Longitudinalno praćenje rasta i razvoja dece majki sa najtežim tipom Rh(D) aloimunizovanih trudnoća posle primene intrauterusne intravaskularne transfuzije

Abstract

Uticaj različitih antepartalnih, intrapartalnih i ranih neonatalnih faktora rizika, značajan je za tok i ishod trudnoće, za rani neonatalni period i za kasniji rast i razvoj deteta. Oštećen plod u trudnoći i/ili porođaju nije samo problem akušera i neonatologa već i izuzetan (veliki) problem sociologa, porodice i društva. Sve ovo nameće potrebu za ranim prepoznavanjem problema ploda sa rizikom u cilju smanjivanja perinatalnog (antenatalnog) morbiditeta i mortaliteta i omogućavanja normalnog rasta i razvoja deteta. Aloimunizacija označava postojanje cirkulišućih antitela majke protiv eritrocita fetusa, koja nastaju kao odgovor na postojanje stranog antigena na membrani eritrocita fetusa. O problemu aloimunizacije u svetu je dosta pisano i rađeno, a ima i zemalja, posebno onih sa razvijenom zdravstvenom zaštitom gde aloimunizacije više nema. U Srbiji, međutim, slično kao i okolnim Balkanskim državama, aloimunizacija je i dalje prisutna i predstavlja jedan od gorućih problema perinatalne kontrole. Hemolitička bolest definisana Rh(D) aloimunizacijom zauzima značajno mesto u perinatalnom morbiditetu i mortalitetu), ona predestavlja oboljenje sa genetskom predispozicijom. Hemolitička bolest fetusa/neonatusa (HBFN), je proces stvaranja IgG anti-D antitela u krvi Rh(D) negativne trudnice koja prelaze u cirkulaciju Rh(D) pozitivnog ploda, apsorbuju se na D pozitivne eritrocite ili ostaju slobodna u fetalnom serumu. Ovako apsorbovana antitela predstavljaju hemolizine koji razaraju eritrocite. Izvesni klinički aspekti Rh(D) aloimunizacije bili su poznati stotinama godina, ali etiologija oboljenja otkrivena je sredinom prošlog veka, što je uslovilo veliki napredak u razumevanju, dijagnostici i terapiji ovog problema. Rh faktor otkrilli su Landsteiner i Weiner 1940. godine, kada su utvrdili da se u serumu eksperimentalnih zečeva, prethodno imunizovanih eritrocitima Rhesus majmuna, stvara antitelo koje aglutiniše ne samo eritrocite majmuna već i eritrocite 85% ljudi bele rase; imunizujući antigen je dobio ime Rhesus antigen. Levine i sar. 1941. godine, pokazali su da je imuni odgovor Rh-negativne trudnice na prisustvo Rh-pozitivnih fetalnih eritrocita uzrok nastanka HBFN, koja je tada nazvana erytroblastosis fetalis (EBF). Landsteiner i Levin daju odgovore na etiologiju i imunohematologiju Rh(D) aloimunizacije, 1940. godine. Pažnja se usmerila ka prevenciji (saznanju da se pojava Rh(D) aloimunizacjie majke na Rh(D) antigen fetusa može sprečiti primenom odgovarajuće količine hiperimunog anti- D imunoglobulina), antenatalnoj dijagnostici i terapiji intrauterusna intravaskularna transfuzija (IUIVT). Napredak medicine tokom poslednjih 20 godina i usavršavanje dijagnostičkih i terapijskih procedura i tehnika izmenio je prognozu života ove dece. Razvoj dijagnostike u trudnoćama sa Rh imunizacijom i terapije HBFN-a obeležilo je pet dostignuća u literaturi poznatih kao "pet velikih skokova unapred": eksangvinotransfuzija (EST), prevremeni porođaj, spektrofotometrija plodove vode, ultrazvučna dijagnostika, pristup fetalnoj cirkulaciji-kordocenteza...

The impact of different antepartal, intrapartal and early neonatal risk factors is significant for the course and outcome of a pregnancy, for an early neonatal period and for later growth and development of a child. The case of fetal damage during pregnancy and/or childbirth is a significant problem not only for obstetricians and neonatologists but also for sociologists, family and society as a whole. This calls for an early problem identification of fetus with a risk in order to decrease perinatal (antenatal) morbidity and mortality, and enable normal growth and development of a child. Allo-immunization indicates the existence of maternal circulating antibodies against fetal erythrocytes, that emerge in response to the existence of extraneous antigen on the fetal erythrocyte membrane. Around the world, a great deal of scientific and practical work has been dedicated to the problem of allo-immunization, and there are countries, especially those with developed health care systems, where alloimmunization is no more existent. However, in Serbia and its neughboring Balkan countries allo-immunization is still present and represents one of the vital problems of perinatal contol. Тhe hemolytic disease defined by Rh(D) allo-immunization contributes significantly to perinatal morbidity and mortality. The hemolytic disease of fetus/neonate is the disease (HDFN) with genetic predisposition and it represents a process of production of IgG anti-D antibodies in blood of a Rh(D) negative pregnant woman that go over into the circulation of Rh(D) positive fetus, get absorbed on D positive erythrocytes or stay free in fetal serum. Antibodies absorbed in this way represent hemolysins that destroy erythrocytes. Certain clinical aspects of Rh(D) allo-immunization have been known for hundreds of years, but the disease etiology was discovered in the middle of 20th centuary, and that greatly improved understanding of the problem, and its diagnostics and treatment. Rh factor was discovered by Landsteiner and Weiner in 1940, when in the serum of experimental rabbits, previously immunized by Rhesus monkey erythrocytes, they determined procreation of an antibody which agglutinates not only monkey erythrocytes but also erythrocytes of 85% of Caucasians; the immunizing antigen was called the Rhesus antigen. In 1941, Levine et al. showed that the immune response of Rh negative pregnant woman to the presence of Rh positive fetal erythrocytes is the cause of the hemolytic disease of fetus/neonate, that has since been called erytroblastosis fetalis (EBF). In 1940, Landsteiner and Levine gave answers regarding etiology and immunohematology of Rh(D) allo-immunization. The focus has then turned to the prevention (knowledge that Rh(D) allo-immunization of a mother to Rh(D) fetal antigen can be prevented by application of sufficient quantity of hyperimmune anti-D immunoglobulin), to antenatal diagnostics and to intrauterine intravascular transfusion (IUIVT) treatment...