History

Fact Explanation
Maternal and paternal blood group[2][1] There are five main types of rhesus antigens( D, C, c, E, e) in humans and the D antigen is the most immunogenic one. When blood passes from Rhesus(Rh) positive individual to Rh negative individual there is formation of anti D antibodies in Rh negative persons. When this happens in a Rh negative pregnant mother and during the subsequent pregnancies with a Rh positive foetus, maternal anti D antibodies can pass into foetal circulation and can cause destruction of the red blood cells. This condition is called Rh incompatibility. Therefore maternal blood group is very important and if the mother is Rh negative paternal blood group also important as if the father is Rh positive there is a chance of getting a Rh positive foetus( homozygous- 100% chance, heterozyhous- 50% chance).
Past history of potentially sensitization events[2] i.e. previous pregnancy with a Rh positive foetus, miscarriages, threatened abortions theraputic/ illegal termination of pregnancy, intra uterine deaths, ectopic pregnancy, antepartum haemorrhage, abdominal/ pelvic trauma, invasive obstetric procedures like amniocenteses/ cordocentesis/ chorionic villous sampling and theraputic procedures like blood transfusion, shunting, external cephalic version, caesarian section, manual removal of placenta. All these causes in previous pregnancy is important as it is useful in further management. At delivery, third stage of labour after separation of placenta is the commonest reason for foeto maternal transfusion.
Whether Rhogam( anti D antibodies) given during previous/ this pregnancy[2]. Rhogam should be given either during special procedures which carry a risk of getting sensitization( in previous/ this pregnancy) or during the antenatal period as prophylactic/ delivery of Rh positive baby in a previous pregnancy. Antenatal silent foeto-maternal transfusion can occur and this is not covered by post delivery Rogam administration. So the prophylactic administration is very important.
Any previous obstetric history of a swollen, ill fetus( hydrops fetalis), yellowish baby( haemolytic disease of the new born[3]), baby with cerebral palsy( kernicterus) or intrauterine death[2]. These can be a result of presence of D antibodies in maternal circulation. Antibodies from maternal circulation can enter( IgG antibodies can pass through placenta) to the fetal circulation during intra uterine period and form antigen- antibody complex wit fetal red blood cells(RBC) and this leads to extra vascular haemolysis. This causes mild to moderate anaemia, extramedullary haemopoesis due to excessive destruction of RBC causing hepatosplenomegaly and high output cardiac failure, scalp oedema, pulmonary oedema and ascites. Combination of these called hydrops fetalis). With the excessive destruction of RBC there is excessive production of billirubin. During intrauterine life this excessive billirubin is removed by maternal circulation but after birth this removal will not happen. This causes yellowish discoloration of the baby and in severe condition these billirubin can deposit in basal ganglia causing kernicterus.
Past history of blood transfusion in an emergency[2] Transfusion with uncross matched Rh positive blood in an emergency can cause sensitization.( exposure of Rh negative individual to Rh positive blood).
Large abdomen more than period of gestation Excessive amount of liquor causing polyhydramnios[2] can occur in presence of hydrops fetalis.
In this pregnancy history of sensitization events[2] i.e. like previous threatened abortion at early period, antepartum haemorrhage, abdominal/ pelvic trauma, invasive obstetric procedures like amniocenteses/ cordocentesis/ chorionic villous sampling and theraputic procedures like blood transfusion, external cephalic version, caesarian section. All these causes in this pregnancy are important as it can stimulate D antibody production in maternal circulation. But as IgM is produced in early stages and it can not crosses the placenta the foetus will not be affected. With time IgG is produced and this can affect the Rh positive foetus of the same pregnancy.
References
  1. SCHILD RL, HOCH J, PLATH H, GEISSEN C, FAHNENSTICH H, DAME C, HANSMANN M. Perinatal management of fetal hemolytic disease due to Rh incompatibility combined with fetal alloimmune thrombocytopenia due to HPA-5b incompatibility. Ultrasound Obstet Gynecol [online] 1999 Jul, 14(1):64-7 [viewed 26 August 2014] Available from: doi:10.1046/j.1469-0705.1999.14010064.x
  2. CACCIATORE A, RAPITI S, CARRARA S, CAVALIERE A, ERMITO S, DINATALE A, IMBRUGLIA L, RECUPERO S, LA GALIA T, PAPPALARDO EM, ACCARDI MC. Obstetric management in Rh alloimmunizated pregnancy J Prenat Med [online] 2009, 3(2):25-27 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279102
  3. MURRAY NA, ROBERTS IA. Haemolytic disease of the newborn Arch Dis Child Fetal Neonatal Ed [online] 2007 Mar, 92(2):F83-F88 [viewed 26 August 2014] Available from: doi:10.1136/adc.2005.076794

Examination

Fact Explanation
Obstetric examination of foetal lie, presentation, position, assessment of amount of liquor and foetal heart sounds Obstetric examination gives an overall idea about the foetal well being[1].
Foetal malpresentation Presentation will be important as in a breach presentation external cepalic version[1] is one of treatment option and in a Rh negative mother it should be done under Rhogam coverage.
Excessive of amount of liquor and presence of shiny abdomen wit fundus larger than dates. Excessive amount of liquor causing polyhydramnios[1] can occur in presence of hydrops fetalis.
Neonatal examination after birth, look for pallor Anaemia[1] can cause the baby pale with the excessive extravascular dystruction of foetal RBCs. This amaemia can vary mild to severe depending on the amount of D antibody exposure.
Look for evidence of hydrops fetalis[1] like generalized body swelling, scalp swelling, portal hypertension giving loud pulmonary heart sounds, pulmonary oedema giving lung signs, hepatosplenomegally, pericardial / pleural/ peritoneal effusion. Severe anaemia leads to heart failure and pulmonary hypertension causing fluid retention in foetal body cavities( pericardial, peritoneal and pleural) and severe foetal oedema. Progressive extramedullary haemopoiesis following excessive RBC dystruction causes hepatosplenomegally. As liver tries to compensate RBC production other functions will be impaired causing hypoalbuminaemia, falling oncotic pressure. Usually these babies dies in utero or soon after the birth.
Yellowish discoloration of the eyes and body[3] This is usually not present at birth. In haemolytic disease of the new born[1][2] with the time jaundice appears as maternal support is no longer present to handle the excessive billirubin level. The maternal IgG which entered to the babies circulation as a life span of 120 days. So the foetal haemolysis will continue upto 3-4 following birth.
Irritability, lethargy, refuse feeding, high pitch cry, involuntary movements, development of seizures later of the life development delay and mental retardation. These features are due to kernicterus[1][2] which is an encephalopathy resulting from deposition of the unconjugated billirubin in basal ganglia and nuclei in brain stem. With the birth as mentioned above baby's biliirubin level goes up as the conjugation is absent due to immature liver function. In neonates until about 10 days of life the blood brain barrier is not functioning properly. So the fat soluble unconjugated bllirubin easily enters to the brain and deposites. As this is neurotoxic this leads to permanent brain damage giving above signs.
Look for evidence of abdominal trauma like bruising during antenatal period[1] Abdominal trauma can leads to development of Rh incompatibility
PV bleeding Antenatal haemarrage[1] is another predisposing factor for Rh incompatibility
Colour of liquor Yellowish, bile stained liquor gives an alarm to suspect Rh incompatibility.
References
  1. CACCIATORE A, RAPITI S, CARRARA S, CAVALIERE A, ERMITO S, DINATALE A, IMBRUGLIA L, RECUPERO S, LA GALIA T, PAPPALARDO EM, ACCARDI MC. Obstetric management in Rh alloimmunizated pregnancy J Prenat Med [online] 2009, 3(2):25-27 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279102
  2. GERRARD JW. Kernicterus in Prematures Can Med Assoc J [online] 1957 Oct 1, 77(7):661-663 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1824218
  3. MURRAY NA, ROBERTS IA. Haemolytic disease of the newborn Arch Dis Child Fetal Neonatal Ed [online] 2007 Mar, 92(2):F83-F88 [viewed 26 August 2014] Available from: doi:10.1136/adc.2005.076794

Differential Diagnoses

Fact Explanation
ABO blood group isoimmunization[1] Isoimmunization occurs when a mother with 'O' blood group conceives a foetus with 'A'. 'B' or 'AB'. As the mother already has antibodies against 'A' and 'B' antigens specific sensitization is not needed. Even the first baby is at a risk.
Kell system antibodies[2] Kell blood group system classify human blood based on the presence on the surfaces of red blood cells of various antigens encoded by the KEL gene. Antibodies are generated against antigens in the Kell system causing dystruction of red blood cells. After the Rh and ABO systems, the Kell system is the third most common blood group to cause these antigen-antibody reactions.
Duffy system antibodies (rare)[2] This also a classification of RBCs depending on surafce Duffy antigen. This also gives a similer picture but rare.
Anaemia Anaemia can cause heart failure giving features of hydrops foetalis[3].
Cardiac failure from congenital heart defects. Severe congenital heart diseases also can end up in hydrops foetalis[3].
References
  1. COHEN BH. ABO and Rh incompatibility. II. Is there a dual interaction in combined ABO and Rh incompatibility? Am J Hum Genet [online] 1970 Jul, 22(4):441-452 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1706587
  2. REVERBERI R, REVERBERI L. Factors affecting the antigen-antibody reaction Blood Transfus [online] 2007 Nov, 5(4):227-240 [viewed 26 August 2014] Available from: doi:10.2450/2007.0047-07
  3. TRAINOR B, TUBMAN R. The Emerging Pattern Of Hydrops Fetalis - Incidence, aetiology and management Ulster Med J [online] 2006 Sep, 75(3):185-186 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1891778

Investigations - for Diagnosis

Fact Explanation
Antenatal diangosis[1] of maternal and paternal blood groups and Rh ststus As this Rh incompatibility only occurs in Rh negative mothers maternal blood group and Rh state is very important and if the mother is Rh negative paternal blood group and Rh state also important as if the father is Rh positive there is a chance of getting a Rh positive foetus( homozygous- 100% chance, heterozyhous- 50% chance).
Check anti D antibodies by direct and indirect tests[1] Screening for the presence of unexplained antibodies done in antenatal period in a R negative mother. First test is being done at booking visit and then repeat at 28, 32 and 36 weeks. If the mother is having D antibodies, regular antibody level checking should be done to decide the management plan. In direct method, directly calculate the antibody titer in maternal circulation and it is a quantitative method of antibody measurement. Indirect method is done using indirect Coomb's test using a ultrasound guided amnoiocentesis.
Kleihauer- Betke test[2] Th determine the amount of faeto-maternal haemorrhage in a possible sensitizing event or following delivery. This helps in determine the dose of Rhogam.
Ultrasonography and doppler studies[1] Antenatal ultrasonographic examination will help in assessing the amount of liquor in a suspected polyhyramnios and assess the foetus to identify presence of hydrops fetalis with scalp and body swelling with pericardial/ peritoneal and pleural effusion. Measuring ductus venosus blood flow and peak systolic velocity of the fetal middle cerebral artery will useful in assessing the degree of anaemia.
Following delivery take cord blood for blood grouping and Rh typing, serum haemoglobin level, serum billirubin, direct coombs test and reticulocyte conunt[1]. Depending on the results further management of the neonate will be decided with a paediatrician.
Billirubin in amniotic fluid[3] This is being done in mothers who have been sensitized to assess the foetal condition. Sample is taken by amniocentesis and measured using spectropotometer and plot in Liley's chart or other relavent chart.
References
  1. CACCIATORE A, RAPITI S, CARRARA S, CAVALIERE A, ERMITO S, DINATALE A, IMBRUGLIA L, RECUPERO S, LA GALIA T, PAPPALARDO EM, ACCARDI MC. Obstetric management in Rh alloimmunizated pregnancy J Prenat Med [online] 2009, 3(2):25-27 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279102
  2. REID MM. Flow cytometry and Kleihauer tests. J Clin Pathol [online] 1996 Apr, 49(4):354 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC500469
  3. MORRIS ED, MURRAY J, RUTHVEN CR. Liquor bilirubin levels in normal pregnancy: a basis for accurate prediction of haemolytic disease. Br Med J [online] 1967 May 6, 2(5548):352-354 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1841712

Investigations - Fitness for Management

Fact Explanation
Cord blood for blood grouping and Rh typing, serum haemoglobin level, serum billirubin, direct coombs test and reticulocyte conunt. These tests will assess the fitness of the baby and level of the impact due to Rh incompatibility[1].
References
  1. CACCIATORE A, RAPITI S, CARRARA S, CAVALIERE A, ERMITO S, DINATALE A, IMBRUGLIA L, RECUPERO S, LA GALIA T, PAPPALARDO EM, ACCARDI MC. Obstetric management in Rh alloimmunizated pregnancy J Prenat Med [online] 2009, 3(2):25-27 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279102

Investigations - Followup

Fact Explanation
Antenatal period direct antibody test[1] This is useful in assessing the antibody titre in a mother with D antibodies. Depending on the antibody level outcome will be different as more antibodies will cause more destruction of foetal RBCs.
Ultrasonography and doppler[1] In a case of diagnosed D antibody level above the critical titre serial ultrasound scans and doppler should be performed to see any evidence of foetal hydrops. Measuring peak systolic velocity of foetal middle cerebral artery is useful in follow up. In a presence of D antibodies in mother's circulation depending on the antibody titre foetal anaemia can be measured using peak systolic velocity of foetal middle cerebral artery. If antibody level is positive but less than 10 IU test should be repeat in every 4 weeks and if the level is more than 10 IU test should be repeat weakly.
billirubin level in amniotic fluid in antenatal perion and serum billirubin after delivery[2]. This is useful in following up a affected baby with Rh incompatibility. Measuring billirubin and plotting on the Liley chart/ Freda chart gives guidance on further management.
References
  1. CACCIATORE A, RAPITI S, CARRARA S, CAVALIERE A, ERMITO S, DINATALE A, IMBRUGLIA L, RECUPERO S, LA GALIA T, PAPPALARDO EM, ACCARDI MC. Obstetric management in Rh alloimmunizated pregnancy J Prenat Med [online] 2009, 3(2):25-27 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279102
  2. MORRIS ED, MURRAY J, RUTHVEN CR. Liquor bilirubin levels in normal pregnancy: a basis for accurate prediction of haemolytic disease. Br Med J [online] 1967 May 6, 2(5548):352-354 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1841712

Investigations - Screening/Staging

Fact Explanation
Check anti D antibodies by direct and indirect tests[1] Screening for the presence of unexplained antibodies done in antenatal period in a R negative mother. First test is being done at booking visit and then repeat at 28, 32 and 36 weeks using direct/ indirect antibody checking.
Ultrasonography[1] In a case of diagnosed D antibody level above the critical titre serial ultrasound scans should be performed to screen the development of foetal hydrops.
Kleihauer-Betke test[3] This can be useful in screening for the presence of foeto-maternal haemorrhage.
Following delivery take cord blood for blood grouping and Rh typing, serum haemoglobin level, serum billirubin, direct coombs test and reticulocyte conunt[1]. This is also useful in screening the child following delivery for the presence of complications.
Serum billirubin level measurement and plotting on the Liley chart/ Freda chart [2] This is useful in assessing the stage of severity caused by the billirubin level.
References
  1. CACCIATORE A, RAPITI S, CARRARA S, CAVALIERE A, ERMITO S, DINATALE A, IMBRUGLIA L, RECUPERO S, LA GALIA T, PAPPALARDO EM, ACCARDI MC. Obstetric management in Rh alloimmunizated pregnancy J Prenat Med [online] 2009, 3(2):25-27 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279102
  2. MORRIS ED, MURRAY J, RUTHVEN CR. Liquor bilirubin levels in normal pregnancy: a basis for accurate prediction of haemolytic disease. Br Med J [online] 1967 May 6, 2(5548):352-354 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1841712
  3. REID MM. Flow cytometry and Kleihauer tests. J Clin Pathol [online] 1996 Apr, 49(4):354 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC500469

Management - General Measures

Fact Explanation
Health education [1] This is important pre-conceptionally as well regarding the possibility of getting this condition and advice early booking visit. During antenatal period susceptible parents need to be educated regarding the high risk condition, complications, treatment options available.
Multidisciplinary team management[1] Obstetrician and Gynaecologist , foetologist neonatologist, paediatrician, haematologist, transfusion specialist should be mainly included in the team. obstetrition and Gynaecologist can manage the susceptible mother from pre conceptional period until delivery. Foetologist can take care of the baby during intrauterine perion and can monitor for possible complications. Neonatologist/ Paediatrition can continue the care with the delivery of the baby. Haematologist can join the team by blood investigations like grouping and cross matchinhg and during the transfusions. Transfusion specilist will take the responsibility in intrauterine and exchange transfusions.
Family planning advice If the mother is sensitized with high levels of D antibodies, family planning advice should be given with the delivery of this baby, this is very important if the father is homozygous for Rh gene as there is a chance of getting a Rh positive baby is 100%.
References
  1. CACCIATORE A, RAPITI S, CARRARA S, CAVALIERE A, ERMITO S, DINATALE A, IMBRUGLIA L, RECUPERO S, LA GALIA T, PAPPALARDO EM, ACCARDI MC. Obstetric management in Rh alloimmunizated pregnancy J Prenat Med [online] 2009, 3(2):25-27 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279102

Management - Specific Treatments

Fact Explanation
Prevention by immunopropylaxis[2] following delivery and in other susceptible situations Screening for the presence of unexplained antibodies done in antenatal period in a R negative mother. First test is being done at booking visit and then repeat at 28, 32 and 36 weeks. If mother is not sensitize previously Rh negative mothers should be given anti D antibodies 500 IU intra muscularly at 28 and 32 weeks of gestation as antenatal prophylaxis. Other than that immunoprophylaxis should be given in susceptible situations with in 2 hours[1]. Eg: In ERPC, Ectopic pregnancy, invasive procedures Rhogam should be give irrespective of period of gestation. In threaten/ complete abortion if occur more then 12 weeks spontaneously or less then 12 weeks with interventions(medical or surgical) prophylaxis is needed while less then 12 weeks with out any interventions no need of prophylaxis. Kleihauer test is determine the presence and amount of foeto-maternal blood transfusion.Depending on the amount of blood entered to foetal circulation, the administrating Rhogam dose will be decided. At least 500 IU should be given if amount less or equal to 4ml. 125 IU for each 1 ml more then that should also be given. Following delivery rhogam should be given to all Rh negative mothers intramuscularly with in 72 hours.
If the mother has been sensitized previously, during antenatal period check paternal blood group and and can go for karyotyping[3]. Antibody levels and foetal monitoring should be monitored regularly[4]. Father's blood group is important; if father is Rh positive there is a chance of being baby's blood group also being positive. Karyotyping can be done in a Rh positive father as the chance of being a Rh positive foetus is 100% if homozygous for Rh gene while 50% chance if heterozygous. If Anti D titre is more than 1:16 or more than 4 IU of if the titre progressively rising this should be consider as significant and serial monitoring of foetus should be done at least 2 weekly with ultrasonography and doppler. Especially look for evidence of hydrops foetalis. Assessing the billirubin level in amniotic fluid can also useful in assessing the foetal complications. Measuring ductus venosus blood flow and peak systolic velocity of the fetal middle cerebral artery can be done using USS and doppler studies.This is useful to assess the degree of anaemia.
During delivery timing is important, close monitoring should be done, mode of delivery should be determined by the doctor, if premature prophylactic dexamethasone should be considered, cord blood should be send for investigations and cord should clamp early and should cut away from the umbilicus. In a affected baby timing of delivery should be balanced between delivering preterm with complications of prematurity and delivering at term with complications of hydrops fetalis and fetal death. If fetus severly affected with fetal hydrops delivery should be done as soon as early. When period of gestation is less than 34 weeks 2 doses of IM dexametnasone injection should be given to induce lung maturity. Also if less than 34 weeks elective caesarian section is recommended. If the antibody levels are not too high and foetus not seem to be severely affected, with close regular monitoring, pregnancy can be continued until term and baby can deliver vaginally. In all cases of rhesus incompatibility, the delivery should be done in a tertiary care hospital with neonatal resuscitation facilities and premature baby unit. At the time of delivery a neonatologist/ paediatric house officer should be present. Cord of the baby should be clam early than usual after delivery to minimize maternal antibody crossing to the foetus. And it should be cut away from the umbilicus as it is helpful in exchange transfusion[5]. After cutting the cord maternal end should not be clamped and should drain manually to remove any foetal blood which can stay in the cord, and mixing to maternal circulation causing sensitization. Following delivery take cord blood for blood grouping and Rh typing, serum haemoglobin level, serum billirubin, direct coombs test and reticulocyte conunt.T
Intra uterine management[6] of the baby of a mother with D antibodies If the antibody level is low in titre, not rising with regular monitoring and not causing complications to the foetus, pregnancy can continue under close supervision. Following delivery, neonate should be closely monitored and examined for haemolytic disease of the newborn. According to the billirubin level phototherapy/ exchange transfusion can be considered[1]. But if the antibody level is raising with evidence of foetal hydrops decision should be done to deliver the baby immediately or if possible intrauterine transfusion can be performed. If baby delivered, exchange transfusion can be consider according to the serum billirubin and haematocrit levels. In here irradicated, rhesus negative, CMV negative, pack cells are being used and transfusion is being done via umbilical vein at cord insertion or into hepatic vein.
References
  1. SCHILD RL, HOCH J, PLATH H, GEISSEN C, FAHNENSTICH H, DAME C, HANSMANN M. Perinatal management of fetal hemolytic disease due to Rh incompatibility combined with fetal alloimmune thrombocytopenia due to HPA-5b incompatibility. Ultrasound Obstet Gynecol [online] 1999 Jul, 14(1):64-7 [viewed 26 August 2014] Available from: doi:10.1046/j.1469-0705.1999.14010064.x
  2. LIUMBRUNO GM, D’ALESSANDRO A, REA F, PICCININI V, CATALANO L, CALIZZANI G, PUPELLA S, GRAZZINI G. The role of antenatal immunoprophylaxis in the prevention of maternal-foetal anti-Rh(D) alloimmunisation Blood Transfus [online] 2010 Jan, 8(1):8-16 [viewed 26 August 2014] Available from: doi:10.2450/2009.0108-09
  3. CACCIATORE A, RAPITI S, CARRARA S, CAVALIERE A, ERMITO S, DINATALE A, IMBRUGLIA L, RECUPERO S, LA GALIA T, PAPPALARDO EM, ACCARDI MC. Obstetric management in Rh alloimmunizated pregnancy J Prenat Med [online] 2009, 3(2):25-27 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279102
  4. HASSANZADEH-NAZARABADI M, SHEKOUHI S, SEIF N. The Incidence of Spontaneous Abortion in Mothers with Blood Group O Compared with other Blood Types Int J Mol Cell Med [online] 2012, 1(2):99-104 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920496
  5. MURRAY NA, ROBERTS IA. Haemolytic disease of the newborn Arch Dis Child Fetal Neonatal Ed [online] 2007 Mar, 92(2):F83-F88 [viewed 26 August 2014] Available from: doi:10.1136/adc.2005.076794
  6. CACCIATORE A, RAPITI S, CARRARA S, CAVALIERE A, ERMITO S, DINATALE A, IMBRUGLIA L, RECUPERO S, LA GALIA T, PAPPALARDO EM, ACCARDI MC. Obstetric management in Rh alloimmunizated pregnancy J Prenat Med [online] 2009, 3(2):25-27 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279102