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

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

  […] instance of disease 1 reference stated in Disease Ontology release 2019-05-13 retrieved 15 May 2019 Disease Ontology ID DOID:1098 subclass of neonatal alloimmune disease 0 references microcytic anemia 1 reference stated in Disease Ontology release 2019 [wikidata.org]

  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

  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]

  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]

  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]

• Intravenous Drugs

  Intravenous drug abuse in young women has been reported as the most common cause of Rh isoimmunization today. [atlases.muni.cz]

• 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

  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]

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

  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]

  These may include the following problems: During pregnancy Hydrops fetalis Mild anemia Jaundice Hyperbilirubinemia Severe anemia accompanied with enlargement of the spleen and liver After pregnancy Severe jaundice Kernicterus Severe hyperbilirubinemia [medicalbite.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]

  The excess amounts of bilirubin circulating in the newborn's body will lead to jaundice, where the skin and eye whites of the infant turn yellow. [medicalnewstoday.com]

• Neonatal Jaundice

  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]

  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]

  One type in particular is associated with neonatal jaundice and circulation of bilirubin in blood at high concentration due to increased hemolysis in conditions such as erythroblastosis fetalis, septicemia, biliary atresia, and other causes of hyperbilirubinemia [readbyqxmd.com]

  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. [pediatrics.aappublications.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

  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 is a blood group present or incompatibility of blood type. [medicalbite.com]

• Hydrops Fetalis

  Antenatal classification of hydrops fetalis. Obstet. Gynecol. 79 :256–259, 1992. [link.springer.com]

  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]

  Other symptoms that may be present include high levels of insulin and low blood sugar, as well as a condition called hydrops fetalis. [medical-dictionary.thefreedictionary.com]

  Before the initial transfusion, 11 of 43 fetuses had some degree of hydrops fetalis, and hemoglobin values ranged between 1.5 and 10.7 g/dL. [ncbi.nlm.nih.gov]

  Fetalis) (Hemolytic Disease of the Newborn) Paediapaedia: Neonatal Chest Diseases Erythroblastosis Fetalis (Immune Hydrops Fetalis) (Hemolytic Disease of the Newborn) Michael P. [virtualpediatrichospital.org]

• Type A Personality

  A person with at least one copy of the gene for the Rh factor has Rh-positive blood; if no copies are inherited, the person's blood type is Rh-negative. [medigoo.com]

  How the genes are paired determines the person’s blood type. [pathologyproject.wordpress.com]

  How the genes are paired determines the person's blood type. [medical-dictionary.thefreedictionary.com]

• 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.

• Microcytic Anemia

  […] instance of disease 1 reference stated in Disease Ontology release 2019-05-13 retrieved 15 May 2019 Disease Ontology ID DOID:1098 subclass of neonatal alloimmune disease 0 references microcytic anemia 1 reference stated in Disease Ontology release 2019 [wikidata.org]

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.