Severity of punctate white matter lesions in preterm infants: antecedents and cerebral palsy prediction

Abstract

Background: The objectives were to investigate antecedent factors of punctate white matter lesions (PWML) severity on MRI at term-corrected age (CA) and to evaluate its ability to independently predict cerebral palsy (CP) in preterm infants.

Methods: We studied infants born at ≤32 weeks' gestational age [GA] with brain MRI at term CA, a standardized neuromotor exam to determine CP diagnosis, and composite scores from Bayley Scales of Infant and Toddler Development-III(BSID-III) at 2 years CA. MRIs with PWML were manually segmented and volume quantified with high reliability. We correlated >50 perinatal antecedent factors with PWML severity and conducted multivariable regression analyses to assess PWML ability to independently predict neurodevelopmental outcomes at age 2.

Results: Of 392 infants, 28 (7.1%) had PWML; 339 (86%) were assessed at age 2, 39 (11.6%) had CP. Moderate-severe acute histologic chorioamnionitis (HCA), prenatal opioid use, and antenatal corticosteroids were independently associated with PWML severity. Increasing PWML severity was significantly predictive of CP (OR 2.12; 95% CI:1.34,3.37), independent of known predictors, but not BSID-III scores.

Conclusions: Increasing burden of PWML was associated with two-fold risk of CP in preterm infants. We also identified HCA, prenatal opioids, and antenatal corticosteroids as modifiable risk and protective factors for PWML that may be amenable to prevention efforts.

Impact: Punctate white matter lesions (PWML) are commonly seen on MRI scans in preterm infants, yet the antecedent factors associated with PWML are not well characterized. While prior literature is conflicting on the ability of PWML to predict neurodevelopmental impairments, our study demonstrated that objectively quantified PWML are independently predictive of the development of cerebral palsy. We identified modifiable factors such as histologic chorioamnionitis as a risk factor and antenatal corticosteroids as a protective factor against PWML development. Our findings may facilitate earlier identification of infants at risk for PWML and cerebral palsy.

Fig. 1. Punctate white matter lesions (PWML) with varying degrees of severity displayed using raw and segmented T1-weighted MRI scans (1 mm resolution) at term-equivalent age in three preterm infants.

a 31 weeks’ gestational age (GA) infant with mild PWML (13 mm³; lowest tercile for volume [3–15 mm³]) in the left periventricular white matter. This infant also had another solitary lesion in the contralateral hemisphere (not shown); b corresponding segmented image; c 32 weeks’ GA infant with moderate PWML severity (71 mm³; middle tercile [23–71 mm³]) in the right central white matter. This infant also had a second contiguous sagittal slice with similar lesions and additional lesions in the contralateral hemisphere (not shown); d corresponding segmented image; e 28 weeks’ GA infant with severe PWML severity (185 mm³; highest tercile [75–338 mm³]) in the right central white matter; f corresponding segmented image; g same 28 weeks’ GA infant with more lesions in a contiguous sagittal slice; this infant also has a third contiguous slice with lesions and additional lesions in the contralateral hemisphere (not shown); h corresponding segmented image.