ESPE Abstracts (2019) 92 FC13.4

Biphasic Glucocorticoid Rhythm in One Month Old Infants: Reflection of a Developing HPA-Axis?

Jonneke J. Hollanders1, Paul de Goede2, Bibian van der Voorn3, Adriaan Honig4, Joost Rotteveel1, Koert Dolman5, Andries Kalsbeek2,6,7, Martijn J.J. Finken1


1Emma's Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Endocrinology, Amsterdam, Netherlands. 2Laboratory of Endocrinology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Gastroenterology & Metabolism, Amsterdam, Netherlands. 3Department of Paediatric Endocrinology, Obesity Center CGG, Sophia Children's Hospital, Rotterdam, Netherlands. 4Department of Psychiatry, Psychiatry Obstetric Pediatric Expert Center, OLVG Hospital, Amsterdam, Netherlands. 5Department of Pediatrics, OLVG Hospital, Amsterdam, Netherlands. 6Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands. 7Hypothalamic Integration Mechanisms Group, Netherlands Institute for Neuroscience (NIN), Amsterdam, Netherlands


Background: The hypothalamus-pituitary-adrenal (HPA) axis displays a diurnal rhythm, peaking in the morning and with a nadir at night. However, not much is known about the development of the HPA- axis, although strikingly some evidence suggests that a rhythm with a peak in the afternoon is already present antenatally. We aimed to describe HPA-axis activity at age 1 month as well as study possible influencing factors.

Methods: Fifty-five mother-infant pairs collected breastmilk and infant saliva samples before every feeding moment for 24 hours one month postpartum. Glucocorticoid (GC, i.e., cortisol and cortisone) concentrations were measured with LC-MS/MS, and data were transformed in the rhythm parameters area-under-the-curve (AUC) increase (i) and ground (g), maximum and time of maximum. Analyses were performed with SPSS and Sigmaplot. Maternal psychopathology (increased Hospital Anxiety and Depression Scale and/or consultation at the Psychiatric-Obstetric-Pediatric clinic), season at sampling, sex and breastmilk GC rhythm parameters were assessed for possible associations.

Results: A significant GC rhythm was detected, which was found to be biphasic with peaks at 6:53±1:01 (mean±SEM) and 18:36±1:49 for cortisol, and at 8:50±1:11 and 19:57±1:13 for cortisone. Maternal psychopathology, season at sampling and sex did not influence the infants' GC rhythm. Breastmilk maximum cortisol levels were positively associated with cortisol AUCi and maximum levels in the infant. Higher breastmilk cortisone AUCi, AUCg and maximum concentrations were associated with an earlier time of maximum in the infant. Additionally, breastmilk and infant GC concentrations were associated between 6:00-9:00, but not during other time intervals.

Conclusion: A biphasic GC rhythm is present in 1-month-old infants at a group level, with peaks in both the morning and the evening, which might be a part of the developmental process towards an adult-type GC rhythm. Maternal psychopathology, season at sampling and sex were not associated with neonatal GC rhythmicity. However, although results were not consistent between cortisol and cortisone outcomes, breastmilk GC parameters might influence the infants' GC rhythm, since a more variable breastmilk GC rhythm was associated with an earlier time of maximum in infants. This could be due to either a causal effect of breastmilk GCs, or because of increased mother-infant synchrony. These findings offer a promising insight into the development of an HPA-axis rhythm, especially with regard to the role of breastmilk, and future research should further elucidate these results.

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