Growth-restricted preterm newborns are predisposed to functional adrenal hyperandrogenism in adult life

Abstract

Background: The long-term effects of perinatal growth and corticosteroid exposure on adrenal steroid concentrations in adults born very preterm are uncertain. Objectives: To examine the effect of birth weight, early postnatal growth, and pre-and postnatal corticosteroid administration on serum adrenal steroids in 19-year-old subjects born very preterm. Design and methods: Subjects born before 32 weeks of gestation in The Netherlands participating in the Project on Preterm and Small for Gestational Age Infants (POPS) were investigated at 19 years of age. Serum cortisol, DHEA sulfate (DHEAS), and androstenedione (Adione) concentrations were measured in 393 out of 676 eligible subjects, compared with controls, and associated with perinatal growth and pre-and postnatal corticosteroids administration using multiple linear regression analyses. Results: Serum DHEAS and Adione in men and women were higher than in controls. In the multiple regression analyses, birth weight SDS showed a statistically significant negative association with serum DHEAS concentrations in women (b: K0.865, 95% confidence interval (CI): K1.254 to K0.476) and in men (b: K0.758, 95% CI: K1.247 to K0.268) and with serum Adione concentrations in women (b: K0.337, 95% CI: K0.593 to K0.082). Early postnatal weight gain showed no association with any of measured adrenal markers. In women, serum Adione was associated with postnatal dexamethasone exposure (b: 0.932, 95% CI: 0.022 -1.843). Conclusions: Young adults born very preterm show elevated adrenal androgens, particularly when born small for gestational age. Postnatal corticosteroid administration is positively associated with serum Adione in young women.

Adrenocortical Hormonal Activity in 20-Year-Old Subjects Born Small or Appropriate for Gestational Age

“…It has only minor diurnal variation due to its long half-life and large vascular pool [34]. A recent study on very preterm born and growth-restricted young adults reported higher DHEAS concentrations compared to the control subjects [23]. SGA children at prepubertal and pubertal age have been shown to have increased DHEAS levels in several [10,11,12,13,14] but not in all studies [35,36].…”

“…Jaquet et al [39] also reported similar serum DHEAS and androstenedione levels in 20-year-old full-term born SGA and AGA women. On the other hand, Meuwese et al [23] reported higher serum DHEAS levels in 19-year-old subjects born with LBW (premature birth <32 weeks of gestation and/or birth weight <1,500 g) than in their reference group (apparently at least mostly full-term born 18–25-year-old subjects). Szathmári et al [22] reported higher serum DHEAS levels in 20-year-old prematurely born (range 27–36 weeks) women (but not in men) compared with full-term born controls.…”

“…Szathmári et al [22] reported higher serum DHEAS levels in 20-year-old prematurely born (range 27–36 weeks) women (but not in men) compared with full-term born controls. The control groups in the two last-mentioned studies [22,23] were not optimal, but it seems that serum DHEAS levels may remain elevated in prematurely born subjects in early adulthood, whereas they are no longer higher in full-term born adult SGA subjects than in AGA born subjects. Thus, it looks that higher DHEAS levels in full-term born SGA than in AGA subjects are detected only at a certain age, such as the prepubertal and pubertal period, from which age most previous reports originate [10,11,12,13,14].…”

“…Serum DHEAS concentrations were measured to find out if adrenal androgen production remains increased in young adult SGA subjects born full-term. Increased adrenal androgen levels have been reported in preterm born adult SGA subjects [22,23], but the situation is not clear in full-term born SGA subjects.…”

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

“…This comes as a surprise even though we know that premature infants run a comparable risk of developing metabolic disturbances [18] and cardiovascular disease [19] later in life, and several studies have shown a postnatal adrenocortical insufficiency in preterm infants [20,21]. However, long-term data on adrenal function in individuals born prematurely are scarce [11,22].…”