Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes

Abstract Background Neonatal encephalopathy (NE) contributes substantially to child mortality and disability globally. We compared cytokine profiles in term Ugandan neonates with and without NE, with and without perinatal infection or inflammation and identified biomarkers predicting neonatal and early childhood outcomes. Methods In this exploratory biomarker study, serum IL-1α, IL-6, IL-8, IL-10, TNFα, and VEGF (<12 h) were compared between NE and non-NE infants with and without perinatal infection/inflammation. Neonatal (severity of NE, mortality) and early childhood (death or neurodevelopmental impairment to 2.5 years) outcomes were assessed. Predictors of outcomes were explored with multivariable linear and logistic regression and receiver-operating characteristic analyses. Results Cytokine assays on 159 NE and 157 non-NE infants were performed; data on early childhood outcomes were available for 150 and 129, respectively. NE infants had higher IL-10 (p < 0.001), higher IL-6 (p < 0.017), and lower VEGF (p < 0.001) levels. Moderate and severe NE was associated with higher IL-10 levels compared to non-NE infants (p < 0.001). Elevated IL-1α was associated with perinatal infection/inflammation (p = 0.013). Among NE infants, IL-10 predicted neonatal mortality (p = 0.01) and adverse early childhood outcome (adjusted OR 2.28, 95% CI 1.35–3.86, p = 0.002). Conclusions Our findings support a potential role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy. Impact Neonatal encephalopathy is a common cause of child death and disability globally. Inflammatory cytokines are potential biomarkers of encephalopathy severity and outcome. In this Ugandan health facility-based cohort, neonatal encephalopathy was associated with elevated serum IL-10 and IL-6, and reduced VEGF at birth. Elevated serum IL-10 within 12 h after birth predicted severity of neonatal encephalopathy, neonatal mortality, and adverse early childhood developmental outcomes, independent of perinatal infection or inflammation, and provides evidence to the contribution of the inflammatory processes. Our findings support a role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy in a sub-Saharan African cohort.

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Early Childhood Outcomes After Neonatal Encephalopathy in Uganda: A Cohort Study

EClinicalMedicine ◽

10.1016/j.eclinm.2018.12.001 ◽

2018 ◽

Vol 6 ◽

pp. 26-35 ◽

Cited By ~ 5

Author(s):

Cally J. Tann ◽

Emily L. Webb ◽

Rachel Lassman ◽

Julius Ssekyewa ◽

Margaret Sewegaba ◽

...

Keyword(s):

Early Childhood ◽

Cohort Study ◽

Neonatal Encephalopathy ◽

Early Childhood Outcomes

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North Dakota Early Childhood Outcomes Project

PsycEXTRA Dataset ◽

10.1037/e518782010-001 ◽

2013 ◽

Keyword(s):

Early Childhood ◽

North Dakota ◽

Early Childhood Outcomes

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Caesarean section and increased neonatal mortality risk in meta‐analysis of 33 sub‐Saharan Africa Demographic and Health Surveys

Acta Paediatrica ◽

10.1111/apa.16032 ◽

2021 ◽

Author(s):

Tawa Olukade ◽

Olalekan A Uthman

Keyword(s):

Caesarean Section ◽

Neonatal Mortality ◽

Mortality Risk ◽

Health Surveys ◽

Meta Analysis ◽

Sub Saharan Africa ◽

Demographic And Health Surveys ◽

Sub Saharan

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Improving neonatal mortality in sub-Saharan Africa: any cause for optimism?

Journal of Perinatology ◽

10.1038/jp.2011.53 ◽

2011 ◽

Vol 31 (12) ◽

pp. 745-748 ◽

Cited By ~ 10

Author(s):

C Engmann

Keyword(s):

Neonatal Mortality ◽

Sub Saharan Africa ◽

Sub Saharan

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GHRH secretion from a pancreatic neuroendocrine tumor causing gigantism in a patient with MEN1

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-20-0208 ◽

2021 ◽

Vol 2021 ◽

Author(s):

Vinaya Srirangam Nadhamuni ◽

Donato Iacovazzo ◽

Jane Evanson ◽

Anju Sahdev ◽

Jacqueline Trouillas ◽

...

Keyword(s):

Neuroendocrine Tumour ◽

Primary Tumour ◽

Elevated Serum ◽

Pancreatic Neuroendocrine Tumor ◽

Pituitary Surgery ◽

List Type ◽

Ki 67 ◽

Subtotal Parathyroidectomy ◽

Cross Sectional ◽

Ectopic Acromegaly

Summary A male patient with a germline mutation in MEN1 presented at the age of 18 with classical features of gigantism. Previously, he had undergone resection of an insulin-secreting pancreatic neuroendocrine tumour (pNET) at the age of 10 years and had subtotal parathyroidectomy due to primary hyperparathyroidism at the age of 15 years. He was found to have significantly elevated serum IGF-1, GH, GHRH and calcitonin levels. Pituitary MRI showed an overall bulky gland with a 3 mm hypoechoic area. Abdominal MRI showed a 27 mm mass in the head of the pancreas and a 6 mm lesion in the tail. Lanreotide-Autogel 120 mg/month reduced GHRH by 45% and IGF-1 by 20%. Following pancreaticoduodenectomy, four NETs were identified with positive GHRH and calcitonin staining and Ki-67 index of 2% in the largest lesion. The pancreas tail lesion was not removed. Post-operatively, GHRH and calcitonin levels were undetectable, IGF-1 levels normalised and GH suppressed normally on glucose challenge. Post-operative fasting glucose and HbA1c levels have remained normal at the last check-up. While adolescent-onset cases of GHRH-secreting pNETs have been described, to the best of our knowledge, this is the first reported case of ectopic GHRH in a paediatric setting leading to gigantism in a patient with MEN1. Our case highlights the importance of distinguishing between pituitary and ectopic causes of gigantism, especially in the setting of MEN1, where paediatric somatotroph adenomas causing gigantism are extremely rare. Learning points It is important to diagnose gigantism and its underlying cause (pituitary vs ectopic) early in order to prevent further growth and avoid unnecessary pituitary surgery. The most common primary tumour sites in ectopic acromegaly include the lung (53%) and the pancreas (34%) (1): 76% of patients with a pNET secreting GHRH showed a MEN1 mutation (1). Plasma GHRH testing is readily available in international laboratories and can be a useful diagnostic tool in distinguishing between pituitary acromegaly mediated by GH and ectopic acromegaly mediated by GHRH. Positive GHRH immunostaining in the NET tissue confirms the diagnosis. Distinguishing between pituitary (somatotroph) hyperplasia secondary to ectopic GHRH and pituitary adenoma is difficult and requires specialist neuroradiology input and consideration, especially in the MEN1 setting. It is important to note that the vast majority of GHRH-secreting tumours (lung, pancreas, phaeochromocytoma) are expected to be visible on cross-sectional imaging (median diameter 55 mm) (1). Therefore, we suggest that a chest X-ray and an abdominal ultrasound checking the adrenal glands and the pancreas should be included in the routine work-up of newly diagnosed acromegaly patients.

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Beyond ratios - flexible and resilient nurse staffing options to deliver cost-effective hospital care and address staff shortages: a simulation and economic modelling study

10.1101/2020.11.30.20240945 ◽

2020 ◽

Author(s):

Peter Griffiths ◽

Christina Saville ◽

Jane E Ball ◽

Jeremy Jones ◽

Thomas Monks

Keyword(s):

Cost Effectiveness ◽

Significant Proportion ◽

Nurse Staffing ◽

Cost Savings ◽

Cost Effective ◽

Adverse Outcomes ◽

List Type ◽

Economic Modelling ◽

The Face ◽

Hospital Wards

AbstractBackgroundIn the face of pressure to contain costs and make best use of scarce nurses, flexible staff deployment (floating staff between units and temporary hires) guided by a patient classification system may appear an efficient approach to meeting variable demand for care in hospitals.ObjectivesWe modelled the cost-effectiveness of different approaches to planning baseline numbers of nurses to roster on general medical/surgical units while using flexible staff to respond to fluctuating demand.Design and SettingWe developed an agent-based simulation model, where units move between being understaffed, adequately staffed or overstaffed as staff supply and demand, measured by the Safer Nursing Care Tool, varies. Staffing shortfalls are addressed firstly by floating staff from overstaffed units, secondly by hiring temporary staff. We compared a standard staffing plan (baseline rosters set to match average demand) with a ‘resilient’ plan set to match higher demand, and a ‘flexible’ plan, set at a lower level. We varied assumptions about temporary staff availability. We estimated the effect of unresolved low staffing on length of stay and death, calculating cost per life saved.ResultsStaffing plans with higher baseline rosters led to higher costs but improved outcomes. Cost savings from low baseline staff largely arose because shifts were left under staffed. Cost effectiveness for higher baseline staff was improved with high temporary staff availability. With limited temporary staff available, the resilient staffing plan (higher baseline staff) cost £9,506 per life saved compared to the standard plan. The standard plan cost £13,967 per life saved compared to the flexible (low baseline) plan. With unlimited temporary staff, the resilient staffing plan cost £5,524 per life saved compared to the standard plan and the standard plan cost £946 per life saved compared with the flexible plan. Cost-effectiveness of higher baseline staffing was more favourable when negative effects of high temporary staffing were modelled.ConclusionFlexible staffing can be guided by shift-by-shift measurement of patient demand, but proper attention must be given to ensure that the baseline number of staff rostered is sufficient.In the face of staff shortages, low baseline staff rosters with high use of flexible staff on hospital wards is not an efficient or effective use of nurses whereas high baseline rosters may be cost-effective. Flexible staffing plans that minimise the number of nurses routinely rostered are likely to harm patients because temporary staff may not be available at short notice.Study registration: ISRCTN 12307968Tweetable abstractEconomic model of hospital wards shows low baseline staff levels with high use of flexible staff are not cost-effective and don’t solve nursing shortages].What is already known?Because nursing is the largest staff group, accounting for a significant proportion of hospital’s variable costs, ward nurse staffing is frequently the target of cost containment measuresStaffing decisions need to address both the baseline staff establishment to roster, and how best to respond to fluctuating demand as patient census and care needs varyFlexible deployment of staff, including floating staff and using temporary hires, has the potential to minimise expenditure while meeting varying patient need, but high use of temporary staff may be associated with adverse outcomes.What this paper addsOur simulation shows that low baseline staff rosters that rely heavily on flexible staff increase the risk of patient death and provide cost savings largely because wards are often left short staffed under real world availability of temporary staff.A staffing plan set to meet average demand appears to be cost effective compared to a plan with a lower baseline but is still associated with frequent short staffing despite the use of flexible deployments.A staffing plan with a higher baseline, set to meet demand 90% of the time, is more resilient in the face of variation and may be highly cost effective

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Texture Consumption Patterns of 8- to 12-Month-Old Infants: A Reflection of Typical Feeding Development

American Journal of Speech-Language Pathology ◽

10.1044/2021_ajslp-21-00048 ◽

2021 ◽

pp. 1-10

Author(s):

Amy L. Delaney ◽

Megan Van Hoorn ◽

Sarah Staskiewicz ◽

Mary Beth Feuling ◽

Stephanie Pladies ◽

...

Keyword(s):

Early Childhood ◽

Consumption Patterns ◽

List Type ◽

Typically Developing ◽

Accurate Identification ◽

Feeding Disorder ◽

Healthy Infants ◽

Age Appropriate ◽

Pediatric Feeding ◽

Feeding Development

Purpose The lack of age-appropriate expectations for the acquisition of feeding skills and consumption of textured food in early childhood inhibits early and accurate identification of developmental delay in feeding and pediatric feeding disorder. The objective of this study was to describe texture intake patterns in a cohort of typically developing infants between 8 and 12 months of age, with the aim of informing future research to establish targets for feeding skill acquisition. Method Using cross-sectional methodology, we studied the presence of liquid and solid textures and drinking methods in the diet, consumption patterns by texture and drinking methods, and caloric intake by texture via caregiver questionnaire and 3-day dietary intake record in 63 healthy infants between 8 and 12 months of age. Descriptive statistics and a one-way analysis of variance were conducted to compare the effect of age on texture intake patterns. Results Findings reveal rapid advancement of intake patterns for texture overall and for energy intake by texture between 8 and 12 months of age. Whereas liquids continue to provide a large proportion of total energy through this time, solids contribute an equal proportion of energy by 12 months of age. Conclusions This study describes texture intake patterns in a cohort of typically developing infants between 8 and 12 months of age by examining the presence of texture and drinking methods, liquid and solid consumption patterns, and energy intake by texture. When applied to data from a future population sample, findings will provide a threshold for age expectations for typical and disordered feeding development to aid in the detection of developmental delay in feeding and pediatric feeding disorder. What Is Known: Expectations regarding early feeding development have been focused on nutrition parameters. Lack of standardized, age-appropriate expectations for texture progression in infancy and early childhood inhibits early and accurate identification and treatment of pediatric feeding disorder. What Is New: We have described changes in dietary composition by texture and drinking method in healthy infants. Together with nutritional composition, this study describes a more comprehensive assessment of infant feeding, particularly to clinicians who need to diagnose feeding skill deficits. Supplemental Material https://doi.org/10.23641/asha.16879615

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Troponin I as an Independent Biomarker of Outcome in Children with Systemic Inflammatory Response

Journal of Pediatric Intensive Care ◽

10.1055/s-0041-1731432 ◽

2021 ◽

Author(s):

Heitor P. Leite ◽

Rodrigo Medina ◽

Emilio L. Junior ◽

Tulio Konstantyner

Keyword(s):

Inflammatory Response ◽

Chronic Diseases ◽

Troponin I ◽

Elevated Serum ◽

Oxygenation Index ◽

Serum Lactate ◽

Systemic Inflammatory Response ◽

Adverse Outcomes ◽

Critically Ill Children ◽

Logistic Organ Dysfunction

AbstractTroponin I (cTnI) is a biomarker of myocardial injury with implications for clinical outcomes. However, other contributing factors that could affect outcomes have not been uniformly considered in pediatric studies. We tested the hypothesis that there is an association between admission serum cTnI and outcomes in critically ill children taking into account the magnitude of the acute systemic inflammatory response syndrome (SIRS), serum lactate concentrations, and nutritional status of the patient. Second, we tested for potential factors associated with elevated serum cTnI. This was a prospective cohort study in 104 children (median age: 21.3 months) consecutively admitted to a pediatric intensive care unit (PICU) of a teaching hospital with SIRS and without previous chronic diseases. Primary outcome variables were PICU-free days, ventilator-free days, and 30-day mortality. Exposure variables: serum cTnI concentration on admission, revised pediatric index of mortality (PIM2), pediatric logistic organ dysfunction (PELOD-2), hypotensive shock, C-reactive protein, procalcitonin, and serum lactate on admission, and malnutrition. Elevated cTnI (>0.01 μg/L) was observed in 24% of patients, which was associated with the reduction of ventilator-free days (β coefficient = − 4.97; 95% confidence interval [CI]: −8.03; −1.91) and PICU-free days (β coefficient = − 5.76; 95% CI: −8.97; −2.55); all patients who died had elevated serum cTnI. The increase of 0.1 μg/L in cTnI concentration resulted in an elevation of 2 points in the oxygenation index (β coefficient = 2.0; 95% CI: 1.22; 2.78, p < 0.001). The PIM2 score, hypotensive shock in the first 24 hours, and serum lactate were independently associated with elevated cTnI on admission. We conclude that elevated serum cTnI on admission is independently associated with adverse outcomes in children with SIRS and without associated chronic diseases.

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Prevalence of Eclampsia and its Maternal-fetal outcomes at Ghandi Memorial Hospital, Addis Ababa Ethiopia, 2019. Retrospective study

10.21203/rs.3.rs-33298/v1 ◽

2020 ◽

Author(s):

Addisu Yeshambel ◽

Walellign Anmut

Keyword(s):

Magnesium Sulfate ◽

Addis Ababa ◽

Fetal Outcome ◽

Cross Sectional Study ◽

Adverse Outcomes ◽

Morbidity And Mortality ◽

Memorial Hospital ◽

Fetal Outcomes ◽

Cross Sectional ◽

Sub Saharan

Abstract Background: Eclamptic disorder of pregnancy is one of the common problems in sub-Saharan countries and forms one of the deadly triads along with hemorrhage and infection which complicates maternal and fetal outcomes of pregnancy. To assess the prevalence of eclampsia and its maternal and fetal outcome in Ghandi Memorial Hospital, Addis Ababa Ethiopia, 2019.Methods: A descriptive retrospective cross-sectional study was used on randomly selected 185 women who attended delivery at Ghandi memorial Hospital from 1st of September 2017 to –last of August 2018. Data were analyzed using SPSS version 25 software. Descriptive statistics were used to calculate frequencies and percentages and data was presented using texts and, tables. Results: Out of the 2,973 deliveries, the prevalence of eclampsia was found to be 16.1%. About 89.7% had reported a history of prior pregnancy-induced hypertension and 73.5% induced their current pregnancy following eclampsia. From mothers required interventions to terminate the pregnancy by induction, 47.8% ended by cesarean section secondary to non-reassuring fetal status (29.2%). The majority (91.9%) had taken magnesium sulfate for the management of convulsion and 86.5% had taken hydralazine for hypertension management. Abruption of the placenta (96.2%), postpartum-hemorrhage (89.2%), and HEELP syndrome (83.8 %) were major maternal adverse outcomes reported, and 33% of pregnancy was ended as stillbirth followed by low birth weight (28.6%). Over 53.6% of delivered babies had an APGAR score of less 4 and 30.4% of neonates required admission to nursery/NICU referral. Conclusion: The prevalence of eclampsia was high, with corresponding high maternal and perinatal morbidity and mortality. Increasing early detection before pregnancy, antenatal screening, and use of magnesium sulfate to control convulsions will reduce the disorder and associated morbidity and mortality for both mother and fetus.

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