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Fetomaternal hemorrhage (FMH),

an update: review of literature


and an illustrative case

Dr.
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Introduction
Fetomaternal hemorrhage (FMH)
Loss of fetal blood cells to maternal circulation.
Moderate to severe FMH 0,3% of all life births.
Transference fetal blood maternal blood system
physiologis in pregnancy and at birth.
Diagnosis : severe blood loss + fetuses exhibiting
symptoms of decompensation.
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Data Sources
Pubmed library to search articles with keyword
Fetomaternal hemorrhage
Fetomaternal infusion and/or bleeding
Exclusive use of english literature.

Review of literature
FMH
Describe since 1950s fetal blood loss or
bleeding into the placenta.
Since introduction of prophylaxis and/or treatment of
Rhesus isoummunization detection rate of FMH .
Kleihauer-Betke stain commonly used in Rh(-)
women to calculate the dosage of RhIG that
has to be injected to prevent isoimmunization.
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Blood flow from fetus to mother and


vice versa
Most often physiological event, low bloof volume
clinically insignificat and undetected.
Severe FMH fetal blood loss > 30 mL
Incidence of clinically significant cases estimated 1
in 3000-10.000 women
Suspected high number of cases that remain
unreported miscarriage, or intrauterine death of
the fetus.
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Blood flow from fetus to mother and


vice versa...
FMH might present subtly when blood loss is
chronic and fetus is adapted to low Hb
Fetuses that lost blood rapidly much more likely
to be stillborn
Brace et al : slower-hemorrhaging fetuses
catecholamines and the renin angiotensin system
more effective prevented the resulting
cardiovascular distress.
Naeslund et al radioactively-labeled RBC
traversing barrier for maternal blood cell to pass
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placenta.

Blood flow from fetus to mother and


vice versa...
Mengert and his group and Macris et al maternal
blood cell encroachment of the placenta.
Transferrence of maternal blood to fetal blood
stream restoration lost blood voume.
Severe FMH does not necessarily mean a fetal
blood loss magnitude of 30 ml.
Determination Severe FMH time frame in which
blood is hemorrhaged, and potential mechanisms to
counteract cardiovascular distress.
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Blood flow from fetus to mother and


vice versa...
Gestational age might play an important role.
Unfortunately it has not yet been fully understood
why and when there is merging of fetal and maternal
blood.
Further studies in animal models need to be
conducted to investigate this placental trafficking.

Conditions associated with FMH


Disturbance in the placental barrier leak
trepassing of fetal and/or maternal cells.
Trauma
Procedure (external cephalic version, manual
removal of placenta, amniocentesis)
Preeclampsia.
Irregularities of placental microarchitecture (in
tumor)
Monochoriotic-monoamnionotic twins
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Detection of FMH
Detect symptoms and signs of potential FMH early
appropriate action to prevent futher damage to
fetus and mother.
Wylie and DAlton in 2010, most common sign :
neonatal anemia, or absent fetal movement,
stillbirth, hydrops fetalis, pathological CTG
pattern, intrauterine growth restriction.

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Detection of FMH
Suspect FMH

Detection of fetal
cells in maternal
blood stream

Kleihauer-Betke
stain

Labor sensitive &


error susceptible
procedure

Flow Cytometry

Not every hospital


has the necessary
analytical
infrrastructure
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Treatment of FMH to prevent


adverse outcome
Two options :
Delivery
Prolongation of pregnancy
Intrauterine blood transfusion
Steroid at gestational age 23 weeks for lung
maturation

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Treatment of FMH to prevent


adverse outcome
Lidenberg et al
IUT can prolong pregnancy to mature gestational
age and improve fetal outcome
Broad study of 30955 Rh(-) women in 1990 in
Canada 27 found have FMH >80 mL, with 26
cases followed up for 7 years
12 out 26 has adverse outcome 10 perinatal
death, 1 deceased at 6 months of age, 1
neurological damage.
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Treatment of FMH to prevent


adverse outcome
Kesckes et al similar adverse outcome : 3 died
(19%), 2 periventricular leukomalacia (12%).
IUT well established method to treat fetal anemia,
perform in specialized perinatal center
Immediate complication : fetal distress, death of
fetus, emergency delivery with resulting
prematurity.
Chronic : suppression erythropoiesis, induction of
additional antibodies.
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Treatment of FMH to prevent


adverse outcome
LOTUS study in 2012 overall adverse
neurological outcome of 4,8% (14 in 291 cases) in
follow up 2-17 years.
Pregnancy is near term emergency delivery &
immediate blood transfusion.

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Illustrative Case
, 31 yo, G2P1,
37 and 2/7
gestational
week

History : cesarean
section due to failure to
progress in labor 1 year
previously.

Localized itching
exanthema on
chest, neck, &
face.

Fetal growth &


blood flow in
umbilical artery
normal

Treated
accordingly

Diagnosis : PUPP
(Pruritic Urticarial
Papules & Plaques
of Pregnancy)

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Illustrative Case
Around estimated
due date

fetal
movement,
consistent
itching
exanthema, joint
pain, fatigue,
nausea

USG and CTG


inconspicuous
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Illustrative Case
40 and 3/7
gestational weeks
with regular
contraction

Emergency
transfusion of 0 Rh(-),
immediately transfer
to perinatal center and
admitted to NICU.

CTG : temporarily a
sinusoidal pattern with
variable decelerations.

Maladaptation of
neonate with pH
7,13. fetal Hb 3,5.

Cesarean delivery
was undertaken

Baby , APGAR 7/9/9,


arterial cord pH 7,20,
very pale & needed
respiratory support
with oxygen mask
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40 and 3/7 gestational weeks


with regular contraction

CTG : temporarily a sinusoidal


pattern with variable decelerations.

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Illustrative Case
Mother felt fine,
expected postoperative
pain & persistent itching
on the chest spreading
to face.

Diagnostic evaluation of
infectious disease
(CMV,Parvovirus B19,
EBV) negative.

Color & consistency of


urine was striking,
appear amber to
brownish and cloudy.

Initial blood work : sign


of hemolysis, liver
enzymes, LDH,
bilirubin,
reticulocytes, &
haptoglobulin

Maternal alpha
fetoprotein highly
elevated

Kleihauer-Betke stain
revealed 25,3% fetal
cell in maternal blood
circulation massive
FMH
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Illustrative Case
Conservative
management, oral and
topical cortisone for
exanthema

Maternal laboratory
result improving,
improvement of
exanthema.

Mother & child


discharge from our
hospital 6 days after
delivery.

After multiple blood


transfusion neonate
was well adapted &
dischrage from NICU to
the mother 5 days later
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Illustrative Case
Mother presented again 39
days after delivery
complaining dry eyes,
aggravation of itching
exanthema on chest, fatigue,
thirstiness, Jaundice & brown
urine

Lab : bilirubin &


liver enzymes,
plasma protein &
albumin normal, AFP
still elevated,
hepatitis serology (-),
ANA (+), slightly +
SMA.

Liver biopsy : sub-acute


toxic parenchymal damage.
No indication for
autoimmune hepatitis or
biliary tract afflicting
disease

Histopathological :
normal weighing placenta with
delayed maturation of
chorionic villi, sign circulatory
disorder. No indication of
malignancy or inflammation.

Mother and infant


closely followed up by
hepatologist and
pediatrician

Within days, symptom


were regressing. Patient
discharged after 6 days.

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Discussion
Final diagnosis was made 24h after delivery.
Neonates extremely low Hb treated immediately by
emergency transfusion, although the cause is
unknown.
The mothers course of the disease was more
complex.

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Discussion
, 31 yo, G2P1,
37 and 2/7
gestational
week

Localized itching
exanthema on
chest, neck, &
face.

Fetal growth &


blood flow in
umbilical artery
normal

Treated
accordingly

Diagnosis : PUPP
(Pruritic Urticarial
Papules & Plaques
of Pregnancy)
Rash caused by immune
reaction of fetal cells in the
maternal
25 blood stream.

Discussion
Adams et al : small population of cells can survive
within another genetically-distinct individual lead
autoimmune disease (primary biliary sclerosis,
Sjorgren syndrome) Microchimerism
Solano et al : maternal cells can also reside in
fetal/neonatal system.

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Discussion
Around estimated
due date

fetal
movement,
consistent
itching
exanthema, joint
pain, fatigue,
nausea

USG and CTG


inconspicuous

Indicative of a variety of
immune and autoimmune
disease

Neither Ultrasound nor doppler


velocity measurement was
done
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Discussion
no further diagnostics have
been performed prenatally.

40 and 3/7 gestational


weeks with regular
contraction

Emergency transfusion
of 0 Rh(-), immediately
transfer to perinatal
center and admitted to
NICU.

Although the
underlying cause
was unknown

CTG : temporarily a
sinusoidal pattern with
variable decelerations.

Cesarean delivery was


undertaken

Maladaptation of
neonate with pH 7,13.
fetal Hb 3,5.

Baby , APGAR 7/9/9,


arterial cord pH 7,20,
very pale & needed
respiratory support
with oxygen mask

Kaddoka et al : initial fetal Hb most


valuable prognostic factor to predict
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further outcome in life.

Discussion
In cases suspect FMH during 2nd & early 3rd
trimester perform flow cytometry or HLPC to
assess fetal Hb and estimate the lost blood volume

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Discussion
Mother felt fine,
expected
postoperative pain &
persistent itching on
the chest spreading to
face.

Diagnostic evaluation
of infectious disease
(CMV,Parvovirus B19,
EBV) negative.

+severe fetal anemia


FMH was suspected

Color & consistency of


urine was striking,
appear amber to
brownish and cloudy.

Initial blood work : sign


of hemolysis, liver
enzymes, LDH,
bilirubin,
reticulocytes, &
haptoglobulin

Maternal alpha
fetoprotein highly
elevated

Kleihauer-Betke stain
revealed 25,3% fetal
cell in maternal blood
circulation massive
FMH

Lost fetal blood volume estimated


1897,5 mL indicate enoormous
blood volume and long time couse

Subjective, error prone


method
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Discussion
Conservative
management, oral and
topical cortisone for
exanthema

Maternal laboratory
result improving,
improvement of
exanthema.

Mother & child


discharge from our
hospital 6 days after
delivery.

After multiple blood


transfusion neonate
was well adapted &
dischrage from NICU to
the mother 5 days later
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Discussion
AFP : screening marker
for embryonal or fetal
abnormalities
up to 32 weeks of
gestation and drops.

liver damage was caused by


a reaction similar to acute
graft-versus-host-disease by
fetal leukocytes reacting
towards maternal antigens

Mother presented again 39


days after delivery
complaining dry eyes,
aggravation of itching
exanthema on chest, fatigue,
thirstiness, Jaundice & brown
urine

Lab : bilirubin & liver


enzymes, plasma protein
& albumin normal, AFP
still elevated, hepatitis
serology (-), ANA (+),
slightly + SMA.

Liver biopsy : sub-acute toxic


parenchymal damage. No
indication for autoimmune
hepatitis or biliary tract
afflicting disease

Histopathological of
placenta : normal weighing
placenta with delayed
maturation of chorionic villi,
sign circulatory disorder. No
indication of malignancy or
inflammation.

Mother and infant closely


followed up by hepatologist
and pediatrician

Within days, symptom were


regressing. Patient
discharged after 6 days.

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Conclusion
Severe FMH fetal distress
Rare, but serious pregnancy complication.
Preinatal death 31-50%
There is trafficking of fetal and maternal cells back
and forth between both blood streams.
Condition that Disrupt placental barrier associated
with FMH.

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Conclusion
Majority of FMH cases present with or absent
fetal movement.
CTG, Doppler velocity, measurement of fetal
cell in maternal blood.
Treatment : prolong pregnancy or deiver, by
experienced physicians and parents
FMH is rare, international register should be initiated
to collect data and do a long term follow up.
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