Skip to main content Accessibility help
×
Hostname: page-component-7c8c6479df-nwzlb Total loading time: 0 Render date: 2024-03-18T23:35:39.010Z Has data issue: false hasContentIssue false

Chapter 5 - Intrauterine Transfusion

from Section 1

Published online by Cambridge University Press:  19 November 2021

Olutoyin A. Olutoye
Affiliation:
Ann & Robert H. Lurie Children's Hospital of Chicago, Illinois
Get access

Summary

Hemolytic disease of the fetus and newborn is a common cause of intrauterine death and increased neonatal morbidity. While this condition may occur as a result of maternal antibody formation to a variety of different antibodies,(alloimmunization), that which occurs in response to the Rhesus D antigen is the most common. Many centers now perform intrauterine fetal blood transfusion, a required mode of therapy for alloimunization, which is necessary to prevent fetal demise. The ability to accurately detect and treat fetuses affected by this condition depends on adequate prenatal care, astute maternal-fetal practitioners, and a robust center with the ability to analyze fetal blood samples which directs transfusion therapy. While intrauterine therapy is not without complications, and is commonly characterized by repeated fetal transfusions, the ability to transfuse fetuses in-utero has drastically improved the prognosis for affected babies.

Type
Chapter
Information
Anesthesia for Maternal-Fetal Surgery
Concepts and Clinical Practice
, pp. 64 - 82
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Fairweather, DV, Tacchi, D, Coxon, A, et al. Intrauterine transfusion in Rh-isoimmunization. Br Med J. 1967;4:189194.Google Scholar
Liley, AW. Intrauterine transfusion of foetus in haemolytic disease. Br Med J. 1963;2:11071109.CrossRefGoogle ScholarPubMed
Rodeck, CH, Kemp, JR, Holman, CA, et al. Direct intravascular fetal blood transfusion by fetoscopy in severe Rhesus isoimmunization. Lancet. 1981;1:625627.Google Scholar
Hendrickson, JE, Delaney, M. Hemolytic disease of the fetus and newborn: modern practice and future investigations. Transfus Med Rev. 2016;30:159164.CrossRefGoogle ScholarPubMed
Weissman, A, Jakobi, P, Bronshtein, M, Goldstein, I. Sonographic measurements of the umbilical cord and vessels during normal pregnancies. J Ultrasound Med. 1994;13:1114.Google Scholar
Medearis, AL, Hensleigh, PA, Parks, DR, Herzenberg, LA. Detection of fetal erythrocytes in maternal blood post partum with the fluorescence-activated cell sorter. Am J Obstet Gynecol. 1984;148:290295.Google Scholar
Zipursky, A, Paul, VK. The global burden of Rh disease. Arch Dis Child Fetal Neonatal Ed. 2011 ;96(2):F8485.CrossRefGoogle ScholarPubMed
Koelewijn, JM, Vrijkotte, TG, van der Schoot, CE, et al. Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands. Transfusion. 2008;48:941952.CrossRefGoogle Scholar
Bombard, AT, Akolekar, R, Farkas, DH, et al. Fetal RHD genotype detection from circulating cell-free fetal DNA in maternal plasma in non-sensitized RhD negative women. Prenat Diagn. 2011;31:802808.Google Scholar
Daniels, G, van der Schoot, CE, Olsson, ML. Report of the First International Workshop on molecular blood group genotyping. Vox Sang. 2005;88:136142.Google Scholar
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;30:12071212.CrossRefGoogle ScholarPubMed
Singleton, BK, Green, CA, Avent, ND, et al. The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in Africans with the Rh D-negative blood group phenotype. Blood. 2000;95:1218.Google Scholar
Tynan, JA, Angkachatchai, V, Ehrich, M, et al. Multiplexed analysis of circulating cell-free fetal nucleic acids for noninvasive prenatal diagnostic RHD testing. Am J Obstet Gynecol. 2011;204:251.e16.Google Scholar
Wikman, AT, Tiblad, E, Karlsson, A, et al. Noninvasive single-exon fetal RHD determination in a routine screening program in early pregnancy. Obstet Gynecol. 2012;120:227234.Google Scholar
Finning, K, Martin, P, Summers, J, Daniels, G. Fetal genotyping for the K (Kell) and Rh C, c, and E blood groups on cell-free fetal DNA in maternal plasma. Transfusion. 2007;47:21262133.CrossRefGoogle Scholar
Gutensohn, K, Muller, SP, Thomann, K, et al. Diagnostic accuracy of noninvasive polymerase chain reaction testing for the determination of fetal rhesus C, c and E status in early pregnancy. BJOG. 2010;117:722729.Google Scholar
Li, Y, Finning, K, Daniels, G, et al. Noninvasive genotyping fetal Kell blood group (KEL1) using cell-free fetal DNA in maternal plasma by MALDI-TOF mass spectrometry. Prenat Diagn. 2008;28:203208.Google Scholar
Moise, KJ, Jr., Gandhi, M, Boring, NH, et al. Circulating cell-free DNA to determine the fetal RHD status in all three trimesters of pregnancy. Obstet Gynecol. 2016;128:13401346.Google Scholar
Moise, KJ, Jr., Carpenter, RJ, Jr. Increased severity of fetal hemolytic disease with known rhesus alloimmunization after first-trimester transcervical chorionic villus biopsy. Fetal Diagn Ther. 1990;5:7678.Google Scholar
Le Roux, MG, Pascal, O, Andre, MT, et al. Non-paternity and genetic counselling. Lancet. 1992;340:607.CrossRefGoogle ScholarPubMed
Rothenberg, JM, Weirermiller, B, Dirig, K, et al. Is a third-trimester antibody screen in Rh+ women necessary? Am J Manag Care. 1999;5:11451150.Google Scholar
Bowman, JM, Pollock, JM, Manning, FA, et al. Maternal Kell blood group alloimmunization. Obstet Gynecol. 1992;79:239244.Google Scholar
McKenna, DS, Nagaraja, HN, O’Shaughnessy, R. Management of pregnancies complicated by anti-Kell isoimmunization. Obstet Gynecol. 1999;93:667673.Google Scholar
van Wamelen, DJ, Klumper, FJ, de Haas, M, et al. Obstetric history and antibody titer in estimating severity of Kell alloimmunization in pregnancy. Obstet Gynecol. 2007;109:10931098.CrossRefGoogle ScholarPubMed
Mari, G. Middle cerebral artery peak systolic velocity: is it the standard of care for the diagnosis of fetal anemia? J Ultrasound Med. 2005;24:697702.Google Scholar
Mari, G, Deter, RL, Carpenter, RL, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. N Engl J Med. 2000;342:914.Google Scholar
Moise, KJ, Jr. The usefulness of middle cerebral artery Doppler assessment in the treatment of the fetus at risk for anemia. Am J Obstet Gynecol. 2008;198(161).e14.CrossRefGoogle ScholarPubMed
Oepkes, D, Seaward, PG, Vandenbussche, FP, et al. Doppler ultrasonography versus amniocentesis to predict fetal anemia. N Engl J Med. 2006;355:156164.Google Scholar
Pretlove, SJ, Fox, CE, Khan, KS, Kilby, MD. Noninvasive methods of detecting fetal anaemia: a systematic review and meta-analysis. BJOG. 2009;116:15581567.Google Scholar
van Dongen, H, Klumper, FJ, Sikkel, E, Vandenbussche, FP, Oepkes, D. Non-invasive tests to predict fetal anemia in Kell-alloimmunized pregnancies. Ultrasound Obstet Gynecol. 2005;25:341345.CrossRefGoogle ScholarPubMed
Sallout, BI, Fung, KF, Wen, SW, Medd, LM, Walker, MC. The effect of fetal behavioral states on middle cerebral artery peak systolic velocity. Am J Obstet Gynecol. 2004;191:12831287.Google Scholar
Shono, M, Shono, H, Ito, Y, et al. The effect of behavioral states on fetal heart rate and middle cerebral artery flow-velocity waveforms in normal full-term fetuses. Int J Gynaecol Obstet. 1997;58:275280.Google Scholar
Ruma, MS, Swartz, AE, Kim, E, et al. Angle correction can be used to measure peak systolic velocity in the fetal middle cerebral artery. Am J Obstet Gynecol. 2009;200:397.e1-3.CrossRefGoogle ScholarPubMed
MacKenzie, IZ, MacLean, DA, Fry, A, Evans, SL. Midtrimester intrauterine exchange transfusion of the fetus. Am J Obstet Gynecol. 1982;143:555559.Google Scholar
Tongsong, T, Wanapirak, C, Sirichotiyakul, S, et al. Middle cerebral artery peak systolic velocity of healthy fetuses in the first half of pregnancy. J Ultrasound Med. 2007;26:10131017.Google Scholar
Klumper, FJ, van Kamp, IL, Vandenbussche, FP, et al. Benefits and risks of fetal red-cell transfusion after 32 weeks gestation. Eur J Obstet Gynecol Reprod Biol. 2000;92:9196.Google Scholar
van Kamp, IL, Klumper, FJ, Meerman, RH, et al. Treatment of fetal anemia due to red-cell alloimmunization with intrauterine transfusions in the Netherlands, 1988–1999. Acta Obstet Gynecol Scand. 2004;83:731737.Google Scholar
Guilbaud, L, Garabedian, C, Cortey, A, et al. In utero treatment of severe fetal anemia resulting from fetomaternal red blood cell incompatibility: a comparison of simple transfusion and exchange transfusion. Eur J Obstet Gynecol Reprod Biol. 2016;201:8588.Google Scholar
Society for Maternal-Fetal Medicine. (SMFM) Clinical Guideline #8: the fetus at risk for anemia–diagnosis and management. Am J Obstet Gynecol. 2015;212:697710.Google Scholar
Tiblad, E, Kublickas, M, Ajne, G, et al. Procedure-related complications and perinatal outcome after intrauterine transfusions in red cell alloimmunization in Stockholm. Fetal Diagn Ther. 2011;30:266273.CrossRefGoogle ScholarPubMed
Osanan, GC, Silveira Reis, ZN, Apocalypse, IG, et al. Predictive factors of perinatal mortality in transfused fetuses due to maternal alloimmunization: what really matters? J Maternal Fetal Neonatal Med. 2012;25:13331337.Google Scholar
Deka, D, Dadhwal, V, Sharma, AK, et al. Perinatal survival and procedure-related complications after intrauterine transfusion for red cell alloimmunization. Arch Gynecol Obstet. 2016;293:967973.CrossRefGoogle ScholarPubMed
Johnstone-Ayliffe, C, Prior, T, Ong, C, et al. Early procedure-related complications of fetal blood sampling and intrauterine transfusion for fetal anemia. Acta Obstet Gynecol Scand. 2012;91:458462.Google Scholar
Schonewille, H, Prinsen-Zander, KJ, Reijnart, M, et al. Extended matched intrauterine transfusions reduce maternal Duffy, Kidd, and S antibody formation. Transfusion. 2015;55:29122919; quiz 1.Google Scholar
Fung, M. Technical Manual of the American Association of Blood Banks, 18th ed., Bethesda, Maryland: American Association of Blood Banks; 2014.Google Scholar
el-Azeem, SA, Samuels, P, Rose, RL, et al. The effect of the source of transfused blood on the rate of consumption of transfused red blood cells in pregnancies affected by red blood cell alloimmunization. Am J Obstet Gynecol. 1997;177:753757.CrossRefGoogle ScholarPubMed
Gonsoulin, WJ, Moise, KJ, Jr., Milam, JD, et al. Serial maternal blood donations for intrauterine transfusion. Obstet Gynecol. 1990;75:158162.Google Scholar
Bleile, MJ, Rijhsinghani, A, Dwyre, DM, Raife, TJ. Successful use of maternal blood in the management of severe hemolytic disease of the fetus and newborn due to anti-Kp(b). Transfus Apher Sci. 2010;43:281283.Google Scholar
Schumacher, B, Moise, KJ, Jr. Fetal transfusion for red blood cell alloimmunization in pregnancy. Obstet Gynecol. 1996;88:137150.Google Scholar
Gaiser, RR, Kurth, CD. Anesthetic considerations for fetal surgery. Semin Perinatol. 1999;23:507514.CrossRefGoogle ScholarPubMed
Okamoto, M, Walewski, JL, Artusio, JF, Jr., Riker, WF, Jr. Neuromuscular pharmacology in rat neonates: development of responsiveness to prototypic blocking and reversal drugs. Anesth Analg. 1992;75:361371.Google Scholar
Shearer, ES, Fahy, LT, O’Sullivan, EP, Hunter, JM. Transplacental distribution of atracurium, laudanosine and monoquaternary alcohol during elective caesarean section. Br J Anaesth. 1991;66:551556.Google Scholar
Zwiers, C, Lindenburg, ITM, Klumper, FJ, et al. Complications of intrauterine intravascular blood transfusion: lessons learned after 1678 procedures. Ultrasound Obstet Gynecol. 2017;50:180186.Google Scholar
Van Kamp, IL, Klumper, FJ, Oepkes, D, et al. Complications of intrauterine intravascular transfusion for fetal anemia due to maternal red-cell alloimmunization. Am J Obstet Gynecol. 2005;192:171177.Google Scholar
Moise, KJ, Jr. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol. 2002;100:600611.Google Scholar
Moise, KJ, Jr., Deter, RL, Kirshon, B, et al. Intravenous pancuronium bromide for fetal neuromuscular blockade during intrauterine transfusion for red-cell alloimmunization. Obstet Gynecol. 1989;74:905908.Google Scholar
Leveque, C, Murat, I, Toubas, F, et al. Fetal neuromuscular blockade with vecuronium bromide: studies during intravascular intrauterine transfusion in isoimmunized pregnancies. Anesthesiology. 1992;76:642644.Google Scholar
Mouw, RJ, Klumper, F, Hermans, J, et al. Effect of atracurium or pancuronium on the anemic fetus during and directly after intravascular intrauterine transfusion. A double blind randomized study. Acta Obstet Gynecol Scand. 1999;78:763767.Google Scholar
Fisk, NM, Gitau, R, Teixeira, JM, et al. Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling. Anesthesiology. 2001;95:828835.Google Scholar
Adama van Scheltema, PN, Borkent, S, Sikkel, E, et al. Fetal brain hemodynamic changes in intrauterine transfusion: influence of needle puncture site. Fetal Diagn Ther. 2009;26:131133.Google Scholar
Adama van Scheltema, PN, Pasman, SA, Wolterbeek, R, et al. Fetal stress hormone changes during intrauterine transfusions. Prenat Diagn. 2011;31:555559.Google Scholar
Weiner, CP, Wenstrom, KD, Sipes, SL, Williamson, RA. Risk factors for cordocentesis and fetal intravascular transfusion. Am J Obstet Gynecol. 1991;165:10201025.Google Scholar
Pasman, SA, Claes, L, Lewi, L, et al. Intrauterine transfusion for fetal anemia due to red blood cell alloimmunization: 14 years experience in Leuven. Facts Views Vis Obgyn. 2015;7:129136.Google Scholar
Sainio, S, Nupponen, I, Kuosmanen, M, et al. Diagnosis and treatment of severe hemolytic disease of the fetus and newborn: a 10-year nationwide retrospective study. Acta Obstet Gynecol Scand. 2015;94:383390.Google Scholar
Nicolini, U, Santolaya, J, Ojo, OE, et al. The fetal intrahepatic umbilical vein as an alternative to cord needling for prenatal diagnosis and therapy. Prenat Diagn. 1988;8:665671.Google Scholar
Nicolini, U, Nicolaidis, P, Fisk, NM, et al. Fetal blood sampling from the intrahepatic vein: analysis of safety and clinical experience with 214 procedures. Obstet Gynecol. 1990;76:4753.Google Scholar
Giannakoulopoulos, X, Sepulveda, W, Kourtis, P, et al. Fetal plasma cortisol and beta-endorphin response to intrauterine needling. Lancet. 1994;344:7781.Google Scholar
Lobato, G, Soncini, CS. Fetal hydrops and other variables associated with the fetal hematocrit decrease after the first intrauterine transfusion for red cell alloimmunization. Fetal Diagn Ther. 2008;24:349352.Google Scholar
Harman, CR, Bowman, JM, Manning, FA, Menticoglou, SM. Intrauterine transfusion–intraperitoneal versus intravascular approach: a case-control comparison. Am J Obstet Gynecol. 1990;162:10531059.CrossRefGoogle ScholarPubMed
Lewis, M, Bowman, JM, Pollock, J, Lowen, B. Absorption of red cells from the peritoneal cavity of an hydropic twin. Transfusion. 1973;13:3740.Google Scholar
Creasman, WT, Duggan, ER, Lund, CJ. Absorption of transfused chromium-labeled erythrocytes from the fetal peritoneal cavity in hydrops fetalis. Am J Obstet Gynecol. 1966;94:586588.Google Scholar
Taylor, WW, Scott, DE, Pritchard, JA. Fate of compatible adult erythrocytes in the fetal peritoneal cavity. Obstet Gynecol. 1966;28:175181.Google Scholar
Fox, C, Martin, W, Somerset, DA, et al. Early intraperitoneal transfusion and adjuvant maternal immunoglobulin therapy in the treatment of severe red cell alloimmunization prior to fetal intravascular transfusion. Fetal Diagn Ther. 2008;23:159163.Google Scholar
Moise, KJ, Jr., Carpenter, RJ, Jr., Kirshon, B, et al. Comparison of four types of intrauterine transfusion: effect on fetal hematocrit. Fetal Ther. 1989;4:126137.Google Scholar
Nicolini, U, Kochenour, NK, Greco, P, et al. When to perform the next intra-uterine transfusion in patients with Rh allo-immunization: combined intravascular and intraperitoneal transfusion allows longer intervals. Fetal Ther. 1989;4:1420.CrossRefGoogle ScholarPubMed
Mackie, FL, Pretlove, SJ, Martin, WL, et al. Fetal intracardiac transfusions in hydropic fetuses with severe anemia. Fetal Diagn Ther. 2015;38:6164.Google Scholar
Allaf, MB, Matha, S, Chavez, MR, Vintzileos, AM. Intracardiac fetal transfusion for parvovirus-induced hydrops fetalis: a salvage procedure. J Ultrasound Med. 2015;34:21072109.Google Scholar
Radunovic, N, Lockwood, CJ, Alvarez, M, et al. The severely anemic and hydropic isoimmune fetus: changes in fetal hematocrit associated with intrauterine death. Obstet Gynecol. 1992;79:390393.Google Scholar
Papantoniou, N, Sifakis, S, Antsaklis, A. Therapeutic management of fetal anemia: review of standard practice and alternative treatment options. J Perinat Med. 2013;41:7182.Google Scholar
Dildy, GA, Smith, LG, Moise, KJ, et al. Porencephalic cyst: a complication of fetal intravascular transfusion. Am J Obstet Gynecol. 1991;165:7678.CrossRefGoogle ScholarPubMed
Drew, JH, Guaran, RL, Cichello, M, Hobbs, JB. Neonatal whole blood hyperviscosity: the important factor influencing later neurologic function is the viscosity and not the polycythemia. Clin Hemorheol Microcirc. 1997;17:6772.Google Scholar
Giannina, G, Moise, KJ, Dorman, K. A simple method to estimate volume for fetal intravascular transfusions. Fetal Diagn Ther. 1998;13:9497.Google Scholar
Mandelbrot, L, Daffos, F, Forestier, F, et al. Assessment of fetal blood volume for computer-assisted management of in utero transfusion. Fetal Ther. 1988;3:6066.Google Scholar
Bowman, JM. The management of Rh-Isoimmunization. Obstet Gynecol. 1978;52:116.Google Scholar
Egberts, J, van Kamp, IL, Kanhai, HH, et al. The disappearance of fetal and donor red blood cells in alloimmunised pregnancies: a reappraisal. Br J Obstet Gynaecol. 1997;104:818824.Google Scholar
Lobato, G, Soncini, CS. Fetal hematocrit decrease after repeated intravascular transfusions in alloimmunized pregnancies. Arch Gynecol Obstet. 2007;276:595599.Google Scholar
Mari, G, Detti, L, Oz, U, et al. Accurate prediction of fetal hemoglobin by Doppler ultrasonography. Obstet Gynecol. 2002;99:589593.Google Scholar
Scheier, M, Hernandez-Andrade, E, Fonseca, EB, Nicolaides, KH. Prediction of severe fetal anemia in red blood cell alloimmunization after previous intrauterine transfusions. Am J Obstet Gynecol. 2006;195:15501556.Google Scholar
Detti, L, Oz, U, Guney, I, et al. Doppler ultrasound velocimetry for timing the second intrauterine transfusion in fetuses with anemia from red cell alloimmunization. Am J Obstet Gynecol. 2001;185:10481051.Google Scholar
Dodd, JM, Andersen, C, Dickinson, JE, et al. Fetal MCA Doppler to time intrauterine transfusions in red cell alloimmunisation: A randomised trial. Ultrasound Obstet Gynecol. 2018;51:306312.Google Scholar
Zwiers, C, van Kamp, I, Oepkes, D, Lopriore, E. Intrauterine transfusion and non-invasive treatment options for hemolytic disease of the fetus and newborn – review on current management and outcome. Expert Rev Hematol. 2017;10:337344.Google Scholar
Canlorbe, G, Mace, G, Cortey, A, et al. Management of very early fetal anemia resulting from red-cell alloimmunization before 20 weeks of gestation. Obstet Gynecol. 2011;118:13231329.Google Scholar
Poissonnier, MH, Picone, O, Brossard, Y, Lepercq, J. Intravenous fetal exchange transfusion before 22 weeks of gestation in early and severe red-cell fetomaternal alloimmunization. Fetal Diagn Ther. 2003;18:467471.Google Scholar
Lindenburg, IT, van Kamp, IL, van Zwet, EW, et al. Increased perinatal loss after intrauterine transfusion for alloimmune anaemia before 20 weeks of gestation. BJOG. 2013;120:847852.CrossRefGoogle ScholarPubMed
Ruma, MS, Moise, KJ, Kim, E, et al. Combined plasmapheresis and intravenous immune globulin for the treatment of severe maternal red cell alloimmunization. Am J Obstet Gynecol. 2007;196:138.e1-6.Google Scholar
Lindenburg, IT, Wolterbeek, R, Oepkes, D, et al. Quality control for intravascular intrauterine transfusion using cumulative sum (CUSUM) analysis for the monitoring of individual performance. Fetal Diagn Ther. 2011;29:307314.CrossRefGoogle ScholarPubMed
Watts, DH, Luthy, DA, Benedetti, TJ, et al. Intraperitoneal fetal transfusion under direct ultrasound guidance. Obstet Gynecol. 1988;71:8488.Google Scholar
De Boer, IP, Zeestraten, EC, Lopriore, E, et al. Pediatric outcome in Rhesus hemolytic disease treated with and without intrauterine transfusion. Am J Obstet Gynecol. 2008;198(54).e1-4.Google Scholar
Rath, ME, Smits-Wintjens, VE, Oepkes, D, et al. Iron status in infants with alloimmune haemolytic disease in the first three months of life. Vox Sang. 2013;105:328333.Google Scholar
Watson, WJ, Wax, JR, Miller, RC, Brost, BC. Prevalence of new maternal alloantibodies after intrauterine transfusion for severe Rhesus disease. Am J Perinatol. 2006;23:189192.Google Scholar
Lindenburg, IT, Smits-Wintjens, VE, van Klink, JM, et al. Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study. Am J Obstet Gynecol. 2012;206:141.e1-8.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×