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Neonatal stroke is a devastating condition that causes brain injury in babies and often leads to lifelong neurological impairment. Recent prospective population studies of neonatal stroke are lacking. Neonatal strokes are different from those in older children and adults. A better understanding of its aetiology, current management, and outcomes could reduce the burden of this rare condition. The study aims to explore the incidence and 2 year outcomes of neonatal stroke across an entire population in the UK and Republic of Ireland. This is an active national surveillance study using a purpose-built integrated case notification-data collection online platform. Over a 13 month period, with a potential 6 month extension, clinicians will notify neonatal stroke cases presenting in the first 90 days of life electronically via the online platform monthly. Clinicians will complete a primary questionnaire via the platform detailing clinical information, including neuroimaging, for analysis and classification. An outcome questionnaire will be sent at 2 years of age via the platform. Appropriate ethics and regulatory approvals have been received. The neonatal stroke study represents the first multinational population surveillance study delivered via a purpose-built integrated case notification-data collection online platform and data safe haven, overcoming the challenges of setting up the study.

Aim Methods Results Conclusion Evaluate the additional burden of centralised neonatal care on families of extremely preterm infants cared for away from their planned hospital of birth.Retrospective cohort study using national data for infants 23+0 to 27+6 weeks of gestation admitted for neonatal care from 2011 to 2016. The number of transfers on the first day of life (potential maternal–infant separation), time away from the maternal booking hospital (BH) and distance from the maternal residence were quantified.Of 14 719 included infants, 2803 (19%) underwent postnatal transfer on the first day of life. A total of 8622 (59%) infants were cared for away from their BH for a median of 39 days (interquartile range [IQR] 15–69), 30% spending >60 days away over a median of two episodes (range 1–12). Median return road travelling distances for parents to their local BH was 13 km (IQR 8–26), but this increased to 74 km (IQR 32–148) for those cared for in a non‐BH.Centralised neonatal care improves infant outcomes but introduces additional burdens on the families of extremely preterm infants cared for away from their BH. Additional support, including accommodation and financial aid, could help minimise the impact on these families, facilitate family integrated care and improve parental wellbeing. [ABSTRACT FROM AUTHOR]

Neurodevelopmental delay following extremely preterm birth or birth asphyxia is common but diagnosis is often delayed as early milder signs are not recognised by parents or clinicians. Early interventions have been shown to improve outcomes. Automation of diagnosis and monitoring of neurological disorders using non-invasive, cost effective methods within a patient's home could improve accessibility to testing. Furthermore, said testing could be conducted over a longer period, enabling greater confidence in diagnoses, due to increased data availability. This work proposes a new method to assess the movements in children. Twelve parent and infant participants were recruited (children aged between 3 and 12 months). Approximately 25 min 2D video recordings of the infants organically playing with toys were captured. A combination of deep learning and 2D pose estimation algorithms were used to classify the movements in relation to the children's dexterity and position when interacting with a toy. The results demonstrate the possibility of capturing and classifying children's complexity of movements when interacting with toys as well as their posture. Such classifications and the movement features could assist practitioners to accurately diagnose impaired or delayed movement development in a timely fashion as well as facilitating treatment monitoring. [ABSTRACT FROM AUTHOR]

This article discusses a study on sound levels in the neonatal intensive care unit (NICU) and during neonatal inter-hospital transport. The authors used a mannequin model to investigate the effectiveness of passive and active noise cancellation in each setting. The study found that the original analysis underestimated the efficacy of the incubator as a barrier to noise and the efficacy of active noise-cancelling headphones. Additionally, the study suggests that the occlusion effect, where occlusion of the ear amplifies low-frequency bone-conducted sound, may be a relevant consideration for sound attenuation during neonatal transport. Further research is needed to improve the experimental model. [Extracted from the article]

As survival of extremely preterm infants continues to improve, there is also an associated increase in bronchopulmonary dysplasia (BPD), one of the most significant complications of preterm birth. BPD development is multifactorial resulting from exposure to multiple antenatal and postnatal stressors. BPD has both short-term health implications and long-term sequelae including increased respiratory, cardiovascular, and neurological morbidity. Transforming growth factor β (TGF-β) is an important signaling pathway in lung development, organ injury, and fibrosis and is implicated in the development of BPD. This review provides a detailed account on the role of TGF-β in antenatal and postnatal lung development, the effect of known risk factors for BPD on the TGF-β signaling pathway, and how medications currently in use or under development, for the prevention or treatment of BPD, affect TGF-β signaling. [ABSTRACT FROM AUTHOR]

Obesity is an independent risk factor for developing chronic kidney disease. Toll-like receptor 4 (TLR4), interleukin (IL)-18, and uncoupling protein 2 (UCP2) are important components of the innate immune system mediating inflammatory renal damage. Early to midgestation maternal nutrient restriction appears to protect the kidney from the deleterious effects of early onset obesity, although the mechanisms remain unclear. We examined the combined effects of gestational maternal nutrient restriction during early fetal kidney development and early onset obesity on the renal innate immune response in offspring. Pregnant sheep were randomly assigned to a normal (control, 100%) or nutrient-restricted (NR, 50%) diet from days 30 to 80 gestation and 100% thereafter. Offspring were killed humanely at 7 days or, following rearing in an obesogenic environment, at 1 yr of age, and renal tissues were collected. IL-18 and TLR4 expression were strongly correlated irrespective of intervention. Seven-day NR offspring had significantly lower relative renal mass and IL-18 mRNA expression. At 1 yr of age, obesity resulted in increased mRNA abundance of TLR4, IL-18, and UCP2, coupled with tubular atrophy and greater immunohistological staining of glomerular IL-6 and medullary tumor necrosis factor (TNF)-[alpha]. NR obese offspring had a marked reduction of TLR4 abundance and renal IL-6 staining. In conclusion, maternal nutrient restriction during early fetal kidney development attenuates the effects of early onset obesity-related nephropathy, in part, through the downregulation of the innate inflammatory response. A better understanding of maternal nutrition and the in utero nutritional environment may offer therapeutic strategies aimed at reducing the burden of later kidney disease. interleukin-18; interleukin-6; Toll-like receptor 4; uncoupling protein 2; nephropathy; nutrition doi: 10.1152/ajprenal.00303.2009.

Background: International newborn resuscitation guidelines recommend electrocardiogram (ECG) heart rate (HR) monitoring at birth. We evaluated the application time of pre-set ECG electrodes fixed to a polyethene patch allowing adhesive-free attachment to the wet skin of the newborn chest. Objectives: Using a three-electrode pre-set ECG patch configuration, application success was calculated using video analysis and measured at three time points, the time to (1) apply electrodes; (2) detect recognizable QRS complexes after application; and (3) display a HR after application. Method: A prospective observational study in two UK tertiary maternity units was undertaken with 71 newborns including 23 who required resuscitation. Results: The median (IQR) time for ECG patch application was 8 (6–10) seconds, detection of recognizable QRS complexes 8 (2–12) seconds, and time to output HR was 23 (15–37) seconds. Conclusion: Pre-set ECG chest electrodes allow rapid HR information at birth without electrode detachment or compromising skin integrity. [ABSTRACT FROM AUTHOR]

Objective: Early postnatal transfer (PNT) of extremely preterm infants is associated with adverse outcomes compared with in utero transfer (IUT). We aimed to explore recent national trends of IUT and early PNT.Design: Observational cohort study using the National Neonatal Research Database.Setting: Neonatal units in England, Scotland and Wales.Patients: Extremely preterm infants 23+0-27+6 weeks' gestation admitted for neonatal care from 2011 to 2016.Main Outcome: The incidence of IUT or PNT within 72 hours of life. Secondary outcomes included mortality, hospital transfer level between centres and temporal changes across two equal epochs, 2011-2013 (epoch 1 (Ep1)) and 2014-2016 (epoch 2 (Ep2)).Results: 14 719 infants were included (Ep1=7363 and Ep2=7256); 4005 (27%) underwent IUT; and 3042 (20.7%) had PNT. IUTs decreased significantly between epochs from 28.3% (Ep1=2089) to 26.0% (Ep2=1916) (OR 0.90, 95% CI 0.84 to 0.97, p<0.01). Conversely, PNTs increased from 19.8% (Ep1=1416) to 21.5% (Ep2=1581) (OR 1.11, 95% CI 1.02 to 1.20, p=0.01). PNTs between intensive care centres increased from 8.1% (Ep1=119) to 10.2% (Ep2=161, p=0.05). Mortality decreased from 21.6% (Ep1=1592) to 19.3% (Ep2=1421) (OR 0.90, 95% CI 0.83 to 0.97, p=0.01). Survival to 90 days of age was significantly lower in infants undergoing PNT compared with IUT (HR 1.31, 95% CI 1.18 to 1.46), with the greatest differences observed in infants <25 weeks' gestational age.Conclusion: In the UK, IUT of extremely preterm infants has significantly decreased over the study period with a parallel increase in early PNT. Strategies to reverse these trends, improve IUT pathways and optimise antenatal steroid use could significantly improve survival and reduce brain injury for these high-risk infants. [ABSTRACT FROM AUTHOR]

Objective: To determine the change in non-invasive ventilation (NIV) use over time in infants born at <32 weeks' gestation and the associated clinical outcomes.Study Design: Retrospective cohort study using routinely recorded data from the National Neonatal Research Database of infants born at <32 weeks admitted to neonatal units in England and Wales from 2010 to 2017.Results: In 56 537 infants, NIV use increased significantly between 2010 and 2017 (continuous positive airway pressure (CPAP) from 68.5% to 80.2% in 2017 and high flow nasal cannula (HFNC) from 14% to 68%, respectively) (p<0.001)). Use of NIV as the initial mode of respiratory support also increased (CPAP, 21.5%-28.0%; HFNC, 1%-7% (p<0.001)).HFNC was used earlier, and for longer, in those who received CPAP or mechanical ventilation. HFNC use was associated with decreased odds of death before discharge (adjusted OR (aOR) 0.19, 95% CI 0.17 to 0.22). Infants receiving CPAP but no HFNC died at an earlier median chronological age: CPAP group, 22 (IQR 10-39) days; HFNC group 40 (20-76) days (p<0.001). Among survivors, HFNC use was associated with increased odds of bronchopulmonary dysplasia (BPD) (aOR 2.98, 95% CI 2.81 to 3.15) and other adverse outcomes.Conclusions: NIV use is increasing, particularly as initial respiratory support. HFNC use has increased significantly with a sevenfold increase soon after birth which was associated with higher rates of BPD. As more infants survive with BPD, we need robust clinical evidence, to improve outcomes with the use of NIV as initial and ongoing respiratory support. [ABSTRACT FROM AUTHOR]

Objective: Therapeutic hypothermia (TH) for neonatal hypoxic-ischaemic encephalopathy (HIE), delivered mainly in tertiary cooling centres (CCs), reduces mortality and neurodisability. It is unknown if birth in a non-cooling centre (non-CC), without active TH, impacts short-term outcomes.Design: Retrospective cohort study using National Neonatal Research Database and propensity score-matching.Setting: UK neonatal units.Patients: Infants ≥36 weeks gestational age with moderate or severe HIE admitted 2011-2016.Interventions: Birth in non-CC compared with CC.Main Outcome Measures: Primary outcome was survival to discharge without recorded seizures. Secondary outcomes were recorded seizures, mortality and temperature on arrival at CCs following transfer.Results: 5059 infants were included with 2364 (46.7%) born in non-CCs. Birth in a CC was associated with improved survival without seizures (35.1% vs 31.8%; OR 1.15, 95% CI 1.02 to 1.31; p=0.02), fewer seizures (60.7% vs 64.6%; OR 0.84, 95% CI 0.75 to 0.95, p=0.007) and similar mortality (15.8% vs 14.4%; OR 1.11, 95% CI 0.93 to 1.31, p=0.20) compared with birth in a non-CC. Matched infants from level 2 centres only had similar results, and birth in CCs was associated with greater seizure-free survival compared with non-CCs. Following transfer from a non-CC to a CC (n=2027), 1362 (67.1%) infants arrived with a recorded optimal therapeutic temperature but only 259 (12.7%) of these arrived within 6 hours of birth.Conclusions: Almost half of UK infants with HIE were born in a non-CC, which was associated with suboptimal hypothermic treatment and reduced seizure-free survival. Provision of active TH in non-CC hospitals prior to upward transfer warrants consideration. [ABSTRACT FROM AUTHOR]

Objective: Hypoxic-ischaemic encephalopathy (HIE) remains a leading cause of neonatal mortality and neurodisability. We aimed to determine the incidence of HIE and management patterns against national guidelines.Design: Retrospective cohort study using the National Neonatal Research Database.Setting: Neonatal units in England and Wales.Patients: Infants 34-42 weeks gestational age (GA) with a recorded diagnosis of HIE.Main Outcomes: Incidence of HIE, mortality and treatment with therapeutic hypothermia (TH) were the main outcomes. Temporal changes were compared across two epochs (2011-2013 and 2014-2016).Results: Among 407 462 infants admitted for neonatal care, 12 195 were diagnosed with HIE. 8166 infants ≥36 weeks GA had moderate/severe HIE, 62.1% (n=5069) underwent TH and mortality was 9.3% (n=762). Of infants with mild HIE (n=3394), 30.3% (n=1027) underwent TH and 6 died. In late preterm infants (34-35 weeks GA) with HIE (n=635, 5.2%), 33.1% (n=210) received TH and 13.1% (n=83) died. Between epochs (2011-2013 vs 2014-2016), mortality decreased for infants ≥36 weeks GA with moderate/severe HIE (17.5% vs 12.3%; OR 0.69, 95% CI 0.59 to 0.81, p<0.001). Treatment with TH increased significantly between epochs in infants with mild HIE (24.9% vs 35.8%, p<0.001) and those born late preterm (34.3% vs 46.6%, p=0.002).Conclusions: Mortality of infants ≥36 weeks GA with moderate/severe HIE has reduced over time, although many infants diagnosed with moderate/severe HIE do not undergo TH. Increasingly, mild HIE and late preterm infants with HIE are undergoing TH, where the evidence base is lacking, highlighting the need for prospective studies to evaluate safety and efficacy in these populations. [ABSTRACT FROM AUTHOR]

Background: Therapeutic hypothermia is standard of care for babies with moderate/severe hypoxic-ischaemic encephalopathy and is increasingly used for mild encephalopathy.Objective: Describe temporal trends in the clinical condition of babies diagnosed with hypoxic-ischaemic encephalopathy who received therapeutic hypothermia.Design: Retrospective cohort study using data held in the National Neonatal Research Database.Setting: National Health Service neonatal units in England, Wales and Scotland.Patients: Infants born from 1 January 2010 to 31 December 2017 with a recorded diagnosis of hypoxic-ischaemic encephalopathy who received therapeutic hypothermia for at least 3 days or died in this period.Main Outcomes: Primary outcomes: recorded clinical characteristics including umbilical cord pH; Apgar score; newborn resuscitation; seizures and treatment on day 1.Secondary Outcomes: recorded hypoxic-ischaemic encephalopathy grade.Results: 5201 babies with a diagnosis of hypoxic-ischaemic encephalopathy received therapeutic hypothermia or died; annual numbers increased over the study period. A decreasing proportion had clinical characteristics of severe hypoxia ischaemia or a diagnosis of moderate or severe hypoxic-ischaemic encephalopathy, trends were statistically significant and consistent across multiple clinical characteristics used as markers of severity.Conclusions: Treatment with therapeutic hypothermia for hypoxic-ischaemic encephalopathy has increased in England, Scotland and Wales. An increasing proportion of treated infants have a diagnosis of mild hypoxic-ischaemic encephalopathy or have less severe clinical markers of hypoxia. This highlights the importance of determining the role of hypothermia in mild hypoxic-ischaemic encephalopathy. Receipt of therapeutic hypothermia is unlikely to be a useful marker for assessing changes in the incidence of brain injury over time. [ABSTRACT FROM AUTHOR]

Transferring sick premature infants between hospitals increases the risk of severe brain injury, potentially linked to the excessive exposure to noise, vibration and driving-related accelerations. One method of reducing these levels may be to travel along smoother and quieter roads at an optimal speed, however this requires mass data on the effect of roads on the environment within ambulances. An app for the Android operating system has been developed for the purpose of recording vibration, noise levels, location and speed data during ambulance journeys. Smartphone accelerometers were calibrated using sinusoidal excitation and the microphones using calibrated pink noise. Four smartphones were provided to the local neonatal transport team and mounted on their neonatal transport systems to collect data. Repeatability of app recordings was assessed by comparing 37 journeys, made during the study period, along an 8.5 km single carriageway. The smartphones were found to have an accelerometer accurate to 5% up to 55 Hz and microphone accurate to 0.8 dB up to 80 dB. Use of the app was readily adopted by the neonatal transport team, recording more than 97,000 km of journeys in 1 year. To enable comparison between journeys, the 8.5 km route was split into 10 m segments. Interquartile ranges for vehicle speed, vertical acceleration and maximum noise level were consistent across all segments (within 0.99 m. s−1, 0.13 m · s−2 and 1.4 dB, respectively). Vertical accelerations registered were representative of the road surface. Noise levels correlated with vehicle speed. Android smartphones are a viable method of accurate mass data collection for this application. We now propose to utilise this approach to reduce potential harmful exposure, from vibration and noise, by routing ambulances along the most comfortable roads. [ABSTRACT FROM AUTHOR]

Aim: A device for newborn heart rate (HR) monitoring at birth that is compatible with delayed cord clamping and minimises hypothermia risk could have advantages over current approaches. We evaluated a wireless, cap mounted device (fhPPG) for monitoring neonatal HR.Methods: A total of 52 infants on the neonatal intensive care unit (NICU) and immediately following birth by elective caesarean section (ECS) were recruited. HR was monitored by electrocardiogram (ECG), pulse oximetry (PO) and the fhPPG device. Success rate, accuracy and time to output HR were compared with ECG as the gold standard. Standardised simulated data assessed the fhPPG algorithm accuracy.Results: Compared to ECG HR, the median bias (and 95% limits of agreement) for the NICU was fhPPG -0.6 (-5.6, 4.9) vs PO -0.3 (-6.3, 6.2) bpm, and ECS phase fhPPG -0.5 (-8.7, 7.7) vs PO -0.1 (-7.6, 7.1) bpm. In both settings, fhPPG and PO correlated with paired ECG HRs (both R2  = 0.89). The fhPPG HR algorithm during simulations demonstrated a near-linear correlation (n = 1266, R2  = 0.99).Conclusion: Monitoring infants in the NICU and following ECS using a wireless, cap mounted device provides accurate HR measurements. This alternative approach could confer advantages compared with current methods of HR assessment and warrants further evaluation at birth. [ABSTRACT FROM AUTHOR]

Background: Hospital-acquired viral respiratory tract infections (VRTIs) cause significant morbidity and mortality in neonatal patients. This includes escalation of respiratory support, increased length of hospital stay, and need for home oxygen, as well as higher healthcare costs. To date, no studies have compared population rates of VRTIs across age groups. Aim: Quantify the rates of hospital-acquired VRTIs in our neonatal population compared with other inpatient age groups in Nottinghamshire, UK. Methods: We compared all hospital inpatient PCR-positive viral respiratory samples between 2007 and 2013 and calculated age-stratified rates based on population estimates. Results: From a population of 4,707,217, we identified a previously unrecognised burden of VRTI in neonatal patients, only second to the 0–1-year-old group. Although only accounting for 1.3% of the population, half of the infections were in infants <1 year old and neonatal intensive care unit (NICU) patients. Human rhinovirus was the most dominant virus across the inpatient group, particularly in neonatal patients. Despite a two- to three-fold increase in the rate of positive samples in all groups during the colder months (1.1/1,000 October–March vs. 0.4/1,000 April–September), rates in the NICU did not change throughout the year at 4.3/1,000. Pandemic H1N1 influenza rates were 20 times higher in neonatal patients and infants <1 year old. Conclusion: Good epidemiological and interventional data are needed to help inform visiting and infection control policies to reduce transmission of hospital-acquired viral infections to this vulnerable population, particularly during pandemic seasons. [ABSTRACT FROM AUTHOR]

The centralisation of neonatal intensive care in recent years has improved mortality, particularly of extremely preterm infants, but similar improvements in morbidity, such as neurodevelopmental impairment, have not been seen. Integral to the success of centralisation are specialised neonatal transport teams who provide intensive care prior to and during retrieval of high-risk neonates when in-utero transfer has not been possible. Neonatal retrieval aims to stabilise the clinical condition and then transfer the neonate during a high-risk period for patient. Transport introduces the hazards of noise and vibration; acceleration and deceleration forces; additional handling and temperature fluctuations. The transport team must stabilise the infant fully prior to transport as when on the move they are limited by space and movement to effectively attend to clinical deterioration. Inborn infants have better neurodevelopmental outcome compared with the outborn and aetiology of this seems to be multifactorial with the impact of transport itself during critical illness, remaining unclear. To improve the neurological outcomes for transported infants, it seems imperative to integrate the advancing intensive care neuromonitoring tools into the transport milieu. This review examines current inter-hospital transport neuromonitoring and how new modalities might be applied to the neurocritical care delivered by specialist transport teams. [ABSTRACT FROM AUTHOR]

Inter-hospital transport of premature infants is increasingly common, given the centralisation of neonatal intensive care. However, it is known to be associated with anomalously increased morbidity, most notably brain injury, and with increased mortality from multifactorial causes. Surprisingly, there have been relatively few previous studies investigating the levels of mechanical shock and vibration hazard present during this vehicular transport pathway. Using a custom inertial datalogger, and analysis software, we quantify vibration and linear head acceleration. Mounting multiple inertial sensing units on the forehead and torso of neonatal patients and a preterm manikin, and on the chassis of transport incubators over the duration of inter-site transfers, we find that the resonant frequency of the mattress and harness system currently used to secure neonates inside incubators is [Formula: see text]. This couples to vehicle chassis vibration, increasing vibration exposure to the neonate. The vibration exposure per journey (A(8) using the ISO 2631 standard) was at least 20% of the action point value of current European Union regulations over all 12 neonatal transports studied, reaching 70% in two cases. Direct injury risk from linear head acceleration (HIC15) was negligible. Although the overall hazard was similar, vibration isolation differed substantially between sponge and air mattresses, with a manikin. Using a Global Positioning System datalogger alongside inertial sensors, vibration increased with vehicle speed only above 60 km/h. These preliminary findings suggest there is scope to engineer better systems for transferring sick infants, thus potentially improving their outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Best oxygenation index on day 1 (BOId1) had been shown to predict survival in congenital diaphragmatic hernia (CDH). Serial oxygenation index (OI) may enable better assessment of response to cardiorespiratory support than BOId1. Methods: All antenatally diagnosed CDH from one tertiary neonatal unit were retrospectively reviewed. Oxygenation index at 6, 12, 24, and 48 hours from birth, as well as BOId1, were compared between survivors and nonsurvivors. The area under the curve and receiver operating characteristic (ROC) curves were used to compare serial OI within the first 24 hours and BOId1 between survivors and nonsurvivors. Statistical significance was set at P < .05. Results: Twenty-four patients with CDH (13 survivors, 11 nonsurvivors) were included. Both groups were comparable in demographics and variables that could affect outcome. In terms of nonsurvival, ROC curve analysis demonstrated a sensitivity of 78% for serial OI greater than 252 and 56% for BOId1 greater than 8.5, both having a specificity of 100%. The area under the ROC curve for serial OI and BOId1 were 0.96 and 0.85, respectively. The positive predictive value of serial OI (>252) and BOId1 (>11) for nonsurvival were both 100%, with an negative predictive value of 87% and 76%, respectively. Conclusions: Our preliminary study showed that serial OI in the first 24 hours of life is a good predictor of survival. It is simple to use and has the added advantage of assessing response to medical support in CDH. The results support the need for a large prospective study exploring the potential of serial OI to guide management and prognosis. [Copyright &y& Elsevier]

Maternal diet during pregnancy can program an offspring's risk of disease in later life. Obesity adversely alters renal and adipose tissue function resulting in chronic kidney disease and insulin resistance, respectively, the latter associated with dysregulation of the unfolded protein response (UPR). In view of the current obesity epidemic, we explored the combined effects of in utero early- to midgestational nutrient restriction and postnatal obesity on the UPR in ovine juvenile offspring. Nutrient restriction was coincident with fetal kidney development but prior to exponential adipose tissue deposition. Nutrient restricted (NR) and normal diet (control) offspring were exposed to an obesogenic environment throughout adolescence, resulting in similar degrees of juvenile obesity. NR offspring showed enhanced adipose tissue dysregulation characterized by activation of the UPR, perturbed insulin signaling, and marked inflammation, as demonstrated by increased abundance of crownlike structures and proinflammatory genes. Conversely, in renal tissue NR offspring had marked attenuation of cellular stress and inflammation evident as reduced activation of the UPR, down-regulation of proinflammatory genes, and less histological damage. In conclusion, obesity-related activation of the UPR can be determined by the in utero nutritional environment, demonstrating organ-specific effects dependent on the developmental phase targeted within the fetus. [ABSTRACT FROM AUTHOR]

Background: Maternal nutrient restriction (NR) during pregnancy can induce obesity and insulin resistance in the offspring but the mechanisms remain unclear. Increasing adiposity is associated with adipose tissue macrophage accumulation and inflammation predisposing to the metabolic syndrome. Aims: To determine the effects of maternal NR on the expression of key genes implicated in this process. Those juveniles exposed to late NR develop insulin resistance and increased adiposity (Gardner 2005). Methods: 17 singleton bearing sheep received either 100% metabolisable energy (ME) throughout pregnancy (controls), and 50% ME from days 0 to 30 (Early NR) or days 110 to 147 (Late NR). At 1 year perirenal adipose tissue (PAT) was analysed for the mRNA expression of CD68 (macrophage marker), toll-like receptor 4 (TLR4) and IL-6. Results: Weight at birth and 1 year were not different between the groups. Irrespective of maternal diet, TLR4 correlated with IL-6 and CD68 (R²=0.92 and 0.69, P<0.0001). Conclusions: Maternal NR induces macrophage accumulation and inflammation within adipose tissue of offspring and in late NR results in insulin resistance and increased adiposity. [ABSTRACT FROM AUTHOR]