Risk Factors, Diagnosis, and Current Practices in the Management of Intraventricular Hemorrhage in Preterm Infants: A Review-Juniper Publishers
Juniper Publishers-Journal of Pediatrics
Abstract
Intraventricular hemorrhage (IVH) is one of the
major complications in premature infants, and its management is quite
challenging. This review article describes the pathophysiology, risk
factors, and complications of IVH. Further, it explains the current
diagnosis and treatment of IVH, along with the recent advances in its
management. IVH can occur due to fragility of germinal matrix
vasculature, impairment of cerebral auto-regulation, coagulation
disorders, genetic factors, and oxygen toxicity. Cranial ultrasonography
has been the gold standard for screening in newborns for detecting
abnormalities like IVH. However, the need of the hour is diagnostic
techniques which not only provide information on brain anatomy, but also
related to the hemodynamics. Thus, various techniques are being
explored like near infra-red spectroscopy (NIRS), advanced magnetic
resonance imaging (MRI) techniques, along with the use of biomarkers.
Regarding management of IVH, various invasive and non-invasive methods
are used for managing intracranial pressure, respiratory distress, and
avoiding complications like bleeding. Nowadays, various bundles of
measures are being adopted to decrease the incidence of IVH like delayed
cord clamping, minimal handling for first few hours, avoiding head down
position, antenatal corticosteroids etc. Establishing standard
diagnostic and management practices for IVH can prove to be really
helpful in its management and prevention.
Abbreviations: IVH:
Intraventricular Hemorrhage; NIRS: Cear Infra-Red Spectroscopy; MRI:
Magnetic Resonance Imaging; PHH: Post-Hemorrhagic Hydrocephalus; PVL:
Periventricular Leukomalacia; CBF: Cerebral Blood Flow; BBB:
Blood-Brain-Barrier; PDA: Patent Ductus Arteriosus; BP: Blood Pressure;
CFOE: Cerebral Fractional Oxygen Extraction; TNF-α:Tumor Necrosis Factor
Alpha; CNS: Central Nervous System; ROP: Retinopathy Of Prematurity;
BPD: Bronchi pulmonary Dysplasia; RI: Resistive Index; PI: Pulsatility
Index; EDBFV: End-Diastolic Blood Flow Velocity; NIRS: Near Infra-Red
Spectroscopy; PICU: pediatric intensive care unit; ICH: Cases Of
Intracranial Hemorrhage; SWI: Susceptibility-Weighted Imaging; NAA:
N-acetyl-aspartate; BOLD: Blood Oxygen Level Dependent; RSNs: Resting
State Networks; PHVD: Post-Hemorrhagic Ventricular Dilatation; VP:
Ventriculo Peritoneal; VON: Vermont Oxford Network; NICQ: Newborn
Improvement Collaborative for QualityIntroduction
Intraventricular hemorrhage (IVH) is one of the major
complications in premature infants which continues to pose challenges
in neonatal intensive care units (NICUs) worldwide. Globally, 14.9
million babies were born preterm in 2010, and approximately 1.08 million
deaths occurred due to preterm birth complications. These preterm
infants were noted with increased rates of short-term morbidities like
IVH and respiratory distress, and demonstrated poor neurodevelopment
outcomes in later years of lives [1,2]. For the past five years, several
studies conducted worldwide have reported the incidence of IVH between
20%-40% in preterm infants [3-6].
Nevertheless, the incidence of IVH has decreased
significantly over the last decade due to worldwide improvements in the
neonatal care. A 15-year cohort study revealed that the incidence of IVH
has declined from 50.9% in 1991 to 11.9% in 2005. This improvement is
primarily attributed to improved practices like use of antenatal
corticosteroids, better infrastructure, effective resuscitation skills,
appropriate handling of infants, and judicious use of ventilation [7].
However, IVH still poses a major problem as the number of very preterm
infants (<32 weeks of gestational age) has increased over the last
few years. A study has revealed that the birth rate of very preterm and
very low birth weight neonates has increased from 0.87% in 1996 to 1.10%
in 2008 [8]. Moreover, there is a direct correlation between increasing
prematurity and
severity of IVH [9].
Low psychomotor and mental developmental indices,
high incidence of cerebral palsy, and visual impairment are
classical triads of preterm infants with IVH. Also, the extent
of developmental impairment rises with increasing grade
of IVH [10,11]. Post-hemorrhagic hydrocephalus (PHH) and
periventricular leukomalacia (PVL) are the two short-term
significant sequelae of IVH, while the long-term effects include
cognitive, physical, and behavioral abnormalities [12]. These
abnormalities create stress on family, educational, health, societal,
and financial resources. A progressive increase in hospital cost
and length of stay for preterm neonates with IVH and PHH has
been noted from the year 2000 to 2010 [13].
IVH continues to be a major complication without any
definitive treatment [9,14,15]. To address the global burden of
IVH, improvements in the diagnostic and management techniques
are needed. This review article discusses the various aspects of
IVH in preterm infants including the risk factors, pathophysiology,
diagnostic tests available, complications (both short and long
term), and present trends in the management of this condition.
Moreover, the focus of this article is to provide an insight on
the advanced diagnostic tools that can be used to improve the
screening of IVH, and the bundle of measures that are being
adopted for prevention and efficient management.
Getting into the Roots: Risk Factors and Pathophysiology of IVH
A clear understanding of the pathophysiology is essential
for appropriate diagnosis and management of IVH. The
pathophysiology of IVH is multifactorial and is primarily
ascribed to inherent fragility of the germinal matrix vasculature,
disturbance in the cerebral blood flow (CBF), and platelet and
coagulation disorders [16].
Fragility of Germinal Matrix Vasculature: The blood-brainbarrier
(BBB) is composed of endothelial tight junctions, basal
lamina, pericytes, and astrocyte end-feet. Out of all the regions of
brain, the germinal matrix exhibits rapid angiogenesis contributing
to its high vascular density and cross-sectional area. Due to large
number of proliferating, migrating, and maturing neuronal and
glial precursor cells, the germinal matrix has high oxygen demand.
However, the blood vessels in germinal matrix are immature.
Immaturity or weakness of these blood vessels can contribute
to fragility of the germinal matrix vasculature. Premature infants
bleed into the germinal matrix primarily because of intrinsic
weakness in this region [16,17].It has been observed that IVH
usually originates from the subependymal veins which are thinwalled
and are surrounded by the germinal matrix tissue [18].
Risk factors: Various conditions
viz. low gestational age, low
birth weight, antenatal maternal hemorrhage, maternal infection/
inflammation, sepsis, hypotension, hypoxia, hypercapnia, seizures,
patent ductus arteriosus (PDA), thrombocytopenia, infection, and
respiratory distress are major risk factors for IVH. These risk factors
are usually responsible for fluctuations in the CBF [16,17].
The combination of inherent fragility of germinal matrix and
fluctuations in CBF causes the rupture of the vasculature, leading
to hemorrhage and thus, filling of blood in the brain’s ventricular
system [16,17].
Cerebral Autoregulation and Impairment: Cerebral
autoregulation constitutes maintenance of constant CBF despite
changes in the arterial blood pressure (BP). This is a wellregulated
process in adults and children, and acts as a buffering
system to maintain a constant tissue perfusion in spite of the
fluctuating systemic BP. However, premature infants with IVH
exhibit disturbances in this process which leads to pressure
passivity of cerebral circulation due to underdevelopment of the
process. Therefore, the premature infants are at a high risk of
cerebro vascular insult during the transition from the fetal life to
the real world [15,19].
Myocardial dysfunction, systemic hypotension, PDA,
hypocarbia, and hyperoxia are some of the factors responsible
for dysregulation in CBF [20]. Lower left ventricular output, left
ventricle stroke volume, cerebral regional oxygen saturation
(rSO2), and higher cerebral fractional oxygen extraction (CFOE)
have been noted in the infants very soon after birth, followed by an
increase in cardiac output just before the occurrence of IVH [21].
In addition, low superior vena cava flow has also been found to
be associated with IVH [22]. Ischemia-reperfusion injury has been
suggested as a potential cause for the development of IVH [20,21].
Various studies have demonstrated the association of cerebral
pressure passivity with the development of the IVH. However, the
data remains limited and there is a need to establish the definitive
relationship [23-25].
Coagulation Disorders: If there are any platelet or coagulation
disorders, hemorrhage may aggravate due to impairment of
homeostasis. Thrombocytopenia and disseminated intravascular
coagulopathy are considered to be important risk factors for
development of IVH [16,17].
Genetic Factors: Mutations in type IV pro collagen gene,
factor V Leiden, pro thrombin G20210A, and interleukin (IL)-1β
have also been implicated in the development of IVH. Moreover,
polymorphisms of inflammatory mediators like IL6 and tumor
necrosis factor alpha (TNF-α) have also been proposed as genetic
risk factors for IVH. Thus, it is believed that mutations in genes
involved in coagulation, inflammation, and thrombophilia might
lead to the occurrence of IVH [16,17].
Oxygen Toxicity: High oxygen levels can be harmful to
premature neonates in terms of central nervous system (CNS),
pulmonary, and ocular manifestations. This is primarily due to
the oxidative stress induced by their rapid environment change
from fetal life (poor oxygen supply) to an extra-uterine world
(relatively oxygen rich environment). Oxygen derived free radicals
are responsible for per oxidation of membrane lipids, inhibition
of nucleic acids and protein synthesis, and inactivation of cellular
enzymes. Ultimately, oxygen toxicity can lead to conditions like IVH, retinopathy of prematurity (ROP), and broncho pulmonary
dysplasia(BPD) in preterm babies. [26,27].
Grading: On the basis of intensity and severity, IVH is
usually described in 4 grades viz. Grade 1-germinal matrix
hemorrhage which is limited to the sub-up endymal parenchyma
or minimally involves the ventricle (<10% of the ventricle); Grade
2-intraventricular blood without distension of the ventricular
system signifies the spreading of IVH into the ventricle but does
not expand or occupy more than 50% of the ventricle; Grade
3-blood filling and distending the ventricular system and involves
more than 50% of the ventricle; and Grade 4-periventricular
venous infarction which is considered as an extensive IVH with
parenchymal involvement [12,15]. In a study of 2386 infants, the
incidences of IVH Grades 1, 2, 3, and 4 were found to be 25.1%,
7.0%, 4.8%, and 5.5%, respectively [5].
Clinical Presentation: IVH can be silent (asymptomatic),
saltatory (symptoms may appear one to several hours after
birth which includes altered level of consciousness, hypotonia,
respiratory distress, and changes in eye movements and position),
or catastrophic (evolves over few minutes to hours after birth
and signs include seizures, stupor, coma, decerebrate posturing,
muscular weakness, and bulging anterior fontanelle) [15,17].
Diagnosis: Present and Future
As IVH cannot be diagnosed clinically, neuroimaging becomes
necessary. As per the Quality Standards Subcommittee of the
American Academy of Neurology and the Practice Committee
of the Child Neurology Society, routine screening cranial
ultrasonography (CS) should be performed in all preterm infants
of <30 weeks’ gestation once between 7-14 days of age and should
be optimally repeated between 36 and 40 weeks’ postmenstrual
age. This helps in the detection of the lesions such as IVH,
which influences clinical care, as well as PVL and low-pressure
ventriculomegaly providing information about long-term neuro
developmental outcomes [12,28].
CS is an inexpensive, non-invasive, and bedside tool which
does not cause any major disturbance to the sick infants. However,
one major limitation with CS is its limited sensitivity to detect
white matter-associated abnormalities like PVL, which are better
detected using MRI. As a result, MRI has become increasingly
available over the last few years due to its high sensitivity.
However, there is insufficient data to prove the utility of MRI in
premature infants for the prognosis of the neurodevelopment
outcomes [28-31].
Current diagnostic techniques can only look into the
anatomy, and not the hemodynamics of the brain. Looking at the
future perspective, there is a need for development of advanced
techniques which can provide an insight into the brain vascular
anatomy along with the hemodynamic information at bedside.
Such newer techniques can prove to be beneficial not only as a
diagnostic tool, but may also help in the prognosis of the longterm
neuro developmental outcomes.
Transcranial Doppler Ultrasonography: Transcranial
Doppler ultrasonography is a non-invasive bedside method
which can be used to monitor cerebral circulation. It allows direct
visualization of the cerebral arteries and easy detection of CBF.
Doppler parameters like resistive index (RI), pulsatility index (PI),
and end-diastolic blood flow velocity (EDV) have shown a good
correlation with the changes in CBF [32].In premature infants
prone to develop IVH, there is a fluctuating pattern in the CBF.
Initially, CBF decreases with high RI due to infarction of the blood
vessels in the germinal matrix, followed by low RI with bleeding
of the vessels [33]. A study conducted in 39 preterm neonates
revealed high values of PI and RI and low value of EDV in the
patients of IVH. However, most sensitive predictor was found to be
EDV [34]. Another study revealed that abnormal RI within the first
72 hours of life was associated with cerebral white matter lesions
[33]. Doppler indices have also been seen as important predictors
of neonatal morbidities like IVH in fetal growth restriction
[35,36].Despite this, the clinical use of transcranial Doppler
ultrasonography is limited due to single local measurements of
velocities and RI in large arteries. Ultrafast plane-wave Doppler
imaging has shown to overcome this limitation, and thus, can
become an alternative technique [37].
Near Infra-Red Spectroscopy (NIRS): NIRS is a
spectroscopic technique which can be used to measure changes
in the oxygenation of the newborn in a non-invasive way. Being
a portable, continuous, and non-invasive bedside monitoring
technique, it has a great potential for use in NICU. It can be used
for measurement of regional CBF as well as imaging of the brain
activity as a function of time. In other words, it allows real-time
monitoring of cerebral oxygenation [38,39].
Evidence from the literature has shown that within few days
of birth, an abnormal left ventricular output, left ventricular
stroke volume, rSO2, and CFOE were observed in IVH infants.
Thus, monitoring of cardiac function, rSO2, and CFOE may help
in identification of infants at risk for IVH, and come up with
considerable preventive actions for the improvement of the
developmental outcomes. Since NIRS is used to measure the
parameters like rSO2 and CFOE, it can be really helpful in IVH
detection and monitoring [21,23,40].
Various studies have shown that NIRS can prove to be a
beneficial tool in detection of cerebral autoregulation and its
maintenance. A prospective case-control study conducted in
a tertiary care pediatric intensive care unit (PICU) correctly
identified the cases of intracranial hemorrhage (ICH) in children
using NIRS [41]. In another study, NIRS proved to be a very useful
tool for monitoring of cerebral oxygenation in preterm neonates
on assisted ventilation [42].
A phase II randomized clinical trial was conducted in
166
premature infants to determine if it is possible to stabilize the
cerebral oxygenation of extremely preterm infants monitored
by cerebral NIRS oximetry. Although the study revealed the
stabilization of cerebral oxygenation by the use of NIRS combined with a
dedicated treatment guideline, larger randomized studies
are needed to assess the long-term benefits and harms of NIRS
[43]. Currently, an observational study “Cerebral Oxygenation
and Autoregulation in Preterm Infants (Early NIRS)”is ongoing
to identify the preterm infants at highest risk for brain injury or
death using NIRS [44]. Once a solid evidence is built, NIRS can
attract a large market.
Advanced MRI Techniques: Nowadays, advanced MRI
techniques in focus include MR spectroscopy (MRS), functional
MRI (f MRI), and susceptibility-weighted imaging (SWI) for
evaluation of premature infants. In contrast to MRI, 1H-MRS
measures the signal of protons attached to carbohydrates,
fatty acids, and lipids involved in the brain biochemical process
and examines the metabolites like N-acetyl-aspartame (NAA),
creatine, choline (Cho), and lactate in the preterm brain. It has
been suggested to be a useful tool in measurement of the neuro
developmental outcomes. However, the utility of MRS is not well
established till now. The method is not absolutely quantified and
measures general outcomes like overall development quotient
[31]. On the other hand, f MRI is a functional neuroimaging
technique that measures the neural activity by assessing
spontaneous, low-frequency fluctuations in blood oxygen level
dependent (BOLD) signal. These fluctuations are consistent within
the different parts of the brain that together constitute the resting
state networks (RSNs). The spatial topography of these RSNs is
repeated in response to various tasks like cognitive, motor, and
sensory. Recent studies have shown the utility of f MRI in neuro
developmental studies as well as impact of brain abnormalities
on RSN development [31,45]. SWI is another advanced MRI
technique that is gaining popularity in pediatric neuroimaging. It
helps in easy visualization of paramagnetic substances like de oxy
hemoglobin, intracellular methemoglobin, and hemosiderin. It has
been found to have greater sensitivity than conventional MRI in
detection of small hemorrhages [46]. However, further studies are
needed to establish the role of MRS, f MRI, or SWI in detection of
IVH as well as prediction of long-term neurological outcomes.
Biomarkers: Recently, there is a growing interest on the
use of biomarkers for early diagnosis of IVH. Activin A, a growth
factor belonging to the transforming growth factor-beta super
family, plays an important role in the physiologic response to
any brain injury. Preterm neonates with IVH have been noticed
with increased activin levels, and thus, it seems to be a promising
biomarker for IVH. Another biomarker, S100b is synthesized by
astrocytes and is reported to be a predictor of IVH and neonatal
mortality. IL-6 and erythropoietin have also been shown to be
potential biomarkers for IVH [47,48].
The way ahead: Although newer diagnostic techniques and
biomarkers appear to be promising in diagnosis of IVH, there is
a need for larger number of studies to prove their benefits. Once
stronger evidence is built, these techniques and biomarkers can
prove to be very helpful in early diagnosis and prediction of IVH,
and thus, can also help in prevention of long-term complications.
Management Of IVH In Preterm Infants: Present and Future
IVH and Associated Complications: The occurrence of IVH
is associated with both short-term and long-term complications.
IVH can prove to be fatal in many premature infants. Those
who survive, may experience post-hemorrhagic ventricular
dilatation (PHVD) and PHH. Ultimately, PHH is associated with
various degrees of neurodevelopment disabilities.IVH may also
lead to white matter abnormalities like PVL, and thus, causing
abnormalities like cognitive impairment, decreased visual fields,
and spastic diplegia [12].
In the first few days of life, infants with IVH are at high risk
of seizures, PHH, and PVL, while they may experience neuro
developmental disabilities at later stages. They may develop
cerebral palsy, mental retardation, or cognitive dysfunctions.
While the premature infants with Grade3-4 IVH are at high risk
of cerebral palsy and mental retardation, infants with Grade1-2
IVH are also at risk of developmental disability. A large number
of preterm infants with Grade 3-4 IVH suffer from cognitive
handicaps, and need special education, thus, it becomes important
to have appropriate measures for the prevention and management
of IVH [12].
Management: Although there is no definitive treatment for
IVH, conventional strategy is managing BP, intracranial pressure,
and respiratory stress of neonates; avoiding complications like
re-bleeding; and correction of coagulation disorders which might
influence the progression of IVH. In addition, management of IVH
aims at screening for IVH-associated sequelae like PHH and PVL,
and their treatment. In the last few years, various invasive and
non-invasive methods have been put forward to prevent as well as
manage the IVH and the development of PHH [9,12,14].
Invasive Methods and Implications for Practice:
Ventricular peritoneal (VP) shunting has been the best definitive
treatment for PHH. It leads to permanent CSF diversion in infants
with PHH. However, the method is associated with poor longterm
outcomes, shunt infections, and risk of shunt obstructions
leading to shunt failure. This has led to the emergence of the use of
temporary shunt placements which can postpone the insertion of
VP shunts. Delayed insertion allows the infants to be mature and
well-nourished, and thus, reduces the risks associated with the
permanent shunt insertion. The two major methods of temporary
CSF diversion are ventricular reservoirs and ventriculo- subgaleal
(VSG) shunts [9,15].
Subcutaneous reservoir is another frequently used method
for the management of PHH. There is no need of repeated needle
tracks with subcutaneous reservoirs, and thus, avoids brain injury.
Early lumbar punctures (LP) or ventricular taps have also been
considered as a way to avoid PHH and protect the brain from
excessive pressure. These methods are often adequate to treat the
transient phase of PHH, and have shown to decrease the need for
surgical intervention or shunt insertion [9,15].
However, none of the above mentioned treatment can be
recommended as a definitive treatment. Ventricular reservoirs and VSG shunts are associated with infections, and their effect on
neurodevelopment outcome is unknown at present. Also, there is
a lack of evidence that early LP/ventricular taps reduce the risk
of shunt dependency, death or poor neurodevelopment outcomes.
Moreover, repeated taps as well as subcutaneous reservoirs have
been associated with infections like meningitis and ventriculitis;
and the removal of CSF with these procedures is intermittent
[9,15].
Non-Invasive Methods and Implications for Practice:
Antenatal corticosteroids have shown to increase the survival rate
and reduce the rate of IVH in premature children. The combination
of antenatal corticosteroids and Vitamin K has also shown to
decrease the incidence of IVH in infants [9,49]. Besides this,
antenatal indo mechanic also seems to be promising. A review of
19 trials with 2872 infants revealed that prophylactic treatment
with indo mechanic can reduce the incidence of PDA as well as
severe IVH. However, there was no evidence that suggested the
effect of indo mechanic on long-term neurodevelopment outcomes
[50]. Recently, a risk prediction model was developed to analyze
the effect of prophylactic indo methacin in very low birth weight
infants. The study revealed that prophylactic indo methacin was
associated with a lower risk-adjusted incidence of severe IVH [51].
However, another study revealed that prophylactic indo methacin
administered before 6 hours of life is not associated with lower
incidence of IVH [52]. Evidence from the literature also suggests
that factor VII may be an effective agent in prevention of bleeding,
and thus, can be a potential treatment for IVH [12,53].
Although these pharmacological interventions have shown
a good potential, there is limited data regarding their effect on
long-term neurodevelopment outcomes, and further studies
are needed. Looking at the positive side, these latest trends
from literature suggest that further research can be focused on
antenatal care for treating IVH and its associated complications.
Drugs which are not recommended anymore: Recently, a
review of 12 controlled trials with 982 infants was conducted to
determine the effect of postnatal administration of phenol barbital
on the risk of IVH, neuro developmental impairment or death.
The review revealed that there is lack of evidence that postnatal
phenol barbital is effective in preventing IVH. Furthermore, it is
associated with an increased need for mechanical ventilation,
and thus, phenol barbital cannot be recommended as prophylaxis
to prevent IVH in preterm infants [54]. Earlier, ethamsylate
was also suggested to have a role in reducing IVH in preterm
infants. However, a review of 7 trials with 1410 preterm infants
revealed that although IVH was reduced in infants, there was no
improvement in developmental outcomes, and thus, its use is not
recommended for IVH [55].
Introduction of bundle of measures: Vermont Oxford
Network (VON) was developed in 1980s to change the landscape
of neonatal care, and is comprised of healthcare professionals
representing NICUs around the whole world. It works via
Newborn Improvement Collaborative for Quality (NICQ) to continually improve the quality, safety, and value of newborn
care. Under NICQ 2000, five NICUs formed a group with a
common goal of decreasing the incidence of IVH and PVL among
neonates ≤1500 g. The evidence-based quality improvement
approach suggests that some potentially better practices were
developed and implemented. The practices included optimal
peripartum management, such as resuscitation, maintaining the
body’s temperature at ≥36°C, optimal surfactant delivery; early
neonatal management; measures to minimize pain and stress
via developmental care and minimal handling; maintenance of
neutral head position; fluid volume therapy for hypotension;
indo methacin prophylaxis in first 24 hours of birth; appropriate
ventilation; avoidance of routine suctioning; and limiting the use
of sodium bicarbonate and postnatal dexamethasone [56,57].
Since then, various NICUs have been introducing certain
bundle of measures to decrease the incidence of IVH. These
measures are concerned with the steps taken during delivery,
immediate care after delivery, and infants’ first few days of birth.
Bed well et al. [58] introduced an IVH prevention bundle based
on VON NICQ 2000 and evidence-based research on cerebral
circulation in OU Medical Center, Oklahoma (US).
The bundle of measures comprised of avoiding head down
position, keeping head of bed at 15 degrees, midline positioning
of head for 72 h, avoiding rapid flushes, and maintaining
body’s temperature >36.5°C. This led to significant decrease
in the incidence of severe IVH [58]. A Swedish Medical Center
NICU also worked to create a standardized care bundle which
included educating the clinical staff on IVH reduction program,
giving antenatal corticosteroids and magnesium to mothers
for neuroprotection, delayed cord clamping and prevention of
hypothermia in delivery room, midline head positioning for first
72h, minimal handling and stimulation, and slow infusions of
fluids, if needed. Though this medical center didn’t demonstrate
significant reduction in IVH, it is currently aiming to improve its
bundle of measures [59]. However, another NICU in Philadelphia
showed measurably reduced incidence of IVH (5.1% from
8.3%) after introduction of bundle of measures like midline
head positioning, minimal handling, increasing IVH awareness,
and standardizing infusion rates for boluses/blood product
[60]. A working group in Germany also revealed the decrease of
incidence of IVH from 22.1% to 10.5% after the introduction of
bundle of preventive measures; the major measures adopted
were: preference of caesarean section as a method of delivery,
delayed clamping of the umbilical cord, and additional dose of
beta methadone during pregnancy [4]. A literature review also
supported the technique of delayed cord clamping in decreasing
the risk of IVH and improving neonatal morbidity [61].
The way ahead: On the basis of available evidences, there
is a need to direct our focus on proper management of IVH with
adequate measures for its prevention. Appropriate maternal care
and method of delivery might help in prevention of IVH. After
birth, a new-born should be under intensive care for first few
days of life and be monitored for oxygen saturation levels, and development of any complications like PHH, PVL, ROP. Looking at
the future perspective, research can be carried out in the fields
of robotics, stem cells, and in utero therapies. Interdisciplinary
approaches can be adopted that can combine the beneficial effects
of antenatal care, pediatric intensive care, as well as neonatal
medicines for IVH.
Conclusion
In conclusion, IVH continues to be a major complication in
premature infants. It may lead to development of PHH and PVL in
the new-born period, and cause cognitive, physical, and behavioral
abnormalities in the long-term period. The major concern
regarding IVH is lack of definite diagnostic and management
techniques. CS remains to be a method of choice for detection
of brain abnormalities like IVH. Although better techniques
like Doppler ultrasonography and NIRS seems to be promising,
their use is limited and solid evidences need to be established.
Furthermore, advanced MRI techniques and biomarkers can
also help in the better diagnosis of IVH. Besides the advanced
diagnostic tools, standard treatment and prevention guidelines
need to be established for IVH.
Currently, there is no definitive treatment for IVH, and the
invasive methods pose a great risk for infections. Moreover, there
is limited data regarding the effect of invasive and non-invasive
methods on long-term neurodevelopment outcomes. Recently,
a bundle of measures has been adopted by various NICUs like
caesarean delivery, delayed cord clamping, minimal handling of
infants, avoiding head down position, midline positioning of head
for 72h, keeping head of bed up at 15 - 20 degrees, slow infusion
of fluids, and giving antenatal corticosteroids for IVH prevention.
Once the standard treatment is established, it will be very helpful
in controlling the IVH and its-associated mortality and long-term
neurodevelopment outcomes.
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