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

Nykänen, Päivi; Raivio, Taneli; Heinonen, Kirsti; Jänne, Olli A.; Voutilainen, Raimo

doi:10.1530/eje-06-0672

Cited by 15 publications

(7 citation statements)

References 34 publications

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“…Providing a control group without antenatal BM would be unethical. As a reasonable substitute, we consider our infants with BM >7 days before birth to be a relevant internal comparison group for immediate BM effects since 7 days is sufficient for BM wash-out [17,18]. To address the timing of antenatal BM, we use three distinct time categories: 24 h to 7 days ‘optimal timing', >7 days ‘too early' and <24 h ‘too late' in figures 1 and 2 and table 2.…”

Section: Methodsmentioning

confidence: 99%

Antenatal Betamethasone Associates with Transient Immunodepression in Very Low Birth Weight Infants

et al. 2013

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Background: Antenatal betamethasone (BM) treatment for mothers at risk for premature delivery is effective in reducing neonatal morbidity. Immunodepression, defined as monocyte human leukocyte antigen (HLA)-DR expression <60%, is common in patients in intensive care. In very low birth weight (VLBW) infants, immunodepression correlates with gestational age and may predispose to infections. Objectives: To evaluate whether timing of antenatal BM associates with immunodepression in VLBW infants. Methods: We determined monocyte HLA-DR expression by flow cytometry and measured 13 cytokines, cortisol, and BM in plasma from 56 VLBW infants. We calculated total glucocorticoid index as the sum of BM and cortisol at the ratio 33.3:1. Results: HLA-DR expression both in cord (R² = 0.175, p = 0.033, n = 26) and on day 1 (R² = 0.125, p = 0.011, n = 51) showed an association with timing of BM. A short interval from BM to birth induced more pronounced and prolonged immunodepression, with lower HLA-DR% on postnatal day 7. On day 3, 25 infants (45%) met the criteria of immunodepression. HLA-DR expression correlated negatively with total glucocorticoid index (cord: R² = -0.573, p = 0.003, n = 13; day 1: R² = -0.213, p = 0.008, n = 32). Elapsed time from maternal BM correlated positively with concentrations of cytokines IL-6 and IL-10 on day 1. Conclusions: In VLBW infants, antenatal BM associated with transient immunodepression in a time-dependent manner. Suppression of both anti- and proinflammatory cytokines occurred. These effects may lead to an increased risk for later infections.

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Section: Methodsmentioning

confidence: 99%

Antenatal Betamethasone Associates with Transient Immunodepression in Very Low Birth Weight Infants

et al. 2013

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“…48, 49 Assessments of cord blood and amniotic fluid indicate acute suppression of endogenous fetal cortisol production 55–57 and an acute increase in GC bioactivity 56, 58 in response to synthetic GCs. The suppression of endogenous fetal/neonatal cortisol production appears to persist into the immediate postnatal period.…”

Section: Human Datamentioning

confidence: 99%

“…Several studies have shown that among preterm infants exposed to antenatal GCs, unstimulated (baseline) cortisol levels are suppressed for several days after treatment during the first postnatal week and then return to normal levels. 58–61 The assessment of cortisol levels at a single time point during the day provides limited information regarding the functioning of the HPA axis. To better understand the influence of prenatal GC treatment on HPA axis functioning it is necessary to use serial assessments to evaluate both responses to stressors and the circadian regulation.…”

Section: Human Datamentioning

confidence: 99%

Effects of antenatal corticosteroids on the hypothalamic-pituitary-adrenocortical axis of the fetus and newborn: experimental findings and clinical considerations

Waffarn

Davis

2012

American Journal of Obstetrics and Gynecology

124

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The hypothalamic-pituitary-adrenocortical (HPA) axis is a major neuro-endocrine pathway that modulates the stress response. The glucocorticoid, cortisol is the principal end product of the HPA axis in humans, and plays a fundamental role in maintaining homeostasis and in fetal maturation and development. Antenatal administration of synthetic glucocorticoids (GCs) accelerates fetal lung maturation and has significantly decreased neonatal mortality and morbidity in infants born before 34 weeks of gestation. Exposure to excess levels of endogenous GCs and exogenous GCs (betamethasone and dexamethasone) has been shown to alter the normal development trajectory. The development and regulation of the fetal HPA axis is discussed and the experimental animal evidence presented suggests long-term adverse consequences of altered HPA function. The clinical data in infants exposed to GCs also suggests altered HPA axis function over the short term. The longer-term consequences of antenatal GC exposure on HPA axis function and subtler neurodevelopmental outcomes including adaptation to stress, cognition, behavior, and the cardiovascular and immune responses are poorly understood. Emerging clinical strategies and interventions may help in the selection of mothers at risk for preterm delivery who would benefit from existing or future formulations of antenatal GCs with a reduction in the associated risk to the fetus and newborn. Detailed longitudinal long-term follow up of those infants exposed to synthetic GCs are needed.

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“…Acute suppression of foetal cortisol synthesis and an increase in cortisol bioactivity occur in response to synthetic steroids given prenatally [52]. The suppression of endogenous cortisol production persists in preterm infants and returns to normal after the first week of life [52].…”

Section: Long-term Effects Of Antenatal Steroidsmentioning

confidence: 99%

Antenatal steroids

Romejko-Wolniewicz¹,

Teliga-Czajkowska

Czajkowski³

2014

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of reviewThe beneficial effects of antenatal steroids in women at risk of preterm birth are evident. A dose of 24 mg appears sufficient, but there are insufficient data to recommend betamethasone or dexamethasone, a single steroid dose, the optimal interval between doses and repeated courses, the gestational age at which treatment is beneficial and the long-term effects of steroid treatment. This review addresses these aspects of antenatal steroid treatment.Recent findingsAlthough the 12-h and 24-h dosing intervals are equivalent with respect to prevention of respiratory distress syndrome, the former enables the completion of treatment in 50% more neonates delivered prematurely. Reducing the single steroid dose in patients at risk for premature birth reduces the associated maternal side effects. An inverse relationship has been demonstrated between the number of corticosteroid courses and foetal growth. The reduced size of exposed foetuses has been attributed to birth at earlier gestational ages and decreased foetal growth. Evidence suggests that antenatal exposure to synthetic glucocorticoids in term-born children has long-lasting effects, which may have important implications in the recommendation of steroids before elective caesarean at term.SummaryThe short-term and long-term effects of the dosage regimen on the pregnant mother and foetus remain unclear.

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

Cited by 15 publications

References 34 publications

Antenatal Betamethasone Associates with Transient Immunodepression in Very Low Birth Weight Infants

Antenatal Betamethasone Associates with Transient Immunodepression in Very Low Birth Weight Infants

Effects of antenatal corticosteroids on the hypothalamic-pituitary-adrenocortical axis of the fetus and newborn: experimental findings and clinical considerations

Antenatal steroids

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