Clinical Evaluation of Rh0(D) Immune Globulin (Human) in Canada

—During 1966, clinical trials were conducted in three Canadian centres to determine the safety and efficacy of Rh₀(D) immune globulin (human) in preventing isoimmunization by the Rh₀(D) antigen in Rh-negative women delivering ABO-compatible Rh-positive infants.The candidates were randomly divided into control and treated groups; the treated mothers received an intramuscular injection of 300 μg. of anti-Rh₀(D) within 72 hours of delivery. Follow-up antibody screening tests were conducted on the sera of all patients six to nine months post partum.Of the 175 control patients, 11 or 6.2% became actively immunized to the Rh antigen, whereas complete protection against maternal Rh immunization was observed in the 191 treated patients.     

Incidence of rhesus immunisation after genetic amniocentesis.

Of 655 Rh negative women without anti-D antibody in their serum at genetic amniocentesis, 361 delivered a Rh positive infant. Prophylactic treatment with anti-D immunoglobulin was not given at amniocentesis. The women were followed prospectively, being given a screening test for antibody after amniocentesis, at delivery, and six months later. Five of these 361 women yielded a positive test result due to anti-D antibody. The immunisation rate after genetic amniocentesis was no higher than the spontaneous immunisation rate during pregnancy. Four women who had two amniocenteses in the same pregnancy and 34 women who had amniocentesis in two consecutive pregnancies with Rh positive fetuses were not immunised. Among six women with anti-D antibody in their serum before amniocentesis the titre of antibody increased in three. Amniocentesis may have worsened the outcome of these pregnancies. These results suggest that the risk of immunisation in Rh negative women is small.     

Efficacy and long term effects of antenatal prophylaxis with anti-D immunoglobulin.

OBJECTIVE--To measure the safety and efficacy of antenatal treatment with anti-D immunoglobulin. DESIGN--Open study with historical controls. SETTING--Multicentre study in 17 hospitals in West Yorkshire. PATIENTS--1238 Rh negative women who delivered Rh positive infants after 34 weeks in their first pregnancy in 1980-1 (group 1) and 2000 similar primigravidas from 1978-9 (group 2). Obstetric data were collected for 616 women in group 1 who had a subsequent pregnancy, 536 similar women in group 2, and 410 Rh positive but otherwise similar primigravidas who delivered in the same hospitals in 1978-81 (group C). INTERVENTIONS--Anti-D immunoglobulin 100 micrograms intramuscularly was given at 28 and 34 weeks to the mothers in their first pregnancy who delivered in 1980-1. END POINTS--Detection of anti-D antibody in the first or any subsequent pregnancy in groups 1 and 2. For all three groups having subsequent pregnancies gestation at delivery, birth weight, fetal survival at one month, pre-eclampsia defined as blood pressure greater than 140/90 on two occasions more than 12 hours apart, and proteinuria greater than 0.25 milligram. MEASUREMENTS AND MAIN RESULTS--Antenatal immunisation to Rh(D) occurred in six mothers in group 1 and 32 group 2. Most immunisations occurred in the first or second pregnancy. The rates of abortion, gestation at delivery, birth weight, and fetal survival were not significantly different among the three groups. The incidence of pre-eclampsia was lower in mothers given antenatal anti-D immunoglobulin, but the difference was not significant. CONCLUSIONS--Antenatal prophylaxis with anti-D immunoglobulin is effective, and the effect of giving it in the first pregnancy persists into at least the second pregnancy. It seems to be safe for the fetus in the index and subsequent pregnancies.     

WinRho: Rh immune globulin prepared by ion exchange for intravenous use.

An Rh immune globulin [Rh IgG] for intravenous use, WinRho, has been prepared by the Winnipeg Rh Institute by a modification of the ion-exchange column method of Hoppe and colleagues. When administered to Rh-negative male and nonpregnant female volunteers WinRho was found to be nonpyrogenic, nontoxic, safe and protective against Rh alloimmunization. In a clinical trial with 240 microgram given at about 28 weeks'' gestation and 120 microgram given after delivery to Rh-negative women at risk of Rh immunization WinRho was effective in preventing Rh immunization. Of the 870 women carrying Rh-positive fetuses who were treated with WinRho during pregnancy and were not tested several months after delivery 14 would have shown evidence of Rh immunization by the time of delivery if WinRho had been ineffective; none showed such evidence. Of the 1122 women carrying Rh-positive fetuses who were retested 4 to 6 months after delivery 83 would have shown evidence of Rh immunization at that time if WinRho had been ineffective; only 1 showed such evidence. The efficiency of yield of anti-D with the modified method of production, the fct that it can be given intravenously (a route that causes the patient less discomfort and immediately results in high anti-D levels) and the lower levels of contaminating IgA and IgM make WinRho the preparation of choice for preventing Rh immunization.     

Role of HLA antigens in Rh (D) alloimmunized pregnant women from Mumbai, Maharashtra, India

Immunogenetic studies in various diseases provide potential genetic markers. We have studied the incidence of HLA A, B, C, DR and DQ loci antigen in Rh (D) antigen isoimmunized mothers compared to those nonimmunized isoimmunized Rh negative mothers. Seventy six mothers who were immunized to Rh (D) antigen due to pregnancy (responders) and fifty four mothers who did not develop Rh (D) isoimmunization despite positive pregnancies (nonresponders) were selected for the study. Standard methods of serological HLA typing, ABO and Rh (D) groups, and screening for Rh D antibodies were used. 392 unrelated individuals from the population were compared as controls. In addition 45 unrelated individuals from the same population were typed for HLA DRB and DQB gene using PCR-SSP kits. The genotype frequencies of HLA A2, A3, A28, B13, B17, B35, B52, B60, Cw2, Cw6, DR4, and DQ3 were significantly increased, while the frequencies of the HLA A11, A29, A31, B7, B37, B51, Cw1 and DR9 were decreased in the responder women when compared to the non-responder women. HLA A30 (19) split antigen was not identified in immunized women while HLA A23 (9) split antigen was not identified in non immunized women. HLA A3, B17, Cw2 and DR4 showed a significant relative risk among the immunized responder women. When compared with Rh immunized women (responders) reported from USA, England and Hungary the phenotype frequencies of HLA A11, A24, A28, B5, B17, B40, DR2 and DR5 were increased while HLA A23, B8, B18, and DR6 were decreased in the Indian Rh immunized women. Two locus haplotype frequency analysis observed among the responders women revealed that among the significant haplotypes expressed A2–B5, B7–Cw1, DR2–DQ1 were highly significant haplotypes in positive linkage, while A1–B5, and A1–B7 were in significant negative linkage disequilibrium. The haplotype frequencies were ≤one when these common hapoltypes were compared with control population. Thus in the present study it is evident that the inheritance of HLA A3, B17, Cw2 and DR4 increases the relative risk factor by 2.6 times among Indian Rh isoimmunized women. Further, it is evident that there are significant differences in the observed HLA antigen frequencies and two locus haplotypes in Rh isoimmunized women when compared to women from USA, UK and Hungary due to extreme HLA polymorphism in different populations of the world     

Effect of breast-feeding on pituitary-ovarian function after childbirth

Pituitary and ovarian function at the end of pregnancy and during the first six weeks after delivery was investigated serially in women who fully breast-fed their infants and in women who did not. In the women who did not breast-feed the plasma prolactin level decreased rapidly and from the third day after delivery was significantly lower than in the breast-feeding mothers, reaching the normal range of the menstrual cycle by the third week of the puerperium. In the breast-feeding mothers the plasma prolactin was still raised six weeks after delivery. The levels of FSH in both groups were identical and increased over the third week of the puerperium. Plasma oestrogen fell steeply in both groups during the first two weeks after delivery. In the breast-feeding mothers plasma oestrogen remained depressed but increased in the non-lactating women, reflecting follicular development in the ovary in response to FSH; the plasma oestrogen levels were significantly higher in the non-lactating women from the 17th day of the puerperium onwards. These findings support the concept that in breast-feeding women prolactin delays the return of ovulation by inhibiting the ovarian response to FSH stimulation.     

An error in Rh testing in pregnancy.

Anti-D (anti-Rho) in the blood of two Rh-negative pregnant women was believed to be due to active immunization. In the first case, however, antibodies were no longer detectable 2 weeks later. In the second case they disappeared by the end of 31 weeks. It was discovered that both women had been given immune globulin (human) because of exposure to rubella. The globulin given to the first woman probably contained about 0.1 mug of anti-D per ml; that given to the second probably contained about 0.6 mug of anti-D per ml. Both babies were O Rh-positive. Both women were given Rh immune globulin after delivery. Both have completed a further pregnancy and no anti-D has been found on many tests. In tests carried out in 1971 all samples of immune globulin (human) examined contained anti-D, but usually in inconsequential trace amounts.     

Induction of Labour for Prevention of Stillbirth from Rh Hemolytic Disease

The fate of 80 infants delivered after induction of labour in 72 Rh-sensitized mothers was studied to determine whether the stillbirth rate could be reduced. Labour was induced at 32 to 39 weeks of gestation; the criteria for induction were based on the history of previously affected infants, and a maternal Rh-antibody titre of 1/40 or greater, using an indirect antiglobulin technique. Nine mothers were delivered by Cesarean section. It was estimated that 26 infants were so severely affected as to be unlikely to have survived to term. However, only seven died, and one was stillborn. Two of these would normally have survived, one being Rh-negative. These two cases demonstrated the main danger in this method of management. There was a probable saving of 18 infants. In 22 mothers there was no history of previous delivery of an affected infant; in all 22 the infants survived, though six probably would not have survived to term. In 15 pregnancies in which the mothers had had a previous stillbirth, 12 infants survived. Sixty-seven infants required a total of 116 exchange transfusions. Despite the hazards it is concluded that early induction has an important place in management of Rh hemolytic disease.     

Antenatal prophylaxis of Rh isoimmunization: 28-weeks'-gestation service program

Two (0.18%) of 1086 Rh-negative primigravidas or multigravidas treated similarly in all previous pregnancies, who were given a single injection of Rh immune globulin (300 μg) at 28 weeks'' gestation and subsequently were delivered of Rh-positive babies, had demonstrable Rh isoimmunization at the time of that injection and must be considered “logistic” failures of antenatal prophylaxis. The remaining 1084 (who were treated again after delivery) had no evidence of Rh isoimmunization at delivery and none of the 512 screened at 6 months after delivery appeared to be immunized. If the 28th-week injection had not been protective, one would have expected 14 of the 1084 to have been demonstrably Rh isoimmunized and evidence of Rh isoimmunization to have persisted in 6 of the 512 observed 6 months after delivery.Six of 719 Rh-negative multigravidas who had not received Rh immune globulin after previous pregnancies or had been treated only after delivery showed evidence of Rh isoimmunization despite a single injection of Rh immune globulin at 28 weeks in a subsequent pregnancy. In three of the six the cause was most likely “sensibilization” due to previous exposure to Rh-positive blood or an untreated Rh-positive pregnancy. in 3 of the remaining 716 (0.42%) there may have been true failure of antenatal Rh prophylaxis administered at the 28th week. One would have expected this figure to be 12 of 716 if antenatal Rh prophylaxis at 28 weeks'' gestation were totally unsuccessful.It is concluded that a single intramuscular injection of Rh immune globulin, 300 μg, is 88% effective in preventing Rh isoimmunization during pregnancy in Rh-negative primigravidas and in multigravidas treated antenatally in all previous pregnancies, and is 75% effective in preventing Rh isoimmunization in Rh-negative multigravidas untreated during previous pregnancies. The majority of failures are due to Rh isoimmunization during pregnancy prior to antenatal prophylaxis at 28 weeks.     

Rh-immunization by Pregnancy: Results of a Survey and Their Relevance to Prophylactic Therapy

A series of Rh-negative primiparae has been studied in order to gain further insight into the process of immunization by pregnancy. The distribution of foetal cell counts in blood samples taken after delivery was determined for 2,029 mothers giving birth to ABO-compatible babies and for 417 mothers with ABO-incompatible babies.A total of 760 mothers were tested for the development of Rh antibodies six months after the delivery of an ABO-compatible Rh-positive baby and 236 were further followed up through a second Rh-positive pregnancy. The incidence of anti-D six months after delivery is estimated to be 8.5%, and there is evidence of a direct relation between the count of foetal cells after delivery and the risk of developing antibodies. A further 8.5% of mothers were estimated to develop anti-D by the end of the second pregnancy, and it is postulated that these individuals had been primed by the first pregnancy. There is some evidence that the larger stimuli of Rh-positive blood in the first pregnancy are more likely to result in overt antibody formation, while the smaller stimuli are more likely to prime, antibodies not being detected until a second stimulus occurs during the second pregnancy.These findings are relevant to the programme for preventing Rh-immunization by injecting anti-D gammaglobulin.     

Rh isoimmunization during pregnancy: antenatal prophylaxis.

Of 3533 Rh-negative women who began a pregnancy without detectable Rh antibodies, 62 (1.8%) demonstrated evidence of Rh isoimmunization during pregnancy or within 3 days after delivery. All denied transfusions as well as abortions or previous pregnancies not followed by the administration of Rh immune globulin. Rh isoimmunization during pregnancy or within 3 days after delivery, which will not be prevented by the administration of Rh immune globulin after delivery, is the most important cause of residual Rh isoimmunization. A clinical trial of antenatal administration of Rh immune globulin, initially at 34 weeks''s and subsequently at 28 and 34 weeks'' gestation, in 1357 Rh-negative pregnant women who were delivered of Rh-positive babies, was effective in preventing the development of Rh isoimmunization during pregnancy or within 3 days after delivery. Antenatal prophylaxis with Rh immune globulin will be necessary if the incidence of Rh isoimmunization is to be reduced to its lowest possible level. Antenatal prophylaxis at 28 weeks'' gestation is now an insured service in Manitoba.     

Determinants of breastfeeding initiation among mothers in Kuwait

Background

Exclusive breastfeeding is recommended as the optimal way to feed infants for the first six months of life. While overall breastfeeding rates are high, exclusive breastfeeding is relatively uncommon among Middle Eastern women. The objective of this study was to identify the incidence of breastfeeding amongst women in the six governorates of Kuwait and the factors associated with the initiation of breastfeeding.

Methods

A sample of 373 women (aged 17-47 years), recruited shortly after delivery from four hospitals in Kuwait, completed a structured, interviewer-administered questionnaire. Multivariate logistic regression analysis was used to identify those factors independently associated with the initiation of breastfeeding.

Results

In total, 92.5% of mothers initiated breastfeeding and at discharge from hospital the majority of mothers were partially breastfeeding (55%), with only 30% of mothers fully breastfeeding. Prelacteal feeding was the norm (81.8%) and less than 1 in 5 infants (18.2%) received colostrum as their first feed. Only 10.5% of infants had been exclusively breastfed since birth, the remainder of the breastfed infants having received either prelacteal or supplementary infant formula feeds at some time during their hospital stay. Of the mothers who attempted to breastfeed, the majority of women (55.4%) delayed their first attempt to breastfeed until 24 hours or more after delivery. Breastfeeding at discharge from hospital was positively associated with paternal support for breastfeeding and negatively associated with delivery by caesarean section and with the infant having spent time in the Special Care Nursery.

Conclusions

The reasons for the high use of prelacteal and supplementary formula feeding warrant investigation. Hospital policies and staff training are needed to promote the early initiation of breastfeeding and to discourage the unnecessary use of infant formula in hospital, in order to support the establishment of exclusive breastfeeding by mothers in Kuwait.     

Prevention of Rh-haemolytic Disease: Final Results of the “High-risk” Clinical Trial: A COMBINED STUDY FROM CENTRES IN ENGLAND AND BALTIMORE

The final results are reported of a trial of about 1,000 μg of anti-D gammaglobulin given intramuscularly to a selected high-risk group of Rh-negative primiparae just delivered of an ABO-compatible Rh-positive baby, the aim being to prevent them becoming immunized to Rh. Six months after delivery only 1 out of 173 treated mothers had been immunized as against 38 out of 176 controls. The crucial test of the prophylactic therapy depends on the presence or otherwise of anti-D at the end of a second Rh-positive pregnancy. Of 86 treated mothers two had antibodies at this time compared with 20 out of 65 controls.The results show a high degree of protection in this group of mothers.     

A mother-child segregation distortion for the Rh system. New evidence for another compatibility system associated with Rh.

In the maternity service of a private hospital in Santiago, Chile, 6,974 mother-infant pairs typed for the D-d alleles of the Rh system were collected. In our analysis, all the paris attended from October 1974 to December 1975 and from January 1977 to September 1979 were used. The segregation analysis, made by means of the T mother-child matrix, assuming Hardy-Weinberg equilibrium, reveals that: Rh(-) mothers have a higher rate of admission than do Rh(+) mothers; Rh(+) mothers produce fewer Rh(-) infants than expected; and, with less significance, Rh(-) mothers produce more Rh(+) infants than expected. This leads to a reduction in the proportion of dd individuals from mothers to their children. Ethnic subdivisions of the sample, the period considered, and the extension of the antiisoimmunization therapy do not seem to affect the general pattern of the distortion. The only plausible hypothesis to explain this finding is that selection is not related to the known Rh antigenic specificities. The reduction of the proportion of dd individuals in 1 generation leads us to review models on Rh polymorphism. It seems clear that no classical compensation is possible and d must disappear unless another mechanism maintains it in populations.     

Incidence of Maternal Rh Immunization by ABO Compatible and Incompatible Pregnancies

The incidence of maternal Rh immunization in Rh-negative women following a single ABO compatible Rh-positive pregnancy is about 17%. This incidence was determined by following Rh-negative women through two Rh-incompatible pregnancies and analysing their sera for anti-Rh at the time of delivery of their second observed pregnancy. Maternal Rh immunization occurs almost exclusively after delivery; however, antibodies may not be detectable in the absence of further antigenic stimulation.The incidence of maternal Rh immunization when maternal-foetal ABO incompatibility is also present is 9–13% and 17% for group O and non-group O women respectively. This study emphasizes the need to offer Rh-immune prophylaxis to Rh-negative women having Rh-positive infants whether or not ABO incompatibility exists between the mother and infant.     

Vaginal Delivery under Caudal Analgesia after Caesarean Section and other Major Uterine Surgery

In the absence of a recurring indication for caesarean section vaginal delivery in subsequent pregnancy is a “trial of scar,” with potentially serious implications for mother and baby. Labour under caudal analgesia was carefully supervised for 75 women with a surgically scarred uterus—due to lower segment section in 72, abdominal hysterotomy in one, and transcavity myomectomy in two. Every caesarean scar was assessed digitally during labour and every uterus was examined after delivery. Caudal analgesia provided a painless labour and delivery and made scar assessment easy. Controlled intravenous Syntocinon infusion was given to 25 patients. One scar dehiscence occurred early in labour and one in the second stage. Seventy mothers had 71 vaginal deliveries with one pair of twins and one breech. There was one stillbirth and no neonatal death. There were five repeat sections.     

Prevention of Rh-haemolytic Disease: Results of the Liverpool “Low-risk” Clinical Trial

A clinical trial is reported in which Rh-negative primiparae, just delivered of an Rh-positive ABO-compatible infant and in whom fetal cell counts after delivery suggested less than 0·2 ml of circulating fetal blood, were treated with about 200 μg of anti-D gammaglobulin. Three (0·36%) out of 844 women thus treated developed anti-D in the subsequent six months; this is 10% of the incidence in untreated controls. Three (1·8%) out of 171 treated mothers had anti-D at the end of the second Rh-positive pregnancy, and this is 18% of the incidence in controls.Possible reasons for the occasional failure of the treatment are discussed and the results of this trial are compared with those of a previous trial in which 1,000 μg or more of anti-D was given to a different group of mothers. The combined results of the two trials lead to the conclusion that the passive administration of anti-D gammaglobulin after delivery affords in this population of Rh-negative women a 95% protection rate in the postdelivery period and an 89% protection rate by the end of the subsequent pregnancy.     

Lack of an association between ABO and Rh blood group polymorphisms and stature, body weight, and BMI in a cohort of British women

Analysis of variance shows no significant associations between stature, weight, or body mass index (BMI) and ABO or Rh blood group phenotypes among a sample of mothers in England, Scotland, and Wales whose children were born during March 3-9, 1958. Social factors are significantly associated with stature and weight; the effects of social class of the women's fathers, regions of birth of the women, their ages, whether their education continued beyond age 16 or not, and the total number of births were separated out by regression analysis. The adjusted residual regression of ABO and Rh phenotypes were not significantly related to reported stature, weight, or BMI.     

THE WORK OF AN Rh COMMITTEE—Experiences in a Private General Hospital

An Rh committee was formed at Saint John''s Hospital in Santa Monica to provide preadmission consultation on all potential Rh and ABO problems and to maintain a file of information on Rh-negative patients in the delivery room. It is urged that no patient go to the delivery room without the known Rh-ABO type as part of the labor record. All obstetrical patients at the hospital are given “obstetrical information cards” for use as a memorandum on the labor record. A pink card identifies the Rh-negative patient.The program keeps the staff “Rh-conscious” and has improved teamwork among the obstetricians, pediatricians, nurses and the laboratory.     

Phosphatidylserine exposure and aminophospholipid translocase activity in Rh-deficient erythrocytes

Endogenous phosphatidylserine (PS) exposure and lipid transport activity have been investigated for seven unrelated cases of Rh_null erythrocytes. Endogenous PS exposure was measured by prothrombinase activity. Out of six cases studied, two Rh_null samples exhibited abnormal aminophospholipid exposure, as suggested by the measurement of a lower Km of factor Xa for prothrombin. Aminophospholipid translocase activity was measured through the transbilayer redistribution of spin-labelled analogues of phospholipids. Provided that incubation conditions allow the maintainance of intracellular ATP level, no difference was observed between Rh_null and control erythrocytes, clearly indicating that the aminophospholipid translocase and Rh polypeptides are different molecular species.