Environmental risk factors for respiratory infection and wheeze in young children: A multicentre birth cohort study.

INTRODUCTION: Respiratory infections and wheeze have a considerable impact on the health of young children and consume significant healthcare resources. We aimed to evaluate the effect of environmental factors on respiratory infections and symptoms in early childhood. METHODS: Environmental risk factors including: daycare attendance; breastfeeding; siblings; damp within the home; environmental tobacco smoke (ETS); child's bedroom flooring; animal exposure; road traffic density around child's home; and solid fuel pollution within home were assessed in children recruited to the GO-CHILD multicentre prospective birth cohort study. Follow-up information on respiratory infections (bronchiolitis, pneumonia, otitis media and cold or flu), wheeze and cough symptoms, healthcare utilisation and medication prescription was collected by postal questionnaires at 12 and 24 months. Log binomial and ordered logistic regression models were fitted to the data. RESULTS: Follow-up was obtained on 1344 children. Daycare was associated with increased odds of pneumonia (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.04-5.49), bronchiolitis (OR = 1.40, 1.02-1.90), otitis media (OR = 1.68, 1.32-2.14) and emergency department attendance for wheeze (RR = 1.81, 1.17-2.80). Breastfeeding beyond 6 months was associated with a reduced odds of bronchiolitis (OR = 0.55, 0.39-0.77) and otitis media (OR = 0.75, 0.59-0.99). Siblings at home was associated with an increased odds of bronchiolitis (OR = 1.65, 1.18-2.32) and risk of reliever inhaler prescription (RR = 1.37, 1.02-1.85). Visible damp was associated with an increased odds of wheeze (OR = 1.85, 1.11-3.19), and risk of reliever inhaler (RR = 1.73, 1.04-2.89) and inhaled corticosteroid prescription (RR = 2.61, 1.03-6.59). ETS exposure was associated with an increased odds of primary care attendance for cough or wheeze (OR = 1.52, 1.11-2.08). Dense traffic around the child's home was associated with an increased odds of bronchiolitis (OR = 1.32, 1.08-2.29). CONCLUSION: Environmental factors likely influence the wide variation in infection frequency and symptoms observed in early childhood. Larger population studies are necessary to further inform and guide public health policy to decrease the burden of respiratory infections and wheeze in young children.

Sexually transmitted infections in suspected child sexual abuse.

Making associations between sexually transmitted infections (STIs) and child sexual abuse can be controversial. To contribute to the paucity of research in this field, this service evaluation aims to (1) define the prevalence of STIs in children aged 0-13 years seen at a regional Children's Sexual Assault Referral Centre, (2) determine whether sexual transmission is the most likely mode of transmission for diagnosed STIs, (3) identify factors affecting application of STI screening and (4) assess follow-up. Methods consisted of retrospective analysis of an anonymous database for all patients seen between 1 July 2016 and 1 July 2019. Of 241 children seen, 114/241 (47.3%) received STI screening and 10/114 (8.8%) tested positive (4.1% of children seen overall). No asymptomatic child was diagnosed with an STI. Sexual transmission was the most likely mode of transmission based on child disclosure and physical examination findings for 6/10 children diagnosed with an STI.

Vestibular and balance dysfunction in children with congenital CMV: a systematic review.

OBJECTIVE: This systematic review evaluates vestibular and balance dysfunction in children with congenital cytomegalovirus (cCMV), makes recommendations for clinical practice and informs future research priorities. DESIGN: MEDLINE, Embase, EMCARE, BMJ Best Practice, Cochrane Library, DynaMed Plus and UpToDate were searched from inception to 20 March 2021 and graded according to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria. PATIENTS: Children with cCMV diagnosed within 3 weeks of life from either blood, saliva and/or urine (using either PCR or culture). INTERVENTION: Studies of vestibular function and/or balance assessments. MAIN OUTCOME MEASURES: Vestibular function and balance. RESULTS: 1371 studies were identified, and subsequently 16 observational studies were eligible for analysis, leading to an overall cohort of 600 children with cCMV. All studies were of low/moderate quality. In 12/16 studies, vestibular function tests were performed. 10/12 reported vestibular dysfunction in ≥40% of children with cCMV. Three studies compared outcomes for children with symptomatic or asymptomatic cCMV at birth; vestibular dysfunction was more frequently reported in children with symptomatic (22%-60%), than asymptomatic cCMV (0%-12.5%). Two studies found that vestibular function deteriorated over time: one in children (mean age 7.2 months) over 10 months and the other (mean age 34.7 months) over 26 months. CONCLUSIONS: Vestibular dysfunction is found in children with symptomatic and asymptomatic cCMV and in those with and without hearing loss. Audiovestibular assessments should be performed as part of neurodevelopmental follow-up in children with cCMV. Case-controlled longitudinal studies are required to more precisely characterise vestibular dysfunction and help determine the efficacy of early supportive interventions. PROSPERO REGISTRATION: CRD42019131656.

Are the doctors of the future ready to support breastfeeding? A cross-sectional study in the UK.

BACKGROUND: Currently there is no published data on the inclusion of breastfeeding education within the UK medical school curriculum. This study aims to address this knowledge gap and explore students' perceptions of their readiness to support breastfeeding. METHODS: An online survey was used to collect data from 32 UK undergraduate medical schools and their students. All students in their final two years of study at the 30 universities offering a 5- or 6-year medicine course, were eligible. RESULTS: Curriculum data was obtained from 26 (81%) institutions. Compulsory breastfeeding education was provided by 85% (N = 22) institutions with 81% (n = 21) providing lecture-based teaching and 19% (n = 5) offering formal clinical education. Overall, 411 students from 22 institutions participated. A moderate ability to identify the benefits of breastfeeding was observed; however, self-rated confidence in practical skills was poor. Assisting with latching was the least confident skill, with confidence in only 3% (14/411) students. Most students (93%) viewed doctors as playing an important role in breastfeeding, with those interested in either women's health, paediatrics or general practice perceiving the role of doctors as more important. Overall, 93% (381/411) students requested further breastfeeding education. CONCLUSIONS: This study suggests UK medical schools are not adequately preparing students to support breastfeeding patients. Further studies should explore the competency of doctors to meet the needs of lactating women, and design optimal training for UK medical students.

Reactivity of Routine HIV Antibody Tests in Children With Perinatally Acquired HIV-1 in England: Cross-sectional Analysis.

We assessed HIV antibody prevalence in children with perinatally acquired HIV in England. Eighteen percent (10/55) of those starting combination antiretroviral therapy <6 months of age were seronegative at median age 9.1 years and had lower viral load at diagnosis and combination antiretroviral therapy start and fewer viral rebounds, than 45 of 55 seropositives. Implications for patient selection for HIV cure research, and interpretation of routine antibody testing, are discussed.

Genetic polymorphisms in the endotoxin receptor may influence platelet count as part of the acute phase response in critically ill children.

PURPOSE: To determine if common polymorphisms in the endotoxin recognition complex influence the acute phase response as determined by the development of the systemic inflammatory response syndrome (SIRS) and platelet count on admission. METHODS: This was a prospective observational cohort study. Paediatric intensive care patients (n = 913) were genotyped for common functional polymorphisms in the endotoxin recognition complex, including Toll-like receptor 4 (TLR4). We also selected potentially confounding polymorphisms in other genes of the innate immune system. SIRS was defined by age-specific consensus criteria. Platelet counts were recorded on admission. RESULTS: The development of SIRS was primarily determined by the nature of the insult, but carriers of TLR4 variant alleles had lower platelet counts than children with wild-type genotype [mean +/- standard error of the mean (SEM) 143 +/- 7 vs. 175 +/- 4; p = 0.0001)--independent of other innate immune system polymorphisms. These findings were validated using a patient cohort of 1,170 adults with coronary artery disease. Carriers of TLR4 polymorphisms with a history of myocardial infarction (n = 573) had lower platelet counts than those with the wild-type genotype (217 +/- 7 vs. 237 +/- 2.8; p = 0.021). CONCLUSIONS: Our results show that TLR4 variant alleles are associated with lower platelet counts across a range of ages and precipitating insults but that they do not influence the incidence of SIRS. This result may reflect redundancy and 'robustness' in the pathways leading to SIRS or the lack of specificity of this endpoint. Platelet count may vary with TLR4 genotype because it may be sufficiently sensitive and more linearly related to inflammation than other markers or, alternatively, there may be a direct TLR4-mediated platelet effect.

Genetic variability in complement activation modulates the systemic inflammatory response syndrome in children.

OBJECTIVE: To determine the impact of genetic variability in complement activation on early development of the systemic inflammatory response syndrome (SIRS) in general pediatric critical care. DESIGN: Prospective, observational, cohort study. SETTING: A tertiary pediatric intensive care unit in the United Kingdom. PATIENTS: Children with at least one organ failure expected to stay in the intensive care unit >12 hrs, or an expected death within 12 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 299 children were genotyped for functional polymorphisms in the complement activation cascade. We identified complement factor H as an important independent genetic modifier of SIRS/sepsis. Homozygosity for the complement factor H Y402H polymorphism, which is thought to reduce complement inhibition, was associated with less frequent SIRS/sepsis (the adjusted odds ratio for the homozygous variant complement factor H Y402H [CC] carriers was 0.3, 95% confidence interval, 0.1-0.7, p = .005). We also confirmed that structural and promoter variant mannose-binding lectin genotypes are a risk factor for SIRS/sepsis in pediatric critical care (adjusted odds ratio, 2.5; 95% confidence interval, 1.3-5.0, p = .008). Both findings were independent of clinical characteristics and other potentially confounding genetic polymorphisms in the innate immune system. CONCLUSIONS: Functional polymorphisms in the complement activation cascade modify the risk for early SIRS/sepsis in general pediatric critical care. The complement factor H Y402H variant allele is protective, whereas the mannose-binding lectin variant polymorphisms increase risk. A genotype that permits vigorous complement activation to an infectious or inflammatory insult may offer protection from development of systemic inflammation.

Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection.

BACKGROUND: Previous studies have shown associations between low mannose-binding lectin (MBL) level or variant MBL2 genotype and sepsis susceptibility. However, MBL deficiency has not been rigorously defined, and associations with sepsis outcomes have not been subjected to multivariable analysis. METHODS: We reanalyzed MBL results in a large cohort with use of individual data from 4 studies involving a total of 1642 healthy control subjects and systematically defined a reliable deficiency cutoff. Subsequently, data were reassessed to extend previous MBL and sepsis associations, with adjustment for known outcome predictors. We reanalyzed individual data from 675 patients from 5 adult studies and 1 pediatric study of MBL and severe bacterial infection. RESULTS: XA/O and O/O MBL2 genotypes had the lowest median MBL concentrations. Receiver operating characteristic analysis revealed that an MBL cutoff value of 0.5 microg/mL was a reliable predictor of low-producing MBL2 genotypes (sensitivity, 82%; specificity, 82%; negative predictive value, 98%). MBL deficiency was associated with increased likelihood of death among patients with severe bacterial infection (odds ratio, 2.11; 95% confidence interval, 1.30-3.43). In intensive care unit-based studies, there was a trend toward increased risk of death among MBL-deficient patients (odds ratio, 1.58; 95% confidence interval, 0.90-2.77) after adjustment for Acute Physiology and Chronic Health Enquiry II score. The risk of death was increased among MBL-deficient patients with Streptococcus pneumoniae infection (odds ratio, 5.62; 95% confidence interval, 1.27-24.92) after adjustment for bacteremia, comorbidities, and age. CONCLUSIONS: We defined a serum level for MBL deficiency that can be used with confidence in future studies of MBL disease associations. The risk of death was increased among MBL-deficient patients with severe pneumococcal infection, highlighting the pathogenic significance of this innate immune defence protein.

Could neonatal disseminated herpes simplex virus infections be treated earlier?

INTRODUCTION: Neonatal disseminated herpes simplex virus (HSV) infection can cause rapidly progressive multiple organ failure with an 85% mortality if untreated. Early recognition and treatment may improve outcome [N Engl J Med 324(1991)450]. OBJECTIVES: (i) To determine the number and presentation of neonates with disseminated HSV admitted to an intensive care unit. (ii) To determine paediatric Specialist Registrar (SpR) awareness of the diagnosis and management of a typical potential case of neonatal disseminated HSV. METHODS: (i) A 10-year review of case notes of neonates admitted to the intensive care unit (ICU) at Great Ormond Street Hospital. (ii) A telephone questionnaire of 'on-call' Paediatric SpR's in the London area. RESULTS: Eight cases of confirmed disseminated HSV infection were identified. All died. Each case followed a similar clinical course with presentation between days 5-9 of life (median day 7). A short prodrome preceded the rapid development of disseminated intravascular coagulopathy (DIC), hepatitis and multiple organ failure. Only three cases received antiviral treatment in the first 24 h after hospital admission. None of the 30 registrars who were interviewed initially considered disseminated HSV in the differential diagnosis of a 7-day-old baby presenting with non-specific signs of sepsis. Only 4/30 referring unit protocols included disseminated HSV in the differential diagnosis of neonatal sepsis. CONCLUSIONS: HSV infection should be considered in the differential diagnosis of the acutely unwell neonate. This condition is rare but well documented in the literature. Effective antiviral therapies exist but are often not started early in the clinical course. Awareness of this condition needs to be increased.

Increased incidence and severity of the systemic inflammatory response syndrome in patients deficient in mannose-binding lectin.

OBJECTIVE: To determine whether pediatric PICU patients with mannose-binding lectin (MBL) gene polymorphisms associated with low levels of the functional protein have an increased risk of developing sepsis and SIRS. DESIGN AND SETTING: A prospective, observational cohort study in a 22-bed PICU in a tertiary referral centre. PATIENTS: One hundred consecutive admissions to a PICU with at least one organ system failure longer than 12 h. Patients were classified into those with infectious or non-infectious insults as the primary reason for intensive care admission. Patients were followed to determine which developed sepsis or non-infection related SIRS using standard criteria. MEASUREMENTS AND RESULTS: Of the 100 patients 50 had infectious and 50 had non-infectious insults as the precipitant for admission. 42 patients had variant MBL alleles (determined by MBL-2 gene exon 1 and promoter polymorphisms) and were significantly over-represented amongst the 59 patients that developed SIRS. This effect was not explained by differences in age, sex or ethnicity and was seen in both the infection and non-infection subgroups. In patients with infection, variant MBL alleles were associated with increased systemic response (2/15 with localised infection, 10/19 with sepsis and 12/16 with septic shock). MBL serum levels showed close concordance with the genotype and indicated that MBL levels less than 1000 ng/ml are associated with a greatly increased risk of SIRS. CONCLUSIONS: MBL-2 exon 1 polymorphisms with low serum levels of functional MBL protein are associated with a greatly increased risk of developing SIRS and of progression from infection to sepsis and septic shock in paediatric ICU patients.

Unique case of Helicobacter sp. osteomyelitis in an immunocompetent child diagnosed by broad-range 16S PCR.

We report the first case of Helicobacter sp. osteomyelitis in an immunocompetent child. The infection was diagnosed by broad-range 16S PCR followed by sequencing of the resulting amplicon. All other microbiological investigations proved negative. This case highlights the importance of molecular methods in the diagnosis of unsuspected etiological agents and the potential role of Helicobacter sp. in human infection.