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1.
Artigo em Inglês | MEDLINE | ID: mdl-32160369

RESUMO

BACKGROUND: Preschool children with recurrent wheezing suffer high morbidity. It is unclear whether objective measures of asthma control, such as pulmonary function tests (PFTs), provide additional information to the clinical assessment. METHODS: We recruited children between 3-6 years old, with a history of recurrent wheezing in the preceding year and treated for acute wheezing exacerbation in the Emergency Department (ED) into an observational cohort study. Children attended two outpatient visits: the first study visit within five days of discharge from the ED and the second study visit 12 weeks after the ED visit. We performed standardized symptom score (Test for Respiratory and Asthma Control in Kids (TRACK)), multiple breath washout (MBW), spirometry, and clinical assessment at both visits. RESULTS: Seventy-four children, mean (standard deviation (SD)) age 4.32 years (0.84), attended both visits. Paired FEV0.75 and LCI measurements at both time points were obtained in 37 and 34 subjects respectively. Feasibility for all tests improved at visit 2 and was not age dependent. At the second study visit, a third had controlled asthma based on the TRACK score, and the mean lung clearance index (LCI) improved from 9.86 to 8.31 (p = 0.003); however, 46% had an LCI in the abnormal range. FEV0.75 z-score improved from -1.66 to -1.17 (p = 0.05) but remained in the abnormal range in 24%. LCI was abnormal in more than half of the children with "well-controlled" asthma based on the TRACK score. There was no correlation between PFT measures and TRACK scores at either visit. CONCLUSIONS: LCI demonstrates a persistent deficit post-exacerbation in a large proportion of preschoolers with recurrent wheezing, highlighting that symptom scores alone may not suffice for monitoring these children.

2.
Lancet Respir Med ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32220282

RESUMO

BACKGROUND: Childhood asthma incidence is decreasing in some parts of Europe and North America. Antibiotic use in infancy has been associated with increased asthma risk. In the present study, we tested the hypothesis that decreases in asthma incidence are linked to reduced antibiotic prescribing and mediated by changes in the gut bacterial community. METHODS: This study comprised population-based and prospective cohort analyses. At the population level, we used administrative data from British Columbia, Canada (population 4·7 million), on annual rates of antibiotic prescriptions and asthma diagnoses, to assess the association between antibiotic prescribing (at age <1 year) and asthma incidence (at age 1-4 years). At the individual level, 2644 children from the Canadian Healthy Infant Longitudinal Development (CHILD) prospective birth cohort were examined for the association of systemic antibiotic use (at age <1 year) with the diagnosis of asthma (at age 5 years). In the same cohort, we did a mechanistic investigation of 917 children with available 16S rRNA gene sequencing data from faecal samples (at age ≤1 year), to assess how composition of the gut microbiota relates to antibiotic exposure and asthma incidence. FINDINGS: At the population level between 2000 and 2014, asthma incidence in children (aged 1-4 years) showed an absolute decrease of 7·1 new diagnoses per 1000 children, from 27·3 (26·8-28·3) per 1000 children to 20·2 (19·5-20·8) per 1000 children (a relative decrease of 26·0%). Reduction in incidence over the study period was associated with decreasing antibiotic use in infancy (age <1 year), from 1253·8 prescriptions (95% CI 1219·3-1288·9) per 1000 infants to 489·1 (467·6-511·2) per 1000 infants (Spearman's r=0·81; p<0·0001). Asthma incidence increased by 24% with each 10% increase in antibiotic prescribing (adjusted incidence rate ratio 1·24 [95% CI 1·20-1·28]; p<0·0001). In the CHILD cohort, after excluding children who received antibiotics for respiratory symptoms, asthma diagnosis in childhood was associated with infant antibiotic use (adjusted odds ratio [aOR] 2·15 [95% CI 1·37-3·39]; p=0·0009), with a significant dose-response; 114 (5·2%) of 2182 children unexposed to antibiotics had asthma by age 5 years, compared with 23 (8·1%) of 284 exposed to one course, five (10·2%) of 49 exposed to two courses, and six (17·6%) of 34 exposed to three or more courses (aOR 1·44 [1·16-1·79]; p=0·0008). Increasing α-diversity of the gut microbiota, defined as an IQR increase (25th to 75th percentile) in the Chao1 index, at age 1 year was associated with a 32% reduced risk of asthma at age 5 years (aOR for IQR increase 0·68 [0·46-0·99]; p=0·046). In a structural equation model, we found the gut microbiota at age 1 year, characterised by α-diversity, ß-diversity, and amplicon sequence variants modified by antibiotic exposure, to be a significant mediator between outpatient antibiotic exposure in the first year of life and asthma diagnosis at age 5 years (ß=0·08; p=0·027). INTERPRETATION: Our findings suggest that the reduction in the incidence of paediatric asthma observed in recent years might be an unexpected benefit of prudent antibiotic use during infancy, acting via preservation of the gut microbial community. FUNDING: British Columbia Ministry of Health, Pharmaceutical Services Branch; Canadian Institutes of Health Research; Allergy, Genes and Environment (AllerGen) Network of Centres of Excellence; Genome Canada; and Genome British Columbia.

4.
CMAJ ; 192(7): E154-E161, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071106

RESUMO

BACKGROUND: Comprehensive longitudinal studies are important for understanding the complex risk factors, pathways, exposures and interactions that lead to the development and persistence of asthma. We aimed to examine associations between use of household cleaning products in early life and childhood respiratory and allergic disease using data from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study. METHODS: We summed responses from parental questionnaires that indicated the frequency of use of 26 household cleaning products in the homes of 2022 children from this birth cohort when they were 3-4 months of age to create a cumulative Frequency of Use Score (FUS). We used multivariable logistic regression models to assess whether frequent compared with less frequent use was associated with recurrent wheeze, atopy or asthma diagnosis, as defined by the questionnaire and clinical assessments at age 3 years. Data were collected between 2008 and 2015. RESULTS: Children in homes with a higher frequency of use of cleaning products in infancy, as determined by an interquartile range increase, had higher odds of recurrent wheeze (adjusted odds ratio [OR] 1.35, 95% confidence interval [CI] 1.11-1.64), recurrent wheeze with atopy (adjusted OR 1.49, 95% CI 1.02-2.16) and asthma diagnosis (adjusted OR 1.37, 95% CI 1.09-1.70), but no increase in the odds of atopy at age 3 years (adjusted OR 1.14, 95% CI 0.96-1.35). Compared with the lowest tertile of FUS exposure, infants in the highest tertile had higher odds of acquiring asthma. Stratification of the results showed that females had higher ORs than males for all outcomes, although the p values for this sex difference did not reach statistical significance. INTERPRETATION: Frequent use of household cleaning products in early life was associated with an increased risk for childhood wheeze and asthma but not atopy at age 3 years. Our findings add to the understanding of how early life exposures to cleaning products may be associated with the development of allergic airway disease and help to identify household behaviours as a potential area for intervention.

6.
Pediatr Pulmonol ; 55(2): 338-345, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31909572

RESUMO

OBJECTIVE: The test for respiratory and asthma control in kids (TRACK score) is a standardized questionnaire tool validated to identify poor symptom control in children with stable preschool wheeze. This study determined if TRACK score measured within 5 days of an Emergency Department (ED) visit for acute wheezing predicts a subsequent wheezing exacerbation requiring an ED visit and/or treatment with systemic corticosteroids within 3 months. METHODS: This was a single-center prospective cohort study of children aged 36 to 71 months who presented to the ED with an acute episode of wheezing and had TRACK score measured at a clinic visit within 5 days of the index ED encounter, focused on information about symptoms occurring before the onset of the current acute episode. The outcomes were the independent association of a repeat wheezing exacerbation with the overall TRACK score (primary) and with mutually uncorrelated TRACK items (secondary), adjusted for sex and atopy. RESULTS: We enrolled 102 children; median age 52.3 (44.1, 59.9) months, 59% males. Of these, 33 (32.4%) had further wheezing exacerbations. For each 10 unit decrease in TRACK, the odds of a future exacerbation was 1.38 (95% CI, 1.10-1.75); male sex demonstrated OR, 5.13 (1.84-14.33). A model that included TRACK items reflecting more than equal to 1 awakenings for wheezing in the past 4 weeks, receipt of more than equal to 2 courses of corticosteroids in the last year and male sex was predictive of wheezing exacerbations: OR, 6.43 (2.18-19.00). CONCLUSION: In preschoolers with acute wheezing episodes in the ED, we have identified the TRACK score components which, together with male sex, can be used to identify children at risk of future exacerbations requiring referral for specialized care. These results need to be confirmed and validated in other populations enrolled at multiple sites before they can be implemented in practice.

8.
J Allergy Clin Immunol Pract ; 8(1): 166-175.e10, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31678300

RESUMO

BACKGROUND: Early dietary introduction of highly allergenic foods has been associated with decreased risk of food allergy in high-risk infants. OBJECTIVE: Early introduction of highly allergenic foods for lower risk infants was examined using Canadian Healthy Infant Longitudinal Development (CHILD) Study data. METHODS: CHILD participants were recruited from the general population before birth. Every 6 months, caregivers reported food introduction and allergic reactions. At ages 1 and 3 years, sensitization to peanut, egg, and cow's milk was measured by skin prick testing (SPT) and atopic dermatitis diagnosed at clinical visits. Multivariable logistic regression was used to examine associations between timing of introduction to peanut, egg, and cow's milk and the presence at 3 years of sensitization (positive SPT) and probable clinical IgE-mediated allergy (sensitization with no current consumption and convincing history of allergic reaction to the specific food). RESULTS: Among 2669 CHILD participants at age 3 years, 101 (3.80%) showed sensitization to peanut, 59 (2.21%) to egg, and 30 (1.12%) to cow's milk; 46 (1.78%) showed probable clinical IgE-mediated allergy to peanut, 4 (0.16%) to egg, and 2 (0.08%) to cow's milk. Infants introduced to peanut after 12 months had increased odds of sensitization (odds ratio [OR]: 2.38, 95% confidence interval [CI]: 1.39-4.07) and probable clinical allergy (OR: 4.04, 95% CI: 1.66-9.85) to peanut at 3 years. Associations persisted after exclusion of high-risk infants with moderate-to-severe atopic dermatitis in the first year/egg sensitization at 1 year. CONCLUSIONS: General-population infants introduced to peanut after age 12 months were more likely to have sensitization and probable clinical allergy to peanut at 3 years.

9.
J Expo Sci Environ Epidemiol ; 30(1): 70-85, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31641275

RESUMO

BACKGROUND: Few studies have examined phthalate exposure during infancy and early life, critical windows of development. The Canadian Healthy Infant Longitudinal Development (CHILD) study, a population-based birth cohort, ascertained multiple exposures during early life. OBJECTIVE: To characterize exposure to phthalates during infancy and early childhood. METHODS: Environmental questionnaires were administered, and urine samples collected at 3, 12, and 36 months. In the first 1578 children, urine was analyzed for eight phthalate metabolites: mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-3-carboxypropyl phthalate (MCPP). Geometric mean (GM) concentrations were calculated by age, together with factors that may influence concentrations. Trends with age were examined using mixed models and differences within factors examined using ANOVA. RESULTS: The highest urinary concentration was for the metabolite MBP at all ages (GM: 15-32 ng/mL). Concentrations of all phthalate metabolites significantly increased with age ranging from GM: 0.5-15.1 ng/mL at 3 months and 1.9-32.1 ng/mL at 36 months. Concentrations of all metabolites were higher in the lowest income categories except for MEHP at 3 months, among children with any breastfeeding at 12 months, and in urine collected on dates with warmer outdoor temperatures (>17 °C), except for MBzP at 3 months and MEHP at 3 and 12 months. No consistent differences were found by gender, study site, or maternal age. CONCLUSIONS: Higher phthalate metabolite concentrations were observed among children in lower income families. Examination of factors associated with income could inform interventions aimed to reduce infant phthalate exposure.

10.
Eur Respir J ; 55(1)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31558662

RESUMO

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force's questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using a blood eosinophil cut-point ≥150 µL-1 to guide anti-IL-5 initiation in adult patients with severe asthma; 3) suggest considering specific eosinophil (≥260 µL-1) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy; 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4-5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies; 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.

11.
Clin Exp Allergy ; 50(2): 178-188, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31845414

RESUMO

BACKGROUND: Maternal pre-postnatal psychosocial distress increases the risk for childhood allergic disease. This may occur through a host immunity pathway that involves intestinal secretory immunoglobulin A (sIgA). Experimental animal models show changes in the gut microbiome and immunity of offspring when exposed to direct or prenatal maternal stress, but little is known in humans. OBJECTIVE: We determined the association between maternal depression and stress symptom trajectories and infant fecal sIgA concentrations. METHODS: 1043 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort were studied. Trajectories of maternal perceived stress and depression were based on scored scales administered in pregnancy and postpartum. sIgA was quantified in infant stool (mean age 3.7 months) with Immundiagnostik ELISA. Linear regression and logistic regression were employed to test associations. RESULTS: Very low fecal sIgA concentrations were more common in infants of mothers in the antepartum and persistent depression trajectories (6% and 2% of women, respectively). Independent of breastfeeding status at fecal sampling, infant antibiotic exposure or other covariates, the antepartum depressive symptom trajectory was associated with reduced mean infant sIgA concentrations (ß=-0.07, P < .01) and a two fold risk for lowest quartile concentrations (OR, 1.86; 95% CI: 1.02, 3.40). This lowering of sIgA yielded a large effect size in older infants (4-8 months)-breastfed and not. No associations were seen with postpartum depressive symptoms (7% of women) or with any of the perceived stress trajectories. CONCLUSION AND CLINICAL RELEVANCE: Despite improved mood postpartum and independent of breastfeeding status, mothers experiencing antepartum depressive symptoms delivered offspring who exhibited lower fecal sIgA concentrations especially in later infancy. The implications of lowered sIgA concentrations in infant stool are altered microbe-sIgA interactions, greater risk for C difficile colonization and atopic disease in later years.

12.
Am J Clin Nutr ; 110(6): 1370-1383, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589250

RESUMO

BACKGROUND: Fatty acids are a vital component of human milk. They influence infant neurodevelopment and immune function, and they provide ∼50% of milk's energy content. OBJECTIVES: The objectives of this study were to characterize the composition of human milk fatty acids in a large Canadian birth cohort and identify factors influencing their variability. METHODS: In a subset of the CHILD cohort (n = 1094), we analyzed milk fatty acids at 3-4 mo postpartum using GLC. Individual and total SFAs, MUFAs, and n-3 and n-6 PUFAs were analyzed using SD scores and principal component analysis (PCA). Maternal diet, sociodemographic, health, and environmental factors were self-reported. Single-nucleotide polymorphisms were assessed in the fatty acid desaturase 1 (FADS1-rs174556) and 2 (FADS2-rs174575) genes. RESULTS: Fatty acid profiles were variable, with individual fatty acid proportions varying from 2- to >30-fold between women. Using PCA, we identified 4 milk fatty acid patterns: "MUFA and low SFA," "high n-6 PUFA," "high n-3 PUFA," and "high medium-chain fatty acids." In multivariable-adjusted analyses, fish oil supplementation and fatty cold water fish intake were positively associated with DHA and the "high n-3 PUFA" pattern. Mothers carrying the minor allele of FADS1-rs174556 had lower proportions of arachidonic acid (ARA; 20:4n-6). Independent of selected dietary variables and genetic variants, Asian ethnicity was associated with higher linoleic acid (18:2n-6) and total n-3 PUFAs. Ethnic differences in ARA were explained by FADS1 genotype. Maternal obesity was independently associated with higher total SFAs, the "high medium-chain fatty acid" pattern, and lower total MUFAs. Lactation stage, season, study site, and maternal education were also independently associated with some milk fatty acids. No associations were observed for maternal age, parity, delivery mode, or infant sex. CONCLUSIONS: This study provides unique insights about the "normal" variation in the composition of human milk fatty acids and the contributing dietary, genetic, sociodemographic, health, and environmental factors. Further research is required to assess implications for infant health.

13.
Eur. respir. j ; 54(3): 1900588, Sept. 2019.
Artigo em Inglês | BIGG | ID: biblio-1026251

RESUMO

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on 6 specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) Suggest using anti-IL5 and anti IL-5Rα for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using blood eosinophil cut-point of ≥150/µL to guide anti-IL5 initiation in adult patients with severe asthma; and 3) Suggest considering specific eosinophil (≥260/µL) and FeNO (≥19.5 ppb) cutoffs to identify adolescents or adults with the greatest likelihood or response to anti-IgE therapy; 4) Suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite GINA step 4-5 or NAEPP step 5 therapies; 5) Suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; 6) Suggest using anti-IL4/13 for adult patients with severe eosinophilic asthma, and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.


Assuntos
Humanos , Asma/complicações , Asma/diagnóstico , Asma/prevenção & controle , Estado Asmático/prevenção & controle
15.
J Allergy Clin Immunol ; 144(6): 1638-1647.e3, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31279007

RESUMO

BACKGROUND: Allergic disease is the most frequent chronic health issue in children and has been linked to early-life gut microbiome dysbiosis. Many lines of evidence suggest that microbially derived short-chain fatty acids, and particularly butyrate, can promote immune tolerance. OBJECTIVE: We sought to determine whether bacterial butyrate production in the gut during early infancy is protective against the development of atopic disease in children. METHODS: We used shotgun metagenomic analysis to determine whether dysbiosis in butyrate fermentation could be identified in human infants, before their developing allergic disease. RESULTS: We found that the microbiome of infants who went on to develop allergic sensitization later in childhood lacked genes encoding key enzymes for carbohydrate breakdown and butyrate production. CONCLUSIONS: Our findings support the importance of microbial carbohydrate metabolism during early infancy in protecting against the development of allergies.

16.
Am J Public Health ; 109(S3): S197-S204, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31242008

RESUMO

Objectives. To identify trajectory patterns of maternal depressive symptoms and perceived stress from midpregnancy to 2 years postpartum and determine relationships with selected sociodemographic factors including income, education, immigration, and postpartum employment. Methods. Pregnant women (n = 3307) recruited from the general population in 4 regions in Canada provided 6 waves of data from pregnancy to 2 years postpartum. The study was conducted from 2009 to 2015. Results. We determined 5 trajectory groups distinguished by time and magnitude for both depressive symptoms and perceived stress. Immigrants living in Canada for more than 5 up to 10 years, but not more recent arrivals, were at higher risk for persistent stress and depression independent of income status. Being employed at 1 year postpartum was associated with a lower likelihood of postpartum depression and perceived stress, while mothers reporting work exhaustion were substantially more likely to experience persistent depression and stress. Conclusions. The study highlighted the heterogeneous nature of depressive symptoms and perceived stress. Targeting interventions toward women 5 to 10 years after immigration and those experiencing exhaustion from postpartum work may be particularly beneficial.

17.
Pediatr Pulmonol ; 54(8): 1267-1276, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31172683

RESUMO

OBJECTIVES: To identify distinctive patterns of respiratory-related health services use (HSU) between birth and 3 years of age, and to examine associated symptom and risk profiles. METHODS: This study included 729 mother and child pairs enrolled in the Toronto site of the Canadian Healthy Infant Longitudinal Development study in 2009-2012; they were linked to Ontario health administrative databases (2009-2016). A model-based cluster analysis was performed to identify distinct groups of children who followed a similar pattern of respiratory-related HSU between birth and 3 years of age, regarding hospitalization, emergency department (ED) and physician office visits for respiratory conditions and total health care costs (2016 Canadian dollars). RESULTS: The majority (estimated cluster weight = 0.905) showed a pattern of low and stable respiratory care use (low HSU) while the remainder (weight = 0.095) showed a pattern of high use (high HSU). From 0 to 3 years of age, the low- and high-HSU groups differed in mean trajectories of total health care costs ($783 per 6 months decreased to $114, vs $1796 to $177, respectively). Compared to low-HSU, the high-HSU group was associated with a constant risk of hospitalizations, early high ED utilization and physician visits for respiratory problems. The two groups differed significantly in the timing of wheezing (late onset in low-HSU vs early in high-HSU) and future total costs (stable vs increased). CONCLUSIONS: One in ten children had high respiratory care use in early life. Such information can help identify high-risk young children in a large population, monitor their long-term health, and inform resource allocation.

18.
Sleep Med ; 59: 24-32, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31153013

RESUMO

RATIONALE: Sleep duration is critical to growth, learning, and immune function development in infancy. Strategies to ensure that national recommendations for sleep duration in infants are met require knowledge of perinatal factors that affect infant sleep. OBJECTIVES: To investigate the mechanistic pathways linking maternal education and infant sleep. METHODS: An observational study was conducted on 619 infants whose mothers were enrolled at the Edmonton site of the CHILD birth cohort. Infant sleep duration at three months was assessed using the Brief Infant Sleep Questionnaire. Maternal education was collected via maternal report. Prenatal and postnatal depression scores were obtained from the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Birth records and maternal report were the source of covariate measures. Mediation analysis (PROCESS v3.0) was used to examine the indirect effects of maternal education on infant sleep duration mediated through prenatal depression and birth mode. MEASUREMENTS AND MAIN RESULTS: At three months of age, infants slept on average 14.1 h. Lower maternal education and prenatal depression were associated with significantly shorter infant sleep duration. Emergency cesarean section birth was associated with 1-hour shorter sleep duration at three months compared to vaginal birth [without intrapartum antibiotic prophylaxis] (ß: -0.99 h; 95% CI: -1.51, -0.48). Thirty percent of the effect of lower maternal education on infant total sleep duration was mediated sequentially through prenatal depression and birth mode (Total Indirect Effects: -0.12, 95% CI: -0.22, -0.03, p < 0.05). CONCLUSIONS: Prenatal depression and birth mode sequentially mediate the effect of maternal education on infant sleep duration.

19.
Front Nutr ; 6: 58, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31157227

RESUMO

Background: Human milk contains many bioactive components that are typically studied in isolation, including bacteria. We performed an integrated analysis of human milk oligosaccharides and fatty acids to explore their associations with milk microbiota. Methods: We studied a sub-sample of 393 mothers in the CHILD birth cohort. Milk was collected at 3-4 months postpartum. Microbiota was analyzed by 16S rRNA gene V4 sequencing. Oligosaccharides and fatty acids were analyzed by rapid high-throughput high performance and gas liquid chromatography, respectively. Dimension reduction was performed with principal component analysis for oligosaccharides and fatty acids. Center log-ratio transformation was applied to all three components. Associations between components were assessed using Spearman rank correlation, network visualization, multivariable linear regression, redundancy analysis, and structural equation modeling. P-values were adjusted for multiple comparisons. Key covariates were considered, including fucosyltransferase-2 (FUT2) secretor status of mother and infant, method of feeding (direct breastfeeding or pumped breast milk), and maternal fish oil supplement use. Results: Overall, correlations were strongest between milk components of the same type. For example, FUT2-dependent HMOs were positively correlated with each other, and Staphylococcus was negatively correlated with other core taxa. Some associations were also observed between components of different types. Using redundancy analysis and structural equation modeling, the overall milk fatty acid profile was significantly associated with milk microbiota composition. In addition, some individual fatty acids [22:6n3 (docosahexaenoic acid), 22:5n3, 20:5n3, 17:0, 18:0] and oligosaccharides (fucosyl-lacto-N-hexaose, lacto-N-hexaose, lacto-N-fucopentaose I) were associated with microbiota α diversity, while others (C18:0, 3'-sialyllactose, disialyl-lacto-N-tetraose) were associated with overall microbiota composition. Only a few significant associations between individual HMOs and microbiota were observed; notably, among mothers using breast pumps, Bifidobacterium prevalence was associated with lower abundances of disialyl-lacto-N-hexaose. Additionally, among non-secretor mothers, Staphylococcus was positively correlated with sialylated HMOs. Conclusion: Using multiple approaches to integrate and analyse milk microbiota, oligosaccharides, and fatty acids, we observed several associations between different milk components and microbiota, some of which were modified by secretor status and/or breastfeeding practices. Additional research is needed to further validate and mechanistically characterize these associations and determine their relevance to infant gut and respiratory microbiota development and health.

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