title: Leading causes of preterm delivery as risk factors for intraventricular hemorrhage in very preterm infants: results of the EPIPAGE 2 cohort study.
abstract: Intraventricular hemorrhage is a major risk factor for neurodevelopmental disabilities in preterm infants. However, few studies have investigated how pregnancy complications responsible for preterm delivery are related to intraventricular hemorrhage.
  
  
  
  We sought to investigate the association between the main causes of preterm delivery and intraventricular hemorrhage in very preterm infants born in France during 2011 between 22-31 weeks of gestation.
  
  
  
  The study included 3495 preterm infants from the national EPIPAGE 2 cohort study who were admitted to neonatal intensive care units and had at least 1 cranial ultrasound assessment. The primary outcome was grade I-IV intraventricular hemorrhage according to the Papile classification. Multinomial logistic regression models were used to study the relationship between risk of intraventricular hemorrhage and the leading causes of preterm delivery: vascular placental diseases, isolated intrauterine growth retardation, placental abruption, preterm labor, and premature rupture of membranes, with or without associated maternal inflammatory syndrome.
  
  
  
  The overall frequency of grade IV, III, II, and I intraventricular hemorrhage was 3.8% (95% confidence interval, 3.2-4.5), 3.3% (95% confidence interval, 2.7-3.9), 12.1% (95% confidence interval, 11.0-13.3), and 17.0% (95% confidence interval, 15.7-18.4), respectively. After adjustment for gestational age, antenatal magnesium sulfate therapy, level of care in the maternity unit, antenatal corticosteroids, and chest compressions, infants born after placental abruption had a higher risk of grade IV and III intraventricular hemorrhage compared to those born under placental vascular disease conditions, with adjusted odds ratios of 4.3 (95% confidence interval, 1.1-17.0) and 4.4 (95% confidence interval, 1.1-17.6), respectively. Similarly, preterm labor with concurrent inflammatory syndrome was associated with an increased risk of grade IV intraventricular hemorrhage (adjusted odds ratio, 3.4; 95% confidence interval, 1.1-10.2]). Premature rupture of membranes did not significantly increase the risk.
  
  
  
  Relationships between the causes of preterm birth and intraventricular hemorrhage were limited to specific and rare cases involving acute hypoxia-ischemia and/or inflammation. While the emergent nature of placental abruption would challenge any attempts to optimize management, the prenatal care offered during preterm labor could be improved.
authors.affiliation: Grenoble Alps University, Centre national de la recherche scientifique, TIMC-IMAG, Unite mixte de recherche 5525 ThEMAS, and Neonatal Intensive Care Unit, Grenoble University Hospital, Grenoble, France. Electronic address: MChevallier3@chu-grenoble.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Chevallier
authors.affiliation: Grenoble Alps University, Centre national de la recherche scientifique, TIMC-IMAG, Unite mixte de recherche 5525 ThEMAS, and Neonatal Intensive Care Unit, Grenoble University Hospital, Grenoble, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Debillon
authors.affiliation: Institut national de la sante de de la recherche médicale, U1153, Epidemiology and Statistics Sorbonne Paris Cité Center, Obstetrical, Perinatal and Pediatric Epidemiology Team, Maternité Port-Royal, Paris, France; Neonatal Intensive Care Unit, Jeanne de Flandre Hospital, Lille, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Pierrat
authors.affiliation: Institut national de la sante de de la recherche médicale, U1153, Epidemiology and Statistics Sorbonne Paris Cité Center, Obstetrical, Perinatal and Pediatric Epidemiology Team, Maternité Port-Royal, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Delorme
authors.affiliation: Institut national de la sante de de la recherche médicale, U1153, Epidemiology and Statistics Sorbonne Paris Cité Center, Obstetrical, Perinatal and Pediatric Epidemiology Team, Maternité Port-Royal, Paris, France; Department of Obstetrics and Gynecology, Trousseau Hospital, Assistance publique des hôpitaux de Paris, Paris, France; Pierre et Marie Curie University, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Kayem
authors.affiliation: Institut national de la sante de de la recherche médicale, U1153, Epidemiology and Statistics Sorbonne Paris Cité Center, Obstetrical, Perinatal and Pediatric Epidemiology Team, Maternité Port-Royal, Paris, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Durox
authors.affiliation: Institut national de la sante de de la recherche médicale, U1153, Epidemiology and Statistics Sorbonne Paris Cité Center, Obstetrical, Perinatal and Pediatric Epidemiology Team, Maternité Port-Royal, Paris, France; Department of Obstetrics and Gynecology, DHU Risks and Pregnancy, Maternity Port-Royal Hospital, Cochin Assistance publique des hôpitaux de Paris, Paris, France; Paris Descartes University France, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Goffinet
authors.affiliation: Region Inserm Team ERI 28, Neovasc, Normandie University, Rouen, France; Neonatal Intensive Care Unit, Rouen University Hospital, Rouen, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Marret
authors.affiliation: Institut national de la sante de de la recherche médicale, U1153, Epidemiology and Statistics Sorbonne Paris Cité Center, Obstetrical, Perinatal and Pediatric Epidemiology Team, Maternité Port-Royal, Paris, France; Paris Descartes University France, Paris, France; Unite de recherche clinique-Centre d'investigation clinique P1419, Département hospitalo-universitaire Risk in Pregnancy, Cochin Hotel-Dieu Hospital, Assistance publique des hôpitaux de Paris, Paris, France.
authors.forename: Pierre Yves
authors.initials: PY
authors.lastname: Ancel
mesh_terms: D000037:Abruptio Placentae / Q000453:epidemiology; D002543:Cerebral Hemorrhage / Q000145:classification / Q000453:epidemiology*; D015331:Cohort Studies; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000145:classification / Q000453:epidemiology*; D007752:Obstetric Labor, Premature / Q000453:epidemiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology; D047928:Premature Birth / Q000453:epidemiology*; D012307:Risk Factors; D018746:Systemic Inflammatory Response Syndrome / Q000453:epidemiology
keywords: cohort study; intraventricular hemorrhage; maternal event; risk factor; very preterm infant