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Author(s): Johan L. Vinther, Tim Cadman, Demetris Avraam, Claus T. Ekstrøm, Thorkild I. A. Sørensen, Ahmed Elhakeem, Ana C. Santos, Angela Pinot de Moira, Barbara Heude, Carmen Iñiguez, Costanza Pizzi, [...]

Background Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. Methods and findings We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. Conclusions This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term., Author(s): Johan L. Vinther 1,*, Tim Cadman 2, Demetris Avraam 3, Claus T. Ekstrøm 4, Thorkild I. A. Sørensen 1,5, Ahmed Elhakeem 2, Ana C. Santos 6,7, Angela Pinot de [...]

Introduction: Previously developed cesarean section (CS) and emergency CS prediction tools use antenatal and intrapartum risk factors. We aimed to develop a predictive model for the risk of emergency CS before the onset of labour utilizing antenatal obstetric and non-obstetric factors. Methods: We completed a secondary analysis of data collected from the CHILD Cohort Study. The analysis was limited to term (≥37 weeks), singleton pregnant women with cephalic presentation. The sample was divided into a training and validation dataset. The emergency CS prediction model was developed in the training dataset and the performance accuracy was assessed by the area under the receiver operating characteristic curve(AUC) of the receiver operating characteristic analysis (ROC). Our final model was subsequently evaluated in the validation dataset. Results: The participant sample consisted of 2,836 pregnant women. Mean age of participants was 32 years, mean BMI of 25.4 kg/m2 and 39% were nulliparous. 14% had emergency CS delivery. Each year of increasing maternal age increased the odds of emergency CS by 6% (adjusted Odds Ratio (aOR 1.06,1.02–1.08). Likewise, there was a 4% increase odds of emergency CS for each unit increase in BMI (aOR 1.04,1.02–1.06). In contrast, increase in maternal height has a negative association with emergency CS. The final emergency CS delivery predictive model included six variables (hypertensive disorders of pregnancy, antenatal depression, previous vaginal delivery, age, height, BMI). The AUC for our final prediction model was 0.74 (0.72–0.77) in the training set with a similar AUC in the validation dataset (0.77; 0.71–0.82). Conclusion: The developed and validated emergency CS delivery prediction model can be used in counselling prospective parents around their CS risk and healthcare resource planning. Further validation of the tool is suggested. [ABSTRACT FROM AUTHOR]

Background: The global prevalence of childhood eczema has increased over the last few decades, with a marked increase in high-income countries. Differences in prevalence of childhood eczema between countries and ethnicities suggest that genetic and early modifiable environmental factors, such as dietary intake, may underlie this observation. To investigate the association between pregnancy diet and infant eczema in a consortium of prospective Canadian birth cohorts predominantly comprised of white Europeans and South Asians. Methods: We evaluated the association of maternal dietary patterns reported during pregnancy (assessed at 24–28 weeks gestation using a semi-quantitiative food-frequency questionnaire) with parent-reported physician-diagnosed infant eczema at 1-year from 2,160 mother-infant pairs. Using three dietary patterns ("Western", "plant-based", and "Balanced") previously derived in this cohort using principal component analysis, we used multivariable logistic regression to determine the association of these dietary patterns with infant eczema, adjusted for potential confounders. Results: We observed a lower odds of eczema in the full sample combining white Europeans and South Asians with greater adherence to a plant-based (OR = 0.65; 95% CI: 0.55, 0.76; <0.001) and Western dietary pattern (OR = 0.73; 95% CI: 0.60, 0.89; P<0.01), after adjusting for other known predictors of eczema, including ethnicity, which was not significant. No associations were observed for the balanced diet. An interaction between the Western diet and ethnicity was observed (P<0.001). Following stratification by ethnicity, a protective association between the plant-based diet and infant eczema was confirmed in both white Europeans (OR = 0.59; 95% CI: 0.47, 0.74; P<0.001) and South Asians (OR = 0.77; 95% CI: 0.61, 0.97; P = 0.025). In white Europeans only, a Western diet was associated with a lower odds of infant eczema (OR = 0.69; 95% CI: 0.56, 0.87; P = 0.001) while a balanced diet increased the odds of infant eczema (OR = 1.23; 95% CI: 1.02, 1.49; P = 0.03). Beyond a plant-based diet, no significant associations with other dietary patterns were observed in South Asians. Conclusion: A plant-based diet during pregnancy is associated with a lowered odds of infant eczema at 1 year in all participants. Future studies of the components of plant-based diet which underlie the lower risk of eczema are needed. [ABSTRACT FROM AUTHOR]

Background: Pre-school children spend an average of two-hours daily using screens. We examined associations between screen-time on pre-school behavior using data from the Canadian Healthy Infant Longitudinal Development (CHILD) study. Methods: CHILD participant parents completed the Child Behavior Checklist (CBCL) at five-years of age. Parents reported their child’s total screen-time including gaming and mobile devices. Screen-time was categorized using the recommended threshold of two-hours/day for five-years or one-hour/day for three-years. Multiple linear regression examined associations between screen-time and externalizing behavior (e.g. inattention and aggression). Multiple logistic regression identified characteristics of children at risk for clinically significant externalizing problems (CBCL T-score≥65). Results: Screen-time was available for over 95% of children (2,322/2,427) with CBCL data. Mean screen-time was 1·4 hours/day (95%CI 1·4, 1·5) at five-years and 1·5 hours/day (95%CI: 1·5, 1·6) at three-years. Compared to children with less than 30-minutes/day screen-time, those watching more than two-hours/day (13·7%) had a 2·2-point increase in externalizing T-score (95%CI: 0·9, 3·5, p≤0·001); a five-fold increased odd for reporting clinically significant externalizing problems (95%CI: 1·0, 25·0, p = 0·05); and were 5·9 times more likely to report clinically significant inattention problems (95%CI: 1·6, 21·5, p = 0·01). Children with a DSM-5 ADHD T-score above the 65 clinical cut-off were considered to have significant ADHD type symptoms (n = 24). Children with more than 2-hours of screen-time/day had a 7·7-fold increased risk of meeting criteria for ADHD (95%CI: 1·6, 38·1, p = 0·01). There was no significant association between screen-time and aggressive behaviors (p>0.05). Conclusion: Increased screen-time in pre-school is associated with worse inattention problems. [ABSTRACT FROM AUTHOR]

Changes in maternal innate immunity during healthy human pregnancy are not well understood. Whether basal immune status in vivo is largely unaffected by pregnancy, is constitutively biased towards an inflammatory phenotype (transiently enhancing host defense) or exhibits anti-inflammatory bias (reducing potential responsiveness to the fetus) is unclear. Here, in a longitudinal study of healthy women who gave birth to healthy infants following uncomplicated pregnancies within the Canadian Healthy Infant Longitudinal Development (CHILD) cohort, we test the hypothesis that a progressively altered bias in resting innate immune status develops. Women were examined during pregnancy and again, one and/or three years postpartum. Most pro-inflammatory cytokine expression, including CCL2, CXCL10, IL-18 and TNFα, was reduced in vivo during pregnancy (20–57%, p<0.0001). Anti-inflammatory biomarkers (sTNF-RI, sTNF-RII, and IL-1Ra) were elevated by ~50–100% (p<0.0001). Systemic IL-10 levels were unaltered during vs. post-pregnancy. Kinetic studies demonstrate that while decreased pro-inflammatory biomarker expression (CCL2, CXCL10, IL-18, and TNFα) was constant, anti-inflammatory expression increased progressively with increasing gestational age (p<0.0001). We conclude that healthy resting maternal immune status is characterized by an increasingly pronounced bias towards a systemic anti-inflammatory innate phenotype during the last two trimesters of pregnancy. This is resolved by one year postpartum in the absence of repeat pregnancy. The findings provide enhanced understanding of immunological changes that occur in vivo during healthy human pregnancy. [ABSTRACT FROM AUTHOR]

Background: The lung clearance index (LCI), measured by multiple breath washout (MBW), reflects global ventilation inhomogeneity and is a sensitive marker of early cystic fibrosis (CF) lung disease. Current evidence is based on a customized mass spectrometry system that uses sulfur hexafluoride (SF6) as a tracer gas, which is not widely available. Nitrogen (N2) washout may be better suited for clinical use and multi-center trials. Objective: To compare the results obtained from a N2 washout system to those generated by the SF6 based system in healthy children and children with CF. Methods: Children with CF were recruited from outpatient clinics; healthy children were recruited from the Research4Kids online portal. Participants performed MBWSF6 (Amis 2000, Innovision, Denmark) and MBWN2 (ExhalyzerD, EcoMedics, Switzerland) in triplicate, in random order on the same day. Agreement between systems was assessed by Bland-Altman plot. Results: Sixty-two healthy and 61 children with CF completed measurements on both systems. In health there was good agreement between systems (limits of agreement −0.7 to 1.9); on average N2 produced higher values of LCI (mean difference 0.58 (95% CI 0.42 to 0.74)). In CF the difference between systems was double that in health with a clear bias towards disproportionately higher LCIN2 compared to LCISF6 at higher mean values of LCI. Conclusion: LCIN2 and LCISF6 have similar discriminative power and intra-session repeatability but are not interchangeable. MBWN2 offers a valid new tool to investigate early obstructive lung disease in CF, but requires independent normative values. [ABSTRACT FROM AUTHOR]