Associations of prenatal exposure to non-steroidal anti-inflammatory drugs with preterm birth and small for gestational age infants among women with autoimmune disorders.

PURPOSE: Estimate associations between prenatal non-steroidal anti-inflammatory (NSAID) exposure and preterm birth and small for gestational age among women with autoimmune conditions. METHODS: Participants were enrolled in the MotherToBaby cohort and had an autoimmune disorder and singleton live birth >20 weeks gestation (n = 2007). We characterized self-reported NSAID exposure over gestation for timing, duration, and average daily dose. Outcomes were preterm birth (i.e., <37 weeks' gestation) and small for gestational age infants (SGA; <10th percentile birthweight). We used Poisson regression to estimate associations between NSAID exposure and study outcomes adjusting for demographics, co-use of other medications (Model 1), and disease severity at baseline (Model 2). Secondarily, we considered the role of acetaminophen use by individually matching NSAID users to controls on cumulative dose of acetaminophen exposure. RESULTS: Overall, 15% of women reported NSAID use in pregnancy, with most use in the first trimester. No NSAID use exposure variables were associated with risk of preterm birth. Any NSAID use was associated with 1.7 (95% CI 1.2, 2.5) times greater risk of SGA and this estimate was attenuated to 1.5 (95% CI 1.0, 2.3) after adjustment for baseline disease severity. NSAID exposure in the first trimester was most strongly associated with SGA. After matching on acetaminophen exposure, associations between any NSAID use and preterm birth and SGA were 0.9 (95% CI 0.6, 1.4) and 1.8 (95% CI 1.1, 2.9). CONCLUSIONS: NSAID use in pregnancy is associated with SGA but not preterm birth. Future research should explore mechanisms that may explain these findings. Future research must also consider alternative explanations for these associations.

Alcohol-related dysmorphic features as predictors of neurodevelopmental delay in infants and preschool-aged children: Results from a birth cohort in Ukraine.

BACKGROUND: Cardinal and non-cardinal dysmorphic features are associated with prenatal alcohol exposure (PAE); however, their association with neurodevelopment is less clear. The objective of this study was to determine whether alcohol-related dysmorphic features predict neurodevelopmental delay in infants and toddlers. METHODS: We analyzed a prospective pregnancy cohort in western Ukraine enrolled between 2008 and 2014. A dysmorphology examination comprising body size and three cardinal and 14 non-cardinal dysmorphic features was performed at approximately 6 to 12 months of age. PAE was self-reported and operationalized as absolute ounces of alcohol per day around the time of conception. Neurodevelopment was assessed at 6 to 12 months with the Bayley Scales of Infant Development-II (BSID-II), and at 3.5 to 4.5 years of age with the Differential Ability Scales-II, the Child Behavior Checklist, and multiple measures that were used to create an executive functioning factor score. We performed logistic regression to predict children's neurodevelopment from dysmorphic features, growth measures, sex, and PAE. RESULTS: From an analytic sample of 582 unique children, 566 had BSID-II scores in infancy, and 289 completed the preschool battery. Models with all cardinal and non-cardinal dysmorphic features, growth measures, sex, and PAE performed better than models with subsets of those inputs. In general, models had poor performance classifying delays in infancy (area under the curve (AUC) <0.7) and acceptable performance on preschool-aged outcomes (AUC ~0.75). When the sample was limited to children with moderate-to-high PAE, predictive ability improved on preschool-aged outcomes (AUC 0.76 to 0.89). Sensitivity was relatively low for all models (12% to 63%), although other metrics of performance were higher. CONCLUSION: Predictive analysis based on dysmorphic features and measures of growth performed modestly in this sample. As these features are more reliably measured than neurodevelopment at an earlier age, the inclusion of dysmorphic features and measures of growth in predictive models should be further explored and validated in different settings and populations.

Chronic hypertension and risk of preterm delivery: National Longitudinal Study of Adolescents to Adult Health.

BACKGROUND: Chronic hypertension during pregnancy is associated with increased risk of adverse birth outcomes. In 2017, the American College of Cardiology and American Heart Association (ACC/AHA) lowered thresholds to classify hypertension in non-pregnant adults to SBP ≥ 130 mmHg and DBP ≥ 80 mmHg (ie stage I hypertension), resulting in an additional 4.5-million reproductive-aged women meeting criteria for hypertension. Little is known about effects of pre-pregnancy blood pressure (BP) in this range. OBJECTIVES: To examine the effect of pre-pregnancy maternal BP on preterm delivery. METHODS: We analysed the data from two waves of the National Longitudinal Study of Adolescent to Adult Health, including participants that had measured BP at Wave IV (2008-09) and a pregnancy that resulted in a singleton live birth between Waves IV and V (2016-18; n = 2038). We categorised BP using ACC/AHA cut-offs: normal (SBP < 120 mmHg and DBP < 80 mmHg), elevated (SBP 120-129 mmHg and DBP < 80 mmHg), hypertension stage I (SBP 130-139 mmHg or DBP 80-89 mmHg) and hypertension stage II (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg). We estimated risk ratios (RR) with log-binomial regression adjusting for maternal demographics, anthropometrics and medication use. RESULTS: The prevalence of preterm delivery was 12.6%. A standard deviation (SD) increment in SBP (SD = 12.2 mmHg) and DBP (SD = 9.3 mmHg) was associated with a 14% (95% confidence interval [CI] 2, 27) and 20% (95% CI 4, 37) higher risk of preterm delivery. Compared to normotensive controls, stage I (RR 1.33, 95% CI 1.01, 1.74) and stage II (RR 1.34, 95% CI 0.89, 2.00) hypertension were associated with increased risk. CONCLUSIONS: We observed greater risk of preterm delivery among women with higher pre-pregnancy BP. Women with stage I hypertension during pregnancy may benefit from increased BP monitoring. Additional studies on the utility of foetal surveillance in this group are warranted.

Chronic Stress Burden, Visceral Adipose Tissue, and Adiposity-Related Inflammation: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: We investigated the role of chronic stress burden on adiposity and adiposity-related inflammation with two hypotheses: a) greater chronic stress is associated with higher central adiposity and selective accumulation of visceral adipose tissue (VAT) compared with subcutaneous adipose tissue (SAT), and b) associations between VAT and inflammatory biomarkers are exacerbated when chronic stress is high. METHODS: Data come from 1809 participants included in a Multi-Ethnic Study of Atherosclerosis ancillary study of body composition and adiposity-related inflammation. Chronic psychosocial stress was measured with a five-item version of the Chronic Stress Burden Scale. First, we tested associations between chronic stress (three-level categorical variable) and VAT, SAT, and VAT/SAT ratio. Second, we tested whether associations between VAT and inflammatory biomarkers varied by level of chronic stress. RESULTS: Participants were approximately 65 years, 50% female, and 40.5% White, 25.6% Hispanic, 21.2% African American, and 12.8% Chinese American. About half of the sample reported little to no stress, and a quarter and a fifth of the sample reported medium and high levels of stress. Higher levels of chronic stress were associated with greater VAT and SAT, but not VAT/SAT ratio. Greater levels of VAT were associated with increased levels of adiposity-related inflammation in a graded pattern. These associations did not vary by stress level. CONCLUSIONS: Greater chronic stress burden is associated with both central and subcutaneous adiposity. We found no evidence that the associations between VAT and inflammatory biomarkers are exacerbated by chronic stress. Findings contribute to ongoing literature untangling pathways in which psychosocial stress contributes to adiposity-related inflammation.

Sodium and Health Outcomes: Ascertaining Valid Estimates in Research Studies.

PURPOSE OF REVIEW: The dietary reference intake (DRI) for sodium has been highly debated with persuasive and elegant arguments made for both population sodium reduction and for maintenance of the status quo. After the 2015 Dietary Guidelines Advisory Committee (DGAC) report was published, controversy ensued, and by Congressional mandate, the sodium DRIs were updated in 2019. The 2019 DRIs defined adequate intake (AI) levels by age-sex groups that are largely consistent with the DRIs for sodium that were published in 2005. Given the overall similarities between the 2005 and 2019 DRIs, one may wonder how the recently published research on sodium and health outcomes was considered in determining the DRIs, particularly, the recent studies from very large observational cohort studies. We aim to address this concern and outline the major threats to ascertaining valid estimates of the relationship between dietary sodium and health outcomes in observational cohort studies. We use tools from modern epidemiology to demonstrate how unexpected and inconsistent findings in these relationships may emerge. We use directed acyclic graphs to illustrate specific examples in which biases may occur. RECENT FINDINGS: We identified the following key threats to internal validity: poorly defined target intervention, poorly measured sodium exposure, unmeasured or residual confounding, reverse causality, and selection bias. Researchers should consider these threats to internal validity while developing research questions and throughout the research process. For the DRIs to inform real-world interventions relating to sodium reduction, it is recommended that more specific research questions be asked that can clearly define potential interventions of interest.

Risk taking, sensation seeking and personality as related to changes in substance use from adolescence to young adulthood.

INTRODUCTION: This study examined changes in substance use from adolescence to young adulthood as related to adolescents' risk taking, sensation seeking, antisocial activities, and personality traits. METHODS: Chilean youth (N = 890, 52% female) were studied in adolescence (14.5 and 16.2 years) and young adulthood (M age 21.3 years). Risk taking was assessed via a laboratory-based performance task (Balloon Analogue Risk Task), and self-administered questionnaires assessed sensation seeking, antisocial behaviors, personality and substance use. RESULTS: Frequent involvement in sensation seeking and antisocial activities were associated with increased odds of continued marijuana use from adolescence to young adulthood and of illicit substance use at young adulthood. High risk taking was associated with a reduced likelihood of discontinuing marijuana use at young adulthood, and high agreeableness and conscientiousness were associated with reduced likelihood of new onset marijuana use and illicit substance use at young adulthood. CONCLUSIONS: Results highlight specific risk-taking tendencies and personality characteristics that relate to initiating, continuing, or discontinuing substance use at entry into adulthood. Sensation seeking and involvement in antisocial activities were the two foremost risk factors for continued use, which is a forecaster of drug dependence. Findings suggest potential prevention and intervention targets for abstaining from or discontinuing substance use as youth transition to adulthood.

Associations Among Household Chaos, School Belonging and Risk Behaviors in Adolescents.

We examined the associations between adolescent risk behaviors and household chaos, and whether associations varied by adolescents' sense of school belonging. We collected data from 801 Chilean adolescents from working-class families (M age 16.2 years). Approximately, one-quarter of participants reported past-month cigarette use, and 8% and 9% reported past-month binge drinking and marijuana use, respectively. More than half of youth reported having sex (52%), 23% of youth reported having unprotected sex at their last encounter, and 14% reported having multiple sex partners. Within the past year, 16%, 36%, and 23% reported carrying a weapon, physically attacking someone, and threatening to physically hurt someone, respectively. Greater household chaos was related to increased odds of each risk behavior except unprotected sex. These associations did not vary significantly by level of school belonging. Results are compared to previously reported results using a U.S., largely Latinx sample in attempts to replicate findings across culture and context.

Randomized Controlled Trial of Iron-Fortified versus Low-Iron Infant Formula: Developmental Outcomes at 16 Years.

OBJECTIVES: To test differences in cognitive outcomes among adolescents randomly assigned previously as infants to iron-fortified formula or low-iron formula as part of an iron deficiency anemia prevention trial. STUDY DESIGN: Infants were recruited from community clinics in low- to middle-income neighborhoods in Santiago, Chile. Entrance criteria included term, singleton infants; birth weight of ≥3.0 kg; and no major congenital anomalies, perinatal complications, phototherapy, hospitalization >5 days, chronic illness, or iron deficiency anemia at 6 months. Six-month-old infants were randomized to iron-fortified (12 mg/L) or low-iron (2.3 mg/L) formula for 6 months. At 16 years of age, cognitive ability, visual perceptual ability, visual memory, and achievement in math, vocabulary, and comprehension were assessed, using standardized measures. We compared differences in developmental test scores according to randomization group. RESULTS: At the follow-up assessment, the 405 participants averaged 16.2 years of age and 46% were male. Those randomized to iron-fortified formula had lower scores than those randomized to low-iron formula for visual memory, arithmetic achievement, and reading comprehension achievement. For visual motor integration, there was an interaction with baseline infancy hemoglobin, such that the iron-fortified group outperformed the low-iron group when 6-month hemoglobin was low and underperformed when 6-month hemoglobin was high. CONCLUSIONS: Adolescents who received iron-fortified formula as infants from 6 to 12 months of age at levels recommended in the US had poorer cognitive outcomes compared with those who received a low-iron formula. The prevention of iron deficiency anemia in infancy is important for brain development. However, the optimal level of iron supplementation in infancy is unclear. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01166451.

Associations Among Mothers' Depression, Emotional and Learning-Material Support to Their Child, and Children's Cognitive Functioning: A 16-Year Longitudinal Study.

This study examined the associations among maternal depression, mothers' emotional and material investment in their child, and children's cognitive functioning. Middle-class Chilean mothers and children (N = 875; 52% males) were studied when children were 1, 5, 10, and 16 years (1991-2007). Results indicated that highly depressed mothers provided less emotional and material support to their child across all ages, which related to children's lower IQ. Children with lower mental abilities at age 1 received less learning-material support at age 5, which led to mothers' higher depression at child age 10. Mothers' low support was more strongly linked to maternal depression as children got older. Findings elucidate the dynamic and enduring effects of depression on mothers' parenting and children's development.

Effect of Infant Iron Deficiency on Children's Verbal Abilities: The Roles of Child Affect and Parent Unresponsiveness.

BACKGROUND: Infants who are iron-deficient anemic seek and receive less stimulation from their caregivers, predisposing such children to be functionally isolated. OBJECTIVES: To test the sequence whereby iron deficiency in infancy contributes to children's disengagement from the environment, which reduces parent stimulation which, in turn, contributes to children's poor verbal skills. METHODS: Chilean children (N = 875, 54% male) were studied, 45% of whom were iron deficient or iron-deficient anemic in infancy. We used structural equation modeling to test the sequence outlined above and to examine the effect of infant iron status on children's verbal performance at ages 5 and 10 years including the roles of child and parent intermediate variables. RESULTS: Severity of iron deficiency in infancy was associated with higher levels of children's dull affect and social reticence at 5 years (ß = .10, B = .26, SE = .12, p < .05), and these behaviors were associated with parent unresponsiveness (ß = .29, B = .13, SE = .03, p < .001), which related to children's lower verbal abilities at age 5 (ß = - .29, B = - 2.33, SE = .47, p < .001) and age 10 (ß = - .22, B = - 3.04, SE = .75, p < .001). An alternate model where poor iron status related directly to children's verbal ability was tested but not supported. CONCLUSIONS: Findings support functional isolation processes resulting from a nutritional deficiency, with iron-deficient anemic infants showing affective and behavioral tendencies that limit developmentally stimulating caregiving which, in turn, hinder children's verbal abilities.

Marijuana use associated with worse verbal learning and delayed recall in a sample of young adults.

BACKGROUND: There is concern about the cognitive consequences of marijuana consumption. AIM: To assess the influence of current and past marijuana use and frequency on verbal learning and memory in a sample of adults aged 21 years old. MATERIAL AND METHODS: Marijuana use was assessed using a clinician administered interview in 654 participants (56% females), who reported frequency of use, age of first use and whether its use led to problems in their lives. The CogState International Shopping List was administered to assess learning and memory. RESULTS: Seventy percent reported ever using marijuana, 46% consuming during the past year and 27% during the past 30 days. The latter scored significantly lower on delayed recall. Current and frequent use were significantly associated with lower accuracy in verbal learning and memory. CONCLUSIONS: In this cohort of adults aged 21 years old, marijuana use was prevalent and related to worse verbal memory.

Associations Among Infant Iron Deficiency, Childhood Emotion and Attention Regulation, and Adolescent Problem Behaviors.

This study examined whether iron deficiency (ID) in infancy contributes to problem behaviors in adolescence through its influence on poor regulatory abilities in childhood. Chilean infants (N = 1,116) were studied when there was no national program for iron fortification (1991-1996), resulting in high rates of ID (28%) and iron-deficiency anemia (IDA, 17%). Infants (54% male) were studied at childhood (Mage  = 10 years) and adolescence (Mage  = 14 years). IDA in infancy was related to excessive alcohol use and risky sexual behavior in adolescence through its effect on poor emotion regulation in childhood. Attentional control deficits at age 10 were also related to both infant IDA and heightened risk taking in adolescence. Findings elucidate how poor childhood regulatory abilities associated with infant IDA compromise adjustment in adolescence.

Neighborhood-Level Drinking Norms and Alcohol Intervention Outcomes in HIV Patients Who Are Heavy Drinkers.

BACKGROUND: Heavy alcohol consumption can be harmful, particularly for individuals with HIV. There is substantial variability in response to interventions that aim to reduce drinking. Neighborhood drinking norms may explain some of this variability among HIV-infected patients. Therefore, we investigated whether neighborhood-level drinking norms modified response to alcohol intervention among HIV-infected heavy drinkers. METHODS: Heavily-drinking HIV comprehensive care patients (n = 230) completed 1 of 3 brief alcohol interventions (an educational intervention, a motivational interviewing [MI] intervention, or an MI intervention with a technological enhancement called HealthCall). Drinking was reported at baseline and end of treatment (60 days). Neighborhood-level drinking norms were obtained from a separate general population study. RESULTS: Patients' reductions in drinks per drinking day in response to MI (as compared with the educational control) were more pronounced in neighborhoods with more permissive drinking norms. In contrast, patients' reductions in drinks per drinking day in response to MI plus HealthCall did not significantly vary between neighborhoods with different drinking norms. Norms did not evidence significant interactions with intervention condition for 3 other exploratory drinking outcomes (drinking frequency, binge frequency, and maximum quantity). CONCLUSIONS: Neighborhood-level drinking norms help explain differential response to an alcohol MI intervention among HIV-infected patients. This study suggests the utility of considering neighborhood context as an effect modifier of alcohol interventions.

Racial discrimination, socioeconomic position, and illicit drug use among US Blacks.

PURPOSE: We assessed the relationship of self-reported racial discrimination with illicit drug use among US Blacks, and whether this differed by socioeconomic position (SEP). METHODS: Among 6587 Black participants in Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (2004-2005), we used multiple logistic regression models to test the association between racial discrimination (measured on the 6-item Experiences of Discrimination scale) and past-year illicit drug use, and whether this differed by SEP. RESULTS: Racial discrimination was associated with past-year drug use [adjusted odds ratio (aOR) 2.32; 95 % confidence interval (CI) 1.70, 3.16] and with frequent drug use (aOR 1.91; 95 % CI 1.22, 2.99). For frequent illicit drug use, this relationship was stronger among higher SEP participants (aOR 3.55; 95 % CI 2.09, 6.02; p interaction < 0.01). CONCLUSIONS: The stronger association between racial discrimination and frequent illicit drug use among higher SEP Blacks suggests a complex interplay between disadvantaged and privileged statuses that merits further investigation. The finding of a significant difference by SEP highlights the importance of considering differences within heterogeneous race/ethnic groups when investigating health disparities.

Childhood Aggressive Behavior and Adolescent Substance Use Initiation.

BACKGROUND: Drug and alcohol use before the age of 14 is associated with adverse outcomes over the life course. While previous studies have identified numerous sociodemographic characteristics associated with youth substance use initiation, few have examined the relationship between behavioral characteristics, such as childhood aggression, and substance use initiation in adolescence. METHODS: This longitudinal study consisted of 2985 children from the Future of Families and Child Wellbeing Study. Aggression was measured using primary caregiver report when the children were about the age of 9 and cigarette, alcohol, and marijuana use was measured using the child report when the children were age 9 and age 15. Separate multivariable Poisson regression models were fitted for each substance use initiation outcome. RESULTS: Childhood aggression was positively associated with the initiation of cigarette and marijuana use in adolescence (aRR = 2.3 [95% CI = 1.5,3.4] and aRR = 1.3 [95% CI = 1.1,1.6], respectively). Childhood aggression was not associated with adolescent alcohol use initiation (aRR = 1.2 [95% CI = 0.9,1.5]). CONCLUSIONS: The presence of aggressive behavior in childhood was associated with the initiation of cigarette and marijuana use in adolescence. These results may be used to identify children at higher risk of cigarette and marijuana use, who may benefit from additional monitoring for substance use initiation.

Prenatal cannabis use disorder and gastroschisis in California, 2007-19.

BACKGROUND: Gastroschisis is a congenital anomaly of the abdominal wall with an unknown aetiology. Recent trends in the prevalence of gastroschisis suggest that changing environmental or behavioural factors may contribute. We examined whether prenatal cannabis use disorder was associated with gastroschisis. METHODS: The Study of Outcomes of Mothers and Infants is a population-based cohort compiled of California birth records that have been linked to Department of Health Care Access and Information hospitalization, emergency department and ambulatory surgery records. We included 2007-19 singleton live births (n = 5 774 656). Cannabis use disorder was measured by diagnosis codes at any visit during pregnancy or at birth. Gastroschisis was measured by diagnosis or surgical repair procedure codes at birth or during the first year of life. RESULTS: The prevalence of cannabis use disorder was about 1%. The prevalence of gastroschisis was 0.14% and 0.06% among those with and without cannabis use disorder, respectively. There were positive associations between cannabis use disorder and gastroschisis when using a multivariable model [adjusted risk ratio (aRR) = 1.3, 95% confidence interval (CI) 1.0, 1.7) and a matched sample approach (aRR = 1.5, 95% CI 1.1, 2.1). The association varied by maternal age and was largest among people aged >34 years (aRR = 2.5, 95% CI 1.0, 5.8). CONCLUSIONS: We confirm findings of a positive association between cannabis exposure and gastroschisis and add that it is strongest when maternal age is greater than 34 years. More investigation into whether the association is causal, and why the association varies by maternal age, is encouraged.

Low to Moderate Prenatal Alcohol Exposure and Neurodevelopmental Outcomes: A Narrative Review and Methodological Considerations.

PURPOSE: Although abstinence is recommended in pregnancy, many pregnancies are exposed to alcohol. Observational studies of the effects of low to moderate prenatal alcohol exposure (PAE) and neurodevelopmental outcomes have yielded inconsistent results, with some studies finding an increased risk of adverse neurobehavioral and cognitive outcomes, and other studies finding no changes or reduced risk of the same outcomes. The purpose of this narrative review is to summarize these inconsistencies and apply a methodological framework to discuss how different parameters contribute to the findings. The authors also provide recommendations on how to advance future research in this area. SEARCH METHODS: The PubMed, Web of Science, and Embase databases were searched, along with reference lists of selected systematic reviews and meta-analyses. Search terms used were (infant or child or children or adolescent or offspring) AND (low or light or mild or moderate or low-to-moderate) AND (drinking or alcohol or drinks) AND (pregnancy or prenatal or fetal) AND (neurodevelopment or behavioral or psychological or cognitive or developmental) NOT (mice or rat or fish or animal) NOT (meta-analysis or review). Peer-reviewed original research studies were included if they analyzed associations between an exposure defined and characterized as low/light or moderate PAE with offspring neurodevelopmental outcomes. Animal studies, studies that did not provide clear cutoff points to classify PAE categories, studies lacking an abstinence control group, and studies that did not present a multivariable-adjusted measure of association were excluded. SEARCH RESULTS: The searches identified 2,422 papers, with 36 papers meeting eligibility criteria. These studies were carried out across nine countries and included samples ranging from approximately 500 to 40,000 participants. Cognitive, academic, socioemotional, and behavioral outcomes were assessed from infancy through age 19. DISCUSSION AND CONCLUSION: When the findings from the selected articles were summarized by geographic region, exposure definition, or neurodevelopmental outcome, no consistent observations or patterns emerged between low to moderate PAE and offspring outcomes. Although some studies found positive (i.e., beneficial) associations between low to moderate PAE and outcomes (primarily outcomes related to cognition) and others found negative (i.e., detrimental) associations (primarily for behavioral outcomes), most findings were null (i.e., showed no effect of PAE). The heterogeneity in study results is likely due to methodological issues, including residual confounding, effect measure modification, and exposure misclassification that make synthesis of studies difficult. Alternative study designs, including longitudinal trajectory analysis, sibling design, negative controls, and instrumental variable analyses, may reduce biases and are discussed. To date, the consequences of light to moderate levels of PAE on neurodevelopment remain unresolved; studies that advance methodological rigor will be important contributions to the field.

Prenatal cannabis use disorder and infant hospitalization and death in the first year of life.

OBJECTIVE: To determine whether maternal cannabis use disorder is associated with infant hospitalization or death in the first year of life. METHODS: We queried an administrative birth cohort derived from the hospital discharge database maintained by the California Office of Statewide Health Planning and Development and linked with vital statistics files. We included singleton, live-birth deliveries between 2011 and 2018. Pregnancies with cannabis use disorder were classified from International Classification of Disease codes. Outcomes included infant emergency department visits and hospital admissions identified from health records, and infant deaths identified from death records. Models were adjusted for sociodemographic variables, psychiatric comorbidities and other substance use disorders. RESULTS: There were 34,544 births (1.0 %) with a cannabis use disorder diagnosis in pregnancy, with increasing prevalence over the study period. The incidence of infant death in the first year of life was greater among those with a maternal cannabis use disorder diagnosis than those without (1.0 % vs 0.4 %; adjusted risk ratio 1.4 95 % CI: 1.2-1.6). When examining specific causes of death, the increased risk estimates were attributable to perinatal conditions and sudden unexpected infant death. After adjustment, there was no increased risk of infant hospitalizations or emergency department visits. CONCLUSIONS: These findings warrant further investigation into the underlying mechanisms of maternal prenatal CUD on infant outcomes, and add to a rapidly expanding body of literature supporting the need for effective treatment options for pregnant individuals with cannabis use disorders.

Prenatal Exposure to Cannabis and Risk of Major Structural Birth Defects: A Systematic Review and Meta-analysis.

OBJECTIVE: To review and perform a meta-analysis of observational studies that examined associations between prenatal cannabis exposure and major structural birth defects. DATA SOURCES: Information sources included Google Scholar, BIOSIS, PubMed/MEDLINE, EMBASE CINAHL, and ClinicalTrials.gov. METHODS OF STUDY SELECTION: Study titles and abstracts were reviewed with Abstrackr software. We included observational studies that examined the risk of major structural birth defects in people who used cannabis during pregnancy compared with those who had not used cannabis. We excluded case reports, ecologic studies, conference abstracts, manuscript preprints, studies designed to examine effects of cannabis used concurrently with other drugs, and studies that included synthetic cannabinoids. This process yielded 23 studies that analyzed data from birth years 1968-2021. TABULATION, INTEGRATION, AND RESULTS: We clustered and meta-analyzed measures of association for birth defects by anatomic group. Eleven articles reported an association between cannabis use and the risk of a nonspecific outcome (eg, congenital anomaly). We estimated a pooled odds ratio of 1.33 (95% CI 1.14-1.56) and a pooled adjusted odds ratio (aOR) of 1.22 (95% CI 1.00-1.50). Anatomic groups examined were cardiac (nine studies), oral cleft (three studies), digestive (four studies), genitourinary (three studies), musculoskeletal (seven studies), and nervous system (five studies). Across most outcomes, we reported positive pooled unadjusted associations that were usually attenuated after the inclusion of only adjusted estimates. Two specific anomalies, with limited data, had pooled effect estimates that did not attenuate to the null after adjustment: Ebstein anomaly (two studies, aOR 2.19, 95% CI 1.25-3.82) and gastroschisis (five studies, aOR 2.50, 95% CI 1.09-5.740). CONCLUSION: Studies examining associations between prenatal exposure to cannabis and major structural birth defects were heterogeneous. Most published effect estimates were unadjusted and scored low on our risk-of-bias assessment. Overall, we found inconsistent evidence to suggest that prenatal cannabis exposure is associated with birth defects. However, findings related to specific anomalies should be considered in further research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022319041.

Socioeconomic position and executive functioning from childhood to young adulthood: Evidence from Santiago, Chile.

BACKGROUND: Optimizing cognitive development through early adulthood has implications for population health. This study aims to understand how socioeconomic position (SEP) across development relates to executive functioning. We evaluate three frameworks in life-course epidemiology - the sensitive period, accumulation, and social mobility hypotheses. METHODS: Participants were young adults from Santiago, Chile who were studied from 6 months to 21 years. Family SEP was measured at ages 1 y, 10 y, and 16 y with the modified Graffar Index. Executive functioning was assessed at ages 16 y and 21 y by the Trail Making Test Part B (Trails B). Analyses estimating 16 y and 21 y executive function involved 581 and 469 participants, respectively. Trails B scores were modeled as a function of SEP at 1 y, 10 y, and 16 y, as the total accumulation of disadvantage, and as change in SEP between 1 y and 10 y and between 10 y and 16 y. RESULTS: Participants were low- to middle-income in infancy and, on average, experienced upwards mobility across childhood. Half of participants (58%) improved Trails B scores from 16 y and 21 y. Most (68%) experienced upward social mobility between infancy and 16 y. When examined independently, worse SEP measured at 10 y and 16 y related to worse (longer time to complete) Trails B scores at Age 21 but did not relate to the other outcomes. After mutual adjustment as a test of the sensitivity hypothesis, no SEP measure was independently related to any outcome. Testing the accumulation hypothesis, cumulative low SEP was associated with worse cognitive performance at 21 y (ß = 3.6, p = 0.04). Results for the social mobility hypothesis showed no relation to cognitive scores or to change in cognitive scores. Comparing all hypotheses, SEP at 16 y explained the most variability in executive functioning at 21 y, providing support for the sensitive period hypothesis. CONCLUSIONS: Results indicate that experiencing cumulatively low socioeconomic position from infancy to adolescence can have a negative impact on cognitive functioning in young adulthood. Findings also provide evidence in support of adolescence as a key developmental period during which SEP can most strongly impact cognitive functioning.