Abstract

ContextThe hypothalamus-pituitary-adrenal (HPA) axis displays a diurnal rhythm. However, little is known about its development in early life.ObjectiveTo describe HPA-axis activity and study possible influencing factors in 1-month-old infants.DesignObservational.SettingAmsterdam University Medical Center, location VU University Medical Center (VUMC), and Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam.ParticipantsFifty-five mother-infant pairs.InterventionsCollection of breast milk and infants’ saliva 1 month postpartum for analysis of glucocorticoids (GCs; ie, cortisol and cortisone) using liquid chromatography– tandem mass spectrometry.Main Outcome MeasureGC rhythm in infants’ saliva and associations with vulnerability for maternal psychological distress (increased Hospital Anxiety and Depression Scale [HADS] score) or consultation at the Psychiatric Obstetric Pediatric (POP clinic), season at sampling, sex, and breast milk GC rhythmicity analyzed with SigmaPlot 14.0 software (Systat Software, San Jose, CA, USA) and regression analyses.ResultsA significant biphasic GC rhythm was detected in infants, with mean peaks [standard error of the mean, SEM] at 6:53 am [1:01] and 18:36 pm [1:49] for cortisol, and at 8:50 am [1:11] and 19:57 pm [1:13] for cortisone. HADS score, POP consultation, season at sampling, and sex were not associated with the infants’ GC rhythm. Breast milk cortisol maximum was positively associated with infants’ cortisol area-under-the-curve (AUC) increase and maximum. Higher breast milk cortisone AUC increase, AUC ground, and maximum were associated with an earlier maximum in infants. Breast milk and infant GC concentrations were associated between 6:00 am and 9:00 am.ConclusionsA biphasic GC rhythm, peaking in the morning and evening, was seen in 1-month-old infants at a group level. Breast milk GC parameters might be associated with the infants’ GC rhythm, possibly caused by a signaling effect of breast milk GCs, or as an associative effect of increased mother-infant synchrony. These results contribute to an increased understanding of early life HPA-axis development.

Highlights

  • In adults, the hypothalamus pituitary adrenal (HPA) axis displays a diurnal rhythm, peaking in the morning and with a nadir at night

  • A significant biphasic GC rhythm was detected in infants, with peaks at 6:53±1:01 and 18:36±1:49 for cortisol, and at 8:50±1:11 and 19:57±1:13 for cortisone

  • Higher breastmilk cortisone AUCincrease, AUCground and maximum were associated with an earlier maximum in infants

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Summary

Introduction

The hypothalamus pituitary adrenal (HPA) axis displays a diurnal rhythm, peaking in the morning and with a nadir at night. It is not exactly clear when this adult-type rhythm is established in children, with studies reporting ages ranging from 2 weeks to 9 months in healthy infants.(1-9). It is conceivable that an HPA-axis rhythm emerges prenatally, and continues to develop into an adulttype rhythm after birth, with a shift from a peak in the afternoon towards a morning peak It is not clear which factors drive the development of an adult-type diurnal rhythm of the HPA-axis

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