Optimization of Management of Pregnant Women with Intrahepatic Cholestasis of Pregnancy Using Plasmapheresis

To increase the efficacy of complex treatment of intrahepatic cholestasis of pregnancy by means of including plasmapheresis

Tasks of the study

1. To determine the features of the clinical course of pregnancy, labor and the early neonatal period in pregnant women with intrahepatic cholestasis of pregnancy, as well as to identify risk factors for the development of this disease on the basis of a retrospective analysis of delivery records of women with intrahepatic cholestasis of pregnancy.

2. To study the HLA class I system locus parameters in pregnant women with intrahepatic cholestasis of pregnancy.

3. To study changes in clinical, hemostasiological and biochemical parameters depending on the therapy administered in pregnant women with intrahepatic cholestasis of pregnancy

4. To evaluate the state of the feto-placental complex in pregnant women with intrahepatic cholestasis of pregnancy and its changes under the influence of various types of therapy

5. To develop an algorithm for examination and treatment of pregnant women with intrahepatic cholestasis of pregnancy

Risk factors for the development of this disease have been identified on the basis of studying the features of the course of pregnancy, outcomes of labor, and the course of the early neonatal period of newborns in pregnant women with intrahepatic cholestasis of pregnancy.

For the first time, the use of plasmapheresis in the complex treatment of intrahepatic cholestasis of pregnancy has been pathogenetically substantiated on the basis of studying clinical, hemostasiological and biochemical blood parameters and their changes under the influence of plasmapheresis, as well as the features of feto-placental blood flow.

On the basis of studying the polymorphism of genes of the HLA class I system, a familial predisposition to the development of intrahepatic cholestasis of pregnancy has been revealed. The role of assisted reproductive technologies in the development and severity of intrahepatic cholestasis in pregnant women has been determined.

An algorithm for examination and treatment of pregnant women with intrahepatic cholestasis of pregnancy has been developed.

On the basis of the results obtained, a method for including plasmapheresis in the complex treatment of intrahepatic cholestasis of pregnancy has been developed and the expediency of its use in pregnant women has been substantiated.

Optimal regimens and variants of plasmapheresis in the treatment of patients with intrahepatic cholestasis of varying severity have been determined. The efficacy of plasmapheresis has been demonstrated in improving the clinical course, reducing the frequency of complications during pregnancy, labor and the postpartum period, and improving the condition of the fetus and newborns.

1. Factors predisposing to, as well as aggravating the course of intrahepatic cholestasis of pregnancy, are chronic diseases of the hepatobiliary system, undergoing assisted reproductive technology (ART) programs, a history of intrahepatic cholestasis of pregnancy in previous pregnancies, and familial predisposition - a high frequency (up to 40%) of the HLA B8 locus in this category of women

2. Plasmapheresis, possessing a broad spectrum of action, is pathogenetically justified and of substantial importance in the treatment of pregnant women with intrahepatic cholestasis of pregnancy; it allows to significantly reduce the clinical manifestations of the disease, improve the state of the uterine-placental complex, reliably reduce biochemical markers of cholestasis by 1.5-fold (p<0.01), stabilize the coagulation and fibrinolytic potentials of blood (p<0.05), and reduce the drug load by 25%.

3. Timely diagnosis of intrahepatic cholestasis of pregnancy and adequate complex treatment using plasmapheresis allow to prolong pregnancy on average by 4 weeks, reduce the frequency of complications in the course of pregnancy and labor by 1.5-fold, and in the postpartum period – by 2.5-fold, and the frequency of pathology in newborns in the early neonatal period by 7.6%, due to a two-fold reduction in the frequency of birth asphyxia and a two-fold reduction in the frequency of hypotrophic newborns (p<0.01).

The main positions of the dissertation were presented and discussed at the conference of the Department of Prevention and Treatment of Pregnancy Pathology jointly with the Department of Gravitational Surgery of Blood on October 23, 2008, and at a meeting of the approval commission of the Federal State Institution “Scientific Center for Obstetrics, Gynecology and Perinatology named after V.I. Kulakova” of Rosmedtechnologii on November 14, 2008.

The research results and the main recommendations derived from them are used in the Department of Prevention and Treatment of Pregnancy Pathology of the Federal State Institution "Scientific Center for Obstetrics, Gynecology and Perinatology named after V.I. Kulakova" of Rosmedtechnologii in the treatment of pregnant women with intrahepatic cholestasis of pregnancy; they are used in the development of educational programs for physicians undergoing training at the Center, as well as in seminars on pregnancy pathology. Eight printed works have been published on the topic of the dissertation.

The dissertation consists of an introduction, 4 chapters, conclusions and practical recommendations; it is written in 148 pages of typescript (including the reference list), and the work is illustrated with 25 tables and 16 figures. The bibliographic index includes 188 sources, of which 88 are by domestic and 100 by foreign authors.