Oxigenación de músculos respiratorios y locomotores durante el test cardiopulmonar en pacientes con circulación de fontan: serie de casos / Patients with fontan: oxygen consumption in respiratory and Locomotor muscles during excersie testing

Resumen: Antecedentes: Los pacientes con circulación de Fontan (PCF) presentan limitación cardíaca durante el esfuerzo máximo lo que repercute en menor capacidad de ejercicio (VO2-peak). La rehabilitación cardiovascular (RC) revierte este desacondicionamiento, al aumentar el gasto cardíaco y diferencia arteriovenosa de oxígeno, aspectos evaluados con monitorización invasiva y gases exhalados. La valoración no invasiva de la saturación muscular de oxígeno (SmO2) es un método de reciente aplicación para evaluar la limitación muscular al ejercicio. En PCF esta limitación puede atribuirse a la mayor acción de músculos respiratorios (cambios ventilatorios) y/o locomotores (carga periférica). Objetivo: Evaluar el trabajo de músculos respiratorios y locomotores durante el ejercicio físico máximo e incremental mediante los cambios en la SmO2. Métodos: A seis PCF (5 hombres; 13.8±2.9 años; 158±9cm; 49.8±13.3 kg) se les valoró el VO2-peak (23.0±4.5mL·kg-1·min-1) mediante ciclo-ergoespirometría sincrónicamente con SmO2 en músculos respiratorios (SmO2-m.Intercostales) y locomotores (SmO2-m.Vastus-Laterallis) mediante espectroscopía cercana al rango infrarrojo durante el test cardiopulmonar. Resultados: SmO2-m.Intercostales disminuyó desde el 60% del VO2-peak (p<0.05), mientras que SmO2-m.Vastus-Laterallis no cambió. La ventilación pulmonar (VE) aumentó progresivamente, siendo significativo a partir del 60% VO2-peak (p<0.05). La mayor desoxigenación de SmO2-m.Intercostales (∆SmO2) se asoció con los máximos cambios en ventilación pulmonar (∆VE) en ejercicio (rho=0.80; p=0.05). Conclusiones: Durante un protocolo de esfuerzo, los pacientes con circulación de Fontan presentan mayor trabajo muscular respiratorio que locomotor. Los cambios en la ventilación pulmonar se asocian a mayor extracción de oxígeno en la musculatura respiratoria, reforzando la necesidad de incorporar el entrenamiento respiratorio en la rehabilitación cardiovascular.

Abstract: Background: During a maximum incremental exercise patients with Fontan circulation (PFC) show cardiac limitation reducing aerobic exercise capacity (VO2-peak). Cardiovascular rehabilitation (CR) reverses this deconditioning by increasing cardiac output and arteriovenous oxygen difference, aspects that can be evaluated by invasive methods and analyzing the exhaled gases. Non-invasive assessment of muscle oxygen saturation (SmO2) is a novel method for recording local oxygen levels. By this technology, it is possible to evaluate the muscle limitation to exercise. In PFC, that limitation could be attributed to higher contractions of respiratory (ventilatory changes) and/ or locomotor muscles (peripheral load). Objective: To evaluate in PFC the changes at SmO2 of respiratory and locomotor muscles during a maximum and incremental exercise protocol (cardiopulmonary test, VO2-peak). Methods: Six PFC (5 men; 13.8±2.9 years; 158±9 cm; 49.8±13.3 kg) were assessed during the VO2peak test (23.0±4.5mL·kg-1·min-1) by cyclo-ergospirometry synchronously with SmO2 at respiratory (SmO2-m.Intercostales) and locomotor (SmO2-m. Vastus-Laterallis) muscles by Near-Infrared Spectroscopy (NIRS). Results: SmO2-m.Intercostales decreased from 60% of VO2-peak (p<0.05), while SmO2-m.Vastus-Laterallis did not change. Minute ventilation (VE) increased progressively, showing changes to rest at 60% of VO2-peak (p<0.05). The higher deoxygenation of SmO2-m.Intercostales (∆SmO2) correlated to maximum changes of lung ventilation (∆VE) (rho=0.80; p=0.05). Conclusions: During an incremental and maximum exercise protocol, patients with Fontan circulation have more work at respiratory than locomotor muscles. Changes in VE are direct associated with greater extraction of oxygen at respiratory muscles, reinforcing the incorporation of respiratory muscle training in cardiovascular rehabilitation.

Hydrocephalus and diffuse choroid plexus hyperplasia in primary ciliary dyskinesia-related MCIDAS mutation.

OBJECTIVE: To report a neuroradiologic phenotype associated with reduced generation of multiple motile cilia (RGMC) and mutations in the multicilin gene. We hypothesize that the observed phenotype may reflect the emerging role that ependymal cilia play in regulating CSF production. METHOD: Clinical and radiologic records were retrospectively reviewed for 7 consecutive patients diagnosed by the Leicester UK national primary ciliary dyskinesia (PCD) diagnostic laboratory. RESULTS: On MRI scanning, all patients demonstrated hydrocephalus, choroid plexus hyperplasia (CPH), and arachnoid cysts. No patient had any sign of neurologic deficit. All patients had significant lung disease. CONCLUSIONS: We conclude that there is a high incidence of hydrocephalus, arachnoid cysts, and CPH in MCIDAS-associated RGMC. In all cases, the observed hydrocephalus seems arrested in childhood without progression or adverse neurologic sequelae. Our new observation of CPH, which is associated with CSF overproduction, is the first macroscopic evidence that ependymal cilia may be involved in the regulation of CSF production and flow. We suggest that brain imaging should be performed in all cases of RGMC and that a diagnosis of PCD or RGMC be strongly considered in patients with unexplained hydrocephalus and a lifelong "wet"-sounding cough.

Clinical features and management of children with primary ciliary dyskinesia in England.

OBJECTIVE: In England, the National Health Service commissioned a National Management Service for children with primary ciliary dyskinesia (PCD). The aims of this study were to describe the health of children seen in this Service and compare lung function to children with cystic fibrosis (CF). DESIGN: Multi-centre service evaluation of the English National Management PCD Service. SETTING: Four nationally commissioned PCD centres in England. PATIENTS: 333 children with PCD reviewed in the Service in 2015; lung function data were also compared with 2970 children with CF. RESULTS: Median age at diagnosis for PCD was 2.6 years, significantly lower in children with situs inversus (1.0 vs 6.0 years, p<0.001). Compared with national data from the CF Registry, mean (SD) %predicted forced expiratory volume in one second (FEV1) was 76.8% in PCD (n=240) and 85.0% in CF, and FEV1 was lower in children with PCD up to the age of 15 years. Approximately half of children had some hearing impairment, with 26% requiring hearing aids. Children with a lower body mass index (BMI) had lower FEV1 (p<0.001). One-third of children had positive respiratory cultures at review, 54% of these grew Haemophilus influenzae. CONCLUSIONS: We provide evidence that children with PCD in England have worse lung function than those with CF. Nutritional status should be considered in PCD management, as those with a lower BMI have significantly lower FEV1. Hearing impairment is common but seems to improve with age. Well-designed and powered randomised controlled trials on management of PCD are needed to inform best clinical practice.

Clinical utility of NGS diagnosis and disease stratification in a multiethnic primary ciliary dyskinesia cohort.

BACKGROUND: Primary ciliary dyskinesia (PCD), a genetically heterogeneous condition enriched in some consanguineous populations, results from recessive mutations affecting cilia biogenesis and motility. Currently, diagnosis requires multiple expert tests. METHODS: The diagnostic utility of multigene panel next-generation sequencing (NGS) was evaluated in 161 unrelated families from multiple population ancestries. RESULTS: Most (82%) families had affected individuals with biallelic or hemizygous (75%) or single (7%) pathogenic causal alleles in known PCD genes. Loss-of-function alleles dominate (73% frameshift, stop-gain, splice site), most (58%) being homozygous, even in non-consanguineous families. Although 57% (88) of the total 155 diagnostic disease variants were novel, recurrent mutations and mutated genes were detected. These differed markedly between white European (52% of families carry DNAH5 or DNAH11 mutations), Arab (42% of families carry CCDC39 or CCDC40 mutations) and South Asian (single LRRC6 or CCDC103 mutations carried in 36% of families) patients, revealing a striking genetic stratification according to population of origin in PCD. Genetics facilitated successful diagnosis of 81% of families with normal or inconclusive ultrastructure and 67% missing prior ultrastructure results. CONCLUSIONS: This study shows the added value of high-throughput targeted NGS in expediting PCD diagnosis. Therefore, there is potential significant patient benefit in wider and/or earlier implementation of genetic screening.

Biallelic Mutations in LRRC56, Encoding a Protein Associated with Intraflagellar Transport, Cause Mucociliary Clearance and Laterality Defects.

Primary defects in motile cilia result in dysfunction of the apparatus responsible for generating fluid flows. Defects in these mechanisms underlie disorders characterized by poor mucus clearance, resulting in susceptibility to chronic recurrent respiratory infections, often associated with infertility; laterality defects occur in about 50% of such individuals. Here we report biallelic variants in LRRC56 (known as oda8 in Chlamydomonas) identified in three unrelated families. The phenotype comprises laterality defects and chronic pulmonary infections. High-speed video microscopy of cultured epithelial cells from an affected individual showed severely dyskinetic cilia but no obvious ultra-structural abnormalities on routine transmission electron microscopy (TEM). Further investigation revealed that LRRC56 interacts with the intraflagellar transport (IFT) protein IFT88. The link with IFT was interrogated in Trypanosoma brucei. In this protist, LRRC56 is recruited to the cilium during axoneme construction, where it co-localizes with IFT trains and is required for the addition of dynein arms to the distal end of the flagellum. In T. brucei carrying LRRC56-null mutations, or a variant resulting in the p.Leu259Pro substitution corresponding to the p.Leu140Pro variant seen in one of the affected families, we observed abnormal ciliary beat patterns and an absence of outer dynein arms restricted to the distal portion of the axoneme. Together, our findings confirm that deleterious variants in LRRC56 result in a human disease and suggest that this protein has a likely role in dynein transport during cilia assembly that is evolutionarily important for cilia motility.

High prevalence of CCDC103 p.His154Pro mutation causing primary ciliary dyskinesia disrupts protein oligomerisation and is associated with normal diagnostic investigations.

RATIONALE: Primary ciliary dyskinesia is a genetically heterogeneous inherited condition characterised by progressive lung disease arising from abnormal cilia function. Approximately half of patients have situs inversus. The estimated prevalence of primary ciliary dyskinesia in the UK South Asian population is 1:2265. Early, accurate diagnosis is key to implementing appropriate management but clinical diagnostic tests can be equivocal. OBJECTIVES: To determine the importance of genetic screening for primary ciliary dyskinesia in a UK South Asian population with a typical clinical phenotype, where standard testing is inconclusive. METHODS: Next-generation sequencing was used to screen 86 South Asian patients who had a clinical history consistent with primary ciliary dyskinesia. The effect of a CCDC103 p.His154Pro missense variant compared with other dynein arm-associated gene mutations on diagnostic/phenotypic variability was tested. CCDC103 p.His154Pro variant pathogenicity was assessed by oligomerisation assay. RESULTS: Sixteen of 86 (19%) patients carried a homozygous CCDC103 p.His154Pro mutation which was found to disrupt protein oligomerisation. Variable diagnostic test results were obtained including normal nasal nitric oxide levels, normal ciliary beat pattern and frequency and a spectrum of partial and normal dynein arm retention. Fifteen (94%) patients or their sibling(s) had situs inversus suggesting CCDC103 p.His154Pro patients without situs inversus are missed. CONCLUSIONS: The CCDC103 p.His154Pro mutation is more prevalent than previously thought in the South Asian community and causes primary ciliary dyskinesia that can be difficult to diagnose using pathology-based clinical tests. Genetic testing is critical when there is a strong clinical phenotype with inconclusive standard diagnostic tests.

DNAAF1 links heart laterality with the AAA+ ATPase RUVBL1 and ciliary intraflagellar transport.

DNAAF1 (LRRC50) is a cytoplasmic protein required for dynein heavy chain assembly and cilia motility, and DNAAF1 mutations cause primary ciliary dyskinesia (PCD; MIM 613193). We describe four families with DNAAF1 mutations and complex congenital heart disease (CHD). In three families, all affected individuals have typical PCD phenotypes. However, an additional family demonstrates isolated CHD (heterotaxy) in two affected siblings, but no clinical evidence of PCD. We identified a homozygous DNAAF1 missense mutation, p.Leu191Phe, as causative for heterotaxy in this family. Genetic complementation in dnaaf1-null zebrafish embryos demonstrated the rescue of normal heart looping with wild-type human DNAAF1, but not the p.Leu191Phe variant, supporting the conserved pathogenicity of this DNAAF1 missense mutation. This observation points to a phenotypic continuum between CHD and PCD, providing new insights into the pathogenesis of isolated CHD. In further investigations of the function of DNAAF1 in dynein arm assembly, we identified interactions with members of a putative dynein arm assembly complex. These include the ciliary intraflagellar transport protein IFT88 and the AAA+ (ATPases Associated with various cellular Activities) family proteins RUVBL1 (Pontin) and RUVBL2 (Reptin). Co-localization studies support these findings, with the loss of RUVBL1 perturbing the co-localization of DNAAF1 with IFT88. We show that RUVBL1 orthologues have an asymmetric left-sided distribution at both the mouse embryonic node and the Kupffer's vesicle in zebrafish embryos, with the latter asymmetry dependent on DNAAF1. These results suggest that DNAAF1-RUVBL1 biochemical and genetic interactions have a novel functional role in symmetry breaking and cardiac development.

Saline in acute bronchiolitis RCT and economic evaluation: hypertonic saline in acute bronchiolitis - randomised controlled trial and systematic review.

BACKGROUND: Acute bronchiolitis is the most common cause of hospitalisation in infancy. Supportive care and oxygen are the cornerstones of management. A Cochrane review concluded that the use of nebulised 3% hypertonic saline (HS) may significantly reduce the duration of hospitalisation. OBJECTIVE: To test the hypothesis that HS reduces the time to when infants were assessed as being fit for discharge, defined as in air with saturations of > 92% for 6 hours, by 25%. DESIGN: Parallel-group, pragmatic randomised controlled trial, cost-utility analysis and systematic review. SETTING: Ten UK hospitals. PARTICIPANTS: Infants with acute bronchiolitis requiring oxygen therapy were allocated within 4 hours of admission. INTERVENTIONS: Supportive care with oxygen as required, minimal handling and fluid administration as appropriate to the severity of the disease, 3% nebulised HS every ± 6 hours. MAIN OUTCOME MEASURES: The trial primary outcome was time until the infant met objective discharge criteria. Secondary end points included time to discharge and adverse events. The costs analysed related to length of stay (LoS), readmissions, nebulised saline and other NHS resource use. Quality-adjusted life-years (QALYs) were estimated using an existing utility decrement derived for hospitalisation in children, together with the time spent in hospital in the trial. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and other databases from inception or from 2010 onwards, searched ClinicalTrials.gov and other registries and hand-searched Chest, Paediatrics and Journal of Paediatrics to January 2015. REVIEW METHODS: We included randomised/quasi-randomised trials which compared HS versus saline (± adjunct treatment) or no treatment. We used a fixed-effects model to combine mean differences for LoS and assessed statistical heterogeneity using the I (2) statistic. RESULTS: The trial randomised 158 infants to HS (n = 141 analysed) and 159 to standard care (n = 149 analysed). There was no difference between the two arms in the time to being declared fit for discharge [median 76.6 vs. 75.9 hours, hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.75 to 1.20] or to actual discharge (median 88.5 vs. 88.7 hours, HR 0.97, 95% CI 0.76 to 1.23). There was no difference in adverse events. One infant developed bradycardia with desaturation associated with HS. Mean hospital costs were £2595 and £2727 for the control and intervention groups, respectively (p = 0.657). Incremental QALYs were 0.0000175 (p = 0.757). An incremental cost-effectiveness ratio of £7.6M per QALY gained was not appreciably altered by sensitivity analyses. The systematic review comprised 15 trials (n = 1922) including our own. HS reduced the mean LoS by -0.36 days (95% CI -0.50 to -0.22 days). High levels of heterogeneity (I (2) = 78%) indicate that the result should be treated cautiously. CONCLUSIONS: In this trial, HS had no clinical benefit on LoS or readiness for discharge and was not a cost-effective treatment for acute bronchiolitis. Claims that HS achieves small reductions in LoS must be treated with scepticism. FUTURE WORK: Well-powered randomised controlled trials of high-flow oxygen are needed. STUDY REGISTRATION: This study is registered as NCT01469845 and CRD42014007569. FUNDING DETAILS: This project was funded by the NIHR Health Technology Assessment (HTA) programme and will be published in full in Health Technology Assessment; Vol. 19, No. 66. See the HTA programme website for further project information.

Case-control study of craniomandibular disorders in patients with fibromyalgia.

BACKGROUND: Fibromyalgia is a clinical syndrome characterized by chronic widespread pain, which is non-articular and is predominantly experienced in the muscles and vertebral column, and by extensive heightened sensitivity to local pressure at many specific points The purpose of this study was to measure differences in the level of painful symptoms and in the movements of the mandible in a group of patients who had been diagnosed as suffering from fibromyalgia, in comparison with a control group. The anxiety and subjective pain levels and their relation with mandibular mobility were also compared. MATERIAL AND METHODS: A case-control study was designed. The temporomandibular joints and masticatory muscles of the cases (n=20) and controls (n=18) were examined, anxiety was assessed by the STAI index and subjective pain was measured on a visual analogue scale. The data analysis was carried out with SPSS v.19.0 software. The descriptive data were expressed as means and proportions at a 95% confidence interval. The proportions were compared with the chi-square test and the means with the Mann-Whitney U test. Pearson's correlation coefficient was used to measure the association between quantitative variables. RESULTS: The fibromyalgia patients (the case group) presented a higher level of pain following the musculoskeletal examination and significantly greater symptoms at the examination points. Regarding joint mobility, significant differences in mandibular opening were found (cases 43.4 mm vs controls 47.2 mm, p = 0.042). The mean pain score of the cases was significantly higher than that of the controls (4.03 vs 1.8, p = 0.001) but no significant differences were found in the anxiety index (23.8 vs 23.4). CONCLUSIONS: patients with fibromyalgia are affected to a greater extent by craniomandibular disorders, with lower mouth opening and higher pain levels than healthy persons. However, the anxiety levels of the two groups are similar. Key words:Fibromyalgia, orofacial pain, temporomandibular disorder.

CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation.

A diverse family of cytoskeletal dynein motors powers various cellular transport systems, including axonemal dyneins generating the force for ciliary and flagellar beating essential to movement of extracellular fluids and of cells through fluid. Multisubunit outer dynein arm (ODA) motor complexes, produced and preassembled in the cytosol, are transported to the ciliary or flagellar compartment and anchored into the axonemal microtubular scaffold via the ODA docking complex (ODA-DC) system. In humans, defects in ODA assembly are the major cause of primary ciliary dyskinesia (PCD), an inherited disorder of ciliary and flagellar dysmotility characterized by chronic upper and lower respiratory infections and defects in laterality. Here, by combined high-throughput mapping and sequencing, we identified CCDC151 loss-of-function mutations in five affected individuals from three independent families whose cilia showed a complete loss of ODAs and severely impaired ciliary beating. Consistent with the laterality defects observed in these individuals, we found Ccdc151 expressed in vertebrate left-right organizers. Homozygous zebrafish ccdc151(ts272a) and mouse Ccdc151(Snbl) mutants display a spectrum of situs defects associated with complex heart defects. We demonstrate that CCDC151 encodes an axonemal coiled coil protein, mutations in which abolish assembly of CCDC151 into respiratory cilia and cause a failure in axonemal assembly of the ODA component DNAH5 and the ODA-DC-associated components CCDC114 and ARMC4. CCDC151-deficient zebrafish, planaria, and mice also display ciliary dysmotility accompanied by ODA loss. Furthermore, CCDC151 coimmunoprecipitates CCDC114 and thus appears to be a highly evolutionarily conserved ODA-DC-related protein involved in mediating assembly of both ODAs and their axonemal docking machinery onto ciliary microtubules.

MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia.

Reduced generation of multiple motile cilia (RGMC) is a rare mucociliary clearance disorder. Affected persons suffer from recurrent infections of upper and lower airways because of highly reduced numbers of multiple motile respiratory cilia. Here we report recessive loss-of-function and missense mutations in MCIDAS-encoding Multicilin, which was shown to promote the early steps of multiciliated cell differentiation in Xenopus. MCIDAS mutant respiratory epithelial cells carry only one or two cilia per cell, which lack ciliary motility-related proteins (DNAH5; CCDC39) as seen in primary ciliary dyskinesia. Consistent with this finding, FOXJ1-regulating axonemal motor protein expression is absent in respiratory cells of MCIDAS mutant individuals. CCNO, when mutated known to cause RGMC, is also absent in MCIDAS mutant respiratory cells, consistent with its downstream activity. Thus, our findings identify Multicilin as a key regulator of CCNO/FOXJ1 for human multiciliated cell differentiation, and highlight the 5q11 region containing CCNO and MCIDAS as a locus underlying RGMC.

Diagnosis and management of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of motile cilia characterised by chronic lung disease, rhinosinusitis, hearing impairment and subfertility. Nasal symptoms and respiratory distress usually start soon after birth, and by adulthood bronchiectasis is invariable. Organ laterality defects, usually situs inversus, occur in ∼50% of cases. The estimated prevalence of PCD is up to ∼1 per 10,000 births, but it is more common in populations where consanguinity is common. This review examines who to refer for diagnostic testing. It describes the limitations surrounding diagnosis using currently available techniques and considers whether recent advances to genotype patients with PCD will lead to genetic testing and screening to aid diagnosis in the near future. It discusses the challenges of monitoring and treating respiratory and ENT disease in children with PCD.

Overcoming challenges in the management of primary ciliary dyskinesia: the UK model.

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease associated with bronchiectasis, chronic rhinosinusitis, infertility and situs inversus. Estimates of prevalence vary widely, but is probably between 1:10,000- 1:40,000 in most populations. A number of observational studies indicate that access to services to diagnose and manage patients with PCD vary both between and within countries. Diagnosis is often delayed and frequently missed completely. The prognosis of patients with PCD is variable, but evidence suggests that it is improved by early diagnosis and specialist care. This article briefly reviews the literature concerning PCD and the evidence that specialist care will improve healthcare outcomes. The article specifically refers to a new national service in the UK.

Bed- and sofa-sharing practices in a UK biethnic population.

OBJECTIVE: To describe the prevalence and associations of bed- and sofa-sharing in a biethnic UK birth cohort. METHODS: We surveyed 3082 participants in the Born in Bradford birth cohort study by using a telephone interview when infants were aged 2 to 4 months. We asked families about sleep surface sharing behaviors, and other sudden unexpected death in infancy (SUDI)-related behaviors. RESULTS: There were 15.5% of families that had ever bed-shared, 7.2% of families regularly bed-shared, and 9.4% of families had ever sofa-shared with their infants; 1.4% reported both. Regular bed-sharers were more commonly Pakistani (adjusted odds ratio [aOR] = 3.02, 95% confidence interval [CI] 1.96-4.66), had further or higher educational qualifications (aOR = 1.62, 95% CI 1.03-2.57), or breastfed for at least 8 weeks (aOR = 3.06, 95% CI 2.00-4.66). The association between breastfeeding and bed-sharing was greater among white British than Pakistani families. Sofa-sharing occurred in association with smoking (aOR = 1.79, 95% CI 1.14-2.80) and breastfeeding for more than 8 weeks (aOR = 1.76, 95% CI 1.19-2.58), and was less likely in Pakistani families (aOR = 0.21, 95% CI 0.14-0.31), or single-parent families (aOR = 0.50, 95% CI 0.29-0.87). CONCLUSIONS: The data confirm that bed-sharing and sofa-sharing are distinct practices, which should not be combined in studies of unexpected infant deaths as a single exposure. The determinants of sleep-surface sharing differ between the UK Pakistani and UK majority communities, and from those of US minority communities. Caution is needed in generalizing SUDI/SIDS risk factors across populations with differing risk factor profiles, and care should be taken in adopting SUDI/SIDS reduction guidelines from other contexts.

Infant care practices related to sudden infant death syndrome in South Asian and White British families in the UK.

In the UK, infants of South Asian parents have a lower rate of sudden infant death syndrome (SIDS) than White British infants. Infant care and life style behaviours are strongly associated with SIDS risk. This paper describes and explores variability in infant care between White British and South Asian families (of Bangladeshi, Indian or Pakistani origin) in Bradford, UK (the vast majority of which were Pakistani) and identifies areas for targeted SIDS intervention. A cross-sectional telephone interview study was conducted involving 2560 families with 2- to 4-month-old singleton infants enrolled in the Born in Bradford cohort study. Outcome measures were prevalence of self-reported practices in infant sleeping environment, sharing sleep surfaces, breast feeding, use of dummy or pacifier, and life style behaviours. We found that, compared with White British infants, Pakistani infants were more likely to: sleep in an adult bed (OR = 8.48 [95% CI 2.92, 24.63]); be positioned on their side for sleep (OR = 4.42 [2.85, 6.86]); have a pillow in their sleep environment (OR = 9.85 [6.39, 15.19]); sleep under a duvet (OR = 3.24 [2.39, 4.40]); be swaddled for sleep (OR = 1.49 [1.13, 1.97]); ever bed-share (OR = 2.13 [1.59, 2.86]); regularly bed-share (OR = 3.57 [2.23, 5.72]); ever been breast-fed (OR = 2.00 [1.58, 2.53]); and breast-fed for 8+ weeks (OR = 1.65 [1.31, 2.07]). Additionally, Pakistani infants were less likely to: sleep in a room alone (OR = 0.05 [0.03, 0.09]); use feet-to-foot position (OR = 0.36 [0.26, 0.50]); sleep with a soft toy (OR = 0.52 [0.40, 0.68]); use an infant sleeping bag (OR = 0.20 [0.16, 0.26]); ever sofa-share (OR = 0.22 [0.15, 0.34]); be receiving solid foods (OR = 0.22 [0.17, 0.30]); or use a dummy at night (OR = 0.40 [0.33, 0.50]). Pakistani infants were also less likely to be exposed to maternal smoking (OR = 0.07 [0.04, 0.12]) and to alcohol consumption by either parent. No difference was found in the prevalence of prone sleeping (OR = 1.04 [0.53, 2.01]). Night-time infant care therefore differed significantly between South Asian and White British families. South Asian infant care practices were more likely to protect infants from the most important SIDS risks such as smoking, alcohol consumption, sofa-sharing and solitary sleep. These differences may explain the lower rate of SIDS in this population.