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UDC 615.38:618.3+616-053.3
PREVENTION OF RHESUS IMMUNIZATION IN PREGNANT WOMEN WITH POTENTIALLY SENSITIZING EVENTS
:Omsk State Medical University, Omsk
2City clinical perinatal center, Omsk
L.V. Kuklina1, M.A. Ozheryelyeva2, Ye.F. Meshchenkova2
The incidence of hemolytic disease of the fetus and the effectiveness of its prevention has been studied. 56 pregnant women with Rh-negative blood without antirhesus- antibodies titers were observed; they had a complication of gestation in the form of threat of termination of pregnancy, accompanied by bloody discharge from the genital tract, some of whom (the main group consisted of 29 women) had an unplanned prophylaxis of Rhesus immunization together with preventive measures in the decreed period. The comparison group consisted of 27 women with the threat of abortion, accompanied by bloody discharge from the genital tract, for whom preventive measures were not performed in full because of the development of immunization or their refusal to participate. The best results were obtained in the main group, where it was possible to prevent the development of Rh- immunization in 100% of cases. In the comparison group, the proportion of immunized pregnant women who did not receive an unscheduled prophylactic dose of immunoglobulin due to complications of gestation was 7.4%, with an abstinence from prenatal prophylaxis at 28-30 weeks -11,1%. With the development of complications of gestation in the form of the threat of termination of pregnancy, accompanied by bloody discharge from the genital tract in women with Rh-negative blood, the method of choice is to carry out unscheduled prevention of Rh-immunization along with preventive measures in the prescribed time.
Key words: Rh-immunization, preventive measures, threat of abortion.
According to statistics, the frequency of hemolytic disease of the fetus and newborns in the Russian federation ranges from 0,1 to 2,5%, has not changed during the recent 10 years and constitutes 9,9% and 1,46% of all born in the structure of perinatal morbidity and lethality [1, 2]. The results of epidemiological researches conducted in various regions of the country considerably differ from the data of foreign authors. In Russia, the rate of rhesus-immunized women reaches 1,2% [3]. The conduction of preventive measures for women with rhesus-negative blood is an extremely important issue. Preventive measures include planned injection of anti-Rh (D) immunoglobulin G to non-immunized women with rhesus-negative blood (28-30 weeks of pregnancy, first 72 hours in the postpartum period) and by potentially sensitizing events, which is the gold standard for prevention of immunization in women, and, consequently, hemolytic disease of the fetus [4, 5, 6].
The list of potentially sensitizing events requiring prevention of rh-immunization: invasive prenatal diagnosis, reduction of one of the embryos, intrauterine treatment of the fetus (shunting, blood transfusion), stomach trauma, intrauterine fetal demise, termination of pregnancy (regardless of the method), prenatal bleeding, spontaneous miscarriage, extra-uterine pregnancy [7, 8]. Preventive measures by the occurrence of potentially sensitizing event include the injection of preventive dose of anti-Rh (D) immunoglobulin depending on the time of occurrence of potentially sensitizing events and period of drug half-life. 28
Research objective: to study the incidence of hemolytic disease of the fetus and effectiveness of its prevention.
Materials and methods
The study included 56 pregnant women at the age of 27-35 years with rh-negative blood without antibody titers receiving medical treatment in the obstetrics department of the City clinical perinatal center, Omsk, during the period of 2012-2016. All examined women referred to the category of recurrently pregnant, underwent examination and treatment for threatened preterm labor (threatened late spontaneous miscarriage). Criteria of inclusion into the research group were: Rh-negative blood without antibody titer, Rh-positive blood of the partner, threatened miscarriage accompanied by bloody discharge from genital tracts, lack of symptoms of hemolytic disease of the fetus and newborns and/or hemotransfusions, intrauterine fetal death of hemolytic disease; lack of severe extragenital pathology.
The main group consisted of 29 pregnant women with threatened miscarriage accompanied by bloody discharge from genital tracts having been exposed to prenatal unplanned prevention of Rh-immunization by human immunoglobulin anti-Rho [D] (Rezonativ, LSR-000970/10, Okta-farma AB, Sweden) in the dose of 250 mkg (1250 IU) and also prevention of Rh-immunization in the decreed terms of 28-32th weeks of gestation and during 72 hours after the delivery. The group of comparison included 27 pregnant women with threatened miscarriage accompanied by bloody
discharge from genital tracts having rejected to undergo prenatal unplanned prevention of Rh-im-munization. In terms of the current study there were examined pregnant women (n=56) from the moment of admission to the hospital pathologic pregnancy department till the delivery be means of the laboratory method of diagnosis of Rh-immu-nization. The titer of anti-Rh antibodies was determined in one laboratory by helium cards (DG Gel® Anti-IgG, №210322). The effectiveness of the conducted prevention was evaluated by the lack of appearance of complete or incomplete anti-Rho (D) antibodies in blood in 10 days, 1 and 3 months after the drug injection in the postpartum period (obstetric patients the titer dynamics of whom was impossible to follow were excluded from the research group).
The clinical study of the course of pregnancy and labor outcome required the search of standard criteria of group homogeneity. The basic feature uniting the groups of pregnant women were: parity of labor, threatened miscarriage accompanied by bloody discharge from genital tracts, with rh-negative blood without antibody titers, Rh-positive blood of the partner or Rh-positive blood of the fetus. The registered group features were
Prenatal unplanned prevention of Rh-immuni-zation in patients of the main group included i.m. injection of human immunoglobulin anti-Rho [D] in the dose of 250 mkg (1250 IU) to all patients °with threatened spontaneous miscarriage and bloody discharge during 48 hours since the moment of hospital admission. In case of recurrent threatened spontaneous miscarriage with bloody discharge the drug was injected again in the dose of 250 mkg (1250 IU) if the time interval since the previous injection did not exceed 6 weeks (n=1). All pregnant patients of the main group received preventive dose of human immunoglobulin anti-Rho [D] on the 28-32th week of gestation (conduction of prevention of Rh-immunization depended on the terms of unplanned prevention and was carried since 6 weeks with compulsory pre-test for presence of anti-Rho (D)-antibodies in blood and in the postpartum
characterized by high significance (p<0,05) which is acceptable for medico-biological studies.
The statistical data processing was performed by "Statistica" program, version Exel 3, OSPPS v. 12. There were implied standard methods of descriptional statistics; the data are presented in the form of median (Me) and interquartile range (25 and 75% percentiles). The comparison of data was performed by non-parametric Mann-Whitney test. The null hypothesis was checked by Wilcoxon signed-rank test. For categorical variables the data were presented as rates (percentage), comparison was conducted by means of x2 criterion. Differences were considered statistically significant by p<0,05.
Results and discussion
The average age of patients in groups constituted 28,5±3 years. The somatic anamnesis of 11 pregnant patients (19,6%) was aggravated by car-dio-vascular pathology (vegetovascular dystonia, gestational arterial hypertension); in 13 patients (23,2%) - gastro-intestinal diseases, in 7 patients (12,5%) - renal diseases, other extragenital pathology was registered in 4,3% of cases. The obstetric-gynecologic anamnesis was assessed in the traditional representation (Table 1).
period. The titer of anti-Rho (D)-antibodies up to 1:8 not tended to increase was considered as residual in case of prenatal unplanned prevention of Rh-immunization and did not affect the decision on the necessity of Rh-immunization prevention conduction.
The complications occurred after the injection of immunoglobulin included infiltration and local painfulness in 5% of cases. In the postpartum period, all pregnant women were exposed to the prevention of Rh-immunization by human immuno-globulin anti-Rho [D] in the dose of 250 mkg (1250 IU) i.m.
The effectiveness of performed prevention was evaluated by the presence of anti-Rho (D)-an-tibodies in blood during 10 days, 1 and 3 months after the delivery. The absence of anti-Rho (D)-an-tibodies titers since 1 and 3 months after the de-
Table 1
Parameters of reproductive function of patients of main and comparison groups
Parameters of reproductive function Groups(M±m) P
I(n=29) II (n=27)
Number of pregnancies 3,1±0,03 3,3±0,03 p> 0,05
Parity 0,6±0,06 0,5±0,04 p> 0,05
Caesarean section 0,1±0,02 0,2±0,05 p> 0,05
Medical abortion 0,2±0,1 0,7±0,01 p> 0,05
Spontaneous miscarriage 0,2±0,03 0,3±0,02 p> 0,05
Extra-uterine pregnancy 0,01±0,03 0,02±0,02 p> 0,05
Non-developing pregnancy 0,01±0,04 0,03±0,01 p> 0,05
livery and also remaining anti-Rho (D)-antibodies titers not exceeding 1:8 up to 10 days with further disappearance were considered a positive effect of Rh-immunization prevention. Gestational terms
and number of pregnant women having received the preventive dose of human immunoglobulin anti-Rho [D] are shown in Table 2.
Table 2
Gestational terms of human immunoglobulin anti-Rho [D] injection
Prenatal unplanned prevention Prenatal planned prevention
20-21weeks n = 7 28 weeks n = 14
22-23weeks n = 8 29 weeks n = 5
23weeks n = 5 30 weeks n = 5
24-25weeks n = 5 32 weeks n = 5
26-27weeks n = 4 - -
In 2 (6,8%) patients with performed prenatal unplanned prevention of Rh-immunization in the rem of 25-26 weeks and in 1 patients in the term of 2627 weeks further there was registered threatened miscarriage accompanied by bloody discharge occurred during 3 weeks since the 1st injection of unplanned preventive dose of human immunoglob-ulin anti-Rho [D], they did not need its recurrent injection. One patient with recurrent threatened miscarriage occurred since 6 weeks after the 1st injection of unplanned preventive dose of human immunoglobulin anti-Rho [D] in the term of 26-27 weeks of pregnancy was injected with the recurrent preventive dose.
In all patients of the main group before the planned prevention by human immunoglob-ulin anti-Rho [D] there was determined the titer of anti-Rho (D )-antibodies: 10 patients (34,40%) had the titer 1:4; 7 patients (24,1%) - 1:2; 12 patients lacked the titer. Considering the period of drug half-life, the current titer was determined as residual.
All pregnant women of the main group performed delivery in the term of 37-40 weeks. The titer of anti-Rho (D)-antibodies 1:2 before the delivery was observed in 13,7% (4 patients) women and was revealed in patients exposed to the planned prevention on the 32nd week of gestation. The stated titer was considered as residual and did not affect the decision on the necessity of Rh-immunization prevention conduction. In the study group incomplete anti-Rho (D)-antibodies in the titer 1:2 in 10 days were registered in 2 out of 29 patients due to their incomplete clearance. In the following period of observation, none of the examined patients had antibodies in blood, which indicates the effective performance of prevention of Rh-immuniza-tion.
The dynamic observation of patients of the comparison group revealed appearance of anti-Rho (D)-antibodies in the blood of 2 pregnant women (7,4%) in the term of gestation up to 28 weeks; 12 patients were not exposed to Rh-immunization on the 28th week due to rejection: 13 patients re-
ceived the preventive dose of drug on the 28-30th week. In 2 patients of the group not receiving the preventive drug dose there appeared anti-Rho (D)-antibodies in titer 1:32 (in dynamics 1:64) after 32 weeks. All non-immunized patients underwent postpartum prevention (n=23). The blood of 1 patient contained anti-Rho (D)-antibodies in the postpartum period in titer 1:16 on the 10th day after the drug injection. The dynamic observation of the mentioned patient showed the presence of titer 1:4 in the 1st and 3rd months which allows to conclude on the inefficiency of the prevention. Thus, the rate of immunized pregnant women having not received the preventive dose of immuno-globulin due for gestation complications constituted 7,4% (n=2); the number of immunized pregnant women having not received the preventive dose of immunoglobulin due for gestation complications and rejected prenatal prevention on the 2830th week of gestation constituted 11,1%.
Conclusion
The main objective of the antenatal fetal health protection in Rh-negative pregnant women are the measures aimed at the prevention of immunization development on non-sensitized patients. The treat of pregnancy miscarriage accompanied by bloody discharge from genital tracts is a risk factor of the development of mother's immunization for erythrocytic antigens. The performance of planned prevention of Rh-immunization in the given category of patients together with decreed antenatal and postpartum prevention precludes the development of Rh-D-antigen immunization.
References
1. Ailamazyan E.K. Isoimmunization by pregnancy. Saint-Petersburg, 2012.
2. Haemolytic disease of the fetus of pregnant women wшth Rh-sensibilization. Diagnosis, treatment, prevention: methodological letter of the Ministry of Health and Social Development of the Russian Federation №
15-4//10/2-12699 of 16.12.2011 Available at: http://www.rosmintrud.ru/docs/mzsr/let-ters/211 Accessed 01.09.2017.
3. Sidelnikova V.M. Haemolytic disease of the fetus and newborn. Moscow, 2004.
4. Karanth L. Anti-D administration after spontaneous miscarriage for preventing Rhesus alloimmunisation. Cochrane Database Syst. Rev, 2013.
5. Qureshi H.. BCSH guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn. Transfus Med. 2014; 1 (24): 8-20.
6. Bolton-Maggs P.H. Errors in anti-D im-munoglobulin administration: retrospective analysis of 15 years of reports to the UK confidential haemovigilance scheme. BJOG. 2013; 7 (120): 873-878.
7. Sabita B., Ravneet K. Hemolytic disease of the fetus and newborn: Current trends and perspectives. Asian. J. Transfus. Sci. 2011; 1 (5): 3-7.
8. Thorp J.M. Utilization of anti-RhD in the emergency department after blunt trauma. Obstet. Gynecol. Surv. 2008; 2 (63): 112-115.
Contacts:
Corresponding author - Kuklina Larisa Vladi-mirovna, Candidate of Medical Sciences, Associate professor of the Department of obstetrics and gy-necology of further vocational education of Omsk State Medical University, Omsk. 644043, Omsk, Lenina Ulitsa, 12. Tel.: (3812) 230293. Email: [email protected]
