROXINE-BINDING GLOBULIN, PREALBUMIN AND ALBUMIN IN HEALTHY FULLTERM, SMALL-FOR-GESTATIONAL AGE AND PRETERM NEWBORN INFANTS

Abstract. Jacobsen, B. B., Peitersen, B., Andersen, H. J. and Hummer, L. (The University Clinic of Paediatrics, Children's Hospital Fuglebakken and the Departments of Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark). Serum concentrations of thyroxine-binding globulin, prealbumin and albumin in healthy fullterm, small-for-gestational age and preterm newborn infants. Acta Paediatr Scand, 68: 49, 1979.—Simultaneous serum concentrations of thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were measured in 130 fullterm, 32 small-for-gestational age and 25 preterm infants during their first six days of life. In all infants serum concentrations of TBG were higher and serum TBPA and Alb were lower than in male adults. Even higher serum TBG levels wer found in the mothers. There was no correlation between serum concentrations in paired maternal and cord sera. In infants with birth weights appropriate for gestation serum TBG, TBPA, and Alb concentrations increased progressively with gestational age. In small-for-gestational age infants born at term serum concentrations of TBG and Alb were lower than those in full-term, but higher than those in premature newborns. Serum TBPA in small-for-gestational age babies was evne lower than seen in prematures. A positive correlation was found between thyroid hormones and TBG concentrations, not between serum TBPA and thyroid hormones. The ratios between serum concentration of thyroid hormones and proteins might indicate that more thyroid hormonebinding sites are occupied in fullterm than in low birth-weight newborns. However, the main reason for the different serum levels of thyroid hormones in fullterm, small-for-gestational age and preterm babies is probably the various serum TBG concentrations demonstrated in these infants.     

SERUM CONCENTRATIONS OF THYROTROPIN, THYROID HORMONES AND THYROID HORMONE BINDING PROTEINS DURING ACUTE AND RECOVERY STAGES OF IDIOPATHIC RESPIRATORY DISTRESS SYNDROME

Abstract. A total number of 27 premature infants with idiopathic respiratory distress syndrome (IRDS) and 52 healthy controls with comparable gestational age and body weights were studied during the first month of life. In infants with IRDS a reduced thyrotropin (TSH) response to birth was suggested, as serum TSH was lower in IRDS patients than in controls during the first two days of life. Low serum concentrations of thyroid hormones were found in the acute stage of IRDS reaching minimal values by day 3–5. After that period an increase in thyroid hormone levels occurred. The serum T₃ increased to the level of healthy prematures by day 6–10, whereas the serum T₄ increased to normal levels by day 21–30. Serum concentrations of thyroxine-binding globulin (TBG) were significantly lower in IRDS patients than in healthy controls; a gradual increase to normal levels occurred during recovery. Serum prealbumin (TBPA) levels in IRDS infants increased rapidly after birth and exceeded levels of healthy infants. Serum albumin values were not significantly different in the two groups of infants. The serum T₄/TBG ratios were low during recovery from IRDS.     

Serum concentrations of thyroxine-binding globulin, prealbumin and albumin in healthy fullterm, small-for-gestational age and preterm newborn infants.

Simultaneous serum concentrations of thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were measured in 130 fullterm, 32 small-for-gestational age and 25 preterm infants during their first six days of life. In all infants serum concentrations of TBG were higher and serum TBPA and Alb were lower than in male adults. Even higher serum TBG levels were found in the mothers. There was no correlation between serum concentrations in paired maternal and cord sera. In infants with birth weights appropriate for gestation serum TBG, TBPA, and Alb concentrations increased progressively with gestational age. In small-for-gestational age infants born at term serum concentrations of TBG and Alb were lower than those in fullterm, but higher than those in premature newborns. Serum TBPA in small-for-gestational age babies was even lower than seen in prematures. A positive correlation was found between thyroid hormones and TBG concentrations, not between serum TBPA and thyroid hormones. The ratios between serum concentration of thyroid hormones and proteins might indicate that more thyroid hormonebinding sites are occupied in fullterm than in low birth-weight newborns. However, the main reason for the different serum levels of thyroid hormones in fullterm, small-for-gestational age and preterm babies is probably the various serum TBG concentrations demonstrated in these infants.     

Changes in serum concentrations of thyroid hormones and thyroid hormone-binding proteins during early infancy. Studies in healthy fullterm, small-for-gestational age and preterm infants aged 7 to 240 days.

Serum concentrations of thyrotropin (TSH), thyroxine (T4), triiodothyronine (T3), thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were determined in 492 blood samples from 127 fullterm (FT), 91 small-for-gestational age (SGA) and 88 preterm (PT) healthy infants aged 7 to 240 days. Serum T4 decreased about 20% during the first month of life. In infants aged 7--49 days, serum T4 concentrations were significantly lower in SGA than in FT infants, and even lower values were found in PT infants. Serum T3 increased 50--70% reaching maximal values by 50--79 days of life. Serum T3 levels were higher in FT than in SGA infants throughout the observation period. In PT infants serum T3 increased from low values to levels which exceeded those of SGA and FT infants by 120--240 days of life. Serum TSH level did not change with age and was less than or equal to 5 mU/l in all infants. Serum TBG values were high compared to normal adult values and did not change significantly with age. Comparable serum TBG values were found in FT, SGA and PT infants. Serum TBPA increased with age. Serum TBPA increased gradually in FT infants. In SGA infants serum TBPA increased from low values to levels which by 120--240 days of life exceeded those of PT and FT infants. In PT infants a decrease in serum TBPA appeared before the rise commenced. Serum Alb increased gradually in FT, SGA and PT infants during the observation period. Serum Alb in PT infants aged 30--119 days was lower than those in FT infants with similar ages. These physiological changes in serum concentrations of thyroid hormones and hormone-binding proteins during early infancy should be considered when interpreting thyroid function tests in infants with various maturity.     

TRI-IODOTHYRONINE AND THYROXINE IN HUMAN MILK

ABSTRACT. The concentration of tri-iodothyronine (T₃) and thyroxine (T₄) in human milk was determined by radioimmunoassay (RIA). The analysis of T₃ was performed on unextracted milk and on ethanol extracts of defatted milk. Analysis of unextracted milk was complicated by artifacts. Reliable and reproducible results were achieved only with the milk extracts. In 10 colostral milk samples the mean T₃ levels ± SD were 0.80 ± 0.52 nmol/l before feeding (early milk) and 0.93 ± 0.62 after feeding (hind milk). The T₃ concentration in colostrum did not change significantly during the feeding to the infant. In 12 mature milk samples collected between infant feedings, the mean T₃± SD was 1.19 ± 0.42 nmol/l. T₄ was not detected in any of the samples analysed (detection limit 3 nmol/l).     

High and low dose initial thyroxine therapy for congenital hypothyroidism

Objective : To assess factors influencing thyroxine (T₄ levels 1 month after initiating replacement therapy for congenital primary hypothyroidism.
Methodology : A retrospective review of 41 children with congenital hypothyroidism who received either high or low dose initial T₄ therapy. Thyroid scintiscan was performed, and T₄ levels determined before starting treatment and after 1 month.
Results : T₄ levels at 1 month were correlated ( r ²=0.38, P <0.001) with the pretreatment T₄ level ( r = 0.48), as well as with the T₄ dose ( r = 0.46). Suboptimal treated T₄ levels (<130nmol/L) were seen with greater frequency in infants with thyroid agenesis (7/11) rather than ectopia (7/28, P <0.03), despite receiving similar doses of thyroxine. Infants with suboptimal treated T₄ levels had lower pretreatment T₄ levels than those with optimal levels (21±7 vs 48±34nmol/L, P <0.02). Biochemical hyperthyroidism (T₄ >216nmol/L) occurred in six patients: four of six had ectopia.
Conclusions : These data suggest that infants with little residual thyroid function should receive higher initial T₄ doses than those with significant ectopia.     

Serum concentrations of thyrotropin, thyroid hormones and thyroid hormone-binding proteins during acute and recovery stages of idiopathic respiratory distress syndrome.

A total number of 27 premature infants with idiopathic respiratory distress syndrome (IRDS) and 52 healthy controls with comparable gestational age and body weights were studied during the first month of life. In infants with IRDS a reduced thyrotropin (TSH) response to birth was suggested, as serum TSH was lower in IRDS patients than in controls during the first two days of life. Low serum concentrations of thyroid hormones were found in the acute stage of IRDS reaching minimal values by day 3--5. After that period an increase in thyroid hormone levels occurred. The serum T2 increased to the level of healthy prematures by day 6--10, whereas the serum T4 increased to normal levels by day 21--30. Serum concentrations of thyroxine-binding globulin (TBG) were significantly lower in IRDS patients than in healthy controls; a gradual increase to normal levels occurred during recovery. Serum prealbumin (TBPA) levels in IRDS infants increased rapidly after birth and exceeded levels of healthy infants. Serum albumin values were not significantly different in the two groups of infants. The serum T4/TBG ratios were low during recovery from IRDS.     

SEASONAL VARIATION IN SERUM-25-OH-D3 IN MOTHERS AND NEWBORN INFANTS IN NORTHERN FINLAND

ABSTRACT. Two groups, each consisting of twenty Finnish mother-neonate pairs and ten non-pregnant controls were studied for serum calcium, serum phosphate, serum alkaline phosphatase, parathormone index (PTH_ind) and S-25-OH-D₃. The first series was collected in winter and the other in summer. The serum samples were taken on the third day after delivery. The concentrations of S-25-OH-D₃ were significantly lower in the mothers than in the non-pregnant controls in winter, but the difference was not significant in summer. The concentrations of S-25-OH-D₃ in the serum of the mothers were similarly significantly lower in winter than in summer, ten mothers exhibiting a value below the detection line in winter, but only two in summer. The concentrations of S-25-OH-D₃ in the mothers and their newborn infants showed a close relationship, but when extremely low values existed in the mothers, the infant concentrations were slightly higher. The seasonal variation in S-25-OH-D₃ was also significant in the neonates. Although calcium was decreased and alkaline phosphatase elevated when compared with the non-pregnant controls in the mothers in both groups, these values showed no seasonal variation, and the mean levels of serum calcium, phosphate, alkaline phosphatase and PTH_ind in the neonates also remained unaltered between the two groups. The results indicate that additional vitamin D should be supplied during pregnancy in the winter months at this latitude.     

Thyroid gland volume as measured by ultrasonography in preterm infants

The volume of the thyroid gland was determined by ultrasonography in 30 preterm infants (27-36 weeks' gestation) born in Madrid. Thyroid gland volume significantly increased (p < 0.01) with postnatal and postmenstrual age and was very well correlated with body weight, height and surface area (p < 0.01). Serum thyroid hormones 3,5,3'-triiodothyronine (T₃) and free thyroxine (FT₄) were linearly correlated with postnatal and postmenstrual age, thus T₃ and FT₄ levels were also correlated with thyroid gland volume (p < 0.05). We report measurements of the thyroid gland volume obtained by ultrasonography in this group of preterm infants. Quantitative determination of thyroid gland volume is more accurate for the diagnosis of goitre than clinical criteria. It is also interesting to determine the thyroid gland volume in the neonatal period when the thyroid is particularly hypersensitive to the effects of iodine deficiency and excess.     

Fetal hypopituitarism: perinatal endocrine and morphological studies in two cases

We report two infants with congenital absence of the anterior pituitary gland, documented by magnetic resonance imaging (MRI) or autopsy. In cord plasma obtained at birth from both infants, prolactin (PRL), pituitary growth hormone (hGH), placental growth hormone (hPGH) and thyrotropin (TSH) were undetectable; cortisol was low; thyroxine (T₄) was 31 nmol/l in one infant and 85 nmol/l in the other infant who had been treated prenatally with intra-amniotic L-T₄ administration. In maternal plasma at birth, PRL, hPGH and T₄ were normal and hGH was undetectable. These observations suggest that plasma hGH and PRL in the fetus are exclusively of fetal pituitary origin, hPGH is secreted into the maternal circulation and is not transferred to the fetus and fetal growth can be normal in the absence of hGH, hPGH and PRL in fetal plasma.     

Subclinical Thyroid Hormone Abnormalities in Type I Diabetic Children and Adolescents. Relationship to Metabolic Control

ABSTRACT. The serum levels of thyroid hormones and thyroid stimulating hormone were compared in 64 type I diabetic children and adolescents without ketosis and in 28 age matched normal subjects. Only T₃ levels were significantly different in the diabetic patients (2.38±0.41 nmol/1) than in controls (2.64±0.52 nmol/1) (p<0.01) confirming the existence of the'low T₃ syndrome'in diabetic children. A negative correlation was found between T₃ and blood glucose as well as glycosylated haemoglobin suggesting that short-term hyperglycaemia could regulate T₃ concentration. Thyroid function was not different in diabetic children with or without thyroid antibodies. We conclude that serum T₃, level is influenced by the degree of metabolic control and that thyroid function in diabetic children should be assessed by the measurement of the serum concentration of T₄, FT₄ and TSH.     

COMPARISON BETWEEN TWO PREPARATIONS OF HUMAN SERUM ALBUMIN IN TREATMENT OF NEONATAL HYPERBILIRUBINAEMIA

ABSTRACT. Thirty-six newborn infants with normal birth weights and with uncomplicated hyperbilirubinaemia, treated with light, were studied. At onset of phototherapy the infants received intravenously 1 g human serum albumin (HSA) per kg body weight as a 9 % solution. Two different preparations of HSA were used and compared. One of these, HSA_I, contained sodium caprylate and N-acetyltryptophan, 5 mmol/1 of each, as stabilizers. HSA_II contained only caprylate, 5 mmol/1. Nineteen infants received HSA_I and seventeen infants HSA_II. The reserve albumin for binding of bilirubin, measured by the [¹⁴C] MADDS method, was low in both preparations in vitro. During the infusion, the serum concentrations of albumin and reserve albumin increased and the serum unconjugated bilirubin concentration decreased, resulting in a fall in the index of plasma bilirubin toxicity in all infants. After completion of the infusion, the serum concentrations of albumin and reserve albumin declined, and a slight rise in index occurred. The increase in the serum reserve albumin concentration was markedly higher during infusion of HSA_II than of HSA_I. It is concluded that infusion of both HSA preparations during phototherapy provides an immediate protection against bilirubin encephalopathy. HSA_I is inferior to HSA_II, probably due to its content of N-acetyltryptophan.     

THYROXINE-BINDING GLOBULIN DEFICIENCY IN EARLY CHILDHOOD

ABSTRACT. Jacobsen, B. B., Hansted, L. C, Brandt, N. J., Haahr, J., Hummer, L., Munkner, T. and Sorensen, S. S. (Department of Paediatrics, Viborg Hospital, Children's Hospital Fuglebakken, Department of Paediatrics, Section of Clinical Genetics and Department of Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark). Thyroxine-binding globulin deficiency in early childhood. Postnatal changes in serum concentrations of thyroid hormones and thyroid hormone-binding proteins. Acta Paediatr Scand, 70:155, 1981. –Serial determinations of serum thyroxine (T4), triiodothyronine (T3), thyrotropin(TSH), thyroid hormone-binding globulin (TBG), prealbumin (TBPA) and albumin were performed in a euthyroid girl with TBG deficiency and in her mother for a period of 22 months after delivery. At 8 days old the child had a serum TBG concentration around 50% of normal level which remained essentially unchanged during infancy. Total serum T4 and T3 concentrations were low, the free serum T4, free serum T3 and serum TSH concentrations were normal. The mother had received thyroid hormone from the age of 15 years. Her serum TBG level at 6 weeks post partum was similar to that of non-pregnant adults but decreased to about 50% of normal level, indicating a TBG deficiency. She remained euthyroid after withdrawal of T4 therapy. Serum TBPA and albumin concentrations were normal in mother and child. An X-linked inheritance of the TBG deficiency was suggested from a study of the family.     

TOTAL PARENTERAL NUTRITION IN INFANTS Blood Levels of Glucose, Lactate, Pyruvate, Free Fatty Acids, Glycerol, D-β-Hydroxybutyrate, Triglycerides, Free Amino Acids and Insulin

Abstract. Two regimens (A and B) for TPN were designed to meet the requirements of newborn infants for calories, amino acids, fatty acids, electrolytes, trace elements and vitamins. Both "A" and "B" included fat emulsion (Intralipid®). "A" contained fructose and glucose, "B" glucose only. "A" provided amino acids (Vamin®) in proportions similar to those of whole egg, "B" similar to those of human milk. All nutrients were given simultaneously into peripheral veins by constant infusion. Nineteen patients (11 newborns, 8 infants) were studied for 1–28 days. Twelve infants recovered, 7 died. In none could TPN be regarded as the cause of death. Treatment was complicated by sepsis in 5 infants. During the course of treatment, blood levels of substrates and insulin were measured before, during and 30 min after discontinuation of TPN. Highly raised concentrations of circulating substrates seen in 3 infants seemed to be related to a poor clinical condition rather than to the regimen used. Infants in good condition tolerated TPN well. Low levels of branch-chained amino acids and tendency to ketonemia, when infusion was stopped, suggested that minimal rather than optimal supply of energy and of amino acids in relation to energy was provided with both regimens. Low insulin levels associated with elevated blood levels of substrates suggested that insulin administration to selected cases might be indicated. Fructose (0.30 g/kg × hour^-1) given with regimen A increased blood lactate concentrations. Homocystinaemia appeared in 2 cases; disappearance after excess vitamin B₆ administration indicated increased B₆ requirement.     

Thyroid function in thalassaemia major.

Serum concentrations of T4, T3, rT3, and TSH were measured by radioimmunoassay in 45 patients suffering from beta-thalassaemia. A TRH stimulation test was performed and the binding capacity of TBG and TBPA for T3 and T4 measured by reverse flow zone electrophoresis in a group of these patients. Mean T4 serum concentration was lower in thalassaemic patients than controls; T3, rT3, TSH levels, and the pituitary response to TRH were normal. TBPA binding capacity for thyroxine was greatly decreased, probably due to iron overload impairing the liver function. The decreased circulating total thyroxine might be explained by the reduced TBPA capacity, serum free thyroid hormone concentration total thyroxine might be explained by the reduced TBPA capacity, serum free thyroid hormone concentration values being normal. It is concluded that thalassaemic children are euthyroid, despite often having low-normal or subnormal thyroxine levels.     

PITUITARY-THYROID RESPONSIVENESS TO THYROTROPIN-RELEASING HORMONE IN PRETERM AND SMALL-FOR-GESTATIONAL AGE NEWBORNS

Abstract. A dose of 40 μg TRH was injected intravenously in 12 preterm (PT) and 15 small-for-gestational age (SGA) babies (with advanced gestational ages) between 5 and 167 hours after birth. Serum-thyrotropin (TSH) was measured prior to and 30 and 180 min after TRH; serum-thyroxine (T₄) and serum-triiodothyronine (T₃) were measured prior to and 180 min after TRH. The percentage increase in serum-TSH in PT and SGA babies was comparable to that of fullterm newborns. The serum-TSH 30 min after TRH in SGA newborns was significantly correlated to basal TSH values, such a correlation could not be shown in the preterms. One SGA and four PT babies had a repeat TRH-test performed later in infancy: In all but one PT with a gestational age of 27 weeks the TSH rise was lower than in the neonatal period. The thyroid hormone responses after TRH were similar in the two groups of babies. The percentage increase above basal levels were: Median serum-T₃ increase about 46% and median serum-T₄ increase about 14%. It is concluded that in low-birth-weight newborn babies the pituitary TSH response to exogenous TRH was like that detected in fullterm newborns and more pronounced than later in infancy. The effect of endogenous TSH as measured by thyroid hormone increases was of the same magnitude as observed in fullterms and in adults.     

Syndrome of Generalized (Peripheral Tissue and Pituitary) Resistance to Thyroid Hormone

Generalized resistance to thyroid hormone (GRTH), or Refetoff syndrome, is a disease in which peripheral tissues show resistance to thyroid hormone. Three patients with this disease were investigated. Cases 1 and 2 involved identical 7-year-old female twins and case 3, a 5-year-old girl. All three patients had goiters, and cases 1 and 2 had sensorineural deafness. In all three, the blood levels of T₄, free T₄, and T₃ were high, while the blood levels of TSH were normal or slightly elevated. The responses shown by blood levels of the thyroid hormone and TSH to administration of propylthiouracil and T₃ suggest that the regulating mechanism in the hypothalamic-pituitary-thyroid system was functional. Upon administration of T₃, no sign of hyperthyroidism was observed.     

SCREENING FOR CONGENITAL HYPOTHYROIDISM

ABSTRACT. Larsson, A., Ljunggren, J. G., Ekman, K., Nilsson, A. and Olin, P. (Departments of Paediatrics and Child Psychiatry, Karolinska Institute, St. Goran's Children's Hospital; the Department of Medicine, St. Göran's Hospital; and the PKU Section of the Department of Bacteriology, National Bacteriological Laboratory, Stockholm, Sweden). Screening for congenital hypothyroidism. I. Laboratory results of a pilot study based on dried blood samples collected for PKU screening. Acta Paediatr Scand, 70:141, 1981. – A pilot study was performed to establish optimal conditions for nation-wide screening for congenital hypothyroidism in Sweden. The levels of T₄ and TSH were determined by automated radioimmunoassay in the dried blood spots, routinely collected for PKU screening on the fifth postnatal day, from all 1979, 2 infants born in the Stockholm area during a 14-month period. To identify safe minimum recall criteria for routine use, infants were recalled if the TSH level was more than 30 mU/l of plasma or–if they were not preterm–the T₄ concentration was less than -2 S.D. of the mean. Altogether 160 infants were recalled. Seven newborns with congenital hypothyroidism were identified, 6 with primary and one with secondary hypothyroidism. Five infants had decreased levels of thyroxine-binding globulin. The results of the follow-up analyses from recalled infants showed that determination of the reverse-T₃ level may be of diagnostic value around the 23rd day of life. The results of the clinical investigation of recalled infants are reported in a subsequent paper and a programme for nation-wide screening for congenital hypothyroidism is proposed.