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Rh Rhesus Isoimmunization
Rh Rhesus Isoimmunization
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  1. 1. PRESENTER: Dr Abhinav Sharma MODERATOR: Ass. Prof. Dr Swati Upadhyay, DNB
  2. 2. HISTORICAL PERSPECTIVE INCIDENCE AND BURDEN OF DISEASE CORE CONCEPTS PATHO-PHYSIOLOGY CLINICAL FEATURES LABORATORY DIAGNOSIS PROPHYLAXIS ANTENATAL TREATMENT POSTNATAL MANAGEMENT SHORT TERM OUTCOMES LOG TERM OUTCOMES
  3. 3.  Hippocrates in 400 BC first described erythroblastosis fetalis  First clinical report - Attributed to a French midwife reported in twins in 1609.  1940 Landsteiner discovered Rh antigen.  In 1941, Levine described alloimmunization.  In 1948, Wiener postulated that feto-maternal hemorrhage triggered isoimmunization  Freda and coworkers efficacy of anti-D IgG in Rh negative volunteers Textbook of Neonatal and Perinatal Medicine, Fanaroff and Martins, 11 edition, 2018
  4. 4.  In 1961 Lilley, for the first time, described intrauterine transfusion.  Exchange transfusion, introduced by Wallerstein.  In 1967 Schneider and Preisler proved that Anti-D is not useful in already sensitized mothers.  Since 1971, the WHO recommended empirical use of Anti-D Ig following any sensitizing events. Textbook of Neonatal and Perinatal Medicine, Fanaroff and Martins, 11 edition, 2018
  5. 5.  RH HDFN 3.7 lac cases/annum worldwide of which 56,672 contributed by India.  It is estimated that in (LMIC) like India, nearly 10 lakh Rh negative women are at risk of developing Rh isoimmunization, and only 2.5 lakh Rh antibody units are distributed.  In developed countries nearly 1.8% and 0.1–0.3% of Rh negative women develop anti D antibodies.  Various Indian studies have reported the prevalence of Rh negative status in Indian women varies between 4 and 10%.  Studies estimating risk of RH alloimmunization are limited with hospital based studies estimating rate between 9-10-%.  Of the total global burden of 26,900 cases of kernicterus and 89,000 cases of neonatal death due to RHDN, south Asian countries contribute nearly 38% caseload in each category Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  6. 6.  HDFN also called as “erythroblastosis fetalis” is characterized by the increased rate of red blood cell (RBC) destruction.  Hemolysis – Immune: Rh, ABO or Minor blood group incompatibility. - Nonimmune: α-thalassemia, RBC membrane, or enzyme defects.  Alloimmunization due to feto-maternal hemorrhage.  Clinical sequela, ranging from anemia and hyperbilirubinemia to fetal hydrops, kernicterus, and death. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  7. 7.  Hydrops fetalis (HF) is defined as the presence of excessive fetal fluid in two or more of the following spaces: abdominal ascites, pleural effusion, pericardial effusion, skin edema, polyhydramnios, or placentomegaly.  HF has been classified into two categories based on etiology: oImmune HF accounts for an estimated 10%-24% oNonimmune HF accounting for 76%-90% of cases Fanaroff and Martin-Textbook of Neonatal and Perinatal Medicine, 18 edition
  8. 8.  An antigen is any substance which, when introduced into the body of an immunocompetent individual, stimulates the immune system by production of an antibody by interacting with the immunoglobulin receptor of B cell.  Each red cell membrane is a bi-phospholipid layer containing millions of antigen on its surface.  The blood group antigens are either protein or carbohydrate structures present on the red cell membrane. Fanaroff And Martin: Textbook of Perinatal and Neonatal Medicine, 11 Edition, 2018.
  9. 9.  Antibodies are recognition proteins found in the serum and other body fluids of vertebrates that react specifically with the antigens that induce their formation.  Antibodies belong to a family of globular proteins called immunoglobulins.  They are produced by the lymphocyte-plasma cell system.  Antibodies bind antigen, fix complement, facilitate phagocytosis, and neutralize toxins in the circulation. Fanaroff And Martin: Textbook of Perinatal and Neonatal Medicine, 11 Edition, 2018.
  10. 10.  The rhesus factor has more than 50 different described antigens.  Three of the most concerning antigens in pregnancy, are encoded at two human loci, found on chromosome #1 (1p36.1).  Fisher and race method is used to describe the genotype. Most common halotype Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  11. 11. Properties D C/c E/e Immunogenicity Severe HDFN: anti D/c Mild HDFN: Anti C/E/e Critical titres 1:16 1:32 1:32 Clinical phenotypes of sensitisation Foetal anaemia, jaundice, hydrops, NNH, anaemia and ABE Delayed anaemia. Can be additive to effects of anti-D Can be additive to effects of anti-D HDFN in RH positive pregnancy ?? Blocked D ? Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  12. 12.  Kell antigen is formed in fetuses of 10–11 weeks and k at 6–7 weeks of gestation.  The Kell blood group gene, located on chromosome #7 (7q33)  Second major cause for HDFN after Rh and ABO incompatibility.  Targets erythroid precursor cells causing severe foetal anaemia and hydrops fetalis. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  13. 13.  Transplacental feto-maternal hemorrhage occurs in over 75% of pregnancies.  The average volume of fetal blood in the maternal circulation following delivery is less than 1 mL.  As the pregnancy progresses, the possibility of feto-maternal hemorrhage increases, 3% in first trimester, 12% in the second, 45% in the third, and 64% at the time of delivery as shown by Bowman et al.  0.1 mL of antigen-positive blood is sufficient to cause sensitization in an antigen- negative mother Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  14. 14. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  15. 15. 1.8 and 0.1-0.3 % in developed countries 14% in developing 14% 30% Severe disease 30% Moderate disease 40% Asymptomatic
  16. 16. Heart failure form profound anemia and hypoxia Portal hypertension due to hepatic parenchymal disruption Decreased colloid oncotic pressure resulting from liver dysfunction • Decreased COP • Increased CVP • Capillary leak Early: Polyhydramnios and placentomegaly, hepatomegaly and pericardial effusions . Late findings: Ascites, scalp edema, pleural effusions Large Pleural effusions: Pulmonary Hypoplasia Hepatomegaly+ splenomegaly + Hydrops = Labour Dystocia----- Perinatal Asphyxia Severe anaemia + Acidosis = Foetal Death Maternal Complications: Antenatal: Polyhydramnios, PET Intrapartum: Placental Abruption, premature labour, prolonged labour, retained placenta. Postpartum: PPH Fanaroff And Martin, Textbook of Neonatal and Perinatal Medicine, 11 edition, 2018
  17. 17. Haemorrhage<0.25 ml ABO Incompatibility Immunosuppression in pregnancy Immunological Non- responders Fanaroff and Martin, Textbook of Neonatal and Perinatal Medicine, 11 edition, 2018
  18. 18. • Blood group ABO and Rh type of mother and father • History of amniocentesis, CVS, cordocentesis or blood transfusion in present pregnancy • History of abortions, ectopic, APH and PPH in previous pregnancies • History of Anti D administration in previous and present pregnancy • History of Indirect coombs test • Review records of USG showing evidence of hydrops, MCA dopplers. • Any history of IVIG, apheresis, IUT or IPT in present or previous pregnancies. • PET, polyhydramnios in presentpregnancy Fanaroff and Martin, Textbook of Neonatal and Perinatal Medicine, 11 edition, 2018
  19. 19.  History of preterm labour, prolonged labour, retained placenta, abruption and PPH.  Placental weight, gross and microscopic examination. NEONATA L HISTORY 1. Perinatal asphyxia and need for resuscitation 2. Respiratory distress: effusions, pulmonary hypoplasia, pericardial effusions and severe anaemia. 3. Neonatal Jaundice: Onset, rate of progression, cord blood levels of Hb, retic and bilirubin, treatment, symptoms of ABE. 4. Neonatal Anaemia EXAMINAT 1. General: Pallor, icterus 2. Respiratory: Rate, RD scores, air entry 3. CVS: Precordium shape, S1, S2 muffling 4. P/A: hepatosplenomegaly, free fluid 5. CNS: Sensorium, tone, movements, reflexes and cry.
  20. 20. Fanaroff and Martin, Textbook of Neonatal and Perinatal Medicine, 11 edition, 2018
  21. 21. Fanaroff and Martin,Textbook of Neonatal and Perinatal Medicine, 11 Edition, 2018
  22. 22. Fanaroff and Martin, Textbook of Neonatal and Perinatal Medicine, 11 edition, 2018
  23. 23.  NON INVASIVE -USG markers for prediction of foetal anemia. -Doppler Study of Foetal MCA  INVASIVE- Amniocentesis Delta OD50 and Plotting on Liley Curve (Historical) - Cordocentesis for Estimation of Foetal Hb (M. Accurate) Fanaroff and Martin, Textbook of Neonatal and Perinatal Medicine, 11 edition, 2018
  24. 24. Fanaroff and Martin, Textbook of Neonatal and Perinatal Medicine, 11 edition, 2018
  25. 25.  MCA is most responsive to changes due to fetal anaemia,  MCA is easy to identify with low interobserver and intra-observer variability.  Mari and colleagues found the optimal threshold was 1.29 times the median for mild anemia, 1.5 times the median for moderate anemia, and 1.55 times the median for severe anemia, with a false-positive rate of 12%.  Thresholds were chosen so as to not miss any fetus with moderate or severe anemia  MCA-PSV can be started as early as 16-18 weeks and should be repeated at 1- to 2-week intervals. Fanaroff and Martin, Textbook of Neonatal and Perinatal Medicine, 11 edition, 2018
  26. 26. Performance of fetal middle cerebral artery peak systolic velocity (MCA-PSV) ≥ 1.5 multiples of the median in diagnosis of moderate–severe and severe fetal anemia, according to number of previous intrauterine transfusions (IUT) Conclusions : MCA-PSV ≥ 1.5 MoM for the prediction of moderate– severe anemia in untransfused fetuses shows moderate accuracy (86% sensitivity and 71% specificity), which declines with increasing number of intrauterine transfusions.
  27. 27. Procedure: • Amniotic fluid is scanned at progressively increasing wavelengths • Readings are plotted against a baseline. • Measure difference between peak and baseline at absorbance peak at 450 nm. Principle: • In presence of Bil in AF a rise in absorbance will be seen at 450 nm, • Amount curve deviates from standard line at 450 nm is directly proportional to bilirubin concentration in AF. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  28. 28.  Fetoscopy or PUBS  16 Weeks POG or later  Most Accurate  Fetal blood can be tested for blood type, DAT, hemoglobin, and hematocrit.  5% risk of fetal loss.
  29. 29. ANTENATAL MANAGEME NT ISOIMMUNI SED PREGNANC Y
  30. 30. • IgG antibody • 300mcg = 15 ml of fetal RBCs = 30 ml of fetal blood • 50 mcg = 2.5 ml of fetal RBCs • Half life = 16-24 days • IM – Deltoid/ Anterolateral aspect of thigh
  31. 31. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  32. 32.  Reduces incidence of isoimmunization from 15% to 1%(antenatal) to 0.1-0.3 (additional postpartum dose).  Mechanisms include macrophage induced clearance of anti-D coated RBCs, down regulation of antigen specific B cells and antigen masking.  Timing And Dose- All Rh negative non-alloimmunised pregnant women 300 microgram once at 28–32 wk which takes care of small FMH happening during pregnancy. -The same amount is again repeated soon after delivery within 72 h (if missed, then up to 28 d) for combatting the FMH happening during parturition. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  33. 33.  As an alternative therapy until an intravascular transfusion is possible.  Mechanism: feedback inhibition of maternal antibody synthesis, blockade of reticuloendothelial Fc receptors, or blockade of placental antibody transport.  Conflicting evidence.  Role in pregnancies less than 18-20 weeks with severe fetal anemia caused by Rh alloimmunization, either with IVIG alone or in combination with other therapies, to prolong the pregnancy.  High Cost Fanaroff and Martin, Textbook of Neonatal and Perinatal Medicine, 11 edition, 2018
  34. 34. AJOG, 2018 Population: Pregnancies of alloimmunized women less than 20 weeks POG with a history of severe hemolytic disease (n=24) Intervention: IVIG Comparison: Alloimmunized pregnancies who did not receive IVIG (n=28) Outcome: Difference in GA for onset of severe anemia requiring IUT. RESULTS: • In fetal anemia developed on average 15 days later compared to previous pregnancies compared to 9 days earlier in non IVIG group. • Fetal hydrops occurred in 4% of immunoglobulin-treated pregnancies and in 24% of those without intravenous immunoglobulin treatment (odds ratio, 0.03; 95% confidence interval, 0-0.5; P= .011). • Exchange transfusions were given to 9% of neonates born from pregnancies with and in 37% without immunoglobulin treatment (odds ratio, 0.1; 95% confidence interval, 0-0.5; P =.009) CONCLUSION: • Intravenous immunoglobulin treatment in mothers pregnant with a fetus at risk for hemolytic disease seems to have a potential clinically relevant, beneficial effect on the course and severity of the disease. • Confirmation in a multicenter randomized trial is needed.
  35. 35.  First performed in 1984.  For first IUT, fetal PCV of less than two standard deviation as per gestation or < 30%, is considered as threshold.  Timing: 18-35 weeks GA.  Blood: O-, cross matched with mother, HCT 75%, CMV -, irradiated.  Site: OT with facility for LSCS.  ANS: Preg between 22-34 weeks Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  36. 36.  Prior to procedure, 6–8 h of fasting is required. -Role of prophylactic antibiotics uncertain. -Maternal sedation.  Potential sites of access (umbilical vein, peritoneal cavity, umbilical artery). -Umbilical vein is the most commonly used route due to ease of access and greater safety.  Approach Umbilical vein >22 weeks, Intraperitoneal<22 weeks GA. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  37. 37. • Procedure: • -A 22 gauge needle per abdominally in USG guided manner in umbilical vein near placental insertion site. -The initial sample of blood is utilized for measuring hematocrit, hemogram and retic count. -Subsequently, the calculated volume of donor blood is injected in a syringe. -For stabilization of needle and preventing its dislodgment, a paralytic agent (pancuronium, vecuronium or atracurium) plus fentanyl is usually injected in fetal thigh. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  38. 38.  Fetal heart rate is monitored closely during the entire procedure.  Transient fetal bradycardia (incidence 4–5% of all procedures) and bleeding from puncture site are the most common complications.  The overall procedure-related fetal loss rate is approximately 1%, and the emergency delivery rate within 24 hours for procedure-related complications and subsequent perinatal demise is 1.8% Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  39. 39.  Careful sonographic surveillance should be instituted, depending on the gestational age.  Daily fetal testing with nonstress tests or biophysical profiles is reasonable for all potentially viable fetuses.  Once there is sonographic evidence of resolution of hydrops, testing can be decreased to twice weekly.  Sonographic surveillance for appropriate fetal growth should continue every 2 week Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  40. 40.  Repetition of IUT is done at 10 d, 2 wk and 3 wk following previous IUT.  Expected drop of hemoglobin as 0.4 g/dl/d (Roughly 1% PCV per day), 0.3 g/dl/d and 0.2 g/dl/d following first, second and third IUT respectively and performing IUT when fetal PCV drops to <25%.  In a recent meta-analysis, the sensitivity of MCA PSV ≥1.5 MoMs in predicting moderate to severe anemia after first, second and third or more IUTs were 78, 74, and 60%, respectively, compared with 86% before first IUT.  subsequent IUTs (third and beyond) should be planned based on predicted decline of hemoglobin or MCA PSV>1.69 MOM.  No further IUTs are planned beyond 35 wk. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  41. 41.  <18 weeks GA when UV cannulation is not feasible.  Absorber via subdiaph.—thoracic lymphatics---circulation.  Less effective in hydropic fetuses.  16-20 G needle is used for entering abdomen between Umbilicus and U.B.  Calc. of amt of blood to prevent Intraperitoneal P> P in Umb V—Fetal demise  Bowman for infused blood volume [volume = (weeks’ gestation − 20) × 10 mL]. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  42. 42. POSTNATAL MANAGEMENT Rh ALLOIMMUNISED NEONATES
  43. 43.  TIMING: Uncomplicated- 37 weeks GA. - Persistent Foetal anaemia and IUT- after 34 weeks GA. - Emergency LSCS: Persistent foetal bradycardia after IUT.  PREPARDNESS: In presence of complicated hydrops -at least two neonatologists - a senior and skilled staff nurse -a well prepared resuscitation tray.  In infants not requiring any form of resuscitation, delayed cord clamping should be attempted. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  44. 44. Paediatrics, 2016. Population: 72 living born neonates followed after fetal anemia requiring in utero transfusion. Exposure: DCC at-least after 30 seconds. Comparison: 36 neonates LB req IUT not exposed to DCC. Outcome: Need for BT or ET after birth. Results: • Hemoglobin at birth was lower in neonates without DCC (10.2 vs 13.4 g/dL, P = .0003) • 7 (25%) neonates in non DCC vs 24 (70.6%) in DCC had no anemia at birth (P = .004). • The rate of transfusion was similar between the 2 groups. • Postnatal exchange transfusions were more likely performed in the group without DCC than in the group with DCC (47.2% vs 19.4%, P = .0124). • Delay between birth and first transfusion was higher in DCC (0 [0–13] vs 1 [0–21], P = .0274). • The maximum level of bilirubin, the rate of intensive phototherapy, and the total duration of phototherapy were similar in the 2 groups. Conclusion: This study highlights a significant benefit of DCC in anemia secondary to red blood cell alloimmunization with - Decreased postnatal exchange transfusion needs - An improvement in the hemoglobin level at birth - longer delay between birth and first transfusion with no severe hyperbilirubinemia.
  45. 45.  Whenever antenatal diagnosis of Rh alloimmunisation is present (i.e., Rh –ve mother and Rh + ve father with ICT positivity), soon after delivery 1–2 ml cord blood is collected which is sent for the following tests: A: Blood grouping, direct coombs test (antiglobin test), peripheral smear (for confirmation of diagnosis and estimation of hemolysis) B: Cord hematocrit, cord bilirubin estimation for guiding decision towards therapeutic interventions like exchange transfusion, partial exchange or phototherapy C: Cross matching of cord blood for subsequent transfusion and if needed, for arrangement of blood for double volume exchange transfusion Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  46. 46. Double volume exchange transfusion of Rh alloimmunised infants is performed in presence of atleast one of the following criteria: 1. At birth, with a cord total serum bilirubin of 5 mg/dl or more or cord hemoglobin of 10 mg/dl or less OR 2. Subsequently when serum bilirubin crossed the exchange transfusion threshold as per AAP chart (≥35 wk gestation) or Maisel’s chart /NICE guideline and rate of rise >0.5mg/dl/hr despite intensive phototherapy. OR 3. Any infant with hyperbilirubinemia and features of acute bilirubin induced neurological damage (poor feeding, hypotonia, poor suck and shrilled/high pitch cry) at any time during hospital stay Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  47. 47. AAP ET CURVES
  48. 48. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  49. 49.  For double volume exchange transfusion, the blood arranged is fresh irradiated O negative (in case there is history of IUT) or Rh –ve PRBC cross-matched against mother’s and infant’s blood and suspended in corresponding antibody negative plasma (in case, there is no IUT).  Transfusion Volume is calculated as: 2 X Wt in Kg x Blood Volume (Rawling Chart). (Usually it is nearly 80 ml/Kg for infants >2 Kg, 90 ml/Kg for infants 1–2 Kg and 100 ml/Kg for infants < 1 Kg birth weight; out of total calculated blood volume PRBC constitutes 70% and plasma constitutes rest 30% or roughly 2/3rd PRBC and 1/3rd plasma) Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  50. 50.  In presence of severe anemia (cord PCV ≤ 35%) with features of hydrops or cardiac decompensation, partial exchange transfusion is performed to increase hemoglobin before double volume exchange transfusion.  The volume of PRBC needed for partial exchange is calculated as: -Expected PCV−Cord PCV /PCV of the Blood bag x Blood volume of the baby, (The expected PCV is assumed to be 30%; PCV of Blood bag is assumed to be 70–80.) Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  51. 51.  For all cases of Rh alloimmunised infants, intensive phototherapy is initiated when serum bilirubin raises above the threshold of phototherapy as per AAP chart for term and near term infants (≥35 wk gestation). In preterm infants (<35 weeks for deciding phototherapy either Maisel’s chart, NICE guideline or Bili app can be used.  Phototherapy is continued as long as two consecutive values are below threshold of phototherapy.  It is the most commonly used, safe and effective intervention to prevent and treat severe hyperbilirubinemia.  the newer LED phototherapy machines are not associated with significant dehydration and most of these babies can be managed with oral feeds (breastfeeding or expressed breastmilk feeding by paladai). Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  52. 52. AAP PT CURVES NICE CHARTS FOR PT/ET IN NEONATES <35 WK
  53. 53.  IVIg acts by increasing IgG catabolism and blocking of IgG receptor on macrophage.  The practice for administering IVIg varies from center to center.  Overall, the evidence of use of IVIG is inconclusive.  The recommended dose is 0.5 g–1 g/Kg per dose, which can be repeated once after 12 h Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  54. 54. Population: Term and preterm infants with Rh or ABO (or both) incompatibility were included. Intervention: IVIg + phototherapy Comparison: phototherapy Conclusion • Based on all included studies, authors could make no conclusions on the benefit of IVIg in preventing ET or top‐up transfusion. • However, the two placebo‐controlled trials provided evidence of moderate quality that IVIg was ineffective in preventing ET or top‐up transfusion, and therefore routine use in alloimmune HDN should not be recommended. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  55. 55.  A common complication of Rh isoimmunised infants.  RF: intrauterine transfusion, postnatal double volume exchange transfusion or red cell transfusion  Mechanism: Marrow suppression or ongoing destruction of erythroid progenitors.  Incidence of late anemia in neonates with Rh isoimmunised infantsvaries from 71 to 83%.  A regular follow up is needed for symptomatic anemia in early infancy.  Role of erythropoietin still unclear.  In the presence of symptomatic late-onset anemia, these children are treated by simple PRBC transfusion. Sahoo T, Sahoo M, Gulla KM, Gupta M. Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management. Indian J Pediatr. 2020 Dec;87(12)
  56. 56.  Preimplantation genetic diagnosis with biopsy of the eight cell embryo is now available in cases of a heterozygous father, to predict the rh status of a future fetus Textbook of Neonatal and Perinatal Medicine, Fanaroff and Martin, 11 edition, 2018.
  57. 57.  A retrospective review of survival in fetuses treated for anemia caused by rh alloimmunization with intrauterine transfusions between 1988 and 1999 in the netherlands was performed in 208 pregnant women treated with 593 blood transfusions.  Overall survival rate was 86%.  Survival of the hydropic fetuses (78%) < 96% without hydrops.  Low survival if fetus hydropic and first iut <20 weeks (52%)  Survival in RH alloimmunization>kell alloimmunization (86 vs 58%). Textbook of Neonatal and Perinatal Medicine, Fanaroff and Martin, 11 edition, 2018.
  58. 58.  In a retrospective review of the short-term outcomes of 116 pregnancies that underwent 457 transfusions in Scotland from 1993-2004.  The survival rate of neonates from birth to discharge was 97.4%.  the rate of IUD was 2.3% for 1993-1998 and 0.8% for 1999-2004.  The majority of the neonates were delivered by cesarean or vaginally at 35 weeks and rate for Em LSCS was 6.5 %.  Roughly 33% of neonates required some type of respiratory support following delivery.  Sixteen of the neonates had an exchange transfusion following delivery, with the number of ET ranging from 1-4. Textbook of Neonatal and Perinatal Medicine, Fanaroff and Martin, 11 edition, 2018.
  59. 59. AJOG, 2012. OBJECTIVE: To determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT). STUDY DESIGN: Neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests, including the BSID, the WSIC, according to the children’s age. Primary outcome was the incidence of NDI defined as at least one of the following: cerebral palsy, severe developmental delay, bilateral deafness, and/or blindness. RESULTS: A total of 291 children were evaluated at a median age of 8.2 years (range, 2–17 years). Cerebral palsy was detected in 6 (2.1%) children, severe developmental delay in 9 (3.1%) children, and bilateral deafness in 3 (1.0%) children. The overall incidence of neurodevelopmental impairment was 4.8% (14/291). In a multivariate regression analysis severe hydrops was independently associated with neurodevelopmental impairment (odds ratio, 11.2; 95% confidence interval, 1.7–92.7). CONCLUSION: Incidence of neurodevelopmental impairment in children treated with intrauterine transfusion for fetal alloimmune anemia is low (4.8%). Prevention of fetal hydrops is most modifiable preventable risk factor.
  60. 60.  RH HDFN is an important avoidable cause of neonatal mortality and morbidity.  ABO incompatibility provides protection against RH HDFN.  Severity increases with subsequent pregnancies.  Anti D immunoglobulin prevents sensitization.  ICT titres >1:16 signify assessment of foetal anemia.  MCA PSV has reduced needs for invasive AF delta OD assessment.  IUT/IPT is treatment of choice if MCA PSV >1.5 MOM.  Short term and long term outcomes following IUT are good.  Presence of hydrops, requirement of IUT <18 weeks and Kell allo-iimm indicate poor prognosis.
  61. 61.  Delivery should occur in a tertiary centre.  Post-natal management requires neonatologist skilled in ICD.  Exchange transfusion guidelines immediately following del. Are based on expert opinions.  ET and PT for babies >35 weeks GA are decided by AAP charts.  ET and PT for babies < 35 weeks GA are decided by Maisel/NICE cutoffs.  PT reduces need for ET.  IVIG usage in babies with HDFN has no strong recommendation for or against.  SVET can be done in HDFN babies with significant anaemia.  Hypo regenerative anaemia is common in this population.
  62. 62. THANKS FOR PATIENT HEARING

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