ESPE Yearbook of Paediatric Endocrinology

Arch Dis Child Fetal Neonatal Ed. 2022 Mar 14:fetalneonatal-2021-323296. doi: 10.1136/archdischild-2021-323296. Epub ahead of print. PMID: 35288450.

Brief Summary: This study tested the hypothesis that the diurnal cortisol area under the curve (mean daily level) and diurnal cortisol slope (decline across the day) differ between infants born preterm and those born at term. Extremely preterm infants showed an abnormal pattern of cortisol secretion characterised by a flat cortisol slope, and this was most marked after the first 6 months of life.

Infants born with low birth weight have an activated hypothalamic–pituitary–adrenal (HPA) axis in early childhood and this may lead to adverse cardiometabolic and neuropsychiatric phenotypes in later adulthood. Previous studies (1) have shown that the basal cortisol concentration of extremely preterm infants, compared with term infants, change from low to high concentrations between 3 and 8 months of age. This suggests that the HPA axis regulation may differ in preterm infants across infancy.

The authors measured the salivary cortisol levels at three-time points, morning, midday and evening on a monthly basis in three cohort of infants (term, very preterm, 28-32 weeks and extremely preterm infants, <27 weeks) until the age of 1 year. The extremely preterm infants (and not the very preterm) had a flat diurnal cortisol slope (defined as the decline in cortisol across the day) when compared to the corrected gestations for infants born at term. The cortisol slope is the difference in the cortisol level between the morning and the evening and thus a flat slope would indicate minimal difference between the cortisol level in the morning and in the evening. This could indicate a loss of diurnal variation in cortisol secretion. These differences were more profound when assessed during corrected ages 7–12 months. The differences between birth groups were more marked when compared at chronological rather than corrected ages. However, the diurnal cortisol area under the curve (indicating total cortisol secretion) did not differ between the birth groups.

These observations suggest that infants who are born extremely preterm (but not the very preterm) have an abnormal pattern of cortisol secretion most marked after the first 6 months of life, characterised by a flat cortisol slope. A metanalysis in adults showed significant associations between flatter diurnal cortisol slopes and poorer health (2). Flatter diurnal cortisol slopes may both reflect and contribute to stress-related dysregulation of central and peripheral circadian mechanisms, with corresponding downstream effects on multiple aspects of biology, behavior, and health. Larger studies will be needed in the extremely preterm infants to replicate these findings.

References: 1. Finken MJ, van der Voorn B, Heijboer AC, de Waard M, van Goudoever JB, Rotteveel J. Glucocorticoid Programming in Very Preterm Birth. Horm Res Paediatr. 2016;85(4):221–31. doi: 10.1159/000443734. Epub 2016 Mar 5. PMID: 26943327. 2. Adam EK, Quinn ME, Tavernier R, McQuillan MT, Dahlke KA, Gilbert KE. Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis. Psychoneuroendocrinology. 2017 Sep;83:25–41. doi: 10.1016/j.psyneuen.2017.05.018. Epub 2017 May 24. PMID: 28578301; PMCID: PMC5568897.