Dear editor,
Hemolytic disease of the newborn (HDN) due to ABO and Rh incompatibility have been reported previously; however, it has rarely been described in association with breastmilk [1–4]. We report two newborns who developed HDN due to ABO and Rh incompatibility, and whose persistent anemia improved spontaneously after discontinuing breastfeeding (Fig. 1a, b). The first non-hydropic newborn had been referred to our hospital for phototherapy and exchange transfusion because of jaundice at birth. His blood type was O Rh+. The mother’s blood type was O Rh– and she had not received anti-D prophylaxis during her first pregnancy because her first child’s blood type was recorded as O Rh– at birth in another hospital. However, this child was 5 years old when the affected baby was born, and repeat testing of his blood type was strongly O Rh+ in our hospital. HDN due to Rh incompatibility was considered because maternal testing revealed anti-D titer 1:2,048 and a positive indirect Coombs test. Three weeks after birth, patient’s hemoglobin (Hb) was 6.7 g/dL, and erythrocyte transfusion was administered. Further testing at 6 weeks showed lower Hb (6.5 g/dL), reticulocytosis (Rtc) (9%), and positive Coombs test; thus, IVIG and erythrocyte transfusion were given. His blood tests revealed Hb 8.5 g/dL, Rtc 4.6%, and normal G6PD level. His parents’ Hb, Rtc, Hb electrophoresis, and osmotic fragility results were normal, the baby’s condition was attributed to breastmilk. Antibody testing in the breastmilk was performed based on gel card (Ortho Clinical Diagnostics®) and tube methods proposed in a previous report [4]. Anti-D titer in the breastmilk was 1:8192. Based on all findings, breastfeeding was discontinued. Three months after birth, the patient’s Hb level had spontaneously increased to 9.8 g/dL. His Hb level had reached 12 g/dL and Coombs test was negative at the fourth month of birth. By the third year, his Hb level was 12.5 g/dL.
Fig. 1.
Hemoglobin (a) and bilirubin (b) values in two newborns with ABO/Rh incompatibility
In the second newborn, he had also received phototherapy and exchange transfusion because of jaundice at birth. The mother’s blood type was O Rh+ and his baby was A Rh+. At 3 weeks of age, his Hb level was found to be low (9 g/dL). Evaluations at 1 month revealed even lower Hb (8.1 g/dL), Rtc 3%, and a negative Coombs test. Hereditary hemolytic anemia were investigated and the findings were unremarkable. By 45 days, his Hb level had decreased to 7.1 g/dL and he was diagnosed with HDN due to ABO incompatibility. Maternal blood testing revealed anti-A and anti-B titers as high as 1:1024 and 1:128, respectively. Concurrent analyses of the mother’s breastmilk using the same method identified anti-A and anti-B titers of 1:4096 and 1:1024, respectively. Based on all findings, breastfeeding was discontinued. By 3 months of age, the patient’s Hb level had increased spontaneously to 9.1 g/dL. By the fourth month, his Hb was 11.7 g/dL. An extensive literature search of this topic revealed very limited publications [1–4]. The first case report due to Rh incompatibility was published in 1947 [1]. The most comprehensive study of HDN in 18 newborns (16 with ABO and 2 with Rh incompatibility) reported that this condition was associated with passive acquisition of anti-A, anti-B, and anti-D isohemagglutinins ranged from 1:64 to 1:2048 titers in maternal breastmilk [2]. Another group reported having detected immunoglobulin A in breastmilk from thrombocytopenic mothers of newborns with refractory immune thrombocytopenia, and that discontinuing breastmilk feeding helped resolve this condition [5]. Li et al. reported the newborn with HDN due to Rh incompatibility whose Hb level had been brought under control by discontinuing breastfeeding [3]. Further studies may provide a better opportunity to address this issue. Based on our experience, physicians should be aware that HDN can be caused by isohemagglutinins in maternal breastmilk, and if HDN does not spontaneously resolve, transient discontinuation of breastfeeding can be advised to improve this condition as this is a raresty entity.
Author’s Contributions
ZK developed the theory and performed the literature screening with support from ŞG, YY, CM, AT, TS. ZK wrote the paper with input from all authors. ŞG performed the analytic tests for breastmilk antibody detection in the Blood bank.
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Conflict of interest
The authors have no conflicts of interest.
Footnotes
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References
- 1.Davies R. Persistent anaemia in a breastfed infant with erythroblastosis foetalis. Br Med J. 1947;1(4490):138. doi: 10.1136/bmj.1.4490.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Lange MM, Fiandino G. Research on the passage of isohemaglutinins into milk in hemolytic disease of the newborn. Minerva Pediatr. 1967;19(38):1728–1734. [PubMed] [Google Scholar]
- 3.Li M, Blaustein JC. Persistent hemolytic disease of the fetus and newborn associated with passive acquisition of anti D in maternal breast milk. Transfusion. 2017;57(9):2121–2124. doi: 10.1111/trf.14171. [DOI] [PubMed] [Google Scholar]
- 4.Leonard A, Hittson Boal L, Pary P, Mo YD, Jacquot C, Luban NL, et al. Identification of red blood cell antibodies in maternal breast milk implicated in prolonged hemolytic disease of the fetus and newborn. Transfusion. 2019;59(4):1183–1189. doi: 10.1111/trf.15154. [DOI] [PubMed] [Google Scholar]
- 5.Hauschner H, Rosenberg N, Seligsohn U, Mendelsohn R, Simmonds A, Shiff Y, et al. Persistent neonatal thrombocytopenia can be caused by IgA antiplatelet antibodies in breast milk of immune thrombocytopenic mothers. Blood. 2015;126(5):661–664. doi: 10.1182/blood-2014-12-614446. [DOI] [PubMed] [Google Scholar]