ABSTRACT
BACKGROUND: Babies born before 28 weeks' gestation have lower plasma thyroid hormone concentrations than more mature infants. This may contribute to their risk of poor developmental outcome. Previous studies have suggested that thyroxine supplementation for extremely preterm neonates may be beneficial. The aim of this study was to investigate the effect of administration of supplemental thyroxine to very premature babies on brain size and somatic growth at 36 weeks' corrected gestational age (CGA). METHODS: In this explanatory multicentre double blind randomised placebo controlled trial, 153 infants born below 28 weeks' gestation were randomised to levothyroxine (LT4) supplementation or placebo until 32 weeks' CGA. The primary outcome was brain size assessed by the width of the subarachnoid space measured by cranial ultrasound at 36 weeks' CGA. Lower leg length was measured by knemometry. RESULTS: Babies in the LT4-supplemented and placebo groups had similar baseline characteristics. There were no significant differences between infants given LT4 (n=78) or placebo (n=75) for width of the subarachnoid space, head circumference at 36 weeks' CGA, body weight at 36 weeks' CGA or mortality. Infants who received LT4 had significantly shorter leg lengths at 36 weeks' CGA although adjusted analysis for baseline length did not find a statistical difference. There was a significant correlation between low FT4 and wider subarachnoid space. No unexpected serious adverse events were noted and incidence of adverse events did not differ between the two groups. CONCLUSION: This is the only randomised controlled trial of thyroxine supplementation targeting extremely premature infants. Supplementing all babies below 28 weeks' gestation with LT4 had no apparent effect on brain size. These results do not support routine supplementation with LT4 for all babies born below 28 weeks' gestation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN89493983EUDRACT number: 2005-003-09939.
Subject(s)
Hormone Replacement Therapy , Infant, Extremely Premature/blood , Thyroxine/therapeutic use , Adult , Brain/drug effects , Brain/growth & development , Cephalometry , Double-Blind Method , Echoencephalography , England , Female , Gestational Age , Hormone Replacement Therapy/adverse effects , Humans , Infant Mortality , Infant, Newborn , Lower Extremity/growth & development , Male , Organ Size , Subarachnoid Space/diagnostic imaging , Thyroxine/adverse effects , Thyroxine/blood , Thyroxine/deficiency , Time Factors , Treatment Outcome , Young AdultABSTRACT
OBJECTIVES: To compare lactate uptake in the microvillous plasma membrane (maternal facing [MVM]) in term and preterm placentas in intrauterine growth restriction (IUGR) and appropriate weight for gestational age (AGA) controls, and in the basal plasma membrane (fetal facing [BM]) at term. In addition, we examine the expression of monocarboxylate transporters (MCT1 and MCT4). METHODS: We measured [14C] L-lactate uptakes into vesicles prepared from MVM and BM, stimulated by an inwardly directed H+ gradient. MCT expression was examined by Western blotting. RESULTS: In term placentas, mean (+/- SE) [14C] L-lactate uptake into MVM vesicles of the IUGR (n = 6) and AGA (n = 11) groups at initial rate was similar (15.4 +/- 2.3 versus 15.0 +/- 1.1 pmol/mg protein/20 s). In preterm placentas, in IUGR (n = 3) and AGA (n = 3) groups, [14C] l-lactate uptake into MVM was also not significantly different. In BM vesicles from term placentas, [14C] L-lactate uptake was significantly lower in IUGR (n = 5) than in AGA (n = 6) controls (3.6 +/- 0.4 versus 5.6 +/- 0.6 pmol/mg protein/20 s, P <.05). MCT1 and MCT4 were expressed in BM vesicles, but there was no difference in expression between the IUGR and AGA groups. CONCLUSIONS: These findings suggest that in IUGR placental lactate transport capacity in the BM is reduced, which may adversely affect placental lactate clearance.
