Open Journal of Obstetrics and Gynecology, 2013, 3, 61-63 OJOG
http://dx.doi.org/10.4236/ojog.2013.39A008 Published Online November 2013 (http://www.scirp.org/journal/ojog/)
Towards simulation of germinal matrix hemorrhage as a
complication of premature birth
Renée Lampe*, Varvara Turova, Tobias Blumenstein, Ana Alves-Pinto
Cerebral Palsy and Children Neuro-Orthopedics Unit, Orthopedic Department, Clinic “Rechts der Isar”, Technical University of
Munich, Munich, Germany
Received 16 September 2013; revised 15 October 2013; accepted 23 October 2013
Copyright © 2013 Renée Lampe et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
The germinal matrix being an accumulation of im-
mature blood vessels in the premature infant brain is
known to be the main cause of the intracranial hem-
orrhage. To investigate the injuring mechanism to the
blood vessels of the germinal matrix, a modeling sce-
nario that consists of three basic steps is proposed.
First, the cerebral blood flow that depends on auto-
regulation, CO2 reactivity, and variations of intrac-
ranial pressure is modeled. Second, the chaotic blood
vessel network of the germinal matrix is generated,
and blood pressures in the vessels of this network are
computed dependent on the outcome of the first step.
In the third step, the pressures computed on the sec-
ond step are used in finite element simulations of
separate blood vessels of the germinal matrix to de-
tect critical values for vessels impairment.
Keywords: Cerebral Palsy; Germinal Matrix
Hemorrhage; Injuring Factors; Mathematical Model;
Computer Simulation
1. RISK FACTORS FOR GERMINAL
MATRIX HEMORRHAGE
A premature birth before completion of the 37th preg-
nancy week increases the risk of intracranial hemorrhage.
According to [1], 85 of 155 newborn infants with the
birth weight less than 1500 gram developed an intrac-
ranial hemorrhage within the first 24 hours of life. An-
other 37 had an intracranial hemorrhage after 24 hours of
age. The place of the brain bleeding is always the germi-
nal matrix of the immature brain. The germinal matrix
consists of richly vascularized neuroepithelial cells and is
located ventrolateral to the lateral ventricle. The vulner-
ability of the germinal matrix is primarily due to the pre-
capillary arteriolar-venular anastomoses and the absence
of muscle and collagen layers in its immature blood ves-
sels. Also changes in oxygen concentration might be
damaging for endothelial cells of the germinal matrix
because increased metabolic activity in this area leads to
high oxygen consumption (see e.g. [2]).
Some risk and protective factors for intracranial hem-
orrhage are described in [3]. Antenatal steroid therapy,
female gender of the infant, increasing gestational age
and birth weight are reported as protective, whereas
lower gestational age and mother bleedings shortly be-
fore the child birth are considered as risk factors. In [4],
acute amnion inflammation, volume expansion at deliv-
ery in the first 3 days of life and magnesium sulfate
anti-contraction medication are indicated as additional
risk factors of early intracranial hemorrhage.
The consequences of the low gestational age and pre-
term birth are acute changes in CO2 and blood pressure,
impaired cerebral autoregulation, and increased cerebral
venous pressure (CVP) due to e.g. pneumothorax, me-
chanical or any pressure ventilation, skull deformations,
and venous anatomy in germinal matrix [5,6]. Both var-
iations in CO2 blood content and impaired cerebral auto-
regulation, which is a dynamic and evolving process,
lead to cerebral blood flow (CBF) pressure-passivity,
which, in turn, causes CBF fluctuations [6-9]. The in-
crease of CVP reduces the cerebral perfusion pressure
(CPP), which is the difference between the mean arterial
pressure (MAP) and cerebral venous pressure (CPP =
MAP − CVP). This can reduce the global CBF down to
20%. Note that CVP is usually replaced by intracranial
pressure (ICP) because CVP is difficult to measure.
Fluctuations in CBF are considered as a main cause of
germinal matrix hemorrhage [5], whereas hypotension
(20% - 45% lower in premature infants) remains under
discussion.
Prevention of neonatal intraventricular hemorrhage in-
cludes different prenatal and postnatal strategies like ef-
*Corresponding author.

R. Lampe et al. / Open Journal of Obstetrics and Gynecology 3 (2013) 61-63 62
forts against preterm delivery, transfer of high risk moth-
ers to tertiary care centers, antenatal maternal steroid use,
and optimal resuscitation regarding especially minimiza-
tion of cerebral blood flow fluctuation [10]. In [11], a
pharmacologic therapy with phenobarbital and vitamin K
during antenatal period is mentioned as having signifi-
cantly reduced severe grades of intraventricular hemor-
rhage. Spinillo et al. [12] note that risk factors for neo-
natal germinal matrix hemorrhage are different from
those for intraventricular hemorrhage. Better understand-
ing of how both of these events are originated remains a
very actual task.
2. MATHEMATICAL MODELING AND
SIMULATION OF BLEEDINGS IN THE
GERMINAL MATRIX
This paper outlines our aim to mathematically simulate
the development and occurrence of bleedings in the ger-
minal matrix. The following three-stage modeling pro-
cedure is proposed.
1) Simulation of the interaction between the autoregu‐
lation, CO2 reactivity and ICP using electric circuit ana-
log models similar to those developed in [13,14]. The
varying CBF obtained as the output of this simulation will
be used as the input data for a mathematical model of the
germinal matrix blood vessel system.
2) Simulation of the germinal matrix blood vessel sys‐
tem, for which the mathematical model of Anderson and
Chaplain [15] that describes the formation of a realistic
capillary sprout network will be applied. With this model,
the processes of sprout branching, anastomosis (loop for‐
mation) and cell proliferation can be accounted for (see
e.g. [16]). Additionally, the dependence of vessels di‐
ameters on the partial CO2 content will be considered. The
outcome of the simulation will be in particular the de‐
pendency of the blood pressure on the partial CO2 pres‐
sure in every vessel of the generated network. Figure 1
shows an example of such dependencies for three types of
vessels of a deterministic blood vessel network described
in [17].
3) Analysis of the impact of pressure variations in the
mechanical properties of different types of vessels like
arterioles, veins, venules with accounting for peculiarities
of germinal matrix (vessels with no muscle and collagen
layers, with relatively large diameters and thin walls). The
vessels will be modeled as tubes made of materials with
complex elasto-plastic properties using finite element
techniques. For different types of vessels, dependency of
basic mechanical characteristics like stress, strain and
deformation on the pressure will be studied, and damag‐
ing pressure values will be detected. Figure 2 shows an
example of a finite element computation for a blood
vessel model.
Figure 1. Blood pressure versus partial CO2 pressure for arte-
rioles (red line), capillaries (green line), and venules (blue line).
Figure 2. Example of a blood vessel simulation performed with
Marc/Mentat solver.
3. CONCLUSION
With this 3-stage model, the role of different factors—
autoregulation mechanisms, CO2 reactivity, and ICP in
the occurrence of germinal matrix hemorrhages will be
quantitatively estimated. This will create a basis for prac-
tical recommendations on the prevention of intraven-
tricular hemorrhages in premature infants.
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