Urban environment during pregnancy and lung function, wheezing, and asthma in school-age children. The generation R study.

The urban environment during pregnancy may influence child's respiratory health, but scarce evidence exists on systematic evaluation of multiple urban exposures (e.g., air pollution, natural spaces, noise, built environment) on children's lung function, wheezing, and asthma development. We aimed to examine the association of the urban environment during pregnancy with lung function, preschool wheezing, and school-age asthma. We included 5624 mother-child pairs participating in a population-based prospective birth cohort. We estimated 30 urban environmental exposures including air pollution, road traffic noise, traffic, green spaces, blue spaces, and built environment during pregnancy. At 10 years of age, lung function was measured by spirometry. Information on preschool wheezing and physician-diagnosed school-age asthma was obtained from multiple questionnaires. We described single-exposure associations with respiratory outcomes using an exposome-wide association study. We also identified patterns of urban exposures with hierarchical clustering on principal components analysis and examined their associations with respiratory outcomes using multivariate regression models. Single-exposure analyses showed associations of higher particulate matter (PM) with lower mid-expiratory flow (FEF25-75%) (e.g., for PM < 2.5 µm of diameter [PM2.5] z-score = -0.06 [-0.09, -0.03]) and higher forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) (e.g., for PM2.5 FEV1 0.05 [0.02, 0.08]) after correction for multiple-hypothesis testing. Cluster analysis described three patterns of urban exposures during pregnancy and showed that the cluster characterised by higher levels of air pollution, noise, walkability, street connectivity, and lower levels of natural spaces were associated with lower FEF25-75% (-0.08 [-0.17, 0.00]), and higher odds of preschool wheezing (1.21 [1.03, 1.43]). This study shows that the characteristics of the urban environment during pregnancy are of relevance to the offspring's respiratory health during childhood.

Maternal caffeine consumption during pregnancy and offspring cord blood DNA methylation: an epigenome-wide association study meta-analysis.

Background: Prenatal caffeine exposure may influence offspring health via DNA methylation, but no large studies have tested this. Materials & methods: Epigenome-wide association studies and differentially methylated regions in cord blood (450k or EPIC Illumina arrays) were meta-analyzed across six European cohorts (n = 3725). Differential methylation related to self-reported caffeine intake (mg/day) from coffee, tea and cola was compared with assess whether caffeine is driving effects. Results: One CpG site (cg19370043, PRRX1) was associated with caffeine and another (cg14591243, STAG1) with cola intake. A total of 12-22 differentially methylated regions were detected with limited overlap across caffeinated beverages. Conclusion: We found little evidence to support an intrauterine effect of caffeine on offspring DNA methylation. Statistical power limitations may have impacted our findings.

Current guidelines recommend pregnant women to limit caffeine intake to less than 200 mg daily, even though there is no clear proof of its effects on human development. A biological explanation for how exposure to caffeine during pregnancy influences development would help clarify if recommended limits are justified. An epigenetic mechanism, called DNA methylation (DNAm), has been suggested as a potential biological explanation for how caffeine intake during pregnancy influences health development. DNAm can switch genes 'on' or 'off' in response to environmental influences and therefore act as a bridge between genes and the environment. Studies have found that smoking during pregnancy is connected to over 6000 changes in DNAm at birth, with lasting effects into adulthood. To explore the link between caffeine intake during pregnancy and DNAm at birth, we analyzed data from 3725 mother­child pairs living in different European countries. We looked at effects from coffee, tea and cola intake during pregnancy on children's DNAm at birth. We found one change in DNAm to be connected to total caffeine and another to cola consumption during pregnancy. These few connections do not provide convincing evidence that caffeine intake during pregnancy impacts children's DNAm at birth. However, because mothers in our study consumed little caffeine, it is possible that results would be different in studies with participants consuming high amounts of caffeine during pregnancy. Potentially, our study did not include enough people to find very small changes in DNAm that are connected to caffeine consumption during pregnancy.

Associations of maternal urinary bisphenol and phthalate concentrations with offspring reproductive development.

Fetal exposure to bisphenols and phthalates may influence development of the reproductive system. In a population-based, prospective cohort study of 1059 mother-child pairs, we examined the associations of maternal gestational urinary bisphenols and phthalates concentrations with offspring reproductive development from infancy until 13 years. We measured urinary bisphenol and phthalate concentrations in each trimester. We obtained information on cryptorchidism or hypospadias after birth from medical records. At 9.7 years, we measured testicular and ovarian volume by MRI. At 13.5 years, we measured child Tanner stages and menstruation through questionnaire. We performed linear or logistic regression models for boys and girls to assess the associations of maternal urinary average and trimester-specific bisphenols and phthalates with child reproductive outcomes. Next, to further explore potential synergistic or additive effects of exposures together, we performed mixed exposure models using a quantile g computation approach. Models were adjusted for maternal age, ethnicity, body-mass index, education, parity, energy intake, smoking and alcohol use, and child's gestational age at birth, birthweight and body-mass index. In boys, no associations of maternal gestational phthalate or bisphenol with offspring cryptorchidism and hypospadias were found. Higher maternal high-molecular-weight phthalate and total bisphenol, but not phthalic acid or low-molecular-weight phthalate, were associated with larger child testicular volume at 10 years. Higher maternal phthalic acid and total bisphenol were associated with earlier genital and pubic hair development at 13 years, respectively (p-values<0.05). In girls, we found no associations of maternal urinary bisphenol and phthalate with ovarian volume or menstrual age. Only higher maternal urinary high-molecular-weight phthalate was associated with earlier pubic hair development at 13 years (p-values <0.05). Higher mixture exposure was associated with earlier pubic hair development in both sexes. In conclusion, higher maternal gestational urinary bisphenol and phthalate concentrations were associated with alterations in offspring reproductive development, mainly in boys.

Parental psychological distress during pregnancy and the risk of childhood lower lung function and asthma: a population-based prospective cohort study.

BACKGROUND: Although maternal psychological distress during pregnancy is associated with increased risks of respiratory morbidity in preschool children, it is unknown whether this association persists into later childhood. OBJECTIVE: To examine the association between parental psychological distress during pregnancy and lung function and asthma in children of school age. METHODS: This study of 4231 children was embedded in a population-based prospective cohort. Parental psychological distress was assessed by the Brief Symptom Inventory during and 3 years after pregnancy, and in mothers also at 2 and 6 months after pregnancy. At age 10 years, lung function was obtained by spirometry and asthma by questionnaire. RESULTS: The prevalence of asthma was 5.9%. Maternal overall psychological distress during pregnancy was associated with a lower forced vital capacity (FVC) (z-score difference -0.10 (95% CI -0.20 to -0.01) per 1-unit increase), maternal depressive symptoms during pregnancy with a lower forced expiratory volume in the first second (FEV1) and FVC (-0.13 (95% CI -0.24 to -0.01) and -0.13 (95% CI -0.24 to -0.02) when using clinical cut-offs) in their children. All maternal psychological distress measures during pregnancy were associated with an increased risk of asthma (range OR: 1.46 (95% CI 1.12 to 1.90) to 1.91 (95% CI 1.26 to 2.91)). Additional adjustment for paternal psychological distress during pregnancy and parental psychological distress after pregnancy did not materially change the associations. Paternal psychological distress during pregnancy was not associated with childhood respiratory morbidity. CONCLUSION: Maternal, but not paternal, psychological distress during pregnancy is associated with an increased risk of asthma and partly lower lung function in children. This suggests intrauterine programming for the risk of later-life respiratory disease.

Understanding the cumulative risk of maternal prenatal biopsychosocial factors on birth weight: a DynaHEALTH study on two birth cohorts.

BACKGROUND: There are various maternal prenatal biopsychosocial (BPS) predictors of birth weight, making it difficult to quantify their cumulative relationship. METHODS: We studied two birth cohorts: Northern Finland Birth Cohort 1986 (NFBC1986) born in 1985-1986 and the Generation R Study (from the Netherlands) born in 2002-2006. In NFBC1986, we selected variables depicting BPS exposure in association with birth weight and performed factor analysis to derive latent constructs representing the relationship between these variables. In Generation R, the same factors were generated weighted by loadings of NFBC1986. Factor scores from each factor were then allocated into tertiles and added together to calculate a cumulative BPS score. In all cases, we used regression analyses to explore the relationship with birth weight corrected for sex and gestational age and additionally adjusted for other factors. RESULTS: Factor analysis supported a four-factor structure, labelled closely to represent their characteristics as 'Factor1-BMI' (body mass index), 'Factor2-DBP' (diastolic blood pressure), 'Factor3-Socioeconomic-Obstetric-Profile' and 'Factor4-Parental-Lifestyle'. In both cohorts, 'Factor1-BMI' was positively associated with birth weight, whereas other factors showed negative association. 'Factor3-Socioeconomic-Obstetric-Profile' and 'Factor4-Parental-Lifestyle' had the greatest effect size, explaining 30% of the variation in birth weight. Associations of the factors with birth weight were largely driven by 'Factor1-BMI'. Graded decrease in birth weight was observed with increasing cumulative BPS score, jointly evaluating four factors in both cohorts. CONCLUSION: Our study is a proof of concept for maternal prenatal BPS hypothesis, highlighting the components snowball effect on birth weight in two different European birth cohorts.

Fetal and infant growth patterns and left and right ventricular measures in childhood assessed by cardiac MRI.

OBJECTIVES: Early life is critical for cardiac development. We examined the associations of longitudinal fetal and childhood growth patterns with childhood right and left ventricular structures measured by cardiac magnetic resonance imaging. METHODS: In a population-based prospective cohort study among 2827 children, we measured growth at 20 and 30 weeks of pregnancy, at birth, 0.5, 1, 2, 6 and 10 years. At 10 years, we measured right ventricular end-diastolic volume, left ventricular end-diastolic volume, left ventricular mass and left ventricular mass-to-volume ratio by cardiac magnetic resonance imaging. RESULTS: Small size for gestational age at birth was associated with smaller right and left ventricular end-diastolic volume relative to current body surface area, but with larger left ventricular mass-to-volume ratio (P < 0.05). Children in the upper 25% of right and left ventricular end-diastolic volume and left ventricular mass at age 10 years were larger at birth and became taller and leaner in childhood (P < 0.05). In contrast, children in the lower 25% of right and left ventricular end-diastolic volume and left ventricular mass were smaller at birth and became shorter and heavier in childhood (P < 0.05). Both fetal and childhood growth were independently of each other associated with childhood right and left ventricular end-diastolic volume and left ventricular mass. CONCLUSION: Children who are larger at birth and grow taller and leaner in childhood have larger hearts relative to body surface area. Small size at birth children, who grow shorter and heavier in childhood, have relatively smaller hearts with larger left ventricular mass-to-volume ratio. Both fetal and childhood growth are important for the development of cardiac dimensions.

Associations of maternal caffeine intake during pregnancy with abdominal and liver fat deposition in childhood.

BACKGROUND: Maternal caffeine intake during pregnancy is associated with an increased risk of childhood obesity. Studies in adults suggest that caffeine intake might also directly affect visceral and liver fat deposition, which are strong risk factors for cardio-metabolic disease. OBJECTIVE: To assess the associations of maternal caffeine intake during pregnancy with childhood general, abdominal, and liver fat mass at 10 years of age. METHODS: In a population-based cohort from early pregnancy onwards among 4770 mothers and children, we assessed maternal caffeine intake during pregnancy and childhood fat mass at age 10 years. RESULTS: Compared with children whose mothers consumed <2 units of caffeine per day during pregnancy, those whose mothers consumed 4-5.9 and ≥6 units of caffeine per day had a higher body mass index, total body fat mass index, android/gynoid fat mass ratio, and abdominal subcutaneous and visceral fat mass indices. Children whose mothers consumed 4-5.9 units of caffeine per day had a higher liver fat fraction. The associations with abdominal visceral fat and liver fat persisted after taking childhood total body fat mass into account. CONCLUSIONS: High maternal caffeine intake during pregnancy was associated with higher childhood body mass index, total body fat, abdominal visceral fat, and liver fat. The associations with childhood abdominal visceral fat and liver fat fraction were independent of childhood total body fat. This suggests differential fat accumulation in these depots, which may increase susceptibility to cardio-metabolic disease in later life.

Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking.

Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.

The Associations of Maternal and Neonatal Vitamin D with Dental Development in Childhood.

BACKGROUND: Vitamin D influences the formation and mineralization of teeth. OBJECTIVE: To investigate the association of maternal and neonatal vitamin D concentrations with the dental development of 10-y-old children, in a population-based prospective cohort study among 3,770 mothers and children in the Netherlands. METHODS: Maternal venous blood samples were collected in the second trimester (median 20.4 weeks of gestation; range: 18.5-23.2 wk) whereas umbilical cord blood samples were collected immediately after delivery (median 40.1 weeks of gestation; range 35.9-42.3 wk). Dental development was defined using the Demirjian method. Multivariate regression models were built to analyze the studied associations. RESULTS: High concentrations of 25-hydroxyvitamin D [25(OH)D] during midpregnancy (ß: -0.04; 95% CI: -0.08, -0.01) and at birth (ß: -0.06; 95% CI: -0.10, -0.02) were associated with a lower dental age in children. The children of mothers with severe vitamin D deficiency [25(OH)D <25.0 nmol/L] during midpregnancy exhibited a higher dental age (ß: 0.14; 95% CI: 0.03, 0.24) and higher developmental stages of the mandibular first premolar (ß: 0.32; 95% CI: 0.04, 0.60) compared with the children of mothers with optimal values of 25(OH)D (≥75.0 nmol/L). Children with vitamin D deficiency [25(OH)D 25.0-49.9 nmol/L] at birth exhibited a higher dental age (ß: 0.11; 95% CI: 0.01, 0.20), higher developmental stages of the mandibular second premolar (ß: 0.27; 95% CI: 0.02, 0.51), and higher developmental stages of the mandibular second molar (ß: 0.24; 95% CI: 0.00, 0.48) compared with children with sufficient-to-optimal values of 25(OH)D (≥50.0 nmol/L) at birth. CONCLUSION: Higher maternal and neonatal 25(OH)D concentrations are associated with decelerated dental development in childhood. The lower the vitamin D level during midpregnancy or at birth, the higher the dental age of children, and the higher the developmental stages of the mandibular teeth.

Bayesian imputation of time-varying covariates in linear mixed models.

Studies involving large observational datasets commonly face the challenge of dealing with multiple missing values. The most popular approach to overcome this challenge, multiple imputation using chained equations, however, has been shown to be sub-optimal in complex settings, specifically in settings with longitudinal outcomes, which cannot be easily and adequately included in the imputation models. Bayesian methods avoid this difficulty by specification of a joint distribution and thus offer an alternative. A popular choice for that joint distribution is the multivariate normal distribution. In more complicated settings, as in our two motivating examples that involve time-varying covariates, additional issues require consideration: the endo- or exogeneity of the covariate and its functional relation with the outcome. In such situations, the implied assumptions of standard methods may be violated, resulting in bias. In this work, we extend and study a more flexible, Bayesian alternative to the multivariate normal approach, to better handle complex incomplete longitudinal data. We discuss and compare assumptions of the two Bayesian approaches about the endo- or exogeneity of the covariates and the functional form of the association with the outcome, and illustrate and evaluate consequences of violations of those assumptions using simulation studies and two real data examples.

Structure, longitudinal invariance, and stability of the Child Behavior Checklist 1½-5's Diagnostic and Statistical Manual of Mental Disorders-Autism Spectrum Disorder scale: Findings from Generation R (Rotterdam).

Although the Child Behavior Checklist 1½-5's 12-item Diagnostic and Statistical Manual of Mental Disorders-Autism Spectrum Problems Scale (formerly called Pervasive Developmental Problems scale) has been used in several studies as an autism spectrum disorder screener, the base rate and stability of its items and its measurement model have not been previously studied. We therefore examined the structure, longitudinal invariance, and stability of the Child Behavior Checklist 1½-5's Diagnostic and Statistical Manual of Mental Disorders-Autism Spectrum Problems Scale in the diverse Generation R (Rotterdam) sample based on mothers' ratings at 18 months (n = 4695), 3 years (n = 4571), and 5 years (n = 5752). Five items that seemed especially characteristic of autism spectrum disorder had low base rates at all three ages. The rank order of base rates for the 12 items was highly correlated over time (Qs ⩾ 0.86), but the longitudinal stability of individual items was modest (phi coefficients = 0.15-0.34). Confirmatory factor analyses indicated that the autism spectrum disorder scale model manifested configural, metric, and scalar longitudinal invariance over the time period from 18 months to 5 years, with large factor loadings. Correlations over time for observed autism spectrum disorder scale scores (0.25-0.50) were generally lower than the correlations across time of the latent factors (0.45-0.68). Results indicated significant associations of the autism spectrum disorder scale with later autism spectrum disorder diagnoses.

Environmental factors explain socioeconomic prevalence differences in myopia in 6-year-old children.

PURPOSE: High myopia (≤-6 D) usually has its onset before 10 years of age and can lead to blinding complications later in life. We examined whether differences in myopia prevalences in socioeconomic risk groups could be explained by differences in lifestyle factors. METHODS: A total of 5711 six-year-old children participating in the prospective population-based birth cohort study Generation R underwent a stepwise ophthalmic examination, which included visual acuity and objective cycloplegic refraction to identify children with myopia (≤-0.5D). Daily activities, ethnicity, factors representing family socioeconomic status and housing were ascertained by questionnaire. Risk assessments of myopia and mediation analyses were performed using logistic regression; attenuation of risks was calculated by bootstrapping. RESULTS: Prevalence of myopia was 2.4% (n=137). Myopic children spent more time indoors and less outdoors than non-myopic children (p<0.01), had lower vitamin D (p=0.01), had a higher body mass index and participated less in sports (p=0.03). Children of non-European descent (OR 2.60; 95% CI 1.84 to 3.68), low maternal education (OR 2.27; 95% CI 1.57 to 3.28) and low family income (OR 2.62; 95% CI 1.8 to 3.74) were more often myopic. Lifestyle factors explained the majority of the increased risk for ethnicity (82%; 95% CI 55 to 120), maternal education (69%; 95% CI 45 to 109) and family socioeconomic status (71%; 95% CI 46 to 104). CONCLUSION: This study found environmental factors to be strong risk factors for myopia already at the age of 6 years. The myopia prevalence differences in socioeconomic groups were greatly determined by differences in distribution of these environmental risk factors, highlighting the importance of lifestyle adjustments in young children developing myopia.

Association of light-to-moderate alcohol drinking in pregnancy with preterm birth and birth weight: elucidating bias by pooling data from nine European cohorts.

Women who drink light-to-moderately during pregnancy have been observed to have lower risk of unfavourable pregnancy outcomes than abstainers. This has been suggested to be a result of bias. In a pooled sample, including 193 747 live-born singletons from nine European cohorts, we examined the associations between light-to-moderate drinking and preterm birth, birth weight, and small-for-gestational age in term born children (term SGA). To address potential sources of bias, we compared the associations from the total sample with a sub-sample restricted to first-time pregnant women who conceived within six months of trying, and examined whether the associations varied across calendar time. In the total sample, drinking up to around six drinks per week as compared to abstaining was associated with lower risk of preterm birth, whereas no significant associations were found for birth weight or term SGA. Drinking six or more drinks per week was associated with lower birth weight and higher risk of term SGA, but no increased risk of preterm birth. The analyses restricted to women without reproductive experience revealed similar results. Before 2000 approximately half of pregnant women drank alcohol. This decreased to 39% in 2000-2004, and 14% in 2005-2011. Before 2000, every additional drink was associated with reduced mean birth weight, whereas in 2005-2011, the mean birth weight increased with increasing intake. The period-specific associations between low-to-moderate drinking and birth weight, which also were observed for term SGA, are indicative of bias. It is impossible to distinguish if the bias is attributable to unmeasured confounding, which change over time or cohort heterogeneity.

Testing the direction of effects between child body composition and restrictive feeding practices: results from a population-based cohort.

Background: Parental restrictive feeding (i.e., limiting food intake of children) has been linked to childhood overweight. However, the directionality of the causal pathway remains unknown.Objective: The objectives of this study were to examine the bidirectional association of maternal restrictive feeding with children's weight and body composition across childhood and to explore a possible mediating role of maternal concern about child weight.Design: Data were available for 4689 mother-child dyads participating in Generation R, a prospective birth cohort in the Netherlands. At ages 4 and 10 y, restrictive feeding was assessed with the parent-reported Child Feeding Questionnaire, and children's body mass index (BMI) was measured. At age 6 y, fat mass index (FMI) and fat-free mass index (FFMI) were measured with dual-energy X-ray absorptiometry. Both directions of the relation between restriction and child body composition were examined with multivariable linear regression analyses and cross-lagged modeling. Mediation analyses were performed to examine concern about child weight (mother reported at child age of 10 y) as a potential mediator.Results: Higher child sex- and age-adjusted BMI SD scores (zBMI) at age 4 y predicted more restrictive feeding at age 10 y (B = 0.15; 95% CI: 0.11, 0.18). Both sex- and age-adjusted FMI SD scores (zFMI) and sex-and age-adjusted FFMI SD scores (zFFMI) at 6 y were also positively associated with restrictive feeding at 10 y. Maternal concern about child weight partially mediated these associations from child body composition to restrictive feeding (e.g., for zBMI at 4 y: Bindirect = 0.10; 95% CI: 0.07, 0.13). There was no temporal association from restrictive feeding at age 4 y to child zBMI at age 10 y after adjustment for baseline zBMI.Conclusions: The continued use of restrictive feeding practices at age 10 y appeared to be primarily a response of mothers to an unhealthy weight of their child rather than a cause of children's overweight. Guidelines discouraging restrictive feeding for preventing childhood overweight should therefore be reconsidered.

Tracking of structural and functional cardiac measures from infancy into school-age.

Objective Cardiac structure and function are important predictors for cardiovascular disease in adults. Not much is known about tracking of cardiac measures, other than left ventricular mass, from early life onwards. We examined whether and to what extent cardiac measures track from infancy into school-age. Methods We performed a population-based prospective cohort study among 1072 children. Aortic root diameter, left atrial diameter, left ventricular mass, relative wall thickness and fractional shortening were measured repeatedly by echocardiography. We explored tracking between infancy (1.5, six and 24 months) and school-age (six and 10 years). Results Of all cardiac measures, aortic root diameter, left atrial diameter and left ventricular mass were significantly correlated between infancy and school-age ( r = 0.10-0.42, all p-values < 0.01), with the strongest correlations between 24 months and 10 years. Of the different structures, aortic root diameter showed the strongest correlations. Approximately 30% of children who were in the lowest or highest quartile of a measure at the age of 1.5 months remained in that quartile at the age of 10 years. When analysing the effects of the infant cardiac measures on the same outcomes at 10 years in conditional regression models, we observed effect estimates of the same size for the different age windows. Conclusion Our results suggest moderate tracking of structural cardiac measures from early infancy until school-age, which become stronger at older ages, but not of relative wall thickness or fractional shortening. Moderate tracking of cardiac structures suggests that cardiac structures are at least partly determined in early life.

Mothers' intake of sugar-containing beverages during pregnancy and body composition of their children during childhood: the Generation R Study.

Background: High intake of sugar-containing beverages (SCBs) has been linked to increased risk of obesity. However, associations of SCB intake during pregnancy with child body composition have been unclear.Objectives: We explored whether SCB intake during pregnancy was associated with children's body mass index (BMI) and detailed measures of body composition. In addition, we examined different types of SCBs (i.e., fruit juice, soda, and concentrate).Design: We included 3312 mother-child pairs of the Generation R Study, a prospective cohort from fetal life onward in the Netherlands. Energy-adjusted SCB intake was assessed in the first trimester with a food-frequency questionnaire. Anthropometric data of the children were collected repeatedly ≤6 y of age, and BMI was calculated. At 6 y of age, we further measured fat mass index (FMI) and fat-free mass index with dual-energy X-ray absorptiometry. All outcomes were sex- and age-standardized. Associations of SCB intake with children's BMI trajectories and body composition were analyzed with multivariable linear mixed and regression models.Results: Results from linear mixed models showed that, after adjustment for confounders including the SCB intake of the child itself, mothers' total SCB intake was positively associated with children's BMI ≤6 y of age [per serving per day: 0.04 SD score (SDS); 95% CI: 0.00, 0.07 SDS]. In addition, intakes of total SCBs and fruit juice, but not of soda or concentrate, were associated with a higher FMI [total SCBs: 0.05 SDS (95% CI: 0.01, 0.08 SDS); fruit juice: 0.04 SDS (95% CI: 0.01, 0.06 SDS)] of the 6-y-old children. These associations remained significant (P < 0.05) after additional adjustment for gestational weight gain, birth weight, and children's insulin concentrations.Conclusion: Our study suggests that maternal SCB intake during pregnancy is positively associated with children's BMI during early childhood and particularly with higher fat mass.

Maternal Midpregnancy Plasma trans 18:1 Fatty Acid Concentrations Are Positively Associated with Risk of Maternal Vascular Complications and Child Low Birth Weight.

Background: Evidence is plentiful that trans fatty acids (TFAs) induce vascular inflammation with adverse metabolic consequences. However, it is not clear whether TFAs increase the risk of vascular pregnancy complications such as preeclampsia.Objective: We investigated associations between midpregnancy maternal plasma trans 18:1 fatty acid (t18:1) concentrations and pregnancy course and outcomes.Methods: Participants were 6695 pregnant women and newborns from the Generation R Study, Rotterdam, Netherlands (enrollment in 2001-2005). Maternal midpregnancy (mean ± SD gestational age: 20.7 ± 1.2 wk) t18:1 plasma concentrations were determined and related to gestational age and sex-adjusted birth weight SD scores, placental weight, and the risk of preeclampsia. In addition, we explored potential time trends by testing the association of maternal plasma t18:1 concentrations with birth weight in birth cohorts given the Dutch industry-initiative to lower food TFA contents during the inclusion period. Multiple logistic and linear regression analyses were performed, taking various socioeconomic and biological covariates into account.Results: A higher midpregnancy maternal plasma t18:1 concentration was associated with lower birth weight (SD score, adjusted ß: -0.10; 95% CI: -0.15, -0.04; P < 0.001) and placental weight (kilograms, adjusted ß: -10,65; 95% CI: -20.23, -1.07; P = 0.03) and with a higher risk of preeclampsia (adjusted OR: 1.65; 95% CI: 1.10, 2.49; P = 0.02). We observed a 31% decrease in the median plasma t18:1 concentration in our population over time, but the association between the plasma t18:1 concentration standardized per birth year and birth weight was comparable between birth-year cohorts (years 2001-2005).Conclusions: A higher maternal midpregnancy plasma t18:1 concentration was associated with lower birth weight and placental weight and with a higher risk of preeclampsia. Although the intake of TFAs in our population decreased during the inclusion period, the association with adverse pregnancy outcomes was unchanged even at lower maternal plasma t18:1 concentrations.

Intake of Different Types of Fatty Acids in Infancy Is Not Associated with Growth, Adiposity, or Cardiometabolic Health up to 6 Years of Age.

Background: Studies in adults indicate that a lower saturated and higher unsaturated fat intake is associated with a lower risk of metabolic syndrome and cardiovascular diseases. However, studies on fat intake in relation to cardiometabolic health during childhood are scarce.Objective: We examined associations between dietary intake of fatty acids (FAs) at age 1 y and measures of growth, adiposity, and cardiometabolic health up to age 6 y.Methods: This study was conducted in 2927 children participating in the Generation R Study, a multiethnic, prospective, population-based cohort in the Netherlands. We measured children's total fat intake and intakes of saturated FAs (SFAs), monounsaturated FAs (MUFAs), and polyunsaturated FAs (PUFAs) at a median age of 12.9 mo (95% range: 12.2, 18.9 mo) with a food-frequency questionnaire. We repeatedly measured their height and weight up to age 6 y. At 6 y of age, we measured body fat percentage, diastolic and systolic blood pressure, and serum insulin, triacylglycerol, and HDL cholesterol. These outcomes were combined into a cardiometabolic risk factor score. We examined associations of FA intake with repeated measures of height, weight, and body mass index by using linear mixed models and with cardiometabolic outcomes by using linear regression models, adjusting for sociodemographic and lifestyle factors and taking into account macronutrient substitution effects.Results: In multivariable models, we observed no associations of a higher intake of total fat or SFAs, MUFAs, or PUFAs with growth, adiposity, or cardiometabolic health when fat was consumed at the expense of carbohydrates. In subsequent models, there were also no associations observed for higher MUFA or PUFA intakes at the expense of SFAs with any of the outcomes. Results did not differ by sex, ethnicity, age, or birth weight.Conclusion: The results of this study did not support our hypothesis that intake of different types of FAs was associated with adiposity or cardiometabolic health among children.

Prenatal exposure to selective serotonin reuptake inhibitors and non-verbal cognitive functioning in childhood.

Selective serotonin reuptake Inhibitors (SSRIs) are frequently used during pregnancy. Evidence about the long-term consequences of prenatal SSRI exposure on child neurodevelopment is controversial. We prospectively investigated whether prenatal SSRI exposure was associated with childhood non-verbal cognition in a population-based study, and contrasted it to exposure to depressive symptoms (without SSRIs). We included 71 children prenatally exposed to SSRIs, 385 children prenatally exposed to maternal depressive symptoms and 5427 unexposed children. Child executive functioning was assessed by maternal report at 4 years ( n=4020). Non-verbal intelligence was measured at 5 years ( n=5001) and children were tested with a neuropsychological battery at 7 years ( n=1194). Prenatal SSRI exposure was not related to maternal reported executive function at 4 years, nor was it related with observed non-verbal intelligence at age 5 or neuropsychological function at 7 years. Exposure to untreated maternal depressive symptoms was related to maternal reported shifting problems and emotional control problems at 4 years. No associations between exposure to depressive symptoms and observed non-verbal IQ at 5 years or neuropsychological function at 7 years were found. This population-based study suggests that neither SSRI use nor untreated depressive symptoms during pregnancy had a major impact on child non-verbal cognition.

Dietary Intake of Protein in Early Childhood Is Associated with Growth Trajectories between 1 and 9 Years of Age.

BACKGROUND: High protein intake in infancy might lead to a higher body mass index (BMI) in childhood. However, whether these associations differ between different sources of protein is unclear. OBJECTIVE: We investigated associations between the intake of total protein, protein from different sources, and individual amino acids in early childhood and repeatedly measured height, weight, and BMI up to the age of 9 y. METHODS: This study was performed in 3564 children participating in the Generation R Study, a population-based prospective cohort study in Rotterdam, Netherlands. Intakes of total protein, animal protein, vegetable protein, and individual amino acids (including methionine, arginine, lysine, threonine, valine, leucine, isoleucine, phenylalanine, tryptophan, histidine, cysteine, tyrosine, alanine, asparagine, glutamine, glycine, proline, and serine) at 1 y were assessed by using a food-frequency questionnaire. Height and weight were measured at the approximate ages of 14, 18, 24, 30, 36, and 45 mo and at 6 and 9 y, and BMI was calculated. RESULTS: After adjustment for confounders, linear mixed models showed that a 10-g higher total protein intake/d at 1 y was significantly associated with a 0.03-SD greater height (95% CI: 0.00, 0.06), a 0.06-SD higher weight (95% CI: 0.03, 0.09), and a 0.05-SD higher BMI (95% CI: 0.03, 0.08) up to the age of 9 y. Associations were stronger for animal than for vegetable protein intake but did not differ between dairy and nondairy animal protein or between specific amino acids. CONCLUSIONS: A higher intake of protein, especially animal protein, at 1 y of age was associated with a greater height, weight, and BMI in childhood up to 9 y of age. Future studies should explore the role of growth hormones and investigate whether protein intake in early childhood affects health later in life.