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MRCOG PART 2 SBAs and EMQs

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ESSAY 254 - Rhesus disease

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		Posted by S M. Wed Jan 16, 2008 08:19 am
Rh isoimmunisation occours when an Rh negative female carries an Rh positive baby. The implementation of National Guidelines for Anti D immunisation introduced in 1969 (and further modified in 1991) have resulted in a massive reduction in perinatal mortality from 46/100000 to 16/100000. The following suggestions made in this guideline have helped to reduce perinatal mortality: firstly recognising women who are Rh negative and a having a detailed discussion with them about the risk of Rh isoimmunisation during sensitizing events in pregnancy and childbirth and its implications to subsequent Rh positive foetuses. Secondly giving routine antenatal anti D (500 IU) to all Rh negative women at 28 and 34 weeks of gestation irrespective of the fact that they might have had anti D for some sensitizing events in pregnancy. Thirdly all women who have had sensitizing events such as PV bleeding after 12 weeks of gestation, amniocentesis, abdominal trauma or ECV need to receive Anti D and also have a Kliehauer test for the amount of fetomaternal haemorrhage. A dose of 250 IU needs to be given for a sensitizing event occurring before 20 weeks and a dose of 500IU needs to be given for and sensitizing event after 20 weeks. Fourthly all women must be given 1500IU of Anti D injection soon after the birth of baby and at the same time they should have anticoagulated bloods taken for Kliehauer test to measure the fetomaternal bleed. Additional Anti D should be given if required. The above information should be given to the mother in verbal and written format to ensure better understanding. Inspite of the above guidelines being in place, there still are cases of perinatal morbidity due to Rh isoimmunisation. The reasons are firstly the national guidelines are not followed strictly. Secondly there might be unrecognized sensitizing events during pregnancy. Thirdly the fetomaternal haemorrhage postnatally might be underestimated. Fourthly there might be delayed administration of anti D during pregnancy. Moreover sensitization might take place in subsequent pregnancies and also by events outside of pregnancy like blood transfusion. Further reduction of Rh isoimmunisation is only possible if the Rh negative women and the medical staff looking after her are educated and made aware of implications of Rh isoimmunization and ways to prevent it. The national guidelines need to be followed judiciously. All women need to be given routine antenatal anti D at 28 and 34 weeks and also postnatally. All Rh negative women should receive anti D after sensitizing events. Kliehauer test needs to be performed after sensitizing events to ensure that there wasn?t severe fetomaternal haemorrhage.
		Posted by Srivas P. Wed Jan 16, 2008 08:32 pm
(a) Evaluate the factors that have resulted in this fall in perinatal mortality [9 marks]. Deaths due to RhD alloimmunizations have fallen from 46/100000births in 1969 to 1.6/100000 births in 1990 and have sustained at this level primarily due to Anti D immuno prophylaxis. Use of Kleihauer tests to administer higher doses depending on quantitative levels of RhD antigen in mother has decreased isoimmunizations as the test helps identify FMH more than 4 ml. This is because Standard 500 I.U Anti D Ig takes care of 4 ml of FMH only. Flow cytometry and Rosetting methods have made quantification of Anti D titres in maternal blood more accurate helping giving higher doses of Anti D Ig. Recent Nice guideline advocating routine antenatal anti-D prophylaxis at 28 and 34 weeks have decreased PNM even further as it was found that 18-27% isoimmunizations occurred in late pregnancy. Giving prophylactic Anti D after every sensitizing event in pregnancy like ECV, IUD, APH,abdominal trauma, MRP, CVS or amniocentesis have also decreased RhD isoimmunisation Multidisciplinary care, referral of RhD isoimmunisation cases to dedicated fetal medicine units have improved care. Intra uterine felal transfusions to affected fetuses-both the earlier used intra peritoneal and the intravascular blood transfusions improved their survival overall to 84%(70 % of hydropic fetuses and 92 % of non-hydropic fetuses.) Planned deliveries including premature induction of severely affected baby, antenatal corticosteroids have diminished PNM. Smaller size of present families have decreased incidence of severe cases of Rh immunization as the severity of fetal affection increases with higher pregnancies with the same partner. (b) Evaluate the factors that contribute to persistent perinatal mortality and morbidity from Rhesus iso-immunisation [6 marks]. Persistent increased PNM may be because guidelines have not been applied due to failure in to impress upon patient the importance of getting RAADP, Post partum prophylaxis, thereby decreasing patient compliance. Administrative failure may also contribute in either missing Anti D dose or delay in receiving antiD, diminishing effectivity. Not doing Kleihauer tests and giving correct dose of anti D too is a cause for failure to prevent isoimmunization and decrease PNM. But some 0.1-0.2% spontaneous immunization occurs despite prophylaxis. Alloimmunization involving atypical blood groups like Kell and c blood groups, anti Duffy, anti Kidd is not yet preventable as there are no effective immunizations against these antigens. Anti kell antibodies do not affect Amniotic fluid bilirubin levels and hence amniocentesis and OD450 measurements miss the diagnosis. Monitoring requires looking for fetal anemia by MCA Doppler study or FBS to detect profound fetal anemia. Invasive methods like amniocentesis, fetal blood sampling, and intra uterine transfusions increase PNM by causing PROM, prematurity, fetal injury and fetal death and as yet there is no substitute to IUT to improve fetal anemia. PNM due to Kell antibodies can be decreased by giving Kell negative blood to all woman of reproductive age. Genotyping of fetus can now be done non-invasively by using maternal blood to detect DNA by using PCR. The invasive procedures live CVS, amniocentesis or FBS which are associated with inherent risk of miscarriage of 0.5 %,1% and 3 % respectively can be avoided. Serial amniocentesis to assess progression of fetal anemia is not necessary and fetal anemia can be assessed non-invasively by monitoring Doppler systolic peak flow in middle cerebral artery which increases in fetal anemia and restricting amniocentesis to times when intra uterine transfusion is planned. Strict implementation of routine antenatal AntiD prophylaxis will further decrease PNM.Patient education, leaflets and counselling can ensure cooperation and greater compliance with receiving treatment.
		Posted by Srivas P. Wed Jan 16, 2008 08:36 pm
Dr Paul I am sorry I had to post the essay again as the section c)was not marked in earlier posting. a) Evaluate the factors that have resulted in this fall in perinatal mortality [9 marks]. Deaths due to RhD alloimmunizations have fallen from 46/100000births in 1969 to 1.6/100000 births in 1990 and have sustained at this level primarily due to Anti D immuno prophylaxis. Use of Kleihauer tests to administer higher doses depending on quantitative levels of RhD antigen in mother has decreased isoimmunizations as the test helps identify FMH more than 4 ml. This is because Standard 500 I.U Anti D Ig takes care of 4 ml of FMH only. Flow cytometry and Rosetting methods have made quantification of Anti D titres in maternal blood more accurate helping giving higher doses of Anti D Ig. Recent Nice guideline advocating routine antenatal anti-D prophylaxis at 28 and 34 weeks have decreased PNM even further as it was found that 18-27% isoimmunizations occurred in late pregnancy. Giving prophylactic Anti D after every sensitizing event in pregnancy like ECV, IUD, APH,abdominal trauma, MRP, CVS or amniocentesis have also decreased RhD isoimmunisation Multidisciplinary care, referral of RhD isoimmunisation cases to dedicated fetal medicine units have improved care. Intra uterine felal transfusions to affected fetuses-both the earlier used intra peritoneal and the intravascular blood transfusions improved their survival overall to 84%(70 % of hydropic fetuses and 92 % of non-hydropic fetuses.) Planned deliveries including premature induction of severely affected baby, antenatal corticosteroids have diminished PNM. Smaller size of present families have decreased incidence of severe cases of Rh immunization as the severity of fetal affection increases with higher pregnancies with the same partner. (b) Evaluate the factors that contribute to persistent perinatal mortality and morbidity from Rhesus iso-immunisation [6 marks]. Persistent increased PNM may be because guidelines have not been applied due to failure in to impress upon patient the importance of getting RAADP, Post partum prophylaxis, thereby decreasing patient compliance. Administrative failure may also contribute in either missing Anti D dose or delay in receiving antiD, diminishing effectivity. Not doing Kleihauer tests and giving correct dose of anti D too is a cause for failure to prevent isoimmunization and decrease PNM. But some 0.1-0.2% spontaneous immunization occurs despite prophylaxis. Alloimmunization involving atypical blood groups like Kell and c blood groups, anti Duffy, anti Kidd is not yet preventable as there are no effective immunizations against these antigens. Anti kell antibodies do not affect Amniotic fluid bilirubin levels and hence amniocentesis and OD450 measurements miss the diagnosis. Monitoring requires looking for fetal anemia by MCA Doppler study or FBS to detect profound fetal anemia. Invasive methods like amniocentesis, fetal blood sampling, and intra uterine transfusions increase PNM by causing PROM, prematurity, fetal injury and fetal death and as yet there is no substitute to IUT to improve fetal anemia. (c ) How can perinatal mortality and morbidity from Rhesus iso-immunisation be further reduced? [5 marks]. PNM due to Kell antibodies can be decreased by giving Kell negative blood to all woman of reproductive age. Genotyping of fetus can now be done non-invasively by using maternal blood to detect DNA by using PCR. The invasive procedures live CVS, amniocentesis or FBS which are associated with inherent risk of miscarriage of 0.5 %,1% and 3 % respectively can be avoided. Serial amniocentesis to assess progression of fetal anemia is not necessary and fetal anemia can be assessed non-invasively by monitoring Doppler systolic peak flow in middle cerebral artery which increases in fetal anemia and restricting amniocentesis to times when intra uterine transfusion is planned. Strict implementation of routine antenatal AntiD prophylaxis will further decrease PNM.Patient education, leaflets and counselling can ensure cooperation and greater compliance with receiving treatment.
		Posted by S D. Wed Jan 16, 2008 10:55 pm
a) The implementation of national guidelines in 1969 with further modification in 1991 has reduced the perinatal mortality from 46/100000 to 1.6/100000. Staff awareness and patient education are very important factors in the increased uptake of immunoprophylaxis. Routine antenatal anti-D prophylaxis at 28 and 34 wks should be given to all non sensitised Rh-D negative women. For potentially sensitising events such as APH, ECV, closed abdominal trauma anti-D should be administered followed by kleihauer testing to detect large feto-maternal haemorrhage. The administration of post-natal immunoprophylaxis irrespective of routine antenatal anti-D prophylaxis and antenatal anti-D for sensitising events has further reduced the perinatal mortality. The administration of 250 iu for miscarriages after 12 wks but before 20 wks and 500 iu after 20 wks with kleihauer testing has reduced the incidence of sensitisation in early pregnancies. b) Silent sensitisation during pregnancy is sometimes difficult to recognise and predict which can potentially affect the fetus. The national guidelines are also not strictly followed and every hospital should develop their own protocol based on national guidelines. Staff unawareness as to the administration of anti-D after sensitising events is one factor. It is important to do kleihauer testing after sensitising events and postnatally to detect large FMH and give appropriate doses of anti-D. Sometimes refusal from patients inspite of counselling about the benefits of anti-D is an additional factor. c) High quality information should be given to women about the benefits of anti-D and should be encouraged to have anti-D. Staff education and awareness as to the indications of anti-D should be known. Atleast 500 iu of anti-D should be given at 28 and 34 wks with further 500 iu after any sensitising event during pregnancy in Rh-negative unsensitised women. Immunoprophylaxis must be given postnatally irrespective of anti-D administration antenatally. Therapeutic termination of pregnancy whether medical or surgical should have anti-D irrespective of gestational age.
		Posted by Azza S. Thu Jan 17, 2008 08:11 am
a-The introduction of anti-D immunoglobin injection post-partum for Rhesus negative women if their new born is Rhesus positive, dramatically reduced the incidence of prenatal morbidity and mortality from Rhesus iso-immunisation .Few cases continued to occur and that lead to the introduction of antenatal injections in the third trimester as it the time of most increased risk during pregnancy of feto- maternal haemorrhage, this reduced the risk even more. Some social factors played a role as well. These include small families, Rhesus iso- immunization usually escape the first pregnancy and may affects the following pregnancies. There is very small risk of iso immunization in first and second trimesters. Pregnant lady may sustain trauma or other sensitizing event and not reporting it. There are different polices regarding doses and to test or not for amount of fetal cells in maternal circulation , so there is always risk of not enough anti-D . Non stable relationships may lead to a desire to have a new pregnancy with the new partner and so more risk. The reduction in cases lead to less experience in dealing with iso- immunization. Post- Partum and during sensitizing events a specific test for fetal red cells quantity, so to calculate the right dose to the mother. Educate and advice women to report any sensitizing event.
		Posted by Sahathevan S. Thu Jan 17, 2008 08:55 am
(a) Evaluate the factors that have resulted in this fall in perinatal mortality [9 marks]. Administration of Anti D immunoglobulin to the mother prevents the initial response that cause Rh immunisation in 97 % of cases.Number of factors influence in falling perinatal mortality and morbidity from Rh iso-immunisaion. Small family size is one of the reasons which. Is reducing the potential sensitising events. Much improved antenatal surveillance and facilities available for intrauterine transfusion of the affected fetus reduce the perinatal mortality and morbidity. Also early planned Delivery (by 34-36 wks) gestation of affected fetus with steroid cover reduce mortality. Advanced neonatal intensive care which includes photo therapy, exchange transfusion significantly reduces the perinatal mortality and morbidity. (b) Evaluate the factors that contribute to persistent perinatal mortality and morbidity from Rhesus iso-immunisation [6 marks]. Failures of the prophylactic programme may be due to errors in its conduct, either due to misidentification of blood samples, laboratory error or failure of Acton by clinical staff. Episodes of omitted or failed prophylaxis and silent feto maternal haemorrhage are the major reasons for persistent incidence. Also 3% percent of erythroblastosis is caused by immunization against other fetal antigenic groups such as C, c, E, e, K.k and M which is not preventable. Patient may have developed antibodies as result of unrecognised mismatched blood transfusion which can cause Rhesus iso-immunisation. Also Women may have declined to receive anti-D prophylaxis have the risk of Rhesus iso-immunisation. (c ) How can perinatal mortality and morbidity from Rhesus iso-immunisation be further reduced? [5 marks]. Antenatal prophylaxis should be given to all rhesus negative women who do not already have antiD antibodies. Additional anti D should be administered after any potentially sensitising episodes such as Termination of pregnancy , CVS ,amniocentesis ECV, abdominal trauma and uterine bleeding. After any potential sensitising events a kleihauer test should be perfomed to identify feto maternal haemorrhage of grater than 4ml, when additional ant D prophylaxis should be given. Use of appropriate dose of anti D titrated by kleihauer test, 25IU before 20 weeks and 500IU after 20 weeks gestation. Anti D should be given as soon as possible after the sensitising events but always within 72 hours, every effort should still be made to administer Anti D Ig as dose given within 9- 10 days may provide some protection.
		Posted by Reiaz M. Thu Jan 17, 2008 03:21 pm
a) Prevention of isoimmunisation by use of anti-D Immunoglobulin has had a major impact on the perinatal mortality from Rhesus isoimmunisation.After the introduction of anti D Ig in 1969 there was a decrease in the perinatal mortality from rhesus isoimmunisation from 46/100000 to 1.6/100000. Optimal dosage of anti D Ig has been enhanced by tests for fetal maternal hemorrhage such as flow cytometry. Routine antenatal prophylaxis given at 28 and 34 weeks gestation has also decreased the incidence of rhesus isoimmunisation. Development of and adherence of protocols for the indications and dosage of anti D Ig has also played a role in the development of the disease. Early detection of isoimmunisation and interventions to decrease the effects have resulted in a decrease in perinatal mortality. Ultrasound scan is able to detect fetal hydrops. Middle cerebral artery doppler of the fetus is a sensitive test for fetal anemia and does not carry the risks of miscarriage and choriomanionitis inherent to amniocentesis. Development of treatment options for the anemic fetus has also resulted in a decreased perinatal mortality. In utero blood transfusion can be used. Use of corticosteroids decreases perinatal mortality in infants delivered prematurely by a reduction in the risk of respiratory distress syndrome, intraventricular hemorrhage and necrotising enterocolitis. advances in neonatal care have undoubtedly reduced the perinatal mortality rate in these infants. Use of surfactant, blood transfusion and intensive care support have all played a malor role. b) Lack of adherence to guidelines for administration of anti d IG remains a major cause for persistent perinatal morbididty and mortality in Rhesus isoimmunisation. Failure to administer anti D Ig when indicated and administration of suboptimal doses can result in rhesus isoimmunisation. Anti D Ig is a blood product and may be refused by some individuals. Failure to prescribe anti D Ig antenatally will fail to porevent the 18-27% of cases that occur antenatally without any identifiable event. In certain areas availability of anti D Ig and the associated costs may preclude its widespread implementation. c) Patients should be counseled on possible sensitising events and advised to seek medical care so that anti D Ig can be administered within 72 hours. Widespread use of Routine antenatal anti D prophylaxis should be implemented. Use of audit to ensure adherence to guidelines should be done. Further studies should be conducted on the causes of failure to prevent isoimmunisation.
		Posted by hoping .. Thu Jan 17, 2008 10:30 pm
A) Perinatal mortality and morbidity secondary to rhesus iso immunisation is rare event now. Administration of anti-D immunoglobulin to rhesus negative mothers postnatalyhas lead to significant fall in incidence. This along with improved neonatal facilities have reduced mortality by 10 fold from 1:2000 to 1:20,000. Recent advances in fetal medicine have enabled Obstetricians to monitor rhesus affected fetuses better. In severe cases intrauterine transfusion is possible and improves outcome.Current neonatal facilities and Betamethasone to reduce respiratory distress provide confidence to deliver early when required. Recently more trusts are adopting NICE guidance on routine antenatal prophylaxis with anti-D at 28 and 34 weeks of gestation to all rhesus negative mothers thought to be carrying rhesus positive fetus.This should reduce sensitisation due to unanticipated exposure in pregnancy and reduce incidence further. Our practice to asses degree of fetomaternal haemorrhage by Kleihauer\'s test after any sensitising event beyond 20 weeks identifies that small percentage of women who will require additional anti-D.This will prevent more than 200 sensitisations each year.Availability of rhesus negative blood group in emergencies helps reduce sensitisation. Anti-D administration after any sensitising event- management misscarriages , ectopic pregnancies, trauma, invasive procedures protects from common sensitising situations. Reduction in family size also reduces incidence. Improved laboratory facilities with provisison of quick results help us acheive administration within most effective period( 72 hours). B) Inspite of our tremendous success in this field rhesus sensitisation continues to affect about 500 fetuses each year and leads to about 30 deaths. Most common reason is sensitisation during pregnancy and majority of these are due to treatment failure. 40% are due to mother not attending or attending late. Sensitisation in previous pregnancy continues to be significant reason.Silent fetomaternal haemorrhage continues to be a hurdle. Other events that can lead to sensitisation are blood transfusion or blood product transfusion which is not Rh negative. platelet tansfusion is often required in pregnancies complicated with coagulation abnormalities due to haemorrhage,infection, autoimmunity and preeclampsia. C) Further reduction in perinatal mortality and morbidity can be acheived by increasing awareness in staff and population. This will reduce failure to administer anti-D and women attending and within effective time period. Hospital protocols should be followed for anti-D. Discharge notes with anti-D tick box will aid as reminder which is especially important in Gynae units dealing with early pregnancy complications. Wide availability of rhesus negative blood and blood products will reduce sensitisation secondary to these. Identification of fetal blood group from fetal DNA in maternal serum will identify pregnancies requiring anti-D when partner heterozygous for rhseus. Affected pregnancies should be managed by specialist multidisciplinary team in tertiary care centre , this improves surveillance and treatment. Advanced Neonatal facilities reduce perinatal mortality. Anti-D manufactured in vitro( recombinant) may improve acceptance especially in jehova\'s witness patients will reduce incidence further. High risk patients may be sensitively advised regarding limiting family size. Most importantly guidelines should be followed up and practised to reduce the incidence of rhesus sensitisation.
		Posted by Anna A. Thu Jan 17, 2008 11:03 pm
a. Routine use of prophylaxis of anti-D immunoglobulin post delivery has resulted improvement of perinatal mortality and morbidity. Presence of advanced neonatal care with phototherapy and exchage-transfusion to affected baby has improved the neonatal outcome. The pattern of small family size is increasing trend thus less number of pregnancy and less exposure to immunization or sensitizing event. The presence of advance of fetomaternal unit and the facility to offer intrauterine blood transfusion has improved the perinatal outcome of affected fetus (hydrop fetalis). Middle cerebral artery (MCA) Doppler can predict those fetuses with significant anaemia, therefore the use of MCA Doppler with intrauterine transfusion has improved fetal outcome in those sensitized mother. Administration of anti D prophylaxis after ectopic pregnancy or evacuation product of conception will reduce possibility of Rh positive red cell exposure to the mother, thus reduce the chances of immunization to the mother. Anti D immunoglobulin during pregnancy after sensitizing event like ante-partum haemorrhage, intrauterine death, external cephalic version and abdominal trauma has reduced the chances of immunization, thus will improve the outcome of future pregnancy. b. Failure to recognized larger feto-maternal haemorrhage (FMH) especially after traumatized delivery like caesarean section and manual removal of placenta contribute to inadequate dosage of anti D immunoglobulin. Presence of spontaneous FMH, which is not detectable clinically has resulted persistent of iso-immunization. Failure to administer antenatal prophylaxis or delayed administration of anti D immunoglobulin post delivery is hazardous to perinatal outcome in the future pregnancy. c. Routine administration of antenatal prophylaxis at 28 weeks and 34 weeks will further reduce the chances of iso-immunization, thus can improve prenatal mortality and morbidity. Strict adherent to the hospital guideline for prophylaxis of administration of anti D immunoglobulin should be implemented. Written information leaflet contain of sensitizing event and the important anti D immunoglobulin injection should be distributed to those patient with Rh negative. Routine measurement of Rh positive red blood cells like Kleihauer test or flow cystometry is important to ensure adequate dosing of anti D immunoglobulin.
		Posted by M M A. Fri Jan 18, 2008 01:18 am
a) Peri-natal morality occurs as a result of sever fetal anemia, fetal heart failure with subsequent development of hydrops fetalis, therefore; adequate prophylaxis, early detection and appropriate management will help to minimize perinatal mortality. The introduction of post natal Anti ?D immunoprophylaxis to Rh negative non sensitized mother reduce the mortality from 46:100 000 to 1.6:100 000, it is very effective especially if given in adequate amount as soon as possible after delivery. Also the current protocol of measuring maternal immunoglobulin at booking, 28, 34 and 36 weeks gestation with giving prophylactic dose at 28 and 34 weeks gestation to non sensitized women will reduce the incidence of sensitization by neutralizing fetal RBC that pass to maternal circulation at later half of pregnancy. Giving a prophylactic Anti-D Ig to all RH negative non sensitized women with ectopic pregnancy, molar pregnancy and those who have therapeutic termination of pregnancy whether medical or surgical minimize a lot of developing sensitization. This also include all cases of spontaneous miscarriage or threatened miscarriage after 12 weeks gestation. Using the appropriate dose is very important, this is done by giving 250 iu before 20 weeks gestation and 500 iu after 20 weeks and depending on Kleihauer test to detect the need for an additional amount of Ant-D Ig for larger fetomaternal haemorrhage. Threatened miscarriage before 12 weeks doesn\'t need prophylaxis unless there is repeated and heavy bleeding , also when we do uterine evacuation or instrumentation for spontaneous miscarriage. The reduction of perinatal mortality can be attributed also to covering the sensitizing events in pregnancy with the appropriate amount of Anti D Ig like bleeding, intrauterine death prenatal invasive test and external cephalic version. Doppler US can detect early feature of hydrops by measuring middle cerebral artery velocity , the lower fetal heamatocrit, the lower velocity, this can be detected before the appearance of ultrasonic features like subcutaneous edema or pleural effusion and this help in early referral and intervention. The improvement in doing intrauterine transfusion reduce many cases of perinatal mortality by elevating fetal PCV and ameliorating fetal heart failure. b) Failure of adherence to the current protocol of Anti-D immunoprophylaxis is responsible for persistence of some cases of Rh isoimmunization. Also failure of prophylaxis in current pregnancy or in the preceding pregnancy whether due to inadequate dose of Anti-D Ig or if it given late after the sensitization had occur. Occasionally sensitization occur without overt sensitizing event , it can occur due to occult fetomaternal heamorrhage. Sensitization can also develop late in the first pregnancy without recognition. Giving Rh positive blood product like platelets without giving Anti-D Ig or even giving Rh positive blood to Rh negative non sensitized women without effective neutralization of that blood or effective exchange transfusion. All can result in development of isoimmunization. c) Women should be further educated about Rh isoimmunization and its implications. They are encouraged to have regular attendance at antenatal clinic with early reporting if they had any sensitizing event like bleeding or abdominal trauma. Good compliance encouraged also. Giving Anti D Ig in accurate dose according to gestational age and amount of fetomaternal haemorrhage. We stress that post natal prophylaxis should be givin as early as possible after delivery and within 72hours. The use of flow cytometry is more accurate than using Rosette test or kleihauer\'s test in detecting the need for an additional amount of anti-D Ig for larger FMH, therefore; flow cytometry should be implemented as much as possible. Regular audit of the current prophylactic protocol with reviewing and up-dating. Early involvement of fetal medicine specialist and early referral to tertiary centers will carries a better out come.
		Posted by Farina A. Fri Jan 18, 2008 01:53 am
a) More clear guidelines regarding antenatal prophylaxis for RH immunisation, are being followed in majority of obstetric units. It has resulted in marked improvements in the perinatal mortality and morbidity. A reduced mortality from 46/100000 births to 1.6/100000 has been noticed in the past few years. Booking screening for antibodies by indirect coombs test in RH negative women followed by routine administration of prophylactic (500 IU) IGg immunoglobulins is widely practiced. All miscarriages after 12 weeks and those with painful heavy bleeding and surgical or medical evacuation before 12 weeks are being given anti-D prophylaxis. Better estimation of size of fetomaternal haemorrhage by flow cytometry and rosetting technique has led to more appropriate and effective dose administration. However Kleihaur?s test is also widely used for the same. Administration of prophylactic anti-D immunoglobulin after ectopic pregnancies, ECV, CVS, amniocenteses, intrauterine fetal therapy, APH and abdominal trauma has their contribution in reducing perinatal mortality and morbidity as unrecognized FMH can occur in these cases. Obstetrics procedures like CS, manual removal of placenta, conditions like hydrops fetalis and IUFD are all indicators of major fetomaternal haemorrhage. Performance of Kleihaur?s test and dose adjusted immunoprophylaxis significantly reduces the incidence of RH disease in future pregnancies thereby reducing the future perinatal mortality and morbidity. Earlier detection and treatment of fetal anemia by MCA Doppler studies and multidisciplinary approach involving a paediatrician, fetal medicine unit and obstetrician has improved the outcome of mild ? moderately severe form of the disease. Routine postnatal administration of anti-D IGg regardless of previous administration within 72 hrs is also widely practiced.Better neonatal care with phototherapy and exchange transfusion, coticosteriod support for fetal lung maturity and preterm delivery for the adequate extrauterine therapy as changed the face of the disease severity. b) Patient refusal, as some patient thinks that they are in a stable relationship with their partner who is RH negative. Inadequate dose administration of anti-D IGg and failure to administer within 72 hrs or missed doses, asymptomatic sensitization with very small size of FMH generating an immune response may be among the few reasons for persistent perinatal mortality. Poor antenatal attendance, ignorance and illiteracy in various part of the world can contribute for the persistent perinatal morbidity and mortality.Transfusion of RH + blood or blood products in emergency situations or inadvertently is also one of the reasons of RH isoimunisation. c) Patient should be given verbal and written information about the prophylactic measures. Appropriate and updated refresher courses to the concerned staff should be conducted. Earlier detection and treatment of high risk cases specially those with previous adverse pregnancy outcome and proper communication and referral to the fetal medicine units. Multidisciplinary approach involving paediatrician fetal physician obstetrician and a trained nurse is obligatory. Wider availability of specific tests (flow cytometry and rosetting technique) should be widely available.
		Posted by Lekshmi B. Fri Jan 18, 2008 11:02 pm
Perinatal mortality from Rhesus iso-immunisation is increasingly uncommon. (a) Evaluate the factors that have resulted in this fall in perinatal mortality [9 marks]. (b) Evaluate the factors that contribute to persistent perinatal mortality and morbidity from Rhesus iso-immunisation [6 marks]. (c ) How can perinatal mortality and morbidity from Rhesus iso-immunisation be further reduced? [5 marks]. a) The introduction of postnatal immunoprophylaxis using anti D Immunoglobulin (anti-D Ig)in 1969 has resulted in a marked reduction in perinatal mortality rate from 46/100000 births to 1.6/100000 births. This occurs by passive immunization of the mother; where by the fetal red cells in maternal circulation are rendered in effective in inducing maternal immune response. Majority of sensitization (90%) occurs due to fetomaternal haemorrhage (FMH) at term. Post natal prophylaxis causes 90% reduction in the risk. The addition of routine antenatal ante-D Ig (RAAD) Prophylaxis at 28 weeks further reduces the risk of sensitization to 0.1%. The practice of giving anti-D prophylaxis following sensitizing events in labour has also contributed to reduced risk of Rh iso-immunisation. Another reason for the improvement in perinatal mortality is the practice of limiting number of children to have small families. This has led to a decline in the severity of fetal disease, contributing to better prenatal outcome. Better antenatal care has resulted in more Rh negative women being screened regularly from booking visit onwards, thereby leading to early detection of cases and better management. The development of a non invasive method to assess risk of fetal anemia by measuring peak systolic velocity of middle cerebral artery has resulted in better patient compliance. This along with ultrasound as adjunct has revolutionized fetal monitoring. Lastly the development in fetal therapy, mainly intra vascular transfusion has helped in rapid resolution of fetal problems and more than 90% survival is noted even in hydropic babies following this procedure. b) Failure to implement RAAD prophylaxis in many centres is one reason for persistent cases of Rh iso-immunisation. Administration of routine doses of anti D (following sensitizing events and postnatal) with out taking into account the extent of FMH has contributed to the failure of prophylaxis. Laboratory errors regarding detection and interpretation of anti D titres also result in improper management of cases leading to poor prognosis. Another limiting factor is the reduced number of physicians experienced in advanced fetal therapy, as a result of decrease in incidence of maternal alloimmunisation.Limited access to specialized fetal medicine unit also results in poor outcome. c) Regular testing of Rh negative ladies with ICT and DCT at monthly intervals from the booking visit, will allow detection of almost all cases of sensitization at the earliest. The obstetrician should be aware of the local laboratory standards and critical titre in order to interpret the results properly.RAAD,AADand post natal prophylaxis should be adopted according to the RCOG guidelines to reduce the risk of sensitization. If found to be sensitized at any stage, centralized management should be followed i.e. the woman should be referred to a fetal medicine unit or an experienced consultant who is dealing with at least 8-10 similar cases per year. After delivery careful monitoring of the newborn by measuring hematocrit and reticulocyte count should be continued and transfusion given if required. These measures can result in a better outcome.
		Posted by Shankaralingaia N. Sat Jan 19, 2008 04:29 am
Rhesus isoimmunisation causes perinatal and neonatal morbidity and mortality. a)There is a fall in the perinatal mortality over the period of time.There are several reasons behind it. First of all there are strict guidelines for the medical staff involved in women\'s care.It lays emphasis on routine antenatal anti D prophylaxsis at 28 and 34 weeks gestation even in non sensitized women.In uk we administer 500IU Anti D immunoglobulins intramuscularly for all Rh negative mother after informed consent. Secondly administering 250IU of Anti D for all sensitizing event before 20 weeks and 500IU after 20 weeks gestation reduced development of antibodies significantly.After 20 weeks keihauer test is done to determine amount of feto maternal transfusion.Sensitising events involves any bleeding after 12 weeks, surgical and medication termination before 12 weeks, after amniocentesis,CVS,ECV,Fetal cord blood sampling or abdominal trauma.Post natally 500 IU of Anti D is administered if baby is Rh positive and keihauer test is done to determine if they need any extra dose of Anti D. Thirdly,screening all women for antibodies at booking and at 28 weeks can diagnose high risk cases and refer to fetal medicine unit for appropriate treatment. Fourthly,Availability of advanced diagnostic tools and treatments ,mortality due to haemolytic disease of fetus and neonate has reduced.Fetal medicine unit can treat fetal anaemia in utero in the form of blood transfusion. Last of all educating women and providing leaflets by midwives and obstetrician make them more aware of the situation. b)In spite of all the above mentioned factors there are deaths due to haemolytic disease from Rh isoimmunisatin.This could be due to treatment failure where adequate dose of Anti D is not administered at the time of sensitisation.It should be ideally administered within 72 hours or maximum 10 days for it to have any effect.Delay in the time period may account for the failure. Women not having any Anti D after sensitising event or prophylaxsis may affect next pregnancy.There could be defect in the production of Anti D from the company. Sensitization in the previous pregnany which was not or adequately treated may be the cause. Treating with Anti D without an event of sensitisation may produce antibodies which may have effects in future. The other cause may be not following the guidelines strictly may lead to the problems.So auditing the practice is vital. c)It can be further reduced by following the guidelines and auditing our practice.It is the duty of the carer to educate and give adequate information regarding Anti D prophylaxsis and reporting after every sensitising event reduces the incidence. Early referral to fetal medicine unit and neonatologist for the management of fetal and neonatal anaemia and hydropic babies. Providing written information and support to the patients is paramount.There could be other antibodies like C,c,e,E and kell antibodies which can cause Haemolytic disease so recognising it at the screening blood tests and acting on it may further reduce it from happening.
		Posted by Hala T. Sat Jan 19, 2008 07:43 am
a) Since the introduction of anti-D prophylaxis ,the incidence of the rhesus sensitization has plummeted and with it the associated perinatal mortality . The fall in the perinatal mortality from this disorder has also influenced by factors ;such as improved antenatal surveillance ,with developments in ultrasound and other technology. This improved technology allowed the non-invasive monitoring ,such as Doppler measurements of peak-systolic velocity of middle cerebral artery . It is a reliable method in assessing fetal anaemia. Survival rates of the fetuses with anaemia have improved since intrauterine transfusion was introduced. The use of routine screening to identify the pregnancies at risk ,has value in reducing the perinatal mortality. It is cost-effective. Improved neonatal intensive care and early planned delivery with steroid cover if necessary. Also, small family size ( one or two children)has obvious value in reducing the risk of interventions, which would contribute in the perinatal mortality . b) Factors that contribute to persistent perinatal mortality and morbidity ;such as diseases caused by other Rhesus antigens such as ( E and c ) for which there is no prophylaxis. There is still some low but persistent incidence of Rhesus immunisiation episodes due to omitted or failed prophylaxis and silent fetomaternal haemorrhage causing sensitization. Those causing potentially sensitizing events during pregnancy are invasive prenatal diagnosis ( amniocentesis, chorion villus sampling ,fetal blood sampling), external cephalic version, abdominal trauma and uterine bleeding . If the appropriate dose of anti-D is not administered following these sensitizing events, the perinatal morbidity would be increased. Decreasing expertise as the disease becomes less common, is one of the reasons of persistence of perinatal mortality and morbidity. c) Further fall in the incidence of the perinatal mortality and morbidity could be achieved by referral of sensitized pregnancies to tertiary centres where espertise can be concentrated . Routine use of antenatal prophylaxis at 28 and 34 weeks ( 500 IU ) . This has been shown to be cost-effective intervention. Improved rigour in the administration of prophylaxis ,including the use of Kleihauer tests after 20 weeks gestation and administration of further doses if requires . It should be administered by IM injection into the deltoid muscle within 72 hrs of a sensitizing event although a dose given within 9-10 days may still offer protection.
		Posted by Idris O. Sat Jan 19, 2008 10:01 am
a)The fall is due to screening and identification of high risk patients with rhesus negative blood who may require anti-D. The use of anti-D in these high risk patients also contribute to the decline.Other contributory factors include the adoption of small family size. In patients already sensitized with rhesus antibodies, anemia is promptly diagnosed with dopplers of the MCA. This fetuses with anemia are offered intrauterine transfusion to prolong gestation and reduce the risk of prematurity. These fetuses are also offered steroids to reduce the risk of RDS and neonatal intensive care.When anemia is diagnosed in late pregnancy, elective delivery is planned for this fetuses..These babies are also able to survive due to improved neonatal care. b) Persistence perinatal mortality and morbidity may be due to omitted prophylaxis.These may be due to patients declining prophylaxis due to fear of adverse effects of these human products like CJD, hepatitis and HIV. The patients may also be unbooked and present late in labour and having missed antenatal prophylaxis. Some patients may also fail to respond despite having prophylaxis. Antibodies may develop as a consequence of spontaneous transplacental hemorrhage. Anti D does not protect against anti Kell antibodies , anti C.c E,e and M. antibodies .. c) A further fall in the incidence may occur following health education involving the patients about implication of rhesus disease. These would be assisted with information leaflets. Training of health care workers and the improved clinical rigour in the administration of anti-D following sensitizing events like abdominal trauma, CVS, amnio, ECV and ectopic pregnancy. Routine use of antenatal 3rd trimester prophylaxis also helps to reduce morbidity and mortality. Anti-D prophylaxis should be determined after a sensitizing event depending on the kleihauer test. Anti ? D prophylaxis can be adminsterd up to 30days from the sensitizing event but most effective within 72h of the event. Audits of patients with rhesus blood would also improve the outcome.
		Posted by Dr seema jain J. Sun Jan 20, 2008 01:18 am
a)Prevention of Rh isoimmunisation by use of antenatal and postnatal prophylactic use of Anti-D immunoglobulin has been one of the main factors.Laying of guidelines fpr use of Anti-D in other situations like surgical termination of pregnancy,ectopic pregnancy,CVS,amniocentesis etc has helped in prevention.Availability and easy accessibility to the Anti-D immunoglobulin in most of the hospitals has helped the Rh negative women.Non invasive techniques to determine the fetal Rh status from maternal blood and determination of paternal zygosity can screen women who will need prophylaxis . Early diagnosis of a Rh sensitized pregnancy with the use of critical titre of anti-D being offered by most of the laboratories has helped in initiating early treatment.Non invasive methods of monitoring an affected fetus by ultrasound Doppler of middle cerebral artery peak systolic velocity can help in deciding about the timing of delivery.Use of antenatal corticosteroids for fetal lung maturity in case an early delivery is required has decreased perinatal morbidity and mortality.Intrauterine blood transfusion in anemic fetuses prevents development of hydrops and improves the prognosis. Use of donor insemination and providing preimplantation genetic diagnosis in women with history of Rh sensitized pregnancies can be considered. b)Failure to strictly adhere to the anti-D immunoglobulin prophylaxis has been one of the most important factors.Women who are deemed not necessary to be given anti-D prophylaxis quite often change their mind later leading to Rh sensitization.Failure to recognize the importance of using anti-D prophylaxis following potential sensitizing situations like CVS,amniocentesis,ECV etc is one of the other reasons for Rh sensitized pregnancy.Lack of laboratory specific cut off values of critical titre can miss early identification of affected fetus.For women from rural areas accessibility is a major issue.Management of a sensitized pregnancy using Liley?s chart instead of non invasive ultrasound Doppler can lead to further sensitization.The learning curve for performing intrauterine blood transfusion is steep which can lead to procedure related complications.Lack of accessibility to dedicated neonatal facilities for women from rural areas can amount to mortality in a potentially salvageable situation. c)Strict adherence to anti-D prophylaxis under any circumstances should be made mandatory.Audit to determine the resons leading to failure in preventing a Rh sensitized pregnancy should be done.Improving awareness and accessibility of women from rural areas for anti-D prophylaxis will go a long way in reducing the perinatal morbidity and mortality.Laying of laboratory specific cut off values for critical titre should be more standardized.Donor insemination and preimplantation genetic diagnosis in women with previously sensitized pregnancies should be offered more often.
		Posted by maha G. Sun Jan 20, 2008 10:07 am
{a} Early booking of pregnant women and detection of blood group and Rh status led to early recognition of any sensitizing events and ultimately proper management. Introduction of anti D played an important role in reduction of perinatal morbidity and mortality especially after devolpment and reviewing the NICE and RCOG guidelines for the use of anti D for immunoprophylaxis which cover any suspecting sensitizing events. Adherence to the RCOG and NICE guidelines and establishment of unit protocol led to dramatic fall in perinatal morbidity and mortality. Routine administration of anti D at 28 and 34 weeks gestation had a major impact in the reduction of Rh isoimmunization and subsequently the associated morbidity and mortality. Quantification of fetomaternal hemorrhage by flow cytometry, rosseting and Kleahieur?s test helped in determining the optimal dose of anti- D for prophylaxis so ultimately reducing the sensitizing events. Availability of ultrasound had a major role in early detection and early management of fetal hydrops. Referral of Rh isoimmunization to tertiary fetal medicine unit improved the outcome and reduced the perinatal morbidity and mortality. Development of non-invasive techniques such as using maternal plasma for fetal genotyping and Doppler study of middle cerebral artery measuring peak velocity volume for monitoring fetal anemia had a dramatic effect, as well, in such way avoiding the morbidity associated with amniocentesis. Advances in neonatal special care units played a role in such improvement. Other responsible factors are the use of antenatal corticosteroids which reduced RDS, inteventricular hemorrhage and necrotizing enterocolitis. Also, intrauterine blood transfusion improved the outcome of hydropic and non-hydropic Rh iso-immunization. {b} Rh isoimmunization is due to five antigens; D, C, E, c and e antigens of which D antigen is the most common one so while Isoimmunization due to D antigen became uncommon,isoimmunization due to other antigens became more apparent. Non adherence to the guidelines is a responsible factor where administration of anti-D is limited to 72 hours of the sensitizing events while later administration (within 10 days) will give some protection. Quantification of fetomaternal hemorrhage is done only after 20 weeks gestation. A limiting factor is the cost of Anti-D that is why its routine administration at 28 and 34 weeks gestation is not available in all areas of the UK. Other contributing factors are non-administration of anti-D, unrecognized sensitizing events, underestimation of fetomaternal hemorrhage and suboptimal doses of anti D. In cases of threatened and spontaneous miscarriage anti-D is given only after 12 weeks gestation leaving 3% of Rh isoimmunization that happens during the first trimester. Anti-D is resented by some women because it is a human product and fear of Jacob?s disease (CJD). {C} Education of GP, midwives and all taking care of pregnant women is warranted to improve the care. Reviewing and updating the guidelines regarding the use of anti-D is needed.Unit protocols should be established. Pregnant women with Rh negative should be given verbal and written information regarding anti-D and explanation to those who are rejecting anti-D on the basis of fear from JCD the rarity of this illness. Furthermore, monoclonal antibodies will solve this issue. Administration of optimal doses of anti-D based on the quantitative test will improve the outcome. Audit should be done regularly to detect the adherence to the guidelines. More researches aiming at devolpment of immonoprophylazis against antigens other than D antigens are essential. Raising more funds will increase the availability of anti-D.
		Posted by M M A. Sun Jan 20, 2008 06:23 pm
Dear Dr Paul , thank you very much for your help anf thank you also for your comment. I just want to make this correction please: = Dopler US can detect early feature of fetal anemia [ yes , it doesn\'t detect Hydrops] , the lower fetal heamatocrit, the more rapid velocity of blood flow in middle cerebral artery, also it cam measure velocity in inferior vena cava and ductus venosus. = Other thing please:Exchange transfusion will minimise the load of RH +ve RBC so the amount of Anti-D needed will be less and calculated according to Kleihauer\'s test. Thank you again and please have my best regards.
		Posted by Azza Shawky E. Mon Jan 21, 2008 06:06 am
a)the Rh allo isoimmunization decreased from46/100.000birth in1969 to 1.6 in 1990 this for many factors as wide immunization programe with improved antenatal surveilance,small family size ,early planned delivary at 34-36 wks with antenatal steroid , advanced and improved NICU with phototherapy and exchange transfusion improve neonatal outcom. Recently use of doppler velocimtry of middle cerebral artery predect need of fetus to exchang transfusion b) Persistance of sensitization against Rhesus disease occure for many reasons . These are ;failure of adminstration of anti D,inadequate dose of adminstration, failure of adher to giudline and late immunization in frist pregnancy and silent fetomaternal heamorrhage. 3 % of erthroplastosis fetalis due to immunization against other antigenic group is not preventable by anti D.Until these are remended Rh isoimmunization continue to occure c) Their are several approaches to overcome mortality and morbidityas counsel and education of patient ,MW,GP and all take care of pregnent. Leaflet and written information should be given to all pregnent Rh -ve woman to identify the importance of given anti D after sensitizing event.Kleihaure elution test detect fetal Hb and is used for screening to identify large FMH.Recently flow cytometry is more accurate yet not readly available It is most effectivly employed when Kleihaure test detect large FMH.Anti D adminstrated IM in deltoid muscle(better absorption) up to 72 hs after sensitization as invasive prenatal diagnosis(CVS- FBS- ameniocentesis), intrauterine procedure(shunt-embryo reduction)APH,IUFD,ECV. anti D can be given after 72hs up to 10 days it give 75%protection of cases. propylactic anti D 250 iu<20 wks-500iu >20wks+kleihaure test should be given after spontanous abortion(complet or incomplet).all TOP(medical or surgical),all ectopic ,threatend miscarriage>12wks and<12wks if their is sever bleeding or pain.RCOG consenus group recommended prophylactic routine anti D 500iu adminstration at 28 and34 wks gestation . however anti D and mono clonal antibody should be available. sensitized pregnent woman and woman had sensitizing event in previous pregnancy should be referred to tertiary center for evaluation and folowup with US (hydrops- polyhydraminos), monthly antibody titer, check husbant phenotype. if titer is increased ;ameniocentesis ,cordocentesis(Hb- platlets -fetal BV),plasmaphoresis should be done intrauterine transfusion may be needed,delivary by CS once viable and organize SCBU support for exchange trnsfusion post delivary. Although Rh isoimmunization may soon uncommen oher rare type of isommunizationare becoming more commen this need to be recognize and prevent as done with Rh isoimmunisation.