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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 [...]

Objective: To describe developmental domain-specific trajectories from ages 1 through 5 years and to estimate the association of trajectory group membership with gestational age for children born between ≥34 and <41 weeks gestation. Methods: Using data from the All Our Families cohort, trajectories of the domain-specific Ages & Stages Questionnaire scores were identified and described using group-based trajectory modeling for children born ≥34 and <41 weeks of gestation (n = 2664). The trajectory groups association with gestational age was estimated using multinomial logistic regression. Results: Across the five domains, 4–5 trajectory groups were identified, and most children experienced changing levels of risk for delay over time. Decreasing gestational age increases the Relative risk of delays in fine motor (emerging high risk: 1.46, 95% CI: 1.19–1.80; resolving moderate risk: 1.11, 95% CI: 1.03–1.21) and gross motor (resolving high risk: 1.21, 95% CI: 1.04–1.42; and consistent high risk: 1.64, 95% CI: 1.20–2.24) and problem solving (consistent high risk: 1.58 (1.09–2.28) trajectory groups compared to the consistent low risk trajectory groups. Conclusion: This study highlights the importance of longitudinal analysis in understanding developmental processes; most children experienced changing levels of risk of domain-specific delay over time instead of having a consistent low risk pattern. Gestational age had differential effects on the individual developmental domains after adjustment for social, demographic and health factors, indicating a potential role of these factors on trajectory group membership. [ABSTRACT FROM AUTHOR]

Objective: The study examined the association between specific childhood adversities and rate of all-cause hospitalization in adulthood in a large sample of the general population and assessed whether adult socioeconomic and health-related factors mediate those associations. Methods: We used linked data available from Statistics Canada i.e., the Canadian Community Health Survey (CCHS-2005) linked to Discharge Abstract Database (DAD 2005–2017) and Canadian Vital Statistics Database (CVSD 2005–2017). CCHS-2005 measured self-reported exposure to childhood adversities, namely prolonged hospitalization, parental divorce, parental unemployment, prolonged trauma, parental substance use, physical abuse, and being sent away from home for wrongdoing, from a sample of household residents aged 18 years and above (n = 11,340). The number and causes of hospitalization were derived from linkage with DAD. Negative binomial regression was used to characterize the association between childhood adversities and the rate of hospitalization and to identify potential mediators between them. Results: During the 12-year follow-up, 37,080 hospitalizations occurred among the respondents, and there were 2,030 deaths. Exposure to at least one childhood adversity and specific adversities (except parental divorce) were significantly associated with the hospitalization rate among people below 65 years. The associations (except for physical abuse) were attenuated when adjusted for one or more of the adulthood factors such as depression, restriction of activity, smoking, chronic conditions, poor perceived health, obesity, unmet health care needs, poor education, and unemployment, observations that are consistent with mediation effects. The associations were not significant among those aged 65 and above. Conclusion: Childhood adversities significantly increased the rate of hospitalization in young and middle adulthood, and the effect was potentially mediated by adulthood socioeconomic status and health and health care access related factors. Health care overutilization may be reduced through primary prevention of childhood adversities and intervention on those potentially mediating pathways such as improving adulthood socioeconomic circumstances and lifestyle modifications. [ABSTRACT FROM AUTHOR]

Background Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. Methods and findings We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. Conclusions In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy., Author(s): Ellis Voerman 1,2, Susana Santos 1,2, Bernadeta Patro Golab 1,2,3, Pilar Amiano 4,5,6, Ferran Ballester 6,7, Henrique Barros 8,9, Anna Bergström 10,11, Marie-Aline Charles 12,13, Leda Chatzi 14,15,16, Cécile [...]

Healthy pregnancy requires a coordinated immune response, yet complications can arise, putting both the mother's and child's health at risk. Hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) are pregnancy-related complications that account for most maternal morbidity and mortality. Cytokines are proteins released as part of the immune response to disease or infection and regulate inflammation. Certain pregnancy complications cause localized and systemic inflammation; however, cytokine profiles specific to such complications are not well understood. This study aims to examine associations between pregnancy complications of HDP and GDM and cytokine profiles in the second trimester of pregnancy. Data was obtained from the All Our Families birth cohort in Calgary, Alberta, Canada. The cohort collected questionnaires at the time of participant enrollment and maternal blood samples at 17–23 weeks gestation. Cases of HDP (n = 27) and GDM (n = 31) were matched to controls on BMI, maternal age, and smoking status in the preconception period at a 1:3 ratio. Cytokine levels were measured in blood samples using Luminex xMAP technology using a panel of 42 cytokines. Using R software, a Classification and Regression Tree (CART) analysis was conducted to identify cytokine profiles and levels associated with each complication. Four cytokines were identified in the HDP CART (in descending order of importance): Monocyte Chemoattractant Protein-1 (cut-off: <480pg/mL), Macrophage Inflammatory Protein-1β (cut-off: ≥26pg/mL), Eotaxin (cut-off: <27/≥27&<36/≥36pg/mL), and Soluble Cluster of Differentiation 40 Ligand (cut-off: <1342pg/mL). Six cytokine levels were identified in the GDM CART: Interleukin-1 Receptor Antagonist (IL-1Ra; cut-off: <25pg/mL), Interleukin-5 (cut-off: ≥0.4pg/mL), Interferon-γ (cut-off: <4.9pg/mL), IL-1Ra (cut-off: ≥111pg/mL), Eotaxin (cut-off: ≥21pg/mL), and Interleukin-18 (cut-off: ≥155pg/mL). By examining the complex inter-relationships between cytokines, findings of cytokine profiles guide further research in identifying biomarkers of pregnancy complications relevant to the design of the future management or prevention of these conditions. [ABSTRACT FROM AUTHOR]

Background: Persons with disability (PWD) experience disproportionately high poverty rates in Canada. This trend is apparent especially among youth compared to those who develop disabilities later in life. PWD in poverty have additional needs that increase barriers to full participation in society and translate to higher basic costs for daily living. Despite the existence of income assistance programs in Canada to mitigate income inequalities faced by PWDs, access to these programs can be limited. Objective: To describe use of income assistance for young adults with disability in British Columbia for the development of potential approaches to improve realized access to these programs. Methods: We conducted a population-based retrospective cohort study using British Columbia linked administrative data. We described differences in income assistance use among PWD by the level of special education funding received during primary school education (from most to least; Level 1, Level 2, Level 3, Unfunded, and no special education) and family composition. We also provided longitudinal patterns of income assistance use. Results: Of 218,324 young adults, 88% received no special education, 0.1% used Level One, 1.6% used Level Two, 2.9% used Level Three, and 7.1% used Unfunded special education coding. Young adults with Level One special education funding had the highest rates of hospitalizations and continuing care, with no hospitalization due to homelessness. Those with Level Three special education coding had higher rates of hospitalization and hospitalization due to homelessness than Level Two young adults. When transitioning to adulthood initially, Level One and Two funded individuals used relatively more disability income assistance than individuals from the other funding levels. Nearly all BCEA users with higher funded special education codes used this disability-specific program, while lesser funded special education codes used the Temporary Assistance more frequently, for a longer duration and were more likely to be persistent Temporary Assistance users. Conclusions: Sustainable and reliable access to income assistance programs remains an issue across the heterogeneity of needs faced by young adults with disability. [ABSTRACT FROM AUTHOR]

Hypertensive disorders in pregnancy (HDP) are associated with increased risk of offspring neurodevelopmental disorders, suggesting long-term adverse impacts on fetal brain development. However, the relationship between HDP and deficits in general child development is unclear. Our objective was to assess the association between HDP and motor and cognitive developmental delay in children at 36 months of age. We analyzed data from the All Our Families community-based cohort study (n = 1554). Diagnosis of HDP–gestational or chronic hypertension, preeclampsia, or eclampsia–was measured through medical records. Child development was measured by maternal-report on five domains of the Ages and Stages Questionnaire (ASQ-3). Standardized cut-off scores were used to operationalize binary variables for any delay, motor delay, and cognitive delay. We calculated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) using logistic regression, sequentially controlling for potential confounders followed by factors suspected to lie on the causal pathway. Overall, 8.0% of women had HDP and hypertension-exposed children had higher prevalence of delay than unexposed children. Hypertension-exposed children had elevated risk for developmental delay, but CIs crossed the null. The aRRs quantifying the fully adjusted effect of HDP on child development were 1.19 (95% CI 0.92, 1.53) for any delay, 1.18 (95% CI 0.86, 1.61) for motor delay, and 1.24 (95% CI 0.83, 1.85) for cognitive delay. We did not find a statistically significant association between HDP and developmental delay. Confidence intervals suggest that children exposed to HDP in utero have either similar or slightly elevated risk of any, motor, and cognitive delay at 36 months after controlling for maternal and obstetric characteristics. The observed direction of association aligns with evidence of biological mechanisms whereby hypertensive pathology can disrupt fetal neurodevelopment; however, more evidence is needed. Findings may have implications for early developmental monitoring and intervention following prenatal hypertension exposure. [ABSTRACT FROM AUTHOR]

Background: The All Our Families (AOF) cohort study is a longitudinal population-based study which collected biological samples from 1948 pregnant women between May 2008 and December 2010. As the quality of samples can decline over time, the objective of the current study was to assess the association between storage time and RNA (ribonucleic acid) yield and purity, and confirm the quality of these samples after 7–10 years in long-term storage. Methods: Maternal whole blood samples were previously collected by trained phlebotomists and stored in four separate PAXgene Blood RNA Tubes (PreAnalytiX) between 2008 and 2011. RNA was isolated in 2011 and 2018 using PAXgene Blood RNA Kits (PreAnalytiX) as per the manufacturer's instruction. RNA purity (260/280), as well as RNA yield, were measured using a Nanodrop. The RNA integrity number (RIN) was also assessed from 5–25 and 111–130 months of storage using RNA 6000 Nano Kit and Agilent 2100 BioAnalyzer. Descriptive statistics, paired t-test, and response feature analysis using linear regression were used to assess the association between various predictor variables and quality of the RNA isolated. Results: Overall, RNA purity and yield of the samples did not decline over time. RNA purity of samples isolated in 2011 (2.08, 95% CI: 2.08–2.09) were statistically lower (p<0.000) than samples isolated in 2018 (2.101, 95% CI: 2.097, 2.104), and there was no statistical difference between the 2011 (13.08 μg /tube, 95% CI: 12.27–13.89) and 2018 (12.64 μg /tube, 95% CI: 11.83–13.46) RNA yield (p = 0.2964). For every month of storage, the change in RNA purity is -0.01(260/280), and the change in RNA yield between 2011 and 2018 is -0.90 μ g / tube. The mean RIN was 8.49 (95% CI:8.44–8.54), and it ranged from 7.2 to 9.5. The rate of change in expected RIN per month of storage is 0.003 (95% CI 0.002–0.004), so while statistically significant, these results are not relevant. Conclusions: RNA quality does not decrease over time, and the methods used to collect and store samples, within a population-based study are robust to inherent operational factors which may degrade sample quality over time. [ABSTRACT FROM AUTHOR]

The heterogeneity of spontaneous preterm birth (SPTB) requires an interdisciplinary approach to determine potential predictive risk factors of early delivery. The aim of this study was to investigate maternal whole blood gene expression profiles associated with spontaneous preterm birth (SPTB, <37 weeks) in asymptomatic pregnant women. The study population was a matched subgroup of women (51 SPTBs, 114 term delivery controls) who participated in the All Our Babies community based cohort in Calgary (n = 1878). Maternal blood at 17–23 (sampling time point 1, T1) and 27–33 weeks of gestation (T2) were collected. Total RNA was extracted and microarray was performed on 326 samples (165 women). Univariate analyses determined significant clinical factors and differential gene expression associated with SPTB. Thirteen genes were validated using qRT-PCR. Three multivariate logistic models were constructed to identify gene expression at T1 (Model A), T2 (Model B), and gene expression fold change from T1 to T2 (Model C) associated with SPTB. All models were adjusted for clinical factors. Model C can predict SPTB with 65% sensitivity and 88% specificity in asymptomatic women after adjusting for history of abortion and anaemia (occurring before T2). Clinical data enhanced the sensitivity of the Models to predict SPTB. In conclusion, clinical factors and whole blood gene expression are associated with SPTB in asymptomatic women. An effective screening tool for SPTB during pregnancy would enable targeted preventive approaches and personalised antenatal care. [ABSTRACT FROM AUTHOR]

Objective: The present study examined back pain (BP) and/or urinary incontinence (UI) impact on the ability to perform daily tasks at 12 months after childbirth in healthy reproductive women who sought maternity care in community based family practice clinics. Methods: This study is a secondary analysis from the All Our Babies Study, a prospective, community-based pregnancy cohort in Calgary, Alberta. Maternal self-reported information on demographics, lifestyle, experiences with pregnancy and childbirth, occurrence of BP, UI and consequent impairment of daily tasks were collected by questionnaires administered before 25 weeks, at 34-36 weeks gestation and at 4 and 12 months postpartum. The occurrence and severity of BP and UI at one year after childbirth was assessed using descriptive and bivariate analyses. Logistic regression models examined the association between demographic and obstetrical variables and the severity of functional impairment due to UI and BP. Results: From 1574 women with singleton pregnancies included in the study, 1212 (77%) experienced BP, 773 (49%) UI, and 620 (40%) both BP and UI. From the 821 women reporting impairment of daily tasks due to BP, 199 (24 %) were moderately and 90 (11%) severely affected with the remainder, 532 (64%) being mildly affected. From 267 women with functional impairment due to UI, 52 (19%) reported moderately to severe impairment in their ability to perform daily tasks. Obesity and parity were risk factors for impairment of daily functioning due to BP, whereas obesity and vaginal delivery increased the risk of moderate to severe impairment due to UI. Conclusions: BP and UI are common occurrences 1 year after childbirth. Maternal performance of daily tasks and women’s health and quality of life are more often impaired due to BP than UI. Our study brings new evidence of the risk factors that predict severity and impact of these conditions on women functioning at 12 months postpartum. [ABSTRACT FROM AUTHOR]

Purpose: Maternal psychological distress is one of the most common perinatal complications, affecting up to 25% of pregnant and postpartum women. Research exploring the association between prenatal and postnatal distress and toddler cognitive development has not been systematically compiled. The objective of this systematic review was to determine the association between prenatal and postnatal psychological distress and toddler cognitive development. Methods: Articles were included if: a) they were observational studies published in English; b) the exposure was prenatal or postnatal psychological distress; c) cognitive development was assessed from 13 to 36 months; d) the sample was recruited in developed countries; and e) exposed and unexposed women were included. A university-based librarian conducted a search of electronic databases (Embase, CINAHL, Eric, PsycInfo, Medline) (January, 1990-March, 2014). We searched gray literature, reference lists, and relevant journals. Two reviewers independently evaluated titles/abstracts for inclusion, and quality using the Scottish Intercollegiate Guideline Network appraisal tool for observational studies. One reviewer extracted data using a standardized form. Results: Thirteen of 2448 studies were included. There is evidence of an association between prenatal and postnatal distress and cognitive development. While variable effect sizes were reported for postnatal associations, most studies reported medium effect sizes for the association between prenatal psychological distress and cognitive development. Too few studies were available to determine the influence of the timing of prenatal exposure on cognitive outcomes. Conclusion: Findings support the need for early identification and treatment of perinatal mental health problems as a potential strategy for optimizing toddler cognitive development. [ABSTRACT FROM AUTHOR]