The newborn behavioural observations system: A relationship-building intervention to support families in the neonatal intensive care unit.

AIM: Relationship-based interventions for neonatal intensive care unit families have potential to improve parent and infant outcomes; yet, their implementation has been modest within systems of care for high-risk newborns. The purpose of this paper is to describe a relationship-building intervention, the newborn behavioural observation system, summarise the evidence supporting its use, and address its clinical application for high-risk parent-infant dyads in the neonatal intensive care unit. METHODS: We summarise the extant literature describing the use of the newborn behavioural observation system in high-risk populations. RESULTS: While the body of literature supporting the use of the newborn behavioural observation system is modest, several randomised controlled studies have highlighted statistically significant and clinically meaningful gains in infant development and parental mental health. In these studies, the intervention was often integrated into existing systems of care and included high-risk parent-infant dyads. CONCLUSION: The newborn behavioural observation system is a promising intervention designed to support the early challenges of high-risk infants and their parents. Future research should examine its effects in diverse neonatal intensive care unit populations and professionals, strive for continuity of care from inpatient to post-discharge follow-up and developmental support services, and include more longitudinal studies.

Targeting thalamocortical circuits for closed-loop stimulation in Lennox-Gastaut syndrome.

This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. We aimed to identify a cortical target by synthesizing prior neuroimaging studies, and to use this knowledge to advance a dual thalamic (centromedian) and cortical (frontal) approach for closed-loop stimulation. Multi-modal brain network maps from three group-level studies of Lennox-Gastaut syndrome were averaged to define the area of peak overlap: simultaneous EEG-functional MRI of generalized paroxysmal fast activity, [18F]fluorodeoxyglucose PET of cortical hypometabolism and diffusion MRI structural connectivity associated with clinical efficacy in a previous trial of thalamic deep brain stimulation. The resulting 'hotspot' was used as a seed in a normative functional MRI connectivity analysis to identify connected networks. Intracranial electrophysiology was reviewed in the first two trial patients undergoing bilateral implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analysed for presence and synchrony of epileptiform activity. The peak overlap was in bilateral premotor cortex/caudal middle frontal gyrus. Functional connectivity of this hotspot revealed a distributed network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-functional MRI and PET. Intracranial electrophysiology showed characteristic epileptiform activity of Lennox-Gastaut syndrome in both the cortical hotspot and thalamus; most detected events occurred first in the cortex before appearing in the thalamus. Premotor frontal cortex shows peak involvement in Lennox-Gastaut syndrome and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for a range of neuromodulation therapies, including thalamocortical stimulation and emerging non-invasive treatments like focused ultrasound or transcranial magnetic stimulation. Compared to thalamus-only approaches, the addition of this cortical target may allow more rapid detections of seizures, more diverse stimulation paradigms and broader modulation of the epileptic network. A prospective, multi-centre trial of closed-loop thalamocortical stimulation for Lennox-Gastaut syndrome is currently underway.

Cracking the code: using educational gaming for high-level thinking in physiology education.

The multidisciplinary nature of physiology requires students to acquire, retain, apply, and evaluate knowledge from different scientific disciplines. Optimal learning techniques, such as active learning, interleaving topics and conditions, and recall, can greatly enhance the speed and effectiveness with which students achieve this type of higher-order thinking. However, developing and implementing optimal learning techniques in the classroom can be both time-intensive and challenging for the instructor. In addition, students may be resistant or slow to accept novel learning processes. One way to potentially introduce these learning techniques in a fun and engaging way is through educational gaming, or using a game or game elements intentionally to support learning. In this article we present an easy-to-implement adaptation of the Codenames board game for the physiology classroom. The activity requires minimal preparation while addressing high-level learning outcomes. Postintervention surveys of students were collected in three different health-related academic programs, both graduate and undergraduate, at two different institutions. Results suggest that participating in the activity both actively engaged the students and pushed them toward high-level, integrative thinking regardless of class level.NEW & NOTEWORTHY An easy-to-implement word game (Codenames) was used to engage students in higher-level Bloom's thinking about physiology. The gameplay required students to recall, apply, evaluate, and debate as they developed and guessed clues as part of the game. Students found the activity fun, engaging, and challenging. The activity is relatively easy to implement both online and in person, requiring at minimum a simple list of vocabulary terms.

Corticothalamic Responsive Neurostimulation for Focal Epilepsy: A Single-Center Experience.

PURPOSE: Owing to its extensive, reciprocal connectivity with the cortex and other subcortical structures, the thalamus is considered an important target for neuromodulation in drug-resistant focal epilepsy. Using corticothalamic stimulation, it is possible to modulate both the thalamus and the cortical seizure onset zone. Limited published clinical experience describes corticothalamic stimulation with depth leads targeting one of the anterior (ANT), centromedian (centromedian nucleus), or pulvinar (PUL) thalamic nuclei. However, it is not clear which of these nuclei is the "best" therapeutic target. METHODS: This study comprised a single-center experience with corticothalamic responsive neurostimulation using the RNS System to target these three thalamic nuclei. Presented here are the methods for target selection and device programming as well as clinical outcomes and a comparison of ictal and nonictal electrophysiological features. RESULTS: In this small retrospective study (N = 19), responsive corticothalamic neurostimulation was an effective therapy for 79% of patients (≥50% reduction in disabling seizure frequency), regardless of whether the thalamic lead was implanted in the ANT (N = 2), PUL (N = 6), or centromedian nucleus (N = 11). Twenty-six percent of patients reported a reduction in disabling seizure frequency ≥90%. Both high frequency (≥100 Hz) and low (≤20 Hz) frequency were used to stimulate the thalamus depending on the patient's response and ability to tolerate higher charge densities. In all patients, a longer burst duration (2000-5000 ms) was ultimately implemented on the thalamic leads. Across patients, peaks in the intracranial EEG were observed at theta, beta, gamma, and sleep spindle frequencies. Changes in frequency content and distribution were observed over time in all three nuclei. CONCLUSIONS: These results indicate that both high frequency and low frequency corticothalamic responsive neurostimulation can potentially be an effective adjunctive therapy in drug-resistant focal epilepsy. These data can also contribute to a broader understanding of thalamic electrophysiology in the context of focal epilepsy.

Incorporating dextrose gel and feeding in the treatment of neonatal hypoglycaemia.

OBJECTIVES: To determine the impact of incorporating dextrose gel in the treatment of neonatal hypoglycaemia (NH) and the role of feeding type in NH outcomes. STUDY DESIGN: We conducted a retrospective analysis of 2688 infants >35 weeks' gestation who were screened for NH before and after implementation of a clinical guideline for NH evaluation and treatment. We analysed the proportion of infants who required intravenous dextrose for NH before and after guideline implementation, the change in blood glucose concentrations with gel by feeding type and the odds of successful NH treatment with gel and feeding by feeding type. RESULTS: Following implementation of the guideline, a lower proportion of infants required intravenous dextrose for NH treatment (8.6% (60 infants) before guideline vs. 5.6% (112 infants) after guideline (p=0.007)). The median rise in blood glucose concentration with gel administration in the entire cohort was 0.61 mmol/L (11 mg/dL) (IQR 0.28-1.06 mmol/L (5-19 mg/dL)). Blood glucose concentration of formula-fed infants rose more in response to feeding and gel than breastfed infants (p≤0.0001). Formula feeding was associated with a lower odds of recurrent hypoglycaemia, as defined by requiring a second gel, in a fully adjusted model. Specifically, in infants with a pregel blood glucose of 2.00-2.17 mmol/L (36-39 mg/dL), formula feeding with gel was associated with a lower odds of recurrent hypoglycaemia. CONCLUSIONS: Dextrose gel is an effective tool in the treatment of NH. An infant's pregel blood glucose concentration may be helpful in guiding decisions around type of feeding provided.

Encephalopathy in neonates with subgaleal hemorrhage is a key predictor of outcome.

BACKGROUND: Subgaleal hemorrhage (SGH) is reported to be associated with severe hemodynamic instability, coagulopathy, and even mortality. The importance of the presence or absence of neonatal encephalopathy in predicting SGH outcomes has not been explored. The aim of this study was to determine the relationship of clinical encephalopathy to short-term outcomes in neonates with SGH. METHODS: Neonates ≥35 weeks gestation, diagnosed radiologically with SGH between 2010 and 2017, were included. Cases were divided into encephalopathic and non-encephalopathic. Demographic, clinical, and outcome data were compared between groups. RESULTS: Of 54,048 live births, 56 had SGH, of them 13 (23%) had encephalopathy. When compared to the non-encephalopathic neonates, encephalopathic neonates had lower Apgar scores, lower hemoglobin, lower platelet count, longer neonatal intensive care unit stay, two (15%) deaths, and four (31%) required blood transfusion. No non-encephalopathic infant with SGH died or required blood transfusion. Notably, on magnetic resonance imaging (MRI), a majority of subgaleal collections had either no or minimal blood products. CONCLUSIONS: In the absence of encephalopathy, SGH is not associated with adverse short-term outcome. Neurological assessment is likely to identify infants at higher risk for adverse outcome. The absence of MRI signal consistent with blood in subgaleal collection warrants further research.

Age and Other Factors Affecting the Outcome of AABR Screening in Neonates.

BACKGROUND: Although the utility of universal newborn hearing screening is undisputed, testing protocols vary. In particular, the impact of the infant's age at the time of automated auditory brainstem response (AABR) screening has not been well studied. METHODS: We conducted a retrospective review of newborn hearing screening data in 6817 low-risk, term and late-preterm newborns at our large, urban, academic medical center for a 1-year period to analyze the impact of age and other factors on the screening failure rate and referral for diagnostic testing. RESULTS: AABR screening failure rates decreased with postnatal age over the first 48 hours; 13.3% failed at <24 hours versus 3.8% at ≥48 hours (P < .0001). Infants who were initially tested at ≥36 hours failed repeat testing more often than those who were tested at <36 hours (11.5% vs 18.9%; P = .03). Other factors that were associated with failure included being a boy and of a race other than white. Sensorineural hearing loss (SNHL) was diagnosed in 18.6% of infants who failed their final screening at ≥48 hours compared with 2.8% of those whose final screening occurred earlier (P = .03). SNHL was more likely in infants who failed their first screening bilaterally (21.2%) than unilaterally (4.4%); P = .03). CONCLUSIONS: Among healthy newborns, delaying AABR screening in the first 48 hours minimized failure rates. SNHL was 6 times as likely in infants who failed their final screening at ≥48 hours compared with those who were screened at <48 hours of age. In our study, we offer guidance for nursery directors and audiologists who determine hearing screening protocols and counsel families about results.

Cortico-Cortical Interactions during Acquisition and Use of a Neuroprosthetic Skill.

A motor cortex-based brain-computer interface (BCI) creates a novel real world output directly from cortical activity. Use of a BCI has been demonstrated to be a learned skill that involves recruitment of neural populations that are directly linked to BCI control as well as those that are not. The nature of interactions between these populations, however, remains largely unknown. Here, we employed a data-driven approach to assess the interaction between both local and remote cortical areas during the use of an electrocorticographic BCI, a method which allows direct sampling of cortical surface potentials. Comparing the area controlling the BCI with remote areas, we evaluated relationships between the amplitude envelopes of band limited powers as well as non-linear phase-phase interactions. We found amplitude-amplitude interactions in the high gamma (HG, 70-150 Hz) range that were primarily located in the posterior portion of the frontal lobe, near the controlling site, and non-linear phase-phase interactions involving multiple frequencies (cross-frequency coupling between 8-11 Hz and 70-90 Hz) taking place over larger cortical distances. Further, strength of the amplitude-amplitude interactions decreased with time, whereas the phase-phase interactions did not. These findings suggest multiple modes of cortical communication taking place during BCI use that are specialized for function and depend on interaction distance.

Extracting spatial-temporal coherent patterns in large-scale neural recordings using dynamic mode decomposition.

BACKGROUND: There is a broad need in neuroscience to understand and visualize large-scale recordings of neural activity, big data acquired by tens or hundreds of electrodes recording dynamic brain activity over minutes to hours. Such datasets are characterized by coherent patterns across both space and time, yet existing computational methods are typically restricted to analysis either in space or in time separately. NEW METHOD: Here we report the adaptation of dynamic mode decomposition (DMD), an algorithm originally developed for studying fluid physics, to large-scale neural recordings. DMD is a modal decomposition algorithm that describes high-dimensional dynamic data using coupled spatial-temporal modes. The algorithm is robust to variations in noise and subsampling rate; it scales easily to very large numbers of simultaneously acquired measurements. RESULTS: We first validate the DMD approach on sub-dural electrode array recordings from human subjects performing a known motor task. Next, we combine DMD with unsupervised clustering, developing a novel method to extract spindle networks during sleep. We uncovered several distinct sleep spindle networks identifiable by their stereotypical cortical distribution patterns, frequency, and duration. COMPARISON WITH EXISTING METHODS: DMD is closely related to principal components analysis (PCA) and discrete Fourier transform (DFT). We may think of DMD as a rotation of the low-dimensional PCA space such that each basis vector has coherent dynamics. CONCLUSIONS: The resulting analysis combines key features of performing PCA in space and power spectral analysis in time, making it particularly suitable for analyzing large-scale neural recordings.

Comparison of subdural and subgaleal recordings of cortical high-gamma activity in humans.

OBJECTIVE: The purpose of this study is to determine the relationship between cortical electrophysiological (CE) signals recorded from the surface of the brain (subdural electrocorticography, or ECoG) and signals recorded extracranially from the subgaleal (SG) space. METHODS: We simultaneously recorded several hours of continuous ECoG and SG signals from 3 human pediatric subjects, and compared power spectra of signals between a differential SG montage and several differential ECoG montages to determine the nature of the transfer function between them. RESULTS: We demonstrate the presence of CE signals in the SG montage in the high-gamma range (HG, 70-110 Hz), and the transfer function between 70 and 110 Hz is best characterized as a linear function of frequency. We also test an alternative transfer function, i.e. a single pole filter, to test the hypothesis of frequency dependent attenuation in that range, but find this model to be inferior to the linear model. CONCLUSIONS: Our findings indicate that SG electrodes are capable of recording HG signals without frequency distortion compared with ECoG electrodes. SIGNIFICANCE: HG signals could be recorded minimally invasively from outside the skull, which could be important for clinical care or brain-computer interface applications.

Effect of early-onset sepsis evaluations on in-hospital breastfeeding practices among asymptomatic term neonates.

OBJECTIVE: To examine the effect of separation for early-onset sepsis (EOS) evaluations due to perinatal risk factors on breastfeeding practices among asymptomatic term newborns. METHODS: This observational study included 692 nulliparous women with term, singleton uncomplicated pregnancies who intended to breastfeed and whose infants were well appearing at birth. We examined the rate of early breastfeeding initiation (within 2 hours of birth) and formula supplementation (in the first 24 hours) among this mother-infant cohort. RESULTS: Asymptomatic infants separated for EOS evaluation within 2 hours of birth were more likely to have delayed initiation of breastfeeding (46.5% vs 12.5%; P<.001). This association remained significant when adjusted for potential confounders (adjusted odds ratio [aOR]: 5.5 [95% confidence interval (CI): 3.4-8.9]; P<.001). Among infants separated for EOS evaluation, mother-infant time together of ≤0.5 hour in the first 2 hours of life significantly delayed initiation (aOR: 8.9 [95% CI: 1.5-53.7]; P=.02) compared with infants spending >1.5 hours with their mothers. In bivariate analysis, both separation and initiation were associated with formula supplementation. After adjusting for confounders, only delayed initiation remained significantly associated with supplementation (aOR: 1.9 [95% CI: 1.1-3.5]; P=.03). CONCLUSIONS: Early separation of asymptomatic infants from their mothers for EOS evaluation was significantly associated with delayed initiation of breastfeeding, which in turn was associated with increased formula supplementation in the first day of life. This unintended consequence of EOS evaluations among asymptomatic infants may be minimized by delaying early separation for performance of the evaluation, attempting breastfeeding initiation before separation, and/or applying more efficient criteria for identifying infants requiring evaluation.

Sequential activation of premotor, primary somatosensory and primary motor areas in humans during cued finger movements.

OBJECTIVE: Human voluntary movements are a final product of complex interactions between multiple sensory, cognitive and motor areas of central nervous system. The objective was to investigate temporal sequence of activation of premotor (PM), primary motor (M1) and somatosensory (S1) areas during cued finger movements. METHODS: Electrocorticography (ECoG) was used to measure activation timing in human PM, S1, and M1 neurons in preparation for finger movements in 5 subjects with subdural grids for seizure localization. Cortical activation was determined by the onset of high gamma (HG) oscillation (70-150Hz). The three cortical regions were mapped anatomically using a common brain atlas and confirmed independently with direct electrical cortical stimulation, somatosensory evoked potentials and detection of HG response to tactile stimulation. Subjects were given visual cues to flex each finger or pinch the thumb and index finger. Movements were captured with a dataglove and time-locked with ECoG. A windowed covariance metric was used to identify the rising slope of HG power between two electrodes and compute time lag. Statistical constraints were applied to the time estimates to combat the noise. Rank sum testing was used to verify the sequential activation of cortical regions across 5 subjects. RESULTS: In all 5 subjects, HG activation in PM preceded S1 by an average of 53±13ms (P=0.03), PM preceded M1 by 180±40ms (P=0.001) and S1 activation preceded M1 by 136±40ms (P=0.04). CONCLUSIONS: Sequential HG activation of PM, S1 and M1 regions in preparation for movements is reported. Activity in S1 prior to any overt body movements supports the notion that these neurons may encode sensory information in anticipation of movements, i.e., an efference copy. Our analysis suggests that S1 modulation likely originates from PM. SIGNIFICANCE: First electrophysiological evidence of efference copy in humans.

Prenatal and newborn screening for critical congenital heart disease: findings from a nursery.

BACKGROUND: Delayed diagnosis of critical congenital heart disease (CCHD) in neonates increases morbidity and mortality. The use of pulse oximetry screening is recommended to increase detection of these conditions. The contribution of pulse oximetry in a tertiary-care birthing center may be different from at other sites. METHODS: We analyzed CCHD pulse oximetry screening for newborns ≥ 35 weeks' gestation born at Brigham and Women's Hospital and cared for in the well-infant nursery during 2013. We identified patients with prenatal diagnosis of CCHD. We also identified infants born at other medical centers who were transferred to Boston Children's Hospital for CCHD and determined if the condition was diagnosed prenatally. RESULTS: Of 6838 infants with complete pulse oximetry data, 6803 (99.5%) passed the first screening. One infant failed all 3 screenings and had the only echocardiogram prompted by screening that showed persistent pulmonary hypertension. There was 1 false-negative screening in an infant diagnosed with interrupted aortic arch. Of 112 infants born at Brigham and Women's Hospital with CCHD, 111 had a prenatal diagnosis, and none was initially diagnosed by pulse oximetry. Of 81 infants transferred to Boston Children's Hospital from other medical centers with CCHD, 35% were diagnosed prenatally. CONCLUSIONS: In our tertiary-care setting, pulse oximetry did not detect an infant with CCHD because of effective prenatal echocardiography screening. Pulse oximetry will detect more infants in settings with a lower prenatal diagnosis rate. Improving training in complete fetal echocardiography scans should also improve timely diagnosis of CCHD.

Distributed cortical adaptation during learning of a brain-computer interface task.

The majority of subjects who attempt to learn control of a brain-computer interface (BCI) can do so with adequate training. Much like when one learns to type or ride a bicycle, BCI users report transitioning from a deliberate, cognitively focused mindset to near automatic control as training progresses. What are the neural correlates of this process of BCI skill acquisition? Seven subjects were implanted with electrocorticography (ECoG) electrodes and had multiple opportunities to practice a 1D BCI task. As subjects became proficient, strong initial task-related activation was followed by lessening of activation in prefrontal cortex, premotor cortex, and posterior parietal cortex, areas that have previously been implicated in the cognitive phase of motor sequence learning and abstract task learning. These results demonstrate that, although the use of a BCI only requires modulation of a local population of neurons, a distributed network of cortical areas is involved in the acquisition of BCI proficiency.

Sleep spindles are locally modulated by training on a brain-computer interface.

The learning of a motor task is known to be improved by sleep, and sleep spindles are thought to facilitate this learning by enabling synaptic plasticity. In this study subjects implanted with electrocorticography (ECoG) arrays for long-term epilepsy monitoring were trained to control a cursor on a computer screen by modulating either the high-gamma or mu/beta power at a single electrode located over the motor or premotor area. In all trained subjects, spindle density in posttraining sleep was increased with respect to pretraining sleep in a remarkably spatially specific manner. The pattern of increased spindle activity reflects the functionally specific regions that were involved in learning of a highly novel and salient task during wakefulness, supporting the idea that sleep spindles are involved in learning to use a motor-based brain-computer interface device.

Acute histologic chorioamnionitis at term: nearly always noninfectious.

BACKGROUND: The link between histologic acute chorioamnionitis and infection is well established in preterm deliveries, but less well-studied in term pregnancies, where infection is much less common. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a secondary analysis among 195 low-risk women with term pregnancies enrolled in a randomized trial. Histologic and microbiologic evaluation of placentas included anaerobic and aerobic cultures (including mycoplasma/ureaplasma species) as well as PCR. Infection was defined as ≥1,000 cfu of a single known pathogen or a ≥2 log difference in counts for a known pathogen versus other organisms in a mixed culture. Placental membranes were scored and categorized as: no chorioamnionitis, Grade 1 (subchorionitis and patchy acute chorioamnionitis), or Grade 2 (severe, confluent chorioamnionitis). Grade 1 or grade 2 histologic chorioamnionitis was present in 34% of placentas (67/195), but infection was present in only 4% (8/195). Histologic chorioamnionitis was strongly associated with intrapartum fever >38°C [69% (25/36) fever, 26% (42/159) afebrile, P<.0001]. Fever occurred in 18% (n = 36) of women. Most febrile women [92% (33/36)] had received epidural for pain relief, though the association with fever was present with and without epidural. The association remained significant in a logistic regression controlling for potential confounders (OR = 5.8, 95% CI = 2.2,15.0). Histologic chorioamnionitis was also associated with elevated serum levels of interleukin-8 (median = 1.3 pg/mL no histologic chorioamnionitis, 1.5 pg/mL Grade 1, 2.1 pg/mL Grade 2, P = 0.05) and interleukin-6 (median levels = 2.2 pg/mL no chorioamnionitis, 5.3 pg/mL Grade 1, 24.5 pg/mL Grade 2, P = 0.02) at admission for delivery as well as higher admission WBC counts (mean = 12,000 cells/mm(3) no chorioamnionitis, 13,400 cells/mm(3) Grade 1, 15,700 cells/mm(3) Grade 2, P = 0.0005). CONCLUSION/SIGNIFICANCE: Our results suggest histologic chorioamnionitis at term most often results from a noninfectious inflammatory process. It was strongly associated with fever, most of which was related to epidural used for pain relief. A more 'activated' maternal immune system at admission was also associated with histologic chorioamnionitis.

Intrapartum temperature elevation, epidural use, and adverse outcome in term infants.

OBJECTIVES: To examine the association of intrapartum temperature elevation with adverse neonatal outcome among low-risk women receiving epidural analgesia and evaluate the association of epidural with adverse neonatal outcome without temperature elevation. METHODS: We studied all low-risk nulliparous women with singleton pregnancies ≥37 weeks delivering at our hospital during 2000, excluding pregnancies where infants had documented sepsis, meningitis, or a major congenital anomaly. Neonatal outcomes were compared between women receiving (n = 1538) and not receiving epidural analgesia (n = 363) in the absence of intrapartum temperature elevation (≤99.5°F) and according to the level of intrapartum temperature elevation within the group receiving epidural (n = 2784). Logistic regression was used to evaluate neonatal outcome while controlling for confounders. RESULTS: Maternal temperature >100.4°F developed during labor in 19.2% (535/2784) of women receiving epidural compared with 2.4% (10/425) not receiving epidural. In the absence of intrapartum temperature elevation (≤99.5°F), no significant differences were observed in adverse neonatal outcomes between women receiving and not receiving epidural. Among women receiving epidural, a significant linear trend was observed between maximum maternal temperature and all neonatal outcomes examined including hypotonia, assisted ventilation, 1- and 5-min Apgar scores <7, and early-onset seizures. In regression analyses, infants born to women with fever >101°F had a two- to sixfold increased risk of all adverse outcomes examined. CONCLUSIONS: The proportion of infants experiencing adverse outcomes increased with the degree of epidural-related maternal temperature elevation. Epidural use without temperature elevation was not associated with any of the adverse outcomes we studied.

Association of epidural-related fever and noninfectious inflammation in term labor.

OBJECTIVE: To investigate the role of infection and noninfectious inflammation in epidural analgesia-related fever. METHODS: This was an observational analysis of placental cultures and serum admission and postpartum cytokine levels obtained from 200 women at low risk recruited during the prenatal period. RESULTS: Women receiving labor epidural analgesia had fever develop more frequently (22.7% compared with 6% no epidural; P=.009) but were not more likely to have placental infection (4.7% epidural, 4.0% no epidural; P>.99). Infection was similar regardless of maternal fever (5.4% febrile, 4.3% afebrile; P=.7). Median admission interleukin (IL)-6 levels did not differ according to later epidural (3.2 pg/mL compared with 1.6 pg/mL no epidural; P=.2), but admission IL-6 levels greater than 11 pg/mL were associated with an increase in fever among epidural users (36.4% compared with 15.7% for 11 pg/mL or less; P=.008). At delivery, both febrile and afebrile women receiving epidural had higher IL-6 levels than women not receiving analgesia. CONCLUSION: Epidural-related fever is rarely attributable to infection but is associated with an inflammatory state.

Mimicking muscle activity with electrical stimulation.

Functional electrical stimulation is a rehabilitation technology that can restore some degree of motor function in individuals who have sustained a spinal cord injury or stroke. One way to identify the spatio-temporal patterns of muscle stimulation needed to elicit complex upper limb movements is to use electromyographic (EMG) activity recorded from able-bodied subjects as a template for electrical stimulation. However, this requires a transfer function to convert the recorded (or predicted) EMG signals into an appropriate pattern of electrical stimulation. Here we develop a generalized transfer function that maps EMG activity into a stimulation pattern that modulates muscle output by varying both the pulse frequency and the pulse amplitude. We show that the stimulation patterns produced by this transfer function mimic the active state measured by EMG insofar as they reproduce with good fidelity the complex patterns of joint torque and joint displacement.

Recombinant human prolactin for the treatment of lactation insufficiency.

CONTEXT: Lactation insufficiency has many aetiologies including complete or relative prolactin deficiency. Exogenous prolactin may increase breast milk volume in this subset. We hypothesized that recombinant human prolactin (r-hPRL) would increase milk volume in mothers with prolactin deficiency and mothers of preterm infants with lactation insufficiency. DESIGN: Study 1: R-hPRL was administered in an open-label trial to mothers with prolactin deficiency. Study 2: R-hPRL was administered in a randomized, double-blind, placebo-controlled trial to mothers with lactation insufficiency that developed while pumping breast milk for their preterm infants. PATIENTS: Study 1: Mothers with prolactin deficiency (n = 5). Study 2: Mothers of premature infants exclusively pumping breast milk (n = 11). DESIGN: Study 1: R-hPRL (60 µg/kg) was administered subcutaneously every 12 h for 28 days. Study 2: Mothers of preterm infants were randomized to receive r-hPRL (60 µg/kg), placebo or r-hPRL alternating with placebo every 12 h for 7 days. MEASUREMENTS: Change in milk volume. RESULTS: Study 1: Peak prolactin (27·9 ± 17·3 to 194·6 ± 19·5 µg/l; P < 0·003) and milk volume (3·4 ± 1·6 to 66·1 ± 8·3 ml/day; P < 0·001) increased with r-hPRL administration. Study 2: Peak prolactin increased in mothers treated with r-hPRL every 12 h (n = 3; 79·3 ± 55·4 to 271·3 ± 36·7 µg/l; P < 0·05) and daily (101·4 ± 61·5 vs 178·9 ± 45·9 µg/l; P < 0·04), but milk volume increased only in the group treated with r-hPRL every 12 h (53·5 ± 48·5 to 235·0 ± 135·7 ml/day; P < 0·02). CONCLUSION: Twice daily r-hPRL increases milk volume in mothers with prolactin deficiency and in preterm mothers with lactation insufficiency.