Sara M. Mensink-Bout

Objectives To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study. Design Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined. Setting Children aged 0–18 years from 26 European birth cohorts. Participants 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood. Main outcome measure Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV₁), FEV₁/forced vital capacity) at age 6–18 years. Results Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3–5 years was not associated with asthma at age 6–18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results. Conclusions Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood.

Background: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age.Methods: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), FEV₁/FVC, forced expiratory flow at 75% of FVC (FEF_75%) and asthma at a median (range) age of 7 (4–15) years.Results: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV₁, FEV₁/FVC and FEF_75%(z-score range: −0.09 (95% CI −0.14– −0.04) to −0.30 (95% CI −0.36– −0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98–2.22) to 6.30 (95% CI 5.64–7.04) and 1.25 (95% CI 1.18–1.32) to 1.55 (95% CI 1.47–1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma.Conclusions: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.

Background: The relation of physical condition with respiratory outcomes in adolescents is unclear. We examined the hypothesis that adolescents with a lower physical condition represented by a lower cardiorespiratory fitness and physical activity, and a higher screen time have a lower lung function and higher risk of asthma.Methods: In a population‐based prospective cohort study on 4854 children aged 13 years, we assessed cardiorespiratory fitness by using the peak work rate measured by the steep ramp test. Information on physical activity and screen time was obtained by self‐reported questionnaires. Lung function was measured by spirometry and current asthma was assessed by a parental‐reported questionnaire.Results: Taking sociodemographic, lifestyle, and growth‐related confounders and multiple hypothesis testing into account, a 1 SD lower cardiorespiratory fitness was associated with a lower FEV₁, FVC, and FEF₇₅ (Z‐score difference (95% CI): −0.31 (−0.35, −0.28), −0.30 (−0.33, −0.26), −0.13 (−0.17, −0.10), respectively), and a higher risk of asthma (Odds Ratio (95% CI) 1.25 (1.06, 1.46)). A 1 SD higher screen time was associated with a lower FVC (Z‐score difference (95% CI): −0.06 (−0.10, −0.03)). Physical activity and screen time were not related to asthma. Results did not materially change after additional adjustment for respiratory outcomes at an earlier age.Conclusion: Adolescents with a lower cardiorespiratory fitness had a lower lung function and a higher risk of asthma. Those with a higher screen time had a lower FVC. Further studies are needed to explore the effect of improvements in physical condition on long‐term respiratory outcomes.

Background: The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts.Methods: We studied 49 334 participants from 14 population-based cohorts in different age groups (≤10, >10–15, >15–20, >20–25 years, and overall, 5–25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV₁/FVC z-score ≥LLN, and FVC z-score −2increase in BMI, respectively). Current smoking was associated with the obstructive phenotype in participants older than 10 years (aOR=1.24, 95% CI 1.05–1.46).Conclusion: Obstructive and restrictive phenotypes were found to be relatively prevalent during childhood, which supports the early origins concept. Several well-known respiratory risk factors were associated with the obstructive phenotype, whereas only low BMI was associated with the restrictive phenotype, suggesting different underlying pathobiology of these two phenotypes.

Rationale: Severe fetal malnutrition has been related to an increased risk of respiratory diseases later in life, but evidence for the association of a suboptimal diet during pregnancy with respiratory outcomes in childhood is conflicting. We aimed to examine whether a pro-inflammatory or low-quality maternal diet during pregnancy was associated with child's respiratory health.Methods: We performed an individual participant meta-analysis among 18 326 mother–child pairs from seven European birth cohorts. Maternal pro-inflammatory and low-quality diets were estimated by energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) scores. Preschool wheezing and school-age asthma were measured using questionnaires and lung function by spirometry.Results: After adjustment for lifestyle and sociodemographic factors, we observed that a higher maternal E-DII score (a more pro-inflammatory diet) during pregnancy was associated only with a lower forced vital capacity (FVC) in children (z-score difference −0.05, 95% CI −0.08– −0.02, per interquartile range increase). No linear associations of the maternal E-DII or DASH score with child's wheezing or asthma were observed. In an exploratory examination of the extremes, a very low DASH score (<10th percentile) (a very low dietary quality) was associated with an increased risk of preschool wheezing and a low forced expiratory volume in 1 s/FVC (z-score <−1.64) (OR 1.20, 95% CI 1.06–1.36 and z-score difference 1.40, 95% CI 1.06–1.85, compared to ≥10th percentile), with corresponding population attributable risk fractions of 1.7% and 3.3%, respectively.Conclusion: The main results from this individual participant data meta-analysis do not support the hypothesis that maternal pro-inflammatory or low-quality diet in pregnancy are related to respiratory diseases in childhood.

Background Cardio‐metabolic risk factors might have an adverse effect on respiratory outcomes, but associations in children are unknown. We aimed to study the longitudinal associations of cardio‐metabolic risk factors with lung function and asthma at school‐age. We also examined whether any association was explained by child’s body mass index (BMI). Methods In a population‐based cohort study among 4,988 children cardio‐metabolic risk factors were measured at 6 and 10 years and included blood pressure, cholesterol, triglycerides, insulin and C‐reactive protein (CRP) concentrations. At age 10 years, lung function was measured by spirometry and current physician diagnosed asthma was assessed by questionnaire. Results After adjustment for confounders, child’s BMI and multiple testing, we observed that a higher diastolic blood pressure at the age of 6 years was associated with a higher forced vital capacity (FVC) at the age of 10 years (Z‐score difference (95% CI): 0.05 (0.01, 0.08), per SDS increase in diastolic blood pressure). Also, child’s CRP concentrations above the 75^th percentile at both age 6 and 10 years were related to a lower FVC as compared to CRP concentrations below the 75^th percentile at both ages (Z‐score difference (95% CI) ‐0.21 (‐0.36, ‐0.06)). No consistent associations of other cardio‐metabolic risk factors with respiratory outcomes were observed. Conclusion Blood pressure and CRP, but not lipids and insulin, were associated with lung function but not with asthma. The underlying mechanisms and long‐term effects of these associations require further investigation.

Background: Adverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes. Methods and findings: We harmonized and pooled individual participant data (IPD) from up to 24,861 mother–child pairs in 7 European mother–offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal height, parity, cigarettes smoking, and alcohol consumption), with subsequent random-effects meta-analyses. Overall, the study mothers had a mean ± SD age of 29.5 ± 4.9 y at delivery and a mean BMI of 23.3 ± 4.2 kg/m². Higher pregnancy DASH score (higher dietary quality) was associated with higher birth weight [β(95% CI) = 18.5(5.7, 31.3) g per 1-SD higher DASH score; P value = 0.005] and head circumference [0.03(0.01, 0.06) cm; P value = 0.004], longer birth length [0.05(0.01, 0.10) cm; P value = 0.010], and lower risk of delivering LBW [odds ratio (OR) (95% CI) = 0.89(0.82, 0.95); P value = 0.001] and SGA [0.87(0.82, 0.94); P value < 0.001] infants. Higher maternal prepregnancy E-DII score (more pro-inflammatory diet) was associated with lower birth weight [β(95% CI) = −18.7(−34.8, −2.6) g per 1-SD higher E-DII score; P value = 0.023] and shorter birth length [−0.07(−0.14, −0.01) cm; P value = 0.031], whereas higher pregnancy E-DII score was associated with a shorter birth length [−0.06(−0.10, −0.01) cm; P value = 0.026] and higher risk of SGA [OR(95% CI) = 1.18(1.11, 1.26); P value < 0.001]. In male, but not female, infants higher maternal prepregnancy E-DII was associated with lower birth weight and head circumference, shorter birth length, and higher risk of SGA (P-for-sex-interaction = 0.029, 0.059, 0.104, and 0.075, respectively). No consistent associations were observed for maternal E-DII and DASH scores with gestational age, preterm and postterm birth, or macrosomia and LGA. Limitations of this study were that self-reported dietary data might have increased nondifferential measurement error and that causality cannot be claimed definitely with observational design. Conclusions: In this cohort study, we observed that maternal diet that is of low quality and high inflammatory potential is associated with lower offspring birth size and higher risk of offspring being born SGA in this multicenter meta-analysis using harmonized IPD. Improving overall maternal dietary pattern based on predefined criteria may optimize fetal growth and avert substantial healthcare burden associated with adverse birth outcomes.

Background: The Dietary Approaches to Stop Hypertension (DASH) diet improves blood pressure in nonpregnant populations. We hypothesized that adherence to the DASH diet during pregnancy improves hemodynamic adaptations, leading to a lower risk of gestational hypertensive disorders. Methods and Results: We examined whether the DASH diet score was associated with blood pressure, placental hemodynamics, and gestational hypertensive disorders in a population‐based cohort study among 3414 Dutch women. We assessed DASH score using food‐frequency questionnaires. We measured blood pressure in early‐, mid‐, and late pregnancy (medians, 95% range: 12.9 [9.8–17.9], 20.4 [16.6–23.2], 30.2 [28.6–32.6] weeks gestation, respectively), and placental hemodynamics in mid‐ and late pregnancy (medians, 95% range: 20.5 [18.7–23.1], 30.4 [28.5–32.8] weeks gestation, respectively). Information on gestational hypertensive disorders was obtained from medical records. Lower DASH score quartiles were associated with a higher mid pregnancy diastolic blood pressure, compared with the highest quartile ( P P ≤0.05) but not with uterine artery resistance index. No associations with gestational hypertensive disorders were present. Conclusions: A higher DASH diet score is associated with lower mid pregnancy diastolic blood pressure and mid‐ and late pregnancy fetoplacental vascular function but not with uteroplacental vascular function or gestational hypertensive disorders within a low‐risk population. Further studies need to assess whether the effects of the DASH diet on gestational hemodynamic adaptations are more pronounced among higher‐risk populations.

Fatty acids might play a role in asthma and allergy development as they can modulate immune responses. We examined among 4260 mother-child pairs participating in a population-based cohort the associations of maternal plasma fatty acid patterns during pregnancy with a child’s respiratory and allergy outcomes at school-age. In mid-pregnancy, 22 individual fatty acids were measured from maternal blood. Three patterns were previously identified by principal component analysis: A ‘high n-6 polyunsaturated fatty acid (PUFA)’, a ‘monounsaturated and saturated fatty acid’, and a ‘high n-3 PUFA’ pattern. At the age of 10 years, a child’s lung function was assessed by spirometry, current asthma and physician-diagnosed inhalant allergy by questionnaire, and inhalant allergic sensitization by skin prick tests. A higher ‘high n-6 PUFA’ pattern was associated with a higher forced expiratory volume in 1 s/forced vital capacity and forced expiratory flow after exhaling 75% of forced vital capacity (Z-score difference (95% CI) 0.04 (0, 0.07) and 0.04 (0.01, 0.07), respectively, per SD increase in the fatty acid pattern). We observed no associations of maternal fatty acid patterns with a child’s asthma or allergy outcomes. Our results showed limited associations of maternal patterns of high n-6 PUFA concentrations in pregnancy with a better lung function in school-aged children.