Retinopathy of prematurity screening at ≥30 weeks: urinary NTpro-BNP performance.

AIM: Urinary N-terminal B-type natriuretic peptide NTproBNP levels are associated with the development of retinopathy of prematurity (ROP) in infants <30 weeks of gestation. The incidence of ROP in more mature infants who meet other ROP screening criteria is very low. We therefore aimed to test whether urinary NTproBNP predicted ROP development in these infants. METHODS: Prospective observational study in 151 UK infants ≥30 + 0 weeks of gestation but also <32 weeks of gestation and/or <1501 g, to test the hypothesis that urinary NTproBNP levels on day of life (DOL) 14 and 28 were able to predict ROP development. RESULTS: Urinary NTproBNP concentrations on day 14 and day 28 of life did not differ between infants with and without ROP (medians 144 vs 128 mcg/mL, respectively, p = 0.86 on DOL 14 and medians 117 vs 94 mcg/mL, respectively, p = 0.64 on DOL28). CONCLUSION: The association previously shown for infants <30 completed weeks between urinary NTproBNP and the development of ROP was not seen in more mature infants. Urinary NTproBNP does not appear helpful in rationalising direct ophthalmoscopic screening for ROP in more mature infants, and may suggest a difference in pathophysiology of ROP in this population.

Weight bias reduction in health professionals: a systematic review.

Innovative and coordinated strategies to address weight bias among health professionals are urgently needed. We conducted a systematic literature review of empirical peer-reviewed published studies to assess the impact of interventions designed to reduce weight bias in students or professionals in a health-related field. Combination sets of keywords based on three themes (1: weight bias/stigma; 2: obesity/overweight; 3: health professional) were searched within nine databases. Our search yielded 1447 individual records, of which 17 intervention studies satisfied the inclusion criteria. Most studies (n = 15) included medical, dietetic, health promotion, psychology and kinesiology students, while the minority included practicing health professionals (n = 2). Studies utilized various bias-reduction strategies. Many studies had methodological weaknesses, including short assessment periods, lack of randomization, lack of control group and small sample sizes. Although many studies reported changes in health professionals' beliefs and knowledge about obesity aetiology, evidence of effectiveness is poor, and long-term effects of intervention strategies on weight bias reduction remain unknown. The findings highlight the lack of experimental research to reduce weight bias among health professionals. Although changes in practice will likely require multiple strategies in various sectors, well-designed trials are needed to test the impact of interventions to decrease weight bias in healthcare settings.

Antenatal magnesium sulfate: Neuro-protection for preterm infants.

The neuro-protective effect of antenatal magnesium sulfate on very preterm infants has been demonstrated in good-quality randomised controlled trials and meta-analyses. Magnesium administered prior to preterm delivery crosses over to the foetal circulation and acts via several pathways to reduce perinatal neuronal damage. Meta-analysis of the trial data indicates that antenatal magnesium sulfate reduces the risk of cerebral palsy by one-third, and results in one fewer case in every 50 women treated. Treatment is associated with discomfort and flushing in some women, but maternal side-effects are mostly transient and manageable. Magnesium sulfate has also been found to be without any serious adverse consequences in newborn infants. Consensus recommendations and guidelines have been developed and implemented internationally, and endorsed by the UK Royal College of Obstetricians and Gynaecologists. However, magnesium sulfate for neuro-protection of very preterm infants has not yet become established widely in UK practice. Paediatricians, neonatologists and advocacy groups for preterm infants and their families could contribute to raising awareness and engage in dissemination activities and implementation initiatives to develop local protocols for adoption of this safe, effective and cost-effective intervention to reduce the burden of cerebral palsy in children born very preterm.

Being baby friendly: evidence-based breastfeeding support.

Breast feeding improves important outcomes for mothers and infants. In the UK, breastfeeding rates have historically been low, particularly among socially disadvantaged young women. Although there have been gradual increases in breastfeeding initiation rates since 2000, rates of exclusive breast feeding and continuation until 6 months remain lower than those in similar countries. This review summarises the evidence for effective and cost-effective strategies to help women, particularly those in low income groups, make informed choices, overcome barriers and establish and maintain breast feeding. We describe the development and impact of the Unicef Baby Friendly Initiative, and the roles and responsibilities, and challenges and opportunities that clinicians have in promoting breast feeding and maintaining a baby-friendly culture and environment.

MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.

The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues.

The value of the postnatal examination in improving child health.

This paper reviews the evidence regarding whether a standardised examination in the newborn period can improve infant health. The review considers aspects of delivering such a service from timing and number of examinations through to who should perform examinations, and whether evidence supports current practice. Infants at higher risk of anomaly such as those born preterm are highlighted. Aspects of the examination itself are reviewed, such as detection of congenital heart disease, and the relatively poor detection rate which does not seem to be improving. Potential advantages of additional screening with pulse oximetry are covered. The paper also discusses screening for developmental dysplasia of the hip, which the UK national screening council is unsure of the benefit of, the difficulties of detecting all cases of cleft palate and problems with screening for the very important congenital cataract. The authors draw attention to the relative rarity of some conditions and reflected on how this complicates screening.

Early discharge and readmission to hospital in the first month of life in the Northern Region of the UK during 1998: a case cohort study.

AIMS: To study the frequency and associations of early postpartum discharge and infant readmission to hospital. METHODS: Infants readmitted to hospital during the first 28 days of life in 1998 in the Northern Region of the UK were studied. RESULTS: A total of 4743 of 11,338 (42%) babies were discharged on or before the first postnatal day. Rates of early discharge varied significantly between hospitals. Infants <2500 g at birth (adjusted odds ratio (AOR) 0.44, 95% CI 0.29 to 0.66), infants 35-37 weeks gestation at birth (AOR 0.65, 95% CI 0.49 to 0.86), and firstborn infants (AOR 0.09, 95% CI 0.08 to 0.10) were less likely to be discharged early. Women from more deprived areas were more likely to be discharged early (AOR 1.37, 95% CI 1.12 to 1.67). A total of 907 of 32,015 (2.8%) babies liveborn in the region were readmitted to hospital during 1998. Readmission rates varied significantly by hospital of birth but not by timing of discharge. Babies <2500 g at birth (AOR 1.95, 95% CI 1.16 to 3.28) and babies born at 35-37 weeks gestation (AOR 1.72, 95% CI 1.15 to 2.57) were more likely to be readmitted. Breast fed babies were less likely to be readmitted (AOR 0.69, 95% CI 0.53 to 0.90). Infants initially discharged early were not more likely to be readmitted. CONCLUSIONS: Early discharge occurred variably in the Northern Region in 1998. It is not associated with readmission to hospital. Breast feeding is associated with lower rates of readmission to hospital.

Measurement of urine output by weighing nappies.

The effect of humidity on measurement of neonatal urine output was assessed by weighing nappies in a clinically relevant context. Saline was used as dummy urine, on modern nappies in incubators at various humidity settings. In at least some additional humidity, no clinically relevant evaporative loss occurred.

An extended interval dosing method for gentamicin in neonates.

Traditional gentamicin dosing every 8-24 h depending on age and weight in neonates does not provide the ideal concentration-time profile to both optimize the concentration-dependent killing by aminoglycosides and minimize toxicity. Fifty-three neonates were audited prospectively while receiving gentamicin 2.5 mg/kg every 8-24 h, aiming for peak concentrations (Cmax) of 6-10 mg/L and trough concentrations (Cmin) <2 mg/L. After the first dose, the mean (+/- s.d.) Cmax was 5.5 +/- 0.7 mg/L with sub-therapeutic concentrations (<6 mg/L) in 62% of patients, while the mean Cmin was >2 mg/L in 15% of the neonates. After the third dose the Cmax was 7.5 +/- 1.5 mg/L, with 17% <6 mg/L, whereas the mean Cmin was 2.2 +/- 1.1 mg/L with 49% of values >2 mg/L. An extended interval dosing method (24, 36 and 48 h) for infant weights of 0.75-5 kg was developed by simulation, and audited prospectively in 51 neonates. Prospective analysis of the extended interval dosing method showed a mean Cmax after the first dose of 13.1 +/- 3.6 mg/L, while the mean Cmin was 0.7 +/- 0.6 mg/L. Seventy-eight per cent had Cmax of >10 mg/L after the first dose. The mean area under the concentration versus time curve AUC0-24 was 93 mg*h/L (target = 100 mg*h/L). The extended interval dosing achieved higher Cmax values while ensuring that overall exposure per 24 h was acceptable. Prospective testing of the method demonstrated good predictive ability.

Theta band oscillation and synchrony in the hippocampal formation and associated structures: the case for its role in sensorimotor integration.

The current review advances the argument that it is naïve to ascribe a unitary function to the hippocampal formation (HPC). Rather, it is more productive to consider the hippocampal formation as consisting of a number of subsystems, each subsystem defined by its own particular neural circuitry. Among examples of neural circuitry appearing in current hippocampal literature are theta, beta and gamma oscillations, sharp waves, place cells and head orientation cells. Data are reviewed supporting the case that theta band oscillation and synchrony is involved in mechanisms underlying sensorimotor integration. Specifically, the neural circuitry underlying the production of oscillation and synchrony (theta) in limbic cortex and associated structures function in the capacity of providing voluntary motor systems with continually updated feedback on their performance relative to changing environmental (sensory) conditions. A crucial aspect of this performance is the intensity with which the motor programs are initiated and maintained. The ascending brainstem HPC synchronizing pathways make the primary contribution in this regard. These pathways originate in the rostral pontine region, ascend and synapse with caudal diencephalic nuclei, which in turn send projections to the medial septal region. The medial septum functions as the node in the ascending pathways, sending both cholinergic and GABA-ergic projections to the HPC. An updated version of the sensorimotor integration model including anatomical details is presented and discussed.

Hypernatraemic dehydration and breast feeding: a population study.

As part of a population based regional review of all neonatal readmissions, the incidence of dehydration with hypernatraemia in exclusively breast fed infants was estimated. All readmissions to hospital in the first month of life during 1998 from a population of 32 015 live births were reviewed. Eight of 907 readmissions met the case definition, giving an incidence of at least 2.5 per 10 000 live births. Serum sodium at readmission varied from 150 to 175 mmol/l. One infant had convulsions. The sole explanation for hypernatraemia was unsuccessful breast feeding in all cases. The eight cases are compared with the 65 cases published in the literature since 1979. Presentation, incidence, risk factors, pathophysiology, treatment, and prevention are discussed.

Mechanisms of neural synchrony in the septohippocampal pathways underlying hippocampal theta generation.

Using urethane-anesthetized rats, 18 simultaneously recorded septohippocampal cell pairs (36 individual cells), each classified as theta-related according to the criteria of, were studied during four spontaneously occurring hippocampal field conditions: (1) large amplitude irregular activity (LIA) only; (2) the transition from LIA to theta; (3) theta only; and (4) the transition from theta to LIA. The main objective was to study the temporal relationships and degree of neural synchrony between the discharges of the cell pairs, using both time-averaged and time-dependent joint peristimulus time histogram correlation techniques, during the four conditions, to determine their contribution to the control of oscillation and synchrony (theta) in the hippocampus. The study demonstrated that the transition from the LIA state to the theta field state in the hippocampus required a temporal sequence of changes in theta-related cellular activity occurring on average 500 msec preceding the transition: (1) the medial septum inhibits hippocampal theta-OFF cells; (2) medial septal tonic theta-ON cells provide tonic depolarizing inputs to initiate membrane potential oscillations (MPOs) in hippocampal phasic theta-ON cells, whereas medial septal phasic theta-ON cells synchronize the MPOs of hippocampal phasic theta-ON cells and the discharges of hippocampal tonic theta-ON cells. Much of the time preceding the LIA to theta transition is accounted for by recruitment of these theta-related cell populations. Conversely, "turning off" the theta state occurs abruptly and involves the medial septal disinhibition of hippocampal theta-OFF cells.

Hippocampal formation theta activity and movement selection.

Hippocampal theta activity results from activation in the ascending synchronizing system. It occurs during sensory/signal processing prior to and coincident with voluntary movements in mammals. The experiments summarized here suggest that it is involved in the organization of motor behaviour. (1) Procaine (a local anaesthetic) infused into the medial septum (MS) abolishes hippocampal theta activity and running behaviour elicited by electrical posterior hypothalamic (PH) stimulation. This indicates that movement elicited by PH stimulation, is dependent on ascending hypothalamo-septal circuitry. (2) Theta can also be recorded in immobile rats prior to the initiation of lateral dodging movements they make in response to conspecific rats attempting to steal their food. Following infusion of atropine into the MS, theta recorded during immobility is abolished and the rats are severely impaired at initiating movements in defence of their food. It is suggested that atropine-sensitive theta is involved in the initiation of movements made by rats in response to sensory stimuli. (3) Rats with fimbria-fornix transections were also less likely to engage in lateral dodging movements in defence of their food, were hyperactive, less thigmotaxic, and defecated more often, compared to control animals. Depth profile analysis of hippocampal field activity in lesioned animals revealed an absence of theta during electrical or chemical pons stimulation. These findings provide evidence that these neural systems are involved in signal processing relevant to movements underlying adaptive behaviour.

Anatomical, electrophysiological and pharmacological studies of ascending brainstem hippocampal synchronizing pathways.

The present review has provided evidence that very potent ascending brainstem hippocampal synchronizing pathways originate in the rostral pons region (RPO and PPT), and ascend to and synapse with several midline caudal diencephalic nuclei (posterior hypothalamic and supramammillary) which send projections to the medial septal region (MS/vDBB). The medial septal region in turn is a critical nodal point, sending projections to limbic structures such as the hippocampal formation, cingulate cortex, and entorhinal cortex. The pontine and diencephalic nuclei appear to play a critical role in determining the translation of increasing levels of activation into moment to moment changes in the frequency of hippocampal theta field and theta-related cellular discharges, relayed to the MS/vDBB nuclei. The MS/vDBB nuclei appear to play a critical role in translating increasing levels of ascending synchronizing activation into moment to moment changes in the amplitude of hippocampal theta field activity and the accompanying rate and pattern of phasic theta-ON cells. The MS/vDBB carries out this role through a balance of activity in the septohippocampal cholinergic and GABA-ergic projections. Cholinergic projections provide the afferent excitatory drive for hippocampal theta-ON cells and the GABA-ergic projections act to reduce the overall level of inhibition by inhibiting hippocampal GABA-ergic interneurons (theta-OFF cells). Both activities must be present for the generation of hippocampal theta and theta-related cellular activities. The balance between the cholinergic and GABA-ergic projections may determine whether hippocampal synchrony (theta) or asynchrony (LIA, large amplitude irregular activity) occurs. These same ascending pathways influence the electrophysiological and pharmacological properties of the neocortex as well. The functional significance of the ascending brainstem synchronizing pathways is the generalized regulation of activities in these cortical structures as they relate to sensorimotor behavior.

Hippocampal formation is involved in movement selection: evidence from medial septal cholinergic modulation and concurrent slow-wave (theta rhythm) recording.

Hippocampal rhythmical slow-wave field activity which occurs in response to sensory stimulation is predominantly cholinergic (atropine-sensitive theta rhythm), can precede movement initiation, and co-occurs during non-cholinergic theta rhythm associated with ongoing movement (atropine-resistant). This relationship suggests that theta rhythm plays some role in movement control. The present naturalistic experiments tested the idea that atropine-sensitive theta rhythm plays a role in sensory integration and planning required for initiating appropriate movements. One of a pair of hungry rats, the victim, implanted with hippocampal field recording electrodes, a septal injection cannula, and a posterior hypothalamic stimulating electrode, was given food which the other, the robber, tries to steal. Since the victim dodges from the robber with a latency, distance, and velocity dependent upon the size of the food, elapsed eating time, and proximity of the robber, the movement requires sensory integration and planning. Although eating behavior seemed normal, atropine-sensitive theta rhythm and dodging were disrupted by an infusion of a cholinergic antagonist into the medial septum. When the victim in turn attempted to steal the food back, Type 1 theta rhythm was present and robbery attempts seemed normal. Prior to cholinergic blockade, posterior hypothalamic stimulation produced theta rhythm and dodges, even in the absence of the robber, but following injections, atropine-sensitive theta rhythm and dodging were absent as the animals dropped the food and ran. The results provide the first evidence to link atropine-sensitive theta rhythm and hippocampal structures to a role in sensory integration and planning for the initiation of movement.

Evidence for differential control of posterior hypothalamic, supramammillary, and medial mammillary theta-related cellular discharge by ascending and descending pathways.

Single-unit discharge was recorded from cells in the posterior hypothalamic nucleus (PH), supramammillary nucleus (SuM), and medial mammillary nucleus (MM) during hippocampal theta (theta) elicited by stimulation of the reticular nucleus pontis oralis (RPO). In agreement with previously published work, theta-related cells in the PH (12 cells) were all classified as tonic theta-ON (increased tonic discharge rate during hippocampal theta), whereas those in the SuM (9 cells) and MM (15 cells) were all classified as phasic theta-ON (rhythmic discharge, in phase with ongoing theta). The effect of RPO stimulation on cell discharge was tested after hippocampal theta was abolished by infusion of procaine into the medial septum/vertical limb of the diagonal band. The RPO-elicited discharge patterns of all PH tonic theta-ON cells and all SuM phasic theta-ON cells survived septal procaine infusion. Further, the discharge rate of PH cells and the frequency of burst discharge of SuM cells during RPO stimulation both increased after the infusion. In contrast, septal procaine infusion abolished the RPO-elicited rhythmic discharge pattern in MM phasic theta-ON cells and attenuated their discharge rates. These results indicate that the PH and SuM form parts of an ascending system mediating hippocampal theta, whereas the MM receives (and perhaps relays to other parts of the limbic system) rhythmic input descending from the septo-hippocampal system. In addition, PH and SuM receive descending inputs that limit the discharge rates of their theta-related cells during hippocampal theta.

Intraseptal microinfusion of muscimol: effects on hippocampal formation theta field activity and phasic theta-ON cell discharges.

The effect of intraseptal microinfusions of the GABA-A agonist muscimol on spontaneously occurring or hypothalamically induced hippocampal formation (HPC) theta field activity and the simultaneously occurring discharge properties of CA1 pyramidal and dentate granule layer phasic theta-ON cells, was investigated in urethane-anesthetized rats. The microinfusion of 5.0-12.5 nmol of muscimol into the medical septum/vertical limb of the diagonal band of Broca (MS/vDBB) resulted in a progressive reduction (beginning 5 min postinfusion) in the power (amplitude) and finally the total loss of theta field activity. In contrast, theta field frequency remained unaffected during the entire postinfusion period that theta field activity was present. In the time immediately following the first 1-min intraseptal microinfusion of 5 nmol muscimol, (before changes in theta amplitude occurred) a brief period of increased phasic theta-ON cell excitability was noted. This was manifested as an increase in the number of discharges per rhythmic burst. Associated with the progressive reduction of the amplitude of theta field activity, phasic theta-ON cell discharge rates progressively decreased for a period beginning 5 min postinfusion of 5 nmol muscimol. Despite the progressive decrease in the number of discharges and a noticeable reduction in the degree of rhythmicity, phasic theta-ON cells maintained their preferred timing of discharges in relation to the phase of theta field activity, while the latter was present. Just prior to the complete abolishment of theta field activity, phasic theta-ON cells ceased discharging. During the period when theta field activity was replaced on low amplitude asynchronous activity, phasic theta-ON cells discharged in bursts correlated with every occurrence of sharp wave field activity. The results support the following conclusions: (1) the brief excitatory effect on HPC theta-ON cell discharges may be correlated pharmacologically with an initial brief increase in HPC ACh turnover. The reduction of phasic theta-ON cell discharges and theta field activity may be correlated with the longer lasting reduction of HPC ACh turnover, controlled by MS/vDBB GABA-A inputs to MS/vDBB cholinergic septohippocampal neurons, possibly along with a direct inhibition of the GABAergic septohippocampal projection; (2) the primary contribution of the MS/vDBB nuclei, as a nodal point in the ascending brainstem HPC synchronizing system, is the modulation of the amplitude of HPC formation theta field activity and secondarily to relay frequency-coded inputs from the posterior hypothalamic region (posterior and supramammillary nuclei); (3) HPC theta and sharp wave field activity represent functionally distinct neural inputs to the same population of phasic theta-ON cells located in both the CA1 pyramidal and dentate granule cell layers.