What maternal educational mobility tells us about the mother's parenting routines, offspring school achievement and intelligence.

BACKGROUND: Educational mobility at the macro-level is a common measure of social inequality. Nonetheless, the correlates of mobility of education at the individual level are less well studied. We evaluated whether educational mobility of the second generation (compared to the first generation level) predicts differences in parenting practices of the second generation and school achievement and intelligence in the third generation. METHODS: Data from a population-based cohort of children in the Netherlands (N = 3547; 49.4% boys) were analyzed. Maternal, grandparental education and family routines, a parenting practice, were reported by the mother. Child school achievement at the end of primary school (∼12 years, with the national Dutch academic test score) and child intelligence (∼6 and 13 years) were measured in a standardized manner. Also, a child genome-wide polygenic score of academic attainment was calculated. To estimate the effect of educational mobility, inverse probability-weighted linear models and Diagonal Reference Models (DRM) were used. RESULTS: Upward maternal educational mobility was associated with better offspring school achievement, higher intelligence, and more family routines if compared to offspring of mothers with no upward mobility. However, mothers did not implement the same level of family routines as similarly educated mothers and grandfathers who already had achieved this educational level. Likewise, children of mothers with upward educational mobility had lower school achievement and intelligence than children of similarly educated mothers with no mobility. Child's genetic potential for education followed a similar association pattern with higher potential in children of upward mobile mothers. CONCLUSION: Policymakers might overlook social inequalities when focused on parental socioeconomic status. Grandparental socioeconomic status, which independently predicts child school achievement, intelligence, and parental family routines, should also be assessed. The child's genetic endowment reflects the propensity for education across generations that partly underlies mobility and some of its effect on the offspring.

A Narrative Review of the Association between Prematurity and Attention-Deficit/Hyperactivity Disorder and Accompanying Inequities across the Life-Course.

Preterm birth is associated with an increased risk of neurodevelopmental and neurobehavioral impairments including attention-deficit/hyperactivity disorder (ADHD), the most common neurobehavioral disorder of childhood. In this narrative review, we examine the known associations between prematurity and ADHD and highlight the impact of both prematurity and ADHD on multiple domains across the pediatric life-course. We develop a framework for understanding the health services journey of individuals with ADHD to access appropriate services and treatments for ADHD, the "ADHD Care Cascade". We then discuss the many racial and ethnic inequities that affect the risk of preterm birth as well as the steps along the "ADHD Care Cascade". By using a life-course approach, we highlight the ways in which inequities are layered over time to magnify the neurodevelopmental impact of preterm birth on the most vulnerable children across the life-course.

Prospective Associations of Childhood Housing Insecurity With Anxiety and Depression Symptoms During Childhood and Adulthood.

Importance: Childhood housing insecurity has dramatically increased in the US in recent decades, but whether an association with adverse mental health outcomes exists after adjusting for repeated measures of childhood poverty is unclear. Objective: To test whether childhood housing insecurity is associated with later anxiety and depression symptoms after adjusting for time-varying measures of childhood poverty. Design, Setting, and Participants: This prospective cohort study included individuals aged 9, 11, and 13 years at baseline from the Great Smoky Mountains Study in western North Carolina. Participants were assessed up to 11 times from January 1993 to December 2015. Data were analyzed from October 2021 to October 2022. Exposure: Participants and their parents reported social factors annually when participants were 9 to 16 years of age. A comprehensive measure of childhood housing insecurity was constructed based on frequent residential moves, reduced standard of living, forced separation from home, and foster care status. Main Outcomes and Measures: Between ages 9 and 16 years, the Child and Adolescent Psychiatric Assessment was used up to 7 times to evaluate childhood anxiety and depression symptoms. Adult anxiety and depression symptoms were assessed at ages 19, 21, 26, and 30 years using the Young Adult Psychiatric Assessment. Results: Of the 1339 participants (mean [SD] age, 11.3 [1.63] years), 739 (55.2%; 51.1% weighted) were male; 1203 individuals assessed up to 30 years of age were included in the adulthood outcome analyses. Standardized mean (SD) baseline anxiety and depression symptom scores were higher among children who experienced housing insecurity than among those who never experienced housing insecurity (anxiety: 0.49 [1.15] vs 0.22 [1.02]; depression: 0.20 [1.08] vs -0.06 [0.82]). Individuals who experienced childhood housing insecurity had higher anxiety symptom scores (fixed effects: standardized mean difference [SMD], 0.21; 95% CI, 0.12-0.30; random effects: SMD, 0.25; 95% CI, 0.15-0.35) and higher depression symptom scores (fixed effects: SMD, 0.18; 95% CI, 0.09-0.28; random effects: SMD, 0.26; 95% CI, 0.14-0.37) during childhood. In adulthood, childhood housing insecurity was associated with higher depression symptom scores (SMD, 0.11; 95% CI, 0.00-0.21). Conclusions and Relevance: In this cohort study, housing insecurity was associated with anxiety and depression during childhood and with depression during adulthood. Because housing insecurity is a modifiable, policy-relevant factor associated with psychopathology, these results suggest that social policies that support secure housing may be an important prevention strategy.

Hospital healthcare utilizers with medical and psychiatric claims in the Netherlands: a nationwide study.

BACKGROUND: Psychiatric and medical multimorbidity is associated with low quality of life, poor functioning and excess mortality. Differences in healthcare utilization between those receiving co-occurring medical and psychiatric healthcare (HUMPCs) and those only receiving medical (HUMCs) or only psychiatric healthcare (HUPCs) may indicate differences in care accessibility, help-seeking behavior and the risk patterns of medical illness. We aimed to assess the occurrence of psychiatric diagnostic groups in HUMPCs compared to HUPCs and to compare their medical and psychiatric claims expenditures. METHODS: Using Dutch claims data covering psychiatric and medical hospital care in 2010-2011, healthcare utilization differences between HUMPCs and HUPCs were expressed as differences and ratios, accounting for differences in age and sex between groups. Median claims expenditures were then compared between HUMPCs and HUPCs. RESULTS: HUMPCs had 40% higher median medical cost of claims compared to HUMCs and a 10% increased number of psychiatric claims compared to HUPCs. HUMPCs were more often diagnosed with: organic disorders; behavioral syndromes associated with physiological disturbances and physical factors; mood [affective] disorders; neurotic, stress related and somatoform disorders; and disorders of adult personality and behavior. By contrast, disorders of psychological development, schizophrenia, schizotypal and delusional disorders, behavioral and emotional disorders with usual onset occurring in childhood, and mental and behavioral disorders due to psychoactive substance abuse were less often diagnosed in this group. CONCLUSIONS: Both medical and psychiatric disease become more costly where both are present. For HUMPCs the costs of both medical and psychiatric claims for almost all diagnostic groups were higher than for HUPCs and HUMCs.

The Role of Breastfeeding in Racial and Ethnic Disparities in Sudden Unexpected Infant Death: A Population-Based Study of 13 Million Infants in the United States.

Sudden unexpected infant death (SUID) disproportionately affects non-Hispanic Black (NHB) and American Indian/Alaskan Native infants, who have lower rates of breastfeeding than other groups. Using 13,077,880 live-birth certificates and 11,942 linked SUID death certificates from 2015 through 2018, we calculated odds ratios and adjusted risk differences of SUID in infants who were not breastfed across 5 racial/ethnic strata in the United States. We analyzed mediation by not breastfeeding in the race/ethnicity-SUID association. The overall SUID rate was 0.91 per 1,000 live births. NHB and American Indian/Alaskan Native infants had the highest disparity in SUID relative to non-Hispanic White infants. Overall, not breastfeeding was associated with SUID (adjusted odds ratio (aOR), 1.14; 95% confidence interval (CI): 1.10, 1.19), and the adjusted risk difference was 0.12 per 1,000 live births. The aOR of not breastfeeding for SUID was 1.07 (95% CI: 1.00, 1.14) in NHB infants and 1.29 (95% CI: 1.14, 1.46) in Hispanic infants. Breastfeeding minimally explained the higher SUID risk in NHB infants (2.3% mediated) and the lower risk in Hispanic infants (2.1% mediated) relative to non-Hispanic White infants. Competing risks likely explain the lower aOR seen in NHB infants of not breastfeeding on SUID, suggesting that social or structural determinants must be addressed to reduce racial disparities in SUID.

Parental Age and Offspring Childhood Mental Health: A Multi-Cohort, Population-Based Investigation.

To examine the contributions of maternal and paternal age on offspring externalizing and internalizing problems, this study analyzed problem behaviors at age 10-12 years from four Dutch population-based cohorts (N = 32,892) by a multiple informant design. Bayesian evidence synthesis was used to combine results across cohorts with 50% of the data analyzed for discovery and 50% for confirmation. There was evidence of a robust negative linear relation between parental age and externalizing problems as reported by parents. In teacher-reports, this relation was largely explained by parental socio-economic status. Parental age had limited to no association with internalizing problems. Thus, in this large population-based study, either a beneficial or no effect of advanced parenthood on child problem behavior was observed.

Application of the Instrumental Inequalities to a Mendelian Randomization Study With Multiple Proposed Instruments.

BACKGROUND: Investigators often support the validity of Mendelian randomization (MR) studies, an instrumental variable approach proposing genetic variants as instruments, via. subject matter knowledge. However, the instrumental variable model implies certain inequalities, offering an empirical method of falsifying (but not verifying) the underlying assumptions. Although these inequalities are said to detect only extreme assumption violations in practice, to our knowledge they have not been used in settings with multiple proposed instruments. METHODS: We applied the instrumental inequalities to an MR analysis of the effect of maternal pregnancy vitamin D on offspring psychiatric outcomes, proposing four independent maternal genetic variants as instruments. We assessed whether the proposed instruments satisfied the instrumental inequalities separately and jointly and explored the instrumental inequalities' properties via simulations. RESULTS: The instrumental inequalities were satisfied (i.e., we did not falsify the MR model) when considering each variant separately. However, the inequalities were violated when considering four variants jointly and for some combinations of two or three variants (two of 36 two-variant combinations and 18 of 24 three-variant combinations). In simulations, the inequalities detected structural biases more often when assessing proposed instruments jointly, although falsification in the absence of structural bias remained rare. CONCLUSIONS: The instrumental inequalities detected violations of the MR assumptions for genetic variants jointly proposed as instruments in our study, although the instrumental inequalities were satisfied when considering each proposed instrument separately. We discuss how investigators can assess instrumental inequalities to eliminate clearly invalid analyses in settings with many proposed instruments and provide appropriate code.

Frequent Bullying Involvement and Brain Morphology in Children.

Background: Over the past few decades, bullying has been recognized as a considerable public health concern. Involvement in bullying is associated with poor long-term social and psychiatric outcomes for both perpetrators and targets of bullying. Despite this concerning prognosis, few studies have investigated possible neurobiological correlates of bullying involvement that may explain the long-term impact of bullying. Cortical thickness is ideally suited for examining deviations in typical brain development, as it has been shown to detect subtle differences in children with psychopathology. We tested associations between bullying involvement and cortical thickness using a large, population-based cohort. Methods: The study sample consisted of 2,602 participants from the Generation R Study. When children were 8 years old, parents and teachers reported on common forms of child bullying involvement (physical, verbal, and relational). Questions ascertained whether a child was involved as a perpetrator (n = 82), a target of bullying (n = 92), as a combined perpetrator and target of bullying (n = 47), or uninvolved in frequent bullying (n = 2,381). High-resolution structural MRI was conducted when children were 10 years of age. Cortical thickness estimates across the cortical mantle were compared among groups. Results: Children classified as frequent targets of bullying showed thicker cortex in the fusiform gyrus compared to those uninvolved in bullying (B = 0.108, p corrected < 0.001). Results remained consistent when adjusted for socioeconomic factors, general intelligence, and psychiatric symptoms. Children classified as frequent perpetrators showed thinner cortex in the cuneus region; however, this association did not survive stringent correction for multiple testing. Lastly, no differences in cortical thickness were observed in perpetrator-targets. Discussion: Bullying involvement in young children was associated with differential cortical morphology. Specifically, the fusiform gyrus, often involved in facial processing, showed thicker cortex in targets of frequent bullying. Longitudinal data are necessary to demonstrate the temporality of the underlying neurobiology associated with bullying involvement.

Cognitive Impairment, Sexual Activity and Physical Tenderness in Community-Dwelling Older Adults: A Cross-Sectional Exploration.

BACKGROUND: The ability to engage in sexual activity and better cognitive functioning are both associated with better health. However, the association between cognitive functioning and sexual activity is understudied. OBJECTIVE: To examine the association between cognitive functioning with sexual activity and physical tenderness among community-dwelling older adults. METHODS: From the Rotterdam Study, cognitive impairment and sexual activity were assessed in 4,201 community-dwelling, 60+ year olds between 2008 and 2014 in the Netherlands. Mild cognitive impairment (MCI) was based upon subjective complaints related to age and education-adjusted test scores. Mini-Mental State Examination (MMSE) impairment was defined by a score of < 26. Sexual activity and physical tenderness (e.g., fondling or kissing) in the last 6 months were assessed at an interview. Analyses were stratified by gender and partner status, with prevalence rates for the "no impairment" categories weighted based on age from the cognitive impairment categories. Inter-rater reliability was examined utilising 74 cohabiting couples of opposite gender. RESULTS: It was found that 14% were categorised as having cognitive impairment, and < 1% as dementia (excluded from subsequent analyses). There was strong evidence that the odds of engaging in physical tenderness (observed through MMSE < 26, OR 2.14, 95% CI 1.32-3.48, p = 0.002) and sexual activity (MCI, OR 2.36, 95% CI 1.35-4.12, p = 0.003) among partnered females with no impairment was twice that observed among cognitively impaired partnered females. There was weak evidence that the odds of engaging in physical tenderness (MMSE < 26, OR 1.59, 95% CI 1.04-2.42, p = 0.03) and sexual activity (MMSE < 26, OR 1.51, 95% CI 1.02-2.24, p = 0.04) among partnered males with no impairment was 50% greater than observed among cognitively impaired partnered males. The associations between cognitive functioning and physical tenderness continued to remain after adjustment for physical function, diabetes, cardiovascular disease and cancer. There was no clear evidence of a difference between amnestic and non-amnestic MCI for sexual behaviour. There was moderate to substantial agreement among the coupled adults who had 1 partner categorised with MCI. CONCLUSION: Having no cognitive impairment was associated with more engagement in sexual activity and physical tenderness among community-dwelling older adults. Sexuality is an important aspect of active aging and our findings illustrate a potential barrier to maintaining or instigating intimate relationships as we age. Longitudinal analyses are required to explore the direction of effect.

Determinants of organophosphate pesticide exposure in pregnant women: A population-based cohort study in the Netherlands.

BACKGROUND: In the Netherlands organophosphate (OP) pesticides are frequently used for pest control in agricultural settings. Despite concerns about the potential health impacts of low-level OP pesticides exposure, particularly in vulnerable populations, the primary sources of exposure remain unclear. The present study was designed to investigate the levels of DAP metabolites concentrations across pregnancy and to examine various determinants of DAP metabolite concentrations among an urban population of women in the Netherlands. METHOD: Urinary concentrations of six dialkyl phosphate (DAP) metabolites, the main urinary metabolites of OP pesticides, were determined at <18, 18-25, and >25 weeks of pregnancy in 784 pregnant women participating in the Generation R Study (between 2004 and 2006), a large population-based birth cohort in Rotterdam, the Netherlands. Questionnaires administered prenatally assessed demographic and lifestyle characteristics and maternal diet. Linear mixed models, with adjustment for relevant covariates, were used to estimate associations between the potential exposure determinants and DAP metabolite concentrations expressed as molar concentrations divided by creatinine levels. RESULTS: The median DAP metabolite concentration was 311 nmol/g creatinine for the first trimester, 317 nmol/g creatinine for the second trimester, and 310 nmol/g creatinine for the third trimester. Higher maternal age, married/living with a partner, underweight or normal weight (BMI of <18.5 and 18.5-<25), high education, high income, and non-smoking were associated with higher DAP metabolite concentrations, and DAP metabolite concentrations tended to be higher during the summer. Furthermore, fruit intake was associated with increased DAP metabolite concentrations. Each 100 g/d difference in fruit consumption was associated with a 7% higher total DAP metabolite concentration across pregnancy. Other food groups were not associated with higher DAP metabolite concentrations. CONCLUSIONS: The DAP metabolite concentrations measured in the urine of pregnant women in the Netherlands were higher than those in most other studies previously conducted. Fruit intake was the main dietary source of exposure to OP pesticides in young urban women in the Netherlands. The extent to which DAP metabolite concentrations reflect exposure to the active parent pesticide rather than to less toxic metabolites remains unclear. Further research will be undertaken to investigate the possible effects of this relatively high level OP pesticides exposure on offspring health.

Automated quality assessment of structural magnetic resonance images in children: Comparison with visual inspection and surface-based reconstruction.

Motion-related artifacts are one of the major challenges associated with pediatric neuroimaging. Recent studies have shown a relationship between visual quality ratings of T1 images and cortical reconstruction measures. Automated algorithms offer more precision in quantifying movement-related artifacts compared to visual inspection. Thus, the goal of this study was to test three different automated quality assessment algorithms for structural MRI scans. The three algorithms included a Fourier-, integral-, and a gradient-based approach which were run on raw T1 -weighted imaging data collected from four different scanners. The four cohorts included a total of 6,662 MRI scans from two waves of the Generation R Study, the NIH NHGRI Study, and the GUSTO Study. Using receiver operating characteristics with visually inspected quality ratings of the T1 images, the area under the curve (AUC) for the gradient algorithm, which performed better than either the integral or Fourier approaches, was 0.95, 0.88, and 0.82 for the Generation R, NHGRI, and GUSTO studies, respectively. For scans of poor initial quality, repeating the scan often resulted in a better quality second image. Finally, we found that even minor differences in automated quality measurements were associated with FreeSurfer derived measures of cortical thickness and surface area, even in scans that were rated as good quality. Our findings suggest that the inclusion of automated quality assessment measures can augment visual inspection and may find use as a covariate in analyses or to identify thresholds to exclude poor quality data.

A multimodal day treatment program for multi-problem young adults: study protocol for a randomized controlled trial.

BACKGROUND: Effective interventions for young adults with severe, multiple problems - such as psychosocial and psychiatric problems, delinquency, unemployment and substance use - are scarce but urgently needed in order to support an adequate transition to adulthood. A multimodal day treatment program called "New Opportunities" (in Dutch: "De Nieuwe Kans"; DNK) was specifically developed to target multi-problem young adults in The Netherlands. The aim of this study protocol is to describe the design of a randomized controlled trial (RCT) in clinical practice to examine the effectiveness of DNK in comparison with care as usual (CAU). METHODS/DESIGN: Multi-problem young adults in Rotterdam, The Netherlands, will be assigned randomly to DNK (expected N = 150) and CAU (expected N = 150). Primary outcome measures are recidivism and self-sufficiency. Secondary outcome measures include quality of life, attending school/work, psychological functioning, cognitive distortions and substance use. Participant and program characteristics will be examined as potential moderators of effectiveness. Additionally, cost-effectiveness will be measured. During 14 months, data from multiple resources will be collected at four time points. DISCUSSION: This study is one of the first RCTs on the effectiveness of interventions developed for multi-problem young adults. The results will contribute to the currently scant knowledge about what works for various multi-problem young adults in their transition to adulthood. In addition, the study protocol will provide insight into implementing an RCT in a dynamic setting of clinical practice. TRIAL REGISTRATION: Dutch Trial Register, identifier: NTR5163 . Registered on 17 April 2015; retrospectively registered during the recruitment phase.

Associations of maternal folic acid supplementation and folate concentrations during pregnancy with foetal and child head growth: the Generation R Study.

PURPOSE: Folic acid supplementation during pregnancy has been associated with a reduced risk of common neurodevelopmental delays in the offspring. However, it is unclear whether low folate status has effects on the developing brain. We evaluated the associations of maternal folic acid supplementation and folate concentrations during pregnancy with repeatedly measured prenatal and postnatal head circumference in the offspring. METHODS: Within a population-based prospective cohort, we measured maternal plasma folate concentrations at approximately 13 weeks of gestation (90 % range 10.5-17.2) and assessed folic acid supplementation by questionnaire (2001-2005). Up to 11 repeated measures of head circumference were obtained during foetal life (20 and 30 weeks of gestation) and childhood (between birth and age 6 years) in 5866 children (2002-2012). RESULTS: In unadjusted models, foetal head growth was 0.006 SD (95 % CI 0.003; 0.009, P < 0.001) faster per week per 1-SD higher maternal folate concentration. After adjustment for confounders, this association was attenuated to 0.004 SD per week (95 % CI 0.000; 0.007, P = 0.02; estimated absolute difference at birth of 2.7 mm). The association was independent of overall foetal growth. No associations were found between maternal folate concentrations and child postnatal head growth. Preconceptional start of folic acid supplementation was associated with larger prenatal head size, but not with prenatal or postnatal head growth. CONCLUSIONS: Our results suggest an independent, modest association between maternal folate concentrations in early pregnancy and foetal head growth. More research is needed to identify whether specific brain regions are affected and whether effects of folate on foetal head growth influence children's long-term functioning.

Assessment and characterization of phenotypic heterogeneity of anxiety disorders across five large cohorts.

To achieve sample sizes necessary for effectively conducting genome-wide association studies (GWASs), researchers often combine data from samples possessing multiple potential sources of heterogeneity. This is particularly relevant for psychiatric disorders, where symptom self-report, differing assessment instruments, and diagnostic comorbidity complicates the phenotypes and contribute to difficulties with detecting and replicating genetic association signals. We investigated sources of heterogeneity of anxiety disorders (ADs) across five large cohorts used in a GWAS meta-analysis project using a dimensional structural modeling approach including confirmatory factor analyses (CFAs) and measurement invariance (MI) testing. CFA indicated a single-factor model provided the best fit in each sample with the same pattern of factor loadings. MI testing indicated degrees of failure of metric and scalar invariance which depended on the inclusion of the effects of sex and age in the model. This is the first study to examine the phenotypic structure of psychiatric disorder phenotypes simultaneously across multiple, large cohorts used for GWAS. The analyses provide evidence for higher order invariance but possible break-down at more detailed levels that can be subtly influenced by included covariates, suggesting caution when combining such data. These methods have significance for large-scale collaborative studies that draw on multiple, potentially heterogeneous datasets. Copyright © 2016 John Wiley & Sons, Ltd.

Splitting hair for cortisol? Associations of socio-economic status, ethnicity, hair color, gender and other child characteristics with hair cortisol and cortisone.

The aim of this study was to examine associations of SES and ethnicity with hair cortisol and cortisone and to identify potential child and family characteristics that can assist in choosing covariates and potential confounders for analyses involving hair cortisol and cortisone concentrations. Hair samples were collected in 2484 6-year-old children from the Generation R Study, a prospective cohort in Rotterdam, the Netherlands. Measurements for cortisol and cortisone were used as the outcome in regression analyses. Predictors were SES, ethnicity, hair color and child characteristics such as birthweight, gestational age at birth, BMI, disease, allergy, and medication use. Lower family income, more children to be supported by this income, higher BMI and darker hair color were associated with higher hair cortisol and cortisone levels. Boys also showed higher levels. Ethnicity (Dutch and North European descent) was related to lower levels. High amounts of sun in the month of hair collection was related to higher levels of cortisone only. More recent hair washing was related to lower levels of cortisol and cortisone. Gestational age at birth, birth weight, age, medication use, hair washing frequency, educational level of the mother, marital status of the mother, disease and allergy were not associated with cortisol or cortisone levels. Our results serve as a starting point for choosing covariates and confounders in studies of substantive predictors or outcomes. Gender, BMI, income, the number of persons in a household, ethnicity, hair color and recency of hair washing are strongly suggested to take into account.

Education plays a greater role than age in cognitive test performance among participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Brazil has gone through fast demographic, epidemiologic and nutritional transitions and, despite recent improvements in wealth distribution, continues to present a high level of social and economic inequality. The ELSA-Brasil, a cohort study, aimed at investigating cardiovascular diseases and diabetes, offers a great opportunity to assess cognitive decline in this aging population through time-sequential analyses drawn from the same battery of tests over time. The purpose of this study is to analyze the influence of sex, age and education on cognitive tests performance of the participants at baseline. METHODS: Analyses pertain to 14,594 participants with aged 35 to 74 years, who were functionally independent and had no history of stroke or use of neuroleptics, anticonvulsants, cholinesterase inhibitors or antiparkinsonian agents. Mean age was 52.0 ± 9.0 years and 54.2% of participants were women. Cognitive tests included the word memory tests (retention, recall and recognition), verbal fluency tests (VFT, animals and letter F) and Trail Making Test B. Multivariable linear regression analysis was used to determine the influence of sociodemographic characteristics on the distribution of the final score of each test. RESULTS: Women had significant and slightly higher scores than men in all memory tests and VFT, but took more time to perform Trail B. Reduced performance in all tests was seen with an increase age and, more importantly, with decrease level of education. The word list and VFT scores decreased at about one word for every 10 years of age; whereas higher-educated participants scored four words more on the word list test, and six or seven more correct words on VFT, when compared to lower-educated participants. Additionally, the oldest and less educated participants showed significant lower response rates in all tests. CONCLUSIONS: The higher influence of education than age in this Brazilian population reinforce the need for caution in analyzing and diagnosing cognitive impairments based on traditional cognitive tests and the importance of searching for education-free cognitive tests, especially in low and middle-income countries.

Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study.

Human chorionic gonadotropin (hCG) is a pregnancy hormone secreted by the placental synctiotrophoblast cell layer that has been linked to fetal growth and various placental, uterine and fetal functions. In order to investigate the effects of hCG on clinical endpoints, knowledge on reference range (RR) methodology and determinants of gestational hCG levels is crucial. Moreover, a better understanding of gestational hCG physiology can improve current screening programs and future clinical management. Serum total hCG levels were determined in 8195 women participating in the Generation R Study. Gestational age specific RRs using 'ultrasound derived gestational age' (US RRs) were calculated and compared with 'last menstrual period derived gestational age' (LMP RRs) and a model-based RR. We also investigated which pregnancy characteristics were associated with hCG levels. Compared to the US RRs, the LMP RRs were lower, most notably for the median and lower limit levels. No considerable differences were found between RRs calculated in the general population or in uncomplicated pregnancies only. Maternal smoking, BMI, parity, ethnicity, fetal gender, placental weight and hyperemesis gravidarum symptoms were associated with total hCG. We provide gestational RRs for total hCG and show that total hCG values and RR cut-offs during pregnancy vary depending on pregnancy dating methodology. This is likely due to the influence of hCG on embryonic growth, suggesting that ultrasound based pregnancy dating might be less reliable in women with high/low hCG levels. Furthermore, we identify different pregnancy characteristics that influence total hCG levels considerably and should therefore be accounted for in clinical studies.

Breastfeeding duration and non-verbal IQ in children.

BACKGROUND: Breastfeeding has been related to better cognitive development in children. However, due to methodological challenges, such as confounding, recall bias or insufficient power, the mechanism and nature of the relation remains subject to debate. METHODS: We included 3761 participants of a population-based cohort study from fetal life onwards and examined the association of breastfeeding duration with non-verbal intelligence in children of age 6 years. Maternal and paternal lifestyle, sociodemographic factors, child factors and maternal IQ were tested for their confounding effects on the association. RESULTS: We observed an initial association between breastfeeding duration and child IQ conferring an advantage of 0.32 (0.20 to 0.44) points for each additional month of breastfeeding. This association strongly attenuated to 0.09 (-0.03 to 0.21) points after adjustment for child factors, sociodemographic factors, parental lifestyle factors and maternal IQ. Similarly, the associations with breastfeeding duration as a categorical variable largely disappeared after confounding factors were added to the models. CONCLUSIONS: The association between breastfeeding and child IQ can be largely explained by sociodemographic factors, parental lifestyle and maternal IQ. Our results cannot confirm beneficial effects of breastfeeding on child intelligence.

The Generation R Study: Biobank update 2015.

The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health from fetal life, childhood and young adulthood. In total, 9,778 mothers were enrolled in the study. Data collection in children and their parents include questionnaires, interviews, detailed physical and ultrasound examinations, behavioural observations, Magnetic Resonance Imaging and biological samples. Efforts have been conducted for collecting biological samples including blood, hair, faeces, nasal swabs, saliva and urine samples and generating genomics data on DNA, RNA and microbiome. In this paper, we give an update of the collection, processing and storage of these biological samples and available measures. Together with detailed phenotype measurements, these biological samples provide a unique resource for epidemiological studies focused on environmental exposures, genetic and genomic determinants and their interactions in relation to growth, health and development from fetal life onwards.

Television viewing through ages 2-5 years and bullying involvement in early elementary school.

BACKGROUND: High television exposure time at young age has been described as a potential risk factor for developing behavioral problems. However, less is known about the effects of preschool television on subsequent bullying involvement. We examined the association between television viewing time through ages 2-5 and bullying involvement in the first grades of elementary school. We hypothesized that high television exposure increases the risk of bullying involvement. METHOD: TV viewing time was assessed repeatedly in early childhood using parental report. To combine these repeated assessments we used latent class analysis. Four exposure classes were identified and labeled "low", "mid-low", "mid-high" and "high". Bullying involvement was assessed by teacher questionnaire (n=3423, mean age 6.8 years). Additionally, peer/self-report of bullying involvement was obtained using a peer nomination procedure (n=1176, mean age 7.6 years). We examined child risk of being a bully, victim or a bully-victim (compared to being uninvolved in bullying). RESULTS: High television exposure class was associated with elevated risks of bullying and victimization. Also, in both teacher- and child-reported data, children in the high television exposure class were more likely to be a bully-victim (OR=2.11, 95% CI: 1.42-3.13 and OR=3.68, 95% CI: 1.75-7.74 respectively). However, all univariate effect estimates attenuated and were no longer statistically significant once adjusted for maternal and child covariates. CONCLUSIONS: The association between television viewing time through ages 2-5 and bullying involvement in early elementary school is confounded by maternal and child socio-demographic characteristics.