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AIM Neonatal encephalopathy (NE) is associated with altered cognitive, motor, sensory abilities and behavioural outcomes. This case-control study aimed to assess whether Quality of Life (QoL) and sleep disorders are affected in older children following NE compared to age-matched controls. METHODS Children at school-age post-NE were recruited and compared to age-matched controls. Sleep and QoL were assessed with the Pediatric Quality of Life Inventory and the Child Sleep Habit Questionnaire. RESULTS One hundred children were recruited with an age range of 4-6 years, including children post-NE (n=45) and age-matched controls (n = 55). Significantly higher pathological sleep scores were evident in 58% of children post-NE compared to controls (43.8 vs 40.2; p = 0.001). Children post-NE had increased bedtime resistance (p = 0.028) and sleep anxiety (p = 0.01) compared to controls. Children in the post-NE group had lower total QoL scores versus controls (mean score 82.5 vs 95.8; p

Summary Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines interleukin (IL)‐1β, IL‐1ra and IL‐18 are activated by the nucleotide‐binding and oligomerization domain (NOD)‐, leucine‐rich repeat domain (LRR)‐ and NOD‐like receptor protein 3 (NLRP3) inflammasome; furthermore, we aimed to examine the role of the inflammasome multiprotein complex involved in proinflammatory responses from the newborn period to childhood in NE. Cytokine concentrations were measured by multiplex enzyme‐linked immunosorbent assay (ELISA) in neonates and children with NE in the absence or presence of lipopolysaccharide (LPS) endotoxin. We then investigated expression of the NLRP3 inflammasome genes, NLRP3, IL‐1β and ASC by polymerase chain reaction (PCR). Serum samples from 40 NE patients at days 1 and 3 of the first week of life and in 37 patients at age 4–7 years were analysed. An increase in serum IL‐1ra and IL‐18 in neonates with NE on days 1 and 3 was observed compared to neonatal controls. IL‐1ra in NE was decreased to normal levels at school age, whereas serum IL‐18 in NE was even higher at school age compared to school age controls and NE in the first week of life. Percentage of LPS response was higher in newborns compared to school‐age NE. NLRP3 and IL‐1β gene expression were up‐regulated in the presence of LPS in NE neonates and NLRP3 gene expression remained up‐regulated at school age in NE patients compared to controls. Increased inflammasome activation in the first day of life in NE persists in childhood, and may increase the window for therapeutic intervention., Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Cytokine concentrations were measured by multiplex ELISA in neonates and children with NE in the absence or presence of LPS endotoxin. Increased inflammasome activation in the first day of life in NE persists in childhood

AIM To examine pro- and anti-inflammatory cytokines in children with cerebral palsy (CP) at baseline and in response to endotoxin (lipopolysaccharide), and correlate outcomes compared with age-matched comparisons, to evaluate their ability to mount an immune response. METHOD Serum cytokines were assessed in 12 children (eight males, four females; mean age 10y 1mo [SD 1y 8mo], 6-16y) with CP against 12 age-matched comparisons (eight males, four females; mean age 9y 1mo [SD 1y 1mo]). Pro- and anti-inflammatory cytokines (interleukin-1β, interleukin-2, interleukin-6, interleukin-8, interleukin-10, interleukin-18, tumour necrosis factor [TNF]-α, TNF-β, interferon-γ, granulocyte-macrophage colony-stimulating factor [GM-CSF], vascular endothelial growth factor [VEGF], erythropoietin, and interleukin-1 receptor antagonist) were measured at baseline and in response to in vitro simulation with lipopolysaccharide by multiplex enzyme-linked immunosorbent assay. RESULTS Significantly higher erythropoietin was found at baseline in children with CP compared with the comparison group. There was a strong response to lipopolysaccharide for interleukin-8, VEGF, TNF-α, and GM-CSF in both children with CP and the comparison group; however, there was significant lipopolysaccharide hyporesponsiveness in children with CP compared with the comparison group for interleukin-1α, interleukin-1β, interleukin-2, and interleukin-6. INTERPRETATION Altered cytokine responses in children with CP compared with the comparison group demonstrate an altered inflammatory state that may contribute to ongoing sequelae and could be a target for therapy. WHAT THIS PAPER ADDS Altered inflammatory responses persist in children with cerebral palsy (CP). Erythropoietin is elevated in children with CP compared with the comparison group. Children with CP have reduced interleukin-1α, interleukin-1β, interleukin-2, and interleukin-6 inflammatory responses to lipopolysaccharide.

Neonatal encephalopathy (NE) is associated with abnormality of neurological function and involves multiorgan dysfunction. There are long-term complications such as cerebral palsy and developmental delay. Cardiac, renal, neurological and other organ dysfunctions are well described. Haematological dysfunction is relatively common and includes anaemia, thrombocytopenia, monocyte and neutrophil activation, hypofibrinogenemia and coagulopathy. There is a lack of consensus definitions of hematological parameters and optimal levels for intervention due to the lack of interventional studies in term neonates and the lack of knowledge of the optimal values during therapeutic hypothermia. However, derangements in hematological values are also associated with neurodevelopmental outcomes. This article outlines the different hematological complications associated with NE and therapeutic hypothermia and suggests a framework for management.

BACKGROUND: Cerebral palsy (CP) is a heterogeneous group of non‐progressive disorders of posture or movement, caused by a lesion of the developing brain. Osteoporosis is common in children with cerebral palsy, particularly in children with reduced gross motor function, and leads to an increased risk of fractures. Gross motor function in children with CP can be categorised using a tool called the Gross Motor Function Classification System (GMFCS). Bisphosphonate increases bone mineral density (BMD) and reduces fracture rates. Bisphosphonate is used widely in the treatment of adult osteoporosis. However, the use of bisphosphonate in children with CP remains controversial, due to a paucity of evidence and a lack of recent trials examining the efficacy and safety of bisphosphonate use in this population. OBJECTIVES: To examine the efficacy and safety of bisphosphonate therapy in the treatment of low BMD or secondary osteoporosis (or both) in children with cerebral palsy (GMFCS Levels III to V) who are under 18 years of age. SEARCH METHODS: In September 2020, we searched CENTRAL, MEDLINE, Embase, six other databases, and two trial registers for relevant studies. We also searched the reference lists of relevant systematic reviews, trials, and case studies identified by the search, and contacted the authors of relevant studies in an attempt to identify unpublished literature. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs), and quasi‐RCTs, comparing at least one bisphosphonate (given at any dose, orally or intravenously) with placebo or no drug, for the treatment of low BMD or osteoporosis in children up to 18 years old, with cerebral palsy (GMFCS Levels III to V). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We were unable to conduct any meta‐analyses due to insufficient data, and therefore provide a narrative assessment of the results. MAIN RESULTS: We found two relevant RCTs (34 participants). Both studies included participants with non‐ambulatory CP or CP and osteoporosis. Participants in both studies were similar in severity of CP, age distribution, and sex distribution. The two trials used different bisphosphonate medications and different intervention durations, but further comparison of the interventions was not possible due to a lack of published data from one trial. One trial received funding and support from research, academic, and hospital foundations, with pharmaceutical companies providing components of the calcium and vitamin supplement; the other trial did not report sources of funding. We judged one study at an overall high risk of bias; the other as overall unclear risk of bias. Primary outcome. Compared to placebo or no treatment, both studies provided very low certainty evidence of improved BMD at least four months post‐intervention in children treated with bisphosphonate. Only one study (12 participants) provided sufficient detail to assess a measure of the effect, and reported an improvement at six months post‐intervention in lumbar spine z‐score (mean difference (MD) 18%, 95% confidence interval (CI) 6.57 to 29.43; very low certainty evidence). Secondary outcomes. Very low certainty evidence from one study found that bisphosphonate reduced serum N‐telopeptides (NTX) more than placebo; the other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced NTX, but did not compare groups. One study reported inconclusive results between groups for serum bone‐specific alkaline phosphatase (BAP). The other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced BAP, but did not compare groups. Neither study reported data for the effect of bisphosphonate treatment on changes in volumetric BMD in the distal radius or tibia, changes in fracture frequency, bone pain, or quality of life. One study reported that two participants had febrile events noted during their first dosing schedule, but no further adverse events were reported in either relevant study. AUTHORS' CONCLUSIONS: Based on the available evidence, there is very low certainty evidence that bisphosphonate treatment may improve bone health in children with cerebral palsy. We could only include one study with 14 participants in the assessment of the effect size; therefore, the precision of the effect estimate is low. We could only evaluate one planned primary outcome, as there was insufficient detail reported in the relevant studies. Further research from RCTs on the effect and safety of bisphosphonate to improve bone health in children with cerebral palsy is required. These studies should clarify the optimal standard treatment regarding weight‐bearing exercises, vitamin D and calcium supplementation, and should include fracture frequency as a primary outcome.

We enumerated conventional and innate lymphocyte populations in neonates with neonatal encephalopathy (NE), school-age children post-NE, children with cerebral palsy and age-matched controls. Using flow cytometry, we demonstrate alterations in circulating T, B and natural killer cell numbers. Invariant natural killer T cell and Vδ2+ γδ T cell numbers and frequencies were strikingly higher in neonates with NE, children post-NE and children with cerebral palsy compared to age-matched controls, whereas mucosal-associated invariant T cells and Vδ1 T cells were depleted from children with cerebral palsy. Upon stimulation ex vivo, T cells, natural killer cells and Vδ2 T cells from neonates with NE more readily produced inflammatory cytokines than their counterparts from healthy neonates, suggesting that they were previously primed or activated. Thus, innate and conventional lymphocytes are numerically and functionally altered in neonates with NE and these changes may persist into school-age.

Background and objective A variety of suction catheters (type, size and design) are recommended for oropharyngeal suctioning of meconium during newborn resuscitation, but it is not known which performs best. In this study we compared different sizes of soft catheters, the Yankauer (YK) and the portable bulb syringe (BS), in suctioning a solution of varying viscosity. Methods Simulated meconium (SM) was made using commercial canned pea soup in two strengths, fullstrength thick-particulate (TP) and 50% strained soup diluted with water, that is, thin-non-particulate (TnP), with saline as a control. A 20 ml aliquot of solution was suctioned over 5 s with each device using an electrical suction pump set at two different pressures, 100 and 150 mm Hg (21 kpa). In addition, the negative pressure of five BSs was measured in order to compare generated pressures with the alternative devices. Results The YK and BS suctioned almost 100% of saline, while the 6F and 8F catheters suctioned 50% and 75% saline, respectively. The YK suctioned 100% of TnP, saline and 30% of TP. At reduced suction pressures (100 and 50 mm Hg) the YK also suctioned all TnP. The 12F and 14F catheters suctioned a minimal amount of TP, whereas YK was the most efficient, suctioning 30% of TP. The mean negative pressure generated with five BSs was 78 and 71 mm Hg by a male and female operator, respectively. Conclusions The YK and BS outperform the catheters in suctioning SM. The YK is the best for TP, but all devices perform poorly in suctioning fluid of this consistency.