Randomized Placebo-controlled Trial of a 42-Day Tapering Course of Dexamethasone to Reduce the Duration of Ventilator Dependency in Very Low Birth Weight Infants

Kothadia, J. M.; O’Shea, T. Michael; Roberts, Donald F.; Auringer, Sam T.; Weaver, Richard G.; Dillard, Robert G.

doi:10.1542/peds.104.1.22

Cited by 93 publications

(61 citation statements)

References 27 publications

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“…Participants were children, 8 to 11 years old, who as neonates participated in a randomized controlled trial of a 42-day tapering course of postnatal DEX to reduce the duration of ventilator dependency (27,28). The children were born between 1992 and 1995, and met the following eligibility criteria: 1) birth weight <1501g; 2) age 15 to 25 days; 3) ventilator dependence without improvement; 4) absence of clinical signs of sepsis; and 5) absence of patent ductus arteriosus by echocardiography.…”

Section: Participantsmentioning

confidence: 99%

Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

Nixon

Washburn

Schechter

et al. 2007

The Journal of Pediatrics

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Objective-To determine if postnatal dexamethasone (DEX) exposure affects pulmonary outcomes at school-age in children born with very low birth weight (VLBW).Study design-Follow-up study of 68 VLBW children who participated in a randomized controlled trial (RCT) of postnatal DEX. Pulmonary function was assessed by spirometry. Current asthma status was obtained from a parent.Results-Sixty-eight % of the placebo group had below normal forced expiratory volume in 1 second (FEV 1 ) compared to 40% of the DEX group (X 2 = 4.84, p=.03), with trends for lower forced vital capacity (FVC) and FEV 1 values in the placebo group. Fifty % of placebo group and 34% of DEX group had below normal FEV 1 /FVC (X 2 =1.59; p =.21). Parent-reported prevalence of asthma did not differ between groups. Logistic regression analysis suggested that the positive effects of DEX on pulmonary function at follow-up were mediated in part by shortened postnatal exposure to mechanical ventilation.Conclusions-Postnatal DEX exposure was associated with higher expiratory flow with no adverse effects on pulmonary outcomes at school-age. The prevalence of asthma and impaired pulmonary function underscore the influence of neonatal illness on health at school age, and stress the importance of repeated follow-up examinations of these children. Keywordsprematurity; chronic lung disease; bronchopulmonary dysplasia; children; corticosteroid; lung function asthma Approximately 1.5% of infants are born prematurely each year with very low birth weight (VLBW) (birth weight < 1501 grams) (1), and about 19-23% of these infants will develop chronic lung disease (CLD) (2,3). A diagnosis of CLD has been associated with greater Address correspondence to: Patricia A. Nixon, Ph.D., Wake Forest University, HES Dept. P.O. Box 7868, Winston-Salem, NC 27109-7868, Phone (336) Fax (336) 758-4680, Email nixonpa@wfu.edu. edited by AJ and WFB Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. hospital readmission rates for respiratory morbidity during the first five years of life (4), increased odds of asthma (4) and respiratory symptoms in childhood (5), and reduced pulmonary function in infancy (6), childhood (7,8), adolescence (9), and young adulthood (10) compared to their VLBW peers without CLD. Systematic reviews indicate that treatment of VLBW infants with corticosteroids, primarily dexamethasone (DEX), in the first few weeks of life significantly decreases duration of ventilator dependence and the incidence of CLD (11-13). The beneficial effects of postnatal corticosteroids on the lung are believed to be related to reduce...

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Section: Participantsmentioning

confidence: 99%

Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

Nixon

Washburn

Schechter

et al. 2007

The Journal of Pediatrics

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“…In fact, both the occurrence of oxygen use at 36 weeks PMA and long-term pulmonary outcomes can be modified independently. Treatment with vitamin A 19,20 or steroids 21,22 can alter the incidence of infants that are on oxygen at 36 weeks PMA without having any measurable impact on longterm pulmonary outcomes. In contrast, treatment with CuZn superoxide dismutase 23 does not alter the incidence of infants on oxygen at 36 weeks PMA; yet it has a significantly positive impact on long-term pulmonary outcome.…”

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confidence: 99%

Bronchopulmonary dysplasia: pathway from disease to long-term outcome

Lefkowitz

Rosenberg²

2008

J Perinatol

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“…Until recently, administration of a prolonged course of postnatal dexamethasone to ELBW infants was frequently practiced in an attempt to lessen the progression of CLD. Although clinical trials using dexamethasone in this fashion failed to consistently demonstrate improvement in mortality or length of hospitalization, exposures of up to 42 days were commonly used in many neonatal units (4,8,17,55,56). A recent study examining the outcome of ELBW infants (birth weight between 500 and 750 g) found that 43% of those infants born from 1990 to 1992 received dexamethasone compared with 84% of ELBW infants born between 1993 and 1995 (40).…”

mentioning

confidence: 99%

Effect of neonatal dexamethasone exposure on growth and neurological development in the adult rat

Neal¹,

Weidemann²,

Kabbaj³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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Neal, Charles R., Jr., Gabrielle Weidemann, Mohamed Kabbaj, and Delia M. Vázquez. Effect of neonatal dexamethasone exposure on growth and neurological development in the adult rat. Am J Physiol Regul Integr Comp Physiol 287: R375-R385, 2004. First published April 29, 2004; 10.1152/ajpregu.00012.2004.-Until recently, the synthetic glucocorticoid dexamethasone was commonly used to lessen the morbidity of chronic lung disease in premature infants. This practice diminished as dexamethasone use was linked to an increased incidence of cerebral palsy and short-term neurodevelopmental delay. Of more concern is the fact that we know little regarding dexamethasone effects on long-term neurodevelopment. To study the effects of neonatal dexamethasone exposure on long-term neurodevelopment, we have developed a rat model where newborn pups are exposed to tapering doses of dexamethasone at time points corresponding to the neurodevelopmental age when human infants are traditionally exposed to this drug in the neonatal intensive care unit. Using a within-litter design, pups were assigned to one of three groups on postnatal day 2 (P2): handled controls, saline-injected controls, and animals receiving intramuscular dexamethasone between P3 and P6. Somatic growth was decreased in dexamethasone-treated animals. Dexamethasone-treated animals demonstrated slight delays in indexes of neurodevelopment and physical maturation at P7 and P14, but not P20. In adolescence (P45), there was no difference between groups in an open field test. However, as adult dexamethasone-treated animals were less active in the open field and spent more time in closed arms of the elevated plus maze. The serum corticosterone response to crowding stress in dexamethasone-treated animals was no different from controls, but they demonstrate a delay in return of corticosterone levels to baseline. These differences in behavior and hormonal stress responsiveness suggest that neonatal dexamethasone exposure may permanently alter function of the neuroendocrine stress axis. steroids; prematurity; brain; corticosterone; limbic-hypothalamicpituitary-adrenal axis SEVERE RESPIRATORY DISTRESS syndrome is commonly experienced in extremely low birth weight (ELBW) infants, resulting in various degrees of ventilator and/or oxygen dependency and subsequent onset of chronic lung disease (CLD). Until recently, administration of a prolonged course of postnatal dexamethasone to ELBW infants was frequently practiced in an attempt to lessen the progression of CLD. Although clinical trials using dexamethasone in this fashion failed to consistently demonstrate improvement in mortality or length of hospitalization, exposures of up to 42 days were commonly used in many neonatal units (4,8,17,55,56). A recent study examining the outcome of ELBW infants (birth weight between 500 and 750 g) found that 43% of those infants born from 1990 to 1992 received dexamethasone compared with 84% of ELBW infants born between 1993 and 1995 (40). Routine use of dexamethasone continued until Yeh and colleag...

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Randomized Placebo-controlled Trial of a 42-Day Tapering Course of Dexamethasone to Reduce the Duration of Ventilator Dependency in Very Low Birth Weight Infants

Abstract: A 42-day tapering course of dexamethasone decreases the duration of ventilator and oxygen dependency in very low birth weight infants and is not associated with an increased risk of short-term adverse effects.

Cited by 93 publications

References 27 publications

Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

Bronchopulmonary dysplasia: pathway from disease to long-term outcome

Effect of neonatal dexamethasone exposure on growth and neurological development in the adult rat

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