U. Fetal development of complex autonomic control evaluated from multiscale heart rate patterns. Am J Physiol Regul Integr Comp Physiol 304: R383-R392, 2013. First published December 26, 2012 doi:10.1152/ajpregu.00120.2012.-Development of the fetal autonomic nervous system's integrative capacity in relation to gestational age and emerging behavioral pattern is reflected in fetal heart rate patterns. Conventional indices of vagal and sympathetic rhythms cannot sufficiently reflect their complex interrelationship. Universal behavioral indices of developing complex systems may provide additional information regarding the maturating complex autonomic control. We investigated fetal magnetocardiographic recordings undertaken at 10-min intervals in active (n ϭ 248) and quiet (n ϭ 111) states between 22 and 39 wk gestational age. Standard deviation of heartbeat intervals, skewness, contribution of particular rhythms to the total power, and multiscale entropy were analyzed. The multiscale entropy methodology was validated for 10-min data sets. Age dependence was analyzed by linear regression. In the quiet state, contribution of sympathovagal rhythms and their complexity over a range of corresponding short scales increased with rising age, and skewness shifted from negative to positive values. In the active state, age dependencies were weaker. Skewness as the strongest parameter shifted in the same direction. Fluctuation amplitude and the complexity of scales associated with sympathovagal rhythms increased. We conclude that in the quiet state, stable complex organized rhythms develop. In the active state, however, increasing behavioral variability due to multiple internal coordinations, such as movement-related heart rate accelerations, and external influences develop. Hence, the state-selective assessment in association with developmental indices used herein may substantially improve evaluation of maturation age and early detection and interpretation of developmental problems in prenatal diagnosis. autonomic nervous system; complexity; developmental biology; fetal maturation; fetal behavioral patterns THERE IS INCREASING CONSENSUS that a certain number of diseases such as cardiovascular disease, metabolic syndrome, atherosclerosis, Type 2 diabetes, learning difficulties, hyperkinetic disorders, as well as cognitive, behavioral, and emotional problems in late postnatal age are associated with adverse influences during fetal development that became permanently programmed (1,2,4,10,11,19,20,23,24,26,31,32,39,40,44,47). However, early identification of fetal developmental problems is a challenging topic of prenatal diagnosis due to the extremely limited number of observable variables from the fetus. During the fetal maturation the emerging complex behavioral patterns are associated with an increasing functional integration in the organism. In that connection the autonomic nervous system (ANS) plays a predominant role for complex coordinated control of multiple vitally important physiological subsystems in the organism. Sin...
