Altered Basal Cortisol Levels at 3, 6, 8 and 18 Months in Infants Born at Extremely Low Gestational Age

Abstract

Objective-Little is known about the developmental trajectory of cortisol levels in preterm infants after hospital discharge.Study design-In a cohort of 225 infants (gestational age at birth <33 weeks) basal salivary cortisol levels were compared in infants born at extremely low gestational age (ELGA, 23-28 weeks), very low gestational age (VLGA, 29-32 weeks) and full-term (37-42 weeks), at 3, 6, 8 and 18 months corrected age (CA). Infants with major neurosensory and/or motor impairment were excluded.Results-At 3 months CA, salivary cortisol levels were lower in both preterm groups compared to the full-term infants (p = .003). Conversely, at 8 and 18 months CA, the ELGA infants had significantly higher basal cortisol levels than the VLGA and full-term infants (p = .016; p = .006 respectively).Conclusions-In ELGA infants, the shift from low basal cortisol levels at 3 months to significantly high levels at 8 and 18 months CA suggests long-term 're-setting' of endocrine stress systems. Multiple factors may contribute to these higher cortisol levels in the ELGA infants, including physiological immaturity at birth, cumulative stress related to multiple procedures and mechanical ventilation during lengthy hospitalization. Prolonged elevation of the cortisol "set-point" may have negative implications for neurodevelopment and later health. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.No author has any potential conflict of interest with this manuscript. Early environmental stress can permanently reorganize hormonal, physiological and behavioral systems, and increase vulnerability to illness and disorders later in life, a process referred to as "early programming." 1-6 For example, in rats, early adverse experiences such as prenatal stress, maternal separation or early deprivation result in increased stress hormone responses throughout the preweaning period and into adulthood. 2,3,6 Increased exposure to endogenous corticosteroids has adverse effects on cognitive abilities 7 and increases emotionality and anxiety-like behaviors in aversive situations. 8,9 NIH Public AccessIn general, sicker and smaller infants often show relatively low cortisol levels while in the neonatal intensive care unit (NICU). 10 We have recently shown a developmental shift whereby greater cumulative neonatal stress (higher number of skin-breaking procedures from birth to term) predicted lower cortisol levels in the NICU, 11 but elevated cortisol levels at 8 months corrected age (CA). 12 Little is known about the developmental trajectories of cortisol secretion in preterm infants after hospital dis...

Salivary and hair glucocorticoids and sleep in very preterm children during school age

“…Decreased cortisol secretion after postnatal treatment with dexamethasone could however not be confirmed by Grunau et al (2007) who studied basal salivary cortisol in preterm children aged 6, 8, and 18 months. Similarly, we found no significant association between pre-and neonatal treatments (including prenatal glucocorticoids, ventilation, intubation, and CPAP) and later HPA axis activity in the present study.…”

“…Second, children born very preterm suffer from the immature functioning of the lungs, often leading to hypoxia (Saigal and Doyle, 2008) and the adrenal gland leading to potential adrenal insufficiency (Fernandez and Watterberg, 2009). Third, children born very preterm are exposed to many distressing medical procedures including blood draws and mechanical ventilation (Anand, 2001;Brummelte et al, 2015;Grunau et al, 2007).…”

Stress : Clinical and Developmental Aspects of Salivary Cortisol in Infants

“…While preterm infants may be capable of producing sufficient cortisol to maintain homeostasis under non-stressful conditions, their developmental immaturity may result in an insufficient or completely absent response to a stressor [158,159]. Preterm infants have exhibited altered HPA axis function at young age (three, eight, and 18 months, as well as at seven years) [160,161]. Elevated salivary cortisol levels in preterm infants have previously been found to correlate with the degree of pain to which the infants were exposed during the neonatal period [162][163][164].…”

“…Due to the lack of impact, we may conclude that NPS in this context is not a sufficiently painful stimulus to evoke a pain reaction in infants, to be eased by the analgesic benefit of glucose. Preterm infants have earlier exhibited altered HPA axis function at young ages (three, eight, and 18 months, as well as at seven years) [160,161] and often but not always they react with elevated salivary cortisol levels [49]. Previously cortisol levels has been found to correlate with the degree of pain to which the infants were exposed to during the neonatal period [162][163][164].…”

Invasive Procedures in Preterm Children: Brain and Cognitive Development at School Age

“…10,11 Children were excluded if they had a major congenital anomaly, major neurosensory impairment (legally blind, nonambulatory cerebral palsy, sensorineural hearing impairment), or severe brain injury evident on neonatal ultrasound (periventricular leukomalacia or grade 3 or 4 intraventricular hemorrhage; Fig 1).…”