Perinatal iron deficiency alters the neurochemical profile of the developing rat hippocampus

Cognitive deficits in human infants at risk for gestationally acquired perinatal iron deficiency suggest involvement of the developing hippocampus. To understand the plausible biological explanations for hippocampal injury in perinatal iron deficiency, a neurochemical profile of 16 metabolites in the iron-deficient rat hippocampus was evaluated longitudinally by 1H NMR spectroscopy at 9.4 T. Metabolites were quantified from an 11-24 microL volume centered in the hippocampus in 18 iron-deficient and 16 iron-sufficient rats on postnatal day (PD) 7, PD10, PD14, PD21 and PD28. Perinatal iron deficiency was induced by feeding the pregnant dam an iron-deficient diet from gestational d 3 to PD7. The brain iron concentration of the iron-deficient group was 60% lower on PD7 and 19% lower on PD28 (P < 0.001 each). The concentration of 12 of the 16 measured metabolites changed over time between PD7 and PD28 in both groups (P < 0.001 each). Compared with the iron-sufficient group, phosphocreatine, glutamate, N-acetylaspartate, aspartate, gamma-aminobutyric acid, phosphorylethanolamine and taurine concentrations, and the phosphocreatine/creatine ratio were elevated in the iron-deficient group (P < 0.02 each). These neurochemical alterations suggest persistent changes in resting energy status, neurotransmission and myelination in perinatal iron deficiency. An altered neurochemical profile of the developing hippocampus may underlie some of the cognitive deficits observed in human infants with perinatal iron deficiency

Perinatal iron deficiency predisposes the developing rat hippocampus to greater injury from mild to moderate hypoxia-ischemia

The hippocampus is injured in both hypoxia-ischemia (HI) and perinatal iron deficiency that are co-morbidities in infants of diabetic mothers and intrauterine growth restricted infants. We hypothesized that preexisting perinatal iron deficiency predisposes the hippocampus to greater injury when exposed to a relatively mild HI injury. Iron-sufficient and iron-deficient rats (hematocrit 40% lower and brain iron concentration 55% lower) were subjected to unilateral HI injury of 15, 30, or 45 mins (n=12 to 13/HI duration) on postnatal day 14. Sixteen metabolite concentrations were measured from an 11 microL volume on the ipsilateral (HI) and contralateral (control) hippocampi 1 week later using in vivo 1H NMR spectroscopy. The concentrations of creatine, glutamate, myo-inositol, and N-acetylaspartate were lower on the control side in the iron-deficient group (P<0.02, each). Magnetic resonance imaging showed hippocampal injury in the majority of the iron-deficient rats (58% versus 11%, P<0.0001) with worsening severity with increasing durations of HI (P=0.0001). Glucose, glutamate, N-acetylaspartate, and taurine concentrations were decreased and glutamine, lactate and myo-inositol concentrations, and glutamine/glutamate ratio were increased on the HI side in the iron-deficient group (P<0.01, each), mainly in the 30 and 45 mins HI subgroups (P<0.02, each). These neurochemical changes likely reflect the histochemically detected neuronal injury and reactive astrocytosis in the iron-deficient group and suggest that perinatal iron deficiency predisposes the hippocampus to greater injury from exposure to a relatively mild HI insult

Nutrition information in pregnancy: Where do women seek advice and has this changed over time?

Aim: Nutrition during pregnancy is fundamental to both the health of the mother and her baby. Sources of nutrition-related information are available via many sources but their accuracy is unknown. The present study aimed to (a) identify where women source their nutrition information during pregnancy and (2) assess the accuracy of nutrition information for pregnancy that is available on the internet. Methods: A survey instrument that identified the main sources of nutrition information was administered to 68 pregnant women recruited online. Data from this survey were compared to previous similar surveys conducted with pregnant mothers across years 2008, 2011 and 2014. A content analysis of websites was simultaneously conducted to assess the accuracy of available information. Results: The main source of nutrition information for a variety of topics was verbal communication from health professionals (% responses affirmative for that source ranged from 6.6% to 69% across survey years). There was an increasing trend in internet sourced information for most nutrition topics, but this source remained low for iodine across all years (range: 7.3%-15.9%). The internet was the main source of information for listeria/food safety (15.3%-32.4%) and healthy eating (25%-42%). Of the n = 165 websites identified by the content analysis, 82.4% (n = 136) were rated as accurate, with government (96.9%) and business/company (100%) sites having the highest accuracy. Conclusion: Verbal communication from health professionals remains the most important source of nutrition information for pregnancy. The high credibility of websites indicates this to be an additional resource. Further study into health literacy levels among women visiting these sites is needed to assess impact on dietary behaviour

Monitoring Outcome after Hospital-Presenting Milder Spectrum Pediatric Traumatic Brain Injury Using the Glasgow Outcome Scale-Extended, Pediatric Revision

The Glasgow Outcome Scale, Pediatric Revision (GOSE-P) is an assessment of “global outcome” designed as a developmentally appropriate version of the Glasgow Outcome Scale-Extended for use in clinical trials of children with traumatic brain injury (TBI). Initial testing describes validity across a wide age and injury severity spectrum, yet the GOSE-P's utility for monitoring children with milder injuries is less clear. We examined the level of agreement between the GOSE-P and the Health and Behavior Inventory (HBI), a TBI-related symptom checklist used to assess children with mild TBI for clinical and research purposes. Participants included children and adolescents 3–16 years of age ( n  = 50) who presented to two level 1 trauma centers within 24 h of injury, with a GCS of 13–15, who underwent clinical neuroimaging. Outcome was assessed 2 weeks and 3 months following injury. We examined the severity of TBI-related symptoms across disability categories identified using the GOSE-P, and the level of agreement between the two measures in identifying deficits 2 weeks following injury and improvement from 2 weeks to 3 months. Using the GOSE-P, 62% had deficits at 2 weeks, and 42% improved from 2 weeks to 3 months. Agreement between the GOSE-P and HBI was fair 2 weeks after TBI (k = 0.24–0.33), and poor for identifying subsequent improvement (k = 0.10–0.16). Modest agreement between the GOSE-P and the HBI may reflect restricted participation from diverse causes, including TBI, other bodily injuries, and prescribed activity restrictions, and highlights the need for multi-dimensional outcome batteries

The influence of chorion type on health measures at birth and dental development in Australian and Dutch twins: a comparative study

Chorion type may significantly influence the prenatal environment of twins. This study explored the associations between chorion type and gestational age, birth weight, birth length, and the timing of emergence of the first primary tooth in two populations of twins, Australian and Dutch. Additionally, we investigated the relationship between chorion type and birth weight discordance (BWD) in order to determine whether a significant relationship existed between discordance in birth weight and discordance in the timing of emergence of the first primary tooth. The two study samples consisted of 409 Australian twin pairs and 301 Dutch twin pairs, all of European ancestry. Data were collected through a combination of questionnaires and recording charts administered to the parents and through linkage with biological databases. In the Australian sample, monozygotic monochorionic (MZMC) twins experienced the shortest mean gestation time (35 weeks), the lowest mean birth length (46 cm) and the lowest mean birth weight (2.3 kg) compared with other twin groups. For the same variables in the Dutch sample, these trends with MZMC twinning were not observed. Chorion type did not significantly affect the mean timing of emergence of the first primary tooth in either sample. Monochorionicity was found to be significantly associated with BWD in both samples, but there was a significant association between BWD in MZMC twin pairs and timing of emergence of the first primary tooth only in the Australian sample. Results from this study support previous findings that the timing of emergence of the first primary tooth is influenced strongly by genetic factors and is well protected from environmental disturbances.Suzanna Mihailidis, Michelle Bockmann, Elise McConnell, Toby Hughes, Toos C. E. M. van Beijsterveldt, Dorret I. Boomsma, Minni McMaster, and Grant Townsen

Meeting Report: Risk Assessment of Tamiflu® use under Pandemic Conditions

On 3 October 2007, 40 participants with diverse expertise attended the workshop Tamiflu and the Environment: Implications of Use under Pandemic Conditions to assess the potential human health impact and environmental hazards associated with use of Tamiflu during an influenza pandemic. Based on the identification and risk-ranking of knowledge gaps, the consensus was that oseltamivir ethylester-phosphate (OE-P) and oseltamivir carboxylate (OC) were unlikely to pose an ecotoxicologic hazard to freshwater organisms. OC in river water might hasten the generation of OC-resistance in wildfowl, but this possibility seems less likely than the potential disruption that could be posed by OC and other pharmaceuticals to the operation of sewage treatment plants. The workgroup members agreed on the following research priorities: a) available data on the ecotoxicology of OE-P and OC should be published ; b) risk should be assessed for OC-contaminated river water generating OC-resistant viruses in wildfowl ; c) sewage treatment plant functioning due to microbial inhibition by neuraminidase inhibitors and other antimicrobials used during a pandemic should be investigated ; and d) realistic worst-case exposure scenarios should be developed. Additional modeling would be useful to identify localized areas within river catchments that might be prone to high pharmaceutical concentrations in sewage treatment plant effluent. Ongoing seasonal use of Tamiflu in Japan offers opportunities for researchers to assess how much OC enters and persists in the aquatic environment

Traumatic Brain Injury-Related Symptoms Reported by Parents: Clinical, Imaging, and Host Predictors in Children with Impairments in Consciousness Less than 24 Hours

This study examined the relationship between acute neuroimaging, host and injury factors, and parent-reported traumatic brain injury (TBI)-related symptoms in children with noncritical head injury at two weeks and three months after injury. Data were collected prospectively on 45 subjects aged three to 16 years old enrolled in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study. Subjects had rapid recovery of mental status (Glasgow Coma Score [GCS] = 15 within 24 h), and had no clinical need for neurosurgical intervention. Intra- or extra-axial magnetic resonance imaging (MRI) lesions were categorized using Common Data Elements (CDE) definitions. Host and acute injury factors including neurobehavioral history, race, extracranial injuries, loss of consciousness (LOC), and GCS were analyzed while controlling for pre-injury symptoms, age, sex, and socioeconomic status. Parent-reported cognitive and somatic symptoms were measured by the Health and Behavior Inventory (HBI). Forty-nine percent of children had MRI lesions, most of which were relatively small. LOC predicted increased cognitive and somatic symptoms at two weeks. At three months, pre-injury neurobehavioral history predicted increased cognitive and somatic symptoms. Neuroimaging findings did not predict parent-reported symptom severity, except at three months where extra-axial lesions were associated with less severe cognitive symptoms. While structural MRI lesions do not predict increased parent-reported symptoms in this population, age-specific child performance measures may be more sensitive outcome measures and require further study. Children with pre-injury neurobehavioral problems have more severe symptoms at three months and thus may benefit from longer follow-up and monitoring after traumatic brain injury

Adrenal volumes in fetuses delivering prior to 32 weeks’ gestation: an MRI pilot study

Introduction: Spontaneous preterm birth prior to 32 weeks' gestation accounts for 1% of all deliveries and is associated with high rates of morbidity and mortality. A total of 70% are associated with chorioamnionitis which increases the incidence of morbidity, but for which there is no noninvasive antenatal test. Fetal adrenal glands produce cortisol and dehydroepiandosterone-sulphate which upregulate prior to spontaneous preterm birth. Ultrasound suggests that adrenal volumes may increase prior to preterm birth, but studies are limited. This study aimed to: (i) demonstrate reproducibility of magnetic resonance imaging (MRI) derived adrenal volumetry; (ii) derive normal ranges of total adrenal volumes, and adrenal: body volume for normal; (iii) compare with those who have spontaneous very preterm birth; and (iv) correlate with histopathological chorioamnionitis. Material and methods: Patients at high risk of preterm birth prior to 32 weeks were prospectively recruited, and included if they did deliver prior to 32 weeks; a control group who delivered an uncomplicated pregnancy at term was also recruited. T2 weighted images of the entire uterus were obtained, and a deformable slice-to-volume method was used to reconstruct the fetal abdomen. Adrenal and body volumes were obtained via manual segmentation, and adrenal: body volume ratios generated. Normal ranges were created using control data. Differences between groups were investigated accounting for the effect of gestation by use of regression analysis. Placental histopathology was reviewed for pregnancies delivering preterm. Results: A total of 56 controls and 26 cases were included in the analysis. Volumetry was consistent between observers. Adrenal volumes were not higher in the case group (p = 0.2); adrenal: body volume ratios were higher (p = 0.011), persisting in the presence of chorioamnionitis (p = 0.017). A cluster of three pairs of adrenal glands below the fifth centile were noted among the cases all of whom had a protracted period at risk of preterm birth prior to MRI. Conclusions: Adrenal: body volume ratios are significantly larger in fetuses who go on to deliver preterm than those delivering at term. Adrenal volumes were not significantly larger, we hypothesize that this could be due to an adrenal atrophy in fetuses with fulminating chorioamnionitis. A straightforward relationship of adrenal size being increased prior to preterm birth should not be assumed.</p

CLINICAL TRIAL OF L-CARNITINE AND VALPROIC ACID IN SPINAL MUSCULAR ATROPHY TYPE I

Introduction: The aim of this study was to determine the safety and therapeutic potential of L-carnitine and valproic acid (VPA) in infants with spinal muscular atrophy (SMA). Methods: Our investigation was an open-label phase 2 multicenter trial of L-carnitine and VPA in infants with SMA type I with retrospective comparison to an untreated, matched cohort. Primary outcomes were: safety and adverse events; secondary outcomes were survival, time to death/> 16 hours/day of ventilator support; motor outcomes; and maximum ulnar compound motor action potential amplitude. Results: A total of 245 AEs were observed in 35 of the 37 treated subjects (95%). Respiratory events accounted for 49% of all adverse events, resulting in 14 deaths. Survival was not significantly different between treated and untreated cohorts. Discussion: This trial provides evidence that, in infants with SMA type I, L-carnitine/VPA is ineffective at altering survival. The substantial proportion of infants reaching end-points within 6 months of enrollment underscores the urgent need for pre-symptomatic treatment in SMA type I