On this page you will find additional information about all of the topics covered on the Allo Hope Foundation’s website. These resources are intended to assist you in your search for more in-depth information about a particular topic. This page is updated with new links, so check back often.
Disclaimer: The purpose of this website is to provide general education, access to resources, and relevant literature. This website does not provide specific medical advice or recommendations for individual patients and is not a substitute for speaking with qualified healthcare professionals. The Allo Hope Foundation strongly recommends that care and treatment related to alloimmunization and HDFN be made in consultation with your physicians who are familiar with your individual health situation.
Table of Contents
- Anemia:
- Antibody Screening and Titers
- Blood Transfusion
- Autologous blood donation and transfusion
- Intrauterine transfusion
- Religious objections to blood products
- Cell-Free Fetal DNA (cffDNA)
- Cholestasis
- Chorioamnionitis
- Cord Blood Testing
- Erythropoietin
- Hyperbilirubinemia
- Iron status
- IVIG – Maternal
- Long Term Outcomes
- MCA Scans
- Neutropenia
- Thrombocytopenia
Anemia
Iron should not be administered to infants with HDFN unless a ferritin test is conducted first. Inappropriately administered iron can be dangerous. See Iron.
Delayed Onset Anemia
https://medlineplus.gov/anemia.html
https://kidshealth.org/en/parents/anemia-hemolytic.html
Hemolytic Anemia
Hemolytic Anemia Treatment & Management. Medscape.
Hyporegenerative Anemia
Antibody Screening and Titers
Management of pregnancy complicated by RhD alloimmunization Author: Kenneth J Moise Jr, MD
Indirect Agglutination Test (IAT) Exceptions
These antibodies have a negative IAT on the mother, but still have an affected fetus/neonate: anti-Jsa, anti-Dia, and anti-Wra. Since anti-Dia and anti-Wra are both in the Diego blood group, it leads to speculation if anti-Dib could produce the same result.
The first case of hydrops from anti-Jsa was reported in 2005. What is startling to note about this was that the mother’s Indirect Coombs test was NEGATIVE despite the infant having hydrops and a positive Direct Coombs (strength of 3+). The woman had lost an infant before due to hydrops, the cause of which was never identified. Further testing revealed the woman to be Jsa- and the baby Jsa+. Both maternal and fetal blood reacted with Jsa+ cells and they were able to identify the antibody as anti-Jsa. Delayed onset anemia was found on day 14 and the infant was treated with a transfusion, phototherapy and erythropoietin.
The first case of hydrops fetalis caused by anti-Jsa. A case report and suggestions on the antenatal diagnosis of haemolysis due to antibodies against rare antigens. Blood Transfusion 2005; 3: 76-83
Blood Transfusion
Autologous Blood Donation and Transfusion
Intrauterine Transfusion
Intrauterine Fetal Transfusion of Red Blood Cells. Up to Date.
Religious objections to blood products
Information about blood products and religious recommendations for patients facing alloimmunization and HDFN. The Allo Hope Foundation does not recommend these treatments, however we do recognize that for a few patients, blood products are not an option. These case reports of experimental treatments are not aligned with current standards of care and should only be used as an absolute last resort for those who cannot receive blood products.
Cell-free fetal DNA (cffDNA)
Australian Red Cross Non-Invasive Prenatal Analysis (NIPA) for RhD
Netherlands Sanquin website – tests for c, C, D, e, E, K, and k.
UK testing for those in the NHS system – click on “Fetal RhD Sampling” for anti-D, and click on “Molecular Diagnostics” and “Fetal Genotype Sample Referral Form”.
Canadian Blood Service – Fetal genotyping from maternal plasma
Cholestasis
Chorioamnionitis
Cord blood testing
Postnatal diagnosis and management of hemolytic disease of the fetus and newborn. Accessed July 11, 2018
Direct Agglutination Test (DAT) Exceptions
Anti-C, anti-c, anti-Fya, anti-Good, anti-H, anti-Jra, anti-M, and anti-Mta are the DAT Exceptions. The test may show negative, but the infant is still severely affected.
The Good Factor as a Possible Cause of Hemolytic Disease of the Newborn. The Blood Journal.
Anti-M Antibody in Pregnancy. Obstet Gynecol Surv. 1989; 44(9):637-641
Postnatal diagnosis and management of hemolytic disease of the fetus and newborn. Up to Date.
Erythropoietin
Hyperbilirubinemia
Kappas A, Drummond GS, Munson DP, Marshall JR. Sn-Mesoporphyrin interdiction of severe hyperbilirubinemia in Jehovah’s Witness newborns as an alternative to exchange transfusion. Pediatrics. 2001;108(6):1374‐1377. doi:10.1542/peds.108.6.1374
Bronze Baby Syndrome
Bronze Baby Syndrome. Journal of Pediatrics. 2017; 188:301. doi:10.1016/j.jpeds.2017.05.005
Bronze Baby Syndrome and the Risk of Kernicterus. Acta Paediatr. 2005;94(7):968‐971. doi:10.1111/j.1651-2227.2005.tb02020.x
Exchange Transfusion
Kappas A, Drummond GS, Munson DP, Marshall JR. Sn-Mesoporphyrin interdiction of severe hyperbilirubinemia in Jehovah’s Witness newborns as an alternative to exchange transfusion. Pediatrics. 2001;108(6):1374‐1377. doi:10.1542/peds.108.6.1374
IVIG – Infant
Intravenous Immunoglobulin (IVIG). About Kids Health
Mundy CA. Intravenous immunoglobulin in the management of hemolytic disease of the newborn. Neonatal Netw. 2005;24(6):17‐24. doi:10.1891/0730-0832.24.6.17
Kernicterus
Kernicterus Center of Excellence
Parents of Infants and Children with Kernicterus
Phenobarbital
Intrauterine fetal transfusion of red cells. Up to Date.
Phototherapy
Iron Status
“On the contrary, iron overload occurs in 70% of neonates with alloimmune HDFN at birth, 50% at the age of 1 month and 18% at the age of 3 months. Therefore, we advise to measure iron status, and we discourage the use of iron supplementation in the first 3 months of life in neonates with alloimmune HDFN. Haemolysis and intrauterine and postnatal transfusions probably both contribute to the high incidence of iron overload in alloimmune HDFN.”
70% of iso babies had iron overload at birth, none were iron deficient at birth, 50% at 1 month had iron overload, and 18% had iron overload at 3 months. “There is a number of case reports published on the risk of severe iron overload, diagnosed by liver biopsies, following IUTs for Rh HDFN. These infants were all born at 33 or 34 weeks of gestation and received 2–5 IUTs and several postnatal transfusions. Their serum ferritin levels ranged from 2479 to 28 800 lg/l. In addition to transfusions for alloimmune HDFN, the haemolysis itself can also contribute to iron overload in alloimmune HDFN.” This article also talks about IUTs as a risk factor for choleostasis. Rath ME, Smits-Wintjens VE, Oepkes D, Walther FJ, Lopriore E. Iron status in infants with alloimmune haemolytic disease in the first three months of life. Vox Sang. 2013;105(4):328‐333. doi:10.1111/vox.12061
“As discussed above, neonates with RHDN often require IUTs and (multiple) transfusions of red blood cells. The risks and potential consequences of iron overload due to these multiple transfusions are poorly recognized. High levels of cord blood ferritine have been reported in infants with RHDN.57 As infants with RHDN already have high iron storage, supplementation of iron is not recommended and should not be used.” Smits-Wintjens VE, Walther FJ, Lopriore E. Rhesus haemolytic disease of the newborn: Postnatal management, associated morbidity and long-term outcome. Semin Fetal Neonatal Med. 2008;13(4):265‐271. doi:10.1016/j.siny.2008.02.005
“A 34 weeks’ gestation baby with RHD, who had received multiple intrauterine transfusions (IUT), developed cholestatic hepatic disease and secondary hemophagocytic lymphohistiocytosis (HLH). Her serum ferritin level increased to 5527 ng/mL, and liver biopsy showed severe iron overload. We suggest that patients who have undergone IUT be evaluated for hyperferritinemia.” Yilmaz S, Duman N, Ozer E, et al. A case of rhesus hemolytic disease with hemophagocytosis and severe iron overload due to multiple transfusions. J Pediatr Hematol Oncol. 2006;28(5):290‐292. doi:10.1097/01.mph.0000212906.07018.93
“Iron therapy is contraindicated in most cases of hemolytic anemia. The reason is that iron released from RBCs in most hemolytic anemias is reused and iron stores are not reduced. ” Hemolytic Anemia Treatment & Management Medscape
“The vast majority of neonates with alloimmune HDFN have iron overload at birth. Incidence of iron overload gradually decreases within the first 3 months without iron supplementation…In recent literature, a ferritin level <12 lg/l is used for the definition of iron deficiency during the first year of life. Based on that definition, no cases of iron deficiency were present until 3 months of age in our study group… On the contrary, iron overload occurs in 70% of neonates with alloimmune HDFN at birth, 50% at the age of 1 month and 18% at the age of 3 months. Therefore, we advise to measure iron status, and we discourage the use of iron supplementation in the first 3 months of life in neonates with alloimmune HDFN.” Iron status in infants with alloimmune haemolytic disease in the first three months of life. Vox Sang. 2013 Nov;105(4):32833. doi: 10.1111/vox.12061.
Hemolytic Disease of the Fetus and Newborn: Managing the Mother, Fetus, and Newborn. Hematology Am Soc Hematol Educ Program. 2015;2015:146-51. doi: 10.1182/asheducation-2015.1.146.
Chelation Therapy
Long-Term Outcomes
MCA scans
Opheim GL, Zucknick M, Henriksen T, Haugen G. A maternal meal affects clinical Doppler parameters in the fetal middle cerebral artery. PLoS One. 2018;13(12):e0209990. Published 2018 Dec 31. doi:10.1371/journal.pone.0209990
Steroids
Steroids can falsely lower the MoM score, making fetal anemia more difficult to detect. Steroids do not treat anemia, and if the baby was anemic before the steroids were administered, the baby will still be anemic after the steroids. Below you will find articles that discuss how steroids can affect MCA scans. Also, Progesterone (oral or as a shot like Makena) has been found to lower the PSV as well (see the last article listed).
Urban R, Lemancewicz A, Przepieść J, Urban J, Kretowska M. Antenatal corticosteroid therapy: a comparative study of dexamethasone and betamethasone effects on fetal Doppler flow velocity waveforms. Eur J Obstet Gynecol Reprod Biol. 2005;120(2):170‐174. doi:10.1016/j.ejogrb.2004.09.009 Conclusion: Our results indicate significant decrease in fetal middle cerebral artery impedance at 72 h after maternal administration of the first dose of dexamethasone.
Piazze JJ, Anceschi MM, La Torre R, Amici F, Maranghi L, Cosmi EV. Effect of antenatal betamethasone therapy on maternal-fetal Doppler velocimetry. Early Hum Dev. 2001;60(3):225‐232. doi:10.1016/s0378-3782(00)00120-1 Conclusion: Betamethasone treatment is associated with a significant, although transient, reduction of MCA PI, especially at gestational ages <32 weeks’.
Piazze J, Anceschi MM, Cerekja A, et al. The combined effect of betamethasone and ritodrine on the middle cerebral artery in low risk third trimester pregnancies. J Perinat Med. 2007;35(2):135‐140. doi:10.1515/JPM.2007.027 Conclusion: In low risk pregnancies, betamethasone therapy in the third trimester is related to a significant but transient reduction of MCA PI, which is more pronounced during tocolytic therapy. Although the physiological basis of this effect is currently unclear, it could be related to the local regulation of intracerebral blood flow.
Rotmensch S, Liberati M, Vishne TH, Celentano C, Ben-Rafael Z, Bellati U. The effect of betamethasone and dexamethasone on fetal heart rate patterns and biophysical activities. A prospective randomized trial. Acta Obstet Gynecol Scand. 1999;78(6):493‐500. Conclusions: Both betamethasone and dexamethasone induce a profound, albeit transient, suppression of fetal heart rate characteristics and biophysical activities in the preterm fetus. However, the effect of betamethasone is more pronounced. Awareness of these phenomena might prevent unwarranted iatrogenic delivery of preterm fetuses.
Chitrit Y, Caubel P, Herrero R, Schwinte AL, Guillaumin D, Boulanger MC. Effects of maternal dexamethasone administration on fetal Doppler flow velocity waveforms. BJOG. 2000;107(4):501‐507. doi:10.1111/j.1471-0528.2000.tb13269.x Conclusions: The current study finds in healthy fetuses a transient, significant and unexplained decrease in fetal middle cerebral artery impedance on the fourth day following maternal dexamethasone administration. Further basic research and clinical studies including larger sample sizes or pregnancies with fetoplacental dysfunction are needed.
Edwards A, Baker LS, Wallace EM. Changes in fetoplacental vessel flow velocity waveforms following maternal administration of betamethasone. Ultrasound Obstet Gynecol. 2002;20(3):240‐244. doi:10.1046/j.1469-0705.2002.00782.x. Recorded a decrease in MoM at 24 hours.
Azza A.Abd El Hameed. Vaginal versus intramuscular progesterone in the prevention of preterm labor and their effect on uterine and fetal blood flow. Middle East Fertility Society Journal. 2012;17 (3):163-169. doi.org/10.1016/j.mefs.2011.12.003 A statistically significant decrease in fetal MCA-PI was noted after progesterone administration both vaginally and IM.
