Published online August 17, 2009
PEDIATRICS Vol. 124 No. 3 September 2009, pp. e450-e458 (doi:10.1542/peds.2008-3249)
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ARTICLE

Fetal Growth Restriction and Chronic Lung Disease Among Infants Born Before the 28th Week of Gestation

Carl Bose, MDa, Linda J. Van Marter, MD, MPHb,c,d, Matthew Laughon, MD, MPHa, T. Michael O'Shea, MD, MPHe, Elizabeth N. Allred, MSf,g,h, Padmani Karna, MDi, Richard A. Ehrenkranz, MDi,j, Kim Boggess, MDk, Alan Leviton, MD, MSf,g for the Extremely Low Gestational Age Newborn Study Investigators

Departments of a Pediatrics
k Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Departments of b Pediatrics
f Neurology, Harvard Medical School, Boston, Massachusetts
Departments of c Pediatrics
g Neurology, Children's Hospital, Boston, Massachusetts
d Department of Pediatrics, Brigham and Women's Hospital, Boston, Massachusetts
e Department of Pediatrics, School of Medicine, Wake Forest University, Winston-Salem, North Carolina
h Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
i Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan
j Department of Pediatrics, School of Medicine, Yale University, New Haven, Connecticut

OBJECTIVE: Improvement in survival of extremely premature infants over the past several decades has resulted in an increase in the number of infants with chronic lung disease (CLD). Historical neonatal exposures associated with CLD now less frequently precede the disease. There is now increasing interest in exposures and events before delivery that predict CLD. The objective of this study was to identify current prenatal predictors of CLD.

METHODS: We collected data about prenatal, placental, and neonatal characteristics of 1241 newborns who were delivered before completion of the 28th week of gestation. Associations between prenatal factors, microbiologic and histologic characteristics of the placenta, and selected neonatal characteristics and CLD risk were first evaluated in univariate analyses. Subsequent multivariate analyses investigated the contribution of prenatal factors, particularly fetal growth restriction (FGR), to CLD risk.

RESULTS: Among the prenatal factors, birth weight z scores, used as a marker of FGR, provided the most information about CLD risk. Indicators of placental inflammation and infection were not associated with increased risk of CLD. Within nearly all strata of prenatal, placental, and neonatal variables, growth-restricted infants were at increased CLD risk, compared with infants who were not growth-restricted. FGR was the only maternal or prenatal characteristic that was highly predictive of CLD after adjustment for other risk factors.

CONCLUSIONS: FGR is independently associated with the risk of CLD. Thus, factors that control fetal somatic growth may have a significant impact on vulnerability to lung injury and in this way increase CLD risk.

Key Words: chronic lung disease • bronchopulmonary dysplasia • prematurity • preterm infant

Abbreviations: ELGAN—extremely low gestational age newborn • BW—birth weight • SGA—small-for-gestational age • CLD—chronic lung disease • FI—fetal indication • FGR—fetal growth restriction • IL-6—interleukin 6 • PMA—postmenstrual age • FIO2—fraction of inspired oxygen

Accepted Apr 10, 2009.


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