Perinatal Risk and Protective Factors in the Development of Diffuse White Matter Abnormality on Term-Equivalent Age MRI in Infants Born Very Preterm
Authors: Parikh Nehal A. , Sharma Puneet , He Lili , Li Hailong , Altaye Mekibib , Priyanka Illapani Venkata Sita ,   for the Cincinnati Imaging & Neurodevelopment Early Prediction Study (CINEPS)
Published: August 2020

Importance

Diffuse white matter abnormality (DWMA) is the most common brain MRI finding in very preterm infants and is predictive of neurodevelopmental impairments. However, its etiology remains elusive and identifying perinatal risk and protective factors may allow clinicians to reduce the burden of DWMA.

Objective

To identify perinatal clinical factors that are associated with the development of objectively diagnosed DWMA in very preterm infants.

Design

A prospective cohort was enrolled between September 2016 and November 2019. Brain MRIs were collected at 39 to 45 weeks postmenstrual age (PMA) to evaluate DWMA volume. A pre-defined list of pertinent maternal characteristics, pregnancy/delivery data, and neonatal ICU data was collected for enrolled patients to identify antecedents of objectively diagnosed DWMA.

Setting

Five level III/IV NICUs in the greater Cincinnati, Ohio area.

Participants

A population-based sample of 392 very preterm infants born before 33 weeks gestational age.

Exposure

Very preterm birth with associated diseases and treatments.

Main Outcome and Measure

Objectively diagnosed DWMA volume on brain MRI at term-equivalent age.

Results

377 of the 392 very preterm infants (96%) had high quality MRI data. Mean (SD) gestational age was 29.3 (2.5) weeks. In multivariable linear regression analyses, pneumothorax (p=.027), severe bronchopulmonary dysplasia (BPD) (p=.009), severe retinopathy of prematurity (ROP) (p<0.001), and male sex (p=.041) were associated with increasing volume of DWMA. The following factors were associated with decreased risk of DWMA – dexamethasone for severe BPD (p=.004), duration of caffeine for severe BPD (p = 0.009), and exclusive maternal milk at NICU discharge (p=.049).

Conclusions and Relevance

Severe ROP and BPD exhibited the strongest adverse association with the development of DWMA. Caffeine and dexamethasone treatments for infants with severe BPD exhibited a protective effect against development of DWMA. The beneficial association with maternal milk is also a modifiable factor that has clinical implications.

Key Points

Question

What perinatal clinical factors are independently associated with the development of diffuse white matter abnormality (DWMA) in very preterm infants?

Findings

In this prospective cohort study, pneumothorax, severe bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity, and male sex were significantly associated with an increased risk of DWMA. Significant protective factors included dexamethasone for severe BPD, duration of caffeine for severe BPD, and exclusive maternal milk diet at NICU discharge.

Meaning

Knowledge of these common and modifiable neonatal diseases and treatments may allow clinicians to reduce the burden of DWMA development through targeted prevention or treatments approaches.