1985;75;714Pediatrics House and Leonard E. Swischuk C. Keith Hayden, Jr, Karen E. Shattuck, C. Joan Richardson, Deborah K. Ahrendt, Ray Subependymal Germinal Matrix Hemorrhage in Full-Term Neonates http://pediatrics.aappublications.org/content/75/4/714 the World Wide Web at: The online version of this article, along with updated information and services, is located on ISSN: 0031-4005. Online ISSN: 1098-4275. PrintIllinois, 60007. Copyright © 1985 by the American Academy of Pediatrics. All rights reserved. by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, at Viet Nam:AAP Sponsored on February 10, 2014pediatrics.aappublications.orgDownloaded from at Viet Nam:AAP Sponsored on February 10, 2014pediatrics.aappublications.orgDownloaded from 714 PEDIATRICS Vol. 75 No. 4 April 1985 Subependymal Germinal Matrix Hemorrhage in Full-Term Neonates C. Keith Hayden, Jr, MD, Karen E. Shattuck, MD, C. Joan Richardson, MD, Deborah K. Ahrendt, MD, Ray House, MD, and Leonard E. Swischuk, MD From the Departments of Radiology and Pediatrics, The University of Texas Medical Branch, Galveston ABSTRACT. A population of healthy, full-term newborn infants was studied in order to obtain documentation of the prevalence of intracranial hemorrhage. Cerebral ul- trasonography was performed within 72 hours of birth on 505 healthy newborn infants, 37 weeks of gestation or greater. Sonographic abnormalities were detected in 23 (4.6%) neonates. Bilateral subependymal germinal ma- trix hemorrhage occurred in 14 and unilateral hemor- rhage in five infants. Other abnormalities detected in- cluded agenesis of the corpus callosum in two infants, a cyst involving the subependymal germinal matrix in one (presumably the result of a previous subependymal hem- orrhage), and mild ventricular dilation of unknown etiol- ogy in one. Newborns with subependymal hemorrhage were compared with newborns without hemorrhage in order to determine whether any significant differences existed between the two populations. No significant dif- ferences existed between infants with and without sub- ependymal hemorrhage with regard to gender, obstetrical presentation, use of forceps, birth trauma, Apgar scores, need for resuscitation, maternal age and parity, and neo- natal clinical problems. Infants with subependymal hem- orrhage were of significantly lower gestational age and birth weight; the overall difference in weight was attrib- utable to lower weight in female infants with subepen- dymal hemorrhage. Significantly more infants with sub- ependymal hemorrhage were small for gestational age, vaginally delivered, and black. Pediatrics 1985;75:714- 718; intracranial hemorrhage, subependymal hemorrhage, premature infants. Spontaneous intracranial hemorrhage in the newborn infant is frequently associated with pre- maturity, trauma, and asphyxia;6 the very low- birth-weight infant of less than 1,500 g appears to Received for publication Aug 20, 1984; accepted Oct 16, 1984. Reprint requests to (C.K.H.) Department of Radiology, Child Health Center, The University of Texas Medical Branch, Gal- veston, TX 77550. PEDIATRICS (ISSN 0031 4005). Copyright © 1985 by the American Academy of Pediatrics. be the most vulnerable.7’8 The association between prematurity and intracranial hemorrhage has been strengthened by routine use of computed tomogra- phy,9’2 and more recently by ultrasonography.135 Using these newer modalities, intracranial hemor- rhage has been demonstrated to occur in 40% to 83% of unselected preterm neonates!6’9 Intracranial hemorrhage in the full-term infant, however, appears to be much less common than in the premature infant. Several case reports and a few small series have recently appeared in the lit- erature,2031 but these have not been comprehensive studies and have not examined the prevalence of hemorrhage in the general newborn population. Thus, we studied prospectively a population of neo- nates, 37 weeks ofgestation or greater, to determine the prevalence of intraparenchymal and intraven- tricular hemorrhage. SUBJECTS AND METHODS Sonographic evaluation of the intracranial struc- tures was performed within 72 hours of birth on 505 neonates of 37 weeks of gestation or greater who were admitted during a 6-week period to the normal newborn nursery at the University of Texas Medical Branch, Galveston. The study was ap- proved by the Institutional Review Board; written, informed parental consent was obtained for all ha- bies who participated. Examination was performed in the nursery using a commercially available Technicare real-time sec- tor scanner with a 5 MHz, 13-mm head with an optimal focal depth of 2 to 6 cm. Patients were scanned in the coronal, sagittal, and parasagittal planes, using the anterior fontanel as an acoustic window. The study population consisted of 265 male and 240 female infants. Birth weight was 3,321 ± 459 g at Viet Nam:AAP Sponsored on February 10, 2014pediatrics.aappublications.orgDownloaded from ARTICLES 715 (mean ± SD) and gestational age was 39.3 ± 1.2 weeks (mean ± SD). Route of delivery was vaginal in 383 (75.8%) infants and cesarean section in 122 (24.2%). When classified according to established standards of intrauterine growth,32 404 (80%) in- fants were appropriate for gestational age, nine (1.8%) were small for gestational age, and 92 (18.2%) were large for gestational age. The group included 274 (54.3%) Anglo-Americans, 121 (24%) blacks, 105 (20.8%) Mexican-Americans, and five (1.0%) Asians. RESULTS Of 505 infants studied, 480 (95%) had normal findings on sonogram. Two infants had sonograms that were inadequate for proper interpretation, and 23 had abnormal findings on sonogram. The follow- ing abnormalities were found: mild lateral ventric- ular dilation in one infant; agenesis of the corpus callosum in two infants; subependymal germinal matrix hemorrhage in 19 infants (bilateral in 14, left unilateral in four, right unilateral in one); and a cyst of the left subependymal germinal matrix in one infant. This latter infant apparently had an old subependymal hemorrhage with complete cystic de- generation, and this infant is included in the group with subependymal hemorrhage. Three other in- fants with subependymal hemorrhage also showed evidence of cystic degeneration within the area of hemorrhage. Bilateral subependymal hemorrhage is shown in the Figure. None of the 20 newborn infants with unilateral or bilateral subependymal hemorrhage demon- strated direct evidence of intraventricular bleeding as manifested by an echogenic clot or cast forma- tion within the ventricular system. However, two infants, both with bilateral subependymal hemor- rhages, demonstrated indirect evidence suggesting some degree of intraventricular extension. Both infants had lateral ventricular dilation, and one demonstrated third ventricular dilation as well. These findings would suggest the possibility of in- traventricular extension causing ventricular or ex- traventicular hydrocephalus. Infants with subependymal hemorrhage were compared with the 480 newborns with normal find- ings on sonogram in order to determine any sig- nificant differences between the two populations (Table). No differences existed between infants with and without hemorrhage with regard to gender, obstetrical presentation (vertex v breech), use of forceps, one- and five-minute Apgar scores, need for resuscitation, and maternal age and parity. There was a significant difference with regard to birth weight and gestational age. Babies with sub- ependymal hemorrhage were of lesser gestational age and lower birth weight. The difference in weight, however, was attributable to lower weight in female infants and black infants with subepen- dymal hemorrhage. As shown in the Table, female infants with hemorrhage were of significantly lower birth weight than female infants without hemor- rhage. Blacks with hemorrhage had lower birth weight than blacks without hemorrhage. Significantly more babies with subependymal hemorrhage were small for gestational age, were delivered vaginally, and were black. The three in- fants who were small for gestational age and who had hemorrhage were black and female. All infants were examined for evidence of birth trauma and were monitored during their nursery stay for the occurrence of clinical problems. Neither trauma nor clinical problems were more frequent or more severe in the group of infants who had subependymal hemorrhages. None ofthe babies had clinical symptoms suggesting the presence of hem- orrhage. DISCUSSION The true incidence of intracranial and/or intra- ventricular hemorrhage in the term newborn has not been established. Intracranial hemorrhage in term neonates was once thought to be primarily subdural or subarachnoid, and to be related to birth trauma. Hemorrhage into the ventricles was almost exclusively considered a problem of the premature infant, although such hemorrhages were described in term infants examined at autopsy by Craig3 and others.34’35 More recently, other reports203’ of term infants with intraventricular hemorrhage demon- strated by computed tomography and ultrasonog- raphy have emerged. Term infants who sustain intracranial hemor- rhage often have other associated problems includ- ing coagulation defects, severe asphyxia, or signifi- cant birth trauma.25’’3637 These patients typically are symptomatic at birth and may die shortly there- after.2125,3435m,39 More recently,26’2931 other term infants with intracranial hemorrhage who have no evidence of asphyxia, trauma, or coagulopathy have been described. Although most of these infants develop clinical symptoms such as apnea or sei- zures, virtually all survive their hemorrhage.26’3’ The infants in our study differed form those pre- viously described in that they were all asympto- matic. Intraventricular hemorrhage in the term neonate has been reported to arise primarily from the cho- roid plexus.35’39 Hemorrhage arising from the sub- ependymal germinal matrix has also been docu- mented.242629’38 The area of the germinal matrix is most extensive early in gestation and decreases in at Viet Nam:AAP Sponsored on February 10, 2014pediatrics.aappublications.orgDownloaded from :: _:4 #{163} 716 SUBEPENDYMAL GERMINAL MATRIX HEMORRHAGE r w 13 ‘I 13 Figure. Bilateral subependymal hemorrhage. Top, Coronal scan demonstrating bilateral subependymal hemorrhages (arrows) with slight dilation of lateral ventricles (V). Bottom, Parasagittal scan demonstrating subependymal hemorrhage (arrows) with small cystic area in center. at Viet Nam:AAP Sponsored on February 10, 2014pediatrics.aappublications.orgDownloaded from ARTICLES 717 TABLE. Characteristics of Neonates With and Without Subependymal Hemorrhage (SEH) No SEH SEH Significance Gender Male 252 (52.5)* 10 (50) NS Female - 228 (47.5) 10 (50) NS Gestational age (wk) 39.4 ± 1.2t 38.8 ± 1.1 .02 Birth weight (g) 3,327 ± 448 3,078 ± 539 .02 By gender Male 3,397 ± 441 3,270 ± 516 NS Female 3,249 ± 445 2,886 ± 515 .01 By race/ethnicity Anglo-American 3,360 ± 435 3,509 ± 316 NS Black 3,199 ± 415 2,780 ± 510 .003 Mexican-American 3,378 ± 488 2,804 NS Asian 3,293 ± 692 2,892 NS Classification Appropriate for gesta- 386(80.4) 16 (80) NS tional age Small for gestational age 6 (1.3) 3 (15) <.005 Large for gestational age 88 (18.3) 1 (5) NS Race/Ethnicity Anglo-American 264 (55.0) 8 (40) NS Black 109 (22.7) 10 (50) .0005 Mexican-American 103 (21.5) 1 (5) NS Asian 4 (0.8) 1 (5) NS Delivery Vaginal 362 (75.4) 19 (95) .04 Cesarean section 118 (24.6) 1 (5) * Values in parentheses are percents. t Values are mean ± SD. :1:Student’s t test. §x2test. size after 32 weeks.7’8 However, remnants of the germinal matrix are present at term. It persists longest in the perivascular tissue, and at term, there are scattered islands of matrix cells in the ventric- ular wall with a thick cushion in the region of the caudate nucleus and thalamus.4#{176} In this study, 20 of 505 newborns had evidence of asymptomatic, localized subependymal germinal matrix hemor- rhage. This underscores the importance of the sub- ependymal germinal matrix in the region of the caudate nucleus as a potential site of hemorrhage in the term newborn. The factors predisposing to the hemorrhages in the infants we studied are not known. When com- pared with the group of infants without hemor- rhage, the 20 infants with evidence of germinal matrix bleeding were smaller and of slightly lower gestational age. The overall difference in weight was attributable to lower weight in female infants and in black infants who had hemorrhage, and was primarily accounted for by three small-for-gesta- tional-age black female infants in the group with hemorrhage. Proportionally more infants with hemorrhage were black, were small for gestational age, and were delivered vaginally. Although these differences are statistically significant, their clini- cal importance is not clear. These findings produce some intriguing associations but provide no real clues to causation. All of our patients were studied within 72 hours of birth and most within 24 to 48 hours of birth. This did not permit us to time the occurrence of the hemorrhage as has been done in studying the premature infant.41 However, in four of the 20 infants, hemorrhage most probably occurred in utero. In one infant, a cyst involving the region of the left subependymal germinal matrix area was demonstrated. Although such cysts have been de- scribed in association with intrauterine infections, cerebrohepatorenal syndrome, and ventriculitis,42 this infant had no evidence of any of these prob- lems. Thus, we conclude that the cyst resulted from a subependymal germinal matrix hemorrhage that occurred in utero. Three other infants with subep- endymal hemorrhage also demonstrated cystic de- generation of the hemorrhagic area; this finding suggested that the hemorrhages were older, were in stages of resolution, and most probably occurred in utero. Hemorrhage into the subependymal germinal matrix is primarily a problem of the premature infant. This study demonstrates, however, that at Viet Nam:AAP Sponsored on February 10, 2014pediatrics.aappublications.orgDownloaded from 718 SUBEPENDYMAL GERMINAL MATRIX HEMORRHAGE such hemorrhages occur with relative frequency (4%) in the term newborn and the hemorrhages may be clinically silent. Although the cause of the hemorrhage is unknown, infants who appeared at greatest risk were black, vaginally delivered, and small for gestational age. ACKNOWLEDGMENTS This work was supported by grant NS 07377-14 from the National Institute of Neurological and Communica- tive Disorders and Stroke, National Institutes of Health. The authors thank Nancy Bertolino, RN, and Lela Thomas, RN, for their help with this project. REFERENCES 1. Cole VA, Durbin GM, Olaffson A, et al: Pathogenesis of intraventricular haemorrhage in newborn infants. Arch Dis Child 1974;49:722-728 2. Hambleton J, Wigglesworth JS: Origin of intraventricular haemorrhage in the preterm infant. Arch Dis Child 1979;51:651-659 3. Kenny JD, Garcia-Prats JA, Hilliard JL, et al: Hypercarbia at birth: A possible role in the pathogenesis of an intraven- tricular hemorrhage. Pediatrics 1978;62:465-467 4. Moriette G, Relier JP, Larroche J: Intraventricular hemor- rhage during the course of hyaline membrane disease. Arch Fr Pediatr 1979;34:492-504 5. Towbin A: Central nervous system damage in the human fetus and newborn infant. Am J Dis Child 1970;1 19:529-542 6. 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