Probiotics, prematurity and neurodevelopment: Follow-up of a randomised trial

Objective To determine the impact of one probiotics combination on the neurodevelopment of very preterm children at 2–5 years corrected gestational age (CA). Design Follow-up study of survivors of a double-blinded, placebo-controlled, randomised trial of probiotic effects on late-onset sepsis in very preterm infants that found reduced necrotising enterocolitis. setting 10 tertiary perinatal centres in Australia and New Zealand. Patients 1099 very preterm infants born <32 weeks’ gestation and weighing <1500 g. Intervention Probiotics (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis) or placebo administered from birth until discharge home or term CA, whichever came sooner. Main outcome measures Major neurodevelopmental impairment comprised any of moderate/severe cerebral palsy (Gross Motor Function Classification System score 2–5), motor impairment (Bayley-III Motor Composite Scale <–2SD or Movement Assessment Battery for Children <15th centile if ≫42 months’ CA), cognitive impairment (Bayley-III Composite Cognitive or Language Scales <–2SD or Wechsler Preschool and Primary Scale of Intelligence Full Scale Intelligence Quotient <–2SD if ≫42 months’ CA), blindness or deafness. Results Outcome data were available for 735 (67%) participants, with 71 deaths and 664/1028 survivors assessed at a mean age of 30 months. Survival free of major neurodevelopmental impairment was comparable between groups (probiotics 281 (75.3%) vs placebo 271 (74.9%); relative risk 1.01 (95% CI 0.93 to 1.09)). Rates of deafness were lower in probiotic-treated children (0.6% vs 3.4%). Conclusion Administration of the probiotics combination Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis to very preterm babies from soon after birth until discharge home or term CA did not adversely affect neurodevelopment or behaviour in early childhood

ERK1/2 signaling dominates over RhoA signaling in regulating early changes in RNA expression induced by endothelin-1 in neonatal rat cardiomyocytes

Cardiomyocyte hypertrophy is associated with changes in gene expression. Extracellular signal-regulated kinases 1/2 (ERK1/2) and RhoA [activated by hypertrophic agonists (e.g. endothelin-1)] regulate gene expression and are implicated in the response, but their relative significance in regulating the cardiomyocyte transcriptome is unknown. Our aim was to establish the significance of ERK1/2 and/or RhoA in the early cardiomyocyte transcriptomic response to endothelin-1.Cardiomyocytes were exposed to endothelin-1 (1 h) with/without PD184352 (to inhibit ERK1/2) or C3 transferase (C3T, to inhibit RhoA). RNA expression was analyzed using microarrays and qPCR. ERK1/2 signaling positively regulated approximately 65% of the early gene expression response to ET-1 with a small (approximately 2%) negative effect, whereas RhoA signaling positively regulated approximately 10% of the early gene expression response to ET-1 with a greater (approximately 14%) negative contribution. Of RNAs non-responsive to endothelin-1, 66 or 448 were regulated by PD184352 or C3T, respectively, indicating that RhoA had a more significant effect on baseline RNA expression. mRNAs upregulated by endothelin-1 encoded a number of receptor ligands (e.g. Ereg, Areg, Hbegf) and transcription factors (e.g. Abra/Srf) that potentially propagate the response.ERK1/2 dominates over RhoA in the early transcriptomic response to endothelin-1. RhoA plays a major role in maintaining baseline RNA expression but, with upregulation of Abra/Srf by endothelin-1, RhoA may regulate changes in RNA expression over longer times. Our data identify ERK1/2 as a more significant node than RhoA in regulating the early stages of cardiomyocyte hypertrophy

Participation in physical play and leisure : developing a theory- and evidence-based intervention for children with motor impairments

Peer reviewedPublisher PD

The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks’ gestation

Background: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and long-term respiratory and neurological morbidity in very preterm infants. While survival rates of very preterm infants have increased over the past two decades there has been no decrease in the rate of BPD in surviving infants. Evidence from animal and human studies has suggested potential benefits of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, in the prevention of chronic lung disease. This randomised controlled trial aims to determine the effectiveness of supplementary DHA in reducing the rate of BPD in infants less than 29 weeks’ gestation. Methods/design: This is a multicentre, parallel group, randomised, blinded and controlled trial. Infants born less than 29 weeks’ gestation, within 3 days of first enteral feed and with parent informed consent are eligible to participate. Infants will be randomised to receive an enteral emulsion containing DHA or a control emulsion without DHA. The DHA emulsion will provide 60 mg/kg/day of DHA. The study emulsions will continue to 36 weeks’ postmenstrual age (PMA). The primary outcome is BPD as assessed by the requirement for supplemental oxygen and/or assisted ventilation at 36 weeks’ PMA. Secondary outcomes include the composite of death or BPD; duration of respiratory support and hospitalisation, major neonatal morbidities. The target sample size is 1244 infants (622 per group), which will provide 90 % power to detect a clinically meaningful absolute reduction of 10 % in the incidence of BPD between the DHA and control emulsion (two tailed α =0.05). Discussion: DHA supplementation has the potential to reduce respiratory morbidity in very preterm infants. This multicentre trial will provide evidence on whether an enteral DHA supplement reduces BPD in very preterm infants

Allergic reactions to the Ad26.COV2.S vaccine in South Africa

BACKGROUND : The Janssen-Ad26.COV2.S vaccine is authorized for use in several countries, with more than 30 million doses administered. Mild and severe allergic adverse events following immunization (AEFI) have been reported. OBJECTIVE : We sought to detail allergic reactions reported during the Sisonke phase 3B study in South Africa. METHODS : A single dose of the Ad26.COV2.S vaccine was administered to 4,77,234 South African health care workers between February 17 and May 17, 2021. Monitoring of adverse events used a combination of passive reporting and active case finding. Telephonic contact was attempted for all adverse events reported as “allergy.” Anaphylaxis adjudication was performed using the Brighton Collaboration and National Institute of Allergy and Infectious Disease case definitions. RESULTS : Only 251 (0.052%) patients reported any allergic-type reaction (<1 in 2000), with 4 cases of adjudicated anaphylaxis (Brighton Collaboration level 1, n = 3) (prevalence of 8.4 per million doses). All anaphylaxis cases had a previous history of drug or vaccine-associated anaphylaxis. Cutaneous allergic reactions were the commonest nonanaphylatic reactions and included self-limiting, transient/localized rashes requiring no health care contact (n = 92) or isolated urticaria and/or angioedema (n = 70; median onset, 48 [interquartile range, 11.5-120] hours postvaccination) that necessitated health care contact (81%), antihistamine (63%), and/or systemic/topical corticosteroid (16%). All immediate (including adjudicated anaphylaxis) and most delayed AEFI (65 of 69) cases resolved completely. CONCLUSIONS : Allergic AEFI are rare following a single dose of Ad26.COV, with complete resolution in all cases of anaphylaxis. Although rare, isolated, delayed-onset urticaria and/or angioedema was the commonest allergic AEFI requiring treatment, with nearly half occurring in participants without known atopic disease.The Sinsonke Study is funded by the South African Medical Research Council. J.P.’s research is supported by a career development award and financial support from the National Institutes of Health; the European Developing Clinical Trials Partnership (EDCTP2 Program supported by the European Union; and the SA Medical Research Council and National Research Foundation.https://www.sciencedirect.com/journal/journal-of-allergy-and-clinical-immunology-globalhj2023Paediatrics and Child HealthSchool of Health Systems and Public Health (SHSPH

The Public Playground Paradox: "Child’s Joy" or Heterotopia of Fear?

Literature depicts children of the Global North withdrawing from public space to“acceptable islands”. Driven by fears both of and for children, the publicplayground – one such island – provides clear-cut distinctions between childhoodand adulthood. Extending this argument, this paper takes the original approach oftheoretically framing the playground as a heterotopia of deviance, examining –for the first time – three Greek public playground sites in relation to adjacentpublic space. Drawing on an ethnographic study in Athens, findings show fear tounderpin surveillance, control and playground boundary porosity. Normativeclassification as “children’s space” discourages adult engagement. However, in anovel and significant finding, a paradoxical phenomenon sees the playground’spresence simultaneously legitimizing playful behaviour in adjacent public spacefor children and adults. Extended playground play creates alternate orderings andnegotiates norms and hierarchies, suggesting significant wider potential toreconceptualise playground-urban design for an intergenerational public realm

Childhood in Sociology and Society: The US Perspective

The field of childhood studies in the US is comprised of cross-disciplinary researchers who theorize and conduct research on both children and youth. US sociologists who study childhood largely draw on the childhood literature published in English. This article focuses on American sociological contributions, but notes relevant contributions from non-American scholars published in English that have shaped and fueled American research. This article also profiles the institutional support of childhood research in the US, specifically outlining the activities of the ‘Children and Youth’ Section of the American Sociological Association (ASA), and assesses the contributions of this area of study for sociology as well as the implications for an interdisciplinary field.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Hypertension in Sub-Saharan Africa: Cross-Sectional Surveys in Four Rural and Urban Communities

Background: Cardiovascular disease (CVD) is the leading cause of adult mortality in low-income countries but data on the prevalence of cardiovascular risk factors such as hypertension are scarce, especially in sub-Saharan Africa (SSA). This study aims to assess the prevalence of hypertension and determinants of blood pressure in four SSA populations in rural Nigeria and Kenya, and urban Namibia and Tanzania. Methods and Findings: We performed four cross-sectional household surveys in Kwara State, Nigeria; Nandi district, Kenya; Dar es Salaam, Tanzania and Greater Windhoek, Namibia, between 2009-2011. Representative population-based samples were drawn in Nigeria and Namibia. The Kenya and Tanzania study populations consisted of specific target groups. Within a final sample size of 5,500 households, 9,857 non-pregnant adults were eligible for analysis on hypertension. Of those, 7,568 respondents ≥18 years were included. The primary outcome measure was the prevalence of hypertension in each of the populations under study. The age-standardized prevalence of hypertension was 19.3% (95%CI:17.3-21.3) in rural Nigeria, 21.4% (19.8-23.0) in rural Kenya, 23.7% (21.3-26.2) in urban Tanzania, and 38.0% (35.9-40.1) in urban Namibia. In individuals with hypertension, the proportion of grade 2 (≥160/100 mmHg) or grade 3 hypertension (≥180/110 mmHg) ranged from 29.2% (Namibia) to 43.3% (Nigeria). Control of hypertension ranged from 2.6% in Kenya to 17.8% in Namibia. Obesity prevalence (BMI ≥30) ranged from 6.1% (Nigeria) to 17.4% (Tanzania) and together with age and gender, BMI independently predicted blood pressure level in all study populations. Diabetes prevalence ranged from 2.1% (Namibia) to 3.7% (Tanzania). Conclusion: Hypertension was the most frequently observed risk factor for CVD in both urban and rural communities in SSA and will contribute to the growing burden of CVD in SSA. Low levels of control of hypertension are alarming. Strengthening of health care systems in SSA to contain the emerging epidemic of CVD is urgently needed

Safety evaluation of the single-dose Ad26. COV2.S vaccine among healthcare workers in the Sisonke study in South Africa : a phase 3b implementation trial

Real-world evaluation of the safety profile of vaccines after licensure is crucial to accurately characterise safety beyond clinical trials, support continued use, and thereby improve public confidence. The Sisonke study aimed to assess the safety and effectiveness of the Janssen Ad26.COV2.S vaccine among healthcare workers (HCWs) in South Africa. Here, we present the safety data.Funding for the Sisonke Study was provided by: The National Department of Health through baseline funding to the South African Medical Research Council; the Solidarity Response Fund NPC; The Michael & Susan Dell Foundation; the ELMA Vaccines and Immunization Foundation; the ELMA Vaccines and Immunization Foundation; and the Bill & Melinda Gates Foundation.https://journals.plos.org/plosmedicinedm2022Paediatrics and Child HealthSchool of Health Systems and Public Health (SHSPH

Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants

Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking.We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age