Published online July 20, 2009
PEDIATRICS Vol. 124 No. 2 August 2009, pp. 637-648 (doi:10.1542/peds.2008-2874)

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ARTICLE

Chronic Lung Disease and Developmental Delay at 2 Years of Age in Children Born Before 28 Weeks' Gestation

Matthew Laughon, MD, MPH^a, Michael T. O'Shea, MD, MPH^b, Elizabeth N. Allred, MS^c,d,e, Carl Bose, MD^a, Karl Kuban, MD^f, Linda J. Van Marter, MD, MPH^g,h,i, Richard A. Ehrenkranz, MD^j, Alan Leviton, MD, MS^c,e for the ELGAN Study Investigators

^a Division of Neonatal-Perinatal Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina
^b Division of Neonatology, School of Medicine, Wake Forest University, Winston-Salem, North Carolina
^c Department of Neurology, Harvard Medical School, Boston, Massachusetts
^d Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
^h Division of Newborn Medicine
^e Department of Neurology, Children's Hospital Boston, Boston, Massachusetts
^f Division of Pediatric Neurology, Boston Medical Center, Boston, Massachusetts
ⁱ Division of Newborn Medicine, Brigham and Women's Hospital, Boston, Massachusetts
^j Division of Perinatal Medicine, School of Medicine, Yale University, New Haven, Connecticut and,
^g Department of Pediatrics, Harvard Medical School, Boston, Massachusetts

INTRODUCTION: Extremely low gestational age newborns (ELGANs) are at increased risk of chronic lung disease (CLD) and of developmental delay. Some studies have suggested that CLD contributes to developmental delay.

PATIENTS AND METHODS: We examined data collected prospectively on 915 infants born before the 28th week of gestation in 2002–2004 who were assessed at 24 months of age with the Bayley Scales of Infant Development-2nd Edition or the Vineland Adaptive Behavior Scales. We excluded infants who were not able to walk independently (Gross Motor Function Classification System score < 1) and, therefore, more likely to have functionally important fine motor impairments. We defined CLD as receipt of oxygen at 36 weeks' postmenstrual age and classified infants as either not receiving mechanical ventilation (MV) (CLD without MV) or receiving MV (CLD with MV).

RESULTS: Forty-nine percent of ELGANs had CLD; of these, 14% were receiving MV at 36 weeks' postmenstrual age. ELGANs without CLD had the lowest risk of a Mental Developmental Index (MDI) or a Psychomotor Developmental Index (PDI) of <55, followed by ELGANs with CLD not receiving MV, and ELGANs with CLD receiving MV (9%, 12%, and 18% for the MDI and 7%, 10%, and 20% for the PDI, respectively). In time-oriented multivariate models, the risk of an MDI of <55 was associated with the following variables: gestational age of <25 weeks; single mother; late bacteremia; pneumothorax; and necrotizing enterocolitis. The risk of a PDI of <55 was associated with variables such as single mother, a complete course of antenatal corticosteroids, early and persistent pulmonary dysfunction, pulmonary deterioration during the second postnatal week, pneumothorax, and pulmonary interstitial emphysema. CLD, without or with MV, was not associated with the risk of either a low MDI or a low PDI. However, CLD with MV approached, but did not achieve, nominal statistical significance (odds ratio: 1.9 [95% confidence interval: 0.97–3.9]) for the association with a PDI of <55.

CONCLUSIONS: Among children without severe gross motor delays, risk factors for CLD account for the association between CLD and developmental delay. Once those factors are considered in time-oriented risk models, CLD does not seem to increase the risk of either a low MDI or a low PDI. However, severe CLD might increase the risk of a low PDI.

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Key Words: lung disease • prematurity • preterm infant • neurodevelopmental outcome

Abbreviations: CLD—chronic lung disease • MV—mechanical ventilation • PDA—patent ductus arteriosus • ELGAN—extremely low gestational age newborn • BSID-II—Bayley Scales of Infant Development-2nd Edition • VABS—Vineland Adaptive Behavioral Scales • MDI—Mental developmental index • PDI—Psychomotor developmental index • GMFCS—Gross Motor Function Classification System • SNAP-II—Score for Neonatal Acute Physiology-II • FIO₂—fraction of inspired oxygen • PD—pulmonary deterioration • EPPD—early and persistent pulmonary dysfunction • PIE—pulmonary interstitial emphysema • ROP—retinopathy of prematurity • PMA—postmenstrual age • CMV—conventional mechanical ventilation • NEC—necrotizing enterocolitis • TORM—time-oriented risk model • CPAP— continuous positive airway pressure • OR—odds ratio • CI—confidence interval

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Accepted Feb 3, 2009.

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