Clinico-Immunological Characterization and Optimization of Treatment of Early Anemia in Premature Newborns with Extremely Low and Very Low Birth Weight

The dissertation is devoted to the clinico-immunological characterization and optimization of treatment of early anemia in premature newborns with extremely low (birth weight ≤ 1000 g) and very low (birth weight ≤ 1500 g) birth weight. The study focuses on the state of the cellular component of immunity in this category of patients and the evaluation of various approaches to the correction of early anemia, including the use of recombinant human erythropoietin and erythrocyte-containing components of donor blood.

The goal of the work is to establish the clinico-immunological characterization of premature newborns with extremely low and very low birth weight under various methods of early anemia correction for the optimization of personalized therapy. The study addresses tasks including the investigation of immunological parameters in the course of life, the clinico-laboratory features of the course of anemia, the assessment of the influence of correction on immune status, as well as the determination of predictors of complications and the mathematical assessment of risks.

An overview of the achievements of perinatal medicine and the problems associated with the care of premature newborns is not so obvious and has become less relevant in recent decades; premature birth determines the level of perinatal mortality and morbidity (Petrikova T.Yu., 2008; Kulakov V.I. et al., 2008; Skvortsova V.A., 2011; Kaija Mikkola et al., 2008). Premature children account for 60–70% of early perinatal mortality and 65–75% of child mortality (WHO, 2005; Frolova O.G., 2008; Baibarina I.N., 2011; Savelieva G.M., 2011).

Modern scientific achievements in various fields of medicine have made it possible to create a unique perinatal technology, including a wide range of pharmacological agents that increase the survival rate of premature newborns with extremely low (ELBW) and very low (VLBW) birth weight, who not long ago were condemned to death (Kulakov V.I. et al., 2008; Zaitseva O.D., 2011; Pedro R. et al., 2011, Decree of the President of the Russian Federation of May 7, 2012 No. 598 "On Improving and State Policy in the Field of Healthcare").

The scientific platform "Pediatrics," as a set of measures aimed at reducing neonatal mortality, is identified as a priority direction for reducing mortality and disability among children born with very low (VLBW) and extremely low (ELBW) birth weight, through personnel selection, targeted treatment, and assessment of its effectiveness and contribution (Strategy for the Development of Medical Science in the Russian Federation for the Period up to 2025).

Despite numerous studies devoted to this problem, many unresolved questions regarding the proximal and distal developmental trajectories of children born with ELBW and VLBW remain; their immunological tactics for many diseases characteristic of premature newborns have not yet been defined.

Early anemia of prematurity (EAP) develops in 17–99% of children with ELBW and VLBW at the 4th–10th week of life and is a polyetiological disease with a complex pathogenesis and unresolved issues of prevention and treatment (Rumina I.I., 2012). Until recently, the virtually sole method of EAP correction was replacement transfusion, which was performed using blood components from adult donors with the physiological characteristics of age, sex, immunology, and other attributes inherent to adults.

Extreme immaturity of premature infants with ELBW and VLBW at birth determines their unique physiology. The immunological reactivity of premature children is generally characterized by immature and labile immunity (Subramanian, Siva, 2006), and the more premature the child, the lower the levels of specific protective factors (Detlyareva M.V., 2010).

The relevance of studying factors influencing health indicators in premature newborns with ELBW and VLBW at birth is high; however, the state of the cellular component of immunity and the clinico-immunological profile during EAP correction, in order to substantiate approaches to personalized therapy, have been insufficiently studied, which prompts the improvement of prevention and treatment of this pathology.

Object of study: premature newborns with extremely low (birth weight ≤ 1000 g) and very low (birth weight ≤ 1500 g) birth weight with early anemia of prematurity.

Goal of the study: based on the study of the state of the cellular component of immunity, to provide a clinico-immunological characterization of premature newborns born with extremely low and very low birth weight, through the application of various methods of EAP correction, for the optimization of personalized immunological therapy.

Tasks of the work:

1. To study the state of the main indicators of the cellular component of immunity in premature newborns with ELBW and VLBW at birth and in the course of life.

2. To establish the clinico-laboratory features of the course of EAP in newborns with VLBW and ELBW depending on the method of correction.

3. To evaluate the influence of various methods of EAP correction in premature newborns with ELBW and VLBW at birth and to scientifically substantiate the choice of the optimal therapeutic tactic on an immunological basis.

4. To determine predictors of a complicated postpartum period in prematurely born children with ELBW and VLBW under various methods of EAP correction.

Scientific novelty:

Based on comprehensive clinico-laboratory studies, the features of the state of the cellular component of immunity in premature newborns with ELBW and VLBW at birth have been established for the first time. The conducted studies have made it possible to assess the cellular composition of immunity in premature newborns with ELBW and VLBW at birth on an immunologically new level and to reveal a significant decrease compared with analogous indicators in full-term newborns.

The clinico-immunological profile of premature newborns with ELBW and VLBW at birth has been determined depending on the application of various methods of corrective therapy for EAP, which makes it possible to provide a scientific substantiation for personalized immunological therapy of EAP.

For the first time, through comprehensive studies, data have been obtained that make it possible to substantiate the use of an effective and safe method of EAP correction in premature newborns with ELBW and VLBW at birth.

Among the studied immunological parameters, a high risk of developing complications (transitional period adaptation disorders) has been identified in premature children born with ELBW and VLBW following the transfusion of erythrocyte-containing components of donor blood; the expediency of using recombinant human erythropoietin preparations for EAP correction in premature children has been substantiated.

A dependence between the method of EAP correction and the risk of developing inflammatory diseases in the late period of prematurely born newborns with ELBW and VLBW at birth has been established.

Scientific and practical significance:

The results of the study make it possible to provide a substantiated personalized approach to the choice of the optimal and safe method of EAP treatment.

The expediency of EAP correction has been scientifically substantiated, and the immunological tactics of EAP have been justified, which influences the improvement of health indicators in premature newborns with ELBW and VLBW at birth.

Positions to be defended:

1. The influence of EAP correction in newborns with ELBW and VLBW at birth does not depend on the type of therapy.

2. EAP correction in newborns with ELBW and VLBW is preferable with recombinant human erythropoietin, which normalizes indicators of cellular immunity during the intrauterine period.

3. Indicators of cellular immunity were statistically significantly reduced in premature newborns with ELBW and VLBW during EAP correction using erythrocyte-containing components of donor blood, and the risk of immunosuppression increased depending on the volume and erythrocyte mass of the transfusion.

4. In newborns with massive transfusions of erythrocyte-containing blood components, the risk of developing congenital immunodeficiency pathology is increased, which should be taken into account in further follow-up of such children.

Implementation of research results in practice:

The main provisions of the dissertation are applied in a complex of diagnostic and therapeutic measures at the KGBUZ "Perinatal Center" of Khabarovsk. The materials of the dissertation have been implemented and are used in the educational process in cycles of professional retraining and professional development of neonatologists, pediatricians, general practitioners, internists, and clinical residents of the Far East region at the departments of pediatrics with a course of neonatology of the FPC DVGMU and the Institute for Advanced Training of Healthcare Specialists of the Khabarovsk Territory. A textbook-methodological manual for physicians entitled "Anemic States in Newborns" (Khabarovsk, 2012) has been published.

Verification of the work: materials of the dissertation have been presented at the Congresses of Pediatricians of Russia with international participation "Relevant Problems of Pediatrics" (Moscow, 2010, 2011, 2012); at the I Congress of Pediatricians of the Far East "Relevant Issues of Maternal and Child Health Protection at the Current Stage" (Khabarovsk, 2010); at the scientific-practical conference dedicated to the 10th anniversary of the establishment of the YBUZ "Perinatal Center" (Khabarovsk, 2010); at the Far Eastern scientific-practical conference "Relevant Problems of Pediatrics" (Khabarovsk, 2011).

The author is a laureate of the XIII regional competition of young scientists and postgraduates of the Government of the Khabarovsk Territory, section "Medical Spiders" (Khabarovsk, 2011).

Publication of research results: 10 printed works have been published on the topic of the dissertation, including 2 articles in leading peer-reviewed journals recommended by the VAK of the Russian Federation for covering the main scientific results of dissertation research for the degree of Candidate of Medical Sciences.

LITERATURE REVIEW