Establishment of hormone reference intervals for infants born
b 30 weeks' gestation
Ronda F. Greaves
a,b
, Margaret R. Zacharin
b,c,d
, Susan M. Donath
b,c
, Terrie E. Inder
b,e
,
Lex W. Doyle
b,c,f
, Rodney W. Hunt
b,c,g,
⁎
a
School of Medical Sciences, RMIT University, Victoria, Australia
b
Murdoch Children's Research Institute, Melbourne, Australia
c
Department of Paediatrics, University of Melbourne, Victoria, Australia
d
Department of Endocrinology & Diabetes, The Royal Children's Hospital, Victoria, Australia
e
Dept of Pediatrics, Neurology and Radiology, WA University, St Louis, USA
f
Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Victoria, Australia
g
Department of Newborn Intensive Care, The Royal Children's Hospital, Victoria, Australia
abstract article info
Article history:
Received 21 March 2014
Received in revised form 27 May 2014
Accepted 2 June 2014
Available online xxxx
Keywords:
Prematurity
Cortisol
DHEAS
Thyroxine
Growth hormone
Objective: Preterm infants, especially those born very preterm (b 32 weeks' gestation), suffer a number of
morbidities. Immaturity of the endocrine system and its potential impact on morbidity is the subject of numerous
studies. Hormone concentrations are sometimes measured in very preterm infants, however there are little
normative data available to be able to interpret the results. The aim of this study was to describe age appropriate
hormone reference intervals for babies born less than 30 weeks' gestation.
Study design: Samples were collected at 1, 4, 7, 14, 21, 28 and 42 days after birth from babies born 23–
29 weeks' gestation. The serum was analyzed for seven hormones by automated chemiluminescent immunoas-
say (Siemens Immulite 2000). Results from the 107 infants who survived beyond 40 weeks' corrected gestational
age were included in the data analysis.
Results: Cortisol, dehydroepiandrosterone sulfate, growth hormone and progesterone levels were highest
during the first seven days with levels up to 10,801 nmol/L; 26.6 μmol/L; 343 mU/L; and N 63.6 nmol/L respec-
tively. Free thyroxine levels were as low as b 2.6 pmol/L for the first 28 days with the nadir at 7 days. Estradiol
levels ranged from b 73 to 1626 pmol/L over the six weeks. Reference intervals for IGF-1 could not be established
as the levels were below the analyzer's sensitivity. There were no differences in reference intervals between male
and female infants.
Conclusions: We describe gestation appropriate reference intervals for six hormones measured in babies
born b 30 weeks' gestation. Utilization of these reference intervals permits the correct and timely interpretation
of results to the clinician.
© 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Introduction
Preterm birth, as defined by a gestational age of b 37 weeks at
delivery, currently accounts for 8.3% of all births in Australia [1], which
mirrors other Western countries [2]. In recent decades neonatologists
have invested significant effort to improve outcomes for preterm in-
fants. Advances in mechanical ventilation, the introduction of exoge-
nous surfactant, and the administration of antenatal corticosteroids
have all reduced respiratory mortality in preterm infants [3]. As a result,
survival rates associated with preterm deliveries of babies have now in-
creased from 85% [4] in the mid-1990s to 93% reported in 2012 [1], with
a decrease in fetal deaths with increasing gestational age at birth [1].
This improvement in survival has brought with it associated morbid-
ities in the form of high rates of neurodevelopmental impairment; pre-
dominantly cognitive and motor deficits [5]. The risk of impairments
increases with greater immaturity at birth; with cerebral palsy reported
to be as high as 15% in very preterm infants [6]. Males have an increased
risk of morbidity compared with gestation-matched females [7] and it
has been speculated that derangements in the neuroendocrine system
may play a role [8,9].
It is clear that early delivery removes the fetus from the intrauterine
environment and the influence of maternal hormones [8]. However, the
endocrine system of the preterm infant does not adapt to the extrauter-
ine environment in the same manner as an infant delivered at term [10,
Clinical Biochemistry xxx (2014) xxx–xxx
Abbreviations: CV, coefficient of variation; DHEAS, dehydroepiandrosterone sulfate;
E2, estradiol; fT4, free thyroxine; GH, growth hormone; IGF-I, insulin like growth factor 1.
⁎ Corresponding author at: Department of Neonatal Medicine, The Royal Children's
Hospital, 50 Flemington Rd., Parkville 3052, Australia. Fax: +61 3 9345 5067.
E-mail address: rod.hunt@rch.org.au (R.W. Hunt).
CLB-08776; No. of pages: 8; 4C:
http://dx.doi.org/10.1016/j.clinbiochem.2014.06.002
0009-9120/© 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Contents lists available at ScienceDirect
Clinical Biochemistry
journal homepage: www.elsevier.com/locate/clinbiochem
Please cite this article as: Greaves RF, et al, Establishment of hormone reference intervals for infants born b 30 weeks' gestation, Clin Biochem
(2014), http://dx.doi.org/10.1016/j.clinbiochem.2014.06.002