Hormone modeling in preterm neonates: establishment of pituitary and steroid hormone reference intervals

J Clin Endocrinol Metab. 2015 Mar;100(3):1097-103. doi: 10.1210/jc.2014-3681. Epub 2015 Jan 6.


Context: Reports suggest significant differences in serum levels of hormones in extremely preterm compared with late preterm and full-term infants.

Objectives: The purpose of this study was to develop reference intervals (RIs) for 3 pituitary hormones and 5 steroid hormones in serum of preterm infants.

Design: Blood samples were collected from 248 (128 male and 120 female) preterm neonates born between 24 and 32 weeks' gestation.

Setting: PARTICIPANTS were recruited from 3 neonatal intensive care wards in Melbourne, Australia.

Participants: No infant in this cohort had ambiguous genitalia or other endocrine abnormalities. All infants included in the RI determination survived beyond the equivalent of term.

Interventions: Serum was analyzed for prolactin, FSH, and LH by automated electrochemiluminescence immunoassay (Roche Cobas 8000-e601). Liquid chromatography coupled with tandem mass spectrometry was used for analysis of 17-hydroxyprogesterone, androstenedione, cortisol, cortisone, and testosterone.

Main outcome measures: The robust method was applied to define the central 95% RI, after each hormone measure was transformed using a Box-Cox transformation to correct for asymmetry.

Results: RIs were established for 8 hormones. Gender-specific intervals were developed for FSH, LH, and testosterone. Cortisone and 17- hydroxyprogesterone required division based on gestational age, with neonates born at <30 weeks' gestation demonstrating higher levels than their older counterparts. Androstenedione, cortisol, and prolactin did not require any division within this cohort for RI assignment.

Conclusions: This report provides the first characterization of serum steroids measured by mass spectrometry in preterm neonates, with the additional characterization of 3 pituitary hormones in infants born at ≤32 weeks' gestation. Use of these data allows for correct interpretation of results for very preterm neonates and reduces the risk of incorrect diagnosis due to misinterpretation of data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Australia
  • Diagnostic Techniques, Endocrine / standards*
  • Female
  • Gestational Age
  • Gonadal Steroid Hormones / blood*
  • Humans
  • Infant, Low Birth Weight / blood
  • Infant, Newborn
  • Infant, Premature / blood*
  • Infant, Premature, Diseases / blood
  • Infant, Premature, Diseases / diagnosis
  • Male
  • Pituitary Hormones / blood*
  • Reference Values


  • Gonadal Steroid Hormones
  • Pituitary Hormones