Periventricular/Intraventricular Hemorrhage in the Newborn

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1 Khalid N. Haque, FRCP(Ed), FRCP(I), FAAP, FICP, DCH, DTM&H; Omar B. A. Basit, MRCP(UK), DCH; Meeralebbae M. Shaheed, MD, MRCP(UK), DCH From the Division of Neonatology, Department of Pediatrics, College of Medicine, King Saud University (Drs. Haque and Shaheed), and Department of Pediatrics, Security Forces Hospital (Dr. Basit), Riyadh. Address reprint requests and correspondence to Dr. Haque: Division of Neonatology, Department of Pediatrics, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia. Accepted for publication 23 November In a retrospective study spanning 4 years ( H) and including a total of 11,050 births, the incidence of periventricular/intraventricular hemorrhage (PVH/IVH) in infants born at King Khalid University Hospital at or before 35 weeks of gestation was 20.9% and in those weighing 1500 g or less at birth was 40.8%. Incidence, grade, associations, and outcome of infants suffering PVH/IVH were tabulated. Most common was grade 1 hemorrhage; PVH/IVH was most frequently seen in infants born between 26 and 30 weeks' gestation (42.5%) and in those weighing between 500 and 750 g (42.9%) at birth. Respiratory distress syndrome was associated in 81.3% of the infants with PVH/IVH. KN Haque, OBA Basit, MM Shaheed,. 1989; 9(4): Improved neonatal intensive care during the past decade has resulted in the survival of many premature infants who formerly would have died. 1 With enhanced perinatal and neonatal care being offered in the Kingdom, survival of preterm and very low-birth-weight infants has improved considerably, 2 but akin to reports from the developed world, a large number of infants weighing 1500 g or less at birth die, and many more are handicapped due to periventricular/intraventricular (PVH/IVH) hemorrhage. 3-7 This report summarizes our experience over a 4-year period ( H) of PVH/IVH at the neonatal service of the King Khalid University Hospital (KKUH), Riyadh. Patients and Methods The neonatal intensive care unit (NICU) is a 22-bed tertiary care unit. It serves infants born at KKUH and at King Abdul Aziz University Hospital, Riyadh; however, only infants born at KKUH have been included in this analysis. The annual delivery rate at KKUH increased from 1709 in 1404H to 3732 in 1407H. All infants born at or before 35 weeks' gestation are admitted to the NICU. Gestation is assessed by maternal dates, antenatal ultrasonographic assessment of fetal biparietal diameter, abdominal circumference, and femur length. Postnatal gestational assessment is performed within the first 24 hours of birth using Ballard's scoring system. 8 A total of 236 infants were born before 35 weeks of gestation out of the total 11,050 births over these 4 years (2.1%). Of the 236 infants, 230 had cranial ultrasonographic examination. These were usually performed at 3 and 7 days of age. All sonograms were performed using Hewlett-Packard real-time sector scanner with a 5-MHz Phasedarry transducer. All examinations were performed in the NICU. No sedation was used. Standard sonographic techniques, including axial and occipital views, were used to obtain sections in coronal and sagittal planes. Intracranial hemorrhage was classified according to Papile. 9 Patients with PVH/lVH were followed by once-

2 weekly ultrasound scans of the brain until discharge from the NICU or their death. Ventricular dilatation was determined by daily occipitofrontal head circumference measurement and repeat ultrasound examination. Whenever necessary, cranial CT scan was also performed. Posthemorrhage hydrocephalus was treated by placement of ventriculoperitoneal shunt, which in most cases was carried out after a period of external ventricular drainage. Follow-up after discharge was carried out by us in the high-risk clinic, where gross motor, social, and developmental screening was done. No formal or detailed screening (such as the Griffiths screening) was applied. The follow-up period in this report ranges from 12 months to 4 years. Results A total of 236 infants were born at or before 35 weeks of gestation during the study period, giving an incidence of 2.1%. Of these 236 infants, six died prior to any sonographic examination of the brain, so have not been included in the analyses shown in Tables 1 and 2. The overall incidence of PVH/IVH in infants under 35 weeks' gestation was 20.9%, but rose to 40.8% when it was correlated to infants weighing 1500 g or less at birth. Table 1. Incidence of PVH/IVH in relation to gestational age. Gestational age (w) No. Grade of PVH/IVH I II III IV Total < (12.5) (18.7) (31.3) (11.3) ( 3.7) (18.7) ( 8.7) (42.5) ( 3.0) (0.7) ( 1.5) ( 1.5) ( 6.7) Total* ( 5.7) (2.6) ( 7.4) (5.2) (20.9) *Total does not include six infants who died prior to any sonographic examination of the brain. Numbers in parentheses are percentages. Table 2. Incidence of PVH/IVH related to birth weight. Birth weight (g). No Grade of PVH/IVH* I II III IV Total (14.2) ( 7.1) (21.4) (42.9) (10.0) ( 6.7) (16.7) ( 6.7) (40.0) (11.9) ( 3.4) (15.3) (10.2) (40.7) Total ( 9.7) ( 5.8) (14.6) (10.7) (40.8) *Numbers in parentheses are percentages. Total does not include six infants who died prior to any sonographic examination of the brain. Six infants born prior to 35 weeks' gestation had birth weight greater than 1500 g, and thus are not included in this table. Associated diagnoses are shown in Table 3. The most common was respiratory distress syndrome, which was associated with PVH/IVH in 39 of 48 cases (81.3%). Patent ductus arteriosus was associated with PVH/IVH in 21 cases (43.7%). The most frequent presenting feature was pallor (41.7%), followed by seizures (39.6%), but the majority (54.2%) had no clinical signs of cerebral hemorrhage. Outcome is shown in Figure 1. A total of 16 (33.3%) infants with PVH/IVH died, while 21 (43.7%) survived without any handicap, neurologic or otherwise. The remaining 11 (22.9%) survived with handicap. Fifteen infants (31.3%) required drainage due to posthemor-rhage hydrocephalus.

3 Table 3. Associated diagnoses and most common presenting features (n = 48). Association No. (%) Respiratory distress syndrome 38(81.3) Need for ventilation 31(64.6) Patent ductus arteriosus 21(43.7) Clinical presentation Shock 3( 6.3) Pallor 20(41.7) Apnea 8(16.7) Hypotension 6(12.5) Seizures 19(39.6) Tachycardia 4( 8.3) Bulging fontanelle 10(20.8) Unexplained acidosis 3( 6.3) None 26(54.2) *More than one sign or symptoms per infant. Figure 1. Outcome of infants with PVH/IVH. Discussion With increasing survival of very low-birth-weight infants, ischemic and hemorrhagic central nervous system lesions have become the major cause of their mortality and morbidity. 3,4,10 PVH/IVH are by far the most important ischemic/hemorrhagic lesions in premature infants. Though incidence of PCH/IVH may be declining, 5,10 prospective studies have consistently reported a 40% to 50% of incidence of IVH in infants weighing 1500 g or less at birth. 3,4,11 At KKUH over a 4-year period, the incidence of PVH/IVH in infants under 35 weeks of gestation at birth was 20.9%, but rose to 40.6% in infants born at or before 30 weeks of gestation. Our incidence of 40.8% of PVH/IVH in infants weighing 1500 g or less is comparable to that reported in the literature. 3,4,10,11 It is understandable that the incidence of PVH/IVH should be higher in infants under 30 weeks of gestation because of the peculiarity of the blood supply and cerebrovascular physiology at this age. 12,13 Much of the bleeding arises from the germinal matrix. The subependymal germinal matrix is a collection of densely packed glioblastic cells in the ganglia lying over the head and body of the caudate nucleus. 13 The blood supply to the germinal matrix is from the recurrent artery of Heubner, lenticulostriate arteries, and the anterior choroidal artery. In the immature brain (24 to 32 weeks), a substantial proportion of the cerebral blood flow is directed to the germinal matrix until the development of the cerebral cortex assumes prominence (>34 weeks). The vascular endothelial cells of this area are highly dependent on oxidative metabolism, which makes them readily susceptible to hypoxic and/or ischemic insults. Moreover, the high fibrinolytic activity of the germinal matrix tissue allows enlargement of an initially small hemorrhage. 14

4 These characteristics explain why hemorrhage arises over the body of the caudate nucleus before 30 weeks' gestation and over the head of the caudate nucleus near the foramen of Monro between 30 to 32 weeks. Since the germinal matrix disappears beyond 32 weeks of gestation, PVH/IVH are rare beyond this gestational age. 13 There are many other factors such as pressure-passive cerebral blood flow in preterm infants, 13,15 hypoxia and asphyxia, 13 respiratory distress syndrome, 13 positive pressure ventilation, 16 and patent ductus arteriosus. 13 The relative contribution of these factors to the pathogenesis of remains controversial; however, better understanding of these factors and neonatal pathophysiology continues to improve the outlook for these tiny infants. Most of the therapeutic modalities phenobar-bital, 17,19 ethamsylate, 20 daily lumbar puncture, 11,21 and others 11 - used for the treatment of PVH/IVH and prevention of posthemorrhage hydrocephalus remain inconclusive. The best hope for preventing PVH/IVH lies in reducing the rate of premature deliveries. It is clear from our study that the target should be to reduce the number of infants born weighing 1500 g or less at birth prior to 30 weeks of gestation. Recent reports have shown continued improved outcome of infants even with grade IV PVH/IVH. Unfortunately, we were not very successful with infants who had grade IV PVH/IVH; 66.6% of these infants died and none of those who survived were normal on follow-up. Posthemorrhagic hydrocephalus developed in 41.6%, requiring ventriculoperitoneal shunt operation. However, for other grades of hemorrhage (I-III), the majority of infants (58.3%) were completely normal at follow-up. (One infant died from necrotizing enterocolitis.) The prognosis of PVH/IVH is not uniformly poor, and every effort should be made to provide these infants with optimum care so that they survive with the best possible chance of being normal. The overall handicap rate of 22.9% for all grades of hemorrhage in our group is comparable to other reports, though it must be taken with caution as we did not do any formal assessment scoring. We conclude that PVH/IVH is a major cause of mortality and morbidity of infants born weighing 1500 g or less. The main hope of reducing this human wastage and suffering lies in reducing the incidence of prematurity with better antenatal and perinatal care after delivery by preventing hypoxia, fluctuations in cerebrovascular blood flow, and the injudicious use of hyperosmolar solutions. Acknowledgment We are grateful to Natasha Haque for helping with data analysis, Shirley Durand for typing the manuscript, and Pam Kline from the ultrasound department for reviewing the manuscript. References 1. Haque KN. Outcome of low and very low birth weight infants: a case for regionalization of perinatal care in Saudi Arabia. Ann Saudi Med 1986;6(4): Haque KN, Bashir O. Perinatal mortality at King Khalid University Hospital, Riyadh. Ann Saudi Med 1988;8(3): Haque KN. A scheme for better perinatal care in the Kingdom of Saudi Arabia. Saudi Med J 1988;9(3): Ahmann PA, Lazzara A, Dykes FD, et al. Intraventricular hemorrhage in the high-risk preterm infant: incidence and outcome. Ann Neurol 1980;7(2): Shinnar S, Molteni RA, Gammon K, et al. Intraventricular hemorrhage in the premature infant. N Engl J Med 1982;306(24): Haque KN. Patterns of cerebral palsy in Riyadh, Saudi Arabia. Pak Pediatr J 1986;10(1): Taha SA, Mahdi AH. Cerebral palsy in Saudi Arabia: a clinical study of 102 cases. Ann Trop Paediatr 1984;4(3): Ballard JL, Kazmaierk K, Driver MA. A simplified assessment of gestational age (abstract). Paediatr Res 1977 ;11(4) : Papile LA, 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 g. J Paediatr 1978;92(4): Harbaugh RE, Saunders RL. Intraventricular hemorrhage in premature infants. In: Contemporary neurosurgery: a biweekly review of clinical neurosurgical practice. 1986;6(3):l Allan WC, Volpe JJ. Periventricular-intraventricular hemorrhage. Pediatr Clin North Am 1986;33(l): Hambleton G, Wigglesworth JS. Origin of intraventricular haemorrhage in the preterm infant. Arch Dis Child 1976;51(9): Pape KE, Wigglesworth JS. In: Haemorrhage, ischaemia and the perinatal brain. Philadelphia: JB Lippincott Co, 1979:1-58.

5 14. Gilles FH, Price RA, Kevy SV, Berenberg W. Fibrinolytic activity in the ganglionic eminence of the premature human brain. Biol Neonate 1971;18: Perlman JM, McMenamin JB, Volpe JJ. Fluctuating cerebral blood-flow velocity in respiratory-distress syndrome: relation to the development of intraventricular hemorrhage. N Engl J Med 1983;309(4): Fitzhardinge PM, Papa P, Arstikaitis M, et al. Mechanical ventilation of infants of less than 1,501 gm birth weight: health, growth and neurologic sequelae. J Pediatr 1976;88(4): Donn SM, Roloff DW, Goldstein GW. Prevention of intraventricular haemorrhage in preterm infants by phenobarbitone: a controlled trial. Lancet 1981;2(8240): Morgan ME, Massey RF, Cooke RW. Does phenobarbitone prevent periventricular hemorrhage in very low-birth-weight babies?: a controlled trial. Pediatrics 1982;70(2): Kuban KC, Leviton A, Krishnamoorthy KS, et al. Neonatal intracranial hemorrhage and phenobarbital. Pediatrics 1986;77(4): Morgan ME, Benson JW, Cooke RW. Ethamsylate reduces the incidence of periventricular haemorrhage in very low birthweight babies. Lancet 1981;2(8251): Mantovani JF, Pasternak JF, Mathew OP, et al. Failure of daily lumbar punctures to prevent the development of hydrocephalus following intraventricular haemorrhage. J Pediatr 1980;97(2): Pasternak JF, Volpe JJ. Full recovery from prolonged brainstem failure following intraventricular hemorrhage. J Pediatr 1979;95(6): Papile LA, Munsick-Bruno G, Schaefer A. Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps. J Pediatr 1983;103(2): McMenamin JB, Shakelford GD, Volpe JJ. Outcome of neonatal intraventricular hemorrhage with periventricular echodense lesions. Ann Neurol 1984; 15(3):