Paeds · fetal-neonatal-and-perinatal
Haemolytic disease of the fetus and newborn
Also known as Haemolytic disease of the newborn · Erythroblastosis fetalis · Rhesus (RhD) alloimmunisation · Alloimmune haemolytic disease · Kell alloimmunisation
Fellowship guide to haemolytic disease of the fetus and newborn: maternal IgG alloantibodies (anti-D, anti-Kell, ABO) crossing the placenta, the severity ladder from mild jaundice to hydrops, middle cerebral artery Doppler surveillance, intrauterine transfusion, and the postnatal bundle of intensive phototherapy, intravenous immunoglobulin and exchange transfusion — all anchored to antenatal anti-D prevention.
On this page
Study tools
Your progress
Saved on this device.
Practise this topic
Target exams
Red flags
- Jaundice within the first 24 hours of life in any newborn
- Rapidly rising serum bilirubin crossing phototherapy or exchange thresholds on an hour-specific nomogram
- Pallor, tachypnoea, hepatosplenomegaly or poor perfusion suggesting fetal anaemia
- Maternal anti-D, anti-c or anti-Kell titre with a rising or high-titre antibody during pregnancy
- Antenatal hydrops — ascites, pleural effusion, pericardial effusion or skin oedema on ultrasound
- Middle cerebral artery peak systolic velocity above 1.5 multiples of the median from 18 weeks
- Lethargy, hypotonia, poor suck or a high-pitched cry signalling acute bilirubin encephalopathy
Life stages
Care settings
Clinical exam formats
Board mappings
- Rh and ABO incompatibility as causes of neonatal jaundice
- First-24-hour jaundice as a red flag requiring investigation
- Antenatal surveillance and management of red-cell alloimmunisation
- Postnatal management ladder: phototherapy, IVIG, exchange transfusion
- Anti-D prophylaxis and its role in preventing RhD sensitisation
- Interpretation of the direct antiglobulin test and bilirubin nomogram
- Long case: a child who received intrauterine transfusions for RhD disease
- Communication: counselling a pregnant Rh-negative woman about anti-D
- Neonatology: haemolytic jaundice and its complications
- Antenatal detection and perinatal planning for red-cell alloimmunisation
- Pathophysiology of IgG-mediated fetal haemolysis and bilirubin toxicity
- Phototherapy, exchange transfusion and immunoglobulin pharmacology
- History and examination of a jaundiced neonate with hepatosplenomegaly
- Communication: explaining anti-D prophylaxis to an expectant mother
- Neonatal hyperbilirubinaemia due to haemolysis: diagnosis and management
- Recognition and prevention of bilirubin-induced neurologic dysfunction
- Patient Care: management of severe neonatal haemolytic jaundice
- Medical Knowledge: fetal and neonatal red-cell alloimmunisation
- Systems-Based Practice: antenatal anti-D prophylaxis programmes
- Medical Expert: haemolytic disease of the newborn
- Collaborator: maternal-fetal-medicine and neonatal teamwork
- Health Advocate: universal anti-D prophylaxis
Overview & Definition
A newborn is deeply jaundiced at twelve hours of age, pale, and the mother is Rhesus-negative and never received anti-D. That is the opening scene of haemolytic disease of the fetus and newborn (HDFN), the condition in which maternal IgG antibodies directed against antigens on fetal red cells cross the placenta, bind those cells, and mark them for destruction. The result is fetal anaemia on one side of birth and neonatal hyperbilirubinaemia on the other, and the same disease can present as hydrops in utero, devastating early jaundice on the first day, or an insidious late anaemia weeks later. [3] [4]
The old name, erythroblastosis fetalis, captures the marrow's frantic response — the fetus pours out immature nucleated red cell precursors (erythroblasts) to replace the cells being haemolysed. The modern term keeps the mechanism central while signalling that the disease spans the fetal and neonatal periods, and that its severity is graded, largely preventable, and highly treatable when anticipated. [4]
Three facts shape every decision in this topic. First, prevention through anti-D prophylaxis is the single most powerful intervention, and it works upstream of all the fetal and neonatal disease. Second, the antibody identifies the mechanism and predicts the severity — RhD and anti-c cause brisk haemolysis, anti-Kell directly suppresses erythropoiesis, and ABO is usually mild. Third, the bilirubin is the threat on the neonatal side, and it is entirely preventable if anticipated and treated early. Hold those three together and the strategic frame falls into place. [1] [5]
References10ShowHide
- [1]Crowther CA, Middleton P Anti-D administration in pregnancy for preventing Rhesus alloimmunisation. Cochrane Database Syst Rev, 2013.PMID 23450526
- [2]Crowther C, Middleton P Anti-D administration after childbirth for preventing Rhesus alloimmunisation. Cochrane Database Syst Rev, 2000.PMID 10796089
- [3]Mari G, Deter RL, Carpenter RL, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. N Engl J Med, 2000.PMID 10620643
- [4]Mari G, Norton ME, Stone J, Berghella V, Sciscione AC, Tate D, Schenone MH Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: the fetus at risk for anemia--diagnosis and management. Am J Obstet Gynecol, 2015.PMID 25824811
- [5]American Academy of Pediatrics Subcommittee on Hyperbilirubinemia Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics, 2004.PMID 15231951
- [6]Maisels MJ, Newman TB, Kaplan M A new hour-specific serum bilirubin nomogram for neonates ≥35 weeks of gestation. J Pediatr, 2021.PMID 34265340
- [7]Hansen TWR, Maisels MJ, Ebbesen F, Vreman HJ, Stevenson DK, Wong RJ, Bhutani VK Sixty years of phototherapy for neonatal jaundice - from serendipitous observation to standardized treatment and rescue for millions. J Perinatol, 2020.PMID 31420582
- [8]Zwiers C, Scheffer-Rath ME, Lopriore E, de Haas M, Liley HG Immunoglobulin for alloimmune hemolytic disease in neonates. Cochrane Database Syst Rev, 2018.PMID 29551014
- [9]Zwiers C, Lindenburg ITM, Klumper FJ, de Haas M, Oepkes D, Van Kamp IL Complications of intrauterine intravascular blood transfusion: lessons learned after 1678 procedures. Ultrasound Obstet Gynecol, 2017.PMID 27706858
- [10]van Klink JM, Lindenburg IT, Inklaar MJ, Verduin E, Koopman HM, van Kamp IL, Schonewille H, Oepkes D, Lopriore E Health-Related Quality of Life and Behavioral Functioning after Intrauterine Transfusion for Alloimmune Anemia. J Pediatr, 2015.PMID 26342721