**2. Preterm birth and perinatal prognostic indicators of further age pathologies**

Due to the high level of technology and quality medical care in the field of neonatology in recent years, noticeable achievements have been made in reducing the mortality rates of small and extremely small premature babies [100, 122]. In many countries, the criteria for live birth have been changed and great achievements have been made in feeding children whose gestational age is older than 22 weeks [123–125]. Although the number of survivors among children born at 23–24 weeks of gestational age has increased, a number of early and late complications among them have become a serious medical and social problem. While the pathologies of the neonatal period in children born prematurely are mainly related to respiratory, gastrointestinal, neurological, and nutritional problems, the complications of premature birth are manifested in children's early age, preschool, school, adolescence, and other developmental periods [126–128].

The lower the gestational age, the more severe are the long-term consequences of a preterm birth. Even in profoundly premature babies without structural changes in the brain, minimal brain dysfunctions are manifested in further development. Deeply premature babies, whose neonatal period is complicated by various pathologies, always require long-term monitoring and rehabilitation [129, 130]. After discharge from neonatal intensive care units, neuro-developmental abnormalities are the most common problem for premature babies. The most common neurodevelopmental anomalies include cerebral palsy, various forms of psychomotor development and behavioral disorders, as well as vision and hearing problems [131–135].

The timely detection of neurodevelopmental delays and implementation of rehabilitation measures lead to a significant reduction in the severity and complications of later age problems. Therefore, in a number of developed countries, monitoring the development of premature children is carried out at the state level, and multicenter randomized clinical studies are given great importance. The lower the age of gestation and the degree of morphofunctional maturity of the brain, the more common are secondary brain damage in hypoxia-ischemia, sepsis, necrotic enterocolitis, meningitis and other infectious inflammatory processes; nutritional disorders are more common in these children, which manifests itself in various ways at later ages. It shows with developmental problems of degree [136–139]. In particular, organic damage to the brain—intraventricular hemorrhage, periventricular leukomalacia, and gross psychomotor developmental disorders with ventriculomegaly, including infantile cerebral palsy, are more likely [140, 141].

Radiological examinations have important diagnostic value in the acute period of brain damage and can form certain ideas about future neurodevelopmental problems [122, 142]. However, at present, the results of early ultrasound examinations are hardly used as a prognostic indicator of neuromotor development. According to the studies by Laptook and co-authors, the specificity and sensitivity of abnormal neurosonography results are very low; cerebral palsy is noted in 9.4% of children with a body mass of less than 1000 g and a normal brain ultrasound examination [143, 144]. In the last few decades, the topical diagnosis of brain injuries has started to be performed using magnetic resonance imaging (MRI), and successful results have been achieved in this direction. While significant changes in brain white matter during the acute phase of central nervous system injuries are detected by ultrasound, MRI is a more sensitive imaging modality for identifying smaller brain lesions [145–147]. Cerebellar lesions, which are difficult to detect by ultrasound, can also be successfully diagnosed by MRI [148]. As a result of this MRI use, monitoring the subsequent development of children with various changes in the brain has led to the discovery of valuable prognostic information [149]. The positive and negative prognostic value of the changes determined as a result of the examination varies depending on the severity of the damage, the gestational age of the child, and the influence of environmental factors affecting developmental delay. For example, among children with white matter damage at the age of five, while the negative prognostic value of a normal MRI for neurodevelopmental retardation is 100%, the positive prognostic value is 75%, excluding cognitive impairment [150–152].

Considering the presence of numerous factors that can affect cognitive development in later development, it can be considered legitimate that there is no relationship between perinatal white matter damage and cognitive development disorders. Studies have shown that diffuse white matter damage causes neuromotor retardation in preschool and school-aged children [153, 154]. In the research done at Turku University in Finland, it was noted that in premature babies, this examination is carried out not only in the first days after birth but also at the age equivalent to term birth, which leads to the acquisition of honest prognostic information about the development of neuromotor functions in the first five years of life. The essence of this scientific conclusion is that the changes detected as a result of MRI only in adult brain tissue cause neurodevelopmental disorders at later ages [155]. It is believed that the development of the brain mass is proportional to the growth of the head circumference, and the child's neuro-motor development can be evaluated and predicted based on this indicator. As a result of MRI examination, it is possible to determine the total volume of the brain, and in children born with a very small mass, the volume of the total or individual parts of the brain has a significant impact on the mental, speech, memory, and psychomotor indicators of the child's further development [156]. Structural damage detected during MRI examination is not always equivalent to brain dysfunction. Thus, psychomotor development may be completely normal in cases where noticeable pathologies are detected [157]. However, in all cases, MRI examination surpasses many development scales and immunohistochemical markers determined on the basis of clinical indicators according to its prognostic value.

Studies on the assessment of early neurological development in premature infants have shown that cerebral palsy and behavioral-developmental pathologies are of greater relevance. Such pathologies are accompanied by abnormal muscle tone and movement disorders, and the clinical course and prognosis depend on the direction in which the motor functions change. Thus, more functional and sensory disorders are observed in hemiplegia and diplegia, while more motor disorders are found in triplegia and quadriplegia [158].

Cerebral palsy is distinguished according to the degree of severity as follows: mild (the child has only mild movement disorders, general muscle activity does not lag behind age norms), moderate (the child can walk with assistive devices, can sit freely), and severe (the child has the ability to move, no assistive devices can be activated) [159]. Of course, along the course of the pathological process, a number of external interventions and the prescription of drugs significantly affect the prognostic indicators. For example, the administration of antenatal steroids and indomethacin in the perinatal period reduces the risk of intraventricular hemorrhage [160]. Corticosteroids used postnatally in the treatment and prevention of bronchopulmonary dysplasia in premature infants increase the risk of developing cerebral palsy [161–163]. In general, according to the incidence of psychomotor developmental pathologies of early age, those born with deep prematurity and extreme small mass

#### *Preterm Birth and Postnatal Developmental Outcomes DOI: http://dx.doi.org/10.5772/intechopen.108061*

are at greater risk, with such pathologies occurring in 9–17% of children who survive various perinatal pathologies [164, 165]. Numerous scientific research projects have been carried out on the further development of children born prematurely; over time, the results found through this research have differed fundamentally from one study to another. Information about classical randomized studies entered the periodical literature in the 1970s. If the first epidemiological studies were devoted only to the study of the form and frequency of developmental delays, since the 1990s, the effectiveness of various scales and diagnostic markers to assess psychomotor and sensory development became the objects of research. Within the framework of the International Institute on Child Health and Development, the assessment of children aged 18–22 months after birth began for the first time, using the Classification System of Gross Motor Development, the Bailey Scale of Children's Development Assessment, and the Amiel–Thison scale of neurological development [92, 150].

In the twentieth century, starting from the perinatal period, various assessment and development programs were implemented one after the other, and large-scale scientific research was carried out in the search for more sensitive indicators of various neuromotor disorders. At present, the Bailey-2 scale of developmental assessment, Denver developmental screening test, CAT/CLAMS scale, and Gessel and Mullen comprehension tests are widely used [134, 166, 167]. The Denver screening test and its modified variants detect and predict gross motor, fine motor, social adaptation, and speech problems in the first 6 years of life starting from the first months after birth [168, 169]. Evaluation by this scale is currently considered the ideal test system for identifying children with developmental delays, playing the role of screening. Evaluation with the Beley scale and its modified versions allows for the detection of the severity of the pathological process in several ways and various clinical forms in children with developmental delays detected through screening [170, 171].

Developmental assessment tests are used to identify and predict the retardation of children's mental and psychomotor development levels in each developmental period. Based on the obtained results, timely preventive measures can lead to the prevention of a number of developmental delays. However, assessment and prediction based on these scales have several difficulties. Specifically, the accuracy of predictions is influenced by a number of external factors, including the social environment surrounding the child, educational level of the parents, and structural changes of the brain with various origins. Furthermore, it is not always possible to involve parents and children in such assessments in a timely and regular manner given that examinations take a long time.

Cognitive and behavioral reactions are of great importance in the proper formation of children's social adaptation. Profoundly preterm infants and children with intrauterine growth retardation constitute a greater risk group for the formation of cognitive functions on a weak basis [127, 172]. It is believed that both the antenatal and postnatal retardation of the child lead to a delay in behavioral and cognitive functions [173]. The psychological state of parents has a significant impact on the behavioral problems of premature children. Studies have found that there is a statistically significant relationship between parents' stress index and children's behavioral responses at 3 years of age [174]. In another study, it was shown that depressive symptoms in mothers led to impaired social adaptation and behavioral responses of children aged 5 years [175]. Experts who study the impact of nutrition on development have sought to prove that the formation of cognitive reactions does not differ in children who lag behind in antenatal or postnatal development and depends more on

proper and balanced nutrition [176, 177]. Many authors have confirmed that there is a dependence between a child's weight and height parameters at birth and physical, psychomotor, and neurological development at later ages. According to Tanabe K. and co-authors, 18.2% of children with intrauterine growth retardation are stunted at school age. In children born with prematurity and intrauterine growth retardation syndrome, various changes occur in the central nervous system, and many are maintained for a long time without recovery at a later age [39, 119]. Especially in deep premature babies, pathologies such as cerebral hemorrhage, periventricular leukomalacia, and hypertension-hydrocephalus syndrome cannot be fully recovered despite continuous dispensary control, proper intensive therapy, and rehabilitation treatment [87, 178]. P. Casolini created experimental subneurotoxic anoxia in mice in the first week of life and observed persistent dysfunction of the hippocampus and cerebral cortex as well as the disruption of behavioral responses in subsequent development [179]. In another scientific study, the results of magnetic resonance examinations showed that in children born with low weight, the development of various structures of the brain was not proportional—the amount of gray matter in some areas was low and was maintained for a long time [180]. The disproportionate development of brain structures in children born with low weight was accompanied by physical and sexual underdevelopment at different ages, disruption of social adaptation, and attention disorders [171, 181, 182].

Research conducted over many years has concluded that in addition to psychomotor developmental delays, somatic and infectious pathologies of various organs and systems are also more likely to occur in the further development of children born prematurely. Children born with low birth weight have a high risk of death due to cardiovascular pathology [1]. Epidemiological studies conducted jointly by several perinatal scientific centers have proven that intrauterine growth retardation created experimentally as a result of hypoxia and nutrient deficiency in pregnant mice was a major risk factor for the development of cardiovascular diseases in later development is a risk [166, 183, 184]. Left ventricular remodeling of the heart has proven that ultrastructural changes caused by both ischemia and nutrient deficiency lead to future cardiac dysfunction [1].

Research on the genetic basis of organ dysfunction has led to certain results. For example, in studies conducted on mice, the removal of the NR2B fraction from the C terminus of the NMDA receptor gene, which plays an important role in the pathogenesis of perinatal damage to the nervous system, resulted in perinatal death. Another group of researchers observed a substantial decrease in NR1 and NR2B subunits as a result of biochemical tests in mice whose mothers were stressed during pregnancy. Later, electrophysiological studies revealed that intrauterine stress causes memory and cognitive impairments in later life as a result of the long-term dysfunction of the hippocampus [179, 180].

Many diagnostic and preventive programs have been proposed to prevent near and far consequences of preterm birth [130, 185, 186]. A number of sources have suggested a control program for children born with intrauterine growth retardation in polyclinic conditions, which serves to reduce their morbidity [23]. Depending on the variant of intrauterine growth retardation syndrome, dynamic dispensary control leads to a decrease in morbidity in such children. G.K. Swamy, with his research, has shown that timely and correct perinatal care has the leading role in reducing the morbidity and mortality rates of premature babies at a later age [187]. However, he has noted that even state-of-the-art medical care does little to reduce perinatal and postnatal morbidity in children born with severe and extreme low birth weight.

*Preterm Birth and Postnatal Developmental Outcomes DOI: http://dx.doi.org/10.5772/intechopen.108061*
