The ELGAN study of the brain and related disorders in extremely low gestational age newborns

O'Shea, T.M.; Allred, E.N.; Dammann, O.; Hirtz, D.; Kuban, K.C.K.; Paneth, N.; Leviton, A.; ELGAN study Investigators,

doi:10.1016/j.earlhumdev.2009.08.060

« Previous Next »Early Human Development
Volume 85, Issue 11 , Pages 719-725, November 2009

The ELGAN study of the brain and related disorders in extremely low gestational age newborns

T.M. O'Shea
- Department of Pediatrics (Neonatology), Wake Forest University Health Sciences, Medical Center Blvd, Winston-Salem, NC 27157, USA
- Corresponding author. Tel.: +1 336 716 252; fax: +1 336 716 2525.
E.N. Allred
- Neuroepidemiology Unit, Children's Hospital of Boston, Boston, MA, USA
O. Dammann
- Neuroepidemiology Unit, Children's Hospital of Boston, Boston, MA, USA
- Department of Pediatrics (Newborn Medicine), Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA
- Perinatal Neuroepidemiology Unit, Departments of Gynecology and Pediatrics, Hannover Medical School, Germany
D. Hirtz
- National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
K.C.K. Kuban
- Department of Pediatrics (Pediatric Neurology), Boston Medical Center, Boston, MA, USA
N. Paneth
- Department of Epidemiology, Michigan State University, East Lansing, MI, USA
A. Leviton
- Neuroepidemiology Unit, Children's Hospital of Boston, Boston, MA, USA
ELGAN study Investigators

Abstract

Background

Extremely low gestational age newborns (ELGANs) are at increased risk for structural and functional brain abnormalities.

Aim

To identify factors that contribute to brain damage in ELGANs.

Study design

Multi-center cohort study.

Subjects

We enrolled 1506 ELGANs born before 28 weeks gestation at 14 sites; 1201 (80%) survived to 2 years corrected age. Information about exposures and characteristics was collected by maternal interview, from chart review, microbiologic and histological examination of placentas, and measurement of proteins in umbilical cord and early postnatal blood spots.

Outcome measures

Indicators of white matter damage, i.e. ventriculomegaly and echolucent lesions, on protocol cranial ultrasound scans; head circumference and developmental outcomes at 24 months adjusted age, i.e., cerebral palsy, mental and motor scales of the Bayley Scales of Infant Development, and a screen for autism spectrum disorders.

Results

ELGAN Study publications thus far provide evidence that the following are associated with ultrasongraphically detected white matter damage, cerebral palsy, or both: preterm delivery attributed to preterm labor, prelabor premature rupture of membranes, or cervical insufficiency; recovery of microorganisms in the placenta parenchyma, including species categorized as human skin microflora; histological evidence of placental inflammation; lower gestational age at delivery; greater neonatal illness severity; severe chronic lung disease; neonatal bacteremia; and necrotizing enterocolitis.

Conclusions

In addition to supporting a potential role for many previously identified antecedents of brain damage in ELGANs, our study is the first to provide strong evidence that brain damage in extremely preterm infants is associated with microorganisms in placenta parenchyma.

Abbreviations: ELGAN, extremely low gestational age newborn, M-CHAT, Modified Checklist for Autism in Toddlers, SNAP, Score for Acute Neonatal Physiology

Keywords: Prematurity, Developmental disability, Autism spectrum disorder, Autism, Cerebral palsy, Chorioamnionitis, Pregnancy, Preeclampsia