The Ultrasound Review of Obstetrics and Gynecology, June 2005; 5(2): 154-168 Taylor & Francis Taylor &Frantj5 Croup Four-dimensional sonography in the assessment of fetal functional neurodevelopment and behavioral patterns AIDA SALIHAGIC-KADIC*'-, MARIJANA MEDIC', ASIM KURJAK^ WIKU ANDONOTOPO*, GUILLERMO AZUMENDI^ TOMISLAV HAFNER\ & DRAGAN MILENKOVIC^ ^Department of Physiology, Medical School, University of Zagreb, Zagreb, Croatia, ^Croatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia, Department of Obstetrics and Gyneeology, School of Medicine, University of Zagreb, Sveti Duh General Hospital, Zagreb, Croatia, "^Department of Health, Ministry of Health, Republic of Indonesia, Jakarta, Indonesia, ^Ecographia Centro Gutenberg, Malaga, Spain Abstract During the past few decades, morphological studies of fetal brains as well as ultrasonic imaging of fetal intrauterine activities in real time have provided invaluable information about the most important events in the development of human central nervous system. Il has been shown that development of fetal brain proceeds through a sequence of complicated histogenetic processes, which are reflected in the fetal behavioral patterns. Major developmental events, such as the establishment of neural connections in different regions of the brain, are accompanied by the occurrence of new panerns of fetal activities or by the transformation of existing patterns. It has been suggested that the ultrasound assessment of fetal behavior could be used for the evaluation of the integrity of fetal central nervous system and, possibly, for the detection of functional or structural brain disorders. The new, advanced imaging techniques such as four-dimensional sonography might open a new perspective for the study of fetal behavioral patterns and facilitate the development of diagnostic strategics for early detection or prevention of brain dysfunctions. The importance of these investigations is underlined by the recent findings that many environmental influences causing the fetal stress can interfere with the fetal neurodevelopment and leave long-term and profound consequences on brain structure and function. The major events in the functional development of fetal brain, as well as the influence of environmental factors on fetal neurodevelopment, are discussed in this review. Keywords: Fetal neurodevelopment, behavioral patterns, 4D ultrasound, fetal stress, brain lesions Introduction There is a growing pool of evidence that many severe neurological disorders as well as the minimal cerebral dysfunctions originate from the intrauterine, rather than the perinatal or posmatal period [1,2]. Although the developmental processes are genetically deter- mined, only in the optimal intrauterine environment can the fetus reach its full genetic potential. There- fore, one should not be surprised by the diversity of the fetal mechanisms that have evolved to protect and defend the interior milieu. For example, a number of physiological control mechanisms that are activated in fetal organism in response to hypoxia include the cardiovascular, endocrine and metabolic systems. As we all know, fetal cardiovascular adaptation to hypoxia is manifested by the redistribution of blood flow primarily toward the fetal brain. However, our latest investigations have shown that severe brain damage can develop despite the fetal blood flow redistribution and increased brain perfusion [3-5]. These results also itidicate that the border between the physiological adaptation and pathophysiological processes is extremely fragile and needs to be determined precisely in order to prevent the brain damage, as well as the lesions of other organ systems. Fortunately, our preliminary results indicate that in the case of chronic fetal hypoxia, this border can be determined by the use of a new vascular score, hypoxia index. It is our belief that this new vascular score might represent a signiflcant advance in the prevention of hypoxic brain damage, which is one of the most frequent causes of perinatal morbidity and mortality [6]. Nevertheless, in many cases perinatal brain damage cannot be explained by the existence of fetal hypoxia. There is also an increasing number of results showing that a large specter of neurological problems, such as minimal cerebral dysfunction, schizophrenia, epi- lepsy or autism, result at least in part from prenatal neurodevelopmental problems [1,2]. Epidemiologi- cal studies have shown that cerebral palsy most frequently results from prenatal rather than perinatal or postnatal causes [1]. Presently, despite the significant advances in prenatal and perinatal care. Correspondence: A. Salihagic-Kadic, Department of Physiology, School of Medicincj University of Zagreb, Salaia 3, 10 000 Zagreb, Croatia. Tel: 385 1 4566964. Fax: 385 1 4590207. E-mail: asalihfwmef.hr ISSN 1472-2240 prinLlSSN 1743-8950 online & 2005 Taylor & Francis DOI: 10.1080/14722240500190640