The therapeutic use of glucocorticoid hormones in the perinatal period: Potential neurological hazards

Weichsel, Morton E.

doi:10.1002/ana.410020503

Cited by 119 publications

(39 citation statements)

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“…These results were consistent with previous animal experiments, which had shown that glucocorticoids administered during critical periods of brain development may impair myelinization, brain cell division, and longer-term behavioral effects. [11][12][13][14]16 As a result of these observations, neonatologists began to abandon PNSs for CLD when they learned of the longterm toxicities associated with PNS use for CLD.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 Metaanalyses of early (Ͻ96 hours of age) 7 and later use of PNSs to reduce CLD 8,9 demonstrated significant benefits with regard to earlier extubation and decreased risks of CLD at both 28 days and 36 weeks, death, or CLD at 28 days and 36 weeks, but there was a disturbing tendency toward an increase in neurodevelopmental impairment consistent with previous animal experiments, which had shown that glucocorticoids administered during critical periods of brain development may impair myelinization, brain cell division, and longer-term behavioral effects. [10][11][12][13][14][15][16] The American Academy of Pediatrics Committee on the Fetus and Newborn cautioned that PNS use outside of randomized trials should be reserved for "exceptional clinical circumstances." 17 The use of PNSs for the prevention or treatment of CLD remains common, especially for the extremely low birth weight infant (ELBW) whose birth weight is Ͻ1000 g, and information from the Vermont Oxford Network (VON), of which the California Perinatal Quality Care Collaborative (CPQCC) is a contributing member, indicates that for the year 2001, 38% of ELBW infants (22-65%) received PNSs.…”

Section: Authorsmentioning

confidence: 99%

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Prospective Evaluation of Postnatal Steroid Administration: A 1-Year Experience From the California Perinatal Quality Care Collaborative

Finer

Powers²,

et al. 2006

Pediatrics

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OBJECTIVE. Postnatal steroids (PNSs) are used frequently to prevent or treat chronic lung disease (CLD) in the very low birth weight (VLBW) infant, and their use continues despite concerns regarding an increased incidence of longer-term neurodevelopmental abnormalities in such infants. More recently, there has been a suggestion that corticosteroids may be a useful alternative therapy for hypotension in VLBW infants, but there have been no prospective reports of such use for a current cohort of VLBW infants. METHODS. The California Perinatal Quality Care Collaborative (CPQCC) requested members to supplement their routine Vermont Oxford Network data collection with additional information on any VLBW infant treated during their hospital course with PNS, for any indication. The indication, actual agent used, total initial daily dose, age at treatment, type of respiratory support, mean airway pressure, fraction of inspired oxygen, and duration of first dosing were recorded. RESULTS. From April 2002 to March 2003 in California, 22 of the 62 CPQCC hospitals reported supplemental data, if applicable, from a cohort of 1401 VLBW infants (expanded data group [EDG]), representing 33.2% of the VLBW infants registered with the CPQCC during the 12-month period. PNSs for CLD were administered to 8.2% of all VLBW infants in 2003, 8.6% of infants in the 42 hospitals that did not submit supplemental data (routine data-set group, compared with 7.6% in EDG hospitals). Of the 1401 VLBW infants in the EDG, 19.3% received PNSs; 3.6% received PNSs for only CLD, 11.8% for only non-CLD indications, and 4.0% for both indications. At all birth weight categories, non-CLD use was significantly greater than CLD use. The most common non-CLD indication was hypotension, followed by extubation stridor, for which 36 (16.3%) infants were treated. For hypotension, medications used were hydrocortisone followed by dexamethasone. Infants treated with PNSs exclusively for hypotension had a significantly higher incidence of intraventricular hemorrhage, periventricular leukomalacia, and death when compared with infants treated only for CLD or those who did not receive PNSs. CONCLUSIONS. The common early use of hydrocortisone for hypotension and the high morbidity and mortality in children receiving such treatment has not been recognized previously and prospective trials evaluating the short- and long-term risk/benefit of such treatment are urgently required.

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Section: Discussionmentioning

confidence: 99%

Section: Authorsmentioning

confidence: 99%

Prospective Evaluation of Postnatal Steroid Administration: A 1-Year Experience From the California Perinatal Quality Care Collaborative

Finer

Powers²,

et al. 2006

Pediatrics

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“…Earlier studies with animals found a variety of alterations in neurobehavioral outcome following PNS exposure (Benesova & Pavlik, 1989;Meaney & Stewart, 1981;Weichsel, 1977). Studies on sheep found that greater exposure to early steroid decreased fetal growth (Jobe, Wadda, Berry, Ikegami, & Ervin 1998).…”

Section: Review Of the Literaturementioning

confidence: 99%

“…They were used to aid in decreasing infant dependence on ventilators and on oxygen (Halliday & Ehrenkranz, 2001a, 2001b. At school-age follow-up, preterm infants whose chronic lung disease was treated with long-term steroid tapering doses were identified to have poor neurodevelopmental outcomes (Yeh et al, 2004).Earlier studies with animals found a variety of alterations in neurobehavioral outcome following PNS exposure (Benesova & Pavlik, 1989;Meaney & Stewart, 1981;Weichsel, 1977). Studies on sheep found that greater exposure to early steroid decreased fetal growth (Jobe, Wadda, Berry, Ikegami, & Ervin 1998).…”

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confidence: 99%

Cumulative Perinatal Steroids: Child Development of Preterm Infants

Purdy

Wiley

Smith

et al. 2008

Journal of Pediatric Nursing

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The development of premature infants may be altered due to exposure to high cumulative doses of the perinatal corticosteroid dexamethasone during critical growth periods. To compare child behavioral development of prematurely born infants who were exposed to higher perinatal steroids (PNS; N0.2 mg/kg) with that of infants exposed to lower PNS (≤0.2 mg/kg), we used the Vineland Adaptive Behavioral Scales to assess school-age behavioral outcomes of a historical cohort of 45 prematurely born infants. Children who had received higher PNS treatment were more likely to have lower overall behavioral developmental scores, especially lower social skills (p < .05). Higher PNS plus higher severity of illness during the first day of life based on the Clinical Risk Index for Babies (p = .016) and lower birth head size (p = .015) were linked with poorer behavioral outcomes among participants. Nursing practice includes promotion of quality care and should include closer evaluation of cumulative steroid therapy, severity of illness, and promotion of long-term follow-up support for premature infants. KeywordsPerinatal steroids; Dexamethasone; Preterm infants; Neurodevelopment PRETERM DELIVERY, ESTIMATED to occur in 7-11% of all North American births, is responsible for 75% of neonatal deaths (National Institutes of Health [NIH] Consensus Development Conference Statement, 1994). The outcomes of preterm infant survival are often dependent upon the provision of high-quality perinatal care, prior to 40 weeks' postconceptual age, as this is a vulnerable time in development. Over the past 30 years, synthetic or exogenous steroids have increasingly been prescribed before and after birth with the intent to improve infant lung maturity and outcomes. The 1994 NIH consensus panel recommendation for antenatal steroids (before birth) consisted of two doses of 12 mg of betamethasone given intramuscularly at 24-hour intervals or four doses of 6 mg of dexamethasone given intramuscularly at 12-hour intervals. In 2000, the panel revisited this recommendation and discouraged the use of multiple-course antenatal steroids because studies identified associations between steroids and impaired infant head growth and neurodevelop-mental outcomes (National Institutes of Health, 2000 Although commonly given for a variety of therapeutic reasons in perinatal care, the risks may not outweigh the benefits of either higher antenatal or postnatal steroid exposure. Perinatal steroids (PNS) are primarily administered for the promotion of infant lung maturation and reduction of respiratory distress syndrome and mortality (Huang, Dunlop, & Harper, 1999). Many premature infants have received multiple doses of therapeutic steroid drugs while in utero as well as in the postnatal period.Studies have retrospectively examined either antenatal or postnatal steroid effects . This study was the first to retrospectively identify the precise milligram amount of cumulative PNS dosed prior to 40 weeks and prospectively examine relationships with neurodevelopment of pre...

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“…Accumulating evidence from clinical trials has also demonstrated an association between postnatal steroid therapy and adverse neuromotor and cognitive outcomes (4,5). Furthermore, experimental studies in neonatal animals have demonstrated adverse effects of potent glucocorticoids, such as dexamethasone, on brain growth, cell division, differentiation, myelination, apoptosis, and neurogenesis (6)(7)(8).…”

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confidence: 99%

Statins prevent adverse effects of postnatal glucocorticoid therapy on the developing brain in rats

et al. 2013

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Background: Postnatal glucocorticoid therapy in the treatment of chronic lung disease benefits lung function, however it adversely affects brain development. We hypothesized that combined postnatal glucocorticoid and statin therapy diminishes adverse effects of glucocorticoids on the developing brain. Methods: On postnatal days (P) 1-3, one male pup per litter received i.p. injections of saline (control (C), n = 13) or dexamethasone (0.5, 0.3, 0.1 µg/g; D, n = 13), ± pravastatin (10 mg/ kg i.p.; CP, n = 12; DP, n = 15). Statins or saline continued from P4-6. At P21, brains were perfusion fixed for histological and stereological analyses. results: Relative to controls, dexamethasone reduced total (837 ± 23 vs. 723 ± 37), cortical (378 ± 12 vs. 329 ± 15), and deep gray matter (329 ± 12 vs. 284 ± 15) volume (mm 3 ), cortical neuronal number (23 ± 1 vs. 19 ± 1 × 10 6 ), and hippocampal neuronal soma volume (CA1: 1,206 ± 32 vs. 999 ± 32; dentate gyrus: 679 ± 28 vs. 542 ± 24 µm 3 ; all P < 0.05). Dexamethasone increased the glial fibrillary acidic protein-positive astrocyte density in the white matter (96 ± 2 vs. 110 ± 4/0.1 mm 2 ); P < 0.05. These effects no longer occurred in brains from pups treated with combined dexamethasone and pravastatin. Pravastatin alone had no effect on these variables. conclusion: Concomitant dexamethasone with statins in premature infants may be safer for the developing brain than dexamethasone alone in the treatment of chronic lung disease. c hronic lung disease is a common outcome in extremely preterm neonates with severe respiratory distress syndrome and carries a high incidence of morbidity and mortality (1). Glucocorticoids, predominantly dexamethasone, are used to decrease inflammatory responses, accelerate surfactant production, and lung maturation, thereby improving respiratory function (2).Despite the well-established beneficial effects of postnatal glucocorticoid therapy, there has been serious growing concern regarding their clinical use because of unwanted side effects on somatic growth and weight gain in premature babies (3,4). Accumulating evidence from clinical trials has also demonstrated an association between postnatal steroid therapy and adverse neuromotor and cognitive outcomes (4,5). Furthermore, experimental studies in neonatal animals have demonstrated adverse effects of potent glucocorticoids, such as dexamethasone, on brain growth, cell division, differentiation, myelination, apoptosis, and neurogenesis (6-8).To date, the mechanism underlying the unwanted side effects of glucocorticoid therapy on the developing brain remains unknown, preventing the identification of plausible modified therapies to maintain the beneficial, but prevent the adverse, effects of steroid treatment. Glucocorticoids are known to decrease nitric oxide (NO) bioavailability and increases in NO via antioxidant treatment have been shown to prevent or partially restore glucocorticoid-induced cardiovascular dysfunction and hypertension (9,10), implying impaired NO physiology as the culprit mecha...

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The therapeutic use of glucocorticoid hormones in the perinatal period: Potential neurological hazards

Cited by 119 publications

References 27 publications

Prospective Evaluation of Postnatal Steroid Administration: A 1-Year Experience From the California Perinatal Quality Care Collaborative

Prospective Evaluation of Postnatal Steroid Administration: A 1-Year Experience From the California Perinatal Quality Care Collaborative

Cumulative Perinatal Steroids: Child Development of Preterm Infants

Statins prevent adverse effects of postnatal glucocorticoid therapy on the developing brain in rats

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