The first pregnancy, the one that induces maternal sensitivity evolves normally. Ulterior pregnancies are characterized by hemolytic disease in the fetus, leading to anemia, immature fetal red blood cells released into circulation, hypoalbuminemia caused by hepatic dysfunction, high-output heart failure and ultimately fetal death. The amniotic fluid is rich in bilirubin and has a yellowish color. Fetal echography shows evidence of hydrops: pericardial and pleural effusions and ascites. Hydrops does not occur until the hemoglobin level drops to 4 g/dl. The biophysical profile becomes worse as the disease progresses. The severity of the hemolytic disease can be predicted using Liley diagrams [1].

If the disease is not as severe and the fetus survives, the newborn develops icterus during the first day of life, that may be as severe as to induce kernicterus. Also, the newborn will be anemic and pale and present splenomegaly and hepatomegaly, caused by extramedullary hematopoiesis. Portal hypertension has the same cause.

The placenta will be enlarged, and transplacental transport is compromised by the edema.

The mother is asymptomatic during the pregnancy and after delivery.

• Anemia

  Fetal erythroblastosis is a condition that occurs when the fetus and the mother are incompatible regarding the blood group, leading to fetal hemolytic anemia. [symptoma.com]

  They can range from mild anemia and jaundice to fetal death in utero. [medindia.net]

  During that time period, delivery may be recommended if there is continuing evidence of severe fetal anemia (based on MCA blood flow). The woman may continue to term delivery if there is no evidence of severe fetal anemia based on MCA blood flow. [msdmanuals.com]

• Pallor

  Diagnostic findings include jaundice (yellow amniotic fluid, yellow vermix, yellow skin), pallor and hepatosplenomegaly. Kernicterus (bilirubin encephalopathy) is a serious risk and hypoglycaemia is common. [patient.info]

  SignsMother• Polyhydramnios in mother.Baby• Pallor ++• Hepatosplenomegaly – signifying active haemolysis• Jaundice MAY NOT be there at birth – since the mother’s kidney will take out the excess bilirubin – Jaundice develops in the next few hours of delivery [de.slideshare.net]

  There were no further concerns until day 12 of life when she presented with a short history of poor feeding, lethargy and pallor. The infant was pale, tachypnoeic and tachycardic with hepatosplenomegaly. [doi.org]

  Untreated profound anemia can cause high-output heart failure, with pallor, enlarged liver and/or spleen, generalized swelling, and respiratory distress. [en.wikipedia.org]

• Nightmare

  We are fully aware that you are kind of having a nightmare because of the weird name you see on the title. Guess what? Even, we had the same helpless look on our faces for the first time. [factslegend.org]

• Tachycardia

  Hydrops from reciprocating atrioventricular tachycardia in a 27-week fetus requiring quinidine for conversion. Obstet. Gynecol. 66 :29S–33S, 1985. [link.springer.com]

  Your baby may have the following symptoms: Yellow coloring of the skin and whites of the eyes (jaundice) Pale-coloring because of anemia Fast heart rate (tachycardia) Fast breathing (tachypnea) Lack of energy Swelling under the skin Large abdomen The [cedars-sinai.edu]

  Affected animals show lethargy, recumbency, tachycardia, and progressive icterus of eye and mouth mucosae, which rapidly leads to death. The condition is also described in newborn pigs and other animals [vjahnavi57.blogspot.com]

• Jaundice

  They can range from mild anemia and jaundice to fetal death in utero. [medindia.net]

  […] when the immune system of an Rh-negative mother produces antibodies to an antigen in the blood of an Rh-positive fetus which cross the placenta and destroy fetal erythrocytes and that is characterized by an increase in circulating erythroblasts and by jaundice [merriam-webster.com]

  […] system) with an Rh positive fetus whose ABO blood… … Universalium erythroblastosis fetalis — erythroblastosis fe·ta·lis fi tal əs n a hemolytic disease of the fetus and newborn that is characterized by an increase in circulating erythroblasts and by jaundice [dic.academic.ru]

  Abstract Jaundice occurs in most newborn infants. [doi.org]

• Neonatal Jaundice

  The newborn can present with a number of features including: clinical evidence of a fetal anemia neonatal jaundice neonatal hepatosplenomegaly generalized body edema The condition usually results from a feto-maternal blood group incompatibility such as [radiopaedia.org]

  After birth, however, the immature neonatal liver is not capable of handling a high bilirubin load and this can result in severe neonatal jaundice. [patient.info]

  A controlled trial of high-intensity double-surface phototherapy on a fluid bed versus conventional phototherapy in neonatal jaundice. Pediatrics. 1995 ; 95 : 914 – 916 9. ↵ Tan KL. Phototherapy for neonatal jaundice. [doi.org]

• Hepatomegaly

  Also, the newborn will be anemic and pale and present splenomegaly and hepatomegaly, caused by extramedullary hematopoiesis. Portal hypertension has the same cause. [symptoma.com]

  […] destruction of the red blood corpuscles is responsible for the morbus haemolyticus neonatorum (fetal erythroblastosis) with the following symptoms: anemia (due to the hemolysis) splenomegaly (location of the macrophages that destroy the erythrocytes) hepatomegaly [embryology.ch]

• Eye Swelling

  Jaundice or the yellowish discoloration of the baby’s skin or the whites of the eyes Swelling of the baby’s body Purple blotches on the baby’s skin Small brown or red spots Diagnosis The precise diagnosis of erythroblastosis fetalis will vary if there [medicalbite.com]

• Hydrops Fetalis

  Other symptoms include high levels of insulin and low blood sugar, as well as a condition called hydrops fetalis. Hydrops fetalis causes fluids to accumulate within the baby's body, making it look swollen. [faqs.org]

  Hydrops fetalis and anemia can also contribute to heart problems. Diagnosis Erythroblastosis fetalis can be predicted before birth by determining the mother's blood type. [medical-dictionary.thefreedictionary.com]

  Nonimmunologic hydrops fetalis. Amer. J. Obstet. Gynecol. 131 :586–587, 1978. [link.springer.com]

  The remaining 25% will have severe disease and either be stillborn or have hydrops fetalis. [patient.info]

  Non-immune hydrops fetalis can be associated with numerous and various disorders... [readbyqxmd.com]

• Dyslexia

  […] undeveloped blood brain barriers and much of the mercury goes to the brain, resulting in significant adverse neurological effects, including autism, persuasive developmental disorders (PDD), Asperger's syndrome, obsessive compulsive disorder (OCD), dyslexia [moondragon.org]

• Compulsive Disorder

  Children have undeveloped blood brain barriers and much of the mercury goes to the brain, resulting in significant adverse neurological effects, including autism, persuasive developmental disorders (PDD), Asperger's syndrome, obsessive compulsive disorder [moondragon.org]

• Grunting

  Signs and symptoms include: (1) Jaundice – usually not present at birth but may appear as soon as 30 minutes later or within 24 hours after birth. (2) Edema. (3) Petechiae. (4) Grunting respirations. (5) Neurologic unresponsiveness. (6) Bile-stained umbilical [brooksidepress.org]

Usual prenatal consultations establish which pregnancies are at risk, namely those of Rh negative women impregnated by Rh positive men. In selected cases, blood workup will include blood type, Coombs test [2], Rh and anti-Rh antibody testing in the mother and blood type and Rh testing in the father [3]. In the mother, measurements are to be repeated every 2 weeks after 20 weeks of gestation.

The fetus is to be monitored by ultrasound regarding middle cerebral blood flow in order to determine if high output heart failure, an indicator of anemia, is present. If so, the fetal Rh should be determined by umbilical blood sampling.

Fetal Rh genotype can be tested using fetal cells or cell-free deoxyribonucleic acid in maternal circulation [4] [5] by polymerase chain reaction.

The newborn will have increased unconjugated bilirubin levels, that are rapidly rising and manifesting as icterus during the first days of life. Sometimes conjugated bilirubin levels are also high, due to hepatic dysfunction. He or she will be anemic, with increased reticulocyte count, anisocytosis, spherocytosis, and young (nucleated, immature) red blood cells released into circulation. Coombs test is positive [6]. Schistocytes, as a sign of disseminated intravascular coagulation and burr cells, are present, as well as neutropenia and thrombocytopenia. Other associated findings include hypoglycemia [7], hypokalemia or hyperkalemia and hypocalcemia. High carboxyhemoglobin levels also point to the presence of hemolysis [8].

Also, the newborn will have peripheral edema and other liquid accumulations, like ascites, pleurisy, and pericardial effusion.

• Anisocytosis

  He or she will be anemic, with increased reticulocyte count, anisocytosis, spherocytosis, and young (nucleated, immature) red blood cells released into circulation. Coombs test is positive. [symptoma.com]

  Increased nucleated red blood cells (RBCs), reticulocytosis, polychromasia, anisocytosis, spherocytes, and cell fragmentation The reticulocyte count can be as high as 40% in patients without intrauterine intervention. [emedicine.medscape.com]

To present intensive intrauterine treatment of recurrent early onset fetal erythroblastosis due to anti-M alloimmunization. A 33-year-old woman, gravid 3, para 1, had anti-M IgG antibody, which caused alloimmunization of her previous pregnancies. [ncbi.nlm.nih.gov]

The only treatment for mirror syndrome is immediate delivery of the baby How do you treat hydrops fetalis? Treatment for hydrops depends on the determined cause, if any. [chw.org]

7, 8 In the neonatal period, IVIG has been used for the treatment of alloimmune thrombocytopenia, 9 as an additional treatment in neonatal infections, 10 and in the rare cases of neonatal Kawasaki disease. 11 As a progression from its use for the treatment [doi.org]

Read this information to clarify your doubts on its treatment. Fetal blood transfusion is the usual treatment for infants with erythroblastosis fetalis. This can be performed intrauterine but only by a specialist. [howshealth.com]

It is important to remember the complication of hydrops has a poor prognosis of survival except for those cases that have a definite cause with established fetal treatment. What is my baby's long-term prognosis? Long-term prognosis is guarded. [chw.org]

Erythroblastosis Fetalis Prognosis The prognosis of erythroblastosis fetalis varies widely. Death may occur even before or after birth. But for most cases treatment is successful and babies do not develop life threatening complications. [howshealth.com]

(MCA) Doppler time average mean velocity (TAMV): may occur before precipitation of fetal hydrops 1 increase in fetal middle cerebral arterial (MCA) Doppler peak systolic velocity (PSV): may occur before precipitation of fetal hydrops 2 Treatment and prognosis [radiopaedia.org]

In the past two and a half years spectrophotometric examination of amniotic fluid has allowed a more accurate prognosis of degree of disease in the fetus,. .. Funding and Disclosures We are indebted to Dr. [nejm.org]

The timely diagnosis by ultrasound and intravascular transfusion improves the prognosis. OBJECTIVE: to evaluate the increase in hemoglobin in the fetus and correlate the red cell transfusion volume with elevation of hemoglobin and perinatal outcome. [readbyqxmd.com]

Definition / general Nucleated fetal red blood cells (nRBCs) are common in preterm placentas but are an abnormal finding in placentas at term Etiology nRBCs reflect a response to fetal hypoxia or anemia due to a variety of causes including uteroplacental [pathologyoutlines.com]

Etiology, pathogenesis Pre-requisite of Rh isoimmunization: Rh- mother and Rh+ fetus. The mother is sensitized to Rh antigen by Rh+ fetal erythrocytes that reach the maternal circulation. [atlases.muni.cz]

Etiology/Pathophysiology: Caused by blood group incompatibilities between fetal and maternal erythrocytes. The mother has been previously exposed to heterotypic fetal erythrocytes and developed antibodies to them. [virtualpediatrichospital.org]

Olaniyan and Kevin Aghatise, Evaluation of Some Etiological Factors of Haemolytic Disease of the New Born in Ile-Ife, Open Journal of Clinical Diagnostics, 04, 01, (5), (2014). [doi.org]

Etiology and Pathophysiology Alloimmunization occurs when maternal blood is exposed to an antigen that is not present on her RBCs; can occur with as little as 1 )[ C ] Can occur during RBC transfusion or fetomaternal bleeding (abortion, ectopic pregnancy [unboundmedicine.com]

System(s) affected: cardiovascular, hematologic, lymphatic, immunologic, nervous Synonym(s): erythroblastosis neonatorum; hemolytic disease of the fetus and newborn (HDFN); congenital anemia of the newborn; immune hydrops fetalis Epidemiology Predominant [unboundmedicine.com]

Summary Epidemiology The incidence has been estimated at 1/800 to 1/1 000 live births. Clinical description NAIT has been considered to be the platelet counterpart of Rh Haemolytic Disease of the Newborn (RHD). [orpha.net]

Epidemiology The incidence of haemolytic disease of the newborn (HDN) depends on the proportion of the population who are RhD negative. [patient.info]

(This information according to Epidemiology of Rh Hemolytic Disease of the Newborn in the United States JAMA. 1991.1 265(24): 3270- 3274). Research, Charities, and Support Groups HDN was first identified in 1932 at Children’s Hospital Boston by Dr. [pathologyproject.wordpress.com]

Etiology/Pathophysiology: Caused by blood group incompatibilities between fetal and maternal erythrocytes. The mother has been previously exposed to heterotypic fetal erythrocytes and developed antibodies to them. [virtualpediatrichospital.org]

The clinical consequences of HTRs are triggered via several pathophysiological pathways like formation of anaphylatoxins, release of cytokines causing a systemic inflammatory response syndrome, activation of the kinin system, the intrinsic clotting cascade [doi.org]

Etiology and Pathophysiology Alloimmunization occurs when maternal blood is exposed to an antigen that is not present on her RBCs; can occur with as little as 1 )[ C ] Can occur during RBC transfusion or fetomaternal bleeding (abortion, ectopic pregnancy [unboundmedicine.com]

It includes a review of historical perspective, pathophysiology of RBC antigen iso-sensitization, hydrops fetalis, clinical presentation, and management of HDN. [omicsonline.org]

Acute hemolytic transfusion reaction, a paradigm of the systemic inflammatory response: new insights into pathophysiology and treatment. Transfusion. 1995 Jun. 35(6):513-20. [Medline]. Davenport RD. [emedicine.medscape.com]

Erythroblastosis Fetalis Prevention Erythroblastosis Fetalis is very preventable. Erythroblastosis Fetalis prevention is easy. Today, nearly all women with Rh-negative blood are identified in early pregnancy through blood tests. [healthncare.info]

Prevention- Rh immune globulin 14. • Rh immune globulin contains antibodies to the Rh factor in blood.• The antibodies come from mother’s blood stream had been sensitized to Rh factor.• Giving these Rh antibodies to an Rh-Negative pregnant woman prevent [de.slideshare.net]

Be cautious and vigilant all the time after all prevention is still better than cure. [howshealth.com]

[…] immature cells (erythroblasts) Preventing Erythroblastosis Fetalis RhoGram is admininstered to Rh- mothers at delivery. RhoGam prevents formation of Anti-Rh antibody in mother's bloodstream. [quizlet.com]

Prevention Erythroblastosis fetalis is a preventable condition. A medication called Rh immunoglobulin (Rhig), also known as RhoGAM, can help prevent Rh sensitization. [medicalnewstoday.com]

1. Liley AW. Liquor amnii analysis in management of pregnancy complicated by rhesus immunization. Am J Obstet Gynecol. 1961;82:1359-1371.
2. Romano EL, Hughes-Jones NC, Mollison PL. Direct antiglobulin reaction in ABO-haemolytic disease of the newborn. Br Med J. 1973;1(852):524-526.
3. Pirelli KJ, Pietz BC, Johnson ST, et al. Molecular determination of RHD zygosity: predicting risk of hemolytic disease of the fetus and newborn related to anti-D. Prenat Diagn. 2010;30(12-13):1207-1212.
4. Bianchi DW, Avent ND, Costa JM, et al. Noninvasive prenatal diagnosis of fetal Rhesus D: ready for Prime(r) Time. Obstet Gynecol. 2005;106(4):841-844.
5. Rouillac-Le Sciellour C, Puillandre P, Gillot R, et al. Large-scale pre-diagnosis study of fetal RHD genotyping by PCR on plasma DNA from RhD-negative pregnant women. Mol Diagn. 2004;8(1):23-31.
6. Murray NA, Roberts IA. Haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed. 2007;92(2):F83-F88.
7. Vidnes J, Finne H. Immunoreactive insulin in amniotic fluid from Rh-immunized women. Biol Neonate. 1977;31(1-2):1-6.
8. Lozar-Krivec J, Bratanic B, Paro-Panjan D. The role of carboxyhemoglobin measured with CO-oximetry in the detection of hemolysis in newborns with ABO alloimmunization. J Matern Fetal Neonatal Med. 2016;29(3):452-456.