Air pollution exposure during pregnancy and lung function in childhood: The LUIS study.

BACKGROUND: The adverse effects of high air pollution levels on childhood lung function are well-known. Limited evidence exists on the effects of moderate exposure levels during early life on childhood lung function. We investigated the association of exposure to moderate air pollution during pregnancy, infancy, and preschool time with lung function at school age in a Swiss population-based study. METHODS: Fine-scale spatiotemporal model estimates of particulate matter with a diameter <2.5 µm (PM2.5) and nitrogen dioxide (NO2) were linked with residential address histories. We compared air pollution exposures within different time windows (whole pregnancy, first, second, and third trimester of pregnancy, first year of life, preschool age) with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) measured cross-sectionally using linear regression models adjusted for potential confounders. RESULTS: We included 2182 children, ages 6-17 years. Prenatal air pollution exposure was associated with reduced lung function at school age. In children aged 12 years, per 10 µg·m-3 increase in PM2.5 during pregnancy, FEV1 was 55 mL lower (95% CI -84 to -25 mL) and FVC 62 mL lower (95% CI -96 to -28 mL). Associations were age-dependent since they were stronger in younger and weaker in older children. PM2.5 exposure after birth was not associated with reduced lung function. There was no association between NO2 exposure and lung function. CONCLUSION: In utero lung development is most sensitive to air pollution exposure, since even modest PM2.5 exposure during the prenatal time was associated with reduced lung function, most prominent in younger children.

Lung structural and functional impairments in young children with cystic fibrosis diagnosed following newborn screening - A nationwide observational study.

BACKGROUND: Non-invasive and sensitive clinical endpoints are needed to monitor onset and progression of early lung disease in children with cystic fibrosis (CF). We compared lung clearance index (LCI), FEV1, functional and structural lung magnetic resonance imaging (MRI) outcomes in Swiss children with CF diagnosed following newborn screening. METHODS: Lung function (LCI, FEV1) and unsedated functional and structural lung MRI was performed in 79 clinically stable children with CF (3 - 8 years) and 75 age-matched healthy controls. Clinical information was collected throughout childhood. RESULTS: LCI, ventilation and perfusion defects, and structural MRI scores were significantly higher in children with CF compared with controls, but FEV1 was not different between groups. Lung MRI outcomes correlated significantly with LCI (morphology score (r = 0.56, p < 0.001); ventilation defects (r = 0.43, p = 0.001); perfusion defects (r = 0.64, p < 0.001), but not with FEV1. Lung MRI outcomes were more sensitive to detect impairments in children with CF (abnormal ventilation and perfusion outcomes in 47 %, morphology score in 30 %) compared with lung function (abnormal LCI in 21 % and FEV1 in 4.8 %). Pulmonary exacerbations, respiratory hospitalizations, and increase in patient-reported cough was associated with higher LCI and higher structural and functional MRI outcomes. CONCLUSIONS: The LCI and lung MRI outcomes non-invasively detect even mild early lung disease in young children with CF diagnosed following newborn screening. Pulmonary exacerbations and early respiratory symptoms were risk factors for structural and functional impairment in childhood.

Differences in autophagy marker levels at birth in preterm vs. term infants.

BACKGROUND: Preterm infants are susceptible to oxidative stress and prone to respiratory diseases. Autophagy is an important defense mechanism against oxidative-stress-induced cell damage and involved in lung development and respiratory morbidity. We hypothesized that autophagy marker levels differ between preterm and term infants. METHODS: In the prospective Basel-Bern Infant Lung Development (BILD) birth cohort we compared cord blood levels of macroautophagy (Beclin-1, LC3B), selective autophagy (p62) and regulation of autophagy (SIRT1) in 64 preterm and 453 term infants. RESULTS: Beclin-1 and LC3B did not differ between preterm and term infants. However, p62 was higher (0.37, 95% confidence interval (CI) 0.05;0.69 in log2-transformed level, p = 0.025, padj = 0.050) and SIRT1 lower in preterm infants (-0.55, 95% CI -0.78;-0.31 in log2-transformed level, padj < 0.001). Furthermore, p62 decreased (padj-value for smoothing function was 0.018) and SIRT1 increased (0.10, 95% CI 0.07;0.13 in log2-transformed level, padj < 0.001) with increasing gestational age. CONCLUSION: Our findings suggest differential levels of key autophagy markers between preterm and term infants. This adds to the knowledge of the sparsely studied field of autophagy mechanisms in preterm infants and might be linked to impaired oxidative stress response, preterm birth, impaired lung development and higher susceptibility to respiratory morbidity in preterm infants. IMPACT: To the best of our knowledge, this is the first study to investigate autophagy marker levels between human preterm and term infants in a large population-based sample in cord blood plasma This study demonstrates differential levels of key autophagy markers in preterm compared to term infants and an association with gestational age This may be linked to impaired oxidative stress response or developmental aspects and provide bases for future studies investigating the association with respiratory morbidity.

Evaluation of the Double-Tracer Gas Single-Breath Washout Test in a Pediatric Field Study.

BACKGROUND: The early life origins of chronic pulmonary diseases are thought to arise in peripheral small airways. Predictors of ventilation inhomogeneity, a proxy of peripheral airway function, are understudied in schoolchildren. RESEARCH QUESTION: Is the double-tracer gas single-breath washout (DTG-SBW) measurement feasible in a pediatric field study setting? What are the predictors of the DTG-SBW-derived ventilation inhomogeneity estimate in unselected schoolchildren? STUDY DESIGN AND METHODS: In this prospective cross-sectional field study, a mobile lung function testing unit visited participating schools in Switzerland. We applied DTG-SBW, fraction of exhaled nitric oxide (Feno), and spirometry measurements. The DTG-SBW is based on tidal inhalation of helium and sulfur-hexafluoride, and the phase III slope (SIIIHe-SF6) is derived. We assessed feasibility, repeatability, and associations of SIIIHe-SF6 with the potential predictors of anthropometrics, presence of wheeze (ie, parental report of one or more episode of wheeze in the prior year), Feno, FEV1, and FEV1/FVC. RESULTS: In 1,782 children, 5,223 DTG-SBW trials were obtained. The DTG-SBW was acceptable in 1,449 children (81.3%); the coefficient of variation was 39.8%. SIIIHe-SF6 was independently but weakly positively associated with age and BMI. In 276 children (21.2%), wheeze was reported. SIIIHe-SF6 was higher by 0.049 g.mol.L-1 in children with wheeze compared with those without and remained associated with wheeze after adjusting for age and BMI in a multivariable linear regression model. SIIIHe-SF6 was not associated with Feno, FEV1, and FEV1/FVC. INTERPRETATION: The DTG-SBW is feasible in a pediatric field study setting. On the population level, age, body composition, and wheeze are independent predictors of peripheral airway function in unselected schoolchildren. The variation of the DTG-SBW possibly constrains its current applicability on the individual level. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03659838; URL: www. CLINICALTRIALS: gov.

Data accuracy, consistency and completeness of the national Swiss cystic fibrosis patient registry: Lessons from an ECFSPR data quality project.

BACKGROUND: Good data quality is essential when rare disease registries are used as a data source for pharmacovigilance studies. This study investigated data quality of the Swiss cystic fibrosis (CF) registry in the frame of a European Cystic Fibrosis Society Patient Registry (ECFSPR) project aiming to implement measures to increase data reliability for registry-based research. METHODS: All 20 pediatric and adult Swiss CF centers participated in a data quality audit between 2018 and 2020, and in a re-audit in 2022. Accuracy, consistency and completeness of variables and definitions were evaluated, and missing source data and informed consents (ICs) were assessed. RESULTS: The first audit included 601 out of 997 Swiss people with CF (60.3 %). Data quality, as defined by data correctness ≥95 %, was high for most of the variables. Inconsistencies of specific variables were observed because of an incorrect application of the variable definition. The proportion of missing data was low with <5 % for almost all variables. A considerable number of missing source data occurred for CFTR variants. Availability of ICs varied largely between centers (10 centers had >5 % of missing documents). After providing feedback to the centers, availability of genetic source data and ICs improved. CONCLUSIONS: Data audits demonstrated an overall good data quality in the Swiss CF registry. Specific measures such as support of the participating sites, training of data managers and centralized data collection should be implemented in rare disease registries to optimize data quality and provide robust data for registry-based scientific research.

Multiple breath washout and oscillometry after allogenic HSCT: a scoping review.

Pulmonary chronic graft-versus-host disease (cGVHD) is a substantial cause of pulmonary morbidity and mortality post-haematopoietic stem cell transplantation (HSCT). Current spirometry-based monitoring strategies have significant limitations. Understanding the utility of novel peripheral airway function tests - multiple breath washout (MBW) and oscillometry - is critical in efforts to improve detection, facilitate earlier intervention and improve outcomes. In this scoping review, we identified 17 studies investigating MBW or oscillometry, or both, after allogenic HSCT. Despite small study numbers limiting the ability to draw firm conclusions, several themes were evident. Detectable peripheral airway abnormality in MBW occurred in a substantial proportion prior to HSCT. MBW indices post-HSCT were more frequently abnormal than spirometry when reporting group data and among those with extrapulmonary cGVHD and pulmonary cGVHD. Changes in MBW indices over time may be more indicative of pulmonary complications than absolute values at any given time point. Oscillometry indices were often normal at baseline, but more frequently abnormal in those who developed pulmonary cGVHD. Pooling currently available individual participant data across these studies may improve our ability to formally compare their respective sensitivity and specificity at specific time points and assess the trajectory of MBW and oscillometry indices over time.

Variability of clinically measured lung clearance index in children with cystic fibrosis.

RATIONALE: The lung clearance index (LCI) is increasingly being used in the clinical surveillance of patients with cystic fibrosis (CF). However, there are limited data on long-term variability and physiologically relevant changes in LCI during routine clinical surveillance. OBJECTIVES: To evaluate the long-term variability of LCI and propose a threshold for a physiologically relevant change. METHODS: In children aged 4-18 years with CF, LCI was measured every 3 months as part of routine clinical surveillance during 2011-2020 in two centers. The variability of LCI during periods of clinical stability was assessed using mixed-effects models and was used to identify thresholds for physiologically relevant changes. RESULTS: Repeated LCI measurements of acceptable quality (N = 858) were available in 100 patients with CF; for 74 patients, 399 visits at clinical stability were available. The variability of repeated LCI measurements over time expressed as the coefficient of variation (CV%) was 7.4%. The upper limit of normal (ULN) for relative changes in LCI between visits was 19%. CONCLUSION: We report the variability of LCI in children and adolescents with CF during routine clinical surveillance. According to our data, a change in LCI beyond 19% may be considered physiologically relevant. These findings will help guide clinical decisions according to LCI changes.

Associations of Mucosal Nerve Fiber Innervation Density with Hirschsprung-Associated Enterocolitis: A Retrospective Three-Center Cohort Study.

OBJECTIVE: Hirschsprung's disease (HSCR) is a congenital intestinal neurodevelopmental disorder characterized by the absence of enteric ganglion cells in the distal colon. Although Hirschsprung-associated enterocolitis (HAEC) is the most frequent life-threatening complication in HSCR, to date reliable biomarkers predicting the likelihood of HAEC are yet to be established. We established a three-center retrospective study including 104 HSCR patients surgically treated between 1998 and 2019. MATERIALS AND METHODS: Patient-derived cryopreserved or paraffin-preserved colonic tissue at surgery was analyzed via ßIII-tubulin immunohistochemistry. We subsequently determined extrinsic mucosal nerve fiber density in resected rectosigmoid specimens and classified HSCR patients accordingly into nerve fiber-high or fiber-low groups. We compared the distribution of clinical parameters obtained from medical records between the fiber-high (n = 36) and fiber-low (n = 68) patient groups. We assessed the association between fiber phenotype and enterocolitis using univariate and multivariate logistic regression adjusted for age at operation. RESULTS: Enterocolitis was more prevalent in patients with sparse mucosal nerve fiber innervation (fiber-low phenotype, 87%) compared with the fiber-high phenotype (13%; p = 0.002). In addition, patients developing enterocolitis had a younger age at surgery (3 vs. 7 months; p = 0.016). In the univariate analysis, the odds for enterocolitis development in the fiber-low phenotype was 5.26 (95% confidence interval [CI], 1.67-16.59; p = 0.005) and 4.01 (95% CI, 1.22-13.17; p = 0.022) when adjusted for age. CONCLUSION: Here, we showed that HSCR patients with a low mucosal nerve fiber innervation grade in the distal aganglionic colon have a higher risk of developing HAEC. Consequently, histopathologic analysis of the nerve fiber innervation grade could serve as a novel sensitive prognostic marker associated with the development of enterocolitis in HSCR patients.

Possible effects of left pulmonary artery stenting in single ventricle patients on bronchial area, lung volume and lung function.

Background: Left pulmonary artery (LPA) stenting is often required in single ventricle (SV) patients. Due to their close anatomical relationship an LPA stent could potentially compress the left main bronchus (LMB). We assessed the impact of LPA stenting on bronchial size, pulmonary volumes, and lung function in a cohort of SV patients. Methods: Forty-nine patients underwent cardiovascular magnetic resonance (CMR) and 36 spirometry 11 (8-15) years after Fontan. All patients were free of respiratory symptoms. LPA stents were inserted in 17 (35%) patients at 8.8 (3.4-12.6) years. Area/shape of the main bronchi (n = 46) and lung volumes (n = 47) were calculated from CMR-ZTE images for each lung and transformed in right-to-left (r/l) ratio and indexed for BSA. The effect of early stent insertion (prior to stage III) was analyzed. Results: Patients with LPA stent had larger r/l ratio for main bronchus area (p < 0.001) and r/l ratio difference for lung volumes was slightly larger in patients with early stenting. A trend toward a deformation of LMB shape in patients with LPA stent and toward a higher prevalence of abnormal spirometry in patients with early stent implantation was observed. Conclusions: In this cohort of patients, early insertion of LPA stents seems to relate with smaller LMB sizes and a trend toward smaller left lung volume and higher prevalence of impaired lung function. Whether these findings are caused by the stent or, at least to a certain degree, present prior to the implantation needs to be verified.

An interoperability framework for multicentric breath metabolomic studies.

Exhaled breath contains valuable information at the molecular level and offers promising potential for precision medicine. However, few breath tests transition to routine clinical practice, partly because of the missing validation in multicenter trials. Therefore, we developed and applied an interoperability framework for standardized multicenter data acquisition and processing for breath analysis with secondary electrospray ionization-high resolution mass spectrometry. We aimed to determine the technical variability and metabolic coverage. Comparison of multicenter data revealed a technical variability of ∼20% and a core signature of the human exhaled metabolome consisting of ∼850 features, corresponding mainly to amino acid, xenobiotic, and carbohydrate metabolic pathways. In addition, we found high inter-subject variability for certain metabolic classes (e.g., amino acids and fatty acids), whereas other regions such as the TCA cycle were relatively stable across subjects. The interoperability framework and overview of metabolic coverage presented here will pave the way for future large-scale multicenter trials.

External validation of the Predicting Asthma Risk in Children tool in a clinical cohort.

INTRODUCTION: The Predicting Asthma Risk in Children (PARC) tool uses questionnaire-based respiratory symptoms collected from preschool children to predict asthma risk 5 years later. The tool was developed and validated in population cohorts but not validated using a clinical cohort. We aimed to externally validate the PARC tool in a pediatric pulmonology clinic setting. METHODS: The Swiss Paediatric Airway Cohort (SPAC) is a prospective cohort of children seen in pediatric pulmonology clinics across Switzerland. We included children aged 1-6 years with cough or wheeze at baseline who completed the 2-year follow-up questionnaire. The outcome was defined as current wheeze plus use of asthma medication. We assessed performance using: sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV), area under the curve (AUC), scaled Brier's score, and Nagelkerke's R2 scores. We compared performance in SPAC to that in the original population, the Leicester Respiratory Cohort (LRC). RESULTS: Among 346 children included, 125 (36%) reported the outcome after 2 years. At a PARC score of 4: sensitivity was higher (95% vs. 79%), specificity lower (14% vs. 57%), and NPV and PPV comparable (0.84 vs. 0.87 and 0.37 vs. 0.42) in SPAC versus LRC. AUC (0.71 vs. 0.78), R2 (0.18 vs. 0.28) and Brier's scores (0.13 vs. 0.22) were lower in SPAC. CONCLUSIONS: The PARC tool shows some clinical utility, particularly for ruling out the development of asthma in young children, but performance limitations highlight the need for new prediction tools to be developed specifically for the clinical setting.

Age and body mass index affect fit of spirometry Global Lung Function Initiative references in schoolchildren.

Background: References from the Global Lung Function Initiative (GLI) are widely used to interpret children's spirometry results. We assessed fit for healthy schoolchildren. Methods: LuftiBus in the School was a population-based cross-sectional study undertaken in 2013-2016 in the canton of Zurich, Switzerland. Parents and their children aged 6-17 years answered questionnaires about respiratory symptoms and lifestyle. Children underwent spirometry in a mobile lung function lab. We calculated GLI-based z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow for 25-75% of FVC (FEF25-75) for healthy White participants. We defined appropriate fit to GLI references by mean values between +0.5 and -0.5 z-scores. We assessed whether fit varied by age, body mass index, height and sex using linear regression models. Results: We analysed data from 2036 children with valid FEV1 measurements, of whom 1762 also had valid FVC measurements. The median age was 12.2 years. Fit was appropriate for children aged 6-11 years for all indices. In adolescents aged 12-17 years, fit was appropriate for FEV1/FVC z-scores (mean±sd -0.09±1.02), but not for FEV1 (-0.62±0.98), FVC (-0.60±0.98) and FEF25-75 (-0.54±1.02). Mean FEV1, FVC and FEF25-75 z-scores fitted better in children considered overweight (-0.25, -0.13 and -0.38, respectively) than normal weight (-0.55, -0.50 and -0.55, respectively; p-trend <0.001, 0.014 and <0.001, respectively). FEV1, FVC and FEF25-75 z-scores depended on both age and height (p-interaction 0.033, 0.019 and <0.001, respectively). Conclusion: GLI-based FEV1, FVC, and FEF25-75 z-scores do not fit White Swiss adolescents well. This should be considered when using reference equations for clinical decision-making, research and international comparison.

Pollen exposure is associated with risk of respiratory symptoms during the first year of life.

BACKGROUND: Pollen exposure is associated with respiratory symptoms in children and adults. However, the association of pollen exposure with respiratory symptoms during infancy, a particularly vulnerable period, remains unclear. We examined whether pollen exposure is associated with respiratory symptoms in infants and whether maternal atopy, infant's sex or air pollution modifies this association. METHODS: We investigated 14,874 observations from 401 healthy infants of a prospective birth cohort. The association between pollen exposure and respiratory symptoms, assessed in weekly telephone interviews, was evaluated using generalized additive mixed models (GAMMs). Effect modification by maternal atopy, infant's sex, and air pollution (NO2 , PM2.5 ) was assessed with interaction terms. RESULTS: Per infant, 37 ± 2 (mean ± SD) respiratory symptom scores were assessed during the analysis period (January through September). Pollen exposure was associated with increased respiratory symptoms during the daytime (RR [95% CI] per 10% pollen/m3 : combined 1.006 [1.002, 1.009]; tree 1.005 [1.002, 1.008]; grass 1.009 [1.000, 1.23]) and nighttime (combined 1.003 [0.999, 1.007]; tree 1.003 [0.999, 1.007]; grass 1.014 [1.004, 1.024]). While there was no effect modification by maternal atopy and infant's sex, a complex crossover interaction between combined pollen and PM2.5 was found (p-value 0.003). CONCLUSION: Even as early as during the first year of life, pollen exposure was associated with an increased risk of respiratory symptoms, independent of maternal atopy and infant's sex. Because infancy is a particularly vulnerable period for lung development, the identified adverse effect of pollen exposure may be relevant for the evolvement of chronic childhood asthma.

Feasibility of nasal NO screening in healthy newborns.

BACKGROUND: Nasal nitric oxide (nNO) measurement is recommended as a first line screening test for primary ciliary dyskinesia (PCD). While reliable velum- and non-velum-closure techniques exist for preschool children and older individuals, no data are available for neonates. AIMS: To determine feasibility of nNO screening and nNO concentration in healthy newborns in the first week of life. METHODS: Nasal NO was analyzed in tidal breathing during natural sleep using a CLD-88 sp NO analyzer (chemoluminescence sensor) and a NIOX MINO (electrochemical sensor). Test success and nNO concentration were determined and compared between the two devices. RESULTS: Nasal NO was measured in 62 healthy neonates within the first week of life. Feasibility of nNO measurement was 100% for at least one nostril and 85.5% for both nostrils using the chemoluminescence device, but significantly lower with the electrochemical device (85.5% and 53.2%; p < .001). Median nNO concentration was 38 ppb (interquartile range, 27-55; range, 9-100) with the ECOMEDICS device and 23 (15-33, 8-59) with the NIOX MINO (p < .001), with a trend towards higher values for older subjects. None of the subjects exceeded nNO levels of 100 ppb. CONCLUSION: Measurement of nNO using a chemoluminescence device is highly feasible in newborns during natural sleep. However, nNO levels are considerably lower compared to the published data for older individuals and in the range of a PCD reference group of infants between 4 and 8 weeks of age, potentially resulting in a great overlap with subjects with PCD in this age group. Therefore, screening for PCD using nasal NO might not be useful in the first week of life. Upon clinical suspicion, other diagnostic tests such as high-speed video analysis of the cilia should be applied.

Increased Impact of Air Pollution on Lung Function in Preterm versus Term Infants: The BILD Study.

Rationale: Infants born prematurely have impaired capacity to deal with oxidative stress shortly after birth. Objectives: We hypothesize that the relative impact of exposure to air pollution on lung function is higher in preterm than in term infants. Methods: In the prospective BILD (Basel-Bern Infant Lung Development) birth cohort of 254 preterm and 517 term infants, we investigated associations of particulate matter ⩽10 µm in aerodynamic diameter (PM10) and nitrogen dioxide with lung function at 44 weeks' postconceptional age and exhaled markers of inflammation and oxidative stress response (fractional exhaled nitric oxide [FeNO]) in an explorative hypothesis-driven study design. Multilevel mixed-effects models were used and adjusted for known confounders. Measurements and Main Results: Significant associations of PM10 during the second trimester of pregnancy with lung function and FeNO were found in term and preterm infants. Importantly, we observed stronger positive associations in preterm infants (born 32-36 wk), with an increase of 184.9 (95% confidence interval [CI], 79.1-290.7) ml/min [Formula: see text]e per 10-µg/m3 increase in PM10, than in term infants (75.3; 95% CI, 19.7-130.8 ml/min) (pprematurity × PM10 interaction = 0.04, after multiple comparison adjustment padj = 0.09). Associations of PM10 and FeNO differed between moderate to late preterm (3.4; 95% CI, -0.1 to 6.8 ppb) and term (-0.3; 95% CI, -1.5 to 0.9 ppb) infants, and the interaction with prematurity was significant (pprematurity × PM10 interaction = 0.006, padj = 0.036). Conclusions: Preterm infants showed significantly higher susceptibility even to low to moderate prenatal air pollution exposure than term infants, leading to increased impairment of postnatal lung function. FeNO results further elucidate differences in inflammatory/oxidative stress response when comparing preterm infants with term infants.

Association of transportation noise with sleep during the first year of life: A longitudinal study.

STUDY OBJECTIVES: During infancy, adequate sleep is crucial for physical and neurocognitive development. In adults and children, night-time noise exposure is associated with sleep disturbances. However, whether and to what extent infants' sleep is affected, is unknown. Thus, this study investigated the relationship between nocturnal transportation noise and actimetry-derived habitual sleep behavior across the first year of life. METHODS: In 144 healthy infants (63 girls), nocturnal (23:00-7:00) transportation noise (i.e., road, railway, and aircraft) was modelled at the infants' individual places of residence. Using actimetry, we recorded movement patterns for 11 days in a longitudinal design at 3, 6, and 12 months of age and derived the recently proposed core sleep composites of night-time sleep duration, activity, and variability. Using linear mixed-effects models, we determined associations between noise exposure and sleep composites. Sex, gestational age, parents' highest educational level, infants' age, and the existence of siblings served as control variables. RESULTS: In models without interactions, night-time transportation noise was unrelated to sleep composites across the first year of life (p > .16). Exploratory analyses of an interaction between noise and the existence of siblings yielded an association between night-time transportation noise and sleep duration in infants without siblings only (p = .004). CONCLUSION: In our study, sleep in infants during the first year of life was relatively robust against external perturbation by night-time transportation noise. However, particularly in children without siblings increasing night-time transportation noise reduced sleep duration. This suggests that the habitual noise environment may modulate individual susceptibility to adverse effects of noise on sleep.

Are children born by cesarean delivery at higher risk for respiratory sequelae?

BACKGROUND: Globally, the number of children born by cesarean delivery is constantly increasing. However, hormonal and physiological changes associated with labor and vaginal delivery are considered necessary for lung maturation. OBJECTIVE: We aimed to assess whether the mode of delivery is associated with changes in respiratory and atopic outcomes during infancy and at school age. STUDY DESIGN: We included 578 children, born at ≥37 weeks of gestation, from a prospective birth cohort study. We compared weekly respiratory symptoms throughout the first year of life and infant lung function (tidal breathing and multiple-breath washout) at 5 weeks of age between children born by cesarean delivery (N=114) and those born by vaginal delivery (N=464) after term pregnancy in healthy women. At a follow-up visit conducted at 6 years of age (N=371, of which 65 were delivered by cesarean delivery), we assessed respiratory, atopic, and lung function outcomes (spirometry, body plethysmography, and multiple-breath washout). We performed adjusted regression analyses to examine the association between cesarean delivery and respiratory and atopic outcomes. To account for multiple testing, we used the Bonferroni correction, which led to an adapted significance level of P<.002. RESULTS: During infancy, children born by cesarean delivery did not have more respiratory symptoms than those born by vaginal delivery (median, 4 weeks; interquartile range, 7 weeks vs median, 5 weeks; interquartile range, 7 weeks; adjusted incidence rate ratio, 0.8; 95% confidence interval, 0.6-1.0; P=.02). Infant lung function was similar between the groups. Children born by cesarean delivery did not have a higher incidence of "ever wheezing" (adjusted odds ratio, 0.9; 95% confidence interval, 0.5-1.8; P=.78) or current asthma (adjusted odds ratio, 0.4; 95% confidence interval, 0.0-3.5; P=.42) at school age than those born by vaginal delivery. There was no difference in the lung function parameters between the groups. CONCLUSION: Cesarean delivery was not associated with respiratory symptoms in the first year of life, nor with different respiratory or atopic outcomes at school age, when compared with vaginal delivery. Our results indicate that there are no long-term consequences on the respiratory health of the child associated with cesarean delivery.