Changes in In-Hospital Survival and Long-Term Neurodevelopmental Outcomes of Extremely Preterm Infants: A Retrospective Study of a Japanese Tertiary Center.

OBJECTIVES: The objective of this study was to elucidate whether the survival and long-term neurodevelopmental outcomes of extremely preterm infants have improved in a Japanese tertiary center with an active treatment policy for infants born at 22-23 weeks of gestation. STUDY DESIGN: This single-centered retrospective cohort study enrolled extremely preterm infants treated at Saitama Medical Center, Saitama Medical University, from 2003 to 2014. Patients with major congenital abnormalities were excluded. Primary outcomes were in-hospital survival and severe neurodevelopmental impairment (NDI) at 6 years of age, which was defined as having severe cerebral palsy, severe cognitive impairment, severe visual impairment, or deafness. We assessed the changes in primary outcomes between the first (period 1; 2003-2008) and the second half (period 2; 2009-2014) of the study period and evaluated the association between birth-year and primary outcomes using multivariate logistic regression models. RESULTS: Of the 403 eligible patients, 340 (84%) survived to discharge. Among 248 patients available at 6 years of age, 43 (14%) were classified as having severe NDI. Between the 2 periods, in-hospital survival improved from 155 of 198 (78%) to 185 of 205 (90%), but severe NDI increased from 11 of 108 (10%) to 32 of 140 (23%). In multivariate logistic regression models adjusted for gestational age, birthweight, sex, singleton birth, and antenatal corticosteroids, the aOR (95% CI) of birth-year for in-hospital survival and severe NDI was 1.2 (1.1-1.3) and 1.1 (1.0-1.3), respectively. CONCLUSION: Mortality among extremely preterm infants has improved over the past 12 years; nevertheless, no significant improvement was observed in the long-term neurodevelopmental outcomes.

Randomized Trial of Perfusion-Based Circulatory Management in Infants of Very Low Birth Weight.

OBJECTIVE: To establish the superiority of blood flow (BF)-based circulatory management over conventional blood pressure (BP)-based management strategies used for preventing intraventricular hemorrhage (IVH) in infants of very low birth weight (VLBW). STUDY DESIGN: We conducted a nonblinded, single-centered randomized trial with the aim to prevent IVH by managing BF. Infants with VLBW were assigned randomly to a BF-based group or BP-based (BP group) circulatory management group. The incidence of IVH was the outcome of interest. The IVH also data were compared among healthy patients and patients responsive and unresponsive to the intervention. RESULTS: A total of 219 and 220 infants with VLBW were assigned to the BF and BP groups, respectively. The IVH incidence rate was lower in the BF group, but the difference was not statistically significant (BF group, 6.8% vs BP group, 10.9%; P = .14). In 21% of patients of the BP group and 20% of the BF group, the intervention failed. In BF group, the IVH incidence rate was significantly greater in infants with unsuccessful intervention when compared with healthy individuals (6% vs 23%, P = .001). Multivariate logistic regression analysis revealed a correlation between low blood flow and IVH (aOR 3.24; 95% CI 1.49-7.08, P = .003) but not between low BP and IVH (P = .73). CONCLUSIONS: The BF management protocol did not significantly decrease the incidence of IVH. However, after further optimization, we speculate the treatment strategy holds promise in decreasing the incidence of IVH. Trial registration UMIN-CTR: UMIN000013296.

Simple decentralized control mechanism that enables limb adjustment for adaptive quadruped running.

Quadrupeds exhibit versatile and adaptive running by exploiting the flying phase during the stride cycle. Various interlimb coordination mechanisms focusing on mechanical loads during the stance phase have been proposed to understand the underlying control mechanism, and various gait patterns have been reproduced. However, the essential control mechanism required to achieve both steady running patterns and non-steady behaviours, such as jumping and landing, remains unclear. Therefore, we focus on the vertical motions of the body parts and propose a new decentralized interlimb coordination mechanism. The simulation results demonstrate that the robot can generate efficient and various running patterns in response to the morphology of the body. Furthermore, the proposed model allows the robot to smoothly change its behaviour between steady running and non-steady landing depending on the situation. These results suggest that the steady and non-steady behaviours in quadruped adaptive running may share a common simple control mechanism based on the mechanical loads and vertical velocities of the body parts.

Is ibuprofen superior to indomethacin for patent ductus arteriosus in Japanese preterm infants?

BACKGROUND: Many clinical trials have indicated that ibuprofen (IBU) has similar effects to indomethacin (IND) on the closure of patent ductus arteriosus (PDA) with fewer adverse effects. Owing to the scarce evidence on IBU use in Japan because of its recent approval we performed this observational study to compare the efficacy and safety of IBU with the efficiency and safety of IND. METHODS: We included infants (gestational age < 30 weeks) with hemodynamically significant PDA under a prophylactic IND protocol for intraventricular hemorrhage who were treated with either IND (n = 30) or IBU (n = 30). We compared a PDA closing effect, changes in ultrasonography findings, and adverse effects between the groups. RESULTS: There was no significant difference in the rates of PDA closure in the first treatment course (IND vs IBU: 46.7% vs 50.0%, P = 0.796) and surgical closure (IND vs IBU: 20.0% vs 20.0%, P = 1.000) between the groups. Both groups showed significant oliguria (IND vs IBU: 30.0% vs 23.3%, P = 0.559) and increased serum creatinine levels after treatment. However, an increase in serum creatinine level by >0.3 mg/dL, a criterion for acute kidney injury, was less frequent in the IBU group (35.7%) compared with that in the IND group (84.2%, P = 0.004). There were no significant differences in echocardiographic changes and jaundice and hypoglycemia incidence rates between the groups. CONCLUSIONS: Except for an increase in serum creatinine levels by >0.3 mg/dL, which was less frequent with IBU, IBU had similar efficacy and safety as IND for preterm PDA. Ibuprofen and IND should be cautiously administered.

Wearable Vibration Sensor for Measuring the Wing Flapping of Insects.

In this study, we fabricated a novel wearable vibration sensor for insects and measured their wing flapping. An analysis of insect wing deformation in relation to changes in the environment plays an important role in understanding the underlying mechanism enabling insects to dynamically interact with their surrounding environment. It is common to use a high-speed camera to measure the wing flapping; however, it is difficult to analyze the feedback mechanism caused by the environmental changes caused by the flapping because this method applies an indirect measurement. Therefore, we propose the fabrication of a novel film sensor that is capable of measuring the changes in the wingbeat frequency of an insect. This novel sensor is composed of flat silver particles admixed with a silicone polymer, which changes the value of the resistor when a bending deformation occurs. As a result of attaching this sensor to the wings of a moth and a dragonfly and measuring the flapping of the wings, we were able to measure the frequency of the flapping with high accuracy. In addition, as a result of simultaneously measuring the relationship between the behavior of a moth during its search for an odor source and its wing flapping, it became clear that the frequency of the flapping changed depending on the frequency of the odor reception. From this result, a wearable film sensor for an insect that can measure the displacement of the body during a particular behavior was fabricated.

Decentralized Control for Swarm Robots That Can Effectively Execute Spatially Distributed Tasks.

A swarm robotic system is a system in which multiple robots cooperate to fulfill a macroscopic function. Many swarm robots have been developed for various purposes. This study aims to design swarm robots capable of executing spatially distributed tasks effectively, which can be potentially used for tasks such as search-and-rescue operation and gathering scattered garbage in rooms. We propose a simple decentralized control scheme for swarm robots by extending our previously proposed non-reciprocal-interaction-based model. Each robot has an internal state, called its workload. Each robot first moves randomly to find a task, and when it does, its workload increases, and then it attracts its neighboring robots to ask for their help. We demonstrate, via simulations, that the proposed control scheme enables the robots to effectively execute multiple tasks in parallel under various environments. Fault tolerance of the proposed system is also demonstrated.

The function of the ophiuroid nerve ring: how a decentralized nervous system controls coordinated locomotion.

Echinoderms lack a centralized nervous control system, yet each extant echinoderm class has evolved unique and effective strategies for locomotion. Brittle stars (Ophiuroidea) stride swiftly over the seafloor by coordinating motions of their five muscular arms. Their arms consist of many repeating segments, requiring them to use a complex control system to coordinate motions among segments and between arms. We conducted in vivo experiments with brittle stars to analyze the functional role of the nerve ring, which connects the nerves in each arm. These experiments were designed to determine how the ophiuroid nervous system performs complex decision making and locomotory actions under decentralized control. Our results show that brittle star arms must be connected by the nerve ring for coordinated locomotion, but information can travel bidirectionally around the nerve ring so that it circumvents the severance. Evidence presented indicates that ophiuroids rely on adjacent nerve ring connections for sustained periodic movements. The number of arms connected via the nerve ring is correlated positively with the likelihood that the animal will show coordinated locomotion, indicating that integrated nerve ring tissue is critical for control. The results of the experiments should provide a basis for the advancement of complex artificial decentralized systems.

Perfusion monitoring and intraventricular hemorrhage in preterm infants.

Cardiovascular instability in preterm infants during the early postnatal period correlates with the development of intraventricular hemorrhage (IVH). Due to the correlation between hypotension and fluctuation of blood pressure, treatment was targeted specifically at hypotension to prevent IVH, but this was not successful. Recently, several novel perfusion markers have been found to be correlated with the development of IVH, and they are of current interest in cardiovascular management. In this review, the correlation between IVH and conventional, as well as novel, perfusion markers is examined.

Short-Term Effect of Prosthesis Transforming Sensory Modalities on Walking in Stroke Patients with Hemiparesis.

Sensory impairments caused by neurological or physical disorders hamper kinesthesia, making rehabilitation difficult. In order to overcome this problem, we proposed and developed a novel biofeedback prosthesis called Auditory Foot for transforming sensory modalities, in which the sensor prosthesis transforms plantar sensations to auditory feedback signals. This study investigated the short-term effect of the auditory feedback prosthesis on walking in stroke patients with hemiparesis. To evaluate the effect, we compared four conditions of auditory feedback from plantar sensors at the heel and fifth metatarsal. We found significant differences in the maximum hip extension angle and ankle plantar flexor moment on the affected side during the stance phase, between conditions with and without auditory feedback signals. These results indicate that our sensory prosthesis could enhance walking performance in stroke patients with hemiparesis, resulting in effective short-term rehabilitation.

Oxygen requirement and surfactant therapy in preterm infants after delivery.

BACKGROUND: Several reports have shown the beneficial effects of early or prophylactic surfactant therapy for preterm infants, who often develop respiratory distress syndrome. No report, however, has addressed which infants should receive surfactant therapy in the delivery room. Therefore, the aim of this study was to assess the validity of identifying infants who need surfactant therapy based on fraction of inspiratory oxygen (FiO2 ) requirement in the delivery room. METHODS: In this observational, retrospective study, FiO2 given in the delivery room, use of surfactant therapy, stable microbubble test (SMT) results, and changes in FiO2 both before and after surfactant therapy were reviewed in infants born at <33 weeks' gestation. RESULTS: Overall, 170 infants were included. Forty infants were given oxygen with FiO2 ≥0.6, and all received surfactant therapy. Of these 40 infants, FiO2 could be reduced in 36 (90%) by an average of 0.46 after surfactant therapy. SMT was done in 22 of 40 infants, and surfactant insufficiency was suspected in 20 (91%). In contrast, 81 of 102 infants (79%) with FiO2 <0.4 did not need surfactant therapy within 48 h after birth. CONCLUSIONS: Preterm infants who need FiO2 ≥0.6 in the delivery room appear to be at high risk of surfactant insufficiency and would benefit from surfactant. Surfactant therapy would provide a more effective resuscitation method for preterm infants, and thus a larger prospective study is needed to confirm these results.

Skin blood flow as a predictor of intraventricular hemorrhage in very-low-birth-weight infants.

BACKGROUND: Cardiovascular instability immediately after birth is associated with intraventricular hemorrhage (IVH) in very-low-birth-weight (VLBW) infants. For circulatory management, evaluation of organ blood flow is important. In this study, the relationship between peripheral perfusion within 48 h after birth and IVH was evaluated in VLBW infants. METHODS: In this prospective observational study involving 83 VLBW infants, forehead blood flow (FBF) and lower-limb blood flow (LBF) were measured for 48 h after birth using a laser Doppler flowmeter. Blood flow was compared between infants with and without IVH. Multivariate logistic regression analysis was performed to identify the risk factors for IVH. RESULTS: IVH developed in nine infants. In eight of these patients, IVH occurred after 24 h. LBF was lower in infants with IVH at 18 and 24 h and increased to the same level as that of infants without IVH at 48 h. Multivariate logistic regression analysis identified a correlation only between LBF and IVH at 18 h. CONCLUSION: These findings were consistent with the hypoperfusion-reperfusion theory, which states that IVH develops after reperfusion subsequent to hypoperfusion. We speculate that measurement of skin blood flow in addition to systemic and cerebral circulation may be helpful in predicting IVH.

Peripheral blood flow monitoring in an infant with septic shock.

Septic shock is associated with impaired vasoregulation, and treatment includes vasoactive drugs. Therefore, evaluation of vasoregulatory change is important. The present report describes the successful characterization of vasoregulatory change in response to a vasoactive drug during septic shock. A male infant born at 23 weeks' gestation developed septic shock. Severe hypotension developed, and treatment with colloid fluid and dopamine failed to increase blood pressure. With continuous measurement of skin blood flow using laser Doppler, noradrenaline was started. Based on changes in the blood flow, the dose was increased. At a dose of 1 µg/kg per min, skin blood flow in the foot decreased without any change in blood pressure. Subsequent blood transfusion succeeded in increasing both blood pressure and skin blood flow. It is concluded that decrease in foot blood flow reflects the vasoconstrictive effect of noradrenaline, although this finding must be validated in larger studies.

Predictability of the neurodevelopmental assessment based on the Kyoto Scale of Psychological Development 2001 at 18-24 months of corrected age and 3 years of age in identifying cognitive impairment at 6 years of age in very preterm infants: A retrospective study at a Japanese tertiary center.

BACKGROUND: It is unknown how accurately the current Japanese classification system for neurodevelopmental delay based on the assessment with the Kyoto Scale of Psychological Development (KSPD) at toddlerhood and pre-school periods predicts cognitive impairment at school age. METHODS: This single-center retrospective cohort study enrolled infants born at 22-29 weeks of gestational age. At 18-24 months of corrected age and 3 years of age, the patients were categorized according to the current Japanese criteria for neurodevelopmental delay based on their overall developmental quotient calculated using the KSPD-2001. Cognitive impairment at 6 years of age was classified according to the calculated or estimated full-scale intelligence quotient. The predictability of the current Japanese classification of neurodevelopmental delay for cognitive impairment at 6 years of age was investigated. RESULTS: Of 566 eligible patients, 364 (64 %) completed the protocol. The current classification for the neurodevelopmental delay showed significant agreement with the severity of cognitive impairment at 6 years of age. The sensitivity and specificity of the KSPD-2001-based assessment for any cognitive impairment at 6 years of age were 0.64 and 0.74 at 18-24 months of corrected age and 0.83 and 0.70 at 3 years of age. The corresponding sensitivity and specificity for moderate/severe cognitive impairment were 0.51 and 0.96 at 18-24 months of corrected age and 0.68 and 0.95 at 3 years of age. CONCLUSION: The KSPD-2001 is a useful tool to predict the severity of cognitive impairment at school age.

Effects of Catecholamines on Blood Flow in Preterm Infants: A Subanalysis of PICC-MBF Trial.

INTRODUCTION: This study evaluated the correlation between skin blood flow and systemic blood flow and whether skin blood flow can determine the circulatory effects of dopamine and dobutamine on blood flow in very low birth weight (VLBW) infants. METHODS: This study was a subanalysis of the PICC-MBF randomized controlled trial. The correlation between skin blood flow and echocardiographic findings was examined. Changes in skin blood flow and blood pressure before and after initiation or dose increase of dopamine and dobutamine were also evaluated. RESULTS: Two hundred and thirty-four participants underwent echocardiography. Skin blood flow was significantly correlated with supra vena cava (SVC) flow (r = 0.31, p < 0.001). Receiver operator characteristic analysis revealed that skin blood flow <17 mL/min effectively detected SVC flow <41 mL/min (area under the curve = 0.83, p < 0.001). Dobutamine significantly increased skin blood flow after initiation or dose increase (p = 0.033) without increasing blood pressure. However, dopamine significantly increased both skin blood flow (p = 0.010) and blood pressure (p < 0.001). CONCLUSIONS: Our findings indicated that skin blood flow could be used as a surrogate marker of systemic blood flow in VLBW infants and revealed differences in the effects of dopamine and dobutamine on circulation.

An Extremely Preterm Infant Born at 23 Weeks' Gestation With an Interrupted Aortic Arch Complex: A Case Report.

We present a case of an infant male born at 23 weeks' gestation with an interrupted aortic arch (IAA) complex. We treated the patient with hypoxic gas ventilation to address developing systemic undercirculation in the acute postnatal phase. As the symptoms of bronchopulmonary dysplasia evolved, hypoxic gas ventilation was no longer required to stabilize the hemodynamics. The patient was discharged home after undergoing the palliative surgical procedure of bilateral pulmonary artery banding and ductus arteriosus stent implantation. Although he suffered from pulmonary hypertension, it was controllable with oxygen supplementation and pulmonary vasodilators. There are limited therapeutic options available for extremely preterm infants with critical congenital heart defects (CHDs). Hypoxic gas ventilation might be considered as one of the options, with its risks taken into account, to manage extremely preterm infants with CHDs with pulmonary overcirculation before performing surgical interventions.

Elongating, entwining, and dragging: mechanism for adaptive locomotion of tubificine worm blobs in a confined environment.

Worms often aggregate through physical connections and exhibit remarkable functions such as efficient migration, survival under environmental changes, and defense against predators. In particular, entangled blobs demonstrate versatile behaviors for their survival; they form spherical blobs and migrate collectively by flexibly changing their shape in response to the environment. In contrast to previous studies on the collective behavior of worm blobs that focused on locomotion in a flat environment, we investigated the mechanisms underlying their adaptive motion in confined environments, focusing on tubificine worm collectives. We first performed several behavioral experiments to observe the aggregation process, collective response to aversive stimuli, the motion of a few worms, and blob motion in confined spaces with and without pegs. We found the blob deformed and passed through a narrow passage using environmental heterogeneities. Based on these behavioral findings, we constructed a simple two-dimensional agent-based model wherein the flexible body of a worm was described as a cross-shaped agent that could deform, rotate, and translate. The simulations demonstrated that the behavioral findings were well-reproduced. Our findings aid in understanding how physical interactions contribute to generating adaptive collective behaviors in real-world environments as well as in designing novel swarm robotic systems consisting of soft agents.

Transient Recovery of Complete Atrioventricular Block Due to Maternal Anti-SS-A Antibody Through Antenatal Steroid Administration After 27 Weeks of Gestation.

Maternal anti-SS-A antibodies may cause complete atrioventricular block or myocardial damage in a fetus. Effective treatment for this has not been established. Although antenatal steroids may be a treatment option for anti-SS-A antibody-related myocarditis or atrioventricular block, a complete atrioventricular block is usually considered irreversible once established. Previous reports have indicated that, in cases where antenatal steroids were effective for atrioventricular block, they were administered earlier in the pregnancy. Here we present a case where maternal steroid administration initiated from 27 weeks, which is beyond the recommended optimal treatment period, was effective in altering a complete atrioventricular block to a grade I atrioventricular block.

Effect of dopamine on peripheral perfusion in very-low-birth-weight infants during the transitional period.

INTRODUCTION: Dopamine is one of the most frequently used inotropic drugs in neonatal intensive care units (NICUs); however, it does not seem to improve outcomes in premature infants. Given that the ultimate aim of cardiovascular management is to stabilize and maintain organ perfusion, an understanding of dopamine's effects on organ blood flow will help in judging when to use dopamine and how to titrate the dosage. Such an approach can lead to improved outcomes. This study aimed to evaluate the effects of dopamine on peripheral perfusion in very-low-birth-weight (VLBW) infants within 72 h of birth. METHODS: This prospective observational study identified and sampled 44 instances of initiation of dopamine treatment or increase in dopamine dose in 29 VLBW infants. Blood pressure, heart rate, and skin and subcutaneous blood flow were measured and compared before and after each instance. RESULTS: Blood pressure and skin and subcutaneous blood flow in the lower limbs increased after initiation of dopamine treatment or after dose increase. DISCUSSION: Dopamine increases blood pressure as well as skin and subcutaneous blood flow in VLBW infants despite its supposed vasoconstrictive action, indicating that it increases both perfusion pressure and blood flow and is devoid of overwhelming peripheral vasoconstrictive effects.

Adaptive Centipede Walking via Synergetic Coupling Between Decentralized Control and Flexible Body Dynamics.

Multi-legged animals such as myriapods can locomote on unstructured rough terrain using their flexible bodies and legs. This highly adaptive locomotion emerges through the dynamic interactions between an animal's nervous system, its flexible body, and the environment. Previous studies have primarily focused on either adaptive leg control or the passive compliance of the body parts and have shown how each enhanced adaptability to complex terrains in multi-legged locomotion. However, the essential mechanism considering both the adaptive locomotor circuits and bodily flexibility remains unclear. In this study, we focused on centipedes and aimed to understand the well-balanced coupling between the two abovementioned mechanisms for rough terrain walking by building a neuromechanical model based on behavioral findings. In the behavioral experiment, we observed a centipede walking when part of the terrain was temporarily removed and thereafter restored. We found that the ground contact sense of each leg was essential for generating rhythmic leg motions and also for establishing adaptive footfall patterns between adjacent legs. Based on this finding, we proposed decentralized control mechanisms using ground contact sense and implemented them into a physical centipede model with flexible bodies and legs. In the simulations, our model self-organized the typical gait on flat terrain and adaptive walking during gap crossing, which were similar to centipedes. Furthermore, we demonstrated that the locomotor performance deteriorated on rough terrain when adaptive leg control was removed or when the body was rigid, which indicates that both the adaptive leg control and the flexible body are essential for adaptive locomotion. Thus, our model is expected to capture the possible essential mechanisms underlying adaptive centipede walking and pave the way for designing multi-legged robots with high adaptability to irregular terrain.

Active-sensing-based decentralized control of autonomous mobile agents for quick and smooth collision avoidance.

There is an increasing demand for multi-agent systems in which each mobile agent, such as a robot in a warehouse or a flying drone, moves toward its destination while avoiding other agents. Although several control schemes for collision avoidance have been proposed, they cannot achieve quick and safe movement with minimal acceleration and deceleration. To address this, we developed a decentralized control scheme that involves modifying the social force model, a model of pedestrian dynamics, and successfully realized quick, smooth, and safe movement. However, each agent had to observe many nearby agents and predict their future motion; that is, unnecessary sensing and calculations were required for each agent. In this study, we addressed this issue by introducing active sensing. In this control scheme, an index referred to as the "collision risk level" is defined, and the observation range of each agent is actively controlled on this basis. Through simulations, we demonstrated that the proposed control scheme works reasonably while reducing unnecessary sensing and calculations.