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
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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.135
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
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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 Craig3 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
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::
_: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.
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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
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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. Tsiantos A, Victorin L, Relier JP, et al: Intracranial hem-
orrhage in the prematurely born infant. J Pediatr
1974;85:854-859
7. Volpe JJ: Neonatal intracranial hemorrhage: Pathophysiol-
ogy, neuropathology, and clinical features. Clin Perinatol
1977;4:77-102
8. Volpe JJ: Neonatal periventricular hemorrhage: Past, pres-
ent, and future. J Pediatr 1978;92:693-696
9. Lee BCP, Grassi AE, Schechner 5, et al: Neonatal intraven-
tricular hemorrhage: A serial computed tomography study.
J Comput Assist Tomogr 1979;3:483-490
10. Rumack CM, McDonald MM, O’Meara OP, et al: CT de-
tecting in course of intracranial hemorrhage in premature
infants. AJR 1978;131:493-497
11. Burstein J, Papile LA, Burstein R: Subependymal germinal
matrix and intraventricular hemorrhage in premature new-
borns: Diagnosis by CT. AJR 1977;128:971-976
12. Burstein J, Papile LA, Burstein R: Intraventricular hemor-
rhage and hydrocephalus in premature newborns: A pro-
spective study with CT. AJR 1979;132:613-635
13. London DA, Carroll BA, Enzmann DR: Sonography of yen-
tricular size and germinal matrix hemorrhage in premature
infants. AJR 1980;135:559-564
14. Grant EJ, Schellinger D, Borts FT, et al: Real time sonog-
raphy of the neonatal and infant head. AJR 1981;136:265-
270
15. Sauerbrei EE, Digney M, Harrison PB, et al: Ultrasono-
graphic evaluation of neonatal intracranial hemorrhage and
its complications. Radiology 1981;139:677-685
16. Papile LA, Burstein J, Burstein R, et al: Incidence and
evaluation of subependymal intraventricular hemorrhage: A
study of infants with birth weights less than 1500 grams. J
Pediatr 1978;92:529-534
17. Ahmann PA, Lazzara A, Dykes FD, et al: Intrayentricular
hemorrhage in the high risk preterm infant: Incidence and
outcome. Ann Neurol 1980;7:118-124
18. Bejar R, Curbelo V, Coen RW, et al: Diagnosis and follow-
up of intraventricular and intracerebral hemorrhages by
ultrasound studies of infant’s brain through the fontanelles
and sutures. Pediatrics 1980;66:661-673
19. Palma PA, Morriss FH, Miner ME, et al: Prospective survey
of intraventricular hemorrhage in infants less than 1800
grams. Pediatr Res 1980;14:635
20. Chaplin ER Jr, Goldstein GW, Norman D: Neonatal sei-
zures, intracerebral hematoma, and subarachnoid hemor-
rhage in full-term infants. Pediatrics 1979;63:812-815
21. Palma PA, Miner ME, Morriss FH, et al: Intraventricular
hemorrhage in the neonate born at term. Am J Dis Child
1979;133:941-944
22. Cartwright DW, Culbertson K, Schreiner RL, et al: Changes
in clinical presentation of term infants with intracranial
hemorrhage. Dev Med Child Neurol 1979;21:730-737
23. Leblanc R, O’Gorman AN: Neonatal intracranial hemor-
rhage: A clinical and serial computerized tomographic study.
J Neurosurg 1980;53:642-651
24. Guekos-Thoni U, Boltshauser E, Mieth D, et al: Intracranial
hemorrhage in the term infant confirmed by computed
tomography. Helv Paediatr Acta 1980;35:531-544
25. Baleriaux D, Ticket L, Dony D, et al: The contribution of
CT to perinatal intracranial hemorrhage including that ac-
companying apparently uncomplicated delivery at full term.
Neuroradiology 1980;19:273-277
26. Ludwig B, Brand M, Brockerhoff P: Postpartum CT exam-
ination of the heads of full term infants. Neuroradiology
1980;20:145-154
27. Flodmark 0, Scotti G, Hardwood-Nash DC: Clinical signif-
icance of ventriculomegaly in children who suffered perina-
tal asphyxia with or without intracranial hemorrhage: An
18 month follow-up study. J Comput Assist Tomogr
1981;5:633-673
28. Guekos-Thoeni U, Boltshauser E, Willi UB: Intraventricu-
lar hemorrhage in full-term neonates. Dev Med Child Neurol
1982;24:704-705
29. Mackay P1J, Crespigny L, Murton U, et al: Intraventricular
hemorrhage in term neonates: Diagnosis by ultrasound. Aust
Paediatr J 1982;18:205-207
30. Scher NS, Wright FS, Lockman LA, et a!: Intraventricular
hemorrhage in the full-term neonate. Arch Neurol
1982;39:769-783
31. Meidell R, Marinelli PE, Randall V, et al: Intracranial
parenchymal hemorrhage in a full-term infant: An unusual
clinical presentation with ultrasonographic diagnosis. Clin
Pediatr 1983;22:780-783
32. Lubchenco LO, Hansman C, Dressier M, et al: Intrauterine
growth as estimated from live born birth weight data at 24
to 42 weeks of gestation. Pediatrics 1966;37:403-408
33. Craig WS: Intracranial hemorrhage in the newborn. Arch
Dis Child 1983;13:89-123
34. Fedrick J, Butler NR: Certain causees of neonatal death: II.
Intraventricular hemorrhage. Biol Neonate 1970;15:257-290
35. Lacey DJ, Terplan K: Intraventricuiar hemorrhage in full
term neonates. Dev Med Child Neurol 1982;24:332-337
36. Lorber J, Lilleyman JS, Peile EF: Acute infantile thrombo-
cytosis and vitamin K deficiency associated with intracra-
nial hemorrhage. Arch Dis Child 1979;54:471-472
37. McCarthy JW, Coble LL: Intracranial hemorrhage and sub-
sequent hydrocephaius in a neonate with classical hemo-
philia. Pediatrics 1973;51:122-124
38. Maki Y, Shirai 5: Angiographic findings in intraventricular
hemorrhage in newborn infants. Acta Radio! 1975;347:167-
174
39. Donat JF, Okazaki H, Kleinberg F, et al: Intraventricular
hemorrhage in full-term and premature infants. Mayo Clin
Proc 1978;53:437-441
40. Friede RL: Developmental Neuropathology. New York,
Springer-Verlag, 1974, pp 7-8
41. Partridge JC, Babcock DS, Steichen JJ, et al: Optimal
timing for diagnostic cranial ultrasound in low birth weight
infants: Detection of intracranial hemorrhage and ventric-
ular dilatation. J Pediatr 1983;102:281-287
42. Shackelford GD, Fulling KH, Glasier CM: Cysts of the
subependymal germinal matrix: Sonographic demonstration
with pathologic correlation. Radiology 1983;149:1 17-121
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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
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Copyright © 1985 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005.
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007.
has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it
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