Association between childhood family structure and longitudinal health behaviour changes in adulthood -Northern Finland birth cohort 1966 study.

BACKGROUND: Childhood family structure is considered to play a role in person's health and welfare. This study investigated the relationships between the longitudinal changes of adult health behaviours and childhood family structure. METHODS: From Northern Finland Birth Cohort 1966 questionnaires, we collected data on childhood family structure at the age of 14 ('two-parent family', 'one parent not living at home/no information on father', and 'father or mother deceased'), and on health behaviours (smoking, alcohol consumption and physical activity status) at the ages of 31 and 46. We used the multinomial logistic regression model to estimate the unadjusted and adjusted associations between childhood family structures and the longitudinal changes between 31 and 46 years of health behaviours (four-category variables). RESULTS: Of the study sample (n = 5431; 55.5% females), 7.1% of the offspring were represented in the 'One parent not living at home/no information on father' subgroup, 6.3% in the 'Father or mother deceased' subgroup and 86.6% in the 'Two-parent family'. 'One parent not living at home/no information on father' offspring were approximately twice as likely to smoke (adjusted OR 2.19, 95% CI 1.70-2.81) and heavily consume alcohol (adjusted OR 1.99, 95% CI 1.25-3.16) at both times in adulthood, relative to not smoking or not heavily consume alcohol, and compared with 'two-parent family' offspring. We found no statistically significant associations between childhood family structure and physical activity status changes in adulthood. CONCLUSIONS: Our findings suggest that the offspring of single-parent families in particular should be supported in early life to diminish their risk of unhealthy behaviours in adulthood.

[Association between maternal peri-conceptional exposures and risk of hypospadias and cryptorchidism in offspring].

Objective: To investigate the relationship between maternal exposures to peri-conceptional risk factors and the risk of hypospadias and cryptorchidism in offspring. Methods: Pregnant women who delivered male newborns and participated in the China birth cohort study between February 2018 and December 2020 at the research center of Beijing Obstetrics and Gynecology Hospital, Capital Medical University were selected for the study. All were enrolled at 6-13+6 weeks of their gestation. Baseline risk factor information was collected by questionnaire survey. Information on the outcome of hypospadias and cryptorchidism was obtained by clinical examination at birth and ultrasonography. Logistic regression was used to analyze the Odds Ratio (OR) and 95% Confidence Interval (95%CI) of each factor with respect to the onset of the outcome. Results: A total of 15, 833 pregnant women with an average age of (31.81±3.84) years were included. Among their offsprings, 113 were diagnosed as hypospadias or cryptorchidism (42 hypospadias, 69 cryptorchidism, and 2 both hypospadias and crypterchidism), with an incidence of 7.14‰. The results of multivariate logistic regression analysis showed that mothers with pregnancy history of birth defects (OR=3.01, 95%CI: 1.09-8.35), with preconception Hepatitis B infection (OR=4.74, 95%CI: 1.10-20.42), fetal growth restriction (OR=4.02, 95%CI: 2.10-7.68), multivitamin use since preconception (OR=1.98, 95%CI: 1.12-3.52), and never cook and eat at home (OR=2.17, 95%CI: 1.23-3.82) were risk factors for hypospadias and cryptorchidism (all P<0.05). Conclusions: Obesity in early pregnancy, preconception Hepatitis B infection, pregnancy history of birth defects, fetal growth restriction, multivitamin use before pregnancy, and rarely cook and eat at home were associated with an increased risk of hypospadias or cryptorchidism in their offsprings.

[Association between prenatal exposure to PM2.5 and fetal growth: a prospective cohort study].

Objective: To investigate the association of exposure to PM2.5 and its constituents during pregnancy and fetal growth and to further identify critical windows of exposure for fetal growth. Methods: We included 4 089 mother-child pairs from the Jiangsu Birth Cohort Study between January 2016 and October 2019. Data of general characteristics, clinical information, daily average PM2.5 exposure, and its constituents during pregnancy were collected. Fetal growth parameters, including head circumference (HC), abdominal circumference (AC), and femur length (FL), were measured by ultrasound after 20 weeks of gestation, and then estimated fetal weight (EFW) was calculated. Generalized linear mixed models were adopted to examine the associations of prenatal exposure to PM2.5 and its constituents with fetal growth. Distributed lag nonlinear models were used to identify critical exposure windows for each outcome. Results: A 10 µg/m3 increase in PM2.5 exposure during pregnancy was associated with a decrease of 0.025 (ß=-0.025, 95%CI: -0.048- -0.001) in HC Z-score, 0.026 (ß=-0.026, 95%CI: -0.049- -0.003) in AC Z-score, and 0.028 (ß=-0.028, 95%CI:-0.052--0.004) in EFW Z-score, along with an increased risk of 8.5% (RR=1.085, 95%CI: 1.010-1.165) and 13.5% (RR=1.135, 95%CI: 1.016-1.268) for undergrowth of HC and EFW, respectively. Regarding PM2.5 constituents, prenatal exposure to black carbon, organic matter, nitrate, sulfate (SO42-) and ammonium consistently correlated with decreased HC Z-score. SO42- exposure was also associated with decreased FL Z-scores. In addition, we found that gestational weeks 2-5 were critical windows for HC, weeks 4-13 and 19-40 for AC, weeks 4-13 and 23-37 for FL, and weeks 4-12 and 20-40 for EFW. Conclusions: Our findings demonstrated that exposure to PM2.5 and its constituents during pregnancy could adversely affect fetal growth and the critical windows for different fetal growth parameters are not completely consistent.

The Effects of Breastfeeding on Childhood Behavioral and Emotional Development: A Prospective Cohort Study in China.

BACKGROUND: Breastfeeding could improve a child's health early on, but its long-term effects on childhood behavioral and emotional development remain inconclusive. We aimed to estimate the associations of feeding practice with childhood behavioral and emotional development. METHODS: In this population-based birth cohort study, data on feeding patterns for the first 6 mo of life, the duration of breastfeeding, and children's emotional and behavioral outcomes were prospectively collected from 2489 mother-child dyads. Feeding patterns for the first 6 mo included exclusive breastfeeding (EBF) and non-exclusive breastfeeding (non-EBF, including mixed feeding or formula feeding), and the duration of breastfeeding (EBF or mixed feeding) was categorized into ≤6 mo, 7-12 mo, 13-18 mo, and >18 mo. Externalizing problems and internalizing problems were assessed with the Child Behavior Checklist (CBCL) and operationalized according to recommended clinical cutoffs, corresponding to T scores ≥64. Multivariable linear regression and logistic regression were used to evaluate the association of feeding practice with CBCL outcomes. RESULTS: The median (interquartile range) age of children at the outcome measurement was 32.0 (17.0) mo. Compared with non-EBF for the first 6 mo, EBF was associated with a lower T score of internalizing problems [adjusted mean difference (aMD): -1.31; 95% confidence interval (95% CI): -2.53, -0.10], and it was marginally associated with T scores of externalizing problems (aMD: -0.88; 95% CI: -1.92, 0.15). When dichotomized, EBF versus non-EBF was associated with a lower risk of externalizing problems (aOR: 0.54, 95% CI: 0.34, 0.87), and it was marginally associated with internalizing problems (aOR: 0.75, 95% CI: 0.54, 1.06). Regarding the duration of breastfeeding, breastfeeding for 13-18 mo versus ≤6 mo was associated with lower T scores of internalizing problems (aMD: -2.50; 95% CI: -4.43, -0.56) and externalizing problems (aMD: -2.75; 95% CI: -4.40, -1.10), and breastfeeding for >18 mo versus ≤6 mo was associated with lower T scores of externalizing problems (aMD: -1.88; 95% CI: -3.68, -0.08). When dichotomized, breastfeeding for periods of 7-12 mo, 13-18 mo, and >18 mo was associated with lower risks of externalizing problems [aOR (95% CI): 0.96 (0.92, 0.99), 0.94 (0.91, 0.98), 0.96 (0.92, 0.99), respectively]. CONCLUSIONS: Exclusive breastfeeding for the first 6 mo and a longer duration of breastfeeding, exclusively or partially, are beneficial for childhood behavioral and emotional development.

Association of prenatal multiple metal exposures with child neurodevelopment at 3 years of age: A prospective birth cohort study.

Prenatal exposures to toxic metals and trace elements have been linked to childhood neurodevelopment. However, existing evidence remains inconclusive, and further research is needed to investigate the mixture effects of multiple metal exposures on childhood neurodevelopment. We aimed to examine the associations between prenatal exposure to specific metals and metal mixtures and neurodevelopment in children. In this prospective cohort study, we used the multivariable linear regressions and the robust modified Poisson regressions to explore the associations of prenatal exposure to 25 specific metals with neurodevelopment among children at 3 years of age in 854 mother-child pairs from the Jiangsu Birth Cohort (JBC) Study. The Bayesian kernel machine regression (BKMR) was employed to assess the joint effects of multiple metals on neurodevelopment. Prenatal manganese (Mn) exposure was negatively associated with the risk of non-optimal cognition development of children, while vanadium (V), copper (Cu), zinc (Zn), antimony (Sb), cerium (Ce) and uranium (U) exposures were positively associated with the risk of non-optimal gross motor development. BKMR identified an interaction effect between Sb and Ce on non-optimal gross motor development. Additionally, an element risk score (ERS), representing the mixture effect of multiple metal exposures including V, Cu, Zn, Sb, Ce and U was constructed based on weights from a Poisson regression model. Children with ERS in the highest tertile had higher probability of non-optimal gross motor development (RR = 2.37, 95 % CI: 1.15, 4.86) versus those at the lowest tertile. Notably, Sb [conditional-posterior inclusion probabilities (cPIP) = 0.511] and U (cPIP = 0.386) mainly contributed to the increased risk of non-optimal gross motor development. The findings highlight the importance of paying attention to the joint effects of multiple metals on children's neurodevelopment. The ERS score may serve as an indicator of comprehensive metal exposure risk for children's neurodevelopment.

Structured early childhood education exposure and childhood cognition - Evidence from an Indian birth cohort.

Experiences in early childhood form the bedrock of future human potential. In impoverished settings, structured early childhood education (ECE) in preschool years can augment overall childhood and later human abilities. The current study evaluates preschool learning exposure and childhood cognition, using longitudinal follow-up of a community-based birth cohort in Vellore, south India. The birth cohort study site in Vellore recruited 251 newborns between 2010 and 2012 from dense urban settlements and further followed up into childhood. Preschool enrolment details were obtained from parents. Childhood cognition was assessed by Weschler's preschool primary scale of intelligence (WPPSI) and Malin's intelligence scale for Indian Children (MISIC) at 5 and 9 years of age respectively. Bivariate and multivariate regression analyses were performed with adjustments for socio-economic status (SES), maternal education, stunting status and home environment. Out of 251 new-borns recruited into the MAL-ED birth cohort, 212 (84.46%) and 205 (81.7%) children were available for the 5 year and 9 year follow-up respectively. At 5 years, structured ECE of 18 to 24 months duration was significantly associated with higher cognition scores, with the highest increase in processing speed [ß: 19.55 (11.26-27.77)], followed by full-scale intelligence [ß: 6.75 (2.96-10.550)], even after adjustments for SES, maternal cognition, home factors and early childhood stunting status. Similarly adjusted analysis at 9 years showed that children who attended 1.5-2 years of structured ECE persisted to have higher cognition, especially in the performance domain [ß: 8.82 (2.60-15.03)], followed by the full-scale intelligence [ß: 7.24 (2.52-11.90)]. Follow-up of an Indian birth cohort showed that structured ECE exposure was associated with better school entry cognition as well as mid-childhood cognition. Strengthening ECE through a multi-pronged approach could facilitate to maximize cognitive potential of human capital.

Scarring In Utero: An Attempt to Validate With Data Unconfounded by Migration and Medical Care.

BACKGROUND: "Scarring in utero" posits that populations exposed to injurious stressors yield birth cohorts that live shorter lives than expected from history. This argument implies a positive historical association between period life expectancy (i.e., average age at death in year t) and cohort life expectancy (i.e., average lifespan of persons born in year t). Tests of the argument have not produced consistent results and appear confounded by autocorrelation, migration, and access to medical care. Here we test whether, as predicted by scarring in utero, sex-specific period and cohort life expectancy appear positively related among Swedes born from 1751 through 1800. If scarring has ever influenced longevity, we should detect signals of its effects in these cohorts because, unlike other populations with known life span, they aged in place and unlikely benefitted from increased access to efficacious medical care. METHODS: We use Box-Jenkins methods to control autocorrelation and measure associations. RESULTS: Contrary to the scarring hypothesis, we find an inverse association between period and cohort life expectancy. Our findings imply that, among males, variation in injurious stress on the population predicted changes in cohort life span ranging from a gain of approximately 67 weeks to a loss of about 45 weeks of life and among females from a gain of approximately 68 weeks to a loss of about 38 weeks of life. CONCLUSION: Epidemiologists trying to understand and explain temporal variation in cohort life expectancy should view the scarring argument with greater skepticism than currently found in the literature.

JA KIDS - Jamaica's second national birth cohort study: aims and methods.

Birth cohort studies across the world have yielded information that has been used to inform policy and programme decisions that have improved the health and well-being of populations. A few such studies have been conducted in low- and middle-income countries due to funding, methodological and other challenges. This paper briefly reviews the methods of comprehensive birth cohort studies with extensive follow-up of participants through the life course conducted in low- and middle-income countries. It then reviews the first Jamaican birth cohort study of 1986 and discusses the methodological advances in implementing JA KIDS, the second Jamaican birth cohort study conducted in 2011. The aims and methods of JA KIDS are described in detail.

The maternal drug exposure birth cohort (DEBC) in China.

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.

Does cardiorespiratory fitness mediate or moderate the association between mid-life physical activity frequency and cognitive function? findings from the 1958 British birth cohort study.

BACKGROUND: Physical activity (PA) is associated with a lower risk of cognitive decline and all-cause dementia in later life. Pathways underpinning this association are unclear but may involve either mediation and/or moderation by cardiorespiratory fitness (CRF). METHODS: Data on PA frequency (exposure) at 42y, non-exercise testing CRF (NETCRF, mediator/moderator) at 45y and overall cognitive function (outcome) at 50y were obtained from 9,385 participants (50.8% female) in the 1958 British birth cohort study. We used a four-way decomposition approach to examine the relative contributions of mediation and moderation by NETCRF on the association between PA frequency at 42y and overall cognitive function at 50y. RESULTS: In males, the estimated overall effect of 42y PA ≥once per week (vs.

Maternal diet quality with child allergic and respiratory multimorbidity in the Elfe birth cohort.

Evidence linking maternal diet during pregnancy to allergic or respiratory diseases in children remains sparse, and outcomes were mainly studied separately. We aim to investigate these associations by considering clusters of allergic and respiratory multimorbidity among 9679 mother-child pairs from the Elfe birth cohort. Maternal diet quality was evaluated using a food-based score (Diet Quality score), a nutrient-based score (PANDiet score) and food group intakes. Adjusted multinomial logistic regressions on allergic and respiratory multimorbidity clusters up to 5.5 years were performed. Child allergic and respiratory diseases were described through five clusters: "asymptomatic" (43%, reference), "early wheeze without asthma" (34%), "asthma only" (7%), "allergies without asthma" (7%), "multi-allergic" (9%). A higher PANDiet score and an increased legume consumption were associated with a reduced risk of belonging to the "early wheeze without asthma" cluster. A U-shaped relationship was observed between maternal fish consumption and the "allergies without asthma" cluster. To conclude, adequate nutrient intake during pregnancy was weakly associated with a lower risk of "early wheeze without asthma" in children. No association was found with food groups, considered jointly or separately, except for legumes and fish, suggesting that maternal adherence to nutritional guidelines might be beneficial for allergic and respiratory diseases prevention.

The Role of Placental DNA Methylation at Reproduction-Related Genes in Associations between Prenatal Bisphenol Analogues Exposure and the Digit Ratio in Children at Age 4: A Birth Cohort Study.

Placental DNA methylation (DNAm) may be a potential mechanism underlying the effects of prenatal bisphenol analogues (BPs) exposure on reproductive health. Based on the Shanghai-Minhang Birth Cohort Study (S-MBCS), this study investigated associations of placental DNAm at reproduction-related genes with prenatal BPs exposure and children's digit ratios at age 4 using multiple linear regression models, and mediation analysis was further used to examine the mediating role of placental DNAm in the associations between prenatal BPs exposure and digit ratios among 345 mother-child pairs. Prenatal exposure to bisphenol A (BPA) was associated with hypermethylation at Protocadherin 8 (PCDH8), RBMX Like 2 (RBMXL2), and Sperm Acrosome Associated 1 (SPACA1), while bisphenol F (BPF) exposure was associated with higher methylation levels of Fibroblast Growth Factor 13 (FGF13). Consistent patterns were found in associations between higher DNAm at the 4 genes and increased digit ratios. Further mediation analysis showed that about 15% of the effect of BPF exposure on increased digit ratios was mediated by placental FGF13 methylation. In conclusion, the altered placental DNAm status might be a mediator underlying the feminizing effect of prenatal BPs exposure.

Relationship between first trimester physical activity and premature rupture of membranes: a birth cohort study in Chinese women.

OBJECTIVE: This study aimed to examine prospective associations of different intensity levels and types of physical activity (PA) in early pregnancy with premature rupture of membranes (PROM) among Chinese pregnant women. METHODS: A total of 6284 pregnant women were included from the Tongji-Shuangliu Birth Cohort. Household/caregiving, occupational, sports/exercise and transportation activities during early pregnancy were investigated by the pregnancy physical activity questionnaire (PPAQ), and the diagnosis of PROM was ascertained during the whole pregnancy. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the associations between PA and PROM. RESULTS: Among the 6284 pregnant women, 1246 were identified to have PROM (19.8%). Women undertaking the highest level (3 third tertile) of PA during pregnancy appeared to have a lower risk of PROM [OR = 0.68, 95%CI 0.58-0.80) when compared to those at the lowest tertile of PA. Similarly, women with increased levels of light intensity activity, moderate-vigorous intensive, household/caregiving activity and meeting exercise guidelines during pregnancy were associated with reduced risks of PROM (OR = 0.69, 95% CI 0.59-0.81, OR = 0.70, 95% CI 0.60-0.82, OR = 0.62, 95% CI 0.53-0.73 and OR = 0.82, 95% CI 0.70-0.97, respectively). CONCLUSIONS: High levels of PA of different intensities and PA of household/caregiving activities and meeting exercise guidelines during the first trimester were associated with a lower incidence of PROM. TRIAL REGISTRATION: The data of human participants in this study were conducted in accordance with the Helsinki Declaration. This study has been approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ([2017] No. S225). All participants provided written informed consent prior to enrollment. A statement to confirm that all methods were carried out in accordance with relevant guidelines and regulations.

Human milk oligosaccharide composition is affected by season and parity and associates with infant gut microbiota in a birth mode dependent manner in a Finnish birth cohort.

BACKGROUND: Human milk oligosaccharides (HMOs), their determinants, infant gut microbiota and health are under extensive research; however, seldom jointly addressed. Leveraging data from the HELMi birth cohort, we investigated them collectively, considering maternal and infant secretor status. METHODS: HMO composition in breastmilk collected 3 months postpartum (n = 350 mothers) was profiled using high-performance liquid chromatography. Infant gut microbiota taxonomic and functional development was studied at 3, 6, and 12 months (n = 823 stool samples) via shotgun metagenomic sequencing, focusing on HMO metabolism via glycoside hydrolase (GH) analysis. Maternal and infant secretor statuses were identified through phenotyping and genotyping, respectively. Child health, emphasizing allergies and antibiotics as proxies for infectious diseases, was recorded until 2 years. FINDINGS: Mother's parity, irritable bowel syndrome, gestational diabetes, and season of milk collection associated with HMO composition. Neither maternal nor infant secretor status associated with infant gut microbiota, except for a few taxa linked to individual HMOs. Analysis stratified for birth mode revealed distinct patterns between the infant gut microbiota and HMOs. Child health parameters were not associated to infant or maternal secretor status. INTERPRETATION: This comprehensive exploration unveils intricate links between secretor genotype, maternal factors, HMO composition, infant microbiota, and child health. Understanding these nuanced relationships is paramount for refining strategies to optimize early life nutrition and its enduring impact on long-term health. FUNDING: Sweet Crosstalk EU H2020 MSCA ITN, Academy of Finland, Mary and Georg C. Ehrnrooth Foundation, Päivikki and Sakari Sohlberg Foundation, and Tekes.

Faster pace of hippocampal growth mediates the association between perinatal adversity and childhood depression.

Early life adversity has been posited to influence the pace of structural neurodevelopment. Most research, however, has relied on cross-sectional data, which do not reveal whether the pace of neurodevelopmental change is accelerated or slowed following early exposures. In a birth cohort study that included neuroimaging data obtained at 4.5, 6, and 7.5 years of age (N = 784), we examined associations among a cumulative measure of perinatal adversity relative to resources, nonlinear trajectories of hippocampal and amygdala volume, and children's subsequent depressive symptoms at 8.5 years of age. Greater adversity was associated with reduced bilateral hippocampal body volume in early childhood, but also to faster growth in the right hippocampal body across childhood. Further, the association between adversity and childhood depressive symptoms was mediated by faster hippocampal body growth. These findings suggest that perinatal adversity is biologically embedded in hippocampal structure development, including an accelerated pace of change in the right hippocampal body that is implicated in children's psychopathology risk. In addition, our findings suggest that reduced hippocampal volume is not inconsistent with accelerated hippocampal change; these aspects of structural development may typically co-occur, as smaller regional volumes in early childhood were associated with faster growth across childhood.

Deciduous teeth from the New Hampshire birth cohort study: Early life environmental and dietary predictors of dentin elements.

BACKGROUND: Sparse research exists on predictors of element concentrations measured in deciduous teeth. OBJECTIVE: To estimate associations between maternal/child characteristics, elements measured in home tap water during pregnancy and element concentrations in the dentin of shed deciduous teeth. METHODS: Our analysis included 152 pregnant person-infant dyads followed from the second trimester through the end of the first postnatal year from the New Hampshire Birth Cohort Study. During pregnancy and early infancy, we collected dietary and sociodemographic information via surveys, measured elements in home tap water, and later collected naturally exfoliated teeth from child participants. We measured longitudinal deposition of elements in dentin using LA-ICP-MS. Multivariable linear mixed models were used to estimate associations between predictors and dentin element concentrations. RESULTS: We measured 12 elements in dentin including those previously reported (Ba, Mn, Pb, Sr, Zn) and less frequently reported (Al, As, Cd, Cu, Hg, Li, and W). A doubling of Pb or Sr concentrations in water was associated with higher dentin Pb or Sr respectively in prenatally formed [9% (95%CI: 3%, 15%); 3% (1%, 6%)] and postnatally formed [10% (2%, 19%); 6% (2%, 10%)] dentin. Formula feeding from birth to 6 weeks or 6 weeks to 4 months was associated with higher element concentrations in postnatal dentin within the given time period as compared to exclusive human milk feeding: Sr: 6 weeks: 61% (36%, 90%) and 4 months: 85% (54%, 121%); Ba: 6 weeks: 35% (3.3%, 77%) and 4 months: 42% (10%, 83%); and Li: 6 weeks: 61% (33%, 95%) and 4 months: 58% (31%, 90%). SIGNIFICANCE: These findings offer insights into predictors of dentin elements and potential confounders in exposure-health outcome relationships during critical developmental periods.

Green space exposure and blood DNA methylation at birth and in childhood - A multi-cohort study.

Green space exposure has been associated with improved mental, physical and general health. However, the underlying biological mechanisms remain largely unknown. The aim of this study was to investigate the association between green space exposure and cord and child blood DNA methylation. Data from eight European birth cohorts with a total of 2,988 newborns and 1,849 children were used. Two indicators of residential green space exposure were assessed: (i) surrounding greenness (satellite-based Normalized Difference Vegetation Index (NDVI) in buffers of 100 m and 300 m) and (ii) proximity to green space (having a green space ≥ 5,000 m2 within a distance of 300 m). For these indicators we assessed two exposure windows: (i) pregnancy, and (ii) the period from pregnancy to child blood DNA methylation assessment, named as cumulative exposure. DNA methylation was measured with the Illumina 450K or EPIC arrays. To identify differentially methylated positions (DMPs) we fitted robust linear regression models between pregnancy green space exposure and cord blood DNA methylation and between cumulative green space exposure and child blood DNA methylation. Two sensitivity analyses were conducted: (i) without adjusting for cellular composition, and (ii) adjusting for air pollution. Cohort results were combined through fixed-effect inverse variance weighted meta-analyses. Differentially methylated regions (DMRs) were identified from meta-analysed results using the Enmix-combp and DMRcate methods. There was no statistical evidence of pregnancy or cumulative exposures associating with any DMP (False Discovery Rate, FDR, p-value < 0.05). However, surrounding greenness exposure was inversely associated with four DMRs (three in cord blood and one in child blood) annotated to ADAMTS2, KCNQ1DN, SLC6A12 and SDK1 genes. Results did not change substantially in the sensitivity analyses. Overall, we found little evidence of the association between green space exposure and blood DNA methylation. Although we identified associations between surrounding greenness exposure with four DMRs, these findings require replication.

Prenatal arsenic metabolite exposure is associated with increased newborn mitochondrial DNA copy number: evidence from a birth cohort study.

While mitochondria are susceptible to environmental detriments, little is known about potential associations between arsenic metabolites and mitochondria DNA copy number (mtDNAcn). We attempted to examine whether maternal urinary arsenic metabolite levels in different trimesters were related to neonatal cord blood mtDNAcn. We included 819 mother-newborn pairs embedded in an in-progress birth cohort survey performed from April 2014 to October 2016 in Wuhan, China. We determined maternal urinary arsenic species concentrations in different trimesters. We determined cord blood mtDNAcn using quantitative real-time polymerase chain reaction. In covariate-adjusted models, each one-unit increment of dimethylated arsenic (DMA) and total arsenic (TAs) in the third trimester was related to 8.43% (95% CI 1.13%, 16.26%) and 12.15% (95% CI 4.35%, 20.53%) increases in mtDNAcn, respectively. The dose-response trend with statistical significance was observed across tertiles of DMA and TAs in the third trimester with mtDNAcn (DMA percent changes (%Δ) = 25.60 (95% CI 6.73, 47.82), for the highest vs the lowest tertile (P = 0.02); TAs %Δ = 40.31 (95% CI 19.25, 65.10), for the highest vs the lowest tertile (P = 0.0002)). These findings may prove the relationships between prenatal arsenic species levels and neonatal mitochondrial dysfunction.

Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.

BACKGROUND: Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth cohort analysis, aimed to determine if repeated exposure to anticholinergic medications was associated with greater decline, and whether decline was reversed with medication reduction. METHODS: From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by the Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified by the Word Learning Test [WLT], and processing speed quantified by the Timed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms. RESULTS: Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p < 0.01). CONCLUSIONS: Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.