Epigenetic gestational age and the relationship with developmental milestones in early childhood.

Shorter gestational age (GA) is a risk factor of developmental delay. GA is usually estimated clinically from last menstrual period and ultrasound. DNA methylation (DNAm) estimates GA using sets of cytosine-guanine-sites coupled with a clock algorithm. Therefore, DNAm-estimated GA may better reflect biological maturation. A DNAm GA greater than clinical GA, known as gestational age acceleration (GAA), may indicate epigenetic maturity and holds potential as an early biomarker for developmental delay risk. We used data from the Upstate KIDS Study to examine associations of DNAm GA and developmental delay within the first 3 years based on the Ages & Stages Questionnaire® (n = 1010). We estimated DNAm GA using two clocks specific to the Illumina Methylation EPIC 850K, the Haftorn clock and one developed from the Effects of Aspirin in Gestation and Reproduction study, in which women were followed to detect pregnancy at the earliest time possible. Among singletons, each week increase in DNAm GA was protective for overall delay (odds ratio:0.74; 95% confidence interval:0.61-0.90) and delay in all domains except for problem-solving skills. Among twins, we observed similar point estimates but lower precision. Results were similar for clinical GA. GAA was largely not associated with developmental delays. In summary, either DNAm GA or clinical GA at birth, but not epigenetic maturity (i.e. GAA), was associated with decreased odds of developmental delay in early childhood. Our study does not support using DNAm GA or GAA as separate risk factors for future risk of developmental delay within the first 3 years of age.

Age of Juice Introduction and Cardiometabolic Outcomes in Middle Childhood.

BACKGROUND: The American Academy of Pediatrics recommends juice introduction after 12 mo of age. Juice consumption has been linked to childhood obesity and cardiometabolic risk. We examined the prospective relationship between the age of juice introduction and primary and secondary cardiometabolic outcomes in middle childhood. OBJECTIVES: . METHODS: Parents reported the age of juice introduction on Upstate KIDS questionnaires completed between 4 and 18 mo. The quantity and type of juice introduced were not measured. Anthropometry, blood pressure (BP), and arterial stiffness by pulse wave velocity (PWV) were measured for 524 children (age, 8-10 y) at study visits (2017-2019). Age- and gender-adjusted z-scores were calculated using the Centers for Disease Control and Prevention reference for anthropometrics. Plasma lipids, hemoglobin A1c (HbA1c), and C-reactive protein (CRP) in a subset of children were also measured (n = 248). Associations between age at juice introduction (categorized as <6, 6 to <12, ≥12 mo), and outcomes were estimated using mean differences and odds ratios, applying generalized estimating equations to account for correlations between twins. RESULTS: Approximately 18% of children were introduced to juice at <6 mo, 52% between 6 and <12 mo, and 30% ≥ 12 mo of age. Children who were introduced to juice before 6 mo had higher systolic BP (3.13 mmHg; 95% confidence interval [CI]: 0.52, 5.74), heart rate (4.46 bpm; 95% CI: 1.05, 7.87), and mean arterial pressure (2.08 mmHg; 95% CI: 0.15, 4.00) compared with those introduced ≥12 mo after covariate adjustment including sociodemographic factors and maternal prepregnancy body mass index. No adjusted differences in anthropometry, lipids, HbA1c, and CRP levels were found. CONCLUSIONS: Early juice introduction during infancy was associated with higher systolic BP, heart rate, and mean arterial pressure in middle childhood. This trial was registered at clinicaltrials.gov as NCT03106493 (https://clinicaltrials.gov/study/NCT03106493?term=upstate%20KIDS&rank=1).

Longitudinal Child Growth Patterns in Twins and Singletons in the Upstate KIDS Cohort.

OBJECTIVES: To investigate childhood growth patterns in twins and to determine whether they show the same signs of excess growth as singletons born small-for-gestational age (SGA), which may confer future cardiometabolic risk. STUDY DESIGN: In the Upstate KIDS cohort of infants delivered from 2008 through 2010, we compared height, weight, and body mass index (BMI) z-scores at 0-3 and 7-9 years of age, as well as risk of rapid weight gain (RWG) in infancy and overweight/obesity beginning at 2 years, among appropriate-for-gestational age (AGA) twins (n = 1121), AGA singletons (n = 2684), and two groups of SGA twins: uncertain SGA twins (<10th percentile for birthweight by a singleton reference but >10th% by a population-based twin birthweight reference; n = 319) and true SGA twins (<10th% by a population-based twin reference; n = 144). RESULTS: Compared with AGA twins, both SGA twin groups had lower weight and BMI z-scores at both time points. By 7-9 years, both groups caught up in height with AGA twins. Compared with AGA singletons, z-score differences decreased between 0-3 and 7-9 years for uncertain SGA and true SGA twins, though true SGA twins had the lowest z-scores for all measures. During infancy, twins were more likely to display RWG compared with AGA singletons (RR = 2.06 to 2.67), which may reflect normal catch-up growth, as no twin group had higher prevalence of overweight/obesity at either time point. CONCLUSIONS: Though twins had lower height, weight, and BMI z-scores at birth and into toddlerhood, differences were reduced by 7-9 years, with no evidence of pathological growth and no group of twins showing elevated risk of overweight/obesity.

Displacement of peer play by screen time: associations with toddler development.

BACKGROUND: Young children's digital media use may adversely affect child development, but the mechanisms of this association are unclear. We evaluated whether screen time displaces reading and peer play time, which are subsequently associated with child development. METHODS: When children were 12, 18, 24, 30, and 36 months, mothers (n = 3894) reported the time their children spent on screens, being read to by an adult, and playing with other children. At 36 months, mothers completed the Ages and Stages Questionnaire©, an assessment of their child's developmental status. RESULTS: In unadjusted models, screen time from 12 to 36 months was not associated with reading but was associated with less time engaging in play with peers. In adjusted models accounting for developmental delay at 12 months, family and child characteristics, screen time was not directly associated with developmental delay. More peer play time was associated with a lower likelihood of developmental delay, and having higher screen time increased the likelihood of developmental delay indirectly through reduced peer play time. Results were similar for developmental delays in fine and gross motor, communication, and personal-social domains. CONCLUSIONS: Screen time in early childhood did not displace reported time spent reading, but did displace reported peer play time. IMPACT: Among children 1-3 years of age, more screen time was associated with less time engaged in peer play but not less reading with an adult. Having higher screen time from 1 to 3 years increased the odds of developmental delay indirectly through reduced peer play time. Ensuring that children engage in adequate time playing with peers may offset the negative associations between screen time and child development.

Common infectious morbidity and white blood cell count in middle childhood predict behavior problems in adolescence.

We examined the associations of middle childhood infectious morbidity and inflammatory biomarkers with adolescent internalizing and externalizing behavior problems. We recruited 1018 Colombian schoolchildren aged 5-12 years into a cohort. We quantified white blood cell (WBC) counts and C-reactive protein at enrollment and prospectively recorded incidence of gastrointestinal, respiratory, and fever-associated morbidity during the first follow-up year. After a median 6 years, we assessed adolescent internalizing and externalizing behavior problems using child behavior checklist (CBCL) and youth self-report (YSR) questionnaires. Behavior problem scores were compared over biomarker and morbidity categories using mean differences and 95% confidence intervals (CI) from multivariable linear regression. Compared with children without symptoms, CBCL internalizing problem scores were an adjusted 2.5 (95% CI: 0.1, 4.9; p = .04) and 3.1 (95% CI: 1.1, 5.2; p = .003) units higher among children with moderate diarrhea with vomiting and high cough with fever rates, respectively. High cough with fever and high fever rates were associated with increased CBCL somatic complaints and anxious/depressed scores, respectively. WBC >10,000/mm3 was associated with both internalizing problem and YSR withdrawn/depressed scores. There were no associations with externalizing behavior problems. Whether or not decreasing the burden of common infections results in improved neurobehavioral outcomes warrants further investigation.

Feeding Problems as an Indicator of Developmental Delay in Early Childhood.

OBJECTIVE: To determine whether feeding problems are indicators of developmental delay. STUDY DESIGN: In this prospective longitudinal cohort study, mothers of 3597 children (49% female, 35% multiples) reported on their children's feeding problems and developmental delays (using the Ages and Stages Questionnaire [ASQ]) when children were age 18, 24, and 30 months. Average scores of feeding problems were computed at each age, as well as a categorical score indicating a persistently high number of feeding problems ≥90th percentile across time. The Battelle Developmental Inventory, Second Edition (BDI-2) was used to assess development in 5 domains for a subset of children at 4 years. RESULTS: In adjusted analyses, feeding problems (per point increase) were increasingly associated with 6 ASQ domains from 18 months (OR, 1.30-1.98) to 24 months (OR, 2.07-2.69) to 30 months (OR, 3.90-5.64). Compared with children who never experienced feeding problems, children who experienced a high number of feeding problems at 1 or 2 time points were more than twice as likely to have a delay on all ASQ domains (OR, 2.10-2.50), and children who experienced a high number of feeding problems at all 3 time points were ≥4-fold more likely to have a delay on all ASQ domains (OR, 3.94-5.05). Children with 1-point higher feeding problems at 30 months scored 3-4 points lower in all BDI-2 domains at 4 years. CONCLUSIONS: Frequent feeding problems, especially those that persist into the third year, could be used to identify children at risk for developmental delay for more targeted screening.

Age of Juice Introduction and Child Anthropometry at 2-3 and 7-9 Years.

OBJECTIVES: To assess the association between age of juice introduction and child anthropometry after the American Academy of Pediatrics changed their guidelines in 2017 to recommend delaying juice introduction until at least 12 months of age (previously 6 months), citing concerns of weight gain. STUDY DESIGN: Upstate KIDS is a prospective birth cohort with follow-up through 9 years of age. Juice introduction was assessed on parental questionnaires at 4-18 months and categorized as <6, 6-<12, and ≥12 months. Child height and weight were recorded at 2-3 and 7-9 years of age. Weight-, height-, and body mass index (BMI)-for-age and sex z scores were calculated using the Centers for Disease Control and Prevention reference. Overweight/obese and obese status were categorized as BMI-for-age z score ≥85th and ≥95th percentiles. Controlling for sociodemographic characteristics and parental BMI, we assessed the associations of age of juice introduction with child anthropometry. RESULTS: Prevalence of childhood obesity was 16.4% at 2-3 (n = 1713) and 22.8% at 7-9 years of age (n = 1283). Juice introduction at <6 vs ≥12 months was associated with higher weight-for-age z score at 2-3 years of age (mean difference = 0.21; 95% CI 0.04-0.37). At 7-9 years of age, juice introduction at <6 vs ≥12 months was related to higher BMI-for-age (0.38; 0.12-0.64) and weight-for-age z scores (0.27; 0.06-0.49). Risk of developing overweight/obesity and obesity was 1.54 (0.99-2.38) and 2.17 (1.11-4.23) times higher among children with juice introduced at <6 months. No associations were found with juice introduced at 6-<12 vs ≥12 months. CONCLUSIONS: Risk of developing overweight/obesity or obesity is higher among children introduced to juice before 6 months of age compared with ≥12 months.

Associations of toddler mechanical/distress feeding problems with psychopathology symptoms five years later.

BACKGROUND: Feeding problems are common in early childhood, and some evidence suggests that feeding problems may be associated with psychopathology. Few prospective studies have explored whether toddler feeding problems predict later psychopathology. METHODS: Mothers of 1,136 children from the Upstate KIDS cohort study provided data when children were 2.5 and 8 years of age. Food refusal (picky eating) and mechanical/distress feeding problems and developmental delays were assessed at 2.5 years. Child eating behaviors (enjoyment of food, food fussiness, and emotional under and overeating) and child psychopathology (attention-deficit/hyperactivity (ADHD), oppositional-defiant (OD), conduct disorder (CD), and anxiety/depression) symptoms were assessed at 8 years. RESULTS: Mechanical/distress feeding problems at age 2.5, but not food refusal problems, were associated with ADHD, problematic behavior (OD/CD), and anxiety/depression symptoms at 8 years in models adjusting for eating behaviors at 8 years and child and family covariates. Associations with mechanical/distress feeding problems were larger for ADHD and problematic behavior than anxiety/depression symptoms, though all were modest. Model estimates were similar for boys and girls. CONCLUSIONS: Much of the research on feeding problems focuses on picky eating. This study suggests that early mechanical and mealtime distress problems may serve as better predictors of later psychopathology than food refusal. Parents and pediatricians could monitor children with mechanical/distress feeding problems for signs of developing psychopathology.

Maternal obesity, gestational weight gain, and offspring asthma and atopy.

BACKGROUND: Maternal obesity may affect offspring asthma and atopic disease risk by altering fetal immune system development. However, few studies evaluate gestational weight gain (GWG). OBJECTIVE: To evaluate relationships between maternal body mass index (BMI), GWG, and persistent wheeze, eczema, allergy, and asthma risk in offspring through middle childhood. METHODS: A total of 5939 children from Upstate KIDS, a population-based longitudinal cohort of children born in upstate New York (2008-2019) were included in the analysis. Persistent wheeze or asthma, eczema, and allergy were maternally reported at multiple study time points throughout early and middle childhood. Poisson regression models with robust SEs were used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for offspring atopic outcomes by maternal prepregnancy BMI and GWG. RESULTS: Prepregnancy BMI was associated with increased risk of persistent wheeze by 3 years of age even after adjustments for maternal atopy (class I obesity: aRR, 1.58; 95% CI, 1.13-2.20; class II or III obesity: aRR, 1.69; 95% CI, 1.22-2.35). Associations with reported asthma in middle childhood did not reach statistical significance. Furthermore, no associations were found between prepregnancy BMI and atopic outcomes in either early or middle childhood. GWG was not associated with higher risk of early childhood persistent wheeze or middle childhood asthma. CONCLUSION: Maternal prepregnancy BMI was associated with increased risk of offspring wheeze, whereas excessive GWG was generally not associated with childhood asthma or atopy.

Predictors of Age at Juice Introduction and Associations with Subsequent Beverage Intake in Early and Middle Childhood.

BACKGROUND: The American Academy of Pediatrics recommends that if parents choose to introduce juice, they wait until ≥12 months, citing concerns of obesity and dental caries. OBJECTIVES: We sought to identify correlates of early juice introduction (<6 months) and determine whether early introduction establishes a pattern of sugary beverage intake in childhood. METHODS: Upstate KIDS is a prospective birth cohort study with follow-up through 7 years (n = 4989). The age of juice introduction was assessed from responses on periodic questionnaires from 4-18 months and categorized as <6,  6 to <12, and ≥12 months. Sociodemographic information was reported using vital records or maternal questionnaires. At 24, 30, and 36 months and 7 years, mothers reported their child's regular juice, soda, water, and milk intakes. The analysis was restricted to singletons and 1 randomly selected twin from each pair with information on juice introduction (n = 4067). We assessed associations of sociodemographic correlates with juice introduction using Cox proportional hazard models. The relations of juice introduction with beverage intake were evaluated using Poisson or logistic regression for adjusted risk ratios (aRR) or ORs, adjusting for sociodemographic covariates and total beverage intake. RESULTS: Of the mothers, 25% and 74% introduced juice prior to 6 and 12 months, respectively. Younger maternal age; black or Hispanic race/ethnicity; lower educational attainment; Special Supplemental Nutrition Program for Women, Infants, and Children participation (yes); smoking during pregnancy; a higher pre-pregnancy BMI; a lower household income; and living in a townhouse/condominium or mobile home were associated with earlier juice introduction. Earlier juice introduction was related to a higher childhood juice intake, any soda intake, and lower water intake, holding total beverage intake constant [aRR, 1.5 (95% CI: 1.3-1.7; P-trend < 0.0001); adjusted OR 1.6 (95% CI: 1.0-2.4; P-trend = 0.01); aRR 0.9 (95% CI: 0.8-0.9; P-trend < 0.0001), respectively]. CONCLUSIONS: Markers of lower socioeconomic status are strongly associated with earlier juice introduction, which, in turn, relates to sugary beverage intake in childhood, potentially replacing water.

Perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) and DNA methylation in newborn dried blood spots in the Upstate KIDS cohort.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are persistent organic pollutants which may alter prenatal development, potentially through epigenetic modifications. Prior studies examining PFOS/PFOA and DNA methylation have relatively few subjects (n < 200) and inconsistent results. We examined relations of PFOA/PFOS with DNA methylation among 597 neonates in the Upstate KIDS cohort study. PFOA/PFOS were quantified in newborn dried blood spots (DBS) using high-performance liquid chromatography/tandem mass spectrometry. DNA methylation was measured using the Infinium MethylationEPIC BeadChip with DNA extracted from DBS. Robust linear regression was used to examine the associations of PFOA/PFOS with DNA methylation at individual CpG sites. Covariates included sample plate, estimated cell type, epigenetically derived ancestry, infant sex and plurality, indicators of maternal socioeconomic status, and prior pregnancy loss. In supplemental analysis, we restricted the analysis to 2242 CpG sites previously identified as Correlated Regions of Systemic Interindividual Variation (CoRSIVs) which include metastable epialleles. At FDR<0.05, PFOA concentration >90th percentile was related to DNA methylation at cg15557840, near SCRT2, SRXN1; PFOS>90th percentile was related to 2 CpG sites in a sex-specific manner (cg19039925 in GVIN1 in boys and cg05754408 in ZNF26 in girls). When analysis was restricted to CoRSIVs, log-scaled, continuous PFOS concentration was related to DNA methylation at cg03278866 within PTBP1. In conclusion, there was limited evidence of an association between high concentrations of PFOA/PFOS and DNA methylation in newborn DBS in the Upstate KIDS cohort. These findings merit replication in populations with a higher median concentration of PFOA/PFOS.

Parental Weight Status and Offspring Behavioral Problems and Psychiatric Symptoms.

OBJECTIVES: To assess relations of prepregnancy maternal and paternal obesity with offspring behavioral problems and psychiatric symptoms at 7-8 years in the Upstate KIDS study, a prospective cohort study. STUDY DESIGN: Maternal body mass index (BMI) was calculated from prepregnancy height and weight provided in vital records or self-report at 4 months postpartum. Mothers reported paternal height and weight. At 7-8 years, mothers indicated if their children had been diagnosed with ADHD or anxiety (n = 1915). Additionally, children's behavior was measured with the Strengths and Difficulties Questionnaire at 7 years of age (n = 1386) and the Vanderbilt ADHD Diagnostic Parent Rating Scale at 8 years of age (n = 1484). Based on Strengths and Difficulties Questionnaire scores, we identified children with borderline behavioral problems. Adjusted risk ratios (aRR) and 95% CIs were estimated with robust multivariable Poisson regression. RESULTS: Compared with children of mothers with a BMI of <25, children whose mothers had BMI 25-30, 30-35, and ≥35 kg/m2 had higher risks of reported ADHD (aRR, 1.14, 95% CI, 0.78-1.69; aRR, 1.96, 95% CI, 1.29-2.98; and aRR, 1.82, 95% CI,1.21-2.74, respectively). Risks of hyperactivity problems identified by the Strengths and Difficulties Questionnaire and a positive screen for inattentive or hyperactive/impulsive behavior with the Vanderbilt ADHD Diagnostic Parent Rating Scale were also higher with increasing maternal prepregnancy BMI. Paternal BMI was not associated with child outcomes. CONCLUSIONS: Our findings suggest that maternal, rather than paternal, obesity is associated with maternal report of child ADHD diagnosis and inattentive or hyperactivity problems. Further research is needed to understand how maternal obesity might influence these behavioral changes during or after pregnancy.

Vitamin D Deficiency in Middle Childhood Is Related to Behavior Problems in Adolescence.

BACKGROUND: Vitamin D deficiency (VDD) is associated with depression and schizophrenia in adults. The effect of VDD in childhood on behavioral development is unknown. OBJECTIVES: We aimed to study the associations of VDD and vitamin D binding protein (DBP) in middle childhood with behavior problems in adolescence. METHODS: We quantified plasma total 25-hydroxyvitamin D [25(OH)D] and DBP in 273 schoolchildren aged 5-12 y at recruitment into a cohort study in Bogota, Colombia. Externalizing and internalizing behavior problems were assessed after a median 6-y follow-up by parental report [Child Behavior Checklist (CBCL)] and self-report [Youth Self-Report (YSR)]. We estimated mean problem score differences with 95% CIs between exposure categories using multivariable linear regression. We also compared the prevalence of clinical behavior problems (score >63) between exposure groups. We assessed whether the associations between DBP and behavior problems were mediated through VDD. RESULTS: Mean ± SD CBCL and YSR externalizing problems scores were 56.5 ± 9.3 and 53.2 ± 9.5, respectively. Internalizing problems scores averaged 57.1 ± 9.8 and 53.7 ± 9.8, respectively. VDD [25(OH)D <50 nmol/L] prevalence was 10.3%. VDD was associated with an adjusted 6.0 (95% CI: 3.0, 9.0) and 3.4 (95% CI: 0.1, 6.6) units higher CBCL and YSR externalizing problems scores, respectively, and an adjusted 3.6 (95% CI: 0.3, 6.9) units higher CBCL internalizing problems scores. The prevalence of clinical total externalizing problems was 1.8 (95% CI: 1.1, 3.1) times higher in children with VDD than that in children without VDD. DBP concentration below the population median was related to higher YSR aggressive behavior and anxious/depressed subscale scores and to higher prevalence of clinical total externalizing problems. The associations between DBP and behavior problems were not mediated through VDD. CONCLUSIONS: VDD and low DBP in middle childhood are related to behavior problems in adolescence.

Iron Deficiency, Anemia, and Low Vitamin B-12 Serostatus in Middle Childhood Are Associated with Behavior Problems in Adolescent Boys: Results from the Bogotá School Children Cohort.

BACKGROUND: Iron deficiency (ID) in infancy is related to subsequent behavior problems. The effects of micronutrient status in middle childhood are uncertain. OBJECTIVE: The aim of the study was to examine the associations of micronutrient status biomarkers in middle childhood with externalizing and internalizing behavior problems in adolescence. METHODS: We assessed whether ID (ferritin <15 µg/L), anemia (hemoglobin <12.7 g/dL), or blood concentrations of zinc, vitamins A and B-12, and folate at ages 5-12 y were associated with externalizing or internalizing behavior problems in adolescence in 1042 schoolchildren from Bogotá, Colombia. Behavior problems were assessed with the Youth Self-Report questionnaire after a median 6.2 y of follow-up. Mean problem score differences with 95% CIs were estimated between categories of micronutrient status biomarkers with the use of multivariable linear regression. RESULTS: Mean ± SD externalizing and internalizing problems scores were 52.6 ± 9.6 and 53.8 ± 9.9, respectively. Among boys, middle-childhood ID, anemia, and low plasma vitamin B-12 were associated with 5.9 (95% CI: 1.0, 10.7), 6.6 (95% CI: 1.9, 11.3), and 2.7 (95% CI: 0.4, 4.9) units higher mean externalizing problems scores in adolescence, respectively-after adjustment for baseline age, time spent watching television or playing video games, mother's height, and socioeconomic status. Also in boys, ID was related to an adjusted 6.4 (95% CI: 1.2, 11.6) units higher mean internalizing problems score. There were no associations among girls. Other micronutrient status biomarkers were not associated with behavior problems. CONCLUSIONS: ID, anemia, and low vitamin B-12 in middle childhood are related to behavior problems in adolescent boys.This study was registered at clinicaltrials.gov as NCT03297970.

Correlates and family aggregation of vitamin D concentrations in school-aged children and their parents in nine Mesoamerican countries.

OBJECTIVE: To determine the associations of sociodemographic characteristics, diet and outdoor activity as an indicator of sun exposure with serum 25-hydroxyvitamin D (25(OH)D) concentrations in children and their parents from Mesoamerica. We also quantified family aggregation of serum 25(OH)D. DESIGN: Cross-sectional study. Serum 25(OH)D concentrations were quantified using immunoassay. We compared the distribution of 25(OH)D concentrations in adults and children by levels of each correlate with the use of linear regression. Family aggregation was estimated using Pearson and intraclass correlation coefficients. SETTING: Capital cities of Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Costa Rica, Panama and Belize, and Tuxtla Gutiérrez in Mexico. SUBJECTS: Children (n 223) aged 7-12 years and 492 parents. RESULTS: Mean (sd) 25(OH)D concentrations in adults and children were 81·3 (21·1) and 79·5 (18·1) nmol/l, respectively. Prevalence of vitamin D deficiency (VDD; 25(OH)D <50 nmol/l) was 3·9 % among adults and 3·6 % among children. In adults, adjusted mean 25(OH)D concentrations were highest in Nicaragua (P<0·0001). Serum 25(OH)D was positively related to time spent gardening (P=0·03). Among children, 25(OH)D concentrations were positively associated with male sex (P=0·005), dairy intake (P=0·03) and mother's serum 25(OH)D concentrations (P<0·0001); and inversely associated with mother's BMI (P=0·02) and number of home assets (P=0·04). Family membership explained 31 % of the variability in 25(OH)D concentrations; aggregation was highest between mothers and children. CONCLUSIONS: VDD prevalence was low in this study. Sociodemographic characteristics, diet and outdoor activity predict serum 25(OH)D. Family aggregation of serum 25(OH)D is high between mothers and children.

MAGA Republicans' views of American democracy and society and support for political violence in the United States: Findings from a nationwide population-representative survey.

BACKGROUND: Identifying groups at increased risk for political violence can support prevention efforts. We determine whether "Make America Great Again" (MAGA) Republicans, as defined, are potentially such a group. METHODS: Nationwide survey conducted May 13-June 2, 2022 of adult members of the Ipsos KnowledgePanel. MAGA Republicans are defined as Republicans who voted for Donald Trump in the 2020 presidential election and deny the results of that election. Principal outcomes are weighted proportions of respondents who endorse political violence, are willing to engage in it, and consider it likely to occur. FINDINGS: The analytic sample (n = 7,255) included 1,128 (15.0%) MAGA Republicans, 640 (8.3%) strong Republicans, 1,571 (21.3%) other Republicans, and 3,916 (55.3%) non-Republicans. MAGA Republicans were substantially more likely than others to agree strongly/very strongly that "in the next few years, there will be civil war in the United States" (MAGA Republicans, 30.3%, 95% CI 27.2%, 33.4%; strong Republicans, 7.5%, 95% CI 5.1%, 9.9%; other Republicans, 10.8%, 95% CI 9.0%, 12.6%; non-Republicans, 11.2%, 95% CI 10.0%, 12.3%; p < 0.001) and to consider violence usually/always justified to advance at least 1 of 17 specific political objectives (MAGA Republicans, 58.2%, 95% CI 55.0%, 61.4%; strong Republicans, 38.3%, 95% CI 34.2%, 42.4%; other Republicans, 31.5%, 95% CI 28.9%, 34.0%; non-Republicans, 25.1%, 95% CI 23.6%, 26.7%; p < 0.001). They were not more willing to engage personally in political violence. INTERPRETATION: MAGA Republicans, as defined, are more likely than others to endorse political violence. They are not more willing to engage in such violence themselves; their endorsement may increase the risk that it will occur.

Purchaser, firearm, and retailer characteristics associated with crime gun recovery: a longitudinal analysis of firearms sold in California from 1996 to 2021.

BACKGROUND: Firearm violence is a major cause of death and injury in the United States. Tracking the movement of firearms from legal purchase to use in crimes can help inform prevention of firearm injuries and deaths. The last state-wide studies analyzing crime gun recoveries used data from over 20 years ago; thus, an update is needed. METHODS: We used data for 5,247,348 handgun and 2,868,713 long gun transactions and law enforcement recoveries from California crime gun recovery (2010-2021) and California's Dealer Records of Sales records. Covariates included characteristics of dealership sales, firearms and their transactions, and purchaser's demographic characteristics, purchasing history, criminal history (from firearm purchaser criminal history records), and neighborhood socioeconomic status. Analyses for handguns and long guns was conducted separately. In multivariable analysis, we included correlates into a Cox proportional hazard model accounting for left truncation and clustering between the same firearm, purchaser, dealerships, and geographic location. Covariates that remained significant (P < 0.05) were retained. For handguns, we evaluated associations of violent and weapons crimes separately. In supplementary analyses, we examined interactions by purchasers' race and ethnicity. RESULTS: In total, 38,441 handguns (0.80%) and 6,806 long guns (0.24%) were recovered in crimes. A firearm dealer's sales volume, percent of transactions that were denials, pawns, pawn redemptions, and firearms that became crime guns were each positively associated with firearm recovery in crime. Handguns that were inexpensive, larger caliber, and that had been reported lost or stolen were positively associated with recovery in crimes. Purchaser characteristics associated with crime gun recovery included: being younger, female, Black, Hispanic, Native American or Pacific Islander, or other race/ethnicity (vs white), having previous arrests, living in close proximity to the firearm dealership, and living in a more socially vulnerable census tract. Associations with race and ethnicity were modified by previous infraction-only arrests. CONCLUSIONS: This study confirms that many previously studied correlates of firearm recovery are still relevant today. We were able to expand on previous research by examining novel associations including purchasers' criminal history and previous firearm transaction history. These results provide evidence that can be used to disrupt firearm use in crimes.

Firearm Ownership and Support for Political Violence in the United States.

Importance: Little is known about support for and willingness to engage in political violence in the United States. Such violence would likely involve firearms. Objective: To evaluate whether firearm owners' and nonowners' support for political violence differs and whether support among owners varies by type of firearms owned, recency of purchase, and frequency of carrying a loaded firearm in public. Design, Setting, and Participants: This cross-sectional nationally representative survey study was conducted from May 13 to June 2, 2022, among US adult members of the Ipsos KnowledgePanel, including an oversample of firearm owners. Exposure: Firearm ownership vs nonownership. Main Outcomes and Measures: Main outcomes concern (1) support for political violence, in general and to advance specific political objectives; (2) personal willingness to engage in political violence, by severity of violence and target population; and (3) perceived likelihood of firearm use in political violence. Outcomes are expressed as weighted proportions and adjusted prevalence differences, with P values adjusted for the false-discovery rate and reported as q values. Results: The analytic sample comprised 12 851 respondents: 5820 (45.3%) firearm owners, 6132 (47.7%) nonowners without firearms at home, and 899 (7.0%) nonowners with firearms at home. After weighting, 51.0% (95% CI, 49.9%-52.1%) were female, 8.5% (95% CI, 7.5%-9.5%) Hispanic, 9.1% (95% CI, 8.1%-10.2%) non-Hispanic Black, and 62.6% (95% CI, 61.5%-63.8%) non-Hispanic White; the mean (SD) age was 48.5 (18.0) years. Owners were more likely than nonowners without firearms at home to consider violence usually or always justified to advance at least 1 of 17 specific political objectives (owners: 38.8%; 95% CI, 37.3%-40.4%; nonowners: 29.8%; 95% CI, 28.5%-31.2%; adjusted difference, 6.5 percentage points; 95% CI, 4.5-9.3 percentage points; q < .001) but were not more willing to engage in political violence. Recent purchasers, owners who always or nearly always carry loaded firearms in public, and to a lesser extent, owners of assault-type rifles were more supportive of and willing to engage in political violence than other subgroups of firearm owners. Conclusions and Relevance: In this study of support for political violence in the United States, differences between firearm owners and nonowners without firearms at home were small to moderate when present. Differences were greater among subsets of owners than between owners and nonowners. These findings can guide risk-based prevention efforts.

Single-year change in views of democracy and society and support for political violence in the USA: findings from a 2023 nationally representative survey.

BACKGROUND: A 2022 survey in the USA found concerningly high prevalences of support for and personal willingness to engage in political violence, of beliefs associated with such violence, and of belief that civil war was likely in the near future. It is important to determine the durability of those findings. METHODS: Wave 2 of a nationally representative cohort survey was conducted May 18-June 8, 2023; the sample comprised all respondents to 2022's Wave 1. Outcomes are expressed as weighted proportions; changes from 2022 to 2023 are for respondents who participated in both surveys, based on aggregated individual change scores. RESULTS: The completion rate was 84.2%; there were 9385 respondents. After weighting, 50.7% (95% confidence interval (CI) 49.4%, 52.1%) were female; weighted mean (SD) age was 48.5 (25.9) years. About 1 in 20 respondents (5.7%, 95% CI 5.1%, 6.4%) agreed strongly/very strongly that "in the next few years, there will be civil war in the United States," a 7.7% decrease. In 2023, fewer respondents considered violence to be usually/always justified to advance at least 1 of 17 specific political objectives [25.3% (95% CI 24.7%, 26.5%), a 6.8% decrease]. However, more respondents thought it very/extremely likely that within the next few years, in a situation where they consider political violence justified, "I will be armed with a gun" [9.0% (95% CI 8.3%, 9.8%), a 2.2% increase] and "I will shoot someone with a gun" [1.8% (95% CI 1.4%, 2.2%), a 0.6% increase]. Among respondents who considered violence usually/always justified to advance at least 1 political objective, about 1 in 20 also thought it very/extremely likely that they would threaten someone with a gun (5.4%, 95% CI 4.0%, 7.0%) or shoot someone (5.7%, 95% CI 4.3%, 7.1%) to advance such an objective. CONCLUSIONS: In this cohort, support for political violence declined from 2022 to 2023, but predictions of firearm use in political violence increased. These findings can help guide prevention efforts, which are urgently needed.

Examination of newborn DNA methylation among women with polycystic ovary syndrome/hirsutism.

Research suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic modifications. Therefore, we assessed the associations of PCOS traits with neonatal DNA methylation (DNAm) using two independent cohorts. DNAm was measured in both cohorts using the Infinium MethylationEPIC array. Multivariable robust linear regression was used to determine associations of maternal PCOS exposure or preconception testosterone with methylation ß-values at each CpG probe and corrected for multiple testing by false-discovery rate (FDR). In the birth cohort, 12% (102/849) had a PCOS diagnosis (8.1% PCOS without hirsutism; 3.9% PCOS with hirsutism). Infants exposed to maternal PCOS with hirsutism compared to no PCOS had differential DNAm at cg02372539 [ß(SE): -0.080 (0.010); FDR p = 0.009], cg08471713 [ß(SE):0.077 (0.014); FDR p = 0.016] and cg17897916 [ß(SE):0.050 (0.009); FDR p = 0.009] with adjustment for maternal characteristics including pre-pregnancy BMI. PCOS with hirsutism was also associated with 8 differentially methylated regions (DMRs). PCOS without hirsutism was not associated with individual CpGs. In an independent preconception cohort, total testosterone concentrations were associated with 3 DMRs but not with individual CpGs, though the top quartile of testosterone compared to the lowest was marginally associated with increased DNAm at cg21472377 near an uncharacterized locus (FDR p = 0.09). Examination of these probes and DMRs indicate they may be under foetal genetic control. Overall, we found several associations among newborns exposed to PCOS, specifically when hirsutism was reported, and among newborns of women with relatively higher testosterone around conception.