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Antecedents of Objectively Diagnosed Diffuse White Matter Abnormality in Very Preterm Infants
Nehal A Parikh1, Lili He2, Hailong Li2
1Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
Insights
Diffuse white matter abnormality in preterm infants is linked to perinatal inflammation. Severe retinopathy and bronchopulmonary dysplasia are risk factors, while maternal 17-hydroxyprogesterone treatment shows protective effects.
Area of Science:
- Neonatal Neurology
- Neuroimaging
- Developmental Pediatrics
Background:
- Diffuse white matter abnormality (diffuse excessive high signal intensity) is common in very preterm infants' brain MRIs.
- The etiology of this abnormality remains poorly understood.
- This study investigates perinatal and neonatal inflammation-associated factors.
Purpose of the Study:
- To evaluate perinatal and neonatal inflammation-associated antecedents of diffuse white matter abnormality on MRI in very preterm infants.
- To identify clinical risk factors and protective elements associated with this condition.
Main Methods:
- Prospective enrollment of 110 very preterm infants (≤31 weeks gestational age).
- Collection of data on perinatal/neonatal exposures, focusing on inflammation.
- Structural MRI at term-equivalent age to quantify diffuse white matter abnormality.
- Multivariable regression analysis to identify clinical antecedents.
Main Results:
- In 98 infants, severe retinopathy of prematurity and bronchopulmonary dysplasia were independent risk factors for diffuse white matter abnormality.
- Maternal treatment with 17-hydroxyprogesterone demonstrated a protective effect.
- Univariate analyses showed associations between inflammation-initiating illnesses and the abnormality.
Conclusions:
- Several perinatal and neonatal clinical factors are associated with diffuse white matter abnormality.
- Inflammation may be a common underlying mechanism, but larger studies are needed for validation.
- Findings highlight potential targets for intervention in very preterm infants.
Background:
Diffuse white matter abnormality (diffuse excessive high signal intensity) is the most common finding on structural brain magnetic resonance imaging (MRI) at term-equivalent age in very preterm infants. Yet, there remains a large gap in our understanding of the etiology of diffuse white matter abnormality. Our objective was to evaluate perinatal and neonatal inflammation-associated antecedents of diffuse white matter abnormality on MRI.
Methods:
We prospectively enrolled 110 very preterm infants born at ≤31 weeks gestational age and collected data on multiple perinatal/neonatal exposures, especially inflammation initiating-illnesses. We performed structural MRI at term-equivalent age and quantified the volume of diffuse white matter abnormality objectively. Multivariable regression was used to identify clinical antecedents of diffuse white matter abnormality.
Results:
The mean (S.D.) birth gestational age of the final study sample of 98 very preterm infants was 28.3 (2.5) weeks. Multiple inflammation initiating-illnesses were associated with diffuse white matter abnormality in univariate analyses. In multivariable linear regression analyses controlling for gestational age, severe retinopathy of prematurity (P < 0.001) and bronchopulmonary dysplasia (P = 0.006) were independent risk factors, whereas maternal treatment with 17-hydroxyprogesterone (P < 0.001) was protective of later development of objectively quantified diffuse white matter abnormality.
Conclusions:
We identified several perinatal and neonatal antecedent clinical factors associated with diffuse white matter abnormality. Although we found some support for inflammation as a common underlying mechanism, larger studies are needed to validate inflammation as a potential common pathway to the development of diffuse white matter abnormality in very preterm infants.
