Phase 1 trial of 4 thyroid hormone regimens for transient hypothyroxinemia in neonates of <28 weeks' gestation.
BACKGROUND
Transiently low levels of thyroid hormones occur in approximately 50% of neonates born 24-28 weeks' gestation and are associated with higher rates of cerebral palsy and cognitive impairment. Raising hormone levels shows promise for improving neurodevelopmental outcome.


OBJECTIVE
To identify whether any of 4 thyroid hormone supplementation regimens could raise T(4) and FT(4) without suppressing TSH (biochemical euthyroidism).


METHODS
Eligible subjects had gestational ages between 24 07 and 2767 weeks and were randomized <24 hours of birth to one of six study arms (n = 20-27 per arm): placebo (vehicle: 5% dextrose), potassium iodide (30 microg/kg/d) and continuous or bolus daily infusions of either 4 or 8 microg/kg/d of T(4) for 42 days. T(4) was accompanied by 1 microg/kg/d T(3) during the first 14 postnatal days and infused with 1 mg/mL albumin to prevent adherence to plastic tubing.


RESULTS
FT(4) was elevated in the first 7 days in all hormone-treated subjects; however, only the continuous 8 microg/kg/d treatment arm showed a significant elevation in all treatment epochs (P < .002 versus all other groups). TT(4) remained elevated in the first 7 days in all hormone-treated subjects (P < .05 versus placebo or iodine arms). After 14 days, both 8 microg/kg/d arms as well as the continuous 4 microg/kg/d arm produced a sustained elevation of the mean and median TT(4), >7 microg/dL (90 nM/L; P < .002 versus placebo). The least suppression of THS was achieved in the 4 microg/kg/d T(4) continuous infusion arm. Although not pre-hypothesized, the duration of mechanical ventilation was significantly lower in the continuous 4 microg/kg/d T(4) arm and in the 8 microg/kg/d T(4) bolus arm (P < .05 versus remaining arms). ROP was significantly lower in the combined 4 thyroid hormone treatment arms than in the combined placebo and iodine arms (P < .04). NEC was higher in the combined 8 microg/kg/d arms (P < .05 versus other arms).


CONCLUSIONS
Elevation of TT(4) with only modest suppression of TSH was associated with trends suggesting clinical benefits using a continuous supplement of low-dose thyroid hormone (4 microg/kg/d) for 42 days. Future trials will be needed to assess the long-term neurodevelopmental effects of such supplementation.
La Gamma
Edmund F
EF
Department of Neonatal-Perinatal Medicine, Regional Neonatal Center, Maria Fareri Children's Hospital at Westchester Medical Center, New York Medical College, Valhalla, New York 10595, USA. Edmund_lagamma@nymc.edu
van Wassenaer
Aleid G
AG
Ares
Susana
S
Golombek
Sergio G
SG
Kok
Joke H
JH
Quero
Jose
J
Hong
Ting
T
Rahbar
Mohammad H
MH
de Escobar
Gabriella Morreale
GM
Fisher
Delbert A
DA
Paneth
Nigel
N
D000284:Administration, Oral; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D007262:Infusions, Intravenous; D007455:Iodine / Q000008:administration & dosage; D008297:Male; D015996:Survival Rate; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000008:administration & dosage* / Q000097:blood / Q000172:deficiency*; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000097:blood
D014284:Triiodothyronine; D013972:Thyrotropin; D007455:Iodine; D013974:Thyroxine; D006854:Hydrocortisone