Advertisement

Leading causes of preterm delivery as risk factors for intraventricular hemorrhage in very preterm infants: results of the EPIPAGE 2 cohort study

Published:January 16, 2017DOI:https://doi.org/10.1016/j.ajog.2017.01.002

      Background

      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.

      Objective

      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.

      Study Design

      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.

      Results

      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.

      Conclusion

      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.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ancel P.-Y.
        • Goffinet F.
        • Kuhn P.
        • et al.
        Survival and morbidity of preterm children born at 22 through 34 weeks’ gestation in France in 2011: results of the EPIPAGE-2 cohort study.
        JAMA Pediatr. 2015; 169: 230
        • Costeloe K.L.
        • Hennessy E.M.
        • Haider S.
        • Stacey F.
        • Marlow N.
        • Draper E.S.
        Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies).
        BMJ. 2012; 345: e7976
        • Zeitlin J.
        • Ancel P.-Y.
        • Delmas D.
        • Breart G.
        • Papiernik E.
        • the EPIPAGE and the MOSAIC Ile-de-France Groups
        Changes in care and outcome of very preterm babies in the Parisian region between 1998 and 2003.
        Arch Dis Child Fetal Neonatal Ed. 2009; 95: F188-F193
        • Back S.A.
        Perinatal white matter injury: the changing spectrum of pathology and emerging insights into pathogenetic mechanisms.
        Ment Retard Dev Disabil Res Rev. 2006; 12: 129-140
        • Platt M.J.
        • Cans C.
        • Johnson A.
        • et al.
        Trends in cerebral palsy among infants of very low birthweight (<1500 g) or born prematurely (<32 weeks) in 16 European centers: a database study.
        Lancet. 2007; 369: 43-50
        • Abily-Donval L.
        • Pinto-Cardoso G.
        • Chadie A.
        • et al.
        Comparison in outcomes at two years of age of very preterm infants born in 2000, 2005 and 2010.
        PLoS One. 2015; 10: e0114567
        • Blickstein I.
        • Reichman B.
        • Lusky A.
        • Shinwell E.S.
        Plurality-dependent risk of severe intraventricular hemorrhage among very low birth weight infants and antepartum corticosteroid treatment.
        Am J Obstet Gynecol. 2006; 194: 1329-1333
        • Fanaroff A.
        • Stoll B.
        • Wright L.
        • et al.
        Trends in neonatal morbidity and mortality for very low birthweight infants.
        Am J Obstet Gynecol. 2007; 196: 147.e1-147.e8
        • Sarkar S.
        • Bhagat I.
        • Dechert R.
        • Schumacher R.
        • Donn S.
        Severe intraventricular hemorrhage in preterm infants: comparison of risk factors and short-term neonatal morbidities between grade 3 and grade 4 intraventricular hemorrhage.
        Am J Perinatol. 2009; 26: 419-424
        • Kusters C.D.J.
        • Chen M.L.
        • Follett P.L.
        • Dammann O.
        Intraventricular hemorrhage and cystic periventricular leukomalacia in preterm infants: how are they related?.
        J Child Neurol. 2009; 24: 1158-1170
        • Stoll B.J.
        • Hansen N.I.
        • Bell E.F.
        • et al.
        Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network.
        Pediatrics. 2010; 126: 443-456
        • Inder T.E.
        • Volpe J.J.
        Mechanisms of perinatal brain injury.
        Semin Neonatol. 2000; 5: 3-16
        • Volpe J.J.
        Intracranial hemorrhage: germinal matrix hemorrhage of the premature infant.
        in: Volpe J.J. Neurology of the Newborn. Fifth Edition. Elsevier, Philadelphia, PA2008: 481-517
        • Ballabh P.
        Intraventricular hemorrhage in premature infants: mechanism of disease.
        Pediatr Res. 2010; 67: 1-8
        • Linder N.
        • Haskin O.
        • Levit O.
        • et al.
        Risk factors for intraventricular hemorrhage in very low birth weight premature infants: a retrospective case-control study.
        Pediatrics. 2003; 111: e590-e595
        • Riskin A.
        • Riskin-Mashiah S.
        • Bader D.
        • et al.
        Delivery mode and severe intraventricular hemorrhage in single, very low birth weight, vertex infants.
        Obstet Gynecol. 2008; 112: 21-28
        • The EXPRESS Group
        Incidence of and risk factors for neonatal morbidity after active perinatal care: extremely preterm infants study in Sweden (EXPRESS).
        Acta Paediatr. 2010; 99: 978-992
        • de Vries L.S.
        • Roelants-van Rijn A.M.
        • Rademaker K.J.
        • van Haastert I.C.
        • Beek F.J.
        • Groenendaal F.
        Unilateral parenchymal hemorrhagic infarction in the preterm infant.
        Eur J Paediatr Neurol. 2001; 5: 139-149
        • Heuchan A.M.
        • Evans N.
        • Smart D.H.
        • Simpson J.M.
        Perinatal risk factors for major intraventricular hemorrhage in the Australian and New Zealand Neonatal Network, 1995-97.
        Arch Dis Child-Fetal Neonatal Ed. 2002; 86: F86-F90
        • Ment L.R.
        • Oh W.
        • Ehrenkranz R.A.
        • Philip A.G.
        • Duncan C.C.
        • Makuch R.W.
        Antenatal steroids, delivery mode, and intraventricular hemorrhage in preterm infants.
        Am J Obstet Gynecol. 1995; 172: 795-800
        • Been J.V.
        • Degraeuwe P.L.
        • Kramer B.W.
        • Zimmermann L.J.I.
        Antenatal steroids and neonatal outcome after chorioamnionitis: a meta-analysis.
        BJOG. 2011; 118: 113-122
        • Goldenberg R.L.
        • Culhane J.F.
        • Iams J.D.
        • Romero R.
        Epidemiology and causes of preterm birth.
        Lancet. 2008; 371: 75-84
        • Blondel B.
        • Lelong N.
        • Kermarrec M.
        • Goffinet F.
        Trends in perinatal health in France from 1995 to 2010. Results from the French National Perinatal Surveys.
        J Gynecol Obstet Biol Reprod (Paris). 2012; 41: e1-e15
        • Ment L.R.
        • Bada H.S.
        • Barnes P.
        • et al.
        Practice parameter: neuroimaging of the neonate: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.
        Neurology. 2002; 58: 1726-1738
        • Papile L.A.
        • 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: 529-534
        • Levene M.I.
        Measurement of the growth of the lateral ventricles in preterm infants with real-time ultrasound.
        Arch Dis Child. 1981; 56: 900-904
        • Delorme P.
        • Goffinet F.
        • Ancel P.-Y.
        • et al.
        Cause of preterm birth as a prognostic factor for mortality.
        Obstet Gynecol. 2016; 127: 40-48
        • Perlman J.M.
        • Risser R.C.
        • Gee J.B.
        Pregnancy-induced hypertension and reduced intraventricular hemorrhage in preterm infants.
        Pediatr Neurol. 1997; 17: 29-33
        • Doshi H.
        • Moradiya Y.
        • Roth P.
        • Blau J.
        Variables associated with the decreased risk of intraventricular hemorrhage in a large sample of neonates with respiratory distress syndrome.
        Arch Dis Child Fetal Neonatal Ed. 2016; 101: F223-F229
        • Rong Z.
        • Liu H.
        • Xia S.
        • Chang L.
        Risk and protective factors of intraventricular hemorrhage in preterm babies in Wuhan, China.
        Childs Nerv Syst. 2012; 28: 2077-2084
        • Ballabh P.
        Pathogenesis and prevention of intraventricular hemorrhage.
        Clin Perinatol. 2014; 41: 47-67
        • Perlman J.M.
        Interruption of placental blood flow during labor: potential systemic and cerebral organ consequences.
        J Pediatr. 2011; 158: e1-e4
        • Szpecht D.
        • Wiak K.
        • Braszak A.
        • et al.
        Role of selected cytokines in the etiopathogenesis of intraventricular hemorrhage in preterm newborns.
        Childs Nerv Syst. 2016; 32: 2097-2103
        • Chau V.
        • McFadden D.E.
        • Poskitt K.J.
        • Miller S.P.
        Chorioamnionitis in the pathogenesis of brain injury in preterm infants.
        Clin Perinatol. 2014; 41: 83-103
        • Leviton A.
        • Allred E.N.
        • Dammann O.
        • et al.
        Systemic inflammation, intraventricular hemorrhage, and white matter injury.
        J Child Neurol. 2013; 28: 1637-1645
        • Ancel P.-Y.
        • Marret S.
        • Larroque B.
        • et al.
        Are maternal hypertension and small-for-gestational age risk factors for severe intraventricular hemorrhage and cystic periventricular leukomalacia? Results of the EPIPAGE cohort study.
        Am J Obstet Gynecol. 2005; 193: 178-184
        • Popowski T.
        • Goffinet F.
        • Maillard F.
        • Schmitz T.
        • Leroy S.
        • Kayem G.
        Maternal markers for detecting early-onset neonatal infection and chorioamnionitis in cases of premature rupture of membranes at or after 34 weeks of gestation: a two-center prospective study.
        BMC Pregnancy Childbirth. 2011; 11: 26
        • Popowski T.
        • Goffinet F.
        • Batteux F.
        • Maillard F.
        • Kayem G.
        Prediction of maternofetal infection in preterm premature rupture of membranes: serum maternal markers.
        Gynecol Obstet Fertil. 2011; 39 ([in French]): 302-308
        • Fisk N.M.
        • Fysh J.
        • Child A.G.
        • Gatenby P.A.
        • Jeffery H.
        • Bradfield A.H.
        Is C-reactive protein really useful in preterm premature rupture of the membranes?.
        Br J Obstet Gynaecol. 1987; 94: 1159-1164
        • Kim M.-A.
        • Lee Y.S.
        • Seo K.
        Assessment of predictive markers for placental inflammatory response in preterm births.
        PLoS One. 2014; 9: e107880
        • Hitti J.
        • Tarczy-Hornoch P.
        • Murphy J.
        • Hillier S.L.
        • Aura J.
        • Eschenbach D.A.
        Amniotic fluid infection, cytokines, and adverse outcome among infants at 34 weeks’ gestation or less.
        Obstet Gynecol. 2001; 98: 1080-1088
        • Yoon B.H.
        • Jun J.K.
        • Romero R.
        • et al.
        Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy.
        Am J Obstet Gynecol. 1997; 177: 19-26
        • Manuck T.A.
        • Varner M.W.
        Neonatal and early childhood outcomes following early vs later preterm premature rupture of membranes.
        Am J Obstet Gynecol. 2014; 211: 308.e1-308.e6
        • Verma U.
        • Tejani N.
        • Klein S.
        • et al.
        Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate.
        Am J Obstet Gynecol. 1997; 176: 275-281