Published online July 2, 2007
PEDIATRICS Vol. 120 No. 1 July 2007, pp. 40-48 (doi:10.1542/peds.2006-3158)

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ARTICLE

Growth and Neurodevelopmental Outcomes After Early Low-Dose Hydrocortisone Treatment in Extremely Low Birth Weight Infants

Kristi L. Watterberg, MD^a, Michele L. Shaffer, PhD^b, Mary J. Mishefske, MD^c, Corinne L. Leach, MD, PhD^d, Mark C. Mammel, MD^e,f, Robert J. Couser, MD^g, Soraya Abbasi, MD^h, Cynthia H. Cole, MDⁱ, Susan W. Aucott, MD^j, Elizabeth H. Thilo, MD^k, Henry J. Rozycki, MD^l and Conra Backstrom Lacy, RN^m

^a Division of Neonatology
^m General Clinical Research Center, University of New Mexico School of Medicine, Albuquerque, New Mexico
^b Department of Health Evaluation Sciences and Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania
^c Department of Pediatrics, St Joseph Regional Medical Center, Milwaukee, Wisconsin
^d Department of Pediatrics, State University of New York, Buffalo, New York
^e Newborn Research, Children's Hospital of St Paul, St Paul, Minnesota
^f Department of Pediatrics, University of Minnesota School of Medicine, St Paul, Minnesota
^g Division of Neonatology, Children's Hospital and Clinics of Minneapolis, Minneapolis, Minnesota
^h Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania
ⁱ Department of Neonatology, Beth Israel Deaconess Hospital, Boston, Massachusetts
^j Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
^k Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado
^l Department of Pediatrics, Virginia Commonwealth University, Richmond, Virginia

BACKGROUND. Low cortisol concentrations in premature infants have been correlated with increased severity of illness, hypotension, mortality, and development of bronchopulmonary dysplasia. A total of 360 mechanically ventilated infants with a birth weight of 500 to 999 g were enrolled in a randomized, multicenter trial of prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia. Mortality and bronchopulmonary dysplasia were decreased in the hydrocortisone-treated patients exposed to chorioamnionitis. We now report outcomes at 18 to 22 months' corrected age.

PATIENTS AND METHODS. Surviving infants were evaluated with standardized neurologic examination and Bayley Scales of Infant Development-II. Neurodevelopmental impairment was defined as a Mental Developmental Index or Psychomotor Developmental Index of <70, cerebral palsy, blindness or deafness.

RESULTS. A total of 252 (87%) of 291 survivors were evaluated. Cerebral palsy was diagnosed in 13% of hydrocortisone-treated versus 14% of placebo-treated infants. Fewer hydrocortisone-treated infants had a Mental Development Index <70, and more of the hydrocortisone-treated infants showed evidence of awareness of object permanence. Incidence of neurodevelopmental impairment was not different (39% [hydrocortisone] vs 44% [placebo]). There were no differences in physical growth measures. Chorioamnionitis-exposed infants treated with hydrocortisone were shorter and weighed less than controls but had no evidence of neurodevelopmental impairment. Among infants not exposed to chorioamnionitis, hydrocortisone-treated patients were less likely to have a Mental Development Index of <70 or to be receiving glucocorticoids at follow-up.

CONCLUSIONS. Early, low-dose hydrocortisone treatment was not associated with increased cerebral palsy. Treated infants had indicators of improved developmental outcome. Together with the short-term benefit previously reported, these data support additional studies of hydrocortisone treatment of adrenal insufficiency in extremely premature infants.

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Key Words: cerebral palsy • hydrocortisone • extremely preterm infant • developmental assessment • postnatal steroid therapy

Abbreviations: BPD—bronchopulmonary dysplasia • NDI—neurodevelopmental impairment • CP—cerebral palsy • ELBW—extremely low birth weight • MDI—Mental Development Index • PDI—Psychomotor Development Index • BRS—Behavior Rating Scale

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Accepted Jan 31, 2007.

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