Intraventricular Hemorrhage in the Neonate Born at Term Paul A. Palma, MD; Michael E. Miner, MD; Frank H. Morriss, Jr, MD; Eugene W. Adcock III, MD; Susan E. Denson, MD \s=b\ Four term infants were found by computerized cerebral tomography (CT) to have intraventricular hemorrhage. All were male infants who had experienced substantial intrapartum complications. One infant had subtle clinical signs at 2 days of age; the others had major neurologic findings including seizures and ophthalmoplegia that occurred at 1,4, and 6 weeks of age, respectively. Three infants inwthe hom hemorrhages were indistinguishable by CT from those described in preterim nfants now have arrested hydrocephalus and normal development. The fourth infant was found to have a large glioblastoma at the site of origin of his initial hemorrhage. These cases emphasize the need to consider this diagnosis in neonates born at term who have abnormal neurologic signs. (Am J Dis Child 133:941-944, 1979) association of intraventricular with prema¬ has been confirmed numer¬ ous postmortem anatomic studies.1'1 Recently this association has been Thehemorrhage (IVH) by turity From the Departments of Pediatrics (Drs Palma, Morriss, Adcock, and Denson) and Neurosurgery (Dr Miner), The University of Texas Health Science Center at Houston Medical School. Presented in part at the annual meeting of the Southern Society for Pediatric Research in New Orleans, Jan 19, 1979. Reprint requests to Department of Pediatrics, the University of Texas Medical School at Houston, PO Box 20708, Houston, TX 77025 (Dr Morriss). strengthened by routine use of com¬ puterized tomography (CT). Papile et al"' demonstrated that subependymal hemorrhage and IVH occurred in 43% of infants with birth weights less than 1,500 g studied with CT in the first week of life. A similarly high inci¬ dence was reported when the subjects chosen for study were less than 35 weeks' gestation." The subependymal germinal matrix of the immature brain seems to be especially vulnera¬ ble to hypoxia and acidosis,7 hypoten¬ sion or hypertension," hyperosmolarity," or increased cerebral venous pres¬ sure."1 In infants born at term, IVH is considered a rare event. Autopsy studies of stillborn infants and infants who died in the neonatal peri¬ od include only small numbers of term infants with IVH. This report de¬ scribes four neonates born at term whose major clinical problems were related to IVH and its complications. It differs from earlier reports of IVH occurring in term infants in two ways: the diagnosis in each was made by cerebral CT, and all but one have survived. REPORT OF CASES Case l.-A 3,090-g male infant was born at term to a 37-year-old gravida 4, para 2, abortus 1 after a two-hour labor induced with oxytocin. Meconium-stained amnionic Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/29/2015 fluid was passed at the somewhat precipi¬ tous forceps delivery. Apgar scores were 7 and 8 at one and five minutes, respectively. Vitamin prophylaxis was given. Results of initial examination were unremarkable except for a bruise behind the left ear. At 1 day of age, an evaluation for possi¬ ble infection was prompted by poor feed¬ ing, jitteriness, a temperature of 37.2 °C (axillary), and hyperbilirubinemia (14 mg/ dL). The spinal fluid was bloody at gross inspection, but the CSF and blood cultures were sterile. A shrill cry and increased lower extremity tone were noted. The anterior fontanel was soft and flat. Ophthalmologic examination disclosed bi¬ lateral preretinal hemorrhages. Laborato¬ ry investigation included a hematocrit of 40%, normal prothrombin time (PT) and partial thromboplastin time (PTT), a platelet count of 225,000/cu mm, and normal skull roentgenograms. The CT demonstrated blood in the right lateral ventricle, a left occipital parenchymal hemorrhage, and mild enlargement of the ventricular system (Figure, A). Clinical signs gradually resolved, and repeated CT scans documented disappearance of old blood and return of the ventricles to nearly normal size. At 15 months of age, the infant is developing normally. Case 2.—A male infant was transferred to Hermann Hospital, Houston, at 10 days of age with a history of a seizure and bloody spinal fluid. He was born at term, weighing 3,250 g, to a 24-year-old primigravida. Labor lasted 24 hours and was followed by spontaneous vaginal delivery from a vertex presentation. Apgar scores Case/Sex 1/M Intrapartum Complications Precipitous delivery; meconium staining 2/ M Prolonged labor (>24 hr) 3/M Prolonged rupture of membranes (36 hr) 4/ M First born of twin gestation *IVH indicates intraventricular hemorrhage. t— indicates absent; +, present; ±. possibly present. fontanel. He was born at term, weighing 3,500 g, to a 19-year-old primigrávida. Membranes ruptured 36 hours before the spontaneous, but prolonged, vaginal deliv¬ Initial tomographic findings. A, Case 1. Blood in posterior horn of right lateral ventricle. Distortion at top is movement artifact. B, Case 2. Hemorrhage into left caudate nucleus and left lateral ventricle. C, Case 3. Massive hemorrhage into left caudate nucleus and thalamus with small amount of blood in posterior horn of left lateral ventricle. D, Case 4. Large left intracerebral hematoma that shifts midline and blood in left posterior horn. were 9 and 10 at one and five minutes, respectively; vitamin was administered. He was discharged with his mother at age 4 days. Activity seemed to be normal until twitching of the face and right arm and leg was noted at 7 days of age. He was read¬ mitted to a local hospital where evaluation showed an abnormal EEG with a left temporal seizure focus, normal skull roent¬ genograms, a hematocrit of 60%, normal serum chemistry results, normal PT and PTT, and a platelet count of 536,000/cu mm. The spinal fluid was bloody. Phéno¬ barbital sodium was given for seizure control. On admission to Hermann Hospital, the physical examination indicated an irritable infant with an axillary temperature of 38.2 °C. The anterior fontanel was soft and flat, and neurologic and funduscopic examina¬ tions showed no abnormalities. Laboratory studies included a hematocrit of 51% and a platelet count of 610,000/cu mm. The CT showed hemorrhage in the region of the left basal ganglia extending into the left lateral ventricle and mild ventricular dila¬ tion (Figure, B). Results of neurologic examination remained normal, and serial CT scans documented disappearance of intraventricular blood and stable ventricu¬ lar size. He was discharged to home in good condition at 18 days of age. He was readmitted at 1 month of age when increased ventricular size was visual¬ ized by CT. Daily lumbar punctures were performed for two weeks, but ventricular size slowly progressed. A lumboperitoneal shunt was placed and subsequently revised; thereafter, ventricular size stabilized. At age 14 months, the infant is developing normally. Case 3.—A male infant was admitted at 28 days of age with a two-day history of opisthotonic posturing and a bulging Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/29/2015 ery. Apgar scores were not assigned, but some stimulation was required. There was had been given at no record that vitamin birth. Examination showed excessive mold¬ ing of the infant's skull. He was discharged with his mother at 1 day of age. He subse¬ quently experienced forceful vomiting and blood-streaked diarrhea during the week after discharge. At 26 days of age, he was readmitted because of stiff extremities. The infant was irritable and had a bulging fontanel and opisthotonic posturing. Labo¬ ratory studies included a hematocrit of 34%, bloody spinal fluid, and a prolonged PT (patient, 24 s; control, 13 s). Bilateral subdural taps were negative, vitamin was administered, and the infant was transferred to Hermann Hospital. On admission, examination indicated an irritable, wasted infant whose weight was less than birth weight. The fontanel was tense, and the neck was stiff to passive motion. Neurologic examination showed hypertonia, left facial and left hand pare¬ sis, and deviation of the eyes downward and to-the right. Fundi were normal. Labo¬ ratory studies included a hematocrit of 20%, a PT of 14 s (control, 10.5 s), and a platelet count of 460,000/cu mm. The CT showed blood throughout the ventricular system and hemorrhage into the left caudate nucleus, the thalamus, and posteri¬ or basal ganglia (Figure, C). Ventricles Within two were moderately dilated. weeks, the fontanel became less full, the gaze defect and hypertonic extremities improved, and the CT demonstrated disap¬ pearance of blood and a stable ventricular size. The platelet count rose to 1,000,000/cu mm at two weeks after admission. At 10 months of age, his moderate hydrocephalus Data for Infants Born at Term in Whom IVH Developed* Clinical Findings t Initial Laboratory Findings No. of Peripheral CSF Age, days Seizure Neurologic Deficit Neck BulgingRigidity Fontanel Hyperpyrexia RBCs/cu mm WBCs cu mm Blood Platelets cu mm Outcome 570,000 1,600 225,000 Normal development; arrested hydro- 447,000 620 536,000 Normal development; arrested hydro- 26 335,000 1,250 460,000 Normal development; arrested hydro- 42 127.500 132 480.000 cephalus cephalus cephalus Craniectomy for tumor; died at age 10 months is nonprogressive, and his development seems to be normal. Case 4.-A male infant was admitted at 6 weeks of age with a one-day history of irritability, tremors, and hypertonic ex¬ tremities. He was the first of twins born near term, weighing 2,650 g, to a 21-yearold gravida 3, para 2 who was hospitalized for one month prior to delivery because of preeclampsia. Vaginal delivery was spon¬ taneous from a vertex position. Apgar scores were 8 and 9 at one and five was minutes, respectively. Vitamin given at birth. The twins were discharged with their mother at 7 days of age. On admission, he was found to be an irritable, pale infant with a high-pitched cry. Axillary temperature was 37.9 °C. The fontanel was depressed. Neurologic exami¬ nation showed a rigid neck, generally increased tone and reflexes, left facial weakness, and sustained left ankle clonus. Fundi were normal. Laboratory evaluation included a hematocrit of 15%, normal PT and PTT, a platelet count of 480,000/cu mm, blood-tinged CSF, and normal skull roentgenograms. The CT showed a left frontal intracerebral hemorrhage with extension into the left lateral and third ventricles (Figure, D). The ventricular system was moderately dilated. Bilateral carotid arteriography failed to demon¬ strate an arteriovenous malformation or aneurysm. A ventriculostomy was per¬ formed because midline structures were shifted. Two weeks later when the infant was less irritable, the CT showed resolving hemorrhage and moderate hydrocephalus, and the platelet count had risen to 990,000/ cu mm. He was discharged in stable condi¬ tion at 9 weeks of age. One month later he was readmitted to the hospital to evaluate a 3.5-cm increase in head circumference. The CT demonstrated bilateral frontal porencephaly and marked hydrocephalus. A ventriculoperitoneal shunt was performed. At 8 months of age, he had another episode of intracranial hemorrhage. Repeated CT and arteriography were suggestive of a left frontal mass; a large tumor identified as a glioblastoma was surgically removed. He died shortly after the institution of chemother¬ apy. COMMENT To our knowledge, this series of is the first to demonstrate the CT findings in term infants with IVH. Fedrick and Butler' suggested that IVH occurs in fewer than 1/1000 live births at term. They reported 15 cases of infants born after 37 weeks' gestation that were found to have IVH at the time of autopsy. The majority had evidence of intrapartum asphyxia; a few had multiple sites of cases hemorrhage, suggesting a bleeding diathesis. Comparison of the clinical and labo¬ ratory features of the present four cases underscores certain similarities (Table). All were male infants with some intrapartum complication. All but one had acute neurologic deterio¬ ration. Hyperpyrexia, which previous¬ ly has been reported to occur with IVH," was present in three cases. Platelet counts were slightly elevated in three cases when the diagnosis of IVH was made; in cases 3 and 4, platelet counts increased to almost 1,000,000/cu mm two weeks after hemorrhage. Thrombocytosis was in¬ terpreted as a sign of bone marrow reactivity after the bleeding epi¬ sode.1-' Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/29/2015 The nonprogressive communicating hydrocephalus that occurred after IVH in cases 1 to 3 is similar to that described for preterm infants with IVH. The survival and short-term development in these three infants was satisfactory considering the mag¬ nitude of their initial symptoms, espe¬ cially in cases 2 and 3. The site of hemorrhage in mature infants with IVH is not yet defined. Donat et al" reported nine cases of term infants with IVH in whom the choroid plexus was presumed at autopsy to be the source of hemor¬ rhage. Maki and Shirai" described six mature infants with IVH. Their histo¬ ries were similar to those of the patients described here in that each had some obstetric complication; in contrast, they all manifested symp¬ toms before 4 days of age. The two infants in their report who died were found to have hemorrhages that origi¬ nated in the subependyma similar to those seen in preterm infants. In the other four infants, carotid anglogra¬ phy demonstrated early filling of the deep-venous system and stasis of contrast material in the choroid plexus. Our first three patients had hemor¬ rhages that by CT scanning were indistinguishable from those seen in immature infants. Cases 2 and 3 had parenchymal hemorrhages extending into the caudate nucleus and thala¬ mus, respectively. Case 4 must be considered separately. He apparently bled as a result of a discreet anatomi¬ cal abnormality. It is this possibility there are scattered islands of matrix cells in the ventricular wall and a thick cushion in the region of the caudate nucleus and thalamus.1' These fullterm infants may represent one end of the spectrum of germinal matrix hemorrhage more often associated with prematurity. The cause of the delayed onset of hemorrhage, or of the signs of hemorrhage, in cases 2 and 3 is not known. This report and review emphasizes the need to consider IVH as a poten- that urges a more detailed diagnostic approach to the full-term infant with IVH. Exclusive of infants with an iden¬ tifiable anatomical defect resulting in hemorrhage, the cause of IVH in neonates born at term is not known. Developmental blood flow alterations described by Maki and Shirai14 may place the neonate at a greater risk for deep-venous hemorrhage. The germi¬ nal matrix is known to persist longest in the perivascular tissue. At term, tial diagnosis in the neonate born at term who has acute neurologic find¬ ings. Further diagnostic studies in¬ cluding CT with contrast injection and, in some cases, arteriography may be warranted to exclude lesions that require neurosurgical intervention. Terms infants who survive IVH may experience a satisfactory outcome. Nonproprietary Name and Trademarks of Drug Oxytocin—Pit ocin, Syntocinon, Uteracon. References 1. Gr\l=o"\ntoft0: Intracranial haemorrhage and blood-brain barrier problems in the newborn. Acta Pathol Microbiol Scand suppl 100, 1954, pp 1-109. 2. Larroche JC: Hemorragies cerebrales intraventriculaires chez le premature: I. Anatomie et physiopatholgie. Biol Neonate 7:26-56, 1964. 3. Fedrick J, Butler NR: Certain causes of neonatal death: II. Intraventricular haemorrhage. Biol Neonate 15:257-290, 1970. 4. Leech RW, Kohnen P: Subependymal and intraventricular hemorrhages in the newborn. Am J Pathol 77:465-475, 1974. 5. Papile L-A, Burstein J, Burstein R, et al: Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1,500 gm. J Pediatr 92:529-534, 1978. 6. Lazzara A, Ahmann PA, Brann AW, et al: Intracerebral hemorrhage in high risk prematures. Pediatr Res 12:553, 1978. 7. Towbin A: Cerebral intraventricular hemorrhage and subependymal matrix infarction in the fetus and premature newborn. Am J Pathol 52:121-133, 1968. 8. Hambleton G, Wigglesworth JS: Origin of intraventricular hemorrhage in the preterm infant. Arch Dis Child 51:651-659, 1976. 9. Simmons MA, Adcock EW, Bard H, et al: Hypernatremia and intracranial hemorrhage in neonates. N Engl J Med 291:6-10, 1974. 10. Cole VA, Durbin GM, Olaffson A, et al: Pathogenesis of intraventricular hemorrhage in newborn infants. Arch Dis Child 49:722-729, 1974. 11. Pomerance JJ, Richardson CJ: pyrexia as a sign of intraventricular hemorrhage in the neonate. Am J Dis Child 126:854-855, 1973. 12. Wintrobe MM: Clinical Hematology, ed 7. Philadelphia, Lea & Febiger Publishers, 1974, pp 1103-1108. 13. Donat JF, Okazaki H, Kleinberg F, et al: Intraventricular hemorrhages in full-term and premature infants. Mayo Clin Proc 53:437-441, 1978. 14. Maki Y, Shirai S: Angiographic findings in intraventricular hemorrhage in newborn infants. Acta Radiol, 347, 1975, pp 167-174. 15. Friede RL; Developmental Neuropathology. New York, Springer-Verlag New York Inc, 1975, pp 7-8. Hyper- waiting room the doll faced patient handles the stethoscope with cautious eyes. he squeezes it and pauses, like a bear cub inspecting a fallen snake then, confident, he listens to his teddy's heart mastering his fears. Howard J. Bennett, MD Children's Hospital National Medical Center 111 Michigan Ave, NW Washington, DC 20010 Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 05/29/2015