Intraventricular and subependymal haemorrhage in infants dying within 10 hours of birth

Intraventricular and Subependymal Haemorrhage in Infants Dying within 10 Hours of Birth Sachio Takashima, MD and Laurence E Becker, MD, FRCP A group of 103 infants was studied who were appropriate for gestational age (AGA), born at less than 36 weeks gestation, and died within 10 hours of birth. Intraventricular haemorrhage (IVH) had occurred in about one quarter of the extremely small, premature infants (28 weeks) within 5 hours of birth, but was rare in infants> 28 weeks gestation. The incidence of subependymal haemorrhage (SEH) was relatively high in babies who died within 5 hours of birth but IVH was more common in those who lived more than 5 hours. There was no relationship between the clinical events studied and the presence of IVH or SEH in the whole group of cases dying within 10 hours of birth, but the babies who died by 5 hours after birth had a high incidence of breech delivery and very low Apgar scores. Takashima S, Becker LE. Intraventricular and sub ependymal haemorrhage in infants dying within 10 hours of birth. Brain Dev 1983;5:9-13

The application of ultrasound and computerized tomography (CT) to the diagnosis of intraventricular (NH) and sub ependymal (SEH) haemorrhage has provided useful information about high risk infants. Papile et al [1] and Curbelo et al [2] reported a high incidence of NH or SEH within 6 hours of birth in infants under 1,500 g. These data suggested that type of delivery, neonatal adaptation, and method of resuscitation were critical factors in the occurrence of these haemorrhages, although therapeutic factors in the early neonatal period were also important. However, since ultrasound and CT sometimes show a false positive image [2], the

From the Department of Pathology, The Hospital for Sick Children, Toronto, Ontario. Received for publication: August 30, 1982. Accepted for pUblication: December 27, 1982. Key words: Subependymal haemorrhage, early neo· natal, autopsy. Correspondence address: Dr. Laurence E Becker, Department of Pathology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G IX8 Canada. * Present address: Division of Child Neurology, Tottori University Medical School, Yonago 683, Japan.

reported incidence of NH and SEH may be too high. Therefore, we investigated the incidence of NH and SEH in high risk, premature infants who had died within 10 hours of birth. Materials and Methods

We found 103 cases of AGA infants < 36 weeks gestation who had died within 10 hours of birth and were autopsied at The Hospital for Sick Children, Toronto, from 1973 to 1980. The infants had been admitted to the neonatal intensive care unit at the hospital because of severe respiratory distress or apnea immediately after birth. We examined the clinical findings reported in the medical records and noted Apgar scores, resuscitation methods, and arterial acid-base values as well as the presence or absence of premature rupture of membranes, breech delivery, pneumothorax, and sodium bicarbonate administration. The brains had been flXed by suspension in 10% formalin for at least 10 days. They were examined grossly and cut coronally at 1 cm intervals. Blocks for microscopic study were taken from the frontal, parietal, temporal, and occipital lobes, thalamus, basal ganglia, and any grossly abnormal areas.

Table I Incidence of subependymal and intraventricular haemorrhage within 10 hours of birth, according to gestational age

Haemorrhage Gestational age (wk)

Intraventricular

Other intracranial % N

Subependymal

N

%

N

%

<24 <28 < 32 <36

11 13 12 1

36.7* 40.6 42.9 7.7

4 5 6 3

13.3 15.6 21.4 23.1

4 5 6 3

Total

37

35.9

18

17.5

18

None

Total

N

%

N

13.3 15.6 21.4 23.1

11

9 4 6

36.7 28.1 14.3 46.2

30 32 28 13

17.5

30

29.1

103

*Percentages are taken from the total number of babies at each gestational age.

Cases were divided into groups according to several factors: gestational age, survival time, and presence or absence of IVH. Results Incidence of IVH and SEH IVH or SEH was seen in 53% of the 103 children who had died less than 10 hours after birth. Intraventricular haemorrhage was more common in babies <32 weeks gestation than in the older newborns but the incidence of sub ependymal haemorrhage did not differ significantly with gestational age (Table I). The incidence of haemorrhage also varied with the survival time (Fig 1). In the very immature infants « 28 weeks gestation), IVH was found in 21-29% of babies who had died during the first 5 hours of life compared with 37-67% of those who died at age 5-10 hours. SEH without IVH was seen in 15-43% of those who died within 5 hours of birth and was rare in those who lived 5 hours or more. Among the infants > 28 weeks gestation, NH occurred in only one of the 11 babies who died less than 5 hours after birth (9%) compared with 36-50% of those who lived longer. In contrast, the incidence of SEH decreased by 13-20%. Relationship between IVH or SEH and Qinical Data In cases <32 weeks gestation, IVH and SEH were not related to the following findings: premature rupture of membranes; mode of delivery; Apgar scores; methods of resuscita10 Brain & Development, Vol 5, No 1.1983

tion; presence of pneumothorax, acidosis, or hypercarbia; or the amount of sodium bicarbonate administered. However, among babies who died early (before 5 hours old), those with IVH or SEH had a higher incidence of breech delivery and lower Apgar scores (86% and 71 % respectively) than those who had no intracranial haemorrhage (ICH) (17% and 33% respectively). SURVIVAL TIME

NO . OF CASES

Ihrl

I

:~&M:4

1~

• • •E:~T~~:~ITKI1] ::::;;1W1]: ] ;i;;1;;~;1] ] :::;:;[:MC=r::J <5 :

7 13

ti):;j4

II:= ::::::r=:=J

. 28WG

-==r:==::J

<7 .: • • • • •

11

<9 .:

8

~ 10 <1

__

• • • • • •[J i:;lj.tilll ]it[:

=r:::=:J 9

h.h:", :;:::::""*....... :::~:"":::::,rrH------...,1

3

13
>28WG

IS

:::%;;:;~;;;MI

<7

~~:::rl

<9

; :::ffi'FM

~ 10

I8 "] 11

,~,~::i::~N,l;:::;1

SO PROPORTION OF CASES

Fig 1 Number of cases with IVH ( _

1 10 100

1'Vol

), SEH

( k;;,;,j,;,;:j!), and other ICH (VA) in premature infants

~ 28 weeks gestation and> 28 weeks gestation who died less than 10 hours after birth.

Table 2 The relationship between the clinical data and the intraventricular or subependymal hemo"hage (~ 32 gestational weeks) Intraventricular hemo"hage (N= 19)

Subependymal hemo"hage (N =10)

Other or no hemo"hage (N=20)

Premature rupture of membranes

9

NS

1

NS

4

Breech delivery

9

NS

9

NS

6

Apgar score (~3, at 1 & 5 min)

9

NS

3

NS

5

Resuscitation Intubation Mask & bag O 2 only

12 6 1

NS NS NS

6 3

NS NS NS

15 4 1

Pneumothorax

10

NS

NS

5

Arterial acid-base balance PH < 7.15

11

NS NS NS NS

7 3 5 5

NS NS NS NS

13 7 13 7

NS NS NS

5 3 2

NS NS NS

7 5 8

~ 7.15

Pco,

> 60

8 8

~ 60

11

Sodium bicarbonate > 3 ml/kg ~ 3 ml/kg

0 Gestational age

11

4 4

26.7 ± 3.1 NS

27.8 ± 3.0 NS

26.5 ± 3.1

NS: Not statistically significant.

Systolic blood pressure at admission ranged widely, from 10-73 mmHg (41.4 ± 13.9). There was no significant difference between the groups with IVH (38.6 ± 12.4 mmHg) and with no ICH (45.0 ± 17.0 mmHg). Discussion

Incidence Recently, very high incidences of IVH and SEH were observed in premature infants with CT scanning or ultrasound techniques. Papile et al [1] reported that 43% of live-born, premature infants whose birth weights were less than 1,500 g had evidence of cerebral intraventricular haemorrhage in the CT scan. Curbelo et al [2] reported IVH and SEH on the ftrst scan in 23 of 53 infants less than 33 weeks gestation. The incidence of IVH and SEH in cases that have undergone autopsy should be higher than in those studied clinically because the babies who died were more seriously ill [3]. From cases autopsied between 1967 to 1970,

Leech and Kohnen [4] reported that SEH occurred in only 56% of premature infants, all under 2,500 g birth weight, and 95% of babies with SEH had respiratory distress syndrome (RDS). Only 60% of infants with RDS had SEH. SEH was most frequent in the small prematures « about 33 weeks gestation or 1,900 g birth weight). It occurred less than 5 hours after birth (48%) but the peak incidence was after 11 hours of age (71 %). In our cases the incidence of IVH and SEH varied between infants who had died at less than 5 hours and those surviving 5 hours or more. Very immature cases have a tendency of early rupture into·IVH. In the babies who live longer the SEH might rupture into the lateral ventricle. However, we must also consider that IVH may be the cause of death in the infants who survived longer. In a previous study [5] of 110 small premature infants «1,500 g) who had survived for more than 3 weeks and died of bronchopulmonary dysplasia, sudden infant death syndrome, or other' diseases, we found old

Takashima and Becker. Sub ependymal haemo"hage in infants 11

SEH and sUbependymal pseudocyst in 36% and IS% of cases respectively.

may be the origin of vascular rupture [22,23]. Lou et al [24, 2S] reported that autoregulation of CBF was easily lost in asphyxiated Pathogenesis premature infants and increased arterial presMany pathogenetic factors involved in IVH or sure preceding IVH might be passively reflected SEH have been noted. Reported predisposing in the cerebral circulation. Kenny et al [18 J factors include large sub ependymal matrix [S] , recognized that the cord arterial blood of thin vessel walls [6], microvasculature with premature infants with IVH had significantly arterial supply [7], haemodynamic factors high PC0 2 , suggesting that hypercarbia might involving the internal cerebral venous system be related to the occurrence of IVH. Goddard [8], and fibrinolytic activity [9]. Suggested et al [26] produced IVH in newborn beagles causal factors include hypoxaemia [10] , trauma with rapid hypercardia and/or drug-induced or compression [11], venous stasis [12], hypertension. Thus, a correlation of IVH and venous thrombosis [8], disseminated intra- SEH with increases in intravascular pressures vascular coagulation [13], haemorrhagic dia- has been suggested [27, 28], but the regional thesis [14], hypernatraemia [1S, 16], increased blood flow or intravascular pressures in the or decreased arterial pressure [17, 18], high subependymal matrix are not clear. In the peak pressure during mechanical ventilation subependymal matrix, hyperperfusion or pool[19], and hypercarbia [20]. ing of blood may differ from that of the In the babies who died within 10 hours of superficial cerebral hemispheres. Therefore, birth, there was no relationship between IVH periventricular blood flow may have to be meaand such clinical factors as breech delivery, sured to understand the pathogenesis of SEH. low Apgar scores, resuscitation, pneumothorax, On the other hand, frequently endothelial acidosis, hypercarbia, or administration of changes and sometimes necrosis occur in the sodium bicarbonate. But the babies who died subependymal matrix of cases with SEH. Since early (less than S hours after birth) had a high this matrix is at an arterial border or end zone, incidence of breech deliyery and very low it is subject to ischaemia in any hypoxaemic Apgar scores. Some factor occurring during or hypotensive event [23]. SEH might be the the birth process is thought to produce SEH result of initial focal ischaemia in the suband sometimes IVH, although the mechanism ependymal matrix followed by local intravascular hypertension. of the bleeding is not known. Previously, theories of the aetiology of IVH centered on the veins draining the subependy- Acknowledgment mal germinal matrix tissue [8, 12]. Recently, This research was supported by a grant from the Hambleton et al [17] reported that they could Medical Research Council (Canada) MA 9323. not recognize any sites of venous rupture in such cases and suggested that IVH or SEH might be due to raised arterial pressure or References cerebral blood flow (CBF). Studies on the 1. Papile L-A, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and vascular anatomy of the immature fetal brain intraventricular hemorrhage: A study of infants have shown that the arteries to the basal ganwith birth weights less than 1,500 gm. J Pediatr glia are unduly large compared with those 1978;92:529-34. supplying the cortex. A relatively large propor2. Curbelo V, Bejar R, Coen RW, Leopold G, James H, Gluck L. Serial ultrasound studies of tion of fetal CBF supplies the basal ganglia intraventricular and germinal layer hemorrhages and periventricular subependymal matrix [21]. (IVH/GLH) in preterm infants. Pediatr Res The vascular network of the sub ependymal 1980;14:630. matrix is characteristic and different from that 3. Flodmark 0, Becker LE, Harwood-Nash DC, of the basal ganglia and cerebral white matter Fitzhardinge PM, Fitz CR, Chuang SH. Correlation between cr and autopsy in premature and [22, 23]. Hambleton et al [17] found that full-term neonates that have suffered perinatal capillary channels often open at right angles asphyxia. Radiology 1980;137:93-103. directly into the veins in the sub ependymal 4. Leech RW, Kohnen P. Subependymal and intramatrix. Locus minoris resistentiae of small ventricular hemorrhages in the newborn. Am J vessels such as arterioles, capillaries, or venules PathoI1974;77:465-75. 12 Brain & Development, Vol 5, No 1.1983

5. Takashima S, Armstrong D, Becker LE. Old sUbependymal necrosis and hemorrhage in the prematurely born infant. Brain Dev (Tokyo) 1979;1:299-304. 6. Gruenwald P. Subependymal cerebral hemorrhage in premature infants, and its relation to various injurious influences at birth. Am J Obstet GynecoI1951;61:1285-92. 7. Pape KE, and Wigglesworth JS. Hemorrhage, ischaemia and the perinatal brain. London: Spastics International Medical Publications, 1979. 8. Larroche JC. Hemorrhagies cerebrales intraventricu1aires chez Ie premature. 1. Anatomie et physiopathologie. Bioi Neonate 1964;7:26-56. 9. Gilles FH, Price RA, Kevy SV, Berenberg W. Fibrinolytic activity in the ganglionic eminence of the premature human brain. Bioi Neonate 1971;18:426-32. 10. Grantoft O. Intracerebral and meningeal haemorrhages in perinatally deceased infants; intracerebral haemorrhages; pathologico-anatomical and obstetric study. Acta Obstet Gynecol Scand 1953;32:308-34. 11. Schwartz P. Birth injuries of the newborn: Morphology, pathogenesis, clinical pathology and prevention. New York: Hafner, 1961. 12. Cole V A, Durbin GM, Olaffson A, Reynolds EOR, Rivers RPA, Smith JF. Pathogenesis of intraventricular haemorrhage in newborn infants. Arch Dis Child 1974;49:722-8. 13. Gray OP, Ackerman A, Fraser AI. Intracranial haemorrhage and clotting defects in low-birthweight infants. Lancet 1968;1 :545-8. 14. Appleyard WJ, Cottom DG. Effect of asphyxia on thrombotest values in low brithweight infants. Arch Dis Child 1970;45 :705-7. 15. Simmons MA, Adcock EW, Bard H, Battaglia FC. Hypernatremia and intracranial hemorrhage in neonates. N Engl J Med 1974 ;291 :6-10. 16. Roberton NRC, Howat P. Hypernatraemia as a cause of intracranial haemorrhage. Arch Dis Child 1975;50:938-42. 17. Hambleton G, Wigglesworth JS. Origin of intraventricular haemorrhage in the preterm infant. Arch Dis Child 1976 ;51 :651-9.

18. Fujimura M, Salisbury DM, Robinson RO, et al. Clinical events relating to intraventricular haemorrhage in the newborn. Arch Dis Child 1979;54:409-14. 19. Dykes FD, Lazzara A, Ahmann P, Blumenstein B, Schwartz J, Brann AW. Intraventricular hemorrhage: a prospective evaluation of etiopathogenesis. Pediatrics 1980 :66:42-9. 20. Kenny JD, Garcia-Prats JA, 'Hilliard JL, Corbet AIS, Rudolph AI. Hypercarbia at birth: A possible role in the pathogenesis of intraventricular hemorrhage. Pediatrics 1978 ;62:465-7. 21. Wigglesworth JS, Pape KE. Pathophysiology of intracranial hemorrhage in the newborn. J Perinat Med 1980;8:119-33. 22. Takashima S, Tanaka K. Postmortem angiography of the neonatal cerebral vascular system. 2. Vascular architecture of cerebral cortex and white matter in the neonates (in Japanese). Acta Neonat Jpn (Tokyo) 1971 ;7:222-8. 23. Takashima S, Tanaka K. Microangiography and vascular permeability of the subependymal matrix in the premature infant. Can J Neurol Sci 1978;5:45-50. 24. Lou HC, Lassen NA, Friis-Hansen B. Impaired autoregulation of cerebral blood flow in the distressed newborn infant. J Pediatr 1979;94: 118-21. 25. Lou HC, Lassen NA, Tweed WA, Johnson G, Jones M, Palahniuk RI. Pressure passive cerebral blood flow and breakdown of the blood-brain barrier in experimental fetal asphyxia. Acta Paediatr Scand 1979;68:57-63. 26. Goddard J, Lewis RM, Armstrong DL, Zeller RS. Moderate, rapidly induced hypertension as a cause of intraventricular hemorrhage in the newborn beagle model. J Pediatr 1980;96: 1057-60. 27. Reynolds ML, Evans CAN, Reynolds EOR, Saunders NR, Durbin GM, Wigglesworth JS. Intracranial haemorrhage in the pre term sheep fetus. Early Hum Dev 1979;3:163-85. 28. Volpe n. Evaluation of neonatal periventricularintraventricular hemorrhage. Am J Dis Child 1980;134:1023-5.

Takashima and Becker. SubependymaZ haemo"hage in infants 13