Intraventricular Hemorrhage

And Hemorrhagic Disease

of the Newborn

James A Singer 2009

• All photographs, MRI and CT Scan
images are from the public domain.
Patient Presentation:
A 15-year-old female presented to
the ED with lower abdominal pain and
bleeding. She states that she has felt
some contractions. A 23 week infant
was born by cesarean section for pre-
term labor and vaginal bleeding.
The past medical history shows that the
pregnancy was complicated by teenage
motherhood, little or no prenatal care. At
delivery, the infant was found to have
the umbilical cord wrapped around the
neck. The pertinent physical exam
shows him to be 760 grams, appropriate
for gestation age.
 He was limp and blue. There were no spontanious breaths or
movements. HR was 60 per minute. The RT began bag/mask at
100% with the nurse providing chest compressions. After 2 minutes
of compressions, the heart rate was 80 per minute with the infant
gasping and started to pink up. Bagging continued at a rate of 40
bpm. At the 5 minute mark the Apgar was 6.

S N/A
O Acrocyanosis. CXR underaerated bilaterally and clouded. ABGs:
pH 7.18, PaCO2 47, HCO3 14, PaO2 60.
A Atelectasis
Metabolic acidosis
RDS
P CMV per protocol with O2 therapy and hyperinflation protocols
Complications of Prematurity
Acute

– RDS
– Pulmonary Interstitial Emphysema (PIE)
– Pneumothorax
– Patent Ductus Arteriosus
– Necrotizing Enterocolitis (NEC)
– Intra-ventricular hemorrhage (IVH)
– Multiple transfusions
– Bacterial and fungal infections
 Complications of Prematurity

Chronic

Bronchopulmonary dysplasia
(BPD)
Retinopathy of prematurity
(ROP)
Periventricular leukomalacia
(PVL)
Learning disabilities
Failure to thrive
Renal stones
Hearing loss
Injury to the germinal matrix has substantial
mortality and morbidity rates.
 IVH

Most common form of intracranial hemorrhage

(subdural and subarachnoid hemorrhage are less
common)
20% in infants <1500 g or <32 weeks
Incidence varies inversely with gestational age
>50% IVH occur in first 24 hours of life,
90% by 10 days
Pathogenesis

Germinal matrix is a highly vascular

weakly supported structure that is prone to
rupture and hypoxic-ischemic injury
 IVH
Risk factors

Extreme prematurity
Birth asphyxia
Need for vigorous resuscitation
Pneumothorax
Sudden elevations or fluctuations in BP
Other: labor, seizures, dyssynchronous
ventilation, hypothermia, hypercarbia, acidosis,
rapid bicarbonate infusion, rapid volume
infusion, PDA/PDA ligation
Clinical Presentation includes:
On Physical Examination:

Alteration in mentation - seizures, posturing, coma or

decreased consciousness
Apnea
Respiratory distress including tachypnea and retractions
Irregular breathing
Fontannel - full or bulging
Hypotension or blood pressure lability
Hypnotic
Pallor
Poor perfusion

Laboratory Values:

Acidosis
Bloody cerebrospinal fluid
Hematocrit drop
Hypoglycemia
The term Intraventricular
Hemorrhage refers to all 4 grades.
The term Periventricular Hemorrhage
refers to a grade IV IVH.
Grade I: hemorrhage limited to the subependymal
germinal matrix

Grade II: hemorrhage in the subependymal germinal

matrix with extension into the ventricular system but
without lateral ventricular dilation

Grade III: hemorrhage in the subependymal germinal

matrix with extension into the ventricular system with
lateral ventricular dilatation

Grade IV: hemorrhage in the subependymal germinal

matrix with extension into the brain tissue (i.e.
intraparenchymal hemorrhage)
 Diagnosis Using
Sonography

Sonography is the Gold Standard for bedside

diagnosis.
Determination of
ventricular
dilation can be
difficult on
sonography, but
is important
clinically.
Grade I: hemorrhage limited to the subependymal germinal matrix
Grade II: Hemorrhage in the
subependymal germinal matrix
with extension into the ventricular
system but without lateral
ventricular dilation
Grade III: Hemorrhage in the
subependymal germinal matrix with
extension into the ventricular system
with lateral ventricular dilatation
Grade IV:
Hemorrhage in the
subependymal
germinal matrix with
extension into the
brain tissue (i.e.
intraparenchymal
hemorrhage)
Grade IV: Hemorrhage in the subependymal germinal
matrix with extension into the brain tissue (i.e.
intraparenchymal hemorrhage) -MRI Scan
This image shows a intraventricular hemorrhage
where the clot forms a cast of the ventricle
Most follow-up studies have found that the neurological outcome is
associated with the grading of the IVH.
Grades I and II do not increase the chance of neurologic morbidity
measurably.

Grades III and IV have a high rate of morbidity including cerebral

palsy, seizures, and mental retardation. Periventricular white matter
ischemia often evolve into cystic lesions called Periventricular
leukomalacia or PVL. The presence of PVL carries a high risk of
neurologic morbidity.
 IVH And Vitamin K

History

Townsend in Boston (1864) described 50 cases of “hemorrhagic

disease of the newborn” during first 2 weeks of life
In 1929, Vitamin K isolated from alfalfa by Dam and Doisy (Nobel
Prize, 1942), and conducted clinical trials showing Vitamin K
protects against HDN
1961, American Academy of Pediatrics and American College of
Obstetrics and Gynecology recommended routine prophylaxis with
Vitamin K for all newborns
 IVH and Vitamin K

Often Fatal Condition

Diffuse hemorrhage in healthy to premature

infants
During the first week of life
Particularly in low birth weight babies
Results of low levels of prothrombin and other
vitamin K dependent clotting
factors, (Factors II, VII, IX and X) caused by
vitamin K deficiency
An exaggerated deficiency of clotting factors
normal in the first few days of life
Incidence between 2.5 to 17.0 per thousand
newborns not given vitamin K prophylactically
 IVH And Vitamin K

Common Clinical Manifestations

Bleeding in the:
– gastrointestinal tract
– urinary tract
– umbilical stump
– nose
– scalp
– intracranial hemorrhage
– Shock
– death
 IVH and Vitamin K

Late HDN

Between 2-12 weeks of life,

Especially in breast-fed babies.
Immaturity of liver affects production of clotting factors
Late HDN ( Hemorrhagic Disease Newborn ) primarily in breast fed
infants without or inadequate vitamin K rates of 4.4-7.2/100,000 live
births
 Vitamin K And The Newborn

Prophylactic use of Vitamin K recommended by the American

Academy of Pediatrics, and by the American College of
Obstetricians and Gynecologists since 1961.
Up until 1987, administration of vitamin K at birth was mandatory in
only five states in the US
AAP recommendation renewed in 1993 and remains current
 IVH And Vitamin K

Controversy regarding oral versus parenteral use of routine Vitamin

K largely resolved
Intramuscular administration within the first 6 hours after birth more
effective in preventing both early and late onset HDN
Role of Opiates for
Pain Control And
IVH
Is there a relationship between chronic
opiate exposure in the first week of life
and incidence of IVH and PVL in VLBW
infants?
Opioid analgesia has been recommended for ventilated
preterm neonates because of:

– Increased pain sensitivity resulting from immature pain modulatory

mechanisms
– Hyperalgesia of long duration after tissue injury
– Acute physiological and behavioral responses to painful stimuli
– Humane and ethical considerations for providing comfort.
NEOPAIN Trial (Neurologic Outcomes and
Preemptive Analgesia in Neonates )

There were higher rates of the composite

outcome and severe IVH in the subgroup born at
27–29 weeks of gestation (K J S Anand)

Open-label morphine during 25 to 72 hours after

starting study drug infusion was associated with
severe IVH (Richard W. Hall, MD*)
Ventilated VLBW infants who are chronically exposed to
higher doses of opiates during the first week of life have
a significant increase in the incidence of cardiovascular
instability and subsequent adverse neurological
outcomes.
Use of higher doses of morphine during the first 7 days in VLBW
infants was associated with increased hemodynamic instability
– Hypotension
– Inotrope use
– Steroids for hypotension

Use of higher doses of morphine during the first 7 days in VLBW

infants was associated with increased incidence of severe IVH and
PVL (periventricular leukomalacia ).

The increased risk of PVL was associated with cumulative morphine

exposure and not to birth weight, gestational age, steroid
administration or indices of disease severity.
 Summary
Most common form of intracranial hemorrhage (subdural and
subarachnoid hemorrhage are less common)
20% in infants <1500 g or <32 weeks
Incidence varies inversely with gestational age
>50% IVH occur in first 24 hours of life, 90% by 10 days

Grades I and II does not increase the chance of neurologic morbidity

measurably. Grades III and IV have a high rate of morbidity including
cerebral palsy, seizures, and mental retardation.

Results of low levels of prothrombin and other vitamin K dependent

clotting factors, (Factors II, VII, IX and X) caused by vitamin K
deficiency increase the incidence of IVH.
Open-label morphine during 25 to 72 hours after drug infusion was
associated with severe IVH.
The increased risk of PVL was associated with cumulative morphine
exposure and not to birth weight, gestational age, steroid
administration or indices of disease severity.