Risk Factors Associated with Intraventricular Hemorrhage in Preterm Infants with ≤28 Weeks Gestational Age

Abstract

Objective: To identify obstetric and neonatal risk factors associated with the development of germinal matrix-intraventricular hemorrhage (GM-IVH) in high-risk preterm neonates.

Methods and Patients: Data from 279 preterm infants (246 mothers) with a gestational age≤28+0 weeks admitted to our NICU between January 2004 and December 2009 were analyzed retrospectively. Occurrence of (GM-IVH) was diagnosed by using ultrasound and important clinical variables were extracted from the patient charts. Infants were divided into 2 groups: GM-IVH and non-GM-IVH. To account for multiple gestation, generalized estimation equations (GEE) were used for univariate analysis and for the evaluation of independent risk factors.

Results: A low 5-min APGAR-Score, multiple birth, low arterial blood pressure at NICU admission, hypercapnia during the first 72 h of life in life and absence of any antenatal corticosteroids were found to be significant independent risk factors in the development of GM-IVH.

Conclusion: Preterm infants with low arterial blood pressure, absence of antenatal corticosteroids, low 5-min APGAR-Score, higher paCO₂ within the first 3 days of life and multiple gestation were at higher risk to develop GM-IVH. Avoiding these risk factors may help to decrease the rate of GM-IVH.

Zusammenfassung

Ziel: Identifikation von geburtshilflichen und neonatalen Risikofaktoren die mit der Entwicklung einer intraventrikulären Hirnblutung bei Hochrisiko-Frühgeborenen assoziiert sein können.

Methodik und Patienten: Es erfolgte ein retrospektive Datenanalyse von 279 Frühgeborenen (246 Mütter) mit einem Gestationsalter von ≤28+0 Schwangerschaftswochen, die in unserem Perinatalzentrum zwischen Januar 2004 und Dezember 2009 behandelt wurden. Die Diagnosesicherung und Graduierung einer GM-IVH erfolgte sonografisch. Wichtige klinische Variablen wurden aus den Patientenakten entnommen und die Einteilung der Kinder erfolgte in 2 Gruppen: GM-IVH-Gruppe und Nicht-GM-IVH-Gruppe. Für die univariate Analyse wurden wegen der Mehrfachgeburten verallgemeinerte Schätzgleichungen (GEE) verwendet, ebenso zur Identifikation von unabhängigen Risikofaktoren.

Ergebnisse: Ein niedriger 5-min-APGAR-Wert, Mehrgeburtlichkeit, niedriger systemarterieller Blutdruck, höhere paCO₂-Werte innerhalb der ersten 72 Lebensstunden und fehlende Lungenreifungsbehandlung waren unabhängige Risikofaktoren die mit der Entwicklung einer intraventrikulären Blutung assoziiert waren.

Schlussfolgerung: Frühgeborene mit einem niedrigeren arteriellen Blutdruck, fehlende Lungenreifungsbehandlung der Mutter, ein niedriger 5-min-APGAR-Wert, Hyperkapnie während der ersten 3 Lebenstage hatten ein höheres Risiko für die Entwicklung einer GM-IVH. Die Vermeidung dieser Risikofaktoren könnte die Rate an Hirnblutungen bei Risikofrühgeborenen reduzieren.

Key words

risk factors - intraventricular haemorrhage - preterm infants - prevention

Schlüsselwörter

Risikofaktoren - Intraventrikuläre Blutung - Frühgeborene - Prävention

• References

• 1 American Academy of Pediatrics . Use and abuse of the Apgar Score. Pediatrics 1986; 1: 1148-1149
• 2 Antoniuk S, da Silva RV. Periventricular and intraventricular hemorrhage in the premature infants. Rev Neurol 2000; 31: 238-243
• 3 Ballabh P. Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res 2010; 67: 1-8
• 4 Bental Y, Reichman B, Shiff Y et al. Collaboration with the Israel Neonatal Network. Impact of maternal diabetes mellitus on mortality and morbidity of preterm infants (24–33 weeks‘ gestation). Pediatrics 2011; 128: 848-855
• 5 Bolisetty S, Dhawan A, Abdel-Latif M et al. Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics 2014; 133: 55-62
• 6 Catlin EA, Carpenter MW, Brann 4th BS et al. The Apgar score revisited: influence of gestational age. J Pediatr 1986; 109: 865-868
• 7 Crowley PA. Antenatal corticosteroid therapy. A meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol 1995; 173: 332-335
• 8 Dalili H, Sheikh M, Hardani AK et al. Comparison of the Combined versus Conventional Apgar Scores in Predicting Adverse Neonatal Outcomes. PLoS One 2016; 11: e0149464
• 9 Di Salvo D. The Development Epidemiology Network Investigators. The correlation between placental pathology and intraventricular hemorrhage in the preterm infant. Pediatr Res 1998; 43: 15-19
• 10 Donovan EF, Ehrenkranz RA, Shankaran S et al. Outcomes of very low birth weight twins cared for in the National Institute of Child Health and Human Development Neonatal Research Network’s intensive care units. Am J Obstet Gynecol 1998; 179: 742-749
• 11 Duppré P, Sauer H, Giannopoulou EZ et al. Cellular and humoral coagulation profiles and occurrence of IVH in VLBW and ELWB infants. Early Hum Dev 2015; 91: 695-700
• 12 Fabres J, Carlo WA, Phillips V et al. Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. Pediatrics 2007; 119: 299-305
• 13 Faust K, Härtel C, Preuß M et al. Short-term outcome of very-low-birthweight infants with arterial hypotension in the first 24 h of life. Arch Dis Child Fetal Neonatal Ed 2015; 100: F388-F392
• 14 Futagi Y, Toribe Y, Ogawa K et al. Neurodevelopmental outcome in children with intraventricular hemorrhage. Pediatr Neurolog 2006; 34: 219-224
• 15 Hegyi T, Carbone T, Anwar M et al. The apgar score and its components in the preterm infant. Pediatrics 1998; 101: 77-81
• 16 Horbar JD, Badger GJ, Carpenter JH et al. Trends in mortality and morbidity for very low birth weight infants, 1991–1999. Pediatrics 2002; 110: 143-151
• 17 Hyttel-Sorensen S, Pellicer A, Alderliesten T et al. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial. BMJ 2015; 5: 350
• 18 Kaiser JR, Gauss CH, Williams DK. The effects of hypercapnia on cerebral autoregulation in ventilated very low birth weight infants. Pediatr Res 2005; 58: 931-935
• 19 Kenny JD, Garcia-Prats JA, Hilliard JL et al. Hypercarbia at birth: a possible role in the pathogenesis of intraventricular hemorrhage. Pediatrics 1978; 62: 465-467
• 20 Limperopoulos C, Bassan H, Kalish LA et al. Current definitions of hypotension do not predict abnormal cranial ultrasound findings in preterm infants. Pediatrics 2007; 120: 966-977
• 21 Lou HC. Perinatal hypoxic-ischemic brain damage and intraventricular hemorrhage. Arch Neurol 1980; 37: 585-587
• 22 O’Donnell CP, Kamlin CO, Davis PG et al. Interobserver variability of the 5-minute Apgar score. J Pediatr 2006; 149: 486-489
• 23 Papile LA, Burstein J, Burstein R et al. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birthweight less than 1500 gm. J Pediatr 1978; 92: 529-534
• 24 Patra K, Wilson-Costello D, Taylor HG et al. Grades I-II intraventricular hemorrhage in extremely low birth weight infants: effects on neurodevelopment. J Pediatr 2006; 149: 169-173
• 25 Pellicer A, Greisen G, Benders M et al. The SafeBoosC phase II randomised clinical trial: a treatment guideline for targeted near-infrared-derived cerebral tissue oxygenation versus standard treatment in extremely preterm infants. Neonatology 2013; 104: 171-178
• 26 Peng W, Zhu H, Shi H et al. Volume-targeted ventilation is more suitable than pressure-limited ventilation for preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2014; 99: 158-165
• 27 Perlman JM, Broyles RS, Rogers CG. Neonatal neurologic characteristics of preterm twin infants <1250 gm birth weight. Paediatr Neur 1997; 17: 322-326
• 28 du Plessis AJ. Cerebrovascular injury in premature infants: current understanding and challenges for future prevention. Clin Perinatol 2008; 35: 609-641
• 29 Schmid MB, Reister F, Mayer B et al. Prospective risk factor monitoring reduces intracranial hemorrhage rates in preterm infants. Dtsch Arztebl Int 2013; 110: 489-496
• 30 Shankaran S, Bauer CR, Bain R et al. Prenatal and perinatal risk and protective factors for neonatal intracranial hemorrhage. National Institute of Child Health and Human Development Neonatal Research Network. Arch Pediatr Adolesc Med 1996; 150: 491-497
• 31 Sheth RD. Trends in incidence and severity of intraventricular hemorrhage. J Child Neurol 1998; 13: 491-497
• 32 Sherlock RL, Anderson PJ, Doyle LW et al. Neurodevelopmental sequelae of intraventricular hemorrhage at 8 years of age in a regional cohort of ELBW/very preterm infants. Early Hum Dev 2005; 81: 909-916
• 33 Soul JS, Hammer PE, Tsuji M et al. Fluctuating pressure-passivity is common in the cerebral circulation of sick premature infants. Pediatr Res 2007; 61: 467-473
• 34 Thome UH, Genzel-Boroviczeny O, Bohnhorst B et al. Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. Lancet Respir Med 2015; 3: 534-543
• 35 Volpe JJ. Intraventricular hemorrhage in the premature infant – current concepts. Part I. Ann Neurol 1989; 25: 3-11
• 36 Watkins AM, West CR, Cooke RW. Blood pressure and cerebral haemorrhage and ischaemia in very low birth weight infants. Early Hum Dev 1989; 19: 103-110
• 37 Wei JC, Catalano R, Profit J et al. Impact of antenatal steroids on intraventricular hemorrhage in very-low-birth weight infants. J Perinatol 2016; 36: 352-356
• 38 Wright LL, Horbar JD, Gunkel H et al. Evidence from multicenter networks on the current use and effectiveness of antenatal corticosteroids in low birth weight infants. Am J Obstet Gynecol 2008; 198: 263-269
• 39 Zayek MM, Alrifai W, Whitehurst Jr RM et al. Acidemia versus hypercapnia and risk for severe intraventricular hemorrhage. Am J Perinatol 2014; 31: 345-352