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Hormone modeling in preterm neonates: establishment of pituitary and steroid hormone reference intervals
Ronda F Greaves1, Janne Pitkin, Chung Shun Ho
1School of Medical Sciences (R.F.G.) and School of Mathematical and Geospatial Sciences (J.B.), RMIT University, Victoria 3000, Australia; Murdoch Children's Research Institute (R.F.G., J.P., R.W.H., M.R.Z.), Melbourne, Victoria 3052, Australia; Prince of Wales Hospital (C.S.H.), Shatin, New Territories, Hong Kong SAR; Department of Newborn Intensive Care (R.W.H.) and Department of Endocrinology and Diabetes (M.R.Z.), The Royal Children's Hospital, Parkville, Victoria 3052, Australia; and Department of Paediatrics (R.W.H., M.R.Z.), University of Melbourne, Parkville, Victoria 3010, Australia.
Insights
This study establishes reference intervals for eight hormones in preterm infants, crucial for accurate diagnosis and care. These findings aid in interpreting hormone levels for very preterm neonates, reducing misdiagnosis risks.
Area of Science:
- Neonatal endocrinology
- Pediatric clinical chemistry
Background:
- Significant differences exist in serum hormone levels between preterm and full-term infants.
- Accurate interpretation of hormone levels is critical for managing preterm neonates.
Purpose of the Study:
- To establish reference intervals (RIs) for 3 pituitary and 5 steroid hormones in preterm infants.
- To provide a basis for accurate clinical interpretation of hormone measurements in this population.
Main Methods:
- Serum samples from 248 preterm neonates (24-32 weeks' gestation) were analyzed.
- Pituitary hormones (prolactin, FSH, LH) measured by immunoassay; steroid hormones (17-hydroxyprogesterone, androstenedione, cortisol, cortisone, testosterone) by liquid chromatography-tandem mass spectrometry.
- Robust statistical methods, including Box-Cox transformation, were used to define central 95% RIs.
Main Results:
- Reference intervals were established for 8 hormones.
- Gender-specific RIs for FSH, LH, and testosterone.
- Cortisone and 17-hydroxyprogesterone RIs were dependent on gestational age (<30 weeks).
Conclusions:
- This study presents the first characterization of serum steroids by mass spectrometry and pituitary hormones in preterm neonates (≤32 weeks' gestation).
- These established RIs are vital for correct interpretation of results in very preterm infants.
- The data will help reduce diagnostic errors stemming from misinterpretation of hormone levels.
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.
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