207:
627:(D) immune globulin (RHIG) after its regulatory approval. Clinical trials were set up in 42 centers in the US, Great Britain, Germany, Sweden, Italy, and Australia. RHIG was finally approved in England and the United States in 1968. The FDA approved the drug under the brand name RhoGAM, with a fixed dose of 300 μg, to be given within three days (72 hours) postpartum. Subsequently, a broader peripartum period was approved for dosing which included prophylaxis during pregnancy. Within a year, the antibody had been injected with great success into more than 500,000 women. Time magazine picked it as one of the top ten medical achievements of the 1960s. By 1973, it was estimated that in the US alone, over 50,000 babies' lives had been saved. The use of Rh immune globulin to prevent the disease in babies of Rh negative mothers has become standard practice, and the disease, which used to claim the lives of 10,000 babies each year in the US alone, has been virtually eradicated in the developed world. In 1980,
193:
336:. However, in many cases there was no apparent sensitizing event. Approximately 50% of Rh-D positive infants with circulating anti-D are either unaffected or only mildly affected requiring no treatment at all and only monitoring. An additional 20% are severely affected and require transfusions while still in the uterus. This pattern is similar to other types of HDFN due to other commonly encountered antibodies (anti-c, anti-K, and Fy(a)).
616:
done with Rh-negative mothers. One of the needs was a dosing experiment that could be used to determine the level of circulating Rh-positive cells in an Rh-negative pregnant female derived from her Rh-positive fetus. This was first done in the rabbit system, but subsequent human tests at the
University of Manitoba conducted under Dr. Pollack's direction confirmed that anti-Rh
445:
fetal DNA in the maternal bloodstream. In healthy pregnancies, at least 5% (fetal fraction) of the cell free DNA in the maternal bloodstream comes from the fetus (placenta cells shed DNA into the maternal bloodstream). This small fraction of cell free DNA from the fetus is enough to determine the fetus's Rh antigen.
149:(HDFN). HDFN due to anti-D antibodies is the proper and currently used name for this disease as the Rh blood group system actually has more than 50 antigens and not only the D-antigen. The term "Rh Disease" is commonly used to refer to HDFN due to anti-D antibodies, and prior to the discovery of anti-Rh
421:
In Arar, Saudi Arabia, results of a study showed that women had a low level of knowledge regarding maternal-fetal blood incompatibility (about 38% of the studied mothers during the research, had knowledge about Rh incompatibility). Regarding their knowledge about anti-D, researchers found that; 68.5%
444:
The fetal Rh can be screened using non-invasive prenatal testing (NIPT). This test can screen for the fetus's Rh antigen (positive or negative) at the 10th week of gestation using a blood sample drawn from the mother. The Unity test uses NGS technology to look for Rh alleles (genes) in the cell free
404:
Blood is generally drawn from the biological father to help determine fetal antigen status. If he is homozygous for the antigen, there is a 100% chance of all offspring in the pairing to be positive for the antigen and at risk for HDFN. If he is heterozygous, there is a 50% chance of offspring to be
349:
In the United States, it is a standard of care to test all expecting mothers for the presence or absence of the RhD protein on their RBCs. However, when medical care is unavailable or prenatal care not given for any other reason, the window to prevent the disease may be missed. In addition, there is
583:
and cross-matching in 1940, which was the culmination of years of work. However, there were multiple participants in this scientific race and almost simultaneous publications on this topic. Levine published his theory that the disease known as erythroblastosis fetalis was due to Rh alloimmunization
219:
During the first pregnancy, the Rh- mother's initial exposure to fetal Rh+ red blood cells (RBCs) is usually not sufficient to activate her Rh-recognizing B cells. However, during delivery, the placenta separates from the uterine wall, causing umbilical cord blood to enter the maternal circulation,
615:
Animal studies had previously been conducted by Dr. Pollack using a rabbit model of Rh. This model, named the rabbit HgA-F system, was an animal model of human Rh, and enabled
Pollack's team to gain experience in preventing hemolytic disease in rabbits by giving specific HgA antibody, as was later
417:
can prevent temporary sensitization of the maternal immune system to RhD antigens, which can cause rhesus disease in the current or in subsequent pregnancies. With the widespread use of RhIG, Rh disease of the fetus and newborn has almost disappeared in the developed world. The risk that an RhD
440:
Routine prenatal labs drawn at the beginning of every pregnancy include a blood type and an antibody screen. Mothers who are Rh negative (A−, B−, AB−, or O− blood types) and have anti-D antibodies (found on the antibody screen) need to determine the fetus's Rh antigen. If the fetus is also Rh
370:
A screening test to detect for the presence or absence of fetal cells can help determine if a quantitative test (Kleihauer-Betke or flow cytometry) is needed. This is done when exposure is suspected due to a potential sensitizing event (such as a car accident or
350:
more widespread use of molecular techniques to avoid missing women who appear to be Rh-D positive but are actually missing portions of the protein or have hybrid genes creating altered expression of the protein and still at risk of HDFN due to Anti-D.
430:
As medical management advances in this field, it is important that these patients be followed by high risk obstetricians/maternal-fetal medicine, and skilled neonatologists postpartum to ensure the most up to date and appropriate standard of care
1870:
206:
1792:
1777:
395:, can detect fetal DNA. This blood test is non-invasive to the fetus and can help determine the risk of HDFN. Testing has proven very accurate and is routinely done in the UK at the International Blood Group Reference Laboratory in Bristol.
214:
as the result of severe Rh disease. A) Ultrasound image of the fetal head showing scalp edema (arrow); (B) ultrasound image showing high abundance ascites (arrow) on a sagittal section of the abdomen; (C) Sinusoidal type fetal heart rate
354:
At the first prenatal visit, the mother is typed for ABO blood type and the presence or absence of RhD using a method sensitive enough to detect weaker versions of this antigen (known as weak-D) and a screen for antibodies is performed.
591:
invented by Wiener and later refined by Dr. Harry
Wallerstein. Approximately 50,000 infants received this treatment. However, this could only treat the disease after it took root and did not do anything to prevent the disease. In 1960,
600:, England proposed that the disease might be prevented by injecting the at-risk mother with an antibody against fetal red blood cells (anti-RhD). Nearly simultaneously, Dr. William Pollack, an immunologist and protein chemist at
304:) as a byproduct. This is not generally a problem during pregnancy, as the maternal circulation can compensate. However, once the infant is delivered, the immature system is not able to handle this amount of bilirubin alone and
988:
Scheffer PG, van der Schoot CE, Page-Christiaens GC, de Haas M (October 2011). "Noninvasive fetal blood group genotyping of rhesus D, c, E and of K in alloimmunised pregnant women: evaluation of a 7-year clinical experience".
231:, which is why no effects to the fetus are seen in first pregnancies for Rh-D mediated disease. However, in subsequent pregnancies with Rh+ fetuses, the IgG memory B cells mount an immune response when re-exposed, and these
2556:
1863:
374:
If the screening test is positive or the appropriate dose of RhoGam needs to be determined, a quantitative test is performed to determine a more precise amount of fetal blood to which the mother has been exposed.
558:
that was present on the husband's red blood cells (RBCs) but not present on his wife's. This suggested for the first time that a mother could make blood group antibodies because of immune sensitization to her
1856:
450:
Once a woman has been found to have made anti-D (or any clinically significant antibody against fetal red cells), she is followed as a high risk pregnancy with serial blood draws to determine the next steps
441:
negative (A−, B−, AB−, or O− blood types) then the pregnancy can be managed like any other pregnancy. The anti-D antibodies are only dangerous to Rh positive fetuses (A+, B+, AB+, or O+ blood types).
192:
485:—This is the method of choice since the late 1980s, and more effective than intraperitoneal transfusion. A sample of fetal blood can be taken from the umbilical vein prior to the transfusion.
1546:
Freda VJ, Gorman JG, Pollack W (January 1964). "Successful
Prevention of Experimental Rh Sensitization in Man With an Anti-Rh gamma2-Globulin Antibody Preparation: A Preliminary Report".
2561:
945:
Finning K, Martin P, Summers J, Daniels G (November 2007). "Fetal genotyping for the K (Kell) and Rh C, c, and E blood groups on cell-free fetal DNA in maternal plasma".
365:
If she is positive for anti-D antibodies, the pregnancy will be followed with monthly titers (levels) of the antibody to determine if any further intervention is needed.
554:. Since both parents were blood group O, which was believed to be compatible for transfusion, they concluded that there must be a previously undiscovered blood group
453:
Once the titer of anti-D reaches a certain threshold (normally 8 to 16), serial
Ultrasound and Doppler examinations are performed to detect signs of fetal anemia
563:'s RBCs as her only previous exposure would be the earlier pregnancy. They did not name this blood group antigen at the time, which is why the discovery of the
418:
negative mother can be alloimmunized by a RhD positive fetus can be reduced from approximately 16% to less than 0.1% by the appropriate administration of RhIG.
2244:
2259:
2249:
1754:
247:, a protein found on the surface of the fetal RBCs. The antibody-coated RBCs are destroyed by IgG antibodies binding and activating complement pathways.
153:(D) immune globulin, it was the most common type of HDFN. The disease ranges from mild to severe, and occurs in the second or subsequent pregnancies of
1729:
Friesen AD, Bowman JM, Price HW (1981). "Column Ion
Exchange Preparation and Characterization of an Rh Immune Globulin (WinRho) for Intravenous Use".
160:
Due to several advances in modern medicine, HDFN due to anti-D is preventable by treating the mother during pregnancy and soon after delivery with an
289:
The severe anemia taxes the heart to compensate by increasing output in an effort to deliver oxygen to the tissues and results in a condition called
258:
of the fetus is taxed as the liver and spleen attempt to put immature RBCs into circulation (erythroblasts, thus the previous name for this disease
422:
of the mothers had knowledge about it, while only 51% of the mothers had knowledge about the administration of prophylactic anti D after delivery.
386:
on a maternal blood sample are the most common ways to determine this, and the appropriate dose of RhoGam is calculated based on this information.
2239:
1429:
Wallerstein H (May 1946). "Treatment of severe erythroblastosis by simultaneous removal and replacement of the blood of the newborn infant".
1036:
456:
Detection of increased blood flow velocities in the fetus are a surrogate marker for fetal anemia that may require more invasive intervention
184:
Symptoms of Rh disease include yellowish amniotic fluid and enlarged spleen, liver or heart or buildup of fluid in the abdomen of the fetus.
2142:
605:
584:
in 1941 while
Landsteiner and Wiener published their method to type patients for an antibody causing transfusion reactions, known as “Rh".
2571:
1521:
2581:
2147:
312:(bilirubin deposition in the brain) can develop which may lead to brain damage or death. Sensitizing events during pregnancy include
1925:
782:
220:
which results in the mother's proliferation of IgM-secreting plasma B cells to eliminate the fetal Rh+ cells from her blood stream.
608:), came to the same realization in New York City. The three of them set out to prove it by injecting a group of male prisoners at
2468:
2443:
2234:
539:
146:
2535:
2485:
2053:
609:
2596:
1681:
Pollack W, Gorman JG, Freda VJ, Ascari WQ, Allen AE, Baker WJ (1968-05-06). "Results of clinical trials of RhoGAM in women".
488:
Often, this is all done at the same PUBS procedure to avoid the needs for multiple invasive procedures with each transfusion
2566:
2227:
1326:
Levine P, Vogel P, Katzin EM, Burnham L (October 1941). "Pathogenesis of
Erythroblastosis Fetalis: Statistical Evidence".
461:
If the flow velocity is found to be elevated a determination of the severity of anemia needs to ensue to determine if an
272:
Liver enlargement and the prolonged need for RBC production results in decreased ability to make other proteins, such as
2463:
2386:
2204:
2152:
652:
2453:
2358:
2295:
601:
82:
2176:
1240:
Landsteiner K, Wiener AS (1940). "An
Agglutinable Factor in Human Blood Recognized by Immune Sera for Rhesus Blood".
1097:
750:
Punt J, Stranford S, Jones P, Owen JA (2018). "Chapter 15: Allergy, Hypersensitivities, and
Chronic Inflammation.".
2300:
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2039:
2035:
1995:
1848:
527:
468:
This is normally done with a procedure called percutaneous umbilical cord blood sampling (PUBS or cordocentesis)
392:
333:
290:
280:(the fluid-retaining ability of blood plasma) leading to leakage of fluid into tissues and body cavities, termed
604:, and Dr. John Gorman (blood bank director at Columbia-Presbyterian) with Dr. Vincent Freda (an obstetrician at
379:
2576:
2396:
2317:
1807:
473:
462:
277:
172:(Rhoclone, Rhogam, AntiD). With successful mitigation of this disease by prevention through the use of anti-Rh
2492:
2458:
2063:
1983:
1973:
1920:
1277:"Studies on an Agglutinogen (Rh) in Hunan Blood Reacting With Anti-Rhesus Sera and With Human Isoantibodies"
636:
161:
2373:
2191:
2100:
2083:
576:
514:
414:
359:
111:
2307:
2015:
564:
358:
If she is negative for RhD protein expression and has not formed anti-D already, she is a candidate for
255:
244:
154:
531:
2586:
2345:
2335:
2137:
2093:
1591:"Antibody-mediated immune suppression to the Rh factor: animal models suggesting mechanism of action"
1438:
1335:
643:
for Clinical Medical Research for their work on rhesus blood types and the prevention of Rh disease.
588:
551:
507:
321:
62:
517:) can be used to reduce the need for exchange transfusion and to shorten the length of phototherapy.
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572:
266:
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1257:
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1014:
970:
802:
301:
1638:
Vossoughi S, Spitalnik SL (July 2019). "Conquering erythroblastosis fetalis: 50 years of RhIG".
858:
Kacker S, Vassallo R, Keller MA, Westhoff CM, Frick KD, Sandler SG, Tobian AA (September 2015).
623:
Ms. Marianne Cummins was the first at risk woman to receive a prophylactic injection of anti-Rh
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1905:
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1187:
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1079:
1032:
1006:
962:
927:
910:
Fasano RM (February 2016). "Hemolytic disease of the fetus and newborn in the molecular era".
889:
860:"Financial implications of RHD genotyping of pregnant women with a serologic weak D phenotype"
778:
732:
547:
501:
329:
305:
240:
77:
49:
1170:
Webb J, Delaney M (October 2018). "Red Blood Cell Alloimmunization in the Pregnant Patient".
703:"[Serious materno-fetal alloimmunization: about a case and review of the literature]"
612:
with antibody provided by Ortho, obtained by a fractionation technique developed by Pollack.
391:
There are also emerging tests using Cell-free DNA. Blood is taken from the mother, and using
2523:
2350:
2010:
1951:
1915:
1690:
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1602:
1555:
1485:
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954:
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568:
232:
221:
2480:
2266:
2158:
2078:
814:
282:
265:
As the liver and spleen enlarge under this unexpected demand for RBCs, a condition called
198:
133:
121:
Of maternal-fetal blood incompatibilities: 16% without antibody therapy, 0.1% with therapy
1442:
1339:
2105:
1963:
1694:
1607:
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1303:
1276:
1147:
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884:
859:
793:
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727:
702:
482:
383:
1801:
1490:
1473:
1226:
1123:"Systematic review of intravenous immunoglobulin in haemolytic disease of the newborn"
673:
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1884:
1667:
1371:
1002:
958:
325:
1710:
1624:
1575:
1261:
1199:
1018:
2164:
2005:
1507:
974:
718:
628:
1750:
National institute of Clinical Excellence (NICE) Guidelines for anti-D prophylaxis
1050:"Maternal-fetal Rhesus (Rh) factor incompatibility in Arar, northern Saudi Arabia"
176:(D) immune globulin, other antibodies are more commonly the cause of HDFN today.
17:
1812:
1450:
2508:
2410:
2276:
1978:
1831:
1347:
632:
593:
543:
317:
309:
58:
54:
1406:
1389:
1183:
923:
2518:
2475:
2416:
1786:
1253:
580:
535:
106:
1213:
Levine P, Stetson RE (1939). "An Unusual Case of Intra-Group Agglutination".
655:– Australian who donated blood over 1150 times to save babies with Rh disease
2421:
1880:
597:
313:
1659:
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1499:
1458:
1415:
1355:
1312:
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893:
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228:
224:
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1937:
1138:
555:
273:
1651:
875:
1941:
1781:
1749:
1031:
Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects
620:(D) immune globulin could prevent alloimmunization during pregnancy.
165:
269:
develops, and this taxes the immature heart and circulatory system.
2325:
2072:
1589:
Pollack W, Gorman JG, Hager HJ, Freda VJ, Tripodi D (1968-05-06).
1065:
560:
205:
191:
72:
Incompatibility between mother antibodies and fetal Rhesus factor
1852:
478:
Intraperitoneal transfusion—blood transfused into fetal abdomen
2557:
Haemorrhagic and haematological disorders of fetus and newborn
1522:"William Pollack dies at 87; helped conquer deadly Rh disease"
534:
published their findings about a 25-year-old mother who had a
44:
Rhesus isoimmunization, Rh (D) disease, rhesus incompatibility
550:
due to blood loss during delivery. However, she had a severe
1127:
Archives of Disease in Childhood. Fetal and Neonatal Edition
300:
The destruction of RBCs leads to elevated bilirubin levels (
843:
Fung MK, Grossman BJ, Hillyer CD, Westhoff CM, eds (2014).
701:
Zineb B, Boutaina L, Ikram L, Driss MR, Mohammed D (2015).
210:
Ultrasound images and electrocardiogram of an infant with
196:
Newborn infant with severe Rhesus disease, suffering from
101:
Prophylactic antibody therapy, intrauterine transfusion
1373:
Rh: The Intimate History of a Disease and Its Conquest
765:
Maitra A (2010). "Diseases of Infancy and Childhood".
639:, Vincent Freda, and William Pollack each received an
546:
O, so the husband's blood was used to give his wife a
481:
Intravascular transfusion—blood transfused into fetal
1759:
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2395:
2372:
2344:
2316:
2213:
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2128:
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2062:
2028:
1992:
1960:
1934:
1902:
1891:
1822:
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117:
105:
97:
89:
76:
68:
48:
40:
35:
1370:
296:If left untreated, the result may be fetal death.
157:women when the biologic father is Rh-D positive.
93:Administration of antibody therapy to the mother
828:Wong EC, ed. (2015). "Alloimmune cytopenias.".
754:(8th ed.). WH Freeman. pp. 1086–1087.
767:Robbins and Cotran Pathologic Basis of Disease
2562:Disorders originating in the perinatal period
1864:
830:Pediatric Transfusion: A physician's handbook
510:if the neonate has moderate or severe disease
8:
1098:"Percutaneous Umbilical Cord Blood Sampling"
769:. Vol. 43. Elsevier. pp. 447–483.
250:The resulting anemia has multiple sequelae:
243:. These antibodies are directed against the
1390:"Alexander S. Wiener: the man and his work"
1275:Landsteiner K, Wiener AS (September 1941).
1215:Journal of the American Medical Association
2125:
1899:
1871:
1857:
1849:
1760:
1755:Summary of transfusion reactions in the US
587:The first treatment for Rh disease was an
147:hemolytic disease of the fetus and newborn
32:
1606:
1489:
1405:
1302:
1292:
1146:
1073:
912:Seminars in Fetal & Neonatal Medicine
883:
792:
726:
362:prophylaxis to prevent alloimmunization.
678:The Children's Hospital of Philadelphia
665:
1121:Gottstein R, Cooke RW (January 2003).
905:
903:
810:
800:
145:, and blue baby disease) is a type of
27:Blood disease of the fetus and newborn
832:(4th ed.). AABB. pp. 45–61.
7:
2143:Infant respiratory distress syndrome
1281:The Journal of Experimental Medicine
847:(18th ed.). Bethesda, MD: AABB.
696:
694:
606:Columbia-Presbyterian Medical Center
2148:Transient tachypnea of the newborn
1695:10.1111/j.1537-2995.1968.tb04895.x
1608:10.1111/j.1537-2995.1968.tb04891.x
1560:10.1111/j.1537-2995.1964.tb02824.x
1048:Aljuhaysh, RM (25 December 2017).
775:10.1016/b978-1-4377-0792-2.50015-8
25:
1926:Twin-to-twin transfusion syndrome
1242:Experimental Biology and Medicine
1227:10.1001/jama.1939.72800270002007a
85:, sonography, physical assessment
2444:Vertically transmitted infection
1003:10.1111/j.1471-0528.2011.03028.x
959:10.1111/j.1537-2995.2007.01437.x
602:Ortho Pharmaceutical Corporation
575:with their first publication of
540:hemolytic disease of the newborn
2536:Fetal Alcohol Spectrum Disorder
2486:Group B streptococcal infection
2054:Intrauterine growth restriction
707:The Pan African Medical Journal
610:Sing Sing Correctional Facility
567:blood type is credited to Drs.
278:plasma colloid osmotic pressure
1879:Conditions originating in the
719:10.11604/pamj.2015.22.137.3508
474:Intrauterine blood transfusion
1:
2228:Vitamin K deficiency bleeding
1491:10.1016/S0140-6736(04)16525-2
239:cross the placenta and enter
202:. The infant did not survive.
2387:Periventricular leukomalacia
2205:Persistent fetal circulation
2153:Meconium aspiration syndrome
1451:10.1126/science.103.2680.583
1394:Transfusion Medicine Reviews
1172:Transfusion Medicine Reviews
653:James Harrison (blood donor)
513:Intravenous Immunoglobulin (
2296:Intraventricular hemorrhage
1348:10.1126/science.94.2442.371
413:In an RhD negative mother,
291:high output cardiac failure
83:Blood compatibility testing
2613:
2572:Health issues in pregnancy
2301:Germinal matrix hemorrhage
2291:Velamentous cord insertion
2182:Bronchopulmonary dysplasia
1407:10.1016/j.tmrv.2008.05.007
1377:. Macmillan Publishing Co.
1184:10.1016/j.tmrv.2018.07.002
924:10.1016/j.siny.2015.10.006
405:positive for the antigen.
2582:Acquired hemolytic anemia
2331:Necrotizing enterocolitis
2040:Large for gestational age
2036:Small for gestational age
1254:10.3181/00379727-43-11151
334:external cephalic version
276:, and this decreases the
1388:Reid ME (October 2008).
463:intrauterine transfusion
260:erythroblastosis fetalis
2493:Neonatal conjunctivitis
1984:Single umbilical artery
1974:Umbilical cord prolapse
1921:Placental insufficiency
1894:complicating pregnancy,
332:, abdominal trauma and
2469:ureaplasma urealyticum
2177:Wilson–Mikity syndrome
2101:Brachial plexus injury
1472:Wright P (June 2004).
415:Rho(D) immune globulin
235:anti-Rh(D) antibodies
216:
203:
143:rhesus incompatibility
112:Rho(D) immune globulin
2597:Polyclonal antibodies
2417:Congenital hypertonia
2308:Anemia of prematurity
2016:Shoulder presentation
1369:Zimmerman DR (1973).
1102:pennmedicine.adam.com
256:haematopoietic system
209:
195:
2567:Transfusion medicine
2422:Congenital hypotonia
2336:Meconium peritonitis
2138:Intrauterine hypoxia
2094:Subgaleal hemorrhage
1294:10.1084/jem.74.4.309
1054:Electronic Physician
589:exchange transfusion
552:transfusion reaction
542:. Both parents were
508:Exchange transfusion
380:Kleihauer–Betke test
322:therapeutic abortion
63:transfusion medicine
2531:Neonatal withdrawal
2514:Perinatal mortality
2364:Sclerema neonatorum
2220:hematologic disease
1443:1946Sci...103..583W
1340:1941Sci....94..371L
641:Albert Lasker Award
573:Alexander S. Wiener
267:portal hypertension
170:(D) immune globulin
2464:mycoplasma hominis
2449:Neonatal infection
2405:Gray baby syndrome
2382:Perinatal asphyxia
2272:Hyperbilirubinemia
2049:Postterm pregnancy
1896:labour or delivery
1823:External resources
1139:10.1136/fn.88.1.F6
538:baby that died of
302:hyperbilirubinemia
245:Rhesus (Rh) factor
217:
204:
180:Signs and symptoms
18:Rh isoimmunization
2544:
2543:
2432:
2431:
2282:Neonatal jaundice
2200:Pneumopericardium
2170:Pneumomediastinum
2111:Klumpke paralysis
2089:Caput succedaneum
2024:
2023:
1892:Maternal factors
1846:
1845:
1652:10.1111/trf.15307
1526:Los Angeles Times
1437:(2680): 583–584.
1334:(2442): 371–372.
1060:(12): 5908–5913.
1037:978-0-12-397788-5
997:(11): 1340–1348.
953:(11): 2126–2133.
876:10.1111/trf.13074
548:blood transfusion
502:neonatal jaundice
500:Phototherapy for
330:ectopic pregnancy
241:fetal circulation
229:placental barrier
227:do not cross the
125:
124:
78:Diagnostic method
30:Medical condition
16:(Redirected from
2604:
2524:Infant mortality
2359:Erythema toxicum
2351:thermoregulation
2318:Gastrointestinal
2126:
2122:Affected systems
1999:
1967:
1952:Chorioamnionitis
1945:
1916:Placenta praevia
1909:
1900:
1873:
1866:
1859:
1850:
1761:
1738:
1731:J. Appl. Biochem
1715:
1714:
1678:
1672:
1671:
1646:(7): 2195–2196.
1635:
1629:
1628:
1610:
1586:
1580:
1579:
1543:
1537:
1536:
1534:
1533:
1518:
1512:
1511:
1493:
1469:
1463:
1462:
1426:
1420:
1419:
1409:
1385:
1379:
1378:
1376:
1366:
1360:
1359:
1323:
1317:
1316:
1306:
1296:
1272:
1266:
1265:
1237:
1231:
1230:
1210:
1204:
1203:
1167:
1161:
1160:
1150:
1118:
1112:
1111:
1109:
1108:
1094:
1088:
1087:
1077:
1045:
1039:
1029:
1023:
1022:
985:
979:
978:
942:
936:
935:
907:
898:
897:
887:
870:(9): 2095–2103.
855:
849:
848:
845:Technical Manual
840:
834:
833:
825:
819:
818:
812:
808:
806:
798:
796:
762:
756:
755:
747:
741:
740:
730:
698:
689:
688:
686:
685:
670:
569:Karl Landsteiner
532:Rufus E. Stetson
33:
21:
2612:
2611:
2607:
2606:
2605:
2603:
2602:
2601:
2577:Blood disorders
2547:
2546:
2545:
2540:
2497:
2481:Neonatal sepsis
2428:
2397:Musculoskeletal
2391:
2368:
2349:
2340:
2312:
2267:Hydrops fetalis
2218:
2209:
2186:
2159:Pleural disease
2117:
2079:Cephalohematoma
2058:
2020:
1993:
1988:
1961:
1956:
1935:
1930:
1903:
1895:
1893:
1887:
1877:
1847:
1842:
1841:
1818:
1817:
1772:
1746:
1741:
1728:
1724:
1722:Further reading
1719:
1718:
1680:
1679:
1675:
1637:
1636:
1632:
1588:
1587:
1583:
1545:
1544:
1540:
1531:
1529:
1520:
1519:
1515:
1471:
1470:
1466:
1428:
1427:
1423:
1387:
1386:
1382:
1368:
1367:
1363:
1325:
1324:
1320:
1274:
1273:
1269:
1239:
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1234:
1212:
1211:
1207:
1169:
1168:
1164:
1120:
1119:
1115:
1106:
1104:
1096:
1095:
1091:
1047:
1046:
1042:
1030:
1026:
987:
986:
982:
944:
943:
939:
909:
908:
901:
857:
856:
852:
842:
841:
837:
827:
826:
822:
809:
799:
785:
764:
763:
759:
752:Kuby immunology
749:
748:
744:
700:
699:
692:
683:
681:
672:
671:
667:
662:
649:
626:
619:
524:
504:in mild disease
497:
437:
428:
411:
402:
347:
342:
283:hydrops fetalis
212:hydrops fetalis
199:hydrops fetalis
190:
188:Pathophysiology
182:
175:
169:
152:
134:isoimmunization
130:(also known as
31:
28:
23:
22:
15:
12:
11:
5:
2610:
2608:
2600:
2599:
2594:
2589:
2584:
2579:
2574:
2569:
2564:
2559:
2549:
2548:
2542:
2541:
2539:
2538:
2533:
2528:
2527:
2526:
2521:
2511:
2505:
2503:
2499:
2498:
2496:
2495:
2490:
2489:
2488:
2478:
2473:
2472:
2471:
2466:
2461:
2459:herpes simplex
2456:
2446:
2440:
2438:
2434:
2433:
2430:
2429:
2427:
2426:
2425:
2424:
2419:
2407:
2401:
2399:
2393:
2392:
2390:
2389:
2384:
2378:
2376:
2374:Nervous system
2370:
2369:
2367:
2366:
2361:
2355:
2353:
2342:
2341:
2339:
2338:
2333:
2328:
2322:
2320:
2314:
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2305:
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2293:
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2279:
2269:
2264:
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2257:
2252:
2247:
2242:
2231:
2230:
2224:
2222:
2211:
2210:
2208:
2207:
2202:
2196:
2194:
2192:Cardiovascular
2188:
2187:
2185:
2184:
2179:
2174:
2173:
2172:
2167:
2155:
2150:
2145:
2140:
2134:
2132:
2123:
2119:
2118:
2116:
2115:
2114:
2113:
2108:
2098:
2097:
2096:
2091:
2086:
2081:
2068:
2066:
2060:
2059:
2057:
2056:
2051:
2042:
2032:
2030:
2026:
2025:
2022:
2021:
2019:
2018:
2013:
2008:
2002:
2000:
1990:
1989:
1987:
1986:
1981:
1976:
1970:
1968:
1964:umbilical cord
1958:
1957:
1955:
1954:
1948:
1946:
1932:
1931:
1929:
1928:
1923:
1918:
1912:
1910:
1897:
1889:
1888:
1878:
1876:
1875:
1868:
1861:
1853:
1844:
1843:
1840:
1839:
1827:
1826:
1824:
1820:
1819:
1816:
1815:
1804:
1789:
1773:
1768:
1767:
1765:
1764:Classification
1758:
1757:
1752:
1745:
1744:External links
1742:
1740:
1739:
1725:
1723:
1720:
1717:
1716:
1689:(3): 151–153.
1673:
1630:
1601:(3): 134–145.
1581:
1538:
1513:
1484:(9427): 2195.
1464:
1421:
1400:(4): 300–316.
1380:
1361:
1318:
1287:(4): 309–320.
1267:
1232:
1205:
1178:(4): 213–219.
1162:
1113:
1089:
1040:
1024:
980:
937:
899:
850:
835:
820:
811:|journal=
783:
757:
742:
690:
664:
663:
661:
658:
657:
656:
648:
645:
637:John G. Gorman
624:
617:
523:
520:
519:
518:
511:
505:
496:
493:
492:
491:
490:
489:
486:
483:umbilical vein
479:
471:
470:
469:
459:
458:
457:
451:
448:
447:
446:
436:
433:
427:
424:
410:
407:
401:
400:Paternal blood
398:
397:
396:
389:
388:
387:
384:Flow Cytometry
372:
368:
367:
366:
363:
346:
345:Maternal blood
343:
341:
338:
298:
297:
294:
287:
270:
263:
189:
186:
181:
178:
173:
167:
150:
139:Rh (D) disease
123:
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119:
115:
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109:
103:
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99:
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94:
91:
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52:
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38:
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29:
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24:
14:
13:
10:
9:
6:
4:
3:
2:
2609:
2598:
2595:
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2590:
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2578:
2575:
2573:
2570:
2568:
2565:
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2560:
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2534:
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2500:
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2238:
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2236:
2233:
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2229:
2226:
2225:
2223:
2221:
2216:
2212:
2206:
2203:
2201:
2198:
2197:
2195:
2193:
2189:
2183:
2180:
2178:
2175:
2171:
2168:
2166:
2163:
2162:
2161:
2160:
2156:
2154:
2151:
2149:
2146:
2144:
2141:
2139:
2136:
2135:
2133:
2131:
2127:
2124:
2120:
2112:
2109:
2107:
2104:
2103:
2102:
2099:
2095:
2092:
2090:
2087:
2085:
2082:
2080:
2077:
2076:
2075:
2074:
2070:
2069:
2067:
2065:
2061:
2055:
2052:
2050:
2046:
2045:Preterm birth
2043:
2041:
2037:
2034:
2033:
2031:
2027:
2017:
2014:
2012:
2009:
2007:
2004:
2003:
2001:
1998:
1997:
1991:
1985:
1982:
1980:
1977:
1975:
1972:
1971:
1969:
1966:
1965:
1959:
1953:
1950:
1949:
1947:
1944:
1943:
1939:
1933:
1927:
1924:
1922:
1919:
1917:
1914:
1913:
1911:
1908:
1907:
1901:
1898:
1890:
1886:
1885:fetal disease
1882:
1874:
1869:
1867:
1862:
1860:
1855:
1854:
1851:
1838:
1834:
1833:
1829:
1828:
1825:
1821:
1814:
1810:
1809:
1805:
1803:
1799:
1798:
1794:
1790:
1788:
1784:
1783:
1779:
1775:
1774:
1771:
1766:
1762:
1756:
1753:
1751:
1748:
1747:
1743:
1736:
1732:
1727:
1726:
1721:
1712:
1708:
1704:
1700:
1696:
1692:
1688:
1684:
1677:
1674:
1669:
1665:
1661:
1657:
1653:
1649:
1645:
1641:
1634:
1631:
1626:
1622:
1618:
1614:
1609:
1604:
1600:
1596:
1592:
1585:
1582:
1577:
1573:
1569:
1565:
1561:
1557:
1553:
1549:
1542:
1539:
1527:
1523:
1517:
1514:
1509:
1505:
1501:
1497:
1492:
1487:
1483:
1479:
1475:
1474:"Ronald Finn"
1468:
1465:
1460:
1456:
1452:
1448:
1444:
1440:
1436:
1432:
1425:
1422:
1417:
1413:
1408:
1403:
1399:
1395:
1391:
1384:
1381:
1375:
1374:
1365:
1362:
1357:
1353:
1349:
1345:
1341:
1337:
1333:
1329:
1322:
1319:
1314:
1310:
1305:
1300:
1295:
1290:
1286:
1282:
1278:
1271:
1268:
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1259:
1255:
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1243:
1236:
1233:
1228:
1224:
1220:
1216:
1209:
1206:
1201:
1197:
1193:
1189:
1185:
1181:
1177:
1173:
1166:
1163:
1158:
1154:
1149:
1144:
1140:
1136:
1132:
1128:
1124:
1117:
1114:
1103:
1099:
1093:
1090:
1085:
1081:
1076:
1071:
1067:
1066:10.19082/5908
1063:
1059:
1055:
1051:
1044:
1041:
1038:
1034:
1028:
1025:
1020:
1016:
1012:
1008:
1004:
1000:
996:
992:
984:
981:
976:
972:
968:
964:
960:
956:
952:
948:
941:
938:
933:
929:
925:
921:
917:
913:
906:
904:
900:
895:
891:
886:
881:
877:
873:
869:
865:
861:
854:
851:
846:
839:
836:
831:
824:
821:
816:
804:
795:
790:
786:
784:9781437707922
780:
776:
772:
768:
761:
758:
753:
746:
743:
738:
734:
729:
724:
720:
716:
712:
708:
704:
697:
695:
691:
679:
675:
669:
666:
659:
654:
651:
650:
646:
644:
642:
638:
634:
630:
621:
613:
611:
607:
603:
599:
595:
590:
585:
582:
578:
574:
570:
566:
562:
557:
553:
549:
545:
541:
537:
533:
529:
528:Philip Levine
526:In 1939 Drs.
521:
516:
512:
509:
506:
503:
499:
498:
494:
487:
484:
480:
477:
476:
475:
472:
467:
466:
465:is necessary
464:
460:
455:
454:
452:
449:
443:
442:
439:
438:
434:
432:
425:
423:
419:
416:
408:
406:
399:
394:
390:
385:
381:
377:
376:
373:
371:miscarriage).
369:
364:
361:
357:
356:
353:
352:
351:
344:
339:
337:
335:
331:
327:
326:amniocentesis
323:
319:
315:
311:
307:
303:
295:
292:
288:
285:
284:
279:
275:
271:
268:
264:
261:
257:
254:The immature
253:
252:
251:
248:
246:
242:
238:
234:
230:
226:
223:
213:
208:
201:
200:
194:
187:
185:
179:
177:
171:
163:
158:
156:
155:Rh-D negative
148:
144:
140:
136:
135:
129:
120:
116:
113:
110:
108:
104:
100:
96:
92:
88:
84:
81:
79:
75:
71:
67:
64:
60:
56:
53:
51:
47:
43:
39:
34:
19:
2409:
2254:
2165:Pneumothorax
2157:
2071:
2064:Birth trauma
2006:Breech birth
1996:presentation
1994:
1962:
1936:
1904:
1830:
1806:
1791:
1776:
1734:
1730:
1686:
1682:
1676:
1643:
1639:
1633:
1598:
1594:
1584:
1551:
1547:
1541:
1530:. Retrieved
1528:. 2013-11-17
1525:
1516:
1481:
1477:
1467:
1434:
1430:
1424:
1397:
1393:
1383:
1372:
1364:
1331:
1327:
1321:
1284:
1280:
1270:
1245:
1241:
1235:
1221:(2): 126–7.
1218:
1214:
1208:
1175:
1171:
1165:
1133:(1): F6-10.
1130:
1126:
1116:
1105:. Retrieved
1101:
1092:
1057:
1053:
1043:
1027:
994:
990:
983:
950:
946:
940:
918:(1): 28–34.
915:
911:
867:
863:
853:
844:
838:
829:
823:
766:
760:
751:
745:
710:
706:
682:. Retrieved
680:. 2014-08-23
677:
674:"Rh Disease"
668:
629:Cyril Clarke
622:
614:
586:
581:blood-typing
577:their tables
525:
429:
420:
412:
403:
348:
299:
281:
259:
249:
236:
218:
211:
197:
183:
159:
142:
138:
131:
127:
126:
2587:Neonatology
2509:Miscarriage
2411:muscle tone
2277:Kernicterus
2130:Respiratory
2106:Erb's palsy
2011:Asynclitism
1979:Nuchal cord
1832:MedlinePlus
1683:Transfusion
1640:Transfusion
1595:Transfusion
1548:Transfusion
947:Transfusion
864:Transfusion
633:Ronald Finn
594:Ronald Finn
544:blood group
318:miscarriage
310:kernicterus
59:haematology
55:Paediatrics
41:Other names
2592:Obstetrics
2551:Categories
2519:Stillbirth
2476:Omphalitis
2437:Infections
2346:Integument
1737:: 164–175.
1532:2019-09-11
1107:2019-09-11
684:2021-11-21
660:References
426:Management
409:Prevention
225:antibodies
128:Rh disease
107:Medication
90:Prevention
36:Rh disease
2245:Anti-Kell
1883:period /
1881:perinatal
1668:195786606
1554:: 26–32.
813:ignored (
803:cite book
598:Liverpool
536:stillborn
495:Postnatal
435:Antenatal
340:Diagnosis
314:c-section
215:recording
162:injection
118:Frequency
98:Treatment
50:Specialty
2215:Bleeding
1906:placenta
1711:42240813
1660:31268587
1625:10535055
1576:35474015
1568:14105934
1500:15248345
1459:21026828
1416:18848157
1356:17820878
1313:19871137
1262:58298368
1200:51958636
1192:30097223
1157:12496219
1084:29560141
1019:32946225
1011:21668766
967:17958542
932:26589360
894:25808011
737:26889318
647:See also
306:jaundice
2454:rubella
2084:Chignon
1938:chorion
1813:D012203
1703:4173363
1617:4173360
1508:2243030
1439:Bibcode
1431:Science
1336:Bibcode
1328:Science
1304:2135190
1248:: 223.
1148:1755998
1075:5843415
975:8292568
885:4739823
794:5182838
728:4742050
713:: 137.
556:antigen
522:History
274:albumin
166:anti-Rh
132:rhesus
2029:Growth
1942:amnion
1837:001600
1709:
1701:
1666:
1658:
1623:
1615:
1574:
1566:
1506:
1498:
1478:Lancet
1457:
1414:
1354:
1311:
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1260:
1198:
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1017:
1009:
973:
965:
930:
892:
882:
791:
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565:rhesus
360:RhoGam
69:Causes
2502:Other
2326:Ileus
2073:scalp
1802:773.0
1787:P55.0
1707:S2CID
1664:S2CID
1621:S2CID
1572:S2CID
1504:S2CID
1258:S2CID
1196:S2CID
1015:S2CID
971:S2CID
596:, in
561:fetus
141:, or
2260:Rh E
2255:Rh D
2250:Rh c
1808:MeSH
1797:9-CM
1699:PMID
1656:PMID
1613:PMID
1564:PMID
1496:PMID
1455:PMID
1412:PMID
1352:PMID
1309:PMID
1188:PMID
1153:PMID
1080:PMID
1033:ISBN
1007:PMID
991:BJOG
963:PMID
928:PMID
890:PMID
815:help
779:ISBN
733:PMID
579:for
571:and
530:and
515:IVIG
378:The
2348:and
2240:ABO
2235:HDN
2217:and
1793:ICD
1778:ICD
1691:doi
1648:doi
1603:doi
1556:doi
1486:doi
1482:363
1447:doi
1435:103
1402:doi
1344:doi
1299:PMC
1289:doi
1250:doi
1223:doi
1219:113
1180:doi
1143:PMC
1135:doi
1070:PMC
1062:doi
999:doi
995:118
955:doi
920:doi
880:PMC
872:doi
789:PMC
771:doi
723:PMC
715:doi
393:PCR
382:or
308:or
233:IgG
222:IgM
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