Physical activity and body mass related to catch-up lung function growth in childhood: a population-based accelerated cohort study.

OBJECTIVE: The existence of catch-up lung function growth and its predictors is uncertain. We aimed to identify lung function trajectories and their predictors in a population-based birth cohort. METHODS: We applied group-based trajectory modelling to z-scores of forced expiratory volume in 1 second (zFEV1) and z-scores of forced vital capacity (zFVC) from 1151 children assessed at around 4, 7, 9, 10, 11, 14 and 18 years. Multinomial logistic regression models were used to test whether potential prenatal and postnatal predictors were associated with lung function trajectories. RESULTS: We identified four lung function trajectories: a low (19% and 19% of the sample for zFEV1 and zFVC, respectively), normal (62% and 63%), and high trajectory (16% and 13%) running in parallel, and a catch-up trajectory (2% and 5%) with catch-up occurring between 4 and 10 years. Fewer child allergic diseases and higher body mass index z-score (zBMI) at 4 years were associated with the high and normal compared with the low trajectories, both for zFEV1 and zFVC. Increased children's physical activity during early childhood and higher zBMI at 4 years were associated with the catch-up compared with the low zFEV1 trajectory (relative risk ratios: 1.59 per physical activity category (1.03-2.46) and 1.47 per zBMI (0.97-2.23), respectively). No predictors were identified for zFVC catch-up growth. CONCLUSION: We found three parallel-running and one catch-up zFEV1 and zFVC trajectories, and identified physical activity and body mass at 4 years as predictors of zFEV1 but not zFVC catch-up growth.

Prenatal exposure to common plasticizers: a longitudinal study on phthalates, brain volumetric measures, and IQ in youth.

Exposure to phthalates, used as plasticizers and solvents in consumer products, is ubiquitous. Despite growing concerns regarding their neurotoxicity, brain differences associated with gestational exposure to phthalates are understudied. We included 775 mother-child pairs from Generation R, a population-based pediatric neuroimaging study with prenatal recruitment, who had data on maternal gestational phthalate levels and T1-weighted magnetic resonance imaging in children at age 10 years. Maternal urinary concentrations of phthalate metabolites were measured at early, mid-, and late pregnancy. Child IQ was assessed at age 14 years. We investigated the extent to which prenatal exposure to phthalates is associated with brain volumetric measures and whether brain structural measures mediate the association of prenatal phthalate exposure with IQ. We found that higher maternal concentrations of monoethyl phthalate (mEP, averaged across pregnancy) were associated with smaller total gray matter volumes in offspring at age 10 years (ß per log10 increase in creatinine adjusted mEP = -10.7, 95%CI: -18.12, -3.28). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (ß for mediated path =-0.31, 95%CI: -0.62, 0.01, p = 0.05, proportion mediated = 18%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. Our findings suggest the global impact of prenatal phthalate exposure on brain volumetric measures that extends into adolescence and underlies less optimal cognitive development.

Residential ambient air pollution exposure and the development of white matter microstructure throughout adolescence.

BACKGROUND: Recent evidence suggests an association of air pollution exposure with brain development, but evidence on white matter microstructure in children is scarce. We investigated how air pollution exposure during pregnancy and childhood impacts longitudinal development of white matter microstructure throughout adolescence. METHODS: Our study population consisted of 4108 participants of Generation R, a large population-based birth cohort from Rotterdam, the Netherlands. Residential air pollution exposure to 14 air pollutants during pregnancy and childhood was estimated with land-use regression models. Diffusion tensor images were obtained around age 10 and 14, resulting in a total of 5422 useable scans (n = 3082 for wave 1 and n = 2340 for wave 2; n = 1314 for participants with data on both waves). We calculated whole-brain fractional anisotropy (FA) and mean diffusivity (MD) and performed single- and multi-pollutant analyses using mixed effects models adjusted for life-style and socioeconomic status variables. RESULTS: Higher exposure to PM2.5 during pregnancy, and PM10, PM2.5, PM2.5-10, and NOX during childhood was associated with a consistently lower whole-brain FA throughout adolescence (e.g. - 0.07 × 10-2 FA [95%CI -0.12; -0.02] per 1 standard deviation higher PM2.5 exposure during pregnancy). Higher exposure to silicon (Si) in PM2.5 and oxidative potential of PM2.5 during pregnancy, and PM2.5 during childhood was associated with an initial higher MD followed by a faster decrease in MD throughout adolescence (e.g. - 0.02 × 10-5 mm2/s MD [95%CI -0.03; -0.00] per year of age per 1 standard deviation higher Si exposure during pregnancy). Results were comparable when performing the analysis in children with complete data on the outcome for both neuroimaging assessments. CONCLUSIONS: Exposure to several pollutants was associated with a consistently lower whole-brain FA throughout adolescence. The association of few pollutants with whole-brain MD at baseline attenuated throughout adolescence. These findings suggest both persistent and age-limited associations of air pollution exposure with white matter microstructure.

The impact of prenatal mercury on neurobehavioral functioning longitudinally assessed from a young age to pre-adolescence in a Spanish birth cohort.

The objective is to investigate the relation between cord blood mercury concentrations and child neurobehavioural functioning assessed longitudinally during childhood until pre-adolescence. METHODS: The study involves mothers and their offspring engaged in the Spanish INMA birth cohort (n = 1147). Total mercury (THg) was determined in cord blood. Behavioural problems were assessed several times during childhood using the ADHD-DSM-IV at age 4, SDQ at ages 7 and 11, CPRS-R:S and the CBCL at ages 7, 9 and 11. Covariates were obtained through questionnaires during the whole period. Multivariate generalised negative binomial (MGNB) models or mixed-effects MGNB (for those tests with information at one or more time points, respectively) were used to investigate the relation between cord blood THg and the children's punctuations. Models were adjusted for prenatal fish intake. Effect modification by sex, prenatal and postnatal fish intake, prenatal fruit and vegetable intake, and maternal polychlorinated biphenyl concentrations (PCBs) was assessed by interaction terms. RESULTS: The geometric mean ± standard deviation of cord blood THg was 8.22 ± 2.19 µg/L. Despite adjusting for fish consumption, our results did not show any statistically significant relationship between prenatal Hg and the children's performance on behavioural tests conducted between the ages of 4 and 11. Upon assessing the impact of various factors, we observed no statistically significant interaction. CONCLUSION: Despite elevated prenatal THg exposure, no association was found with children's behavioural functioning assessed from early childhood to pre-adolescence. The nutrients in fish could offset the potential neurotoxic impact of Hg. Further birth cohort studies with longitudinal data are warranted.

Childhood exposure to outdoor air pollution in different microenvironments and cognitive and fine motor function in children from six European cohorts.

BACKGROUND: Exposure to air pollution during childhood has been linked with adverse effects on cognitive development and motor function. However, limited research has been done on the associations of air pollution exposure in different microenvironments such as home, school, or while commuting with these outcomes. OBJECTIVE: To analyze the association between childhood air pollution exposure in different microenvironments and cognitive and fine motor function from six European birth cohorts. METHODS: We included 1301 children from six European birth cohorts aged 6-11 years from the HELIX project. Average outdoor air pollutants concentrations (NO2, PM2.5) were estimated using land use regression models for different microenvironments (home, school, and commute), for 1-year before the outcome assessment. Attentional function, cognitive flexibility, non-verbal intelligence, and fine motor function were assessed using the Attention Network Test, Trail Making Test A and B, Raven Colored Progressive Matrices test, and the Finger Tapping test, respectively. Adjusted linear regressions models were run to determine the association between each air pollutant from each microenvironment on each outcome. RESULTS: In pooled analysis we observed high correlation (rs = 0.9) between air pollution exposures levels at home and school. However, the cohort-by-cohort analysis revealed correlations ranging from low to moderate. Air pollution exposure levels while commuting were higher than at home or school. Exposure to air pollution in the different microenvironments was not associated with working memory, attentional function, non-verbal intelligence, and fine motor function. Results remained consistently null in random-effects meta-analysis. CONCLUSIONS: No association was observed between outdoor air pollution exposure in different microenvironments (home, school, commute) and cognitive and fine motor function in children from six European birth cohorts. Future research should include a more detailed exposure assessment, considering personal measurements and time spent in different microenvironments.

Social inequalities in child mental health trajectories: a longitudinal study using birth cohort data 12 countries.

BACKGROUND: Social inequalities in child mental health are an important public health concern. Whilst previous studies have examined inequalities at a single time point, very few have used repeated measures outcome data to describe how these inequalities emerge. Our aims were to describe social inequalities in child internalising and externalising problems across multiple countries and to explore how these inequalities change as children age. METHODS: We used longitudinal data from eight birth cohorts containing participants from twelve countries (Australia, Belgium, Denmark, France, Germany, Greece, Italy, Netherlands, Poland, Norway, Spain and the United Kingdom). The number of included children in each cohort ranged from N = 584 (Greece) to N = 73,042 (Norway), with a total sample of N = 149,604. Child socio-economic circumstances (SEC) were measured using self-reported maternal education at birth. Child mental health outcomes were internalising and externalising problems measured using either the Strengths and Difficulties Questionnaire or the Child Behavior Checklist. The number of data collection waves in each cohort ranged from two to seven, with the mean child age ranging from two to eighteen years old. We modelled the slope index of inequality (SII) using sex-stratified multi-level models. RESULTS: For almost all cohorts, at the earliest age of measurement children born into more deprived SECs had higher internalising and externalising scores than children born to less deprived SECs. For example, in Norway at age 2 years, boys born to mothers of lower education had an estimated 0.3 (95% CI 0.3, 0.4) standard deviation higher levels of internalising problems (SII) compared to children born to mothers with high education. The exceptions were for boys in Australia (age 2) and both sexes in Greece (age 6), where we observed minimal social inequalities. In UK, Denmark and Netherlands inequalities decreased as children aged, however for other countries (France, Norway, Australia and Crete) inequalities were heterogeneous depending on child sex and outcome. For all countries except France inequalities remained at the oldest point of measurement. CONCLUSIONS: Social inequalities in internalising and externalising problems were evident across a range of EU countries, with inequalities emerging early and generally persisting throughout childhood.

Association between telomere length and neuropsychological function at 4-5 years in children from the INMA project: a cross-sectional study.

Shortened telomere length (TL) has been associated with lower cognitive performance, different neurological diseases in adults, and certain neurodevelopmental disorders in children. However, the evidence about the association between TL and neuropsychological developmental outcomes in children from the general population is scarce. Therefore, this study aimed to explore the association between TL and neuropsychological function in children 4-5 years of age. We included 686 children from the INMA Project, a population-based birth cohort in Spain. Leucocyte TL was determined by quantitative PCR method, and neuropsychological outcomes were measured using the McCarthy Scales of Children's Abilities (MCSA). Multiple linear regression models were used to estimate associations adjusted for potential confounding variables. Main findings showed that a longer TL was associated with a higher mean working memory score (ß = 4.55; 95% CI = 0.39, 8.71). In addition, longer TL was associated with a higher mean global quantitative score (ß = 3.85; 95% CI = -0.19, 7.89), although the association was marginally significant. To our knowledge, this is the first study that shows a positive association between TL and better neuropsychological outcomes in children. Although further research is required to confirm these results, this study supports the hypothesis that TL is essential in protecting and maintaining a child's health, including cognitive functions such as working memory.

Sleep duration in preschool age and later behavioral and cognitive outcomes: an individual participant data meta-analysis in five European cohorts.

Short sleep duration has been linked to adverse behavioral and cognitive outcomes in schoolchildren, but few studies examined this relation in preschoolers. We aimed to investigate the association between parent-reported sleep duration at 3.5 years and behavioral and cognitive outcomes at 5 years in European children. We used harmonized data from five cohorts of the European Union Child Cohort Network: ALSPAC, SWS (UK); EDEN, ELFE (France); INMA (Spain). Associations were estimated through DataSHIELD using adjusted generalized linear regression models fitted separately for each cohort and pooled with random-effects meta-analysis. Behavior was measured with the Strengths and Difficulties Questionnaire. Language and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or the McCarthy Scales of Children's Abilities. Behavioral and cognitive analyses included 11,920 and 2981 children, respectively (34.0%/13.4% of the original sample). In meta-analysis, longer mean sleep duration per day at 3.5 years was associated with lower mean internalizing and externalizing behavior percentile scores at 5 years (adjusted mean difference: - 1.27, 95% CI [- 2.22, - 0.32] / - 2.39, 95% CI [- 3.04, - 1.75]). Sleep duration and language or non-verbal intelligence showed trends of inverse associations, however, with imprecise estimates (adjusted mean difference: - 0.28, 95% CI [- 0.83, 0.27] / - 0.42, 95% CI [- 0.99, 0.15]). This individual participant data meta-analysis suggests that longer sleep duration in preschool age may be important for children's later behavior and highlight the need for larger samples for robust analyses of cognitive outcomes. Findings could be influenced by confounding or reverse causality and require replication.

Children who sleep more may have longer telomeres: evidence from a longitudinal population study in Spain.

BACKGROUND: Inadequate sleep duration has been suggested as a chronic stressor associated with changes in telomere length (TL). This study aimed to explore the association between sleep duration and TL using the INMA birth cohort study data. METHODS: A total of 1014 children were included in this study (cross-sectional: 686; longitudinal: 872). Sleep duration (h/day) was reported by caregivers at 4 years and classified into tertiles (7-10 h/day; >10-11 h/day; >11-14 h/day). Leucocyte TL at 4 and 7-9 years were measured using quantitative PCR methods. Multiple robust linear regression models, through log-level regression models, were used to report the % of difference among tertiles of sleep duration. RESULTS: In comparison to children who slept between >10 and 11 h/day, those in the highest category (more than 11 h/day) had 8.5% (95% CI: 3.56-13.6) longer telomeres at 4 years. Longitudinal analysis showed no significant association between sleep duration at 4 years and TL at 7-9 years. CONCLUSION: Children who slept more hours per day had longer TL at 4 years independently of a wide range of confounder factors. Environmental conditions, such as sleep duration, might have a major impact on TL during the first years of life. IMPACT: Telomere length was longer in children with longer sleep duration (>11 h/day) independently of a wide range of confounder factors at age 4 and remained consistent by sex. Sleep routines are encouraged to promote positive child development, like the number of hours of sleep duration. Considering the complex biology of telomere length, future studies still need to elucidate which biological pathways might explain the association between sleep duration and telomere length.

Prenatal and child vitamin D levels and allergy and asthma in childhood.

BACKGROUND: Early-life vitamin D deficiency may impair immune system development contributing to allergy and asthma onset. Findings from prospective studies are inconsistent. OBJECTIVE: To examine whether maternal and child vitamin D levels are associated with allergic and asthma-related symptoms throughout childhood in a Spanish birth cohort. METHODS: 25-Hydroxyvitamin D3 (25(OH)D3) levels were measured in the serum of pregnant women (N = 2525) and children (N = 803). Information on allergic and asthma-related symptoms was obtained from repeated questionnaires from 1 to 9 years. RESULTS: A total of 19% of mothers and 24% of children had deficient 25(OH)D3 levels (<20 ng/ml). Higher child 25(OH)D3 levels at 4 years were associated with lower odds of atopic eczema from 4 to 9 years (adjusted odds ratio = 0.90; 95% CI = 0.84-0.97 per 5 ng/ml). Higher maternal and child 25(OH)D3 levels were associated with a lower prevalence of late-onset wheezing at the limit of statistical significance (adjusted relative risk ratio (RRRadj) = 0.86; 95% CI = 0.74-1.00 and RRRadj = 0.76; 95% CI = 0.58-1.02 per 5 ng/ml, respectively). All the remaining associations were null. CONCLUSION: Child 25(OH)D3 levels at pre-school age are associated with a reduced odds of atopic eczema in later childhood and both maternal and child levels may reduce the prevalence of late-onset wheezing. IMPACT: In this Spanish birth cohort, with a total of 19% of mothers and 24% of children with deficient levels of vitamin D, higher child vitamin D at 4 years of age was associated with reduced odds of atopic eczema up to 9 years. There was also some evidence that higher maternal and child vitamin D levels reduced the prevalence of late-onset wheezing. Although these findings need replication, they may imply optimal vitamin D levels at pre-school age to prevent atopic eczema.

Exploration of thyroglobulin as a biomarker of iodine status in iodine-sufficient and mildly iodine-deficient pregnant women.

PURPOSE: Urinary iodine-to-creatinine ratio (UI/Creat) reflects recent iodine intake but has limitations for assessing habitual intake. Thyroglobulin (Tg) concentration, which increases with thyroid size, appears to be an indicator of longer-term iodine status in children and adults, however, less is known in pregnancy. This study investigated the determinants of serum-Tg in pregnancy and its use as an iodine-status biomarker in settings of iodine-sufficiency and mild-to-moderate deficiency. METHODS: Stored blood samples and existing data from pregnant women from the Netherlands-based Generation R (iodine-sufficient) and the Spain-based INMA (mildly-to-moderately iodine-deficient) cohorts were used. Serum-Tg and iodine status (as spot-urine UI/Creat) were measured at median 13 gestational weeks. Using regression models, maternal socio-demographics, diet and iodine-supplement use were investigated as determinants of serum-Tg, as well as the association between UI/Creat and serum-Tg. RESULTS: Median serum-Tg was 11.1 ng/ml in Generation R (n = 3548) and 11.5 ng/ml in INMA (n = 1168). When using 150 µg/g threshold for iodine deficiency, serum-Tg was higher in women with UI/Creat < 150 vs ≥ 150 µg/g (Generation R, 12.0 vs 10.4 ng/ml, P = 0.010; INMA, 12.8 vs 10.4 ng/ml, P < 0.001); after confounder adjustment, serum-Tg was still higher when UI/Creat < 150 µg/g (regression coefficients: Generation R, B = 0.111, P = 0.050; INMA, B = 0.157, P = 0.010). Iodine-supplement use and milk intake were negatively associated with serum-Tg, whereas smoking was positively associated. CONCLUSION: The association between iodine status and serum-Tg was stronger in the iodine-deficient cohort, than in the iodine-sufficient cohort. Serum-Tg might be a complementary (to UI/Creat) biomarker of iodine status in pregnancy but further evidence is needed.

Outdoor residential noise exposure and sleep in preadolescents from two European birth cohorts.

OBJECTIVE: To examine whether outdoor residential exposure to annual average road traffic and multiple (i.e., road traffic, railway, aircraft, industry) noise levels is related with preadolescents' sleep using maternal-reported and wrist-actigraphy data in two European birth cohorts. METHODS: This cross-sectional study used data of 1245 preadolescents from the Dutch Generation R Study and 232 from the Spanish INMA-Sabadell cohort with a mean age of 12.3 years old. We used noise maps to assess average outdoor road traffic and multiple noise levels (day-evening-night noise indicator, LDEN) at each child's residential address for the year before the sleep assessment. Sleep disturbances were reported by mothers through the Sleep Disturbance Scale for Children and objectively recorded using GeneActiv wrist-actigraphy during seven subsequent days. Linear and Poisson regression models adjusted for several potential confounding variables were performed. RESULTS: The mean (SD) exposure to road traffic noise was 53.2 dB (7.3) in the Generation R Study and 61.3 dB (5.9) in the INMA-Sabadell cohort. Exposure to road traffic was related with reduced total sleep time and longer wake after sleep onset (e.g. -3.62 min (95%CI -6.87; -0.37) and 6.88 min (95%CI 1.15; 12.61) per an increase of 10 dB in road traffic noise, respectively) collected by wrist-actigraphy. We observed no association between road traffic exposure and maternal-reported sleep disturbances. Results were similar for multiple noise exposure. CONCLUSIONS: These findings indicate that sleep may be compromised for preadolescents living in areas highly exposed to outdoor residential noise. Future studies using longitudinal designs to further explore these associations during the different stages of sleep development across childhood and adolescence are warranted. Also, wrist-actigraphy measurements which provide more accurate information and may be complementary to the parental- and self-reported data should be considered.

Air pollution exposure during pregnancy and childhood, APOE ε4 status and Alzheimer polygenic risk score, and brain structural morphology in preadolescents.

BACKGROUND: Air pollution exposure is associated with impaired neurodevelopment, altered structural brain morphology in children, and neurodegenerative disorders. Differential susceptibility to air pollution may be influenced by genetic features. OBJECTIVES: To evaluate whether the apolipoprotein E (APOE) genotype or the polygenic risk score (PRS) for Alzheimer's Disease (AD) modify the association between air pollution exposure during pregnancy and childhood and structural brain morphology in preadolescents. METHODS: We included 1186 children from the Generation R Study. Concentrations of fourteen air pollutants were calculated at participants' home addresses during pregnancy and childhood using land-use-regression models. Structural brain images were collected at age 9-12 years to assess cortical and subcortical brain volumes. APOE status and PRS for AD were examined as genetic modifiers. Linear regression models were used to conduct single-pollutant and multi-pollutant (using the Deletion/Substitution/Addition algorithm) analyses with a two-way interaction between air pollution and each genetic modifier. RESULTS: Higher pregnancy coarse particulate matter (PMcoarse) and childhood polycyclic aromatic hydrocarbons exposure was differentially associated with larger cerebral white matter volume in APOE ε4 carriers compared to non-carriers (29,485 mm3 (95% CI 6,189; 52,781) and 18,663 mm3 (469; 36,856), respectively). Higher pregnancy PMcoarse exposure was differentially associated with larger cortical grey matter volume in children with higher compared to lower PRS for AD (19436 mm3 (825, 38,046)). DISCUSSION: APOE status and PRS for AD possibly modify the association between air pollution exposure and brain structural morphology in preadolescents. Higher air pollution exposure is associated with larger cortical volumes in APOE ε4 carriers and children with a high PRS for AD. This is in line with typical brain development, suggesting an antagonistic pleiotropic effect of these genetic features (i.e., protective effect in early-life, but neurodegenerative effect in adulthood). However, we cannot discard chance findings. Future studies should evaluate trajectorial brain development using a longitudinal design.

Susceptible windows of exposure to fine particulate matter and fetal growth trajectories in the Spanish INMA (INfancia y Medio Ambiente) birth cohort.

While prior studies report associations between fine particulate matter (PM2.5) exposure and fetal growth, few have explored temporally refined susceptible windows of exposure. We included 2328 women from the Spanish INMA Project from 2003 to 2008. Longitudinal growth curves were constructed for each fetus using ultrasounds from 12, 20, and 34 gestational weeks. Z-scores representing growth trajectories of biparietal diameter, femur length, abdominal circumference (AC), and estimated fetal weight (EFW) during early (0-12 weeks), mid- (12-20 weeks), and late (20-34 weeks) pregnancy were calculated. A spatio-temporal random forest model with back-extrapolation provided weekly PM2.5 exposure estimates for each woman during her pregnancy. Distributed lag non-linear models were implemented within the Bayesian hierarchical framework to identify susceptible windows of exposure for each outcome and cumulative effects [ßcum, 95% credible interval (CrI)] were aggregated across adjacent weeks. For comparison, general linear models evaluated associations between PM2.5 averaged across multi-week periods (i.e., weeks 1-11, 12-19, and 20-33) and fetal growth, mutually adjusted for exposure during each period. Results are presented as %change in z-scores per 5 µg/m3 in PM2.5, adjusted for covariates. Weeks 1-6 [ßcum = -0.77%, 95%CrI (-1.07%, -0.47%)] were identified as a susceptible window of exposure for reduced late pregnancy EFW while weeks 29-33 were positively associated with this outcome [ßcum = 0.42%, 95%CrI (0.20%, 0.64%)]. A similar pattern was observed for AC in late pregnancy. In linear regression models, PM2.5 exposure averaged across weeks 1-11 was associated with reduced late pregnancy EFW and AC; but, positive associations between PM2.5 and EFW or AC trajectories in late pregnancy were not observed. PM2.5 exposures during specific weeks may affect fetal growth differentially across pregnancy and such associations may be missed by averaging exposure across multi-week periods, highlighting the importance of temporally refined exposure estimates when studying the associations of air pollution with fetal growth.

Measures of Early-life Behavior and Later Psychopathology in the LifeCycle Project - EU Child Cohort Network: A Cohort Description.

BACKGROUND: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. METHODS: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. RESULTS: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. CONCLUSION: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Sleep problems at ages 8-9 and ADHD symptoms at ages 10-11: evidence in three cohorts from INMA study.

Sleep problems and attention deficit hyperactivity disorder (ADHD) are interrelated during childhood and preadolescence. The objective of this work is assessing if sleep problems at ages 8-9 represent an alarm sign for presenting ADHD problems at ages 10-11 in three cohorts from INMA Study. Participants were 1244 children from Gipuzkoa, Sabadell, and Valencia cohorts. Sleep problems were assessed (ages 8-9) with the sleep items of the Child's Behaviour Checklist (CBCL), and ADHD problems were collected through the Conner's Parent Rating Scales-Revised: Short Form (CPRS-R:S) (age 10-11). Minimally and fully adjusted negative binomial models were fitted for each CPRS-R:S scale. Linearity of the relationship was assessed with generalized additive models (cubic smoothing splines with 2, 3, and 4 knots). For sensitivity analyses, children with previous symptoms, those born preterm and small for gestational age, and cases with extreme values, were excluded. Sleep problems presented IRR (95% CI) of 1.14 (1.10-1.19), 1.20 (1.14-1.26), 1.18 (1.11-1.25), and 1.18 (1.13-1.23) for opposition, inattention, hyperactivity, and ADHD scales, respectively. Fully adjusted models slightly decreased the IRR, but the association remained similar and significant. Sensitivity analyses showed similar results to fully adjusted models with only hyperactivity shown a slight decrease on significance (p = 0.051) when ADHD cases at age 9 were excluded.   Conclusion: Sleep problems are an alarm sign for later neurodevelopment problems such as ADHD. Healthcare systems could take advantage implementing policies to pay special attention on the sleep habits and sleep hygiene. This could contribute to add evidence to public health programmes such as the Healthy Child Programme.

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.

Identifying Sensitive Windows of Exposure to NO2 and Fetal Growth Trajectories in a Spanish Birth Cohort.

BACKGROUND: We previously identified associations between trimester-specific NO2 exposures and reduced fetal growth in the Spanish INfancia y Medio Ambiente (INMA) project. Here, we use temporally refined exposure estimates to explore the impact of narrow (weekly) windows of exposure on fetal growth. METHODS: We included 1,685 women from INMA with serial ultrasounds at 12, 20, and 34 gestational weeks. We measured biparietal diameter (BPD), femur length, and abdominal circumference (AC) and from them calculated estimated fetal weight (EFW). We calculated z-scores describing trajectories of each parameter during early (0-12 weeks), mid (12-20 weeks), and late (20-34 weeks) pregnancy, based on longitudinal growth curves from mixed-effects models. We estimated weekly NO2 exposures at each woman's residence using land-use regression models. We applied distributed lag nonlinear models to identify sensitive windows of exposure. We present effect estimates as the percentage change in fetal growth per 10 µg/m3 increase in NO2 exposure, and we calculated cumulative effect estimates by aggregating estimates across adjacent lags. RESULTS: We identified weeks 5-12 as a sensitive window for NO2 exposure on late EFW (cumulative ß = -3.0%; 95% CI = -4.1%, -1.9%). We identified weeks 6-19 as a sensitive window for late growth in BPD (cumulative ß = -2.0%; 95% CI = -2.7%, -1.4%) and weeks 8-13 for AC (cumulative ß = -0.68%; 95% CI = -0.97%, -0.40%). We found suggestive evidence that third trimester NO2 exposure is associated with increased AC, BPD, and EFW growth in late pregnancy. CONCLUSIONS: Our findings are consistent with the hypothesis that NO2 exposure is associated with alterations in growth of EFW, BPD, and AC dependent on the specific timing of exposure during gestation.

Maternal occupational exposure to chemicals and child cognitive function.

BACKGROUND: Limited data exist regarding child neurodevelopment in relation to maternal occupational exposure to endocrine-disrupting chemicals (EDCs). METHODS: We included 1058 mother-child pairs from the INfancia y Medio Ambiente (INMA) project (2003-2008). Using a job-exposure matrix, exposure probability scores for ten EDC groups were assigned to each mother based on her longest held job during pregnancy. At the child's 5-year visit, the McCarthy Scales of Children's Abilities was administered, yielding the general cognitive index and scales for specific cognitive domains. We analyzed region-specific associations between EDC exposures and each outcome separately using adjusted linear regression and combined region-specific effect estimates using random-effects meta-analyses. RESULTS: Approximately 24% of women were exposed to at least one EDC group, but exposure to most individual EDC groups was low (<5%). Maternal organic solvent exposure was associated with lower quantitative scores among children (-5.8 points, 95% confidence interval: -11.0, -0.5). Though statistically non-significant, exposures to polycyclic aromatic hydrocarbons, phthalates, alkylphenolic compounds, and miscellaneous chemicals were associated with poorer offspring performance for most or all cognitive domains. CONCLUSIONS: This study found limited evidence for a role of maternal occupational EDC exposures on child cognition. Further research is needed to better characterize exposures among pregnant workers. IMPACT: Using data from a prospective birth cohort, we help fill an important research gap regarding the potential consequences of work-related exposure to endocrine-disrupting chemicals (EDCs) among pregnant women on child neurodevelopment. We expand on existing literature-largely limited to pesticide and organic solvent exposures-by using a job-exposure matrix to estimate exposure to several EDC groups. We found limited evidence of an association between maternal occupational EDC exposure and children's overall cognition. We did observe specific associations between exposure to organic solvents and lower quantitative reasoning scores.

Malignant lymphoma and occupational exposure to extremely low frequency magnetic fields and electrical shocks: a nested case-control study in a cohort of four Nordic countries.

BACKGROUND: Exposure to extremely low frequency magnetic fields (ELF-MFs) and electric shocks is a common occupational risk factor in many workplaces. Recent investigations have highlighted a possible association between such exposures and lymphoma risk. This study was carried out to further explore the association between occupational exposure to ELF-MFs and electric shocks and risk of lymphoma in a large Nordic census-based cohort. METHODS: We included cases of non-Hodgkin's lymphoma (NHL, n=68 978), chronic lymphocytic leukaemia (CLL, n=20 615) and multiple myeloma (MM, n=35 467) diagnosed between 1961 and 2005 in Finland, Iceland, Norway and Sweden. Cases were matched to five controls by year of birth, sex and country. Lifetime occupational ELF-MF and electric shock exposures were assigned to jobs reported in population censuses using job-exposure matrices. The risk of cancer was assessed based on cumulative exposure to ELF-MF and electric shocks. ORs with 95% CIs were estimated using logistic models adjusted for occupational co-exposures relevant to lymphomas. RESULTS: Less than 7% of the cases experienced high levels of ELF-MF. We observed no increased risks among workers exposed to high levels of ELF-MF for NHL (OR: 0.93; CI 0.90 to 0.97), CLL (OR: 0.98; CI 0.92 to 1.05) or MM (OR: 0.96; CI 0.90 to 1.01). CONCLUSION: Our results do not provide support for an association between occupational exposure to ELF-MFs and electric shocks and lymphoma risk.