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Neonatal reference intervals for salivary steroids: focus on prematurity, stressful events and perinatal
Svetlana N Zykova1,2, Anna Plaksienko3, Anne Lee Solevåg4,5
1Hormone Laboratory, Department of Medical Biochemistry, Endocrinology and Metabolism Research Group, Oslo University Hospital, Oslo, Norway.
Context:
Painlessly obtained samples can improve diagnostics and care in paediatric conditions with affected steroidogenesis.
Objective:
To establish neonatal reference intervals (RIs) and identify sources of biological variation for steroid hormones in saliva.
Methods:
Steroid concentrations were determined using LC-MS/MS in 412 saliva samples from 174 infants aged 0-4 weeks, born at gestational age 26-42 weeks, recruited from three neonatal intensive care units and one maternity ward. We used six approaches to construct RIs with partitioning based on results from linear mixed models.
Results:
RIs in nmol/L calculated with robust method using median of up to six samples with sufficient volume from each infant were for salivary 17OH-pregnenolone: <4.0; 17OH-progesterone: <2.5; 11-deoxycortisol: 0.02-0.99; 21-deoxycortisol: <0.2; cortisol: 0.65-39; cortisone: 18-154; deoxycorticosterone: <0.04; corticosterone: <0.76; aldosterone: 0.21-4.2; dehydroepiandrosterone: <2.4; dehydroepiandrosterone sulphate: <100; androstenedione: <1.5; testosterone girls: <0.10; testosterone boys: <0.32. Following multivariable adjustment, prematurity was associated with elevated concentrations of mineralocorticoids, androgens and glucocorticoid-precursors (up to 240%, 500% and 1060% respectively), but not cortisol or cortisone. Being on respiratory support was linked with qualitative and quantitative changes in all corticosteroid pathways, while sampling during the first 48 h of life was associated with an increase in adrenocorticotropin-regulated glucocorticoids and androgens (except dehydroepiandrosterone) but not mineralocorticoids. Perinatal exposure to synthetic glucocorticoids led to 33% reduction in salivary cortisol, but not other hormones. Betamethasone was detectable in infants' saliva up to 12 days following maternal administration.
Conclusions:
We present neonatal reference intervals for steroid hormones in saliva thereby supporting a non-invasive and painless option for obtaining a steroid hormone profile in this fragile population.
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