Neuropediatrics 2023; 54(01): 006-013
DOI: 10.1055/s-0042-1759789
Original Article

Comparison of the Clinical Characteristics of Infants with Punctate White Matter Lesions and/or Cystic Lesions

1   Neonatal Division, Maternal and Perinatal Center, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
2   Division of Neuropediatrics, Nagano-Children's Hospital, Azumino, Nagano, Japan
Hiroko Hara
3   Department of Diagnostic Radiology, Kurashiki Central Hospital, Kurashiki, Okayama, Japan
Tatsuo Sawada
4   Department of Pathology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
Masaki Wada
1   Neonatal Division, Maternal and Perinatal Center, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
› Institutsangaben
Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.


Background We aimed to investigate the differences in the clinical characteristics of preterm infants with punctate white matter lesions (PWMLs) and those with cystic periventricular leukomalacia (cPVL) using term-equivalent age magnetic resonance imaging.

Methods We conducted a retrospective case–control study to explore the clinical characteristics of infants (< 35 weeks gestation, born between 2007 and 2017 in a single Level III perinatal center) with PWML, cPVL or with PWML plus cPVL and compared them with those of gestational-age-matched controls.

Results Among 602 infants, 29, 5, and 4 were assigned to the PWML group, cPVL group, and PWML plus cPVL group (PWML-cPVL group), respectively. Compared to the control group (n = 87), the PWML group had higher birth weights (p = 0.04), rates of histological chorioamnionitis (p = 0.04), vaginal delivery (p = 0.008), and early heart contraction failure (within 72 hours after birth) (p = 0.003). The cPVL group had lower umbilical blood gas base excess (p = 0.01), higher rate of late-onset circulatory collapse (p = 0.008), and higher hydrocortisone requirements (p = 0.03) than the control group (n = 15). The PWML-cPVL group had a higher rate of intraventricular hemorrhage (p = 0.03) than the control group (n = 12). In the multivariate logistic regression analysis, vaginal delivery (odds ratio [OR] = 3.5; 95% confidence interval [CI] = 1.37–9.40; p = 0.009), higher birth weight (per 1 g) (OR = 1.001; 95% CI = 1.0001–1.002; p = 0.03), and early heart contraction failure (OR = 5.4; 95% CI = 1.84–16.8; p = 0.002), were independent risk factors for PWML.

Conclusion Clinical characteristics of infants with PWML compared with gestational-age-matched controls differed from those with cPVL or PWML plus cPVL, as PWML were not related to severe disruption of hemodynamics.

Authors' Contributions

K.I. designed the study, collected clinical data, and drafted the initial manuscript. H.H. interpreted the brain imaging scans and revised the manuscript for radiological content. T.S. revised the manuscript for pathological content. M.W. coordinated and supervised the study and reviewed the manuscript.

Data Availability Statement

All data generated or analyzed during this study are included in this article and its [Supplementary Material] (online only). Further enquiries can be directed to the corresponding author.

Supplementary Material


Eingereicht: 03. November 2021

Angenommen: 13. Oktober 2022

Artikel online veröffentlicht:
21. Dezember 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 van Haastert IC, Groenendaal F, Uiterwaal CS. et al. Decreasing incidence and severity of cerebral palsy in prematurely born children. J Pediatr 2011; 159 (01) 86-91.e1
  • 2 Cornette LG, Tanner SF, Ramenghi LA. et al. Magnetic resonance imaging of the infant brain: anatomical characteristics and clinical significance of punctate lesions. Arch Dis Child Fetal Neonatal Ed 2002; 86 (03) F171-F177
  • 3 Wagenaar N, Chau V, Groenendaal F. et al. Clinical risk factors for punctate white matter lesions on early magnetic resonance imaging in preterm newborns. J Pediatr 2017; 182: 34-40.e1
  • 4 Parodi A, Malova M, Cardiello V. et al. Punctate white matter lesions of preterm infants: risk factor analysis. Eur J Paediatr Neurol 2019; 23 (05) 733-739
  • 5 Perlman JM, Risser R, Broyles RS. Bilateral cystic periventricular leukomalacia in the premature infant: associated risk factors. Pediatrics 1996; 97 (6 Pt 1): 822-827
  • 6 Al Tawil KI, El Mahdy HS, Al Rifai MT, Tamim HM, Ahmed IA, Al Saif SA. Risk factors for isolated periventricular leukomalacia. Pediatr Neurol 2012; 46 (03) 149-153
  • 7 Resch B, Neubauer K, Hofer N. et al. Episodes of hypocarbia and early-onset sepsis are risk factors for cystic periventricular leukomalacia in the preterm infant. Early Hum Dev 2012; 88 (01) 27-31
  • 8 Wang LW, Lin YC, Tu YF, Wang ST, Huang CC. Taiwan Premature Infant Developmental Collaborative Study Group. Isolated cystic periventricular leukomalacia differs from cystic periventricular leukomalacia with intraventricular hemorrhage in prevalence, risk factors and outcomes in preterm infants. Neonatology 2017; 111 (01) 86-92
  • 9 Kidokoro H, Neil JJ, Inder TE. New MR imaging assessment tool to define brain abnormalities in very preterm infants at term. AJNR Am J Neuroradiol 2013; 34 (11) 2208-2214
  • 10 Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med 2006; 355 (07) 685-694
  • 11 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92 (04) 529-534
  • 12 Kersbergen KJ, Benders MJ, Groenendaal F. et al. Different patterns of punctate white matter lesions in serially scanned preterm infants. PLoS One 2014; 9 (10) e108904
  • 13 De Vries LS, Van Haastert IL, Rademaker KJ, Koopman C, Groenendaal F. Ultrasound abnormalities preceding cerebral palsy in high-risk preterm infants. J Pediatr 2004; 144 (06) 815-820
  • 14 Blanc WA. Pathology of the placenta, membranes, and umbilical cord in bacterial, fungal, and viral infections in man. Monogr Pathol 1981; 22 (22) 67-132
  • 15 Kawai M. Late-onset circulatory collapse of prematurity. Pediatr Int 2017; 59 (04) 391-396
  • 16 Sehgal A, Crispi F, Skilton MR, de Boode WP. Clinician performed ultrasound in fetal growth restriction: fetal, neonatal and pediatric aspects. J Perinatol 2017; 37 (12) 1251-1258
  • 17 Sehgal A, Allison BJ, Gwini SM, Miller SL, Polglase GR. Cardiac morphology and function in preterm growth restricted infants: relevance for clinical sequelae. J Pediatr 2017; 188: 128-134.e2
  • 18 Tao K, Hara Y, Ishihara Y, Ohshima Y. Cesarean section predominantly affects right ventricular diastolic function during the early transitional period. Pediatr Neonatol 2019; 60 (05) 523-529
  • 19 Vogl SE, Worda C, Egarter C. et al. Mode of delivery is associated with maternal and fetal endocrine stress response. BJOG 2006; 113 (04) 441-445
  • 20 Noori S, Stavroudis TA, Seri I. Principles of developmental cardiovascular physiology and pathophysiology. In: Hemodynamics and Cardiology: Neonatology Questions and Controversies. 2nd ed. Philadelphia: Saunders; 2012: 3-27
  • 21 Wu YW, Colford Jr JM. Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis. JAMA 2000; 284 (11) 1417-1424
  • 22 Chau V, Poskitt KJ, McFadden DE. et al. Effect of chorioamnionitis on brain development and injury in premature newborns. Ann Neurol 2009; 66 (02) 155-164
  • 23 Bierstone D, Wagenaar N, Gano DL. et al. Association of histologic chorioamnionitis with perinatal brain injury and early childhood neurodevelopmental outcomes among preterm neonates. JAMA Pediatr 2018; 172 (06) 534-541
  • 24 Kobayashi S, Fujimoto S, Fukuda S. et al. Periventricular leukomalacia with late-onset circulatory dysfunction of premature infants: correlation with severity of magnetic resonance imaging findings and neurological outcomes. Tohoku J Exp Med 2006; 210 (04) 333-339
  • 25 Shin SM, Chai JW. Brain ultrasonographic findings of late-onset circulatory dysfunction due to adrenal insufficiency in preterm infants. Ultrasonography 2016; 35 (03) 258-264
  • 26 Ng PC. Adrenocortical insufficiency and refractory hypotension in preterm infants. Arch Dis Child Fetal Neonatal Ed 2016; 101 (06) F571-F576
  • 27 Benders MJ, Kersbergen KJ, de Vries LS. Neuroimaging of white matter injury, intraventricular and cerebellar hemorrhage. Clin Perinatol 2014; 41 (01) 69-82
  • 28 El-Khuffash A, McNamara PJ. Hemodynamic assessment and monitoring of premature infants. Clin Perinatol 2017; 44 (02) 377-393