Increased Steroid Excretion in Children with Extremely Low Birth Weight at a Median Age of 9.8 years

Abstract

Background: Events during foetal or early extrauterine life may affect bodily structure and/or functions and even pave the way for adult diseases. Aims: To find whether extremely low birth weight (ELBW) infants differ from healthy controls regarding the excretion of steroid metabolites. Methods: The study compared 17 female and 10 male ELBW infants, all prepubertal, aged 8-11 years, birth weight <1,000 g, with 27 age- and sex-matched controls. All were healthy at the time of the study. Height, weight and BMI did not differ between the groups. Results were adjusted according to body surface area. 36 urinary steroid metabolites were quantified by gas chromatography-mass spectrometry. Results: In the ELBW girls 33/36 steroid metabolites were higher (19 significantly) than in the controls. All 36 steroid metabolites were higher in the ELBW boys (9 significantly) than in the controls. Sums of mineralocorticoid precursors, metabolites descriptive for cortisol and parameters of adrenal androgen production were significantly higher in ELBW infants (both sexes). Only the sum of the metabolites known to be illustrative for adrenal 11β-hydroxysteroid dehydrogenase activity was not different. Conclusion: Prepubertal ELBW children have an augmented urinary excretion of adrenal androgens, cortisol and mineralocorticoid precursors. These findings corroborate and help to explain the link between early-life adversity and subsequent adrenocortical function.

Sex differences in early-life programming of the hypothalamic–pituitary–adrenal axis in humans suggest increased vulnerability in females: a systematic review

“…Findings from later in life were also not consistent. Studies on diurnal cortisol secretion either did not find a sex difference, 10 , 26 , 30 found altered secretion in males 23 or in females 24 . Although the findings of HPA axis measures in the studies conducted in children and adults were not consistent, the only sex difference in HPA axis reactivity reported was consistent with increased reactivity in females 19 …”

“…Two studies found increased morning salivary or serum cortisol in offspring exposed to neonatal corticosteroids or low birth weight, but found no sex differences in this effect either in early adulthood 10 or adolescence 34 . Another study investigated urinary steroid metabolites in extremely low birth weight children, with extremely low birth weight males and females having increased cortisol production compared with controls, but did not test whether there was any sex difference 26 . A study investigating GR gene methylation in DNA extracted from buccal cells collected in infancy found that females whose mothers had experienced a significant life event during pregnancy had increased methylation of NR3C1 compared with control females, finding no such relationship in males 31 …”

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

“…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. 1) [28,31,32].…”

Glucocorticoid Programming in Very Preterm Birth

“…In contrast, no differences in cortisol parameters were observed in men. Yet another study found that ELBW was associated with higher excretion rates of adrenal steroid metabolites at age 10 years [68]. Two out of 4 studies that assessed the cortisol response to psychosocial stress found that preterm birth was associated with blunted rather than enhanced responses [69,70,71,72].…”