Benchmark dose profiles for bivariate exposures.

While benchmark dose (BMD) methodology is well-established for settings with a single exposure, these methods cannot easily handle multidimensional exposures with nonlinear effects. We propose a framework for BMD analysis to characterize the joint effect of a two-dimensional exposure on a continuous outcome using a generalized additive model while adjusting for potential confounders via propensity scores. This leads to a dose-response surface which can be summarized in two dimensions by a contour plot in which combinations of exposures leading to the same expected effect are identified. In our motivating study of prenatal alcohol exposure, cognitive deficits in children are found to be associated with both the frequency of drinking as well as the amount of alcohol consumed on each drinking day during pregnancy. The general methodological framework is useful for a broad range of settings, including combinations of environmental stressors, such as chemical mixtures, and in explorations of the impact of dose rate rather than simply cumulative exposure on adverse outcomes.

Effects of prenatal alcohol exposure on cognitive and behavioral development: Findings from a hierarchical meta-analysis of data from six prospective longitudinal U.S. cohorts.

BACKGROUND: Cognitive and behavioral sequelae of prenatal alcohol exposure (PAE) continue to be prevalent in the United States and worldwide. Because these sequelae are also common in other neurodevelopmental disorders, researchers have attempted to identify a distinct neurobehavioral profile to facilitate the differential diagnosis of fetal alcohol spectrum disorders (FASD). We used an innovative, individual participant meta-analytic technique to combine data from six large U.S. longitudinal cohorts to provide a more comprehensive and reliable characterization of the neurobehavioral deficits seen in FASD than can be obtained from smaller samples. METHODS: Meta-analyses were performed on data from 2236 participants to examine effects of PAE (measured as oz absolute alcohol/day (AA/day)) on IQ, four domains of cognition function (learning and memory, executive function, reading achievement, and math achievement), sustained attention, and behavior problems, after adjusting for potential confounders using propensity scores. RESULTS: The effect sizes for IQ and the four domains of cognitive function were strikingly similar to one another and did not differ at school age, adolescence, or young adulthood. Effect sizes were smaller in the more middle-class Seattle cohort and larger in the three cohorts that obtained more detailed and comprehensive assessments of AA/day. PAE effect sizes were somewhat weaker for parent- and teacher-reported behavior problems and not significant for sustained attention. In a meta-analysis of five aspects of executive function, the strongest effect was on set-shifting. CONCLUSIONS: The similarity in the effect sizes for the four domains of cognitive function suggests that PAE affects an underlying component or components of cognition involving learning and memory and executive function that are reflected in IQ and academic achievement scores. The weaker effects in the more middle-class cohort may reflect a more cognitively stimulating environment, a different maternal drinking pattern (lower alcohol dose/occasion), and/or better maternal prenatal nutrition. These findings identify two domains of cognition-learning/memory and set-shifting-that are particularly affected by PAE, and one, sustained attention, which is apparently spared.

Alcohol Use Thresholds for Identifying Alcohol-related Problems Before and Following Roux-en-Y Gastric Bypass.

OBJECTIVE: The aim of this study was to determine the sensitivity and specificity of potential thresholds of alcohol use for identifying alcohol-related problems in women post-Roux-en-Y gastric bypass (RYGB). BACKGROUND: Despite evidence that RYGB alters alcohol pharmacokinetics and is associated with an increased risk for alcohol-related problems, the level of alcohol use that should prompt further screening for alcohol-related problems following RYGB is unclear. METHODS: The Longitudinal Assessment of Bariatric Surgery-2 is a prospective cohort study. Before surgery and annually for ≤7 years following surgery, participants completed the 10-item Alcohol Use Disorder Identification Test (AUDIT), which assesses past-year frequency and quantity of alcohol, frequency of consuming ≥6 drinks, and alcohol-related problems (ie, symptoms of alcohol dependence and/or alcohol-related harm). The AUDIT-Consumption (AUDIT-C) score was determined from the first 3 AUDIT items. RESULTS: Post-RYGB, 835 women reported current drinking at 1 or more annual assessment(s). Compared with higher frequency thresholds, drinking ≥2 times/month had the highest combined sensitivity (85.3%) and specificity (61.4%) for identifying alcohol-related problems. Compared with higher quantity thresholds, drinking ≥3 drinks/drinking day had the highest combined sensitivity (64.2%) and specificity (87.2%). An AUDIT-C score ≥3, versus other thresholds, had the highest combined sensitivity (76.4%) and specificity (81.6%). CONCLUSION: The sensitivity and specificity of these thresholds indicate assessment of alcohol consumption alone may be inadequate for identifying women at risk for alcohol-related problems post-RYGB. Additional screening tools for alcohol-related problems, which assess symptoms of alcohol-related problems, should be conducted in this population.

Do Associations Between Alcohol Use and Alcohol Use Disorder Vary by Weight Status? Results From the National Epidemiologic Survey on Alcohol and Related Conditions-III.

BACKGROUND: Understanding whether the associations between alcohol use and alcohol use disorder (AUD) differ by weight status may be useful in screening for AUD in populations where obesity is common. We aimed to determine whether the associations between alcohol use and AUD differ by weight status. METHODS: A total of 24,869 adult participants of the National Epidemiologic Survey on Alcohol and Related Conditions-III with a body mass index ≥18.5 kg/m2 who reported past-year alcohol use were included. The AUD and Associated Disabilities Interview Schedule-5 were administered to identify past-year AUD. Logistic regression was used to test the associations between weight status and levels and patterns of alcohol use with AUD; interactions between weight status and alcohol use variables in relation to AUD were examined. Analyses were stratified by gender. RESULTS: For males and females, the odds of AUD were higher with greater frequency of any alcohol use and heavy drinking, higher average quantity of drinks per drinking day, and past-year high-risk drinking. Among males, at the same average quantity of drinks per drinking day, frequency of heavy drinking, or presence of high-risk drinking, those with class 3 obesity had higher odds of AUD versus lower classes or no obesity (p for all interactions <0.01). Among females, at the same frequency of any alcohol use, those with healthy weight had the highest odds of AUD, while females with class 3 obesity had the lowest odds of AUD (p for interaction <0.001); interactions between weight status and other alcohol use variables were not significant (p ≥ 0.05). CONCLUSIONS: The associations between some measures of alcohol use and AUD differed by weight status, with inconsistent results between males and females. Alcohol use thresholds typically used in AUD screening may be too high in males with class 3 obesity.

Adolescent cannabis use and brain systems supporting adult working memory encoding, maintenance, and retrieval.

Given prior reports of adverse effects of cannabis use on working memory, an executive function with a protracted developmental course during adolescence, we examined associations between developmental patterns of cannabis use and adult working memory (WM) processes. Seventy-five adults with longitudinal assessments of cannabis use (60 with reported use, 15 with no reported use) and prenatal drug exposure assessment completed a spatial WM task during fMRI at age 28. All subjects passed a multi-drug urine screen on the day of testing and denied recreational drug use in the past week. A fast event-related design with partial trials was used to separate the BOLD response associated with encoding, maintenance, and retrieval periods of the WM task. Behavioral results showed that subjects who began using cannabis earlier in adolescence had longer reaction times (RT) than those with later initiation. Cannabis age of onset was further associated with reduced posterior parietal cortex (PPC) encoding BOLD activation, which significantly mediated age of onset WM RT associations. However, cannabis age of onset brain-behavior associations did not differ between groups with a single reported use and those with repeated use, suggesting age of onset effects may reflect substance use risk characteristics rather than a developmentally-timed cannabis exposure effect. Within repeated cannabis users, greater levels of total cannabis use were associated with performance-related increases in dorsolateral prefrontal cortex (DLPFC) activation during maintenance. This pattern of significant results remained unchanged with inclusion of demographic and prenatal measures as covariates. Surprisingly, however, at the group level, cannabis users generally performed better than participants who reported never using cannabis (faster RT, higher accuracy). We extend previous investigations by identifying that WM associations with cannabis age of onset may be primary to PPC stimulus encoding activity, while the amount of cannabis use is associated with DLPFC maintenance processes. Poorer performance of participants who reported never using cannabis and the consistency of cannabis age of onset associations across single and repeated users limit interpretation of direct developmental effects of cannabis on WM in adulthood.

Child maltreatment as a social determinant of midlife health-related quality of life in women: do psychosocial factors explain this association?

PURPOSE: We examined if child maltreatment (CM) is associated with worse health-related quality of life (HRQoL) in midlife women and if the association is mediated by psychosocial factors. METHODS: A total of 443 women were enrolled in the Pittsburgh site of the longitudinal Study of Women's Health Across the Nation-Mental Health Study. The analytic sample included 338 women who completed the SF-36 and the Childhood Trauma Questionnaire. Generalized linear regression was used to assess the association between CM and two HRQoL component scores. Structural nested mean models were used to evaluate the contribution of each psychosocial mediator (lifetime psychiatric history, depressive symptoms, sleep problems, very upsetting life events, low social support) to the association. RESULTS: Thirty-eight percent of women reported CM. The mean mental (MCS) and physical (PCS) SF-36 component scores were 2.3 points (95% CI - 4.3, - 0.3) and 2.5 points (95% CI - 4.5, - 0.6) lower, respectively, in women with any CM than in those without. When number of CM types increased (0, 1, 2, 3+ types), group mean scores decreased in MCS (52, 51, 48, 47, respectively; p < .01) and PCS (52, 52, 49, 49, respectively; p = .03). In separate mediation analyses, depressive symptoms, very upsetting life events, or low social support, reduced these differences in MCS, but not PCS. CONCLUSIONS: CM is a social determinant of midlife HRQoL in women. The relationship between CM and MCS was partially explained by psychosocial mediators. It is important to increase awareness among health professionals that a woman's midlife well-being may be influenced by early-life adversity.

The role of family history of depression and the menopausal transition in the development of major depression in midlife women: Study of women's health across the nation mental health study (SWAN MHS).

BACKGROUND: This study evaluated whether family history of depression predicts major depression in midlife women above and beyond static risk factors (such as personal history of depression prior to midlife) and risks that may change dynamically across midlife (such as menopausal, psychosocial, and health profiles). METHODS: Participants were 303 African American and Caucasian women (42-52 years at baseline) recruited into the Study of Women's Health across the Nation (SWAN) Mental Health Study (MHS) in Pittsburgh. Major depression was assessed annually with Structured Clinical Interviews for DSM-IV. Family mental health history was collected at the ninth or tenth annual follow-up. Random effects logistic regression was used to assess the relationship between family history of depression and midlife depression, controlling for baseline sociodemographic characteristics and time-varying risk factors. RESULTS: Family history of depression was associated with midlife depression after adjusting for participant's history of major depression prior to midlife, trait anxiety and baseline age, and time-varying menopausal status, body mass index, very upsetting life events, and chronic difficulties (OR = 2.24, 95% CI = 1.17-4.29, P = .02). Higher odds of major depression were found when women were late perimenopausal or postmenopausal relative to when they were premenopausal or early perimenopausal (OR = 3.01, 95% CI = 1.76-5.15, P < .0001). However, menopausal status was only associated with major depression among women without a family history. CONCLUSIONS: Family history of depression predicts major depression in midlife women independent of the menopausal transition and other time-varying covariates. Notably, the menopausal transition was associated with increased risk only among women without a family history of depression.

Maternal Obesity and Excessive Gestational Weight Gain Are Associated with Components of Child Cognition.

BACKGROUND: Maternal overweight and obesity affect two-thirds of women of childbearing age and may increase the risk of impaired child cognition. OBJECTIVE: Our objective was to test the hypothesis that high/low gestational weight gain (GWG) and high/low prepregnancy BMI were associated with offspring intelligence quotient (IQ) and executive function at age 10. METHODS: Mother-infant dyads (n = 763) enrolled in a birth cohort study were followed from early pregnancy to 10 y postpartum. IQ was assessed by trained examiners with the use of the Stanford Binet Intelligence Scale-4th edition. Executive function was assessed by the number of perseverative errors on the Wisconsin Card Sorting Test and time to complete Part B on the Trail Making Test. Self-reported total GWG was converted to gestational-age-standardized GWG z score. Multivariable linear regression and negative binomial regression were used to estimate independent and joint effects of GWG and BMI on outcomes while adjusting for covariates. RESULTS: At enrollment, the majority of women in the Maternal Health Practices and Child Development cohort were unmarried and unemployed, and more than one-half reported their race as black. The mean ± SD GWG z score was -0.5 ± 1.8, and 27% of women had a pregravid BMI ≥ 25. The median (IQR) number of perseverative errors was 23 (17, 29), the mean ± SD time on Part B was 103 ± 42.6 s, and 44% of children had a low average IQ (≤ 89). Maternal obesity was associated with 3.2 lower IQ points (95% CI: -5.6, -0.8) and a slower time to complete the executive function scale Part B (adjusted ß: 12.7 s; 95% CI: 2.8, 23 s) compared with offspring of normal-weight mothers. Offspring of mothers whose GWG was >+1 SD, compared with -1 to +1 SD, performed 15 s slower on the executive function task (95% CI: 1.8, 28 s). There was no association between GWG z score and offspring composite IQ score (adjusted ß: -0.32; 95% CI: -0.72, 0.10). Prepregnancy BMI did not modify these associations. CONCLUSIONS: Although GWG may be important for executive function, maternal BMI has a stronger relation than GWG to both offspring intelligence and executive function. Our findings contribute to evidence linking maternal obesity to long-term child outcomes.

Does family history of depression predict major depression in midlife women? Study of Women's Health Across the Nation Mental Health Study (SWAN MHS).

This study aims to determine whether family history of depression predicts major depression in midlife women independent of psychosocial and health profiles at midlife. Participants were 303 African American and Caucasian women (42-52 years at baseline) recruited into the Study of Women's Health Across the Nation (SWAN) and the Women's Mental Health Study (MHS) in Pittsburgh. Major depression was assessed annually with the Structured Clinical Interview for DSM-IV. Family mental health history was collected at the ninth or tenth follow-up. Multivariable logistic regression was used to determine whether family history of depression predicted major depression in midlife, adjusting for covariates. The odds of experiencing major depression during the study were three times greater for those with a family history than for those without a family history (OR = 3.22, 95% CI = 1.95-5.31). Family history predicted depression (OR = 2.67, 95% CI = 1.50-4.78) after adjusting for lifetime history of depression, age, trait anxiety, chronic medical conditions, and stressful life events. In analyses stratified by lifetime history of depression, family history significantly predicted depression only among women with a lifetime history of depression. Family history of depression predicts major depression in midlife women generally, but particularly in those with a lifetime history of depression prior to midlife.

Pathways from prenatal cocaine exposure to adult substance use and behavior.

This is a report from the most recent adult follow-up of the longest running cohort study of prenatal cocaine exposure (PCE), in which women were enrolled prenatally and offspring were assessed in infancy, childhood, adolescence, and young adulthood. In previous studies, PCE was linked to offspring behavior problems such as early substance use and externalizing behavior problems. The current analyses examine pathways from PCE to behavioral outcomes in offspring at the 25-year assessment. Prenatal cocaine exposure was moderate in this cohort; most women decreased or discontinued use after the first trimester. During the first and third trimesters, 38% and 11% used cocaine, respectively. This represents the most common pattern of PCE in non-treatment samples. At this phase, the adult offspring were, on average, 27.3 years old (range = 25-30), had 13.4 years of education, 83% were employed, 55% were Black, and 55% were female. Offspring who were exposed to cocaine during the first trimester were significantly more likely to use marijuana in the past year, report more arrests, and have poorer scores on a decision-making task, controlling for other prenatal substance exposure, demographic, and socioeconomic factors. In mediation analyses, there were indirect pathways from PCE to current marijuana use through early initiation of marijuana use and 21-year marijuana use, and through 15-year status offenses and 21-year marijuana use. There was also an indirect pathway from PCE to lifetime arrests through early initiation of marijuana use and 21-year Conduct Disorder, although the direct pathway from PCE to arrests also remained significant. These findings are consistent with those from previous phases and are an indication that there are detrimental associations with PCE that persist across developmental stages and into adulthood.

Prenatal Substance Use Among Young Pregnant Sexual Minority People.

Purpose: Sexual minority (SM) youth have higher rates of substance use and pregnancy but are absent from the prenatal substance use literature. We modeled the impact of SM identity and syndemic factors on prenatal substance use among 14- to 21-year-olds. Methods: Pregnant people completed an online survey (n = 357). Prenatal substance use was regressed on SM identity, controlling for other syndemic factors (e.g., depressive symptoms, intimate partner violence) and household substance use. Results: Pregnant SM participants (n = 125) were primarily bisexual and were more likely to use tobacco and illicit drugs than heterosexual participants (n = 232). The association between SM identity and prenatal tobacco use was not attenuated by syndemic factors, prenatal cannabis use, or household tobacco use. Conclusion: SM people need increased support for smoking cessation to redress health inequities in tobacco use, prevent prenatal exposures to tobacco, and limit the long-term consequences of tobacco use on health.

A dose-response analysis of the effects of prenatal alcohol exposure on cognitive development.

BACKGROUND: Most studies of the effects of prenatal alcohol exposure (PAE) on cognitive function have assumed that the dose-response curve is linear. However, data from a few animal and human studies suggest that there may be an inflection point in the dose-response curve above which PAE effects are markedly stronger and that there may be differences associated with pattern of exposure, assessed in terms of alcohol dose per drinking occasion and drinking frequency. METHODS: We performed second-order confirmatory factor analysis on data obtained at school age, adolescence, and early adulthood from 2227 participants in six US longitudinal cohorts to derive a composite measure of cognitive function. Regression models were constructed to examine effects of PAE on cognitive function, adjusted for propensity scores. Analyses based on a single predictor (absolute alcohol (AA)/day) were compared with analyses based on two predictors (dose/occasion and drinking frequency), using (1) linear models and (2) nonparametric general additive models (GAM) that allow for both linear and nonlinear effects. RESULTS: The single-predictor GAM model showed virtually no nonlinearity in the effect of AA/day on cognitive function. However, the two-predictor GAM model revealed differential effects of maternal drinking pattern. Among offspring of infrequent drinkers, PAE effects on cognitive function were markedly stronger in those whose mothers drank more than ~3 drinks/occasion, and the effect of dose/occasion was strongest among the very frequent drinkers. Frequency of drinking did not appear to alter the PAE effect on cognitive function among participants born to mothers who limited their drinking to ~1 drink/occasion or less. CONCLUSIONS: These findings suggest that linear models based on total AA/day are appropriate for assessing whether PAE affects a given cognitive outcome. However, examination of alcohol dose/occasion and drinking frequency is needed to fully characterize the impact of different levels of alcohol intake on cognitive impairment.

Exposure to maternal pre- and postnatal depression and anxiety symptoms: risk for major depression, anxiety disorders, and conduct disorder in adolescent offspring.

This study evaluated whether exposure to maternal pre- or postnatal depression or anxiety symptoms predicted psychopathology in adolescent offspring. Growth mixture modeling was used to identify trajectories of pre- and postnatal depression and anxiety symptoms in 577 women of low socioeconomic status selected from a prenatal clinic. Logistic regression models indicated that maternal pre- and postnatal depression trajectory exposure was not associated with offspring major depression, anxiety, or conduct disorder, but exposure to the high depression trajectory was associated with lower anxiety symptoms in males. Exposure to medium and high pre- and postnatal anxiety was associated with the risk of conduct disorder among offspring. Male offspring exposed to medium and high pre- and postnatal anxiety had higher odds of conduct disorder than did males with low exposure levels. Females exposed to medium or high pre- and postnatal anxiety were less likely to meet conduct disorder criteria than were females with lower exposure. To the best of our knowledge, this is the first study to examine the effect of pre- and postnatal anxiety trajectories on the risk of conduct disorder in offspring. These results suggest new directions for investigating the etiology of conduct disorder with a novel target for intervention.

Change in marijuana use from adolescence to young adulthood and its relation to gestational alcohol and marijuana exposure.

INTRODUCTION: Many studies have examined changes in marijuana use across adolescence, but few have examined factors associated with transitions from adolescence to young adulthood. We examined prenatal exposures to alcohol and marijuana and adolescent risk and protective factors that best distinguished among abstinence, continuity, or cessation of marijuana use from 16 to 22 years. METHOD: Data were from the Maternal Health Practices and Child Development Project at the prenatal and 16- and 22-year follow-up phases. The offspring were of lower socioeconomic status with an average of 12.8 years of education at 22 years. Participants' frequency and quantity of marijuana use over the past year were used to determine change in use. A discriminant analysis was applied to distinguish among the identified groups. The risk factors considered included prenatal substance exposures and age 16 demographics, behavior, and home environment. RESULT: Four categories of transitions were defined based on marijuana use from 16 to 22 years: non-users (n = 193), stop/decrease (n = 81), continue at same level/increase (n = 125), and initiation after the 16-year phase (n = 122). The factors that best distinguished among these groups were peers' marijuana use, delinquency, caregivers' financial strain, prenatal exposure to alcohol and marijuana, and race. CONCLUSION: Prenatal alcohol and marijuana exposure were significantly related to transitions of marijuana use from adolescence to young adulthood, controlling for peers' use, behavior problems, and home environment. While gestational marijuana exposure was associated with early initiation/increasing use, alcohol exposure was related to later initiation. The findings emphasize the long-term effects of prenatal exposure to alcohol and marijuana.

Factors associated with ever using cannabidiol in a cohort of younger pregnant people.

One in four Americans have used cannabidiol (CBD) products in the past year, and use has become prevalent in many Western countries with recent deregulation from a controlled or illicit substance to an unrestricted product. CBD is also marketed to pregnant people to treat common medical conditions. However, preclinical work has linked cannabidiol exposure to embryotoxicity, as well as neuroendocrine, reproductive, and behavioral effects in offspring. No studies have examined the prevalence or correlates of CBD use among pregnant people. Demographic, medical, and psychosocial correlates of cannabidiol use were examined in the YoungMoms study, a cohort of pregnant people under the age of 22, a population that is at high risk for cannabis use during pregnancy. Few of the participants (n = 186; 75% Black or Biracial) reported use of cannabidiol during pregnancy, but one in five had tried these products. Participants who reported ever using CBD were more likely to report alcohol and other drug use prior to pregnancy, controlling for race.As the use of CBD among people of reproductive age is increasingly prevalent, more research on CBD use in pregnant human populations is needed to investigate the effects of CBD on fetal development and infant outcomes.

Prenatal cocaine exposure, early cannabis use, and risky sexual behavior at age 25.

BACKGROUND: Prior research on prenatal cocaine exposure (PCE) indicates that exposed children experience behavioral dysregulation resulting in risky adolescent behavior including earlier initiation of cannabis use and sexual intercourse. The goal of this study was to examine the long-term effects of PCE on adult sexual behavior. METHODS: This is a prospective cohort study of the association between PCE and risky adult sexual behavior and sexually transmitted infections (STIs) in 202 young adults (mean age = 27, SD = 0.98 years). The sample was 55% female, 46% White, and 54% Black. Data from the prenatal, childhood, and adolescent phases of the study were used to delineate pathways from PCE to adult sexual behavior. RESULTS: The most common risky sexual behavior was having sex while drunk or high (63%). One-third of the sample reported that they "almost always" had sex while drunk or high. We found evidence for an indirect pathway from PCE to adult sex while drunk or high via early cannabis initiation. There were no other effects of PCE on adult risky sexual behavior or on risk for STIs, after controlling for sex assigned at birth, race, age at sexual initiation, and family history of drug and alcohol problems. CONCLUSIONS: Although PCE has been associated with earlier initiation of sex in prior studies, PCE was not directly associated with risky adult sex or history of STI. Exposed individuals were at greater risk of sex under the influence of alcohol or drugs via earlier initiation of cannabis use during adolescence.

Long-term effects of prenatal cannabis exposure: Pathways to adolescent and adult outcomes.

With the increased prevalence, potency, and acceptability of cannabis use during pregnancy, it is important to understand the developmental effects of prenatal cannabis exposure (PCE). This review discusses methodological considerations for studies of PCE, including the assessment of exposures, covariates, and outcomes, and reviews findings from prospective, longitudinal studies of PCE. There is some evidence for associations between PCE and restricted growth at birth, but not for long-term effects on growth. PCE appears to have subtle yet enduring effects on memory and achievement in children and adolescents. Despite differences in sample demographics and measurement, there are remarkably consistent effects of PCE on externalizing behaviors, such as delinquency and substance use, which persist into adulthood. Longitudinal analyses demonstrate the importance of early cannabis initiation for pathways between PCE and adult functioning, including substance use and abuse, memory deficits, and psychotic symptoms. Animal studies demonstrate direct effects on the development of the brain via activation of endogenous endocannabinoid systems. Cannabis-induced activation of the endocannabinoid system causes alterations in the release of neurotransmitters and the modulation of brain plasticity in neural pathways that underlie cognition, motivation, and behavior regulation. Future research should consider cannabis use before pregnancy, the timing and route of exposure, polysubstance exposures, and inter-generational effects.

Maternal trajectories of cannabis use and young adult cannabis and nicotine dependence.

INTRODUCTION: The goals of this study were to model maternal patterns of cannabis use from one year pre-pregnancy to 16 years postpartum and to determine if different patterns of maternal cannabis use predicted offspring substance use at age 22. METHODS: Women were recruited from a prenatal clinic between 1982 and 1984. Maternal cannabis use was assessed by trained interviewers twice during pregnancy, at delivery, 8 and 18 months, 3, 6, 10, 14, and 16 years postpartum. At age 22, substance use and dependence were measured in offspring. Growth mixture models of maternal cannabis use were calculated and adult offspring substance use outcomes were regressed onto maternal cannabis trajectory classes (n = 551). RESULTS: There were five distinct patterns of maternal cannabis use. Offspring of mothers who were chronic cannabis users were more likely to use cannabis (p < 0.001) and develop CUD (p < 0.05) than offspring whose mothers did not use cannabis. Offspring of chronic cannabis users were also more likely to be nicotine dependent by age 22 than offspring whose mothers did not use cannabis (p < 0.01) and than offspring whose mothers were decreasingly likely to use over time (p < 0.01). CONCLUSIONS: Integrated variable- and person-centered analyses revealed long-term and meaningful patterns of cannabis use and desistance. Chronic maternal cannabis use is a risk factor for regular and dependent cannabis use and for dependent tobacco use among young adult offspring. These findings have implications for maternal-child health given the increasing prevalence of cannabis use among women.

A hierarchical meta-analysis for settings involving multiple outcomes across multiple cohorts.

Evidence from animal models and epidemiological studies has linked prenatal alcohol exposure (PAE) to a broad range of long-term cognitive and behavioural deficits. However, there is a paucity of evidence regarding the nature and levels of PAE associated with increased risk of clinically significant cognitive deficits. To derive robust and efficient estimates of the effects of PAE on cognitive function, we have developed a hierarchical meta-analysis approach to synthesize information regarding the effects of PAE on cognition, integrating data on multiple outcomes from six U.S. Iongitudinal cohort studies. A key assumption of standard methods of meta-analysis, effect sizes are independent, is violated when multiple intercorrelated outcomes are synthesized across studies. Our approach involves estimating the dose-response coefficients for each outcome and then pooling these correlated dose-response coefficients to obtain an estimated "global" effect of exposure on cognition. In the first stage, we use individual participant data to derive estimates of the effects of PAE by fitting regression models that adjust for potential confounding variables using propensity scores. The correlation matrix characterizing the dependence between the outcome-specific dose-response coefficients estimated within each cohort is then run, while accommodating incomplete information on some outcome. We also compare inferences based on the proposed approach to inferences based on a full multivariate analysis.

Prenatal exposure to tobacco and cannabis, early cannabis initiation, and daily dual use of combustible cigarettes and cannabis during young adulthood.

INTRODUCTION: Daily combustible cigarette use is common among cannabis users, and dual use of cigarettes and cannabis is associated with detrimental outcomes. This study addresses gaps in the literature by examining data from the prenatal and adolescent phases of a prospective, longitudinal study to predict adult daily dual use. METHODS: Young adult offspring (M age = 22.8 years, 53% female) from a prenatal cohort reported on combustible cigarette and cannabis use (N = 500, 58% Black, 42% White). Pathways to daily dual use were modeled using variables from the gestational and adolescent phases of the study including prenatal tobacco, alcohol, and cannabis exposures; ages at initiation of cigarettes and cannabis; and adolescent learning/memory, impulsivity, and behavior problems. RESULTS: Prenatal cannabis and tobacco use were not directly linked to adult daily dual use of cannabis and tobacco. However, structural equation modeling revealed three significant indirect pathways from prenatal cigarette and cannabis exposures to adult daily dual use of cigarettes and cannabis via early cigarette initiation, early cannabis initiation, and adolescent behavior problems. CONCLUSIONS: This study identified pathways from prenatal cannabis and tobacco exposure to adult daily dual use, in addition to clarifying adolescent outcomes that may be part of the pathways. In a climate of growing acceptance of cannabis use and increasing legalization of recreational use, these findings serve as a warning that early exposure to cannabis may have an important role in shaping long-term dual use of tobacco and cannabis.