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BACKGROUND: Vitamin D is a hormone that regulates gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. Transcriptome-wide RNA sequencing can provide a more complete representation of the placental effects of vitamin D. OBJECTIVES: We investigated the association between prenatal vitamin D concentrations and placental gene expression in a large, prospective pregnancy cohort. METHODS: Participants were recruited from Shelby County, TN, United States, in the Conditions Affecting Neurocognitive Development and Learning in Early childhood (CANDLE) study. Vitamin D (plasma total 25-hydroxyvitatmin D, [25(OH)D]) was measured at midpregnancy (16-28 wk) and delivery. RNA was sequenced from placental samples collected at birth. We identified differentially expressed genes (DEGs) using adjusted linear regression models. We also conducted weighted gene coexpression network analysis. RESULTS: The median 25(OH)D of participants was 21.8 ng/mL at midpregnancy (N = 774; IQR: 15.4-26.5 ng/mL) and 23.6 ng/mL at delivery (n = 753; IQR: 16.8-29.1 ng/mL). Placental expression of 17 DEGs was associated with 25(OH)D at midpregnancy, but only 1 DEG was associated with 25(OH)D at delivery. DEGs were related to energy metabolism, cytoskeletal function, and transcriptional regulation. We identified 2 weighted gene coexpression network analysis gene modules whose expression was associated with 25(OH)D at midpregnancy and 1 module associated with 25(OH)D at delivery. These modules were enriched for genes related to mitochondrial and cytoskeletal function and were regulated by transcription factors including ARNT2 and FOSL2. We also identified 12 modules associated with 25(OH)D in females and 1 module in males. CONCLUSIONS: 25(OH)D during midpregnancy, but not at delivery, is associated with placental gene expression at birth. Future research is needed to investigate a potential role of vitamin D in modulating placental mitochondrial metabolism, intracellular transport, and transcriptional regulation during pregnancy.

OBJECTIVES: To predict behavioral disruptions in middle childhood, we identified latent classes of prenatal substance use. STUDY DESIGN: As part of the Environmental influences on Child Health Outcomes Program, we harmonized prenatal substance use data and child behavior outcomes from 2195 women and their 6- to 11-year-old children across 10 cohorts in the US and used latent class-adjusted regression models to predict parent-rated child behavior. RESULTS: Three latent classes fit the data: low use (90.5%; n = 1986), primarily using no substances; licit use (6.6%; n = 145), mainly using nicotine with a moderate likelihood of using alcohol and marijuana; and illicit use (2.9%; n = 64), predominantly using illicit substances along with a moderate likelihood of using licit substances. Children exposed to primarily licit substances in utero had greater levels of externalizing behavior than children exposed to low or no substances (P = .001, d = .64). Children exposed to illicit substances in utero showed small but significant elevations in internalizing behavior than children exposed to low or no substances (P

Women's social experiences can have long-term implications for their offspring's health, but little is known about the potential independent contributions of multiple periods of stress exposures over time. This study examined associations of maternal exposure to adversity in childhood and pregnancy with children's anxiety and depression symptoms in a large, sociodemographically diverse sample. Participants were 1389 mother-child dyads (child age M = 8.83 years; SD = 0.66; 42% Black, 42% White; 6% Hispanic) in the ECHO-PATHWAYS Consortium's three U.S. pregnancy cohorts. Women reported their exposure to childhood traumatic events (CTE) and pregnancy stressful life events (PSLE). Children self-reported on their symptoms of anxiety and depression at age 8-9 years. Regression analyses estimated associations between maternal stressors and children's internalizing problems, adjusting for confounders, and examined child sex as a modifier. Exploratory interaction analyses examined whether geospatially-linked postnatal neighborhood quality buffered effects. In adjusted models, PSLE counts positively predicted levels of children's anxiety and depression symptoms ([ßAnxiety=0.08, 95%CI [0.02, 0.13]; ßDepression=0.09, 95%CI [0.03, 0.14]); no significant associations were observed with CTE. Each additional PSLE increased odds of clinically significant anxiety symptoms by 9% (95%CI [0.02, 0.17]). Neither sex nor neighborhood quality moderated relations. Maternal stressors during pregnancy appear to have associations with middle childhood anxiety and depression across diverse sociodemographic contexts, whereas maternal history of childhood adversity may not. Effects appear comparable for boys and girls. Policies and programs addressing prevention of childhood internalizing symptoms may benefit from considering prenatal origins and the potential two-generation impact of pregnancy stress prevention and intervention.

BackgroundVitamin D is critical to embryonic neuronal differentiation and other developmental processes that may affect future neurocognitive function. However, observational studies have found inconsistent associations between gestational vitamin D and neurocognitive outcomes.ObjectivesWe examined the association of gestational 25-hydroxyvitamin D [25(OH)D] with children's IQ at 4-6 y, and explored whether associations differed by race.MethodsThis study used data from the CANDLE (Conditions Affecting Neurocognitive Development and Learning in Early Childhood) cohort. Between 2006 and 2011, CANDLE recruited 1503 women in their second trimester of healthy singleton pregnancies. Inclusion criteria for this analysis were gestation of ≥34 wk and availability of 25(OH)D and IQ data. Associations between second-trimester 25(OH)D plasma concentration and Stanford-Binet IQ scores in offspring at 4-6 y were examined using multivariable linear regression; interaction terms were used to explore possible effect modification by race.ResultsMean ± SD 25(OH)D concentration among 1019 eligible dyads was 21.6 ± 8.4 ng/mL, measured at a mean ± SD gestational age of 23.0 ± 3.0 wk. Vitamin D deficiency [25(OH)D

Objective: This study examined several questions about the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in young adults using data from a childhood-diagnosed sample of 200 individuals with ADHD (age M = 20.20 years) and 121 demographically similar non-ADHD controls (total N = 321). Method: We examined the use of self- versus informant ratings of current and childhood functioning and evaluated the diagnostic utility of adult-specific items versus items from the "Diagnostic and Statistical Manual of Mental Disorders" ("DSM"). Results: Results indicated that although a majority of young adults with a childhood diagnosis of ADHD continued to experience elevated ADHD symptoms (75%) and clinically significant impairment (60%), only 9.6%-19.7% of the childhood ADHD group continued to meet "DSM-IV-TR" ("DSM", 4th ed., text rev.) criteria for ADHD in young adulthood. Parent report was more diagnostically sensitive than self-report. Young adults with ADHD tended to underreport current symptoms, while young adults without ADHD tended to overreport symptoms. There was no significant incremental benefit beyond parent report alone to combining self-report with parent report. Non-"DSM"-based, adult-specific symptoms of ADHD were significantly correlated with functional impairment and endorsed at slightly higher rates than the "DSM-IV-TR" symptoms. However, "DSM-IV-TR" items tended to be more predictive of diagnostic group membership than the non-"DSM" adult-specific items due to elevated control group item endorsement. Conclusions: Implications for the assessment and treatment of ADHD in young adults are discussed (i.e., collecting informant reports, lowering the diagnostic threshold, emphasizing impairment, and cautiously interpreting retrospective reports). (Contains 3 tables and 2 footnotes.)

This study examined potential differences between the inattentive and combined ADHD subtypes using laboratory tasks assessing behavioral inhibitory processes. Seventy-five children completed two tasks of behavioral inhibition believed to isolate different processes: the cued reaction time task (CRT), a basic inhibition task, and the go/no-go task (GNG), a complex inhibition task that incorporates motivational contingencies. Three groups of participants were identified, including ADHD/Inattentive (n=17), ADHD/Combined (n=37), and comparison (n=21). Results indicated that rather than showing behavioral inhibition deficits, the ADHD/I children appeared overly inhibited, as evidenced by slower reaction times across the two tasks and significantly higher errors of omission in the GNG task. Additionally, the ADHD/I children did not demonstrate cue dependency effects on the CRT task, suggesting that they were failing to incorporate relevant information before making a response. The sluggish and inhibited performance of the ADHD/I group challenges the idea that it is a subtype of ADHD.

Although growing consensus supports the role of deficient behavioral inhibition as a central feature of the combined subtype of ADHD (ADHD/C; Barkley 1997 "Psychol Bull" 121:65-94; Nigg 2001 "Psychol Bull" 127:571-598), little research has focused on how this finding generalizes to the primarily inattentive subtype (ADHD/I). This question holds particular relevance in light of recent work suggesting that ADHD/I might be better characterized as a disorder separate from ADHD/C (Diamond 2005 "Dev Psychopathol" 17:807-825; Milich et al. 2001 "Clin Psychol Sci Pract" 8:463-488). This article describes major findings in the area of inhibitory performance in ADHD and highlights recent research suggesting important areas of divergence between the subtypes. In particular, preliminary findings point to potential differences between the subtypes with respect to how children process important contextual information from the environment, such as preparatory cues that precede responses and rewarding or punishing feedback following behavior. These suggestive findings are discussed in the context of treatment implications, which could involve differential intervention approaches for each subtype targeted to the specific deficit profiles that characterize each group of children. Future research avenues aimed toward building a sound theoretical model of ADHD/I and a better understanding of its relation to ADHD/C are also presented. Specifically, investigators are encouraged to continue studying the complex interplay between inhibitory and attentional processes, as this area seems particularly promising in its ability to improve our understanding of the potentially distinct pathologies underlying the ADHD subtypes.

This study examined the content validity of a juvenile psychopathy measure, the Childhood Psychopathy Scale (CPS; D. R. Lynam, 1997), based on a downward translation of an adult instrument, the Hare Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991). The CPS was compared with two other indices of juvenile psychopathy: (a) an index derived from expert ratings and (b) an empirical index based on correlations with adult psychopathy. The 100 items of the Common Language Q-Sort (CLQ; A. Caspi et al., 1992) provided a common metric for the comparison. Psychopathy and personality were assessed at age 13 years with the mother-reported CPS and the CLQ. Psychopathy was assessed at age 24 years with the interviewer-rated Psychopathy Checklist: Screening Version (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995). Data from over 250 participants of the middle sample of the Pittsburgh Youth Study were used to examine these relations. Item content analyses demonstrated considerable overlap among the three indices, indicating that the downward translation utilizes criteria similar to those of experts and the empirically-derived measure. In addition, these indices, even after removing overlapping items, demonstrated considerable convergence, also supporting the content validity of the downward translation. These results suggest that the downward translation method is adequate for understanding the juvenile psychopathy construct.

Background: Opioid use has disproportionally impacted pregnant people and their fetuses. Previous studies describing opioid use among pregnant people are limited by geographic location, type of medical coverage, and small sample size. We described characteristics of a large, diverse group of pregnant people who were enrolled in the Environmental Influences on Child Health Outcomes (ECHO) Program, and determined which characteristics were associated with opioid use during pregnancy. Materials and Methods: Cross-sectional data obtained from 21,905 pregnancies of individuals across the United States enrolled in the ECHO between 1990 and 2021 were analyzed. Medical records, laboratory testing, and self-report were used to determine opioid-exposed pregnancies. Multiple imputation methods using fully conditional specification with a discriminant function accounted for missing characteristics data. Results: Opioid use was present in 2.8% (n = 591) of pregnancies. The majority of people who used opioids in pregnancy were non-Hispanic White (67%) and had at least some college education (69%). Those who used opioids reported high rates of alcohol use (32%) and tobacco use (39%) during the pregnancy; although data were incomplete, only 5% reported heroin use and 86% of opioid use originated from a prescription. After adjustment, non-Hispanic White race, pregnancy during the years 2010–2012, higher parity, tobacco use, and use of illegal drugs during pregnancy were each significantly associated with opioid use during pregnancy. In addition, maternal depression was associated with increased odds of opioid use during pregnancy by more than two-fold (adjusted odds ratio 2.42, 95% confidence interval: 1.95–3.01). Conclusions: In this large study of pregnancies from across the United States, we found several factors that were associated with opioid use among pregnant people. Further studies examining screening for depression and polysubstance use may be useful for targeted interventions to prevent detrimental opioid use during pregnancy, while further elucidation of the reasons for use of prescription opioids during pregnancy should be further explored. [ABSTRACT FROM AUTHOR]