Outcomes of neonatal congenital diaphragmatic hernia in a non-ECMO center in a middle-income country: a retrospective cohort study.

BACKGROUND: Most studies examining survival of neonates with congenital diaphragmatic hernia (CDH) are in high-income countries. We aimed to describe the management, survival to hospital discharge rate, and factors associated with survival of neonates with unilateral CDH in a middle-income country. METHODS: We retrospectively reviewed the medical notes of neonates with unilateral CDH admitted to a pediatric intensive care unit (PICU) in a tertiary referral center over a 15-year period, from 2003-2017. We described the newborns' respiratory care pathways and then compared baseline demographic, hemodynamic, and respiratory indicators between survivors and non-survivors. The primary outcome measure was survival to hospital discharge. RESULTS: Altogether, 120 neonates were included with 43.3% (52/120) diagnosed antenatally. Stabilization occurred in 38.3% (46/120) with conventional ventilation, 13.3% (16/120) with high-frequency intermittent positive-pressure ventilation, and 22.5% (27/120) with high frequency oscillatory ventilation. Surgical repair was possible in 75.0% (90/120). The overall 30-day survival was 70.8% (85/120) and survival to hospital discharge was 66.7% (80/120). Survival to hospital discharge tended to improve over time (p > 0.05), from 56.0% to 69.5% before and after, respectively, a service reorganization. For those neonates who could be stabilized and operated on, 90.9% (80/88) survived to hospital discharge. The commonest post-operative complication was infection, occurring in 43.3%. The median survivor length of stay was 32.5 (interquartile range 18.8-58.0) days. Multiple logistic regression modelling showed vaginal delivery (odds ratio [OR] = 4.8; 95% confidence interval [CI] [1.1-21.67]; p = 0.041), Apgar score [Formula: see text] 7 at 5 min (OR = 6.7; 95% CI [1.2-36.3]; p = 0.028), and fraction of inspired oxygen (FiO2) < 50% at 24 h (OR = 89.6; 95% CI [10.6-758.6]; p < 0.001) were significantly associated with improved survival to hospital discharge. CONCLUSIONS: We report a survival to hospital discharge rate of 66.7%. Survival tended to improve over time, reflecting a greater critical volume of cases and multi-disciplinary care with early involvement of the respiratory team resulting in improved transitioning from PICU. Vaginal delivery, Apgar score [Formula: see text] 7 at 5 min, and FiO2 < 50% at 24 h increased the likelihood of survival to hospital discharge.

Maternal diet during pregnancy and infant respiratory morbidity: A prospective study.

BACKGROUND AND OBJECTIVES: Maternal diet during pregnancy may impact infant respiratory morbidity. The aim was to determine the association between antenatal maternal diet and respiratory morbidity of their infants during their first 6 months of life. METHODS AND STUDY DESIGN: This prospective cohort study included healthy motherinfant pairs. Maternal diet during the last trimester was determined with a validated food frequency questionnaire. Infant respiratory morbidity was solicited at 1, 3 and 6 months. RESULTS: Three hundred mother-baby pairs were recruited. Maternal consumption of milk and dairy products was associated with reduced respiratory symptoms at 1 month (aOR 0.29 [95% CI: 0.10, 0.86], p=0.03) and 3 months old (aOR 0.43 [95% CI: 0.20, 0.93], p=0.03), while intake of confectionery items was associated with increased unscheduled doctor visits at 3 months (aOR 2.01 [95% CI 1.33, 3.06], p=0.001) and increased nebuliser treatment at both 3 months (aOR 1.88 [95% CI 1.12, 3.17], p=0.02) and 6 months (aOR 1.64 [95% CI 1.05, 2.54], p=0.03). Finally, at 6 months, hypertensive disorders during pregnancy was associated with increased nebuliser treatment (aOR 17.3 [95% CI 1.50, 199], p=0.02) while exclusive breastfeeding was associated with reduced incidence of respiratory symptoms (OR 0.47 [95% CI 0.26, 0.83], p=0.01). CONCLUSIONS: Increased antenatal maternal consumption of milk and dairy products may reduce respiratory morbidity while increased consumption of confectionery items may increase respiratory morbidity in their infants during the first 6 months of life.

Parents are poor at labelling wheeze in children: a cross-sectional study.

BACKGROUND: Noisy breathing is a common presenting symptom in children. The purpose of this study is to (a) assess parental ability to label wheeze, (b) compare the ability of parents of children with and without asthma to label wheeze and (c) determine factors affecting parental ability to label wheeze correctly. METHODS: This cross-sectional study in a tertiary hospital in Kuala Lumpur, Malaysia involved parents of children with asthma. Parents of children without asthma were the control group. Eleven validated video clips showing wheeze, stridor, transmitted noises, snoring or normal breathing were shown to the parents. Parents were asked, in English or Malay, "What do you call the sound this child is making?" and "Where do you think the sound is coming from?" RESULTS: Two hundred parents participated in this study: 100 had children with asthma while 100 did not. Most (71.5 %) answered in Malay. Only 38.5 % of parents correctly labelled wheeze. Parents were significantly better at locating than labelling wheeze (OR 2.4, 95 % CI 1.64-3.73). Parents with asthmatic children were not better at labelling wheeze than those without asthma (OR1.04, 95 % CI 0.59-1.84). Answering in English (OR 3.4, 95 % CI 1.69-7.14) and having older children with asthma (OR 9.09, 95 % CI 3.13-26.32) were associated with correct labelling of wheeze. Other sounds were mislabelled as wheeze by 16.5 % of respondents. CONCLUSION: Parental labelling of wheeze was inaccurate especially in the Malay language. Parents were better at identifying the origin of wheeze rather than labelling it. Physicians should be wary about parental reporting of wheeze as it may be inaccurate.

Morbidity and treatment costs of cystic fibrosis in a middle-income country.

Introduction: : Asian children with cystic fibrosis (CF) managed in Malaysia have significant morbidity with limited access to life-sustaining treatments. We determined the morbidity and treatment cost of CF in a resource-limited country. Methods: This cross-sectional study included all children diagnosed with CF in our centre. Data on clinical presentation, genetic mutation, serial spirometry results and complications were collected. Out-of-pocket (OOP) and healthcare costs over 1 year were retrieved for patients who were alive. Cohen's d and odds ratio (OR) were used to determine the effect size. Results: Twenty-four patients were diagnosed with CF. Five patients died at a median (range) age of 18 (0.3-22) years. F508deletion (c. 1521_1523delCTT) was found in 20% of the alleles, while 89% of the variants were detected in nine patients. Body mass index (BMI) Z score was >-1.96 in 70.6% of patients. Two thirds (68%) were colonised with Pseudomonas aeruginosa, and this was associated with lower weight (P = 0.009) and BMI (P = 0.02) Z scores. Only 18% had FEV1 Z scores >-1.96. Early symptom onset (d = 0.74), delayed diagnosis (d = 2.07), a low FEF25-75 Z score (d = 0.82) and a high sweat conductance (d = 1.19) were associated with death. Inpatient cost was mainly from diagnostic tests, while medications contributed to half of the outpatient cost.Healthcare utilisation cost was catastrophic, amounting to 20% of the total income. Conclusion: Asian children with CF suffer significant complications such as low weight, low lung function and shortened lifespan. P. aeruginosa colonisation was frequent and associated with poor growth. Healthcare cost to parents was catastrophic.

Colonization of the newborn respiratory tract and its association with respiratory morbidity in the first 6 months of life: A prospective cohort study.

OBJECTIVES: We aimed to determine the association between newborn bacterial colonization and infant respiratory morbidity in the first 6 months of life. METHODS: This prospective study included healthy newborn infants. Nasopharyngeal swabs performed within 72 hours of delivery were analyzed using polymerase chain reaction. We assessed cumulative respiratory morbidity of infants at 6 months. RESULTS: A total of 426 mother-infant pairs were recruited. In 53.3% (n = 225) of newborns, Streptococcus pneumoniae (46%) and Staphylococcus aureus (7.3%) were isolated. None had Haemophilus influenzae nor Moraxella catarrhalis. At the age of 6 months, 50.7% of infants had experienced respiratory symptoms, 25% had unscheduled doctor visits, and 10% were treated with nebulizers. Colonization with S. pneumoniae was associated with reduced risk of any respiratory symptom (adjusted odds ratio [aOR] 0.39, 95% confidence interval [CI] 0.16, 0.50), unscheduled doctor visits (aOR 0.35; 95% CI 0.18, 0.67), and nebulizer treatment (aOR 0.23, 95% CI 0.07, 0.72) at 6 months. Pregnancy-induced hypertension was also associated with increased need for nebulizer treatment (aOR 9.11, 95% CI 1.43, 58.1). CONCLUSION: Colonization of the newborn respiratory tract occurred in 53% of infants. S. pneumoniae was the most common organism, and this was associated with a reduced risk for respiratory morbidity at 6 months of life.

Obstructive sleep apnoea syndrome (OSAS) as a risk factor for secondary osteoporosis in children.

Repetitive hypoxia seen in obstructive sleep apnoea syndrome (OSAS) may affect bone metabolism increasing the risk for secondary osteoporosis. This study investigates the association between OSAS in children and secondary osteoporosis. This cross-sectional study included 150 children aged 10-17 years: 86 with OSAS and 64 with no OSAS. OSAS was confirmed by polysomnography. Quantitative ultrasound (QUS) of calcaneum measuring speed of sound (SoS) and broadband ultrasound attenuation (BUA) were collected. Other parameters collected including bone profile, vitamin D levels, physical activity scoring and dietary calcium intake. Majority were male and Malay ethnicity. OSAS children were mostly obese (84%) and 57% had moderate to severe OSAS. Most had lower physical activities scores. Mean (SD) phosphate and Alkaline phosphatase were lower in OSA children compared to controls: PO4, p = 0.039 and ALP, p < 0.001. Using both single and multivariate analysis, children with OSAS had a lower mean SoS value, p < 0.001 and p = 0.004 respectively after adjusting for age, BMI and bone profile. Children with OSAS had lower SoS suggesting risk for secondary osteoporosis. QUS calcaneus is a non-invasive, feasible tool and can be used to screen risk of osteoporosis in children. Further bone mineral density assessment is needed in these groups of children to confirm diagnosis of osteoporosis.

Socioeconomic costs of children <5 years hospitalised with acute respiratory infections in Kuala Lumpur, Malaysia.

BACKGROUND: Acute respiratory infections (ARI) are a major cause of morbidity and mortality in Malaysian children < 5 years. Knowledge of associated economic costs is important for policymakers to determine cost-effectiveness of interventions, such as pneumococcal or influenza vaccines, which are underused in Malaysia. METHODS: Children < 5 years admitted with ARI to a teaching hospital in Kuala Lumpur were prospectively recruited between July 2013 and July 2015. Medical (with and without government subsidies), non-medical and indirect costs from pre-admission, admission and post-discharge were obtained by interviews with carers and from medical records. Respiratory viruses were diagnosed by immunofluorescence and virus culture. RESULTS: 200 patients were recruited, and 74 (37%) had respiratory viruses detected. For each admitted ARI, the median direct out-of-pocket cost (subsidized) was USD 189 (interquartile range, 140-258), representing a median 16.4% (10.4-22.3%) of reported monthly household income. The median total direct cost (unsubsidized) was USD 756 (564-987), meaning that government subsidies covered a median 75.2% (70.2-78.4%) of actual costs. Median direct costs for 50 respiratory syncytial virus (RSV) cases were higher than the 126 virus-negative cases (USD 803 vs 729, p = 0.03). The median societal cost (combining direct and indirect costs) was USD 871 (653-1,183), which is 1.8 times the Malaysian health expenditure per capita in 2014. Costs were higher with younger age, presence of comorbidity, prematurity, and detection of a respiratory virus. CONCLUSION: These comprehensive estimated costs of ARI admissions in children < 5 years are high. These costs can be used as a basis for planning treatment and preventive strategies, including cost-effectiveness studies for influenza and, in future, RSV vaccines.

Health-related quality of life and developmental outcome of children on home mechanical ventilation in a developing country: A cross-sectional study.

BACKGROUND: Provision of home mechanical ventilation (HMV) to children with chronic respiratory insufficiency enhances growth and quality of life. The hypothesis was that health-related quality of life (HRQoL) and the development of these children were poorer than in healthy children. OBJECTIVES: To determine the HRQoL and developmental outcome of children on HMV. METHODS: This cross-sectional study used the TNO-AZL Preschool children's Quality Of Life (TAPQOL; <5 years old) and Health Utilities Index (HUI) 2/3 (≥5 years old) to assess the quality of life and the Schedule of Growing Skills-II to assess development. Instruments were used on children currently or previously on HMV (≥3 months) and compared with age and sex-matched controls. RESULTS: Sixty-five patients and 130 controls were recruited. Patients' median (interquartile range) age was 3.12 (1.65, 5.81) years. Patients had significantly lower TAPQOL scores in the domains of lung, liveliness, positive mood, social functioning, motor functioning, and communication, and lower HUI 2/3 scores in hearing, sensation, pain, speech, mobility, ambulatory, dexterity, and self-care domains. The developmental outcome of patients was poorer in all domains. However, patients had fewer behavioral problems. Those with respiratory tract disease and without comorbidities had better HRQoL and developmental scores. Having a parent as the primary caregiver was associated with better speech and language skills. CONCLUSIONS: HRQoL and the developmental outcome are lower in children on HMV compared to controls. Children with respiratory tract disease and without comorbidities have a better outcome. Parents play a crucial role in the acquisition of speech.

Bacterial pneumonia and its associated factors in children from a developing country: A prospective cohort study.

INTRODUCTION: Pneumonia in children is a common disease yet determining its aetiology remains elusive. OBJECTIVES: To determine the a) aetiology, b) factors associated with bacterial pneumonia and c) association between co-infections (bacteria + virus) and severity of disease, in children admitted with severe pneumonia. METHODS: A prospective cohort study involving children aged 1-month to 5-years admitted with very severe pneumonia, as per the WHO definition, over 2 years. Induced sputum and blood obtained within 24 hrs of admission were examined via PCR, immunofluorescence and culture to detect 17 bacteria/viruses. A designated radiologist read the chest radiographs. RESULTS: Three hundred patients with a mean (SD) age of 14 (±15) months old were recruited. Significant pathogens were detected in 62% of patients (n = 186). Viruses alone were detected in 23.7% (n = 71) with rhinovirus (31%), human metapneumovirus (HMP) [22.5%] and respiratory syncytial virus (RSV) [16.9%] being the commonest. Bacteria alone was detected in 25% (n = 75) with Haemophilus influenzae (29.3%), Staphylococcus aureus (24%) and Streptococcus pneumoniae (22.7%) being the commonest. Co-infections were seen in 13.3% (n = 40) of patients. Male gender (AdjOR 1.84 [95% CI 1.10, 3.05]) and presence of crepitations (AdjOR 2.27 [95% CI 1.12, 4.60]) were associated with bacterial infection. C-reactive protein (CRP) [p = 0.007]) was significantly higher in patients with co-infections but duration of hospitalization (p = 0.77) and requirement for supplemental respiratory support (p = 0.26) were not associated with co-infection. CONCLUSIONS: Bacteria remain an important cause of very severe pneumonia in developing countries with one in four children admitted isolating bacteria alone. Male gender and presence of crepitations were significantly associated with bacterial aetiology. Co-infection was associated with a higher CRP but no other parameters of severe clinical illness.

Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia.

OBJECTIVES: To describe the severity, human adenovirus (HAdV) type and respiratory morbidity following adenovirus pneumonia in children. METHODOLOGY: Retrospective review of children under 12 years of age, admitted with HAdV pneumonia, between January 2011 and July 2013, in a single centre in Malaysia. HAdV isolated from nasopharyngeal secretions were typed by sequencing hypervariable regions 1-6 of the hexon gene. Patients were reviewed for respiratory complications. RESULTS: HAdV was detected in 131 children of whom 92 fulfilled inclusion criteria. Median (range) age was 1.1 (0.1-8.0) years with 80% under 2 years. Twenty percent had severe disease with a case-fatality rate of 5.4%. Duration of admission (p = 0.02) was independently associated with severe illness. Twenty-two percent developed respiratory complications, the commonest being bronchiolitis obliterans (15.2%) and recurrent wheeze (5.4%). The predominant type shifted from HAdV1 and HAdV3 in 2011 to HAdV7 in 2013. The commonest types identified were types 7 (54.4%), 1(17.7%) and 3 (12.6%). Four out of the five patients who died were positive for HAdV7. Infection with type 7 (OR 8.90, 95% CI 1.32, 59.89), family history of asthma (OR 14.80, 95% CI 2.12-103.21) and need for invasive or non-invasive ventilation (OR 151.84, 95% CI 9.93-2.32E) were independent predictors of respiratory complications. CONCLUSIONS: One in five children admitted with HAdV pneumonia had severe disease and 22% developed respiratory complications. Type 7 was commonly isolated in children with severe disease. Family history of asthma need for invasive or non-invasive ventilation and HAdV 7 were independent predictors of respiratory complications.

Correction: Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia.

[This corrects the article DOI: 10.1371/journal.pone.0205795.].

Review: Quality of Life in Children with Non-cystic Fibrosis Bronchiectasis.

Non-cystic fibrosis bronchiectasis (NCFB) has gained renewed interest, due to its increasing health-care burden. Annual mortality statistics in England and Wales showed that under 1,000 people die from bronchiectasis each year, and this number is increasing by 3% yearly. Unfortunately, there is a severe lack of well-powered, randomized controlled trials to guide clinicians how to manage NCFB effectively. Quality-of-life (QOL) measures in NCFB are an important aspect of clinical care that has not been studied well. Commonly used disease-specific questionnaires in children with NCFB are the St George's Respiratory Questionnaire, Short Form-36, the Leicester Cough Questionnaire, and the Parent Cough-Specific Quality of Life questionnaire (PC-QOL). Of these, only the PC-QOL can be used in young children, as it is a parent-proxy questionnaire. We reviewed pediatric studies looking at QOL in children with NCFB and cystic fibrosis. All types of airway clearance techniques appear to be safe and have no significant benefit over each other. Number of exacerbations and hospitalizations correlated with QOL scores, while symptom subscales correlated with lung function, worse QOL, frequent antibiotic requirements, and duration of regular follow-up in only one study. There was a correlation between QOL and age of diagnosis in children with primary ciliary dyskinesia. Other studies have shown no relationship between QOL scores and etiology of NCFB as well as CT changes. As for treatments, oral azithromycin and yoga have demonstrated some improvement in QOL scores. In conclusion, more studies are required to accurately determine important factors contributing to QOL.

Thirteen years of invasive and noninvasive home ventilation for children in a developing country: A retrospective study.

INTRODUCTION: Home ventilation (HV) for children is growing rapidly worldwide. The aim was to describe (1) the sociodemographic characteristics of children on HV and (2) the indications for, means and outcome of initiating HV in children from a developing country. METHODOLOGY: This retrospective study included patients sent home on noninvasive or invasive ventilation, over 13 years, by the pediatric respiratory unit in a single center. Children who declined treatment were excluded. RESULTS: Seventy children were initiated on HV: 85.7% on noninvasive ventilation, 14.3% on invasive ventilation. There was about a threefold increase from 2001-2008 (n = 18) to 2009-2014 (n = 52). Median (range) age of initiating HV was 11 (1-169) months and 73% of children were <2 years old. Common indications for HV were respiratory (57.2%), chest/spine anomalies (11.4%), and neuromuscular (10.0%). Fifty-two percent came off their devices with a median (interquartile range) usage duration of 12 (4.8, 21.6) months. Ten children (14.3%) died with one avoidable death. Children with neuromuscular disease were less likely to come off their ventilator (0.0%) compared to children with respiratory disease (62.1%). Forty-one percent of parents bought their equipment, whereas 58.6% borrowed their equipment from the medical social work department and other sources. CONCLUSION: HV in a resource-limited country is possible. Children with respiratory disease made up a significant proportion of those requiring HV and were more likely to be weaned off. The mortality rate was low. The social work department played an important role in facilitating early discharge. Pediatr Pulmonol. 2017;52:500-507. © 2016 Wiley Periodicals, Inc.