White matter damage and intraventricular hemorrhage in very preterm infants: the EPIPAGE study

doi:10.1067/S0022-3476(03)00417-7

The Journal of Pediatrics

Volume 143, Issue 4, October 2003, Pages 477-483

https://doi.org/10.1067/S0022-3476(03)00417-7 Get rights and content

Abstract

Objective

To evaluate the prevalence of cranial ultrasound abnormalities in very preterm infants as a function of gestational age, plurality, intrauterine growth restriction, and death before discharge.

Study design

A prospective, population-based cohort of 2667 infants born between 22 and 32 weeks of gestation in 1997 in nine regions of France, transferred to a neonatal intensive care unit, for whom at least one cranial ultrasound scan was available.

Results

The frequencies of white matter damage (WMD), major WMD, cystic periventricular leukomalacia (PVL), periventricular parenchymal hemorrhagic involvement, and intraventricular hemorrhage with ventricular dilatation were 21%, 8%, 5%, 3%, and 3%, respectively. The risk of WMD increased with decreasing gestational age. Mean age at diagnosis of cystic PVL was older for the most premature infants. Intraventricular hemorrhage with ventricular dilatation was associated with a higher risk of cystic PVL. Intrauterine growth restriction was not associated with a lower prevalence of cystic PVL.

Conclusion

The frequency of WMD is high in very preterm babies and is strongly related to gestational age. The incidence of cystic PVL did not differ between babies with intrauterine growth restriction and babies who were appropriate for gestational age.

Section snippets

Methods

We included all the births for 1997 for which the GA of the infant was 22 to 32 weeks that occurred in the maternity wards of nine French regions accounting for about one third of all births in France.⁵ Quadruplets were excluded. Of the remaining 2774 liveborn infants, 2767 were admitted to a neonatal intensive care unit (NICU). Cranial US was performed with high-frequency 7.5-MHz transducers. At all the participating centers, cranial US was performed by qualified neonatologists or radiologists

Results

Among the 2767 infants admitted to the NICU, 2667 (96.4%) infants had one or more US scans, 67 (2.4%) had no US scan, and for the 33 (1.2%) remaining infants, no information was available concerning US scans. Of the infants with US scans, 11% had only one US scan (20% of these children died in the NICU), 23% had two scans (10% died in the NICU), and 66% had three or more scans (8% died in the NICU); 59% of the infants who died within 48 hours had at least one scan.

White matter damage was

Discussion

In our study, GA was highly predictive of WMD (defined as PHI, cystic PVL, isolated ventricular dilatation, or persisting echodensities) and, in particular, of major WMD (cystic PVL and PHI). IUGR was associated with a higher risk of PHI but did not affect the risk of cystic PVL. Half the infants with major WMD died in the NICU. Cystic PVL was associated with IVH with or without ventricular dilatation.

The power of this study is high, given the number (2667) of very preterm infants included on a

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Neonates can develop periventricular hemorrhagic infarction (PVHI) in association with intraventricular hemorrhage (IVH). The prognosis of this condition remains under debate. The aim of this study was to compare the neurological outcome at 2 years of age for neonates who have IVH with and without PVHI.
This retrospective single-center study (2010–2017) included all neonates who had at least a grade II IVH on ultrasound (US). The population was divided into two groups: Group 1 had grade II–III IVH without PVHI and Group 2 had grade II–III IVH with PVHI. All clinical and imaging (US and magnetic resonance images) data were reviewed. Neurological sequelae were classified as either mild (favorable outcome), or moderate or severe (unfavorable outcome), based on the follow-up report at the age of 2 years.
A total of 25 of the 46 infants meeting the inclusion criteria were excluded due to missing clinical or imaging data at diagnosis or follow-up. Of the remaining 21 infants, all were preterm and had grade II–III IVH, either with PVHI (n = 10) or without (n = 11). The neurological prognosis was unfavorable for both groups. Except for the size of the lesion, no radiological findings appeared to be significantly associated with an unfavorable prognosis. Overall, 11 of the infants died early in life; i.e., the mortality rate was 52% (n = 11/21). The deaths were not due to neurological complications of prematurity. C-section was more common in the PVHI group.
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One hundred eighty-six studies evaluating 95 risk factors for PVL were included. Of the 2,509,507 neonates assessed, 16,569 were diagnosed with PVL. Intraventricular hemorrhage [adjusted odds ratio: 3.22 (2.52-4.12)] had moderate CoE for its association with PVL. Other factors such as hypocarbia, chorioamnionitis, PPROM >48 hour, multifetal pregnancy reduction, antenatal indomethacin, lack of antenatal steroids, perinatal asphyxia, ventilation, shock/hypotension, patent ductus arteriosus requiring surgical ligation, late-onset circulatory collapse, sepsis, necrotizing enterocolitis, and neonatal surgery showed significant association with PVL after adjustment for confounders (CoE: very low to low). Amongst the risk factors associated with mother placental fetal (MPF) triad, there was paucity of literature related to genetic predisposition and defective placentation. Sensitivity analysis revealed that the strength of association between invasive ventilation and PVL decreased over time (P < 0.01), suggesting progress in ventilation strategies. Limited studies had evaluated diffuse PVL.
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^☆: Supported by INSERM (National Institute of Health and Medical Research), Merck-Sharp and Dohme-Chibret, the Medical Research Foundation, and the Directorate General for Health of the French Ministry for Social Affairs.

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Original ArticleWhite matter damage and intraventricular hemorrhage in very preterm infants: the EPIPAGE study☆

Abstract

Objective

Study design

Results

Conclusion

Section snippets

Methods

Results

Discussion

Arch Pediatr

J Pediatr

BJOG

J Pediatr

Changing panorama of cerebral palsy in Sweden, VIII: prevalence and origin in the birth year period 1991–94

Acta Paediatr

Grande prématurité, risque de handicap neuropsychiques et neuroprotection

J Gynecol Obstet Biol Reprod

The relationships between antenatal management, the cause of delivery and neonatal outcome in a large cohort of very preterm singleton infants

BJOG

Periventricular leukomalacia: risk factors revisited

Dev Med Child Neurol

Etude Epipage: mortalité des enfants grands prématurés et état d'avancement de l'étude

J Gynecol Obstet Biol Reprod

Survival of very preterm infants: Epipage, a population-based study

Arch Dis Child Fetal Neonatal Ed

The etiology and outcome of cerebral ventriculomegaly at term in very low birth weight preterm infants

Pediatrics

Neonatal cranial ultrasound interpretation: a clinical audit

Arch Dis Child Fetal Neonatal Ed

Development of the main indicators of perinatal health in metropolitan France between 1995 and 1998: results of the national perinatal survey

J Obstet Gynecol

Fetal and neonatal neurology and neurosurgery

Are neonatal brain lesions due to intrauterine infection related to mode of delivery?

Br J Obstet Gynaecol

Original Article
White matter damage and intraventricular hemorrhage in very preterm infants: the EPIPAGE study☆