Severe anti-C hemolytic disease of the newborn John M. Bowman, MD: Janet M. Pollock, RT: Frank A. Manning, MD," and Chris R. Harman, MD b Winnipeg, Manitoba, Canada OBJECTIVE: Because of referral of a C-alloimmunized pregnant woman with a previous hydropic death whose fetus survived after four intraperitoneal transfusions, prevalence and severity of anti-C hemolytic disease of the newborn were investigated. STUDY DESIGN: The numbers of C- or Ce-alloimmunized pregnancies in Manitoban women and their outcome for the 28-year period ending Oct. 31, 1990, were reviewed. The literature relating to C or Ce alloimmunization from 1944 to 1990 was surveyed. RESULTS: In Manitoba for the period reviewed there were 120 pregnancies in 80 C- or Ce-alloimmunized women. Twenty-two ended in abortion and two in fetal death unrelated to anti-C or anti-Ceo Of the remaining 96, 33 fetuses of 32 pregnancies were affected but only eight (6.7%) required treatment after birth. None were severely affected. In the literature there are only three other reported deaths from C or Ce hemolytic disease; two of the three may have been the same patient. The prevalence of C or Ce alloimmunization reported in various series, including our own, ranged from 8.7 to 185 per 100,000 pregnancies. CONCLUSIONS: Because on rare occasions, C or Ce alloimmunization can cause severe hemolytic disease, criteria for investigative measures such as amniocentesis or cordocentesis do not differ from the criteria for instituting these measures in Rho (D)-alloimmunized pregnancies. (AM J OBSTET GVNECOL 1992;166:1239-43.)
Key words: Anti-C hemolytic disease, fer.al transfusions Although anti-C is listed as an antibody capable of causing severe hemolytic disease of the newborn,l reports of anti-C causing severe hemolytic disease are extremely rare. In 1986 the Rh Laboratory and the Division of Fetal and Maternal Medicine, Faculty of Medicine, University of Manitoba, and the Health Sciences Centre, Winnipeg, participated in the management of an anti-C alloimmunized pregnant women whose fetus required intrauterine transfusions to survive. In 46 years of experience with maternal alloimmunization, this was the Rh Laboratory's first example of anti-C hemolytic disease of such severity. We report this case in detail, with a review of the Rh Laboratory experience and the experience of others with anti-C or anti-Ce alloimmunization.
Case report At the time of her first pregnancy this para 2, gravida 3, group A, Rh-positive, C-negative, Cw-negative, e-negative (R2R2) woman was transfused at cesarean From the Rh Laboratory, Department of Pediatrics and Child Health' and the Division of Fetal and Maternal Medicine, Departmeut of Obstetrics, Gynecology, and Reproductive Sciences,' FaClllty of Medicine, University of Manitoba, and the Health Sciences Centre. Received for publication May 30,1991; revised August 20,1991; acrepted October 8, 1991. Reprint requests: John A1. Bowman, MD, Rh Laboratory, Women's Hospital, Health Sciences Centre, 735 Notre Dame Ave., Winnipeg, Manitoba, Canada R3E OL8.
6/1 /34297
section for abruptio placentae. Her second pregnancy ended at 37 weeks' gestation with a hydropic stillbirth. At that time she was found to have very strong anti-C and anti-Cw and very weak anti-e blood group antibodies. Her husband was group B, Rh positive, C positive, e positive, and Cw negative (R'R'). Thus anti-C was the alloantibody responsible for the hydropic fetal death. Mrs. S. was referred to Winnipeg in 1986, in her third pregnancy at 221/2 weeks' gestation. The anti-C titer was 256 in albumin and I in saline solution. Two amniocenteses had been carried out at the referring center, the d optical density readings at 450 nm (dOD.,,,) were 0.355 and 0.362 at 201/2 and 221/2 weeks' gestation. Two days later in Winnipeg, at the time of the first intraperitoneal fetal transfusion, the dOD.,o reading was 0.346. Hepatomegaly was evident on ultrasonography, but the fetus was not hydropic. Four intraperitoneal fetal transfusions were carried out with infusion of tightly packed, fresh, compatible, group 0, C-negative, Cw-negative, e-negative (WR 2 ), Kell-negative red blood cells at 221/2, 24, 271/2, and 31 weeks' gestation. She was delivered of a female infant by elective cesarean section at 331/2 weeks' gestation in the tertiary-level center from which she had been referred. Jaundice was present and there was marked hepatosplenomegaly. Cord red blood cells were 99.7% adult donor in origin by Kleihauer acid elution testing. Cord hemoglobin level was 117 gm/L; cord serum bilirubin level was 138 f.lmollL total and 38 f.lmollL by direct reaction. 1239
1240 Bowman et a\.
April 1992 Am J Obstet Gynecol
Table I. Anti-C or anti-Ce alloimmunization, Manitoba, Nov. 1, 1962, to Oct. 31, 1990 475,000 pregnancies Anti-C or anti-Ce Total anti-C Abortions and Affected, no (Direct antiglobulin Perinatal or intrauterine unrelated Unaffected (direct antiglobulin treatment or anti-Ce test-positive) death caused by anti-C immunized pregnancies losses test-negative) infants required treatment required* women and anti-Ce
80
120t
64
25§
811
o
*Treatment: exchange transfusion and/or phototherapy. tFifty of the 120 were not detectable by an indirect antiglobulin test. tTwenty-two spontaneous or induced abortions, two fetal deaths unrelated to anti-C or anti-Ceo Both women had subsequent healthy surviving infants. §One set of twins, 24 pregnancies. 1I0ne woman accounted for four of the eight babies.
An immediate double-volume exchange transfusion was carried out, followed by a second exchange transfusion on the second day of life. The highest indirect serum bilirubin level was 228 f,LmoliL (13.4 mg/dl). She had evidence of transient hepatocellular damage!' 3 an index of severe hemolytic disease, with the direct (conjugated) bilirubin level peaking at 125 f,Lmol/L. The neonatal nursery course was uneventful. At 7 months of age she was progressing normally.
Results Prevalence of anti-C or anti·Ce alloimmuni. zation. The Rh Laboratory records for the 28-year period, Nov. 1, 1962, to Oct. 31, 1990, were reviewed. The laboratory is responsible for antibody screening of all women in Manitoba (population of 1 million with 17,000 pregnancies annually). The policy of the laboratory is that all pregnant women should be screened at their first prenatal visit. Unimmunized Rh-negative women are then screened at monthly intervals. A second blood sample for screening of unimmunized Rhpositive women is requested at 28 to 34 weeks' gestation but is not always obtained. Antibody screening of maternal serum is carried out by a sensitive two-stage, enzyme-treated red blood cell method' and a low-ionic autoanalyzer method.' If an Rh-positive pregnant woman has a blood group alloantibody, further blood samples are requested at 2to 8-week intervals, depending on length of gestation, the specificity of the antibody, and its strength (titer). If the antibody is one that is known to cause fetal hemolytic disease, amniotic fluid spectrophotometry or, in the past 5 years, fetal blood sampling is carried out, on the basis of the same criteria used for initiating either procedure in Rh-negative, Rho (D)-immunized pregnant women (history of a prior perinatal death, a fetus or infant requiring treatment, or antibody titers of ~ 16 in albumin or ~32 to 64 by indirect antiglobulin).6 Because the Rh Laboratory carries out all cord blood testing and treatment of affected babies after birth and, in conjunction with the Division of Fetal and Maternal Medicine, carries out all amniotic fluid measurements,
fetal blood testing, and fetal transfusions in Manitoba, the subsequent course of each pregnancy and the fetalneonatal outcome are known and are part of each alloimmunized woman's Rh Laboratory record. The numbers of anti-C or anti-Ce alloimmunized pregnancies, excluding those in Rh-negative women with anti-D, for the 28-year period ending Oct. 31, 1990, are set out in Table I, with their respective outcomes. There were 80 C- or Ce-alloimmunized women who had 120 pregnancies (121 conceptuses) in the 28year period. Nineteen women, six of whom were Native Americans, had 59 ofthe pregnancies (60 conceptuses). Of the remaining 61 women who had one C- or Cealloimmunized pregnancy, only three were Native Americans. There were 22 abortions and two fetal deaths unrelated to C or Ce alloimmunization in the study group. Of the remaining 96 cases, 33 fetuses of 32 pregnancies (27.5%) were affected. However, only eight fetuses (6.7%) required treatment after birth: Two needed exchange transfusions and six required only phototherapy. Two of the six subsequently required simple transfusions. All eight treated babies were only moderately affected. None required induced early delivery and none required intrauterine fetal transfusion. In this series there were no deaths caused by C or Ce alloimmunization. One woman, a Native American, accounted for four of the eight babies who needed treatment (one required exchange transfusion and the other three required phototherapy only). Her next baby, again affected, did not need treatment. In all, she accounted for seven of the 120 C- or Ce-alloimmunized pregnancies. Some Manitoban C-alloimmunized women had antiC or anti-Ce antibody titers as high as that of our patient (256 in albumin, 1 in saline solution). Five women with affected babies who required treatment had anti-C titers of 128 in albumin and 8 in saline solution, 64 in albumin and 8 in saline solution, 64 in albumin and 32 in saline solution, 16 in albumin and 16 in saline so-
Severe anti-C hemolytic disease
Volume 166 Number 4
1241
Table II. Surveys that include C and Ce maternal alloimmunization No. with anti-C or anti-Ce
Author
Hardy and Napier8 Clarke et al."
Pregnant population
No.
507,720
44
Per 100,000 pregnancies
8.7
6-7 million
Bowell et al." Pepperell et al. 18 Polesky'9
280,000 72,138
38 9
13.6 12.5
43,100
5
11.6
Queenan et aUo Spielman and Seidl 2l Beaj22
18,378
34
16,643
0
41,078
5
12.2
Zuliani et al. 2' Solola et al. 24 Giblett25
9,525t 5,559 6 yr Seattle
2 0 4
21.0
Current investigation
475,000
120t
25.3
185
Babies requiring treatment
Affected offspring
No.
No. per 100,000 pregnancies
No.
25
4.9
3
Perinatal mortality report only 5 1.8 4 5.5
6.8
Death from hemolytic disease of fetus and newborn
2* 1*
I
2
Hemolytic disease of fetus and newborn not described 10.9 2 0
Proportion (% of whole)
2.6 22.2
0 0
2.9
0
0
Hemolytic disease of fetus and newborn not described 0 0 0 0 (Degree of hemolytic disease of 2 fetus and newborn not described) 8§ 33 6.9 6.7
0
0 0
0
*One of the deaths in the series of Hardy and Napier8 may also be the one in the series of Clarke et al. 9 tHighly selected referred population. tOne set of twins, therefore 121 conceptuses; 50 of the 120 had enzyme-only detectable antibodies. §One woman accounted for four of the eight babies.
'lution, and 8 in albumin and 0 in saline solution, respectively. Three women who had mildly affected babies not requiring treatment had anti-C titers of 2048 in albumin and 512 in saline solution, 256 in albumin and 16 in saline solution, and 256 in albumin and 8 in saline solution, respectively. Literature survey. The literature relating to anti-C or anti-Ce alloimmunization was surveyed from 1944 to 1990 (Quarterly Cumulative Index Medicus, 1944 to 1956; Current List of Medical Literature, 1950 to 1959; and Cumulated Index Medicus, 1960 to 1990). Although the review of the non-English literature was thorough, it may not have been complete; the review of the English literature was comprehensive. Perinatal deaths from anti-C or anti-Ce hemolytic disease. Reports of perinatal deaths or fetuses requiring transfusions for anti-C or anti-Ce hemolytic disease are extremely rare. In 1981 Baker et aU reported on a group A, Rh-positive, C-negative woman in whom anti-C developed as a result of blood transfusion in childhood. Her first affected baby required phototherapy. Her second pregnancy ended at 39 weeks' gestation in a macerated stillbirth. There was autopsy evidence of eryth-
roblastosis. The anti-C titer at that time was 1024 in albumin. At the beginning of her third pregnancy, the anti-C titer was 512 in albumin. Because of amniotic fluid bilirubin levels of 4.8 and 6.0 J.LmollL at 27 and 29 weeks' gestation, three intraperitoneal fetal transfusions were carried out (90, 110, and 130 ml of C-negative compatible blood at 30, 32, and 34 weeks' gestation). The infant, delivered at 36 weeks' gestation, had a cord hemoglobin concentration of 162 gm/L (65 gm/L of which was residual fetal C positive in origin). He did well after phototherapy and one exchange transfusion. Hardy and Napier 8 in their review of red blood cell antibodies in Rh-positive women in south and mid Wales over a 30-year period (1948 to 1978) described two infants with hemolytic disease caused by anti-C who died, one after an exchange transfusion and one without undergoing exchange transfusion. They gave no further details of these two cases. Clarke et al. 9 in their report of deaths from hemolytic disease in England and Wales in 1984 and 1985 report, without giving any details, one perinatal death from C hemolytic disease in the 9-year period from 1977 to 1985. It is quite possible
1242 Bowman et al.
that the perinatal death reported by Clarke et aJ. is one of the deaths reported by Hardy and Napier. Remaining case reports. All remaining case reports of anti-C or anti-Ce ailoimmunization lO. 17 described affected infants who did not require treatment or who needed only exchange transfusion or phototherapy. None were severely affected, other than that of Wailer et aJ.1O (1944). This, the first reported example of hemolytic disease caused by anti-C, was a baby born at 39 weeks' gestation who had moderately severe hemolytic disease and required seven simple transfusions. The syndrome of transient hepatocellular damage developed in the baby, but it recovered with no neurologic sequelae. Atypical or irregular blood group antibody surveys. Various surveys of the prevalence of non-Rho (D) blood group alloimmunization, including anti-C and anti-Ce, have been published8.g.l8'25 (Table II). The prevalence of antiC and anti-Ce alloimunization ranged from 8.7 8to 185 20 per 100,000 pregnancies. In the current series the prevalence was 25.3 per 100,000 pregnant women (Table II).
The numbers of affected babies requiring treatment in all of the series reporting affected babies needing treatment totaled 15, eight of them in our series. The incidence of affected babies requiring treatment compared with the total number of anti-C and anti-Ce alloimmunized pregnancies ranged from 2.6% to 22.2% (6.7% in our series).
Comment Anti-C, Ce alloimmunization occurs rarely and when it does occur does not often cause serious hemolytic disease. The reported prevalence of C and Ce alloimmunization in un selected pregnant populations ranges from 8.7 to 13.6 per 100,000 pregnancies, except in the series of Queenan et aUO and our series. We have no explanation for the extremely high prevalence of C alloimmunization in the series of Queenan et aJ. (185/100,000). The reasons for the increased prevalence in our series are twofold. First, a sensitive twostage, enzyme-treated red blood cell screening method was used.' Forty-two percent of our C or Ce alloimmunized population had antibodies detected only by this method and not by indirect antiglobulin. 6 If indirect antiglobulin screening alone had been used, which may well have been the case in the other series, the prevalence of C or Ce alloimmunization in our series would have been 14.7 per 100,000 pregnancies. Second, the prevalence of anti-C or anti-Ce in Manitoban women has an overrepresentation of Native Americans, six of 19 such women (32%) accounting for 25 of the 59 multiple alloimmunized pregnancies (42%). There is no such overrepresentation in the 61 women who had only one C or Ce alloimmunized pregnancy (3
April 1992 Am J Obstet Gynecol
or 5%). If one corrects for the multiparity of Manitoban Native American C and Ce alloimmunized women, the prevalence of Cor Ce alloimmunization becomes 12.2 per 100,000 pregnancies, well within the 8.7 to 13.6 per 100,000 pregnancies reported by others. Although anti-C or anti-Ce alloimmunization very rarely causes perinatal deaths (four or five in all reported series in the past 46 years), it does so on occasion. We believe that the C or Ce alloimmunized pregnant woman should be managed in the same manner as the D, c, or Kell alloimmunized pregnant woman. It would appear from the case of Baker et aU and our case that blood transfusion causing C alloimmunization is a significant risk factor. From the standpoint of the critical anti-C or anti-Ce antibody titer at which invasive, investigative procedures such as amniocentesis or cord blood sampling should be carried out, our patient had a titer of 256 in albumin. The patient of Baker et aJ. 7 had a titer of 512 in albumin. These titers are considerably higher than the critical anti-D titers for similar investigations. Several of our patients with mildly or moderately affected babies had similar or even higher antibody titers, although most had greater immunoglobulin M (saline solution) components. However, because one of the women had an affected baby who required treatment in spite of a titer of 16 in albumin and 16 in saline solution and another had a titer of only 8 in albumin and 0 in saline solution, we recommend that the same titer criteria for invasive investigations in C or Ce alloimmunized pregnancies as in D alloimmunized pregnancies should be used, ;?:16 in albumin and ;?:32 to 64 by indirect immunoglobulin. REFERENCES 1. Mollison PL, EngeJfriet CP, Contreras M. Blood transfusion in clinical medicine. ed 8. Oxford: Blackwell Scientific, 1987:639-40. 2. Dunn PM. Obstructive jaundice and haemolytic disease of the newborn. Arch Dis Child 1963;38:54-61. 3. Bowman]M. Neonatal management. In: Queenan]T, ed.
4. 5. 6. 7.
8.
Modern management of the Rh problem. ed 2. Hagerstown, Maryland: Harper & Row, 1977:200-39. Lewis M, Kaita H, Chown B. Kell typing in the capillary tube.] Lab Clin Med 1958;52:163-8. Lalezari P. A polybrene method for the detection of red cell antibodies. Fed Proc 1967;26:756. Coombs RRA, Mourant AE, Race RR. A new test for the detection of weak and "incomplete" Rh agglutinins. Br ] Exp Pathol 1945;26:255-66. Baker ]W, Harrison KL, Harvey P]. Anti-C haemolytic disease requiring intrauterine and exchange transfusion. Med] Aust 1981;296:2. Hardy j, Napier jAF. Red cell antibodies detected in antenatal tests on Rhesus positive women in South and Mid Wales, 1948-1978. Br j Obstet Gynaecol 1981;88:91-
100. 9. Clarke CA, Whitfield AGW, Mollison PL. Deaths from Rh haemolytic disease in England and Wales in 1984 and 1985. BM] 1987;294:1001. 10. Waller RK, Levine P, Garrow 1. A case of erythroblastosis
Severe anti-G hemolytic disease
Volume 166 Number 4
11.
12. 13. 14.
15. 16.
17.
caused by immunization of an Rh-positive mother by the Rh factor. Am] CIin PathoI1944;14:577-81. Van Loghem Jj, Hart MVD. Iso-immunization by rare Rh-antigens as a cause of haemolytic disease of the newborn and transfusion reactions. ] Clin Pathol 1949;2: 284-8. Yesus YW, Akhter ]E. Hemolytic disease of the newborn due to anti-C and anti-G masquerading as anti-D. Am] Clin Pathol 1985;84:769-72. Dahl ]R, Giblett ER. Hemolytic disease of the newborn due to anti-Ce(rhi) in twins. Vox Sang 1963;8:452-4. Chiewsilp P, Ratanasirivanich P, Marsh WL, Blank M. Anti-C, anti-e, and anti-Ce(rhi) as a cause of hemolytic disease of the newborn in a Thai family.] Med Assoc Thai 1974;57:269-71. Tisdale.' Cited by Pickles MM. Textbook of haemolytic disease of the newborn. Oxford: University Press, 1949. Iwaszko-Krawczuk W, Kochanska-Leonczak], Dzienis K, Dabrowski S. Konflikt serologiczny u noworodka spowodowany antygenem C Z ukladu Rh. Acta Haematol Pol 1988; 19: 199-20 I. Bowell P], Inskip M], Jones MN. The significance of anti-C sensitization in pregnancy. Clin Lab Haematol 1988;10:251-5.
18. Pepperell R], Barrie ]U, Fliegner ]R. Significance of red cell irregular antibodies in the obstetric patient. Med ] Aust 1977;2:453-6. 19. Polesky HF. Blood group antibodies in prenatal sera. Minn Med 1967;50:601-3. 20. Queenan]T, Smith BD, Haber ]M,]effrey], Gadow He. Irregular antibodies in the obstetric patient. Obstet GynecoI1969;34:767-77. 21. Spielman W, Seidl S. Prevalence of irregular red cell antibodies and their significance in blood transfusion and antenatal care. Vox Sang 1974;26:551-9. 22. Beal RW. Non-rhesus (D) blood group iso immunization in obstetrics. Clin Obstet Gynaecol 1979;6:493-508. 23. Zuliani G, Moroni GA, Buscaglia M, Marotti R, Pardi G. Hemolytic disease of the newborn due to rare alloantibodies. Ric Clin Lab 1983;13:449-57. 24. Solola A, Sibai B, Mason ]M. Irregular antibodies: an assessment of routine prenatal screening. Obstet Gynecol 1983;61:25-30. 25. Giblett ER. Blood group antibodies causing hemolytic disease of the newborn. Clin Obstet Gynecol 1964;7:104455.
An integrated therapy for peripartum pelvic instability: A study of the biomechanical effects of pelvic belts Andry Vleeming, PhD: H. Muzaffer Buyruk, MD; Rob Stoeckart, PhD,. Sacid Karamursel, MD,c and Chris J. Snijders, PhDb Rotterdam, The Netherlands, and Istanbul, Turkey OBJECTIVES: The objectives of this study were to investigate the influence of pelvic belts on the stability of the pelvis and to discuss the treatment of peripartum pelvic instability. STUDY DESIGN: In six human pelvis-spine preparations, sagittal rotation in the sacroiliac jOints was induced by bidirectional forces directed at the acetabula. Weight-bearing was mimicked by the application of a compressive force to the spine. The biomechanical effect of a pelvic belt was measured in 12 sacroiliac joints. RESULTS: The pelvic belt caused a significant decrease in the sagittal rotation in the sacroiliac jOints. The effect of a 100 N belt did not differ significantly from that of a 50 N belt. CONCLUSION: The combination of a pelvic belt and muscle training enhances pelvic stability. The load of the belt can be relatively small; location is more important. The risk of symphysiodesis, especially as a result of the insertion of bone grafts, is emphasized. (AM J OBSTET GVNECOL 1992;166:1243-7.)
Key words: Pelvic instability, low back pain, sacroiliac joint, symphysiolysis, symphysiodesis
From the Research Group of Clinical Anatomy and Medical Technology, Departments of Anatomy" and Medical Technology/ and the Department of Anatomy and Physiology, Medical University of Istanbul.' Received for publication May 14, 1991; revised September 5, 1991; accepted October 8, 1991. Reprint requests: A. Vleeming, PhD, Faculty of Medicine and Allied Health Sciences, Department of Anatomy, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. 611134300
The pelvis must be considered part of a complex kinematic chain between the legs and spine. Important connections in this chain are the joints between the sacrum and the L-S (intervertebral disc and zygapophyseal joints) and the sacroiliac joints. Several studies demonstrate mobility in the sacroiliac joints. t . 5 Profound effects on the kinematic performance of the spine result from exceptional laxity of the sacroiliac 1243
Key words: Anti-C hemolytic disease, fer.al transfusions Although anti-C is listed as an antibody capable of causing severe hemolytic disease of the newborn,l reports of anti-C causing severe hemolytic disease are extremely rare. In 1986 the Rh Laboratory and the Division of Fetal and Maternal Medicine, Faculty of Medicine, University of Manitoba, and the Health Sciences Centre, Winnipeg, participated in the management of an anti-C alloimmunized pregnant women whose fetus required intrauterine transfusions to survive. In 46 years of experience with maternal alloimmunization, this was the Rh Laboratory's first example of anti-C hemolytic disease of such severity. We report this case in detail, with a review of the Rh Laboratory experience and the experience of others with anti-C or anti-Ce alloimmunization.
Case report At the time of her first pregnancy this para 2, gravida 3, group A, Rh-positive, C-negative, Cw-negative, e-negative (R2R2) woman was transfused at cesarean From the Rh Laboratory, Department of Pediatrics and Child Health' and the Division of Fetal and Maternal Medicine, Departmeut of Obstetrics, Gynecology, and Reproductive Sciences,' FaClllty of Medicine, University of Manitoba, and the Health Sciences Centre. Received for publication May 30,1991; revised August 20,1991; acrepted October 8, 1991. Reprint requests: John A1. Bowman, MD, Rh Laboratory, Women's Hospital, Health Sciences Centre, 735 Notre Dame Ave., Winnipeg, Manitoba, Canada R3E OL8.
6/1 /34297
section for abruptio placentae. Her second pregnancy ended at 37 weeks' gestation with a hydropic stillbirth. At that time she was found to have very strong anti-C and anti-Cw and very weak anti-e blood group antibodies. Her husband was group B, Rh positive, C positive, e positive, and Cw negative (R'R'). Thus anti-C was the alloantibody responsible for the hydropic fetal death. Mrs. S. was referred to Winnipeg in 1986, in her third pregnancy at 221/2 weeks' gestation. The anti-C titer was 256 in albumin and I in saline solution. Two amniocenteses had been carried out at the referring center, the d optical density readings at 450 nm (dOD.,,,) were 0.355 and 0.362 at 201/2 and 221/2 weeks' gestation. Two days later in Winnipeg, at the time of the first intraperitoneal fetal transfusion, the dOD.,o reading was 0.346. Hepatomegaly was evident on ultrasonography, but the fetus was not hydropic. Four intraperitoneal fetal transfusions were carried out with infusion of tightly packed, fresh, compatible, group 0, C-negative, Cw-negative, e-negative (WR 2 ), Kell-negative red blood cells at 221/2, 24, 271/2, and 31 weeks' gestation. She was delivered of a female infant by elective cesarean section at 331/2 weeks' gestation in the tertiary-level center from which she had been referred. Jaundice was present and there was marked hepatosplenomegaly. Cord red blood cells were 99.7% adult donor in origin by Kleihauer acid elution testing. Cord hemoglobin level was 117 gm/L; cord serum bilirubin level was 138 f.lmollL total and 38 f.lmollL by direct reaction. 1239
1240 Bowman et a\.
April 1992 Am J Obstet Gynecol
Table I. Anti-C or anti-Ce alloimmunization, Manitoba, Nov. 1, 1962, to Oct. 31, 1990 475,000 pregnancies Anti-C or anti-Ce Total anti-C Abortions and Affected, no (Direct antiglobulin Perinatal or intrauterine unrelated Unaffected (direct antiglobulin treatment or anti-Ce test-positive) death caused by anti-C immunized pregnancies losses test-negative) infants required treatment required* women and anti-Ce
80
120t
64
25§
811
o
*Treatment: exchange transfusion and/or phototherapy. tFifty of the 120 were not detectable by an indirect antiglobulin test. tTwenty-two spontaneous or induced abortions, two fetal deaths unrelated to anti-C or anti-Ceo Both women had subsequent healthy surviving infants. §One set of twins, 24 pregnancies. 1I0ne woman accounted for four of the eight babies.
An immediate double-volume exchange transfusion was carried out, followed by a second exchange transfusion on the second day of life. The highest indirect serum bilirubin level was 228 f,LmoliL (13.4 mg/dl). She had evidence of transient hepatocellular damage!' 3 an index of severe hemolytic disease, with the direct (conjugated) bilirubin level peaking at 125 f,Lmol/L. The neonatal nursery course was uneventful. At 7 months of age she was progressing normally.
Results Prevalence of anti-C or anti·Ce alloimmuni. zation. The Rh Laboratory records for the 28-year period, Nov. 1, 1962, to Oct. 31, 1990, were reviewed. The laboratory is responsible for antibody screening of all women in Manitoba (population of 1 million with 17,000 pregnancies annually). The policy of the laboratory is that all pregnant women should be screened at their first prenatal visit. Unimmunized Rh-negative women are then screened at monthly intervals. A second blood sample for screening of unimmunized Rhpositive women is requested at 28 to 34 weeks' gestation but is not always obtained. Antibody screening of maternal serum is carried out by a sensitive two-stage, enzyme-treated red blood cell method' and a low-ionic autoanalyzer method.' If an Rh-positive pregnant woman has a blood group alloantibody, further blood samples are requested at 2to 8-week intervals, depending on length of gestation, the specificity of the antibody, and its strength (titer). If the antibody is one that is known to cause fetal hemolytic disease, amniotic fluid spectrophotometry or, in the past 5 years, fetal blood sampling is carried out, on the basis of the same criteria used for initiating either procedure in Rh-negative, Rho (D)-immunized pregnant women (history of a prior perinatal death, a fetus or infant requiring treatment, or antibody titers of ~ 16 in albumin or ~32 to 64 by indirect antiglobulin).6 Because the Rh Laboratory carries out all cord blood testing and treatment of affected babies after birth and, in conjunction with the Division of Fetal and Maternal Medicine, carries out all amniotic fluid measurements,
fetal blood testing, and fetal transfusions in Manitoba, the subsequent course of each pregnancy and the fetalneonatal outcome are known and are part of each alloimmunized woman's Rh Laboratory record. The numbers of anti-C or anti-Ce alloimmunized pregnancies, excluding those in Rh-negative women with anti-D, for the 28-year period ending Oct. 31, 1990, are set out in Table I, with their respective outcomes. There were 80 C- or Ce-alloimmunized women who had 120 pregnancies (121 conceptuses) in the 28year period. Nineteen women, six of whom were Native Americans, had 59 ofthe pregnancies (60 conceptuses). Of the remaining 61 women who had one C- or Cealloimmunized pregnancy, only three were Native Americans. There were 22 abortions and two fetal deaths unrelated to C or Ce alloimmunization in the study group. Of the remaining 96 cases, 33 fetuses of 32 pregnancies (27.5%) were affected. However, only eight fetuses (6.7%) required treatment after birth: Two needed exchange transfusions and six required only phototherapy. Two of the six subsequently required simple transfusions. All eight treated babies were only moderately affected. None required induced early delivery and none required intrauterine fetal transfusion. In this series there were no deaths caused by C or Ce alloimmunization. One woman, a Native American, accounted for four of the eight babies who needed treatment (one required exchange transfusion and the other three required phototherapy only). Her next baby, again affected, did not need treatment. In all, she accounted for seven of the 120 C- or Ce-alloimmunized pregnancies. Some Manitoban C-alloimmunized women had antiC or anti-Ce antibody titers as high as that of our patient (256 in albumin, 1 in saline solution). Five women with affected babies who required treatment had anti-C titers of 128 in albumin and 8 in saline solution, 64 in albumin and 8 in saline solution, 64 in albumin and 32 in saline solution, 16 in albumin and 16 in saline so-
Severe anti-C hemolytic disease
Volume 166 Number 4
1241
Table II. Surveys that include C and Ce maternal alloimmunization No. with anti-C or anti-Ce
Author
Hardy and Napier8 Clarke et al."
Pregnant population
No.
507,720
44
Per 100,000 pregnancies
8.7
6-7 million
Bowell et al." Pepperell et al. 18 Polesky'9
280,000 72,138
38 9
13.6 12.5
43,100
5
11.6
Queenan et aUo Spielman and Seidl 2l Beaj22
18,378
34
16,643
0
41,078
5
12.2
Zuliani et al. 2' Solola et al. 24 Giblett25
9,525t 5,559 6 yr Seattle
2 0 4
21.0
Current investigation
475,000
120t
25.3
185
Babies requiring treatment
Affected offspring
No.
No. per 100,000 pregnancies
No.
25
4.9
3
Perinatal mortality report only 5 1.8 4 5.5
6.8
Death from hemolytic disease of fetus and newborn
2* 1*
I
2
Hemolytic disease of fetus and newborn not described 10.9 2 0
Proportion (% of whole)
2.6 22.2
0 0
2.9
0
0
Hemolytic disease of fetus and newborn not described 0 0 0 0 (Degree of hemolytic disease of 2 fetus and newborn not described) 8§ 33 6.9 6.7
0
0 0
0
*One of the deaths in the series of Hardy and Napier8 may also be the one in the series of Clarke et al. 9 tHighly selected referred population. tOne set of twins, therefore 121 conceptuses; 50 of the 120 had enzyme-only detectable antibodies. §One woman accounted for four of the eight babies.
'lution, and 8 in albumin and 0 in saline solution, respectively. Three women who had mildly affected babies not requiring treatment had anti-C titers of 2048 in albumin and 512 in saline solution, 256 in albumin and 16 in saline solution, and 256 in albumin and 8 in saline solution, respectively. Literature survey. The literature relating to anti-C or anti-Ce alloimmunization was surveyed from 1944 to 1990 (Quarterly Cumulative Index Medicus, 1944 to 1956; Current List of Medical Literature, 1950 to 1959; and Cumulated Index Medicus, 1960 to 1990). Although the review of the non-English literature was thorough, it may not have been complete; the review of the English literature was comprehensive. Perinatal deaths from anti-C or anti-Ce hemolytic disease. Reports of perinatal deaths or fetuses requiring transfusions for anti-C or anti-Ce hemolytic disease are extremely rare. In 1981 Baker et aU reported on a group A, Rh-positive, C-negative woman in whom anti-C developed as a result of blood transfusion in childhood. Her first affected baby required phototherapy. Her second pregnancy ended at 39 weeks' gestation in a macerated stillbirth. There was autopsy evidence of eryth-
roblastosis. The anti-C titer at that time was 1024 in albumin. At the beginning of her third pregnancy, the anti-C titer was 512 in albumin. Because of amniotic fluid bilirubin levels of 4.8 and 6.0 J.LmollL at 27 and 29 weeks' gestation, three intraperitoneal fetal transfusions were carried out (90, 110, and 130 ml of C-negative compatible blood at 30, 32, and 34 weeks' gestation). The infant, delivered at 36 weeks' gestation, had a cord hemoglobin concentration of 162 gm/L (65 gm/L of which was residual fetal C positive in origin). He did well after phototherapy and one exchange transfusion. Hardy and Napier 8 in their review of red blood cell antibodies in Rh-positive women in south and mid Wales over a 30-year period (1948 to 1978) described two infants with hemolytic disease caused by anti-C who died, one after an exchange transfusion and one without undergoing exchange transfusion. They gave no further details of these two cases. Clarke et al. 9 in their report of deaths from hemolytic disease in England and Wales in 1984 and 1985 report, without giving any details, one perinatal death from C hemolytic disease in the 9-year period from 1977 to 1985. It is quite possible
1242 Bowman et al.
that the perinatal death reported by Clarke et aJ. is one of the deaths reported by Hardy and Napier. Remaining case reports. All remaining case reports of anti-C or anti-Ce ailoimmunization lO. 17 described affected infants who did not require treatment or who needed only exchange transfusion or phototherapy. None were severely affected, other than that of Wailer et aJ.1O (1944). This, the first reported example of hemolytic disease caused by anti-C, was a baby born at 39 weeks' gestation who had moderately severe hemolytic disease and required seven simple transfusions. The syndrome of transient hepatocellular damage developed in the baby, but it recovered with no neurologic sequelae. Atypical or irregular blood group antibody surveys. Various surveys of the prevalence of non-Rho (D) blood group alloimmunization, including anti-C and anti-Ce, have been published8.g.l8'25 (Table II). The prevalence of antiC and anti-Ce alloimunization ranged from 8.7 8to 185 20 per 100,000 pregnancies. In the current series the prevalence was 25.3 per 100,000 pregnant women (Table II).
The numbers of affected babies requiring treatment in all of the series reporting affected babies needing treatment totaled 15, eight of them in our series. The incidence of affected babies requiring treatment compared with the total number of anti-C and anti-Ce alloimmunized pregnancies ranged from 2.6% to 22.2% (6.7% in our series).
Comment Anti-C, Ce alloimmunization occurs rarely and when it does occur does not often cause serious hemolytic disease. The reported prevalence of C and Ce alloimmunization in un selected pregnant populations ranges from 8.7 to 13.6 per 100,000 pregnancies, except in the series of Queenan et aUO and our series. We have no explanation for the extremely high prevalence of C alloimmunization in the series of Queenan et aJ. (185/100,000). The reasons for the increased prevalence in our series are twofold. First, a sensitive twostage, enzyme-treated red blood cell screening method was used.' Forty-two percent of our C or Ce alloimmunized population had antibodies detected only by this method and not by indirect antiglobulin. 6 If indirect antiglobulin screening alone had been used, which may well have been the case in the other series, the prevalence of C or Ce alloimmunization in our series would have been 14.7 per 100,000 pregnancies. Second, the prevalence of anti-C or anti-Ce in Manitoban women has an overrepresentation of Native Americans, six of 19 such women (32%) accounting for 25 of the 59 multiple alloimmunized pregnancies (42%). There is no such overrepresentation in the 61 women who had only one C or Ce alloimmunized pregnancy (3
April 1992 Am J Obstet Gynecol
or 5%). If one corrects for the multiparity of Manitoban Native American C and Ce alloimmunized women, the prevalence of Cor Ce alloimmunization becomes 12.2 per 100,000 pregnancies, well within the 8.7 to 13.6 per 100,000 pregnancies reported by others. Although anti-C or anti-Ce alloimmunization very rarely causes perinatal deaths (four or five in all reported series in the past 46 years), it does so on occasion. We believe that the C or Ce alloimmunized pregnant woman should be managed in the same manner as the D, c, or Kell alloimmunized pregnant woman. It would appear from the case of Baker et aU and our case that blood transfusion causing C alloimmunization is a significant risk factor. From the standpoint of the critical anti-C or anti-Ce antibody titer at which invasive, investigative procedures such as amniocentesis or cord blood sampling should be carried out, our patient had a titer of 256 in albumin. The patient of Baker et aJ. 7 had a titer of 512 in albumin. These titers are considerably higher than the critical anti-D titers for similar investigations. Several of our patients with mildly or moderately affected babies had similar or even higher antibody titers, although most had greater immunoglobulin M (saline solution) components. However, because one of the women had an affected baby who required treatment in spite of a titer of 16 in albumin and 16 in saline solution and another had a titer of only 8 in albumin and 0 in saline solution, we recommend that the same titer criteria for invasive investigations in C or Ce alloimmunized pregnancies as in D alloimmunized pregnancies should be used, ;?:16 in albumin and ;?:32 to 64 by indirect immunoglobulin. REFERENCES 1. Mollison PL, EngeJfriet CP, Contreras M. Blood transfusion in clinical medicine. ed 8. Oxford: Blackwell Scientific, 1987:639-40. 2. Dunn PM. Obstructive jaundice and haemolytic disease of the newborn. Arch Dis Child 1963;38:54-61. 3. Bowman]M. Neonatal management. In: Queenan]T, ed.
4. 5. 6. 7.
8.
Modern management of the Rh problem. ed 2. Hagerstown, Maryland: Harper & Row, 1977:200-39. Lewis M, Kaita H, Chown B. Kell typing in the capillary tube.] Lab Clin Med 1958;52:163-8. Lalezari P. A polybrene method for the detection of red cell antibodies. Fed Proc 1967;26:756. Coombs RRA, Mourant AE, Race RR. A new test for the detection of weak and "incomplete" Rh agglutinins. Br ] Exp Pathol 1945;26:255-66. Baker ]W, Harrison KL, Harvey P]. Anti-C haemolytic disease requiring intrauterine and exchange transfusion. Med] Aust 1981;296:2. Hardy j, Napier jAF. Red cell antibodies detected in antenatal tests on Rhesus positive women in South and Mid Wales, 1948-1978. Br j Obstet Gynaecol 1981;88:91-
100. 9. Clarke CA, Whitfield AGW, Mollison PL. Deaths from Rh haemolytic disease in England and Wales in 1984 and 1985. BM] 1987;294:1001. 10. Waller RK, Levine P, Garrow 1. A case of erythroblastosis
Severe anti-G hemolytic disease
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11.
12. 13. 14.
15. 16.
17.
caused by immunization of an Rh-positive mother by the Rh factor. Am] CIin PathoI1944;14:577-81. Van Loghem Jj, Hart MVD. Iso-immunization by rare Rh-antigens as a cause of haemolytic disease of the newborn and transfusion reactions. ] Clin Pathol 1949;2: 284-8. Yesus YW, Akhter ]E. Hemolytic disease of the newborn due to anti-C and anti-G masquerading as anti-D. Am] Clin Pathol 1985;84:769-72. Dahl ]R, Giblett ER. Hemolytic disease of the newborn due to anti-Ce(rhi) in twins. Vox Sang 1963;8:452-4. Chiewsilp P, Ratanasirivanich P, Marsh WL, Blank M. Anti-C, anti-e, and anti-Ce(rhi) as a cause of hemolytic disease of the newborn in a Thai family.] Med Assoc Thai 1974;57:269-71. Tisdale.' Cited by Pickles MM. Textbook of haemolytic disease of the newborn. Oxford: University Press, 1949. Iwaszko-Krawczuk W, Kochanska-Leonczak], Dzienis K, Dabrowski S. Konflikt serologiczny u noworodka spowodowany antygenem C Z ukladu Rh. Acta Haematol Pol 1988; 19: 199-20 I. Bowell P], Inskip M], Jones MN. The significance of anti-C sensitization in pregnancy. Clin Lab Haematol 1988;10:251-5.
18. Pepperell R], Barrie ]U, Fliegner ]R. Significance of red cell irregular antibodies in the obstetric patient. Med ] Aust 1977;2:453-6. 19. Polesky HF. Blood group antibodies in prenatal sera. Minn Med 1967;50:601-3. 20. Queenan]T, Smith BD, Haber ]M,]effrey], Gadow He. Irregular antibodies in the obstetric patient. Obstet GynecoI1969;34:767-77. 21. Spielman W, Seidl S. Prevalence of irregular red cell antibodies and their significance in blood transfusion and antenatal care. Vox Sang 1974;26:551-9. 22. Beal RW. Non-rhesus (D) blood group iso immunization in obstetrics. Clin Obstet Gynaecol 1979;6:493-508. 23. Zuliani G, Moroni GA, Buscaglia M, Marotti R, Pardi G. Hemolytic disease of the newborn due to rare alloantibodies. Ric Clin Lab 1983;13:449-57. 24. Solola A, Sibai B, Mason ]M. Irregular antibodies: an assessment of routine prenatal screening. Obstet Gynecol 1983;61:25-30. 25. Giblett ER. Blood group antibodies causing hemolytic disease of the newborn. Clin Obstet Gynecol 1964;7:104455.
An integrated therapy for peripartum pelvic instability: A study of the biomechanical effects of pelvic belts Andry Vleeming, PhD: H. Muzaffer Buyruk, MD; Rob Stoeckart, PhD,. Sacid Karamursel, MD,c and Chris J. Snijders, PhDb Rotterdam, The Netherlands, and Istanbul, Turkey OBJECTIVES: The objectives of this study were to investigate the influence of pelvic belts on the stability of the pelvis and to discuss the treatment of peripartum pelvic instability. STUDY DESIGN: In six human pelvis-spine preparations, sagittal rotation in the sacroiliac jOints was induced by bidirectional forces directed at the acetabula. Weight-bearing was mimicked by the application of a compressive force to the spine. The biomechanical effect of a pelvic belt was measured in 12 sacroiliac joints. RESULTS: The pelvic belt caused a significant decrease in the sagittal rotation in the sacroiliac jOints. The effect of a 100 N belt did not differ significantly from that of a 50 N belt. CONCLUSION: The combination of a pelvic belt and muscle training enhances pelvic stability. The load of the belt can be relatively small; location is more important. The risk of symphysiodesis, especially as a result of the insertion of bone grafts, is emphasized. (AM J OBSTET GVNECOL 1992;166:1243-7.)
Key words: Pelvic instability, low back pain, sacroiliac joint, symphysiolysis, symphysiodesis
From the Research Group of Clinical Anatomy and Medical Technology, Departments of Anatomy" and Medical Technology/ and the Department of Anatomy and Physiology, Medical University of Istanbul.' Received for publication May 14, 1991; revised September 5, 1991; accepted October 8, 1991. Reprint requests: A. Vleeming, PhD, Faculty of Medicine and Allied Health Sciences, Department of Anatomy, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. 611134300
The pelvis must be considered part of a complex kinematic chain between the legs and spine. Important connections in this chain are the joints between the sacrum and the L-S (intervertebral disc and zygapophyseal joints) and the sacroiliac joints. Several studies demonstrate mobility in the sacroiliac joints. t . 5 Profound effects on the kinematic performance of the spine result from exceptional laxity of the sacroiliac 1243
