title: The influence of amino-acid supplementation, gestational age and time on thyroxine levels in premature neonates.
abstract: OBJECTIVE
  Newborn screening laboratories vary in the values that are used to define congenital hypothyroidism. Defining congenital hypothyroidism is particularly complex in premature neonates because prematurely born infants often have a low free thyroxine value and low or normal TSH value, termed as transient hypothyroxinemia of prematurity. In a multicenter (n=11 sites) trial, we randomly allocated premature neonates with a gestational age of 23 to 29 and 6/7 weeks to one of two parenteral nutrition approaches. The primary objective of our trial was to measure the effect of two distinct strategies of parenteral nutrition on neonatal growth and blood amino acids. A protocol defined secondary aim of our clinical trial was the evaluation of the influence of gestational age, time and the degree of amino-acid supplementation on total thyroxine levels. We hypothesized that an increase of amino-acid supplementation would be associated with the normalization of serum amino acids and that this would improve thyroxine synthesis.
  
  
  METHODS
  Premature neonates (23 to 29 and 6/7 weeks) were randomly allocated to one of two approaches to intravenous amino-acid administration. In one group, amino-acid supplementation started at 1.0 g kg(-1) per day and advanced by 0.5 g kg(-1) per day to a maximum of 2.5 g kg(-1) per day (2.5 group). The other group received amino acids at 1.5 g kg(-1) per day and advanced by 1.0 g kg(-1) per day to a maximum of 3.5 g kg(-1) per day (3.5 group). Filter paper blood spots were obtained on the day of randomization, and on days 7 and 28 of age to monitor laboratory values.
  
  
  RESULTS
  Enrollment included 122 neonates, 64 in the 3.5 group and 58 in the 2.5 group. There were no differences in demographics or baseline characteristics between the two treatment groups. There were no significant differences in thyroid levels at baseline, on days 7 and 28 between the two treatment groups. Growth was similar in both groups. It was noted that thyroxine levels changed over time and that the changes with time were greatest in the most preterm neonates.
  
  
  CONCLUSIONS
  The degree of amino-acid supplementation does not influence thyroxine levels and both time from birth and gestational age do influence thyroxine levels.
authors.affiliation: The Pediatrix-Obstetrix Center for Research and Education and Pediatrix Analytical, Sunrise, FL, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Kelleher
authors.forename: R H
authors.initials: RH
authors.lastname: Clark
authors.forename: M
authors.initials: M
authors.lastname: Steinbach
authors.forename: D H
authors.initials: DH
authors.lastname: Chace
authors.forename: A R
authors.initials: AR
authors.lastname: Spitzer
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D006801:Humans; D007037:Hypothyroidism / Q000517:prevention & control*; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000517:prevention & control*; D008297:Male; D010288:Parenteral Nutrition / Q000379:methods*; D013974:Thyroxine / Q000097:blood*; D013997:Time Factors
chemical_list: D000596:Amino Acids; D013974:Thyroxine