ANEMIA IN THE NEWBORN

MARIAN GARCIA-COLASITO
Pediatrician-Neonatologist
 ANEMIA IN THE NEWBORN
is defined as less than the normal
range of hemoglobin for birth weight
and postnatal age or 2 standard
deviation below the mean for age

Hemoglobin increases with advancing

gestational age:

Term - cord hemogblobin16.8 g/dl

(14-20g/dl)
VLBW – 1-2 g/dl below of term
“PHYSIOLOGIC ANEMIA”

Physiologic Anemia : PT vs Term

Hemoglobin(mg/dl) Age
Term 11 8 -12 weeks

Preterm 7 - 10 6 weeks
 Physiologic anemia
Preterm are deprived of third trimester
hematopoiesis and Fe transport
Shorter RBC life span
Hemodilution caused by rapidly increasing
body mass
Phlebotomy
Physiologic drop caused by low
erythropoietin in response to anemia
 Anemia at birth

Manifestations:
PALLOR
HEART FAILURE
SHOCK

Causes: Acute or chronic fetal blood

loss
Hemolysis
Underproduction of
erythrocytes
 Anemia at birth
SPECIFIC CAUSES OF ANEMIA :

1. Hemolytic disease of the Newborn

2. Tearing or cutting of cord during delivery
3. Abnormal cord insertion
4. Placenta previa or abruptio
5. Incision into the placenta
6. Internal hemorrhage (liver, spleen,
intracranial)
7. Congenital parvovirus infection
8. Twin-twin transfusion – arteriovenous
placental connections
Transplacental hemorrhage
– with bleeding from the fetal into the
maternal circulation
has been reported in 5-15 % of
pregnancies –
not sufficient to cause clinically
apparent anemia at birth
severe – anemia at birth

Cause is unknown
Transplacental hemorrhage

Diagnosis
KLEIHAUER-BETKE TEST – will
demonstrate significant amount of fetal
hemoglobin and red blood cells in maternal
blood
Treatment
Severe anemia and heart failure –
emergency exchange transfusion to
restore hematocrit
 ACUTE BLOOD LOSS
Results in severe distress at birth
Initially – hemoglobin level normal
No hepatosplenomegaly
Early onset of shock

CHRONIC BLOOD LOSS IN UTERO

at birth:
marked pallor, less distress, low
hemoglobin
severe – heart failure
ANEMIA in the first few days
after birth
Hemolytic disease of the newborn
Hemorrhagic disease of the newborn
Bleeding from improperly tied cord
Large cephalhematoma
Intracranial hemorrhage
Subcapsular bleeding from rupture of
the liver, spleen, adrenals, kidneys
 Later in the neonatal period –
delayed anemia
1. Hemolytic disease of the Newborn
a. Congenital hemolytic anemia
(Spherocytosis) – 1st month
b. Hereditary nonspherocytic
hemolytic anemia secondary to G6PD

2. Bleeding from hemangioma of

upper gastrointestinal tract
3. Repeated blood sampling
 ANEMIA OF PREMATURITY
-Occurs in LBW infants 1-3 months
after birth, associated with
hemoglobin levels below 7-10 gm
Manifestations
-Pallor, apnea, poor weight gain,
decreased activity, tachypnea,
tachycardia and feeding problems
 ANEMIA OF PREMATURITY
-Causes
Repeated phlebotomy for blood tests
Shortened RBC survival
Rapid growth
Physiologic effects of the transition
from fetal (low PaO2 and hemoglobin
saturation) to neonatal life (high PaO2
and hemoglobin saturation)
 NEONATAL ANEMIA
TREATMENT

BLOOD TRANSFUSION – depends on severity of

symptoms, hemoglobin level, presence of co-
morbid diseases
( BPD, HMD, cyanotic congenital heart disease)

Asymptomatic full-term infants with hgb level of 10

g/dl – monitor
Indication for transfusion:
 ANEMIA

The need for the treatment with blood

should be balanced against the risks of
transfusion
Hemolytic transfusion reactions
Exposure to blood product preservatives
Volume overload
Transfusion acquired infection (CMV,
HIV, Hepatitis B and C)
 TREATMENT
Symptomatic full- term infant with
Hgb level of 10g/dl – monitor

Symptomatic neonates born after

abruptio or with severe hemolytic
disease – blood transfusion

Preterm with repeated episodes of

apnea and bradycardia despite
theophylline therapy and Hgb level
<8g/dl
 ANEMIA
pRBC (10-20ml/kg) at a rate of 2-3 ml/kg/hr
2ml/kg raise the hemoglobin level 0.5-1g/dl
Recombinant erythropoietin
Ferrous sulfate
HEMOLYTIC DISEASE OF THE
NEWBORN
• Also called ERYTHROBLASTOSIS
FETALIS
Transplacental passage of maternal
antibody active against paternal RBC
antigens of the infant
Increased rate of RBC destruction
- Rh or ABO
- associated with D antigens of Rh blood
 Rh INCOMPATIBILITY

1. Rh positive blood is infused into Rh

negative woman through error or
when small quantities (> 1 ml) of Rh+
fetal blood containing D antigen
inherited from an Rh + father enter the
maternal circulation during pregnancy,
with spontaneous or induced abortion,
or at delivery
 Rh Incompatibility
Antibody formation against D antigen
may be induced in the unsensitized Rh-
negative recipient mother
If sensitization takes place, smaller
doses of Antigen can stimulate an
increase in Antibody titer.
Initially, a rise in IgM antibody occurs
which later replaced by IgG antibody -
which readily pass to placenta -
HEMOLYSIS
 Rh Incompatibilty

Hemolytic disease rarely occurs

during first pregnancy
- Because transfusions of Rh-positive
fetal blood into an Rh-negative mother
tend to occur near the time of delivery –
too late for the mother to become
sensitized and transmit antibody to her
infant before delivery
 Rh Incompatibilty
The overall incidence of
isoimmunization of Rh-negative
mothers at risk is low
-only about 5% of babies with
hemolytic disease
 Rh Incompatibilty
- severity of Rh illness tends to worsen
with successive pregnancies
Prevention : Injection of anti-D gamma
globulin (RhoGAM) into the mother
immediately after the delivery of each
Rh-positive infant
 PREVENTION OF RH
SENSITIZATION
Intramuscular injection of 300ug
human anti-D globulin (RHOGAM)
within 72 hr of delivery of an Rh-
positive infant, ectopic pregnancy,
abdominal trauma, abortion

RHOGAM administered at 28-32

wk and again at birth is more
effective than single dose
 Rh Incompatibilty
Clinical Manifestation
Laboratory evidence hemolysis
Severe anemia ( pallor, signs of
cardiac decompensation –
cardiomegaly, respiratory distress,
massive anasarca and circulatory
collapse
HYDROPS FETALIS – excessive
abnormal fluid in 2 or > compartments
Jaundice – more prominent
 Rh Incompatibilty
Laboratory data
Direct Coombs test positive – antibody
bound to the infant’s RBC
Anemia
Reticulocyte count is increased
WBC count usually normal
Blood smear : increased nucleated
RBCs
 Rh Incompatibilty
Treatment

Main goals of therapy

Avoid neurotoxicity from

hyperbilirubinemia
 Rh Incompatibilty
Treatment

Exchange transfusion
high risk of rapid development of
dangerous degree of anemia or
hyperbilirubinemia
fresh whole blood, Group O, Rh-
negative blood crossmatched
against maternal blood
 ABO Incompatibility
The most common cause of hemolytic disease of
the newborn
-Major blood group incompatibility between the mother and
fetus generally results in milder disease than Rh
incompatibility

Usually the mother is type O and the infant is type A or B

Low antigenicity of the ABO factors in the fetus – low

incidence of severe ABO hemolytic disease

Mothers who have become immunized against A or B

factors from previous incompatible pregnancy – exhibit IgG
antibody
 Clinical Manifestation
Most cases mild
Jaundice
Pallor not present at birth
Hydrops fetalis is rare
 ABO Incompatibility
Diagnosis
ABO incompatibility
Baby – B, A
Mother – O
Coombs test – weakly positive
Spherocytes in the blood smear pathognomonic
Hyperbilirubinemia – often the only laboratory
abnormality

Treatment
PHOTOTHERAPY
Exchange transfusion
 PHLETHORA
(POLYCYTHEMIA)
Plethora- a ruddy, deep red purple
appearance, associated with high
hematocrit

 defined as central hematocrit of

65% or higher
 PHLETHORA
(POLYCYTHEMIA)
Incidence is increased :
High altitude
Postmature
SGA
LGA
During 1st day of life (peak 2-3 hours)
Recipient infant of twin-twin transfusion
After delayed clamping of the umbilical cord
 PHLETHORA

Manifestations
Anorexia, lethargy, tachypnea,
respiratory distress, feeding
disturbance, hyperbilirubinemia,
hypoglycemia, thrombocytopenia

Severe complications : Seizure,

NEC, pulmonary hypertension
 PHLETHORA
(POLYCYTHEMIA)
Treatment : Symptomatic – partial
exchange transfusion with normal
saline

Reported adverse outcomes :

Speech deficits, abnormal fine
motor control, reduced IQ
 HEMORRHAGIC DISEASE of
the Newborn
Moderate decrease in factors II,VII,IX,X
– all normal in newborn 48-72 hours after
birth

- Lack of free Vitamin K in the mother

- Absence of bacterial intestinal flora –
synthesis of Vitamin K
HEMORRHAGIC Disease of the
Newborn
rarely in term infants and more
frequently in premature
- accentuation and prolongation of this
deficiency between 2nd and 7th days of
life result to spontaneous and
prolonged bleeding

Breast milk – poor source of Vitamin K

Responsive to Vitamin K
 HEMORRHAGIC Disease of the Newborn

Early-onset life-threatening Vit K deficiency

induced bleeding – onset from birth to 24
hours) – mother has been treated with
drugs
Phenobarbital
Phenytoin
Warfarin
Rifampicin
Isoniazid
interfere with Vitamin K function
HEMORRHAGIC Disease of the Newborn

Late-onset (>1 week)

often associated with Vitamin K
malabsorption
- biliary atresia
- neonatal hepatitis
 Hemorrhagic Disease of the Newborn

Manifestations:
Bleeding tends to be gastrointestinal,
nasal, subgaleal, intracranial or due to
circumcision
Lab exams
PT, Blood coagulation time, PTT are
prolonged and levels of II, VII,IX, X
are decreased
 Hemorrhagic Disease of the Newborn

Management

Vit K 1 mg Intramuscular injection at

the time of birth prevents the decrease
in Vitamin K -dependent factors

Fresh frozen plasma 10ml/kg – PT

greatly prolonged and fails to improve
 Swallowed Blood Syndrome

Blood or bloody stools are passed –

2nd-3rd day of life, may be confused
with hemorrhage from GI tract

The blood may be swallowed during

delivery or from fissure in the
mother’s nipple
 Swallowed Blood Syndrome
GI Bleeding
Infants blood contains mostly Fetal
hemoglobin, which is alkali-
resistant
Swallowed blood from a maternal
source contains adult hemoglobin,
which promptly changed to alkali
hematin after addition of alkali
 Swallowed Blood Syndrome
APT TEST
Rinse a blood-stained diaper with water
to obtain pink supernatant – centrifuge
– add to five part of supernatant one
part of 1% Sodium hydroxide, within 1-2
min , color reaction is noted
Persistent pink- fetal blood
Yellow – brown color – maternal blood
 What is Jaundice?
• Visible yellowish discoloration of the skin
• usually first noted when the serum bilirubin
is about 5-7 mg/dl
• may be an early diagnostic clue to a
number of diseases
 JAUNDICE and
HYPERBILIRUBINEMIA

• Benign condition for most infants

• About 50% of full-term infants and 80%

of premature infants become jaundiced in
the first few days of life
 JAUNDICE

• Color results from accumulation in the skin

of unconjugated, non-polar, lipid-soluble
bilirubin pigment (indirect-reacting)
BILIRUBIN METABOLISM
1 gm hgb – 35 mg
bilirubin
 PHYSIOLOGIC JAUNDICE

Icterus Neonatorum
- neonatal hyperbilirubinemia is an almost
universal finding during the first week of
life
- this transient elevation of the indirect-
reacting fraction of bilirubin has been
called physiologic jaundice
- increased bilirubin production after the
breakdown of fetal RBC and transient
limitation in the conjugation of bilirubin by
the liver
 PHYSIOLOGIC JAUNDICE
1. Indirect-reacting bilirubin rises at a rate <
5mg/dl/day
2. Jaundice becomes visible between 2nd and 3rd
day of life
3. Jaundice peaks between 2nd and 4th days at 5-
6mg/dl in full term infants and decreases below
2 mg/dl between 5th and 7th days of life.
A rise to 10-12 mg/dl is in physiologic range
4. In premature infants, the peak may be 10-12
mg/dl on the 5th day of life, possibly rising over
15mg/dl without any specific abnormality in
bilirubin metabolism
 PHYSIOLOGIC JAUNDICE
CAUSES :
Increased bilirubin load due to :
1. Increased RBC volume /kg and
decreased RBC survival (90 days vs
120 days) in infants compared to
adults
2. Increased ineffective erythropoeisis
and increased turnover of non-
hemoglobin heme proteins
 PHYSIOLOGIC JAUNDICE
CAUSES :
3. Increased enterohepatic circulation
caused by high levels of intestinal beta-
glucoronidase , decreased intestinal
bacteria, and decreased gut motility with
poor evacuation of bilirubin-laden
meconium
4. Defective conjugation due to decreased
UDPG-T activity
5. Decreased hepatic excretion of bilirubin.
 PATHOLOGIC JAUNDICE
Jaundice appears in the first 24-36 hours of life
Serum bilirubin is rising at a rate >
5mg/dl/day
Serum bilirubin is greater than 12mg/dl in full term
or 10-14 mg/dl in preterm infants
Jaundice persist after 10-14 days (excluded are
exclusively breasfeeding babies)
Direct-reacting bilirubin is greater than 2 mg/dl at
any time
 ETIOLOGY
UNCONJUGATED HYPERBILIRUBINEMIA
1. Increase load of bilirubin to be
metabolized by the liver

(hemolytic anemia, polycythemia, shortened

red cell life, increased enterohepatic
circulation, infection)
UNCONJUGATED HYPERBILIRUBINEMIA

2. Damage or reduce activity of transferase

enzyme
(genetic deficiency, hypoxia, infection,
thyroid deficiency, hypothermia)

3. Competes for or blocks the transferase

enzyme (drugs)

4. Reduction of bilirubin uptake by liver cells

(genetic defect , prematurity)
 JAUNDICE Risk factors for Neonatal
Hyperbilirubinemia

• Jaundice visible on the 1st day of life

• A sibling with neonatal jaundice or anemia
• Unrecognized hemolysis
• Non-optimal feeding (Formula or
breastfeeding)
 JAUNDICE Risk factors for Neonatal
Hyperbilirubinemia

Deficiency of glucose-6-phosphate
dehydrogenase
Cephalhematoma or bruising
Central hematocrit >65%
 Clinical manifestation

Begins on the face, and as serum levels

increase, progress to abdomen and
then to feet

Dermal pressure may reveal the

anatomic progression
Face – 5 mg/dl
Mid- abdomen – 15mg/dl
Soles – 20 mg/dl
 Clinical manifestation
• Visual inspection
– costs nothing
– dependent on available light
– dependent on infant’s skin color
– dependent on clinical experience of
observer
5

2 0
8
15
 Clinical Manifestation

• Jaundice resulting from deposition of

indirect bilirubin in the skin
– Bright Yellow or orange

• Jaundice of obstructive type (Direct

bilirubin ) – Greenish or Muddy
yellow

• Affected infants – lethargic , may feed

poorly
 DIFFERENTIAL DIAGNOSIS
JAUNDICE AT BIRTH OR within 24 hr of life
Erythroblastosis fetalis
Concealed hemorrhage hematoma
Sepsis
TORCH
Hemolysis : rapid rise in serum bilirubin
(>0.5mg/dl/hr)
anemia, pallor,
reticulocytosis,
hepatosplenomegaly,
DIFFERENTIAL DIAGNOSIS
JAUNDICE 2nd or 3rd day of life
Usually physiologic
Familial non-hemolytic icterus (Crigler-
Najjar)
Early-onset breastfeeding jaundice

JAUNDICE AFTER 3rd day /or within the

1st week
Sepsis
Urinary tract infection
TORCH
 DIFFERENTIAL DIAGNOSIS

JAUNDICE after 1st week of life

• Sepsis
• Congenital atresia or paucity of bile
ducts
• Hepatitis
• Galactosemia, Hypothyroidism
• Congenital hemolytic anemia
(Spherocytosis)
• G6PD
 DIFFERENTIAL DIAGNOSIS

Persistent jaundice during the 1st

month of life
Inspissated bile syndrome
Hyperalimentation-associated
cholestasis
Hepatitis
TORCH
Congenital atresia of bile ducts
Galactosemia
 COMPLICATIONS Of
Hyperbilirubinemia/BILIRUBIN
TOXICITY

Kernicterus or bilirubin encephalopathy:

– a neurologic syndrome resulting from
deposition of unconjugated bilirubin in the
basal ganglia and brainstem nuclei
 Kernicterus
CLINICAL FEATURES

ACUTE FORM
Phase 1 (1st 1-2 days) : Poor sucking,
stupor, hypotonia, seizures
Phase 2 (Middle of 1st week) : Hypertonia of
extensor muscles, opisthotonus, fever

Phase 3 (after the 1st week) : Hypertonia

 Kernicterus
CHRONIC FORM

First year : Hypotonia, active DTRs , deleyed

motor skills
After 1st year : Movement disorder
(Choreoathetosis, tremor), upward gaze,
sensorineural hearing loss
PROGNOSIS :
Kernicterus will develop in one third of infants (all
gestational ages) with untreated hemolytic
disease and bilirubin levels in excess of 25-30
mg/dl

Overt neurologic signs have poor

prognosis :
75% - die
80% of survivors – bilateral choreoathetosis
with involuntary spasms, mental retardation,
deafness, spastic quadriplegia
 LABORATORY EXAMINATIONS

1. Total bilirubin
2. Blood type, Rh, and Coombs’test of infant
- isoimmune hemolytic disease
3. Blood type, Rh, and antibody screen of
the mother
4. Peripheral smear for RBC morphology
and reticulocyte count (spherocytosis)
5. Reticulocyte count
 DIAGNOSTIC TESTS
• 6. CBC, WBC – infection, polycythemia
or suggest blood loss from occult
hemorrhage
• 7. Direct bilirubin – jaundice > 2wk or with
signs of cholestasis (light-colored stools
and bilirubin in urine)
8. In prolonged jaundice, test for liver
disease, congenital infection, metabolic
defects, sepsis, hypothyroidism
9. G6PD screen
 TREATMENT
Goal : To prevent the concentration of
indirect-reacting bilirubin in the blood from
reaching levels at which neurotoxicity may
occur

Protoporphyrin - inhibit the conversion of

biliverdin to bilirubin
Intravenous Immunoglobulin- with
Coombs-positive hemolytic anemia
Exchange transfusion (Double volume)
 TREATMENT
PHOTOTHERAPY – When bilirubin absorbs
light :

1. Photoisomerization – natural isomer of

unconjugated bilirubin is converted to a less
toxic polar isomer that diffuses into the blood
and is excreted into the bile without
conjugation

2. Structural isomerization – native bilirubin is

converted to structural isomer lumirubin,
which is excreted by the kidneys in the
unconjugated state
 Suggested Maximal Indirect Serum bilirubin
concentration (mg/dl) in preterm infants

Birth weight Uncomplicated Complicated

< 1000 gms 12 – 13 10 -12
1000 – 1250 12 – 14 10 – 12
1251 – 1499 14 – 16 12 – 14
1500 – 1999 16 – 20 17 – 17
2000 – 2500 20 – 22 18 – 20
 Approach to Indirect Hyperbilirubinemiab in
Healthy Term Infants without hemolysis

Age (hr) Phototherapy Intensive photo Exchange

and preparation transfusion
for exchange
transfusion
24-48 <15-18 > 25 >20
49-72 >18 – 20 > 30 > 25
> 72 > 20 > 30 >25
 TREATMENT

Complications of Phototherapy :

Loose stools, erythematous macular

rash, purpuric rash, overheating,
dehydration, chilling from exposure o
the infant and bronze baby syndrome
(dark, grayish discoloration of the
skin), retinal damage
 TREATMENT

Exchange Transfusion

Complications : Acidosis, electrolyte

imbalance (hypocalcemia,
hypomagnesemia, hyperkalemia),
hypoglycemia, thrombocytopenia, volume
overload, arrythmias, NEC, infection, graft
vs host disease, and death