Perinatal Risk and Protective Factors in the Development of Diffuse White Matter Abnormality on Term-Equivalent Age Magnetic Resonance Imaging in Infants Born Very Preterm

J Pediatr. 2021 Jun:233:58-65.e3. doi: 10.1016/j.jpeds.2020.11.058. Epub 2020 Nov 28.


Objective: To identify perinatal clinical diseases and treatments that are associated with the development of objectively diagnosed diffuse white matter abnormality (DWMA) on structural magnetic resonance imaging (MRI) at term-equivalent age in infants born very preterm.

Study design: A prospective cohort of 392 infants born very preterm (≤32 weeks of gestational age) was enrolled from 5 level III/IV neonatal intensive care units between September 2016 and November 2019. MRIs of the brain were collected at 39 to 45 weeks of postmenstrual age to evaluate DWMA volume. A predefined list of pertinent maternal characteristics, pregnancy/delivery data, and neonatal intensive care unit data were collected for enrolled patients to identify antecedents of objectively diagnosed DWMA.

Results: Of the 392 infants in the cohort, 377 (96%) had high-quality MRI data. Their 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 (P < .001), and male sex (P = .041) were associated with increasing volume of DWMA. The following factors were associated with decreased risk of DWMA: postnatal dexamethasone therapy for severe BPD (P = .004), duration of caffeine therapy for severe BPD (P = .009), and exclusive maternal milk diet at neonatal intensive care unit discharge (P = .049).

Conclusions: Severe retinopathy of prematurity and BPD exhibited the strongest adverse association with development of DWMA. We also identified treatments and nutritional factors that appear protective against the development of DWMA that also have implications for the clinical care of infants born very preterm.

Keywords: epidemiology; etiology; infant; magnetic resonance imaging; preterm.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bronchopulmonary Dysplasia / drug therapy
  • Bronchopulmonary Dysplasia / epidemiology
  • Caffeine / therapeutic use
  • Cohort Studies
  • Dexamethasone / therapeutic use
  • Female
  • Gestational Age
  • Glucocorticoids / therapeutic use
  • Humans
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Intensive Care Units, Neonatal
  • Magnetic Resonance Imaging*
  • Male
  • Milk, Human
  • Multivariate Analysis
  • Pneumothorax / epidemiology
  • Protective Factors
  • Retinopathy of Prematurity / epidemiology
  • Sex Factors
  • White Matter / abnormalities*
  • White Matter / diagnostic imaging*


  • Glucocorticoids
  • Caffeine
  • Dexamethasone