Rhesus iso-immunization

Management

Dr. P. A. Awoyesuku
Dept. of Obs & Gynae
UPTH
 Introduction
Major cause of perinatal mortality and a complete mystery before
the 1940s
Haemolytic disease continues to occur despite well organized
prophylaxis programmes
Care now given by specialized fetal medicine units
Perinatal mortality has therefore decreased 100-fold in the last 3
decades
Fetal disease varies from clinically insignificant to intrauterine fetal
death (IUFD) as early as 17 weeks
Management has improved in western countries as a result of
technical advances in the last decade
 History / Diagnosis
Help to predict severity of haemolytic disease
– MATERNAL BLOOD TYPE / ANTIBODY SCREEN
Husband’s blood type
Husband’s zygosity
Mother’s antibody status
Antibody type – IgM or IgG

– PREVIOUS EPISODES OF SENSITIZATION

Ectopic pregnancy (<1%)
Spontaneous aborton >6/52 (3-4%)
Inadequate rhogam dosage
Previous Rh - +ve blood transfusion (90-95%)
Previous full term delivery (14-17%)
Sensitization in-utero (Grandmother theory)

– PREVIOUSLY AFFECTED FETUSES

Determine severity of haemolytic disease
Information about delivery
– Gestational age
– Type of delivery / events
– Type of therapy
– Knowledge of previous titres
 Antibody titre monitoring
Help to predict severity of haemolytic disease in current pregnancy in 62%

+ Amniocentesis and Ultrasound in 89%

Most laboratories use indirect antiglobulin (Coomb’s) test and titre

– 1:16 – carries 10% risk

– 1:32 - carries 25%

– 1:64 – 50%

– 1:128 – 75%

Auto analyser should be used in preference to titres as they are more

quantitative
– <4 IU/mL no severe disease, repeat 2-4 weekly

Functional bioassays e.g. antibody-dependent cell-mediated (ADDC) test

now available and show benefit over quantitative tests
 Amniocentesis
When anti-D level is >4 IU/mL but <10 IU/mL, monitoring is by amniotic fluid bilirubin
determinations which reflect degree of haemolysis

Spectrophotometry is employed to measure the optical density (OD) reading at 450nm

wavelength – ΔOD450

The optical density is plotted on the standard Liley’s chart with Whitfield action line modification

Timing of amniocentesis depends on antibody titre and history of previously affected fetuses

First amniocentesis is generally performed 10 weeks prior to time of expected ominous event

Repeat at 1 – 4 week interval

Downward trend after 2nd or 3rd amniocentesis is good prognostic sign

If no downward trend, the ΔOD450 trend line on Liley’s curve is extrapolated until it crosses the

action line
– If this occurs <34weeks, fetal blood sampling is undertaken

– If after 34 weeks delivery is recommended at the time of intersection

NB: recently limit of 4Iu/mL has been challenged and an absolute level of ≥15 IU/mL has been
proposed as threshold for prenatal intervention
Liley’s chart
 Percutaneous umbilical blood sampling
(Cordocentesis)
Can be performed under direct visualizaton (Fetoscopy) or indirect

visualization (Ultrasound directed needle aspiration)

Provides information about fetal Hb/PCV, Blood group, direct

Coomb’s titer, bilirubin level, reticulocyte count

Fetal PCV preferable in 2nd trimester to Liley’s curve in estimating

degree of fetal anaemia ( Liley’s curve more predictive in 3rd than 2nd

trimester)
 Ultrasound scan (USS)
Now mainstay of fetal monitoring and timing of first
intervention if anti-D level is ≥ 10 IU/mL
With anti-D levels > 4IU/mL fetus should be scanned
weekly from 18 weeks
Partner homozygous or fetus Rhesus positive – continue
weekly USS till you detect either fetal skin/scalp
oedema, ascites, pericardial or pleural effusion
Other USS features
– Polyhydramnios
– Fetal hepatosplenomegaly
– Cardiomegaly
– Placental hypertrophy
– Abnormal fetal posture (Buddha stance)
 Treatment by fetal transfusion
When ΔOD450 falls in the highest zone after 34 weeks patient should be delivered

If < 34 weeks, an intrauterine transfusion is performed since the risk of transfusion is less than
risk of prematurity

Transfusion may be started as early as 18 weeks

Blood can be administered either peritoneally or intravascularly

Blood compatible with mothers blood is used; after the serum is depleted to a PCV of 90-95%

Fetal transfusions are managed as out-patient procedures

If sampled fetal PCV is below gestational reference range, fetus is usually transfused to a target
PCV of 50-55%

Second transfusion is always given 2 weeks after the first, which allows assessment of rate of fall
in PCV and change in percentage of fetal cells left in fetal circulation

These 2 factors determine timing of subsequent transfusions, usually given at 3-4 week intervals

Since RDS is common in these fetuses, transfusions at ≥ 28 weeks should be preceeded by

betamethasone in case emergency delivery becomes necessary
 Timing of delivery
The last transfusion is given around 32-33
weeks and the fetus is delivered 3 weeks later
before it becomes too anaemic
Delivery should be vaginal unless there is an
obstetric indication for cs
Trans placental passage of fetal RBCs increase
after 37 weeks and worsens antibody status so
there is little point in delaying delivery after this
GA
Caesarean section is usually the best alternative
for deliveries before 34 weeks
 Prevention
A 300mg dose of Rhesus immune globulin covers fetomaternal
haemorrhage of 30ml so 350mg should be given
If an appropriate dose has been given, there should be a positive
indirect Coomb’s test (excess free antibody) measured a day after the
dose
Failure of prophylaxis
– Dose too small
– Dose too late >72 hours
– Patient already immunized but antibody titre too low for laboratory
recognition
– Defective immune globulin given
Indications for prophylaxis
– At 28/52 to a Rhesus –ve non-immunized woman whose husband is Rhesus
+ve
– Postpartum if the woman remains unimmunized and delivers a Rhesus +ve
fetus
– Following amniocentesis or chorionic villus sampling
– Following evacuation of a molar pregnancy or termination of pregnancy
– Following an ectopic pregnancy
– Following abruptio placenta or undiagnosed uterine bleeding