In this paper, the process of CNS development in human embryos and fetuses is described. The primordium of the nervous system appears as early as during the third week after fertilization, but its differentiation and maturation require a considerably long period of time until after birth. Therefore, the developing brain is vulnerable to various kinds of deleterious environmental effects during the preand perinatal life. This paper aims at giving an overview of the major organogenesis of the brain in human embryos and fetuses.

The vertebral body, neural arch and its processes develop from the sclerotome of the primitive mesodermal segments. After chondrification, separate ossification centres appear for the body and one for each of the neural arches. Vertebrae are composed of a body and a vertebral arch. The vertebral foramina, which consist of the vertebral arch and back of vertebral body, form the vertebral canal including and protecting the spinal cord. The vertebral arches are formed by two pedicles and two laminae which unite as a spinous process.

Relation between the vertebrae and spinal cord during pregnancy is interesting. In embryonal period, the CNS develops earlier than other part of embryonal structures and occupies approximately one third of the whole embryonal body. At the 3rd month of development the length of the spinal cord equals that of the vertebral column. The spinal nerves and the relationship of the spinal nerves to the vertebra are established. Therefore the spinal cord segment is at the same level as the corresponding vertebral level. In subsequent fetal period, however, fetal body structure including vertebral column develops faster than the neural tube. As the consequence of this different development of the column and nerves, caudal end of the spinal cord within the vertebral column relatively moves upward with advancing gestation and reaches to the level of the third lumber vertebra at birth.

The human brain function is certainly one of the most amazing phenomena known. All behavior is the result of the brain function. The 100 billion nerve cells are the home to our centers of feelings and senses, pleasure and satisfaction; it is where the centers for learning, memory and creative work are located; where laughing and crying areas and the centers of our mind are. Our cognitive functions, such as thinking, speaking or creating works of art and science, all reside within the cerebral cortex. One of the tasks of the neural science is to explain how the brain marshals its millions of individual nerve cells to produce behavior and how these cells are affected by the environment.1 The brain function still remains shrouded in a veil of mystery. But what is known is that over 99 percent of the human neocortex is produced during the fetal period.2 Owing to the employment of state-of-the-art methods and techniques in prenatal investigations, a growing pool of information on the development of the central nervous system (CNS) and behavioral patterns during intrauterine life has been made available. This review outlines these events, along with the development of the fetal sensory system and circadian rhythms, the senses of vision and hearing, fetal learning and memory, and long-term effects of fetal stress on behavior. In brief, this review offers a glimpse of the fascinating world of the intrauterine life.

Direct assessment of functional development of the fetal central nervous system is not possible, but the assessment of fetal behavior may provide the possibility to distinct between normal and abnormal brain development. Since the ultrasonographic technique allowed the investigation of spontaneous fetal motor activity in utero first studies of spontaneous prenatal movements and fetal behavior were performed and published. 2D ultrasound was considered somewhat subjective method because information needs observer interpretation. The latest development of three-dimensional (3D) and four dimensional (4D) sonography that overcame some of the limitations of 2D methods enable precise study of fetal and even embryonic activity and behavior. In the following text we reviewed the literature on the behavior in the high-risk pregnancies for cerebral palsy assessed by the ultrasonographic techniques.

As early as possible, neonatologists try to identify neonates at risk of unfavorable neurodevelopmental outcomes. They are fairly reliable in predicting very poor outcomes as well as optimal outcomes. However, within these two extremes, the prediction still remains a challenge. Immaturity of the neonatal brain constitutes a limit in itself. During decades with the growing knowledge of brain development, many methods have been developed for neurological assessment of the neonate. Neither of them applied alone was perfect in terms of clinical applicability, sensitivity, reproducibility and specificity.

The motor function is the first to provide the clinician with clues. Higher functions, in particular language and other cognitive functions, will develop later. However, recent researchers give credit to the brainstem for controlling exceedingly rudimentary learning-related cognitive-like activity. At present, the anticipation of late emerging developmental disabilities remains difficult even though early motor dysfunction has repeatedly been associated with a higher risk of intellectual or other learning disabilities. Despite our modest recent contribution to the domain of prediction, further studies on welldefined high risk populations with rigorous methodology that aim to demonstrate these links are still needed. Besides neurological observations, research is in process of including behavioral and stress/ reactivity measures; feasibility and benefits have to be demonstrated.

At present, fetal neurology is supported by neonatal neurology. Obstetricians are wise enough to take from both methods described above the elements they are able to transpose to fetal life. A comparative table of neonatal and fetal assessment is to be found elsewhere. As for neonatal neurology, the future of fetal neurology will have to rely on short- and long-term follow-up studies to define the predictive value of the chosen items. Obstetricians will have to be as patient as pediatricians, to work, step by step, towards defining optimality and impairment. They will have to be very careful when deciding to interrupt pregnancies; at the time being, such decisions are restricted to cases of very severe impairment. In line with the spectrum described above, they can expect to find more cases with moderate to mild abnormalities than cases with severe ones. However the most pleasant aspect for the echographer is to check fetal optimality. Just as a newborn infant categorized as at risk of brain damage is competent enough to demonstrate CNS integrity from birth, a high risk fetus will soon be competent enough to demonstrate CNS integrity before birth.

As the development of the brain is unique and continuing process throughout the gestation and after birth, it is expected that there is also continuity of fetal and neonatal movements which are the best functional indicator of developmental processes of the brain. Understanding the relation between fetal and infant behavior and developmental processes of the brain in different periods of gestation may make achievable the distinction between normal and abnormal brain development. Epidemiological studies revealed that many neurologically impaired infants belong to low risk population, which means that they seemed to be developmentally normal as fetuses and as infants, while later childhood neurological disability was diagnosed. Which methods of neurological assessment are available for that purpose? Prenatally we have not many possibilities for neurological assessment, while postnatally the repertoire of diagnostic possibilities is increasing. Among the postnatally available methods for neurological assessment, the most important are: clinical neurological assessment, neuroimaging methods, assessment of general movements (GMs) and combinations. Postnatal neurological assessment is probably easier to perform than prenatal, by using a simple and suitable for everyday work screening clinical test with good reliability, specificity and sensitivity.

There is a possibility for the early and simple neurological assessment of the term and preterm newborns with the aim to detect associated risks and anticipate long-term outcome of the infant, and to establish a possible causative link between pregnancy course and neurodevelopmental outcome. The evaluation of infant's developmental optimality should be assessed in order to investigate whether the infant is neurologically normal or damaged. Neurological assessment at term by Amiel-Tison (ATNAT) is taking into account neurological maturation exploring so called lower subcortical system developing earlier from the reticular formation, vestibular nuclei and tectum, and upper cortical system developing from the corticospinal pathways.

Conventional acquisition neuroimaging techniques together with modern diffusion neuroimaging techniques can identify typical patterns of brain injury, even in the early course of the disease. However, even though highly suggestive, these patterns cannot be considered as pathognomonic. Nevertheless neuroimaging methods alone are not sufficient to predict the neurological outcome in neonates from highrisk population.

Prechtl stated that spontaneous motility, as the expression of spontaneous neural activity, is a marker of brain proper or disturbed function. The observation of unstimulated fetus or infant which is the result of spontaneous behavior without sensory stimulation is the best method to assess its central nervous system capacity. All endogenously generated movement patterns from un-stimulated central nervous system could be observed as early as from the 7-8 weeks of postmenstrual age, with developing a reach repertoire of movements within the next two or three weeks, continuing to be present for 5 to 6 months postnatally. This remarkable fact of the continuity of endogenously generated activity from prenatal to postnatal life is the great opportunity to find out those high-risk fetuses and infants in whom development of neurological impairment is emerging. The most important among those movements are GMs involving the whole body in a variable sequence of arm, leg, neck and trunk movements, with gradual beginning and the end. They wax and wane in intensity, force and speed being fluent and elegant with the impression of complexity and variability. Assessment of GMs in high-risk newborns has significantly higher predictive value for later neurological development than neurological examination. Kurjak and co-workers conducted a study by 4D ultrasound and confirmed earlier findings made by 2D ultrasonography, that there is behavioral pattern continuity from prenatal to postnatal life. Assessment of neonatal behavior is a better method for early detection of cerebral palsy than neurological examination alone.

Are we approaching the era when there will be applicable neurological test for fetus and assessment of neonate will be just the continuation? This is still not easy question to answer, because even postnatally there are several neurological methods of evaluation, while in utero we are dealing with more complicated situation and less mature brain. Could neonatal assessment of neurologically impaired fetuses bring some new insights into their prenatal neurological status is still unclear and to be investigated. New scoring system for prenatal neurological assessment of the fetus proposed by Kurjak et al will give some new possibilities to detect fetuses at high neurological risk, although it is obvious that dynamic and complicated process of functional CNS development is not easy to investigate.

The aim of this review is to present continuity of the functional central nervous system assessment from prenatal to postnatal life.

The aim of this study was to evaluate the hemodynamic patterns in the proximal (M1) and distal (M2) portions of the middle cerebral artery (MCA) during different fetal behavioral states (FBSs) in healthy and IUGR fetuses. After identification of the FBS in 20 normal (group A) and 8 IUGR (group B) singleton pregnancies (36- 40 weeks), flow velocity evaluation was performed on the M1 and M2 segment of the MCA during “quiescence” (FBS 1F) and “activity” (FBS 2F). In the group A, a statistically significant decrease of impedance to flow values was identified in both segments of the MCA during “activity”. In the group B not statistically significant differences were identified in the impedance to flow values during different FBSs. For each segments of MCA it was found significant lower impedance to flow values in the group B for all FBSs. The mean fetal heart rate during “quiescience” was significantly lower than during “activity” in both groups. The results of this study provide evidences of the influence of different FBSs on fetal cerebral hemodynamic patterns. These information should be considered in the evaluation of fetal cerebral hemodynamics.

Modern imaging methods enabled systematic studies of fetal behaviour as well as a continuation of that behaviour in prematurely born infants (for a review, see 1-4). The following question represents a great challenge for human developmental neurobiologist: what is the neurobiological basis of various behavioural patterns observed in human fetuses and preterm infants?2 First of all, it is essential to determine whether there is an early spontaneous (nonsensory- driven) activity and to what extent the cerebrum and the cerebral cortex may be involved. In addition, it is necessary to describe for each successive phase, the developmental status of neuronal circuitry and synaptic organization.

In this review, we present evidence on the development of cortical connections during different phases of fetal development and evaluate a possible functional significance of cerebral involvement.

Molecular aspects of genetic diseases that affect the nervous system are in the focus of scientific interest investigators from many fields of medicine and the knowledge of genetic abnormalities as well as phenotypic heterogeneity is rapidly expanding. This review is aimed to provide clinician's practical insight into molecular aspects of certain brain abnormalities and disorders based on prenatal ultrasound assessment and clinical findings. Additionally some risk determinants are included in order to elucidate its contribution to molecular mechanism underlying the disease development. Making a specific diagnosis of a genetically determined neurological disorder or defects requires access to a laboratory that can assist in arranging for appropriate testing to be carried out. Therefore this review contains technological aspects of molecular genetic testing, international guidelines and policies related to genetic testing and recommendation for application in clinical medicine.

Dilatation of the fetal cerebral ventricles (ventriculomegaly) is a generic sonographic sign, which is common to several pathological entities carrying different prognosis.

Ventriculomegaly is easily recognized by ultrasound by measuring the atrial width. This simple measure allows the recognition of even mild forms of ventricular dilatation and is used as a screening method for ventriculomegaly. However, although the diagnosis of ventriculomegaly is easy, the prenatal identification of the cause of ventricular dilatation is a more difficult task. The recognition of associated brain anomalies is a crucial point. The research of the cause of ventriculomegaly is clinically useful, since the prognosis mainly depends on the etiology and on the presence of associated abnormalities.

In this article the role of prenatal sonography in recognizing the cause of the ventriculomegaly is reviewed.