RationaleAsthma in pregnancy is associated with respiratory diseases in the offspring.ObjectiveTo investigate if maternal asthma is associated with lung function in early life.MethodsData on lung function measured at 5–6 weeks of age were combined from two large birth cohorts: the Bern Infant Lung Development (BILD) and the Australian Breathing for Life Trial (BLT) birth cohorts conducted at three study sites (Bern, Switzerland; Newcastle and Sydney, Australia). The main outcome variable was time to reach peak tidal expiratory flow as a percentage of total expiratory time(tPTEF:tE%). Bayesian linear hierarchical regression analyses controlling for study site as random effect were performed to estimate the effect of maternal asthma on the main outcome, adjusting for sex, birth order, breast feeding, weight gain and gestational age. In separate adjusted Bayesian models an interaction between maternal asthma and sex was investigated by including an interaction term.Measurements and main resultsAll 406 BLT infants were born to mothers with asthma in pregnancy, while 193 of the 213 (91%) BILD infants were born to mothers without asthma. A significant interaction between maternal asthma and male sex was negatively associated with tPTEF:tE% (intercept 37.5; estimate: –3.5; 95% credible interval –6.8 to –0.1). Comparing the model posterior probabilities provided decisive evidence in favour of an interaction between maternal asthma and male sex (Bayes factor 33.5).ConclusionsMaternal asthma is associated with lower lung function in male babies, which may have lifelong implications on their lung function trajectories and future risk of wheezing and asthma.
Author contribution: KAA meditated the project, reviewed papers and drafted the paper. EQA and GB contributed to the design of the study and review of papers identified at each stage. EH, JM, SK and AC provided manuscript concept, revised the drafts and critically edited the manuscript.
ObjectiveTo evaluate what is known about active tobacco use during pregnancy and the association with infant respiratory health.DesignSystematic review and meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sourcesMEDLINE, EMBASE, Cochrane, CINAHL, and Maternity and Infant Care were searched thoroughly until June 2020.Eligibility criteria for selecting studiesWe included case–control and cohort studies estimating the association between active tobacco use during pregnancy and infant respiratory health (wheezing and apnoea) and lung function parameters in the first 12 months of life.Data extraction and synthesisExtraction and risk of bias assessment were conducted by two independent reviewers. The odds ratio, relative risk and mean differences were pooled with a 95% CI using the generic inverse variance method. Heterogeneity was assessed and expressed by percentage using I2.ResultsWe identified 4423 abstracts, and 21 publications met the eligibility criteria. Pooled OR showed an increase in wheezing episodes in infants born to mothers who were active tobacco users during pregnancy (OR 1.50, 95% CI 1.27 to 1.77, p<0.01). Mixed results were found on lung function parameters, and a meta-analysis including two studies with comparable methodology showed a trend towards reduced maximum flow rate at functional residual capacity of −34.59 mL/s (95% CI −72.81 to 3.63, p=0.08) in 1-month-old infants born to women who smoked during pregnancy. A higher risk of apnoea was described for infants born to mothers who used smokeless tobacco during pregnancy, while the results in infants born to women who actively smoked tobacco during pregnancy were non-conclusive.ConclusionInfants born to mothers who actively smoked during pregnancy are at higher odds of having wheeze and may have lower lung function. Smokeless tobacco use in pregnancy may increase the risk of apnoea in infancy.PROSPERO registration numberCRD42018083936.
Fetal exposure to tobacco smoke is an adverse risk factor for newborns. A plausible mechanism of how this exposure may negatively impact long term health is differential methylation of deoxyribonucleic acid (DNAm) and its relation to birth weight. We examined whether self-reported gestational smoking status and maternal exhaled carbon monoxide (eCO) during early pregnancy were associated with methylation of cytosine by guanines (CpG) sites that themselves predicted birth weight. We focused first on CpGs associated with maternal smoking, and secondly, among these, on CpGs related to birth weight found in another cohort. Then in 94 newborns from the Breathing for Life Trial (BLT) DNAm levels in cord blood were determined using Infinium Methylation EPIC BeadChip measuring >850K CpGs. We regressed CpGs on eCO and tested via mediation analysis whether CpGs link eCO to birth weight. Nine smoking related CpG sites were significantly associated with birth weight. Among these nine CpGs the methylation of cg02264407 on the LMO7 gene was statistically significant and linked with eCO measurements. eCO greater than six ppm showed a 2.3% decrease in infant DNAm (p = 0.035) on the LMO7 gene. A 1% decrease in methylation at this site resulted in decreased birth weight by 44.8 g (p = 0.003). None of the nine CpGs tested was associated with self-reported smoking. This is the first study to report potential mediation of DNA methylation, linking eCO measurements during early pregnancy with birth weight.
BackgroundNitric oxide in exhaled air (eNO) is used as a marker of type 2 immune response-induced airway inflammation. We aimed to investigate the association between eNO and bronchiolitis incidence and respiratory symptoms in infancy, and its correlation with eosinophil protein X (EPX).MethodsWe followed up infants at 6 weeks of age born to mothers with asthma in pregnancy and measured eNO during natural sleep using a rapid response chemiluminescense analyser (CLD88; EcoMedics), collecting at least 100 breaths, interpolated for an expiratory flow of 50 mL/s. EPX normalised to creatinine was measured in urine samples (uEPX/c). A standardised questionnaire was used to measure symptoms in first year of life. Associations were investigated using multiple linear regression and robust Poisson regression models.ResultseNO levels were obtained in 184 infants, of whom 125/184 (68%) had 12 months questionnaire data available and 51/184 (28%) had uEPX/c measured. Higher eNO was associated with less respiratory symptoms during the first 6 weeks of life (n=184, ß-coefficient: –0.49, 95% CI –0.95 to –0.04, p=0.035). eNO was negatively associated with uEPX/c (ß-coefficient: –0.004, 95% CI –0.008 to –0.001, p=0.021). Risk incidence of bronchiolitis, wheeze, cold or influenza illness and short-acting beta-agonist use significantly decreased by 18%–24% for every unit increase in eNO ppb.ConclusionHigher eNO levels at 6 weeks of age may be a surrogate for an altered immune response that is associated with less respiratory symptoms in the first year of life.
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