Essay 280 - Rhesus disease

A healthy 29 year old woman in her third pregnancy is found to have raised anti-Rhesus D antibodies at 28 weeks gestation. (a) Evaluate the subsequent assessments that could be undertaken. [15 marks] (b) Discuss the antenatal management of fetal anaemia secondary to Rhesus disease at 28 weeks gestation. [5 marks]

Reveiw of her case notes should be done to look for previous pregnancies and their outcome like hydrops fetalis may indicates previous affected pregnancy.  check if she has received anti D in last 8 weeks  as passive anti D can be detected upto 8 weeks in maternal blood.    she should be asked whether  previous pregnancies were affected by rhesus alloimmunization .it helps in counselling the woman as severity of disease increases with parity.

referral to specialist fetal medicine unit for further assessments should be made .

serial anti D antibody titres by indirect Coombs test or quantification using auto analyser  every 2weeks should be done   .if levels are below 4 iu/ml , severe anemia of fetus is not expected. fetal anemia is rare below 10-15 iu/ml. Above 15 iu/ml there is high risk of fetal hydrops. 

Non red cell antibodies like anti Kell , Anti c and Anti E  are also checked to assess risk of hemolytic disease of fetus and newborn (HDFN) 

father blood group testing and  genotype testing should be done.if father is Rh positive , then genotyping to know homozygosity or heterozygocity should be done. homozygous status means  most babies are effected and at the risk of HDFN , while heterozygous means 50% babies are at the risk of HDFN.

fetal blood group testing by non invasive cell free fetal DNA found in maternal plasma is carried out .it is 96% sensitive test . repeat testing may be required if Rh negative as fetus will be only effected if Rh positive.

 invasive methods like amniocentesis can be carried out . it carries risk of further alloimmunization . 

fetal monitoring by middle cerebral artery peak systolic velocity MCA PSV for fetal anemia. if it is more than 1.5 multiple of median for specipic gestational age  indicates moderate to severe  fetal anemia . it has 100% sensitivety with 12% false +ve rate . it is carried out weekly for monitoring fetus at high risk of developing HDFN . 

ultrasound is undertaken to find hydrops fetalis that indicates poor prognosis. ultrasound will detect reduced fetal movements ,but severely anemic fetus may not develop hydrops and reduced fetal movements .

CTG is not good predictor of HDFN .sinosidal pattern is rare even in severe anemic fetuses .

amniotic fluid taken by amniocentesis ,is checked for bilirubin level and using spectral analysis at wave length 450nm , the amount of bilirubin is compared with uneffected pregnancies . liley 's graph is drawn for this purpose , if value reaches liley's zone 3 , fetal blood sampling is needed. amniocentesis is associated with fetal hemorrhage , infection  and preterm rupture of membranes . it may boost maternal antibodies.

fetal blood sampling if MCA PSV indicates anemia , is required.it is direct accurrate diagnosis of fetal anemia and acidosis . it carries risk of fetal loss 1-3% per procedure .blood is taken from either placental cord insertion site or intrahepatic vein.  

(b) Discuss the antenatal management of fetal anaemia secondary to Rhesus disease at 28 weeks gestation. [5 marks]

management involves  referral to fetal specialist medicine unit . weekly MCA PSV measurements to detect the severity of anemia. in cases of moderate to severe anemia or if hematocrit is below 30%  inutero fetal blood transfusion is carried out.   packed O  RH Negative cells compatiable with both mother and fetus are transfused . transfusion to supranormal levels of HB  provides longer intervals between transfusions ( 2-4wks ) . intravascular route is preferred , however it can be done by intraperitoneal route.

fetal loss rate per procedure is about 2-4% . plan for delivery at 34-36wks. 

other treatments like plasmaparesis and maternal immunoglobulin therapy have limited efficacy. 

I will take detailed history including previous baby delivered with RH disease &time passed since that pregnancy. Tha loger the duration the stronger the response with high quality & quantity of antibodies. I will chech the titre  ,fetal anemia is not expected if below 1: 64. Serial  estimation of antibodies level every 2 weeks using titre (ICT) or autoanalyser is recommended.severe fetal anemia is not expected if antiD <4iu/ml by autoanalyser & is rare if < 10-15 iu/ml.

There is possibility that the baby is RH –ve if father is heterozygous. PCR to test paternal zygozity is helpful as if father is homozygous the baby definitely RH+ &further management is planned. However this is not helpful if there is a problem with father identification. Fetal RH can be determined using non invasive cell free fetal DNA in maternal serum with accuracy of 96% .I will repeat test if baby RH –ve for assurance. Fetal RH can be determined by invasive testing chorionic villous sampling & amniocentesis but these carry risk of fetal loss , fetomaternal hemorrhage & further stimulation of antibodies production

Doppler study of middle cerebral artery is indicated to detect fetal anemia .It is non invasive & reliable technique. should be done every 2weeks.Fetal hydrops is late sign & associated with poor prognosis, moreover not all cases of severe fetal anemia presented by hydrops. Other ultrasound markers such as amniotic fluid volume , placental thickness fetal movements are not proven to be beneficial.

CTG for sinusoidal pattern is very rare & many cases of severe fetal affection don't show sinusoidal CTG, so it is not reliable for fetal assessment.

Amniocentesis and estimation of bilirubin level plotted over Liyles chart & fetal blood sampling once optical desity reaches zone 3.It is invasive monitoring &uses bilirubin as indirect method of fetal heamoglobin estimation with lack of data about its timing & frequency .It carries 1% risk of fetal loss over background per procedoure.

Cordocentesis allows direct estimation of fetal heamoglobin & heamatocrit, however it is invasive has 2% risk of fetal loss over background per procedure.

B) Antenatal management of fetal anemia 2ry to RH should be in tertiary centre (fetal medicine unit) with available expertise & facilities for fetal monitoring & blood trasfution. Multidisciplinary  team is needed (fetal medicine specialist, senior obstetrician, neonatologist,counseller)

I know that psychological support for the woman & her partner in needed to alleviate anxiety  associated with the condition & the need for sensitive approach.

Cordocentesis is indicated to estimate hematocrite which if < 30 fetal blood transfution is indicated by packed o-ve RBCs compatible with both fetus &mother. It carries fetal loss rate of 2-4% per procedure.It is repeated /2-4 weeks till 34 week where consideration of delivery at 36 weeks is considered safer than continuing transfution.

Maternal plasmapharesis &IV immunoglobulin injections to reduce antibodies are of limited efficacy. If fetal anemia is mild & the baby did not need intrauterine transfution plan delivery at 37-38week.   

a)     a.) Detailed obstetric history is taken regarding previous affected pregnancies.  Previous baby with hydrops , intrauterine transfusions, neonatal anaemia asked  as severity of disease increases with parity.  Number of living children, mode of delivery noted.

Ask with discretion of partner change as if father of this pregnancy is  rhesusD negative fetus will be D negative and not affected. If father is Rh positive, zygosity is determined . If father is homozygous ,fetus will be rh D positive and  at risk of haemolytic disease. If father is heterozygous , fetal rh status can be determined by free fetal DNA using maternal plasma.If negative repeat testing advised.

 Review level of antibody as passive anti D level <1mu/l can be due to recent RAADP routine anti d prophylaxis detected upto 8 weeks. Ask for recent blood transfusion, sensitising events. Anti D level < 4 Mu/L not associated with severe fetal haemolytic disease and repeat test in two weeks.  Level  4 – 15 mu/L associated with moderate anaemia and > 15 mu/L with severe anemia.

 Further assessment done by  middle cerebral artery MCA-PSV Doppler study in liason with Fetal medicine centre. Doppler of peak systolic velocity measurement of middle cerebral artery is best non invasive method  to assess fetal anemia. Repeat Doppler done once on 1-2 weeks as per unit protocol and findings.

USG evidence of hydrops  pleural effusions, fetal ascites would need urgent referral and assessment in fetal medicine centre.

CTG is not sensitive for monitoring, sinusoidal pattern due to severe anemia is late finding.

Multidisciplinary team (MDT) comprising consultant obstetrician, senior midwife, neonatologist, fetal medicine specialist should assess fetus at risk of anemia and further management.

Invasive test like amniocentesis for spectrophotometric analysis of amniotic fluid for bilirubin levels is an indirect measure of Hb and not done routinely nowadays. Liley graph plotted and zone 3 would indicate severe anaemia.

MCA-PSV> 1.5MOM would require urgent referral to fetal medicine unit for intra uterine transfusion (IUT).

Fetal blood sampling using cordocentesis for HB levels carries fetal loss rate of 2-4%

b) Fetal anaemia need management in fetal medicine unit by MDT comprising senior obstetrician, fetal medicine specialist, neonatologist.  The woman and her partner are counselled about the procedure of codocentesis, need for repeated intrauterine transfusions and need for early delivery. Fetal loss rate of 2-4%, higher if hydrops is explained.

Cordocentesis done , Hb hematocrit, bilirubin, blood group type done. If hematocrit < 30 IUT done . O negative blood cross matched with mother and fetal blod transfused. Aim to achieve supranormal Hb levels so frequency of IUT is 2-4 weeks.  Monitor with weekly MCA-PSV.

Antenatal steroids offered as risk of preterm delivery .,Couseling by neonatologist done. Individualise plan for labour depending on fetal anemia, development of hydrops. Deliver by 37 weeks .

Aim for vaginal delivery , caesarean for obstetric indications. In case multiple transfusions , doppler changes plan to deliver after 34 weeks by caesarean after senior review.

Provide written information

A)

History of the previous pregnancy should be taken to now if there is complication due to rhesus incompatibility, like hydrops fetalis, still birth  or IUFD. Revise The record of the current pregnancy asking about the father is he  the father previous pregnancy which mean that sensitization may happened in previous pregnancy and could affect this fetus. Asking about ante partum haemorrhage and if anti D was taken or not. Revising US scan report to see if IUGR or hydrops have occurred or not. Inquire about the fetal movement which can indicate fetal viability. Examine the  mother to see the fundal hight and symphsio fundal measurement to see if there is polyhydramnios or IUGR. Fetal heart sound by Doppler checked to exclude IUFD.  Blood group and RH  of the mother and father should be done if not already known. If father is RH positive heterogenicity must be known. Anti bodies repeated two weeks later to know if there is increase or not. Investigation to know the fetal well being, either non invasive like US scan to see if hydrops fetalis develop. Middle cerebral artery peak velocity (MCA PV) to know if anaemia develop but it depend on examiner and the machine although it have high sensitivity.  biophysical profile is important  to know the well being. Invasive procedures like amniocentesis to do optical density 450 (OD450) against lilys chart. and bilurubin measure, but it carries risk of miscarriage 1-2 %. Fetal blood sampling by cordocentesis to check for HB if babies is anaemic or not, also blood group can be known, but it have a risk of still birth and miscarriage. Free DNA  to know the blood group is a sensitive test.

B)

the aim of ante natal management is to know the severity of the disease so regular monitoring by weekly biophysical profile will reflect fetal condition, weekly MCA PV to know anemia, amniocentesis repeated for billrubin measure and OD450 . regular cordocentesis for blood sampling, growth scan every two weeks to monitor the growth. CTG could reflect the acute fetal compromise and may be helpful. Treatment depend on the gestational age, severity of the condition, and facilities available so treatment should be done in tertiary fetal unit. If gestational age less than 32 weeks corticosteroid 2 doses given. if severe anaemia intra uterine blood transfusion given, it need fetal unit and experience person and it carries the risk of preterm labour, PPROM. If gestational age near term after 32 weeks, deliver the baby and transfuse outside but also it depend on neonatal facilities. If condition of the fetus is stable and all investigation are normal delivery after 34 week. Psychological support to parent is very important throughout and information must be given backed with leaflet informaions       

Consultant obstetrician with a special interest in Rh negative/immunised pregnancies should be involved in the management of the case.The management would depend on whether this is the first affected pregnancy or not.

A detailed history must be sought such as the outcomes of the previous two pregnancies,history of any hydrops,need of in-utero blood transfusions,gestational age at which transfusions were needed,neonatal exchange transfusions,prolonged jaundice,etc should be asked.Present antenatal history in terms of booking antibody status,history of any vaginal bleeding,need of Anti D antenatally,h/o any invasive procedures,h/o trauma,etc should be asked.History of whether paternal zygosity has been performed should be noted.

If this is the first  pregnancy with anti-D positive status,in addition to the routine investigations done at 28 weeks,the antibody titres/quantification should be measured.If the levels are >10-15 IU/l,a referral to the Fetal Medicine unit should be sought.If the levels are <10-15 Iu/L,serial monitoring of these values(1-2 weekly) may be done to check if the critical values are reached.

If this is not the first affected pregnancy,a Fetal Medicine referral should be considered for monitoring of the MCA-PSV values every 1-2 weeklyand to look out for signs of fetal anemia.

After referral to the Fetal Medicine Unit,if the MCA levels reach >1.5 Moms ,significant fetal anaemia (false positive rate of 12%) should be considered and the parents counselled regarding the need of in-utero blood transfusion versus preterm delivery requiring neonatal transfusions.The parents should be counselled that the fetuses tolerate the transfusions better than the neonates.The risks of preterm delivery,PPROM,infections  and fetal loss(2-4%) should be explained.The rh sensitised pregnancy may be continued with Intrauterine transfusions till 35-36 weeks after which delivery could be considered.The mode of delivery would depend on other obstetric indications.

b)The parents should be sensitively counselled regarding the development of fetal anaemia by the Fetal Medicine Specialist and the consultant obstetrician.

The ultrasound should specifiaclly look out for the signs of fetal anaemia such as ascitis,subcutaneous edema,pleural/pericardial effusion.The parents must be explained about the need for in-utero  blood transfusion.Blood transfusion  of O rh negative gamma irradiated,leucocyte poor blood would be given,usually intravascularly by cordocentesis or intrahepatic or if inaccesible,peritoneally.After explaiining the risks of preterm delivery,PPROM,infections  and fetal loss(2-4%),If the parents consent,O negative blood (calculated volume) to raise the fetal hematocrit to 40%(non hydropic),25%(if hydropic) should be considered.Post transfusion Hb noted.The need for second transfusion will depend on MCA -PSv levels.If the pregnancy reaches 35-36 weeks and transfusions are still considered risks of a fetal loos vs preterm delivery should be considered.

At delivery,the consultant neonatologist should be informed.

A detailed obstetric history must be asked from the woman to know if she was sensitised and was there any fetal hydrops .Any h/o intrauterine transfusions should be asked to know the severity of affection and the fetal outcome must be noted.Any sensitising event in the current pregnancy like chorion villus sampling ,amniocentesis,trauma causing fetomaternal bleed must be asked.It should be asked in a very sensitive manner if the current pregnancy was with a new partner as that may influence the outcome by a change in fetal blood group.The womans antibody titre must be looked into as the critical titre to cause haemolytic disease of newborn is taken as 1:32. Quantification of the actual antibody levels by an autoanalyser is more accurate than this and 1:32 corresponds to a value of 4iu/ml. this causes mild haemolytic disease,4-15iu/ml moderate disease and a value >15iu/ml causes severe affection. If the woman had got anti D recently as per the RAADP ,it can result in low antibody titres of 1iu/ml not significant to affect the fetus.
        The fetus will be affected only if it is rhesus positive. By checking the paternal blood If the father is homozygous positive the fetus will be rh positive,while if he is heterozygous the fetus may or may not be rh positive.Another  way to know the fetal group is to extract the cell free fetal DNA from mothers blood and doing PCR. If fetus is rhesus positive,next step is to find out if it is affected or not.Middle cerebral artery Doppler is a non invasive method for this and is to be done by a fetalmedicine trained sonologist.A peak systolic velocity of >1.5 mom is suggestive of fetal anemia.This increase in velocity  is due to a low viscosity of blood in anemia and a cerebral response to hypoxemia.Invasive method namely Amniocentesis,spectrophotometry plotting the change in optical density caused by bilirubin on Lileys graphs no longer recommended.If in zone 3 again needs a fetal blood sampling. Cordocentesis to check fetal blood group,bilirubin.direct coombs test for antibody level is again invasive.Both procedures have a 1-2% risk of pregnancy loss above the background risk. Sluggish movements on Ultrasound is a late sign of hydrops and treatment  should not wait till this.Also a sinusoidal pattern on CTG is a sign of severe anemia not to be waited for.Serial monitoring with MCA Doppler to be done weekly at a fetal medicine centre to detect any affection at the earliest.
              Antenatal care must be multidisciplinary involving fetal medicine specialist,consultant obstetrician,neonatologist and trained midwife at a tertiary centre.Steroids for fetal lung maturity to be given as  baby may need to be delivered preterm .If MCA Doppler suggests fetal anemia, cordocentesis to be done ,checking the fetal haemoglobin,haematocrit.Also in the same sample blood group,bilirubin and direct coombs test for antibodies can be done.If hematocrit <30% an intrauterine transfusion is to be given using O neg packed cells compatible with mother and fetus.Aim is to achieve supranormal hematocrit(2_3 times normal)so that transfusions can be spaced 2 to 3 weekly .A procedure related pregnancy loss of 2 to 4% over the background risk has to be explained.Serial ultrasound for growth,polyhydramnios and hydropic features to be done, though unlikely in treated foetuses.If need for repeated transfusions, delivery to be considered  at 34 weeks,otherwise in milder cases corrected with one or two transfusions,safe to deliver at 37 weeks to avoid prematurity.Caesarean section is reserved for obstetric indications only decided by a consultant.Couple to be provided information leaflets to support the counselling.

A)

Recognize that a history of previous pregnancy outcomes is a poor predictor for gestation of onset and severity of rhesus disease in the index pregnancy. Maternal serum for fetal blood grouping (using free fetal DNA) should be done if available. If the fetus is Rhesus negative the fetus is not at risk for rhesus disease. If Rhesus positive the fetus is at risk for Rhesus disease. Maternal serum anti-D antibodies should be measured by IDCT or an auto-analyser serially(every 2-4weeks) as the risk of fetal anaemia is minimal at values less than 1:64.Peak systolic velocimetry using doppler scans of the fetal middle cerebral artery is a non-invasive screening tool for fetal anaemia. Consider its use if maternal anti-D levels are above 1:64. If  elevated referral should be to a fetal medicine center for cordocenthesis. Cordocenthtesis allows direct measurement of fetal Haemoglobin concentration, blood group and bilirubin levels. It also allows for fetal karyotyping with parental consent. Cordocenthesis enables fetal blood transfusion if the fetal haematocrit is <30%. Cordocenthesis has a fetal loss of 1-2% and risks increased maternal antibody production with significant feto-maternal haemorrhage. Amniocenthesis with spectrophotometry of liquor for optical density is an indirect invasive measure of fetal haemoglobin with a 1% risk of fetal loss and is not recommended. Ultrasound scanning for fetal hydrops is a late inconsistent sign and is not recommended. Ultrasound scanning for liver length and dilated fetal veins is a poor predictor of fetal anaemia and is not recommended. Monitoring of Biophysical profile, fetal movements and CTG’s are poor indicators of fetal anaemia and are not recommended.

B)

Refer to a fetal medicine center for urgent review. Administer steroids to accelerate fetal lung maturity. Cordocenthesis should be done by a fetomedicine specialist to determine the fetal haemoglobin concentration, haematocrit and bilirubin levels. If the haematocrit is <30% a fetal blood transfusion should be done with O negative blood cross mathched to both the fetal and maternal serum. Transfusion maybe trans-peritoneal or intra-vascular. Transfuse to supra-normal levels to maximize transfusion intervals. Counsel the mother that fetal transfusion has fetal loss rate is 2-4% and that the procedure may have to be done again if fetal anaemia re-occurs. Timing of delivery should be individualized. If fetal transfusion is required recommend delivery at 34 weeks. Consider delivery at 36-37 weeks with transfusion at 34 weeks in some cases. If transfusion not needed, recommend delivery at 37-38 weeks to avoid fetal respiratory morbidity.

Ans. I will review her notes , for antibody  screen at booking visit . I will check results of serial antibody  titer if done so far.  Negative results earlier in pregnancy point towards recent sensitization. I will ask for  history of any sensitizing event , like vaginal bleeding, abdominal trauma, invasive procedure ,like amniocnentesis and chorionic villous sampling. Any of these, or if she has received anti Rh immunoglobulin  (Ig) for any event  recently,  can lead to raised antibody titer though level will be different depending on degree of exposure. I will ask about previous pregnancies, and any adverse outcome,like severe fetal anemia, hydrops, fetal death or hemolytic disease of newborn. Risk of alloimmunization and its consequences increases with parity. I will ask her, if  she received adequate routine anti Rh D prophylaxis(RAADP) during previous pregnancies and deliveries, as it  decreases risks in subsequent  pregnancy). She will be sensitively asked about change of partner.  Abdominal  examination may reveal excessive liquor in case of a hydropic fetus. Test of paternal zygosity( by PCR  on blood) is done  to assess  susceptibility of fetus. If father is homozygous for Rh D antigen, baby will be Rh positive and at risk of hemolysis. If heterozygous, fetal blood group can be checked by cell free fetal DNA (cff DNA) from maternal plasma, or by amniocentesis and PCR. Amniocentesis is invasive, and further increases the risk of fetomaternal haemorrhage(FMH). cff DNA is non invasive with 96.5% sensitivity. If negative, repeat testing will be done( more than 3 % risk of missing out Rh positive baby).  Maternal  antibody titer correlates with degree of hemolysis . Severe anemia is not expected with antibody level below 4 iuand it is rare below 10-15 iu. Doppler studies of peak systolic velocity of middle cerebral artery(MCA-(PSV)) is a noninvasive method , with 100 sensitivity  and 12 % false positive rate for detection of fetal anemia and is now preferred modality if expertise available. Ultrasound detection of reduced fetal movements and hydrops on ultrasound scan are late manifestations and a significant number of severely anaemic fetuses have normal movements and no detectable hydrops . Other markers such as amniotic fluid volume, placental thickness, umbilical vein diameter and liver length have not been shown to be useful. CTG is not of much value in assessment of anemia - sinusoidal pattern is rare, even in severe fetal anaemia.

b) Antenatal management of fetal anemia should be done in a tertiary centre in liason with fetal medicine center  and the method used should reflect the facilities available and expertise .Multidicsiplinary team should comprise of consultant obsterician , fetal medicine speciaist, and specialist midwife.Couple will be counseled about the procedures and risks involved and informed consent will be  taken. Maternal antibody titer will be checked two weekly.  Doppler studies should be done weekly. Antibody titer more than 15 iu, or PSV of MCA more than 1.5 Multiples of median for given gestation, is thresh hold for moderate to severe  anemia, and fetal blood sampling and transfusion. Amniocentesis and spectophotometry to estimate bilirubin levels (OD450) can be plotted on Liley’s chart, with fetal blood sampling once zone 3 is reached. Cordocentesis  for FBS, has a fetal loss rate of 1-2% per procedure. Both procedures carry a risk of FMH  and increased maternal antibody levels.  Intrauterine blood transfusion  is done when haematocrit is below 30%, using packed O Rh negative red cells compatible with both the mother and fetus.  Transfusion will be done  to supranormal Hb concentration, with longer interval between transfusions (2-4 weeks). It carries risk of infection, haemorrhage, fetal bradycardia, cord haematoma, tamponade; and fetal death .Procedure-related fetal loss rate is 2-4%. Intra-vascular route is preferred   to  intra-peritoneal route.  Delivery after 34 weeks gestation may be considered safer than continued intra-uterine transfusion.  Other treatments such as plasmapheresis and maternal intravenous immune globulin have limited efficacy. Last intravascular transfusion at 34 weeks (unless difficult or dangerous) with delivery at 37 weeks can be considered.  

A] Take  detail history of previous pregnancies and there fetal out come whether  they recieved intra uterine transfusion , any still birth or neonatal death due to severe jaundice. ask the women  whether she  had taken anti d prophylaxis before and following any sensitising event or after child birth . ask if having recieved any  recent dose of anti d prophylaxis as the antibodies titre tend to raise up to 8 weeks . ask the women if any recent  history of  abdominal trauma, vaginal bleeding  that could have resulted in FMH and raise in antibody titre .  counsel the women that the severity of the disease raises  with increasing parity . Refer the patient to fetal medicine unit  where there are facilities to manage rhesus iso immunisation . screen the partners blood group and genotype . if he is homozygous almost all the fetus are affected . if he is heterozygous then 50% of the fetus will be affected .review her  antenatal notes to detect the booking antibody level and the  recent antibody level by indirect coombs test . if the level was below 4 IU then there is no fear of the fetus being  affected .monitor the fetus by  checking the antibody level every 2 weeks ,if more than 10-15 IU there is risk of the fetus being  affected .do invasive and non invasive method of fetal monitoring  .if the antibody titre is raised , early intervension and prompt treatment can be given .non invasive method such as CFFDNA  for fetal blood group and RH status in maternal blood is done . it has a high sensitivity  . if the fetus is rh negative then repeat it  after confirmation reassure the patient  .  Invasive method of fetal monitoring such as amniocentesis is done .  fetal blood group and rh status is done check antibody level if >10 -15 iu   then do sphectrometry OD 450  to estimate bilirubin level in fetus and plot on lilleys chart . this is indirect method of estimating  fetal HB level after  28 weeks of gestation . level 3 indicates severe anemia . amniocentesis is associated with 1% risk of miscarriage and allo immunisation .then do fetal blood sampling for haemoglobulin level, haematocrit level ,reticulocyte count .if haematocrit level is <30% the fetus  is having anemia and needs intrauterine transfusion  .Usg is done to see for the signs of hydrops and this is repeated every 2  weeks . doppler studies is done to assess the amount of blood flow in the middle cerebral artery increased flow suggest fetal anemia . and the peak systolic velocity is measured if it is > 1.5 mom then the fetus is anemic . CTG is done ,sinusoidal pattern and decceleration suggest fetus at risk of anemia .but it has   poor predictor  value .

B] The fetus is monitored in fetal medicine centre where there are facilities for fetal monitoring ,scbu  and intrauterine transfusion  . MDT approach involving neonatologist and sonologist  is needed .the fetus is treated with USG guided intrauterine transfusion . transfusion is done  intraperitonially or via the umbilical vein  .  O negative packed red  cells cross matched against maternal blood  is used .intrauterine transfusion is done up to super normal level to increase the interval of transfusion for 2-4 weeks . until the haematocrit level is 40-45% .the procedure related fetal death is 2-4 % . the baby is delivered by 34 weeks and  corticosteroide is given for lung maturity .this is to prevent reccurent intrauterine transfusion  in case of severe anemia and the risk associated with it .if transfusion is needed it can be given extrauterine .the fetus is monitored  weekly by middle cerebelar artery dopler . the need of plasmapheresis and intravenous immunoglobulin is not benefitted .in case of mild anemia pregnancy can be prolonged up to 37-38 weeks by regular monitoring .