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Neonatal hypoxia-ischemia (HI) is responsible for movement disorders in preterm infants. Non-pharmacological strategies, such as environmental enrichment (EE) during adulthood, have shown positive effects on promoting sensorimotor recovery after HI. However, little is known about the effects of perinatal EE on sensorimotor function following HI. In present study we investigated the hypothesis that enriched experiences during pregnancy and lactation would reduce motor impairments caused by a model of neonatal HI in rats. At postnatal day (PND) 3, Wistar pups of both sexes were subject to the modified Rice-Vannucci model. Motor function was evaluated from PND 60 to PND 64. HI caused a reduction in the forepaws strength and worsening of movement quality in the right forepaw. These effects were attenuated in animals receiving prenatal or lactational EE, which showed better performance when compared to the control group. Moreover, enriched experiences during lactation reversed HI-induced asymmetric use of the forepaws and the trend to increased paw errors in a walking test. Lower scores were found in the contralateral forepaw placement in HI animals, except when EE was provided at both stages of neurodevelopment . These results indicate that enriched experiences reduce motor impairments, i.e , measured in force, asymmetry and coordination domains, and that EE during lactation is more effective in promoting post-injury recovery. These data support that early therapeutic interventions might enhance functional reorganization at a period of high brain plasticity and that enriched-like experience might be encouraged in pediatric rehabilitation programs, in order to reduce long-term movement disorders after neonatal brain insults.

Although the adverse effects of neonatal hypoxia associated with premature birth on the central nervous system are well known, the contribution of hypoxic damage to the peripheral nervous system (PNS) has not been addressed. We demonstrate that neonatal hypoxia results in hypomyelination and delayed axonal sorting in mice leading to electrophysiological and motor deficits that persist into adulthood. These findings support a potential role for PNS hypoxic damage in the motor impairment that results from premature birth and suggest that therapies designed to protect the PNS may provide clinical benefit.

We compared the efficacy of three automated brain injury detection methods, namely symmetry-integrated region growing (SIRG), hierarchical region splitting (HRS) and modified watershed segmentation (MWS) in human and animal magnetic resonance imaging (MRI) datasets for the detection of hypoxic ischemic injuries (HIIs). Diffusion weighted imaging (DWI, 1.5T) data from neonatal arterial ischemic stroke (AIS) patients, as well as T2-weighted imaging (T2WI, 11.7T, 4.7T) at seven different time-points (1, 4, 7, 10, 17, 24 and 31 days post HII) in rat-pup model of hypoxic ischemic injury were used to assess the temporal efficacy of our computational approaches. Sensitivity, specificity, and similarity were used as performance metrics based on manual ('gold standard') injury detection to quantify comparisons. When compared to the manual gold standard, automated injury location results from SIRG performed the best in 62% of the data, while 29% for HRS and 9% for MWS. Injury severity detection revealed that SIRG performed the best in 67% cases while 33% for HRS. Prior information is required by HRS and MWS, but not by SIRG. However, SIRG is sensitive to parameter-tuning, while HRS and MWS are not. Among these methods, SIRG performs the best in detecting lesion volumes; HRS is the most robust, while MWS lags behind in both respects.

Therapeutic hypothermia in term infants with neonatal asphyxial encephalopathy has been shown to have beneficial effects in relation to neurodevelopmental outcome and survival. This paper is a critical appraisal of two studies, which compares and contrasts the methodology and findings, and incorporates a synthesis of findings with reflection on clinical practice.

Acute hypoxia at postnatal day (P) 10 is an accepted model of human neonatal hypoxia which results, among other consequences, in increased hippocampal excitability. Hypoxic–ischemic injury, which mimics stroke, has been shown to result in changes in connexins (Cxs), however, changes in Cxs have not been studied in the P10 hypoxia model. The aim of this study was to investigate changes in the hippocampal expression of three different connexins at consecutive developmental stages after acute hypoxia at P10 (10 min and 30 min after reoxygenation, P11, P14, P17, P29, and P45) as compared to sham manipulated pups. After acute hypoxia at P10, Cx30 protein levels were increased at 30 min after reoxygenation, at P11 and at P14, and then returned to control levels. Cx36 protein levels transiently decreased at P11 after acute hypoxia then returned to control levels. Cx43 protein levels did not change at any of the time points. Although changes in mRNA expression were observed during development for Cx30 only, acute hypoxia did not result in changes in mRNA expression of all these Cxs when compared to age matched controls suggesting that acute hypoxia induced posttranslational changes in protein expression.

Although recent studies have documented compensatory generation of neurons in adult brains in response to various insults, a noninjurious short episode of hypoxia in rat neonates has been shown to trigger neurogenesis within the ensuing weeks, without apparent brain lesions. Very little is known of the long-term consequences. We therefore investigated the effects of such a conditioning-like hypoxia (100% N(2), 5 min) on the brain and the cognitive outcomes of rats at 40 to 100 days of age. Control and posthypoxic rats developed similar learning capacities over postnatal days 14 to 18, but hypoxia was associated with enhanced scores in a test used to evaluate memory retrieval between 40 and 100 days. A striking sexual dimorphism was observed, with an earlier functional gain observed in female (40 days) compared with male (100 days) rats; gains were associated with matching structural changes in areas involved in cognition, including the hippocampus and frontal cortex. Therefore, it is proposed that brief neonatal hypoxia may exert long-term beneficial effects through neurogenesis stimulation.

OUTCOMES: THE INTEROBSERVER VARIABILITY SUNEET CHAUHAN, CHAD KLAUSER, THOMAS WOODRING, MAUREEN SANDERSON, EVERETT MAGANN, JOHN C. MORRISON, Society for Maternal-Fetal Medicine, West Allis, Wisconsin, University of Mississippi Medical Center, Jackson, Mississippi, University of Mississippi Medical Center, Obstetrics & Gynecology, Jackson, Mississippi, University of Texas Health Science Center at Houston, Brownsville, Texas, Naval Medical Center, Obstetrics & Gynecology, Portsmouth, Virginia, University of Mississippi Medical Center, Obstetrics and Gynecology, Jackson, Mississippi OBJECTIVE: The purpose of this study was, among patients with non-reassuring (NR) fetal heart tracings (FHT), determine the interobserver variability (IV) in interpretation of FHT (using the definitions in ACOG practice bulletin on the topic) and the ability to predict 1) patients requiring emergency cesarean delivery (ECD); 2) umbilical arterial [UA] pH 7.00; 3) base excess [BE] -12 mmol/L; and 4) Apgar score [AS] 3 at 5 min. STUDY DESIGN: Five clinicians (1 generalist and 4 MFM), not involved with the care of cohorts, reviewed 100 FHT. Ten tracings with objective evidence of fetal compromise were matched with 9 other FHT from the same time period. The FHT were divided into two phases: an hour prior to periodic decelerations and, if applicable, the hour before delivery. Weighted kappa coefficients (WKC) were calculated to assess inter-observer variability for episodic decelerations, whether the FHT is reassuring or uninterruptible, and the four outcomes. Spearman correlation coefficients (SCC) were calculated to assess the correlation between predicted and actual outcomes overall and by observer. RESULTS: Among 100 cohorts, 46% had CD for NR FHT; 2%, UApH 7.00 (acidosis); BE 12 in 14% and 3% had AS 3 at 5 min (low AS). The WKC for classifying the FHT as being reassuring in early labor was 0.12 and before delivery 0.15. The WKC for the 5 clinicians for predicting ECD was 0.26; for acidosis, 0.21; for abnormal base excess 0.16, and; for low AS at 5 min, 0.17. The SCC for each observer was 0.005 to 0.21 for ECD; for UApH, 0.01 to 0.46; for BE 0.03 to 0.29 and; for low AS 0.0 to 0.31. In the prediction of the UApH 7.00, three observers differed significantly (P 0.05) from one of the clinicians. The SCC range from 0.10 to 0.19 for the 4 outcomes. CONCLUSION: The reproducibility of and utility of FHT as a predictor of neonatal hypoxia is questionable because, there is a poor agreement among clinicians regarding interpretation of FHT and they cannot reliably identify newborn with hypoxia.

Our current ability to predict long-term neurologic outcome based upon intrapartum information is very limited. Adding information on the neurologic state during the first days of life adds powerfully to the ability to predict outcome. An understanding of causation requires consideration of antepartum factors, since many characteristics commonly labelled as indicators of "neonatal hypoxia" may be the first evidence in the infant of abnormality that predated labor.

Forty-six neonates with hypoxemia were treated with tolazoline, a pulmonary vasodilator, within the first two days of life. Eight of ten (80%) infants without apparent lung disease responded with a mean increase in PaO2 of 116 torr within one hour of beginning tolazoline infusions. One of the responding infants and two nonresponders died. Thirty-six additional infants with a variety of pulmonary disorders had severe hypoxemia which was refractory to mechanical ventilation. Twenty-one (58%) responded with a mean increase in PaO2 of 130 torr within one hour after beginning tolazoline and 13 (62%) of these survived. Fifteen patients had little or no improvement in PaO2 following tolazoline and only three (20%) of these infants survived. Responders could not be distinguished from nonresponders by clinical or laboratory features prior to therapy with tolazoline. Fourteen infants experienced complications possibly related to tolazoline.