Influence of isolated low‐grade intracranial haemorrhages on the neurodevelopmental outcome of infants born very low birthweight

Abstract

AimTo determine whether isolated low‐grade germinal matrix‐intraventricular haemorrhages (LG‐GMH‐IVH) and low‐grade punctate cerebellar haemorrhages (LG‐CBH) contribute to the neurodevelopment of infants born preterm with very low birthweight (VLBW).MethodA prospective observational cohort study was conducted on infants born with VLBW hospitalized from January 2012 to July 2017 who had undergone serial cranial ultrasounds since birth and magnetic resonance susceptibility‐weighted imaging of the brain at term‐corrected age. Only those with VLBW carrying isolated LG‐GMH‐IVH (grades 1 or 2) or isolated LG‐CBH (punctate cerebellar haemorrhages ≤4 mm in diameter) or absence of lesions (no‐lesion) were enrolled and followed up to 3 years. The Griffiths Mental Development Scales, Extended and Revised version (GMDS‐ER), were used to assess neurodevelopment, considering unsatisfactory scores less than 85. Behaviour, according to the criteria of the International Classification of Diseases, 10th Revision, and rehabilitation data were noted.ResultsTwo‐hundred and forty infants with VLBW were enrolled: 34 with LG‐GMH‐IVH, 17 with LG‐CBH, and 189 as no‐lesion. The LG‐GMH‐IVH and LG‐CBH groups scored worse than the no‐lesion group on all GMDS‐ER scores for 1 year, 2 years, and 3 years. The LG‐CBH group scored lower than the LG‐GMH‐IVH group for total GMDS‐ER scores at 1 year and 2 years but not at 3 years. At 3 years, compared with the LG‐CBH group, those with LG‐GMH‐IVH received less and later physical therapy, with more frequent attention problems. The odds ratio for unsatisfactory GMDS‐ER scores corrected for gestational age was 5.75 for LG‐CBH (95% confidence interval 1.92–17.25; p = 0.002) and 2.67 for LG‐GMH‐IVH (95% confidence interval 1.16–6.13; p = 0.02).InterpretationLow‐grade haemorrhages affect the neurodevelopment of very‐low‐birthweight infants. Early rehabilitation might have contributed to their development.

Early Extra-Uterine Growth Restriction in Very-Low-Birth-Weight Neonates with Normal or Mildly Abnormal Brain MRI: Effects on a 2–3-Year Neurodevelopmental Outcome

“…Lastly, other well-known risk factors like GA [4][5][6], male sex [68,69], NEC [28,29] and major surgeries [33,34] were identified and confirmed by our study as the risk factors for worse GMDS scores in different areas. Regarding MRI findings, in our population, PWML was confirmed to be a risk factor for worse GMDS scores, particularly for locomotor development (scale A) and performance (scale E) at 2 years, which is in agreement with previous findings [24]. PWML was not significant at 3 years of GA.…”

“…Patients with major brain lesions such as periventricular leukomalacia (PVL), periventricular hemorrhagic infarction (PVHI), post-hemorrhagic ventricular distention (PHVD) and massive-limited CBH [23]-known to significantly affect neurological outcome-or with congenital brain malformations were excluded from this study. Patients with minor brain lesions such as low-grade GMH-IVH (I-II grade for Volpe's Classification [20]), punctate white matter lesions (PWMLs) [24] or micro-CBH were included [21].…”

“…Major brain lesions like cystic periventricular leukomalacia (PVL), germinal matrixintraventricular hemorrhage (GMH-IVH) complicated by periventricular hemorrhagic venous infraction (PVHI), or post-hemorrhagic ventricular distension (PHVD) and massive cerebellar hemorrhage (CBH) are strongly associated with important neurological impairment [17][18][19][20][21][22][23]. The roles of minor lesions like low-grade GMH-IVH, punctate white matter lesions (PWMLs) and micro CBH are still debated, although some recent works seems to be associated with an impaired neurological development [24,25].…”

Early IGF-1 receptor inhibition in mice mimics preterm human brain disorders and reveals a therapeutic target

“…In particular, we assessed the clinical profile of a cohort of severely preterm children born before 32 weeks of gestation carefully selected (fig. S11B) for being devoid of any brain lesion related to prematurity [even the minor that escape routine brain ultrasound and anatomical brain magnetic resonance diagnosis ( 7 – 9 )], as we evaluated at their term-corrected age (see Materials and Methods for imaging details). The ad hoc neuropsychological evaluation, which we assembled based on existing tests, involved both cognitive and autistic trait assessments of the preterm children at their standard follow-up visit of 5 years of age (defined below as ex-preterm children; fig.…”

“…However, these lines of research did not focus on the intrinsic biology of prematurity and were originally designed based on the health needs of preterm babies who were born 30 years ago and who mostly presented with severe brain lesions ( 1 ). Although neonatal infection/inflammation, hypoxia, and fetal growth restriction are associated with severely impaired neurodevelopment ( 5 ), even minor or no brain lesions were linked to negative outcomes ( 6 – 9 ) within the context of an ongoing debate about impaired/delayed maturation of white matter in the preterm brain ( 3 ). Brain lesions such as intraventricular and cerebellar hemorrhage continue to be associated with brain disorders of prematurity in some preterms also nowadays and are thus yet an active field of investigation ( 7 ).…”