Antenatal and Early Postnatal Dexamethasone Treatment Decreases Cortisol Secretion in Preterm Infants

Karlsson, Riikka; Kallio, Johanna; Toppari, Jorma; Scheinin, Mika; Kero, Pentti

doi:10.1159/000023563

Cited by 32 publications

(35 citation statements)

References 29 publications

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“…The lack of significant differences in the cord and D0 serum F levels between the different ANS treatment groups is at least partly explained by the small number of infants without ANS treatment making the type two statistical error possible. However, the tendency to lower F levels in the infants treated with ANS within 72 h before birth is in concordance with previous studies (9,12,(16)(17)(18). The association of decreased cord and D0 serum GBA with the increasing number of ANS courses is probably mediated by the suppression of the respective F levels after multiple ANS courses administered several days before delivery (17,19).…”

Section: Discussionsupporting

confidence: 91%

“…Treatment of a preterm infant with Dx for a week or longer is associated with suppression of the hypothalamo-pituitary-adrenal (HPA) axis (20)(21)(22)(23)(24), and therefore shorter Dx courses have been introduced to treat severe RDS and to wean the infant from mechanical ventilation (11,17,(25)(26)(27)(28). In some studies, even 2-5 days of Dx treatment has been shown to suppress F levels (17,27), although this is not a constant finding in all studies (28).…”

Section: Discussionmentioning

confidence: 99%

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Circulating glucocorticoid bioactivity and serum cortisol concentrations in premature infants: the influence of exogenous glucocorticoids and clinical factors

et al. 2007

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Objective: Glucocorticoids are widely used before preterm delivery and in preterm infants may bear serious adverse effects. Better knowledge about the circulating glucocorticoid milieu after glucocorticoid treatment could improve treatment modalities. Therefore, we investigated the influence of exogenous glucocorticoids and clinical factors on serum cortisol (F) levels and circulating glucocorticoid bioactivity (GBA) in preterm infants. Design: Eighty-nine infants (gestational age (GA) 23.6-33.1 weeks at birth) were enrolled in a prospective cohort study in two tertiary neonatal centres. Methods: Cord, day of birth (D0), fourth day (D4) and 36 weeks postmenstrual age serum F and GBA levels were measured. Results: The cord GBA was 5.8-fold and D0 GBA 2.3-fold higher in the infants exposed to antenatal steroids within 12 h before birth when compared with those unexposed or exposed O7 days before birth (95% CI 3.8-8.6; P!0.0001, and 1.8-3.0; P!0.0001 respectively). In the infants treated with early postnatal dexamethasone, D4 GBA was 1.7-fold (1.3-2.2; P!0.0005) higher when compared with levels in the infants without this treatment. Clinical factors indicating perinatal distress, such as Apgar scores !7 and low GA, were associated with higher cord, D0 and D4 serum F levels. Conclusions: Both ante-and postnatally administered glucocorticoids increase circulating GBA not attributable to endogenous F. Perinatal distress and preceding glucocorticoid treatment need to be taken into account when circulating glucocorticoid milieu is evaluated in preterm infants. The GBA assay may prove to be a useful instrument in the development of new glucocorticoid treatment strategies.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Circulating glucocorticoid bioactivity and serum cortisol concentrations in premature infants: the influence of exogenous glucocorticoids and clinical factors

et al. 2007

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“…The cortisol levels in infants born before 30 wk of gestation were lower after stimulation and showed less variation compared with more mature preterm infants. These findings suggest that the human adrenal function is not yet fully matured in preterm infants and indicates a decreased capacity for cortisol synthesis and/or a decreased responsiveness to ACTH (15). This may be related to a gradual maturation of the human fetal HPA axis during the third trimester of gestation and is in agreement with the work of Mesiano and Jaffe in primates (16,17).…”

Section: Discussionsupporting

confidence: 84%

“…In children and adults stimulated levels of cortisol below 500 nmol/L are commonly used to suggest adrenal insufficiency (14). However, a lower level of cortisol of 500 nmol/L may not be appropriate for very preterm infants and Korte et al suggested a level of 360 nmol/L as cut-off value (15). In the present study only two infants had stimulated cortisol concentration less than 360 nmol/L.…”

Section: Discussioncontrasting

confidence: 47%

Maturity of the Adrenal Cortex in Very Preterm Infants Is Related to Gestational Age

Bolt

2002

Pediatric Research

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To study the maturity of the adrenal cortex in preterms born before 33 wk of gestation, basal levels of cortisol and cortisone and the cortisol and 17-hydroxyprogesterone (17-OHP) response to 1 g/kg adrenocorticotropic hormone stimulation were measured in 24 appropriate-for-gestational age preterm infants (26-33 wk; 690-1985 g). Gestational age influenced the response of cortisol, 17-OHP, and the ratio between cortisol/17-OHP in the studied infants. In preterms born Ͻ30 wk of gestation, levels of cortisol, and the ratio between cortisol/17-OHP were lower compared with preterms born between 30 and 33 wk. Levels of cortisone were higher in preterms born Ͻ30 wk, suggesting a lower activity of 11␤-hydroxysteroid dehydrogenase that may be related to maturity as well. The adrenal gland plays an important role during gestation. Steroid hormones produced by the fetal adrenal cortex are involved in the maturation of organ systems necessary for intrauterine and extrauterine life. For example, secretion of cortisol in late gestation is essential for lung maturation in sheep, rats, monkeys, and possibly humans (1, 2). It has been suggested that the adrenal cortex function may be more closely related to gestational age rather than to birth (3, 4), which implicates that in very preterm infants the adrenal activity may still be immature. Immaturity of the hypothalamic-pituitaryadrenal (HPA)-axis in preterm infants has been suggested to be associated with the occurrence of respiratory distress syndrome, chronic lung disease of prematurity, or even cardiovascular instability (5-7). Therefore, the ability of the HPA-axis to regulate, synthesize, and secrete cortisol in response to stress may be critical for survival and pulmonary development in very preterm infants.To evaluate the adrenal function the plasma cortisol response to i.v. administered ACTH is a common screening test. In general, 250 g synthetic ACTH is given as a bolus dose to stimulate cortisol release from the adrenal cortex, in adults as well as children as described by Wood et al. in 1965 (8). This supra-physiologic dose is much higher than required to produce a maximal adrenal response and could elicit an appropriate response despite of adrenal insufficiency (9, 10). Therefore, a lower dose of ACTH has been proposed to study the adrenal function.We hypothesize that differences in the maturity of the HPAaxis related to gestational age can be observed in the levels of hormones produced by the adrenal cortex and the adrenal response to ACTH in preterm infants of different gestational ages. The objective was to study basal levels of glucocorticoids and to establish the effect of stimulation of the adrenal cortex with ACTH in very preterm infants at the end of the 1st week of life. PATIENTS AND METHODS Patients.The study group consisted of 24 preterm infants with gestational ages ranging from 26 to 33 wk and birth weights ranging from 690 to 1985 g. Patients admitted to our July 11, 2001; January 10, 2002

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“…Prenatal steroid exposure has been shown to cause rebound suppression of cortisol levels in the immediate postnatal period. 43,44 Since all but one of the infants in our study received antenatal steroids; our ELBW population would be expected to have a fairly homogenous decline in cortisol availability during the first few days of life. This antenatal confounder was evenly distributed across both treatment cohorts and our results are consistent with the possibility that prophylactic HC supplementation may reduce the incidence of rebound adrenal suppression in the first days of life.…”

Section: Discussionmentioning

confidence: 99%

A Randomized-Controlled Trial of Prophylactic Hydrocortisone Supplementation for the Prevention of Hypotension in Extremely Low Birth Weight Infants

Efird

Heerens²,

Gordon

et al. 2004

J Perinatol

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Extremely low birth weight (ELBW) infants are at risk for hypotension. Abnormal adrenal function may play a role in the pathogenesis of hypotension, and therefore, the administration of hydrocortisone (HC) may be an effective treatment for hypotension in some infants. However, the efficacy of prophylactic HC to prevent the use of vasopressors for a defined hypotensive state has not been studied. We conducted a randomized-controlled trial to determine the potential role on adrenal insufficiency in early neonatal hypotension and to determine the effectiveness of prophylactic HC in reducing treatment of hypotension in ELBW infants. STUDY DESIGN:Infants were assigned to receive either HC or placebo within the first 3 hours of life. Therapy was continued for 5 days. The presence of hypotension was based on an operational definition and treatment with vasopressors (VP) was standardized based on an a priori protocol. RESULTS:A total of 34 patients were enrolled. Baseline characteristics were similar between groups. Of the HC group 25% received VP at 24 hours of age compared to 44% of the placebo group. On day of life 2, only 7% of the HC group received VP compared to 39% of the placebo group (p<0.05). CONCLUSION:Prophylactic treatment with HC reduces the incidence of hypotension, defined by treatment with VP, among ELBW infants during the first 2 days of life. However, the mounting evidence that prophylactic administration of glucocorticoids in the first days of life is harmful to ELBW infants makes HC prophylaxis unwise until the efficacy of treatment relative to safety can be clearly established.

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Antenatal and Early Postnatal Dexamethasone Treatment Decreases Cortisol Secretion in Preterm Infants

Cited by 32 publications

References 29 publications

Circulating glucocorticoid bioactivity and serum cortisol concentrations in premature infants: the influence of exogenous glucocorticoids and clinical factors

Circulating glucocorticoid bioactivity and serum cortisol concentrations in premature infants: the influence of exogenous glucocorticoids and clinical factors

Maturity of the Adrenal Cortex in Very Preterm Infants Is Related to Gestational Age

A Randomized-Controlled Trial of Prophylactic Hydrocortisone Supplementation for the Prevention of Hypotension in Extremely Low Birth Weight Infants

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