Dr Gayathri Vemavarapu

• SeniorConsultant - Fetal MedicineBirthRight by Rainbow Hospitals – Hyderabad

• She is accredited by the fetal Medicine Foundation (UK )for specialized fetal scans and risk assessment.

• Does Fetal intervention procedures

• Areas of Interest

• Screening

• Foetal interventions

• Prenatal Genetic evaluation and Counselling

• Protocol based and structured training

Rh Isoimmunisationantenatal diagnosis and

interventions

INTRODUCTION

• Despite anti-D prophylaxis , Hemolytic disease of newborn

continues to occur

• With appropriate pregnancy monitoring and intervention,

this disorder can be treated successfully in almost all cases,

with minimal long-term sequelae in offspring

What is the Rhesus factor?

• It is a Red blood cell antigen

• Other Red cell antigens include

• A, B – blood groups

• Duffy, Kell, Kidd

What red cell antigens are clinically significant during pregnancy ?

• The risk of fetal anaemia is greatest with anti-D, anti-c and anti-K antibodies.

• Other antibodies that potentially cause significant fetal anaemia include anti-E, -Fya , -Jka , -C and -Ce.

• There are numerous other antibodies that usually only cause mild haemolysisthat is only rarely significant

Green-top Guideline No. 65

Genetics of Rh factor

• C, D and E antigens

• D antigen is the most important and

determines Rh positivity

• cDe is Rh positive

• Two alleles – heterozygotes or homozygotes

• Rh negative person has dd genotype

Zygosity matters

Rh negative mother- Pathophysiology

• Carrying a Rh positive fetus

• Some Rh positive RBCs cross over into

the maternal circulation

• Since the mother has not been exposed

to these antigens,

• She makes antibodies to this “D” antigen

These circulating “anti-D” antibodies enter fetus

• They will attack fetal RBCs that are rhesus positive

• This causes RBC destruction (hemolysis)

• This leads to fetal anemia

• Fetus does not get hyperbilirubimemiaManifests as hydrops and fetal loss

Approach to Rh negative mother

• Careful history

• Previous pregnancy losses

• h/o blood transfusions

• Check husband‟s blood group and Rh factor

• Check anti-D antibodies

• If no antibodies at “booking”, then repeat titres at 28 weeks

First pregnancy complicated by RhDalloimmunization

Anti D- low

Severe anemia –may not develop

In subsequent affected pregnancies, fetal anemia usually is

more severe and develops earlier in gestation.

Once detected how often should antibody levels be monitored during pregnancy?

Rh antibodies Positive

Titres <1:32

Titres > 1:32

Titres 4 weekly till 28 wks and 2 wkly

till term

Serial fetal MCA dopplers every 1-2

wks

Green-top Guideline No. 65

Should RhD-negative women who have anti-D or non-anti-D antibodies receive routine antenatal or postnatal prophylaxis?

• If immune anti-D is detected, prophylaxis is no longer necessary

Green-top Guideline No. 65

What ancillary tests should follow identification of maternal antibodies to diagnose HDN?

• Determination of paternal genotype

• Fetal genotype –cell free DNA testing

• Spectral analysis of amniotic fluid bilirubin levels (delta

OD)

• MCA Dopplers

• Cordocentesis

• Paternal zygosity testing

• Cell free DNA

• It is also reasonable to omit paternal testing and proceed directly to fetal genotyping to avoid issues of nonpaternity

Green-top Guideline No. 65

ACOG-practical bulletin

Cell free DNA testing

• Using polymerase chain reaction techniques, the fetal RHD status can be detected with great sensitivity using free fetal DNA (ffDNA) extracted from maternal plasma

• Genotyping can be undertaken from 16 weeks of gestation

• Accuracy-95-98%

UOG-2015,45;156-161 De Vore-late onset IUGR assessment

MCA Doppler

• Ultrasound monitoring should be performed by a professional with appropriate expertise to reliably perform MCA Doppler assessment (ISUOG guidelines)

• If the MCA PSV rises beyond the interventional threshold then referral to a fetal medicine specialist with expertise in IUT should be made.

• MCA PSV monitoring is predictive of moderate or severe fetal anaemia with 100% sensitivity and a false positive rate of 12

Green top guideline GTG65

MCA weekly

• MCA PSV monitoring is predictive of moderate or severe fetal anaemia with 100% sensitivity and a false positive rate of 12%. Dopplers most sensitive to pick up Fetal anemia

• Monitoring with MCA PSV should be used with caution after 36 weeks as its sensitivity for the detection of fetal anaemiadecreases.

• Further management should also be discussed with a fetal medicine specialist if MCA PSV levels are normal despite high or increasing antibody levels beyond 36 weeks of gestation.

• The risk of fetal loss following an FBS is 1–3%, but is higher if the fetus is hydropic.

Fetal assessment of hemolysis –invasive procedures

amniotic fluid bilirubin levels (delta OD

• amniocentesis-traditional method

• derives from fetal pulmonary and tracheal effluents and

correlates with the degree of fetal hemolysis

• Doppler velocimetry is as, or more, sensitive and specific

delta OD assay is no longer readily available at most laboratories

Fetal blood sampling

• Fetal blood can be sampled to precisely determine the

severity of fetal anemia, but this procedure carries a 1 to 2

percent risk of fetal loss, with the highest risk at lower

gestational ages and in hydropic fetuses

• We reserve fetal blood sampling for pregnancies in which

MCA-PSV suggests moderate to severe anemia

Case 1

• Mrs.SV,G2P1L1,Rhnegative mother , husband positive • Taken AntiD in I Pregnancy

• ICT at booking –positive • (3 cell panel )

• Anti D titres

• 1 in 16

Next step

• Serial antibodty titres from the same lab

• 28 weeks

• 1 in 32

Next step

• Should we give antidD?• How should we follow up?• MCA monitoring

MCA-monitoring

• MCA-PSV under normal limits

• Growth parameters and amniotic fluid normal.

What is the optimum mode, place and timing of birth?

depend on the

• Antibody levels/titres,

• Rate of rise

• Fetal therapy

mode, timing and place of delivery are otherwise dependent on standard obstetric groundsTertiaty care centre wuth blood bank facilities and close fetal monitoring during labor

Case 2

• Mrs CT

• 28 yrs

• 26 weeks booking , ICT positive

• Previous H/o postnatal transfusion of the baby

• MCA monitoring

• In 32

• 1 in 64

• MCA monitoring

Take home messages

• H.Rnegative mother –ICT 93 cell panel)in first visit and and28 weeks

• In case if negative , review at 28w, and antiD to be administered at 32 weeks

• Serial titres are to be from the same lab

• In case of rising titres if critical levels reached –MCA Doppler

• Amniocentesis for bilirubin obsolete in clinical practice

• Maternal titres are screening tets for severe anemia , not diagnostic , and can be discontinued once critical level is reaches

• Cell free DNA testing of fetal Rh typing not yet available in India

• MCA PSV monitoring is predictive of moderate or severe fetal anaemia with 100% sensitivity and a false positive rate of 12%.20CA-Dopplers most sensitive to pick up Fetal anemia

• . Monitoring with MCA PSV should be used with caution after 36 weeks as its sensitivity for the detection of fetal anaemia decreases.

• Cord blood sampling confirms the fetal anemia

• Preconceptional counseling in subsequent pregnanacies is essential

Green top guidelines s