Longitudinal associations of air pollution and green space with cardiometabolic risk factor clustering among children in the Netherlands

Background: This study examines longitudinal associations of air pollution and green space with cardiometabolic risk among children in the Netherlands. Methods: Three Dutch prospective cohorts with a total of 13,822 participants aged 5 to 17 years were included: (1) the Amsterdam Born Children and their Development (ABCD) study from Amsterdam (n = 2,547), (2) the Generation R study from Rotterdam (n = 5,431), and (3) the Lifelines study from northern Netherlands (n = 5,844). Air pollution (PM2.5, PM10, NO2, and elemental carbon (EC)) and green space exposures (density in multiple Euclidean buffer sizes) from 2006 to 2017 at home address level were used. Cardiometabolic risk factor clustering was assessed by a MetScore, which was derived from a confirmatory factor analysis of six cardiometabolic risk factors to assess the overall risk. Linear regression models with change in Metscore as the dependent variable, adjusted for multiple confounders, were conducted for each cohort separately. Meta-analyses were used to pool cohort-specific estimates. Results: Exposure to higher levels of NO2 and EC was significantly associated with increases in MetScore in Lifelines (per SD higher exposure: βNO2 = 0.006, 95 % CI = 0.001 to 0.010; βEC = 0.008, 95 % CI = 0.002 to 0.014). In the other two cohort studies, these associations were in the same direction but these were not significant. Higher green space density in 500-meter buffer zones around participants’ residential addresses was not significantly associated with decreases of MetScore in all three cohorts. Higher green space density in 2000-meter buffer zones was significantly associated with decreases of MetScore in ABCD and Lifelines (per SD higher green space density: βABCD = -0.008, 95 % CI = -0.013 to −0.003; βLifelines = -0.002, 95 % CI = -0.003 to −0.00003). The pooled estimates were βNO2 = 0.003 (95 % CI = -0.001 to 0.006) for NO2, βEC = 0.003 (95 % CI = -0.001, 0.007) for EC, and β500m buffer = -0.0014 (95 % CI = -0.0026 to −0.0001) for green space. Conclusions: More green space exposure at residence was associated with decreased cardiometabolic risk in children. Exposure to more NO2 and EC was also associated with increased cardiometabolic risk.</p

Mediating role of C-reactive protein in associations between pre-pregnancy BMI and adverse maternal and neonatal outcomes: the ABCD-study cohort

Objectives: Increased body mass index (BMI) is associated with several adverse pregnancy outcomes, though the underlying mechanism of this association has not been fully elucidated. A mediating role of low-grade systemic inflammation in these associations is suspected but has been understudied. Our objective was to examine the effect of pre-pregnancy BMI (pBMI) on maternal and neonatal pregnancy outcomes and to explore potential mediation of these effects by C-reactive protein (CRP), a first trimester peripheral marker of inflammation. Methods: Data from the prospective community-based ABCD-study cohort (n = 3547) was used to assess associations between self-reported continuous and categorized pBMI and outcome measures gestational hypertension (GH) and preeclampsia (PE), preterm birth (PTB) and small for gestational age (SGA) based on national perinatal registration linkage data. High-sensitivity CRP concentrations determined in serum were used to explore potential mediation of these associations by inflammation. Results: Multivariable logistic regression analyses, adjusted for confounders, showed that pBMI was significantly related to gestational hypertensive disorders (odds ratio (OR) per standard deviation (SD) 1.66, 95% confidence interval (CI) 1.51–1.83) and PTB (OR 1.20, 95% CI 1.05–1.37). Dose–response relationships between categorical pBMI and gestational hypertensive disorders (overweight OR 2.37, 95% CI 1.85–3.03 and obese OR 4.45, 95% CI 2.93–6.72) and PTB (obese OR 2.12, 95% CI 1.16–3.87) were found as well. SGA was only significantly more prevalent in the underweight BMI category (OR 2.06, 95% CI 1.33–3.19). Mediation analyses revealed small but significant indirect effects of pBMI on overall PTB (0.037, bootstrapped 95% CI 0.005–0.065) and spontaneous PTB (0.038, bootstrapped 95% CI 0.002–0.069) through higher CRP. CRP was not a significant mediator of associations between BMI and gestational hypertensive disorders although larger mediation was found for GH than for PE. Conclusion: Our findings provide additional evidence that high(er) pBMI increases the risk of adverse maternal and neonatal outcomes and that systemic inflammation mediates some of these risks. Further research in large cohorts including (morbidly) obese women is warranted to identify pathways that may be incorporated in future interventions to reduce the risk of adverse pregnancy outcomes due to maternal obesity

European birth cohorts for environmental health research

Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning

Risk factors for thyroid dysfunction in pregnancy: an individual participant data meta-analysis

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction

Socioeconomic inequalities in psychosocial problems of children:mediating role of maternal depressive symptoms

Background: Socioeconomically disadvantaged children often have psychosocial problems. This study examined the mediating role of maternal depressive symptoms during pregnancy, infancy and early childhood in the association between maternal education, as indicator of socioeconomic status (SES), and child's psychosocial problems. Methods: Included were 3410 children from the Amsterdam Born Children and their Development (ABCD) study. To assess the child's psychosocial problems at age 5-6 years, mothers and teachers completed the Strengths and Difficulties Questionnaire (SDQ). Maternal depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale and the Depressive Anxiety and Stress Scale 21. Mediation analysis was performed to calculate the direct effect of maternal education on SDQ score and indirect effects through maternal depressive symptoms. Results: The mean mother-reported SDQ total score was significantly higher (P < 0.001) for children of low-educated mothers (6.74 ± 4.41) compared with children of highly educated mothers (4.47 ± 3.73). Levels of maternal depressive symptoms were also higher in low-educated mothers during pregnancy, infancy and early childhood. Maternal depressive symptoms explained 27.5% of the association between maternal education and mother-reported SDQ scores and 22.9% for combined mother/teacher SDQ scores. Maternal depressive symptoms during pregnancy had the strongest indirect effect. Conclusion: Maternal depressive symptoms during pregnancy mediate the association between low maternal education and child's psychosocial problems. Early recognition and treatment of maternal depressive symptoms is important to prevent psychosocial problems in children, especially in those with low education

Infant feeding and ethnic differences in body mass index during childhood: a prospective study

This study investigated ethnic differences in childhood body mass index (BMI) in children from Dutch and Turkish descent and the role of infant feeding factors (breastfeeding duration, milk feeding frequency, as well as the timing, frequency and variety of complementary feeding (CF)). We used data from 244 children (116 Dutch and 128 Turkish) participating in a prospective study in the Netherlands. BMI was measured at 2, 3 and 5 years and standard deviation scores (sds) were derived using WHO references. Using linear mixed regression analyses, we examined ethnic differences in BMI-sds between 2 and 5 years, and the role of infant feeding in separate models including milk or CF factors, or both (full model). Relative to Dutch children, Turkish children had higher BMI-sds at age 3 (mean difference: 0.26; 95%CI: 0.04, 0.48) and 5 (0.63; 0.39, 0.88), but not at 2 years (0.08; −0.16, 0.31). Ethnic differences in BMI-sds were somewhat attenuated by CF factors at age 3 (0.16; −0.07, 0.40) and 5 years (0.50; 0.24, 0.77), whereas milk feeding had a minor impact. Of all factors, only CF variety was associated with BMI-sds in the full model. CF factors, particularly CF variety, explain a small fraction of the BMI-sds differences between Dutch and Turkish children. The role of CF variety on childhood BMI requires further investigatio

Maternal hypothyroxinaemia in early pregnancy and problem behavior in 5-year-old offspring

Introduction There is evidence, though not consistent, that offspring born to mothers with subtle decreases in thyroid function early in their pregnancies may be at risk of cognitive impairments and attention problems. However, other types of problem behavior have not been addressed thus far. We tested whether maternal thyroid function in early pregnancy is associated with several types of problem behavior in offspring at age 5–6 years. Methods This was a longitudinal study that included the data of 2000 mother-child pairs from the Amsterdam Born Children and their Development study. At a median gestational age of 12.9 (interquartile range: 11.9–14.1) weeks, maternal blood was sampled for assessment of free T4 and TSH. Overall problem behavior, hyperactivity/inattention, conduct problems, emotional problems, peer relationship problems and prosocial behavior were measured at age 5–6 years using the Strengths and Difficulties Questionnaire, which was filled out by both parents and teachers. Results Maternal hypothyroxinaemia <5th percentile was associated with a 1.70 (95% confidence interval (CI): 1.01–2.86) increased odds of teacher-reported hyperactivity/inattention after adjustment for confounders. By increasing the cut-off level to <10th percentile, the odds ratio became 1.47 (95% CI: 0.99–2.20). There were no associations between maternal thyroid function parameters and hyperactivity/inattention as reported by parents, nor with teacher or parent reports of other types of problem behavior. Conclusions Our results partially confirm previous observations, showing that early disruptions in the maternal thyroid hormone supply may be associated with ADHD symptoms in offspring. Our study adds that there is no evidence for an effect on other types of problem behavior

Creatine kinase is associated with blood pressure during pregnancy

Objective:Hypertensive disorders in pregnancy pose a major burden during pregnancy and are also associated with an increased risk for hypertension later in life. Plasma creatine kinase activity is identified in the general population as an independent risk factor for hypertension. We hypothesize that plasma creatine kinase activity is similarly associated with blood pressure during pregnancy.Methods:Women who participated in the 'Amsterdam Born Children and their Development-study' were eligible for the current study. The associations between plasma creatine kinase activity and blood pressure measurements during pregnancy, and between plasma creatine kinase activity and hypertensive disorders in pregnancy (gestational hypertension, HELLP, preeclampsia and eclampsia) were evaluated using multiple linear regression and logistic regression models.Results:In 3619 pregnant women, plasma creatine kinase activity was significantly associated with all blood pressure outcomes. This was most pronounced for the mean SBP throughout pregnancy, with a regression coefficient of 3.48 mmHg (CI 1.67-5.28, P < 0.001) per 1-unit logCK. With respect to the hypertensive disorders in pregnancy, we found a significant association between severe gestational hypertension diagnosed before 34 weeks of gestation (OR 9.16, CI 1.32-63.86, P = 0.025) per 1-unit logCK activity. HELLP and preeclampsia were not significantly associated.Conclusion:Our data show that plasma creatine kinase activity measured in early pregnancy is associated with blood pressure during pregnancy and associated with severe gestational hypertension diagnosed before 34 weeks of gestation, whereas no significant association was found between creatine kinase and other hypertensive disorders in pregnancy