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The ELGAN study of the brain and related disorders in extremely low gestational age newborns
T M O'Shea1, E N Allred, O Dammann
1Department of Pediatrics (Neonatology), Wake Forest University Health Sciences, Medical Center Blvd, Winston-Salem, NC 27157, USA. moshea@wfubmc.edu
Insights
Extremely low gestational age newborns (ELGANs) face brain damage risks. This study found placental microorganisms strongly linked to brain abnormalities in these vulnerable infants, highlighting a new factor in their care.
Area of Science:
- Neonatal neurology
- Perinatology
- Developmental pediatrics
Background:
- Extremely low gestational age newborns (ELGANs) exhibit a high incidence of structural and functional brain abnormalities.
- Identifying contributing factors to brain damage in ELGANs is crucial for improving outcomes.
Purpose of the Study:
- To identify factors associated with brain damage in extremely low gestational age newborns (ELGANs).
Main Methods:
- A multi-center cohort study involving 1506 ELGANs born before 28 weeks gestation.
- Data collected via maternal interviews, chart reviews, placental examination (microbiologic and histologic), and cord/blood spot protein analysis.
- Brain injury assessed via cranial ultrasound, head circumference, and neurodevelopmental outcomes at 2 years corrected age.
Main Results:
- Associations found between white matter damage/cerebral palsy and preterm labor, ruptured membranes, placental inflammation, and microorganisms in placental parenchyma.
- Lower gestational age, increased neonatal illness severity, chronic lung disease, bacteremia, and necrotizing enterocolitis were also linked to brain damage.
- Microorganisms in placenta, including skin microflora, were identified as a significant factor.
Conclusions:
- The study confirms known risk factors for brain damage in ELGANs.
- Provides strong evidence for the association between placental microorganisms and brain damage in extremely preterm infants.
- Suggests a potential role for placental microbial environment in neonatal brain injury.
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.
