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 rst 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 rst 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 dened 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 signicant 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 decits [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 inuence 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) xxxxxx Abbreviations: CV, coefcient 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