Clinicolaboratory Criteria for the Diagnosis of Intrauterine Hypoxia and Prediction of Perinatal Outcomes in Pregnant Women

The dissertation is dedicated to the development of clinicolaboratory criteria for the diagnosis of intrauterine fetal hypoxia and prediction of perinatal outcomes in pregnant women. The research is based on a comprehensive analysis of risk factors — social, somatic, and reproductive — in the formation of intrauterine hypoxia, as well as on the assessment of the state of the fetoplacental complex. Biochemical blood indicators of pregnant women and newborns were studied, including the concentration of lactate, glucose, malondialdehyde, and total antioxidant activity, reflecting the degree of severity of hypoxic damage.

The scientific novelty lies in the identification of patterns of change in biochemical indicators in pregnant women and children in the context of intrauterine hypoxia of varying severity, as well as in the substantiation of the diagnostic and prognostic significance of a number of biochemical markers. The practical significance of the work is expressed in the development of prognostic tables for assessing the risk of hypoxia and developmental delay in newborns, additional diagnostic criteria, and the improvement of the monitoring algorithm for pregnant women with intrauterine fetal hypoxia.

Relevance of the Scientific Research

Prevention, diagnosis, and treatment of fetal hypoxia remain one of the urgent problems of modern obstetrics (Fedorova M.V., 1997; Savel'eva G.M., 2003).

Intrauterine hypoxia occupies one of the leading positions in the structure of perinatal diseases and mortality. This pathology, as a rule, is a consequence of placental insufficiency, which accompanies virtually all complications of pregnancy — fetal wastage, gestoses, developmental delay or fetal death, preterm birth, acute or chronic infections (Savel'eva G.M., 1995; Fedorova M.V., 1997, Sidel'nikova V.M., 1999; Radzinsky V.E., 1999; Serov V.N., 2002).

In recent years, various etiological factors and separate pathogenetic mechanisms underlying the development of fetal hypoxia have been identified. Research on risk factors of this pregnancy complication has shown that their influence on the placenta and fetus is non-specific and is primarily associated with the development of perinatal hypoxia accompanied by hemodynamic and metabolic disturbances in the fetoplacental system (Fedorova M.V., 1982, 1997; Savel'eva G.M., 1991, Kuznetsova V.A., 1992; Serov V.N., 2002; Afanasyeva N.V., Strizhakov A.N., 2004; Ailamazyan E.K., 1998).

Taking into account the formulated concepts of fetal damage in pathological pregnancy, various diagnostic methods are applied: clinical, functional (ultrasonography, cardiotocography, Dopplerometry), laboratory — determination of hormones (estriol, placental lactogen, etc.), trophoblastic beta-glycoprotein (TBG), acid-base state, and enzyme activity.

Detailed analysis of pathophysiological changes associated with oxygen deficiency indicates that modern functional diagnostic technologies can reveal only the consequences of hypoxia, gross pathology — intrauterine developmental delay, changes in hemodynamics and fetal heart rate, hemorrhages, etc. Hypoxic-ischemic organ damage at the cellular level remains inaccessible to diagnosis, which is why biochemical research methods are the most promising (Barashnyov Yu.I., 1997).

The high level of hypoxia and the increasing number of newborns with perinatal CNS lesions indicate that existing methods of diagnosis and treatment of hypoxia during pregnancy are insufficiently effective and require improvement (Serov V.N., 2002; Savel'eva G.M., 2003).

The problem of intrauterine hypoxia has not only medical but also social significance. In childhood, 60–80% of all nervous system diseases are consequences of hypoxic-ischemic CNS damage of varying severity, intracranial hemorrhages, which among premature children occur in 40–70%, and among term children in 9–27%, caused by hypoxia in the perinatal period (Milovanov A.P., 1999; Strizhakov A.N., Timokhina T.F., Baev O.P., 2003; Kornilov A.V., 2002; Serov V.N., 2002).

Particular attention is attracted by the consequences of intrauterine hypoxia experienced by the child during the antenatal period. It has been established that these children have delayed neuropsychological development, disturbances of liver function, dysfunction of the hypothalamic-pituitary-adrenal system, etc. (Kuznetsova V.A., 1992; Kornilov A.V., 2002).

According to G.N. Samsigina (1997), K. Sridhar, P. Kumar (2001), in recent years the percentage of children with perinatal hypoxia has been increasing against the background of declining birth rates, which determines the social significance of research on prediction and prevention of this pathology.

Thus, the high level of perinatal hypoxia and its consequences dictates the need to improve diagnostic methods and develop an algorithm for predicting this pathology. The application of additional diagnostic and prognostic criteria in healthcare will allow to improve the management strategy for pregnant women with fetal hypoxia and reduce perinatal mortality and morbidity in children who have experienced intrauterine hypoxia:

Objective of the Research

To develop clinicolaboratory criteria for the diagnosis of intrauterine fetal hypoxia and prediction of perinatal outcomes in pregnant women based on identified risk factors, clinical, functional, and biochemical data reflecting hypoxia in the fetoplacental system.

Tasks of the Research

1. To provide a comprehensive characterization of the somatic and reproductive health of pregnant women and to identify risk factors for the development of intrauterine fetal hypoxia in the population under modern conditions.

2. To assess the state of the fetoplacental complex in women with hypoxia and to develop the most informative criteria for prediction of pregnancy outcomes.

3. To investigate in the blood of women with pregnancy complicated by fetal hypoxia biochemical indicators reflecting the degree of hypoxia, lipid peroxidation, the state of antioxidant defense, and energy provision, and to evaluate their significance for the diagnosis of hypoxia.

4. To investigate in the blood of newborn children the concentration of lactate, glucose, malondialdehyde, total antioxidant activity, and to compare them with the indicators of mothers for the development of criteria for prediction of perinatal outcomes.

5. To develop additional criteria for the diagnosis of intrauterine fetal hypoxia and prediction of perinatal outcomes in pregnant women.

Scientific Novelty of the Research

- Risk factors (social, somatic, related to reproductive health, and others) for the formation of intrauterine fetal hypoxia in pregnant women have been identified, their significance has been clarified, and their differences from population data have been established.

- Clinicolaboratory, ultrasonographic, and functional features in pregnant women with intrauterine fetal hypoxia developing against the background of varying degrees of fetoplacental insufficiency (FPI) have been established.

- It has been proven that diagnostic criteria for the development of severe intrauterine fetal hypoxia are hemodynamic disturbances manifested by decreased blood flow in the uterine, spiral, and umbilical arteries, changes in cardiotocography, and metabolic disturbances.

- Patterns of change in biochemical blood indicators and their interrelationships in pregnant women and newborns with hypoxia of mild, moderate, and severe degrees have been identified.

- The diagnostic and prognostic significance of biochemical blood indicators (lactate, malondialdehyde, total antioxidant activity, glucose) for the pregnant woman, fetus, and newborn in the context of intrauterine hypoxia has been established.

- Biochemical and functional criteria of intrauterine developmental delay (IUD) developing against the background of hypoxia and intrauterine infection have been identified.

- The features of the course of pregnancy and childbirth in women with intrauterine fetal hypoxia have been determined.

- Biochemical criteria for diagnosing the degree of hypoxia in women during pregnancy and in children at birth have been developed.

- It has been established that the concentration of lactate, glucose, malondialdehyde, and total antioxidant activity in the blood of pregnant women may serve as prognostic criteria for the outcome of pregnancy — the birth of a child in a state of hypoxia of varying severity and the delay of intrauterine development.

Practical Significance of the Work

- Prognostic tables for assessing the risk of hypoxia and developmental delay in newborns during the antenatal period have been developed.

- New additional criteria for the diagnosis of fetal hypoxia of varying severity, the syndrome of intrauterine developmental delay, and the prediction of these complications in newborns have been identified.

- The algorithm for monitoring pregnant women with intrauterine fetal hypoxia has been supplemented.

Dissertation Propositions to be Defended

1. Under modern conditions, the course of pregnancy and perinatal outcomes in women with intrauterine fetal hypoxia are associated with the presence of a complex of social, hygienic, and medical-biological risk factors.

2. The most informative criteria for the diagnosis of intrauterine hypoxia and prediction of perinatal outcomes are the dynamic assessment of the functional state of the fetus and biochemical blood indicators in pregnant women — lactate, glucose, malondialdehyde, total antioxidant activity, reflecting the degree of severity of hypoxia, intrauterine developmental delay of the fetus and newborn.

Implementation of the Research Results

The results of the research have been implemented in the practice of MUZ "Maternity Hospital No. 1" of the city of Ivanovo and MLPU "Maternity Hospital No. 5" of the city of Nizhny Novgorod. The main provisions of the dissertation are used in the educational process at the Department of Obstetrics and Gynecology and the Department of Clinical Laboratory Diagnostics of the Faculty of Additional Postgraduate Professional Education of GOU VPO "Ivanov State Medical Academy of the Federal Agency for Healthcare and Social Development".

Validation of the Work

The main provisions and conclusions of the work were reported at the international conference "Reproductive Health of Society" (Saint Petersburg, 2006), at the international scientific-practical conference "Health and Education in the XXI Century" (Moscow, 2006), at the V Russian Congress "Modern Technologies in Pediatrics and Pediatric Surgery" (Moscow, 2006). Six printed works have been published on the topic of the dissertation, of which four are in conference proceedings and collections of scientific works, one is in a peer-reviewed journal, and one is clinical recommendations for obstetrician-gynecologists.