Glucocorticoid Programming in Very Preterm Birth

Finken, Martijn J J; Voorn, Bibian van der; Heijboer, Annemieke C.; Waard, Marita de; Goudoever, Johannes B. van; Rotteveel, Joost

doi:10.1159/000443734

Cited by 22 publications

(15 citation statements)

References 98 publications

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“…Our findings are consistent with Meuwese and colleagues, who reported that young adults born very preterm showed elevated DHEAS and androstenedione, particularly when born small for gestational age (SGA) (11). We speculate that inconsistent data regarding the effect of preterm birth and birth weight on subsequent adrenal androgen secretion may be due to differences in gestational age, degree of illness, and/or growth between birth and 36 weeks PMA (24, 26, 35).…”

Section: Discussionmentioning

confidence: 95%

“…Based on previously published data from individuals born preterm or IUGR at term gestation, we had hypothesized that extremely preterm birth would result in increased cortisol and adrenal androgen concentrations at age 6 compared to term-born children (1–3, 6, 7, 11, 26, 34). Our results were both more complex and physiologically compelling.…”

Section: Discussionmentioning

confidence: 99%

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Adrenal function links to early postnatal growth and blood pressure at age 6 in children born extremely preterm

Watterberg

Hintz

et al. 2018

Pediatr Res

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Background: Low birth weight in term-born individuals correlates with adverse cardiometabolic outcomes; excess glucocorticoid exposure has been linked to these relationships. We hypothesized that cortisol and adrenal androgens would correlate inversely with birthweight and directly with markers of cardiometabolic risk in school-aged children born extremely preterm; further, preterm-born would have increased cortisol and adrenal androgens compared to term-born children. Methods: Saliva samples were obtained at age 6 from 219 preterm-born children followed since birth and 40 term-born children and analyzed for dehydroepiandrosterone (DHEA) and cortisol. Cortisol was also measured at home (awakening, 30’ later, evening). Results: For preterm-born children, cortisol and DHEA correlated inversely with weight and length Z-scores at 36 weeks PMA and positively with systolic BP. DHEA was higher in preterm-born than term-born children (boys p<0.01; girls p=0.04). Cortisol was similar between preterm-born and term-born at study visit; however, preterm-born children showed a blunted morning cortisol. In term-born children, DHEA correlated with BMI (p=0.04), subscapular, and abdominal skinfold thicknesses (both p<0.01). Conclusion: Cortisol and DHEA correlated inversely with early postnatal growth and directly with systolic BP in extremely preterm-born children, suggesting perinatal programming. Blunted morning cortisol may reflect NICU stress, as seen after other adverse childhood experiences (ACEs).

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Adrenal function links to early postnatal growth and blood pressure at age 6 in children born extremely preterm

Watterberg

Hintz

et al. 2018

Pediatr Res

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“…Both these mechanisms can lead to a suppression of fetal hypothalamic CRH that may continue after birth. Indeed, studies showed that the pituitary response to exogenous CRH was impaired in preterm newborns [12], suggestive of enhanced central feedback suppression by glucocorticoids. Another mechanism contributing to RAI is the immaturity of adrenal cortex enzymes, notably decreased 11β-hydroxylase activity, which is necessary for the conversion of 11-deoxycortisol to cortisol [13,14].…”

Section: Relative Adrenal Insufficiencymentioning

confidence: 99%

“…Several studies have addressed the long-term impact of prematurity on HPA axis activity [12]. Evidence encompassed a higher corticosteroid production rate [30], and increases in the serum or salivary cortisol concentration during early morning, at nadir, or throughout the day in subjects born preterm were observed (Fig.…”

Section: Adrenocortical Function In Childhood and Its Clinical Correlmentioning

confidence: 99%

Programming of the Hypothalamus-Pituitary-Adrenal Axis by Very Preterm Birth

et al. 2017

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Background: Many very preterm (i.e., <32 weeks of gestation) newborns fail to mount an adequate adrenocortical response to stress or illness, termed relative adrenal insufficiency. Conversely, later in life these infants show features of increased glucocorticoid bioactivity, such as abdominal adiposity, insulin resistance, raised blood pressure, shorter stature and internalizing problem behavior. Summary: Studies suggested that very preterm newborns have impairments along multiple levels of the hypothalamus-pituitary-adrenal (HPA) axis. Among the impairment were defects in: (1) the pituitary responsiveness to exogenous corticotropin-releasing hormone, (2) 11β-hydroxylase activity, and (3) the interconversion between cortisol and inert cortisone. There is some evidence suggesting that later in life these infants have an increased basal secretion rate of cortisol and adrenal hyperandrogenism. However, the response to acute (psychosocial) stress was blunted rather than enhanced in them. The mechanisms explaining this switch in HPA axis activity are complex and not yet fully understood. Key Messages: Very preterm newborns have several impairments along the HPA axis that could impede an adequate adrenocortical response to stress or illness. Later in life, these infants are predisposed to increased HPA axis activity, which could partially explain their phenotype.

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“…Given its effects on fat disposition and metabolism, the hypothalamus-pituitary-adrenal (HPA) axis has been implicated to play a role in the pathway leading to obesity [2,3]. Not only endogenous but also maternal glucocorticoids (GCs) appear to be involved.…”

Section: Introductionmentioning

confidence: 99%

No Association between Glucocorticoid Diurnal Rhythm in Breastmilk and Infant Body Composition at 3 Months

et al. 2019

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Objective: Glucocorticoids (GCs) in breastmilk have previously been associated with infant body growth and body composition. However, the diurnal rhythm of breastmilk GCs was not taken into account, and we therefore aimed to assess the associations between breastmilk GC rhythmicity at 1 month and growth and body composition at 3 months in infants. Methods: At 1 month postpartum, breastmilk GCs were collected over a 24-h period and analyzed by LC-MS/MS. Body composition was measured using air-displacement plethysmography at 3 months. Length and weight were collected at 1, 2, and 3 months. Results: In total, 42 healthy mother–infant pairs were included. No associations were found between breastmilk GC rhythmicity (area-under-the-curve increase and ground, maximum, and delta) and infant growth trajectories or body composition (fat and fat free mass index, fat%) at 3 months. Conclusions: This study did not find an association between breastmilk GC rhythmicity at 1 month and infant’s growth or body composition at 3 months. Therefore, this study suggests that previous observations linking breastmilk cortisol to changes in infant weight might be flawed by the lack of serial cortisol measurements and detailed information on body composition.

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Glucocorticoid Programming in Very Preterm Birth

Cited by 22 publications

References 98 publications

Adrenal function links to early postnatal growth and blood pressure at age 6 in children born extremely preterm

Adrenal function links to early postnatal growth and blood pressure at age 6 in children born extremely preterm

Programming of the Hypothalamus-Pituitary-Adrenal Axis by Very Preterm Birth

No Association between Glucocorticoid Diurnal Rhythm in Breastmilk and Infant Body Composition at 3 Months

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