THYROID-FUNCTION IN VERY-LOW-BIRTH-WEIGHT INFANTS

OBJECTIVES The purpose of this study was to test the hypothesis that l ow circulating thyroxine concentrations characteristic of very low bir th weight (VLBW) neonates (<1500 g) are the result of decreased protei n binding of thyroid hormones and to elucidate the mechanism(s) respon sible and possible significance thereof. DESIGN Cross-sectional compar ison of thyroid related measurements in cord blood specimens from VLBW infants and from full term infants. Longitudinal comparison in cord a nd 2- and 4-week blood specimens from VLBW infants. PATIENTS Cord bloo d specimens were analysed from 47 VLBW and 45 full term infants weighi ng greater than or equal to 2500 g. Repeat analyses in venous bloods f rom 32 of the VLBW infants were analysed at 2 weeks of age and again a t 4 weeks in 23. The first cohort of patients was studied in 1994 and comprised 28 VLBW and 24 full term infants (Cohort A). The studies wer e repeated in 1995-96 in 19 VLBW infants and 21 full term infants (Coh ort B). MEASUREMENTS T4, free T4 (FT4), T3, thyroxine binding globulin (TBG), and TSH were measured in cord blood and 2- and 4-week venous s pecimens from VLBW infants and in cord blood specimens of full term in fants. Molar ratios of T4/TBG were calculated. RESULTS (1) Cord blood TBG, T4 and T3 concentrations of VLBW infants were each 60% of those o f term infants. TBG concentrations were 397 +/- 111 vs 680 +/- 172 nmo l/l (P<0.0005). T4 concentrations were 76 +/- 22 vs 139 +/- 26 nmol/l (P<0.0005). FT4 concentrations were in the normal adult range in both neonatal groups. T4/TBG ratios did not differ between the neonatal gro ups but were significantly less than that of adults (P<0.001). (2) TSH concentrations in VLBW infants at 2 and 4 weeks were less than 50% of cord blood values. At 2 weeks, TBG concentrations of VLBW infants wer e unchanged from cord blood concentrations but mean T4 concentration f ell by 18% and T4/TBG ratios by 21% (P<0.005). Mean FT4 rose by 78% (P <0.02). The changes in mean T4 and FT4 were due largely to FT4 concent rations of 37-113 pmol/l and T4 concentrations of 13-48 nmol/l in 5 in fants. These infants also had lower T4/TBG ratios and were smaller and more ill than the remainder of the cohort. The changes disappeared by 4 weeks in 3 of the 4 infants tested. CONCLUSIONS Cord T4/TBG ratios are the same in very low birth weight and term infants and are signifi cantly lower than in adult blood. These are more than compensated for in term infants by a 236% increase in thyroxine binding globulin conce ntrations. The lower thyroxine binding globulin concentrations in very low birth weight infants explain their much lower T4 concentrations. Cord FT4 concentrations of full term and very row birth weight infants are in the normal adult range. T4 concentrations are further depresse d and free T4 concentrations elevated in the most ill very low birth w eight infants at 2 weeks of age in a manner analogous to that of the ' sick euthyroid syndrome'.