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.

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.

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.

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.

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.

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.

A longitudinal study of the impact of marijuana on adult memory function: Prenatal, adolescent, and young adult exposures.

More Americans are using marijuana than in previous decades but there are concerns over its long-term impact on cognitive functioning, especially memory. The literature on marijuana use and cognitive functioning is mixed, with some studies showing recovery of functioning upon abstinence from the drug and others showing long-term effects that persist. The latter seems especially true for individuals who initiate marijuana at a younger age and engage in more chronic patterns of use. The goal of the current study is to use prospectively collected data on young adults from a prenatal cohort to determine if there is an effect of early and/or current marijuana use on young adult memory, controlling for prenatal exposure to marijuana use, childhood memory deficits, and other significant covariates of memory functioning. At the 22-year follow-up phase of the Maternal Health Practices and Child Development (MHPCD) study, 524 young adults (58% Black, 42% White, 52% female) completed the Wechsler Memory Scale-III. Multiple regression analyses and structural equation modeling were used to determine the effect of marijuana exposure during gestation, early adolescence, and young adulthood on young adult memory function. Results indicated that initiating marijuana use before age 15 placed young adults at greater risk of memory deficits, even after controlling for childhood memory and current marijuana use. First trimester marijuana exposure also indirectly predicted young adult memory function via childhood memory deficits and early initiation of marijuana. These findings highlight the risk of prenatal marijuana exposure and early initiation of marijuana for long-term memory function in adulthood.

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.

Beliefs and attitudes regarding prenatal marijuana use: Perspectives of pregnant women who report use.

OBJECTIVE: With the increasingly permissive legal and social environments regarding marijuana, it is important to understand prenatal marijuana use from the perspective of women who use marijuana. Our objective was to qualitatively describe the marijuana use experiences, beliefs, and attitudes of women who used marijuana during pregnancy. METHODS: We conducted semi-structured interviews with pregnant women who had either reported current marijuana use or had urine testing positive for marijuana. Interviews were transcribed verbatim and analyzed for patterns and themes. RESULTS: Twenty-five pregnant women who used marijuana during their pregnancies participated in our study interviews. Main themes that emerged from the interviews were that women: 1) reported higher amounts of marijuana use prior to pregnancy and attempted to reduce their use once they realized they were pregnant; 2) used marijuana to help with nausea and appetite changes during pregnancy or to improve mood; 3) described marijuana as "natural" and "safe" compared to other substances such as alcohol, tobacco, other recreational drugs, and prescribed medications; 4) had conflicting opinions regarding whether marijuana was addictive; and 5) were uncertain but had some concerns regarding potential risks of prenatal marijuana use. CONCLUSION: Pregnant women who used marijuana in pregnancy held contradictory beliefs about continued use; they reported trying to reduce usage and were worried about potential risks, but also felt that marijuana is more natural and safer than other substances, including prescribed medicines. These findings have implications for how practitioners address prenatal marijuana use and highlight the need for further research on developmental outcomes.

Prenatal alcohol exposure and offspring alcohol use and misuse at 22 years of age: A prospective longitudinal study.

Studies have shown that prenatal alcohol exposure (PAE) is related to drinking problems during adulthood, but the level of prenatal exposure associated with young adults' quantity and frequency of alcohol use and drinking problems has not yet been established. The relation between PAE and offspring levels of alcohol use and alcohol abuse/dependency was examined in 608 22-year-olds. Mothers were recruited in early pregnancy and maternal alcohol use data were collected for each trimester of pregnancy. The offspring were assessed at multiple phases from birth to young adulthood. The average daily volume of drinking was calculated based on a self-report questionnaire developed by the Maternal Health Practices and Child Development Project and alcohol abuse/dependence was assessed using the Diagnostic Interview Schedule-IV. Exposure to one or more drinks/day during the first trimester of pregnancy was significantly related to increased levels of drinking at 22 years of age, controlling for other predictors of alcohol use. PAE was also related to two or more symptoms of Alcohol Use Disorder, but not to a full diagnosis of young adult alcohol abuse/dependence. These results indicate that individuals exposed to as little as one drink per day during gestation are at risk of higher levels of drinking and more problems with alcohol by age 22.

Trajectories of pre- and postnatal co-use of cannabis and tobacco predict co-use and drug use disorders in adult offspring.

Co-use of cannabis and tobacco is increasingly common among women and is associated with tobacco and cannabis dependence and poorer cessation outcomes. However, no study has examined maternal patterns of co-use over time, or the impact of maternal co-use on co-use and drug problems in adult offspring. Pregnant women (M age = 23, range = 18-42; 52% African American, 48% White) were asked about substance use during each trimester of pregnancy, and at 8 and 18 months, 3, 6, 10, 14, 16, and 22 years postpartum. We examined patterns of any maternal cigarette and cannabis use during pregnancy and the postpartum years. As young adults (M age = 22.8 years, range = 21-26), 603 offspring completed the Diagnostic Interview Schedule (DIS). Growth mixture modeling (GMM) was used to identify four maternal trajectories through 16 years postpartum: (1) no co-use (66%), (2) decreasing co-use (16%), (3) postpartum-only co-use (11%), and (4) chronic co-use (7%). Offspring whose mothers were in the decreasing co-use group (co-users primarily during prenatal and preschool periods) were more likely to be co-users than the offspring of non-co-users. Offspring whose mothers were chronic co-users of cigarettes and cannabis were more than twice as likely to have a drug use disorder than young adults whose mothers were not co-users. The results of this study highlight the heterogeneity in maternal co-use of tobacco and cannabis over time, with some women quitting during pregnancy but resuming co-use in the postpartum, and other women co-using during pregnancy but desisting co-use over time. Maternal trajectories of co-use were associated with inter-generational transfer of risk for substance use and dependence in adult offspring.

Early Cannabis Use and Neurocognitive Risk: A Prospective Functional Neuroimaging Study.

BACKGROUND: Retrospective neuroimaging studies have suggested an association between early cannabis onset and later neurocognitive impairment. However, these studies have been limited in their ability to distinguish substance use risk factors from cannabis-induced effects on neurocognition. We used a prospective cohort design to test whether neurocognitive differences preceded cannabis onset (substance use risk model) and if early cannabis use was associated with poorer neurocognitive development (cannabis exposure model). METHODS: Participants (N = 85) completed a visuospatial working memory task during functional magnetic resonance imaging and multiple cognitive assessments (Wechsler Intelligence Scale for Children-IV, Cambridge Neuropsychological Test Automated Battery) at 12 years of age, before any reported cannabis use (baseline), and at 15 years of age (follow-up: N = 85 cognitive assessments, n = 67 neuroimaging). By follow-up, 22 participants reported using cannabis and/or failed a Δ9-tetrahydrocannabinol urine screen (users). RESULTS: At baseline, group differences supported a risk model. Those who would initiate cannabis use by 15 years of age had activation differences in frontoparietal (increased) and visual association (decreased) regions and poorer executive planning scores (Stockings of Cambridge) compared with noninitiators. Limited support was found for a cannabis exposure model. At follow-up, activation in the cuneus displayed a significant cannabis dose-response relationship, although neither cannabis dose nor cuneus activation was associated with cognitive performance. CONCLUSIONS: The purported neurocognitive effects of early cannabis onset may not be due to cannabis initiation alone but also driven by limitations or late development of neurocognitive systems predictive of substance use. In addition, more prolonged cannabis exposure may be required to observe the cognitive effects of early cannabis onset.

Prenatal exposures to tobacco and cannabis: Associations with adult electronic cigarette use.

INTRODUCTION: Prenatal exposures to tobacco and cannabis are associated with combustible cigarette use. This study evaluated pathways from these prenatal exposures to adult electronic cigarette use. We tested whether there were indirect effects of these prenatal exposures via childhood behavior dysregulation, early tobacco use, and adolescent tobacco dependence. METHODS: Telephone interviews were conducted with 427 adult offspring (22-33 years old) from 3 prenatal cohorts with trimester-specific data on exposures to tobacco, alcohol, and cannabis. The offspring were 59% Black and 41% White (61% female). Prenatal exposures included quantity/frequency of tobacco, alcohol, and cannabis use by mothers during the first trimester. Using logistic regression and structural equation modeling, we examined the effects of gestational exposures on adult electronic cigarette use via early cigarette use (prior to age 14), controlling for covariates of combustible and electronic cigarette use. RESULTS: There were no effects of childhood behavioral dysregulation on electronic cigarette use. However, there was a significant indirect effect of prenatal exposures to tobacco and cannabis on electronic cigarette use via early adolescent combustible cigarette use and adolescent risk for tobacco dependence. CONCLUSIONS: One implication of these findings is that the inter-generational risk for tobacco use conferred via gestational exposures to tobacco and cannabis generalizes to novel products such as electronic cigarettes. These results have implications for public health, as more women use cannabis and co-use cigarettes and cannabis during pregnancy.

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.

Maternal Age and Trajectories of Risky Alcohol Use: A Prospective Study.

BACKGROUND: No prospective study of maternal alcohol use has focused on age at transition to motherhood as a predictor of trajectories of risky drinking. The goal of this study was to examine the impact of maternal age at first birth on trajectories of alcohol use beyond recommended levels over a 17-year span. METHODS: Pregnant women (N = 456) were recruited at an urban prenatal clinic. The women (13 to 42 years old; 64% African American, 36% White) were interviewed about alcohol use during pregnancy and at 6, 10, 14, and 16 years postpartum. Growth mixture modeling (GMM) was used to identify trajectories of risky drinking. Maternal age at first birth was then regressed onto trajectory class membership. RESULTS: The GMM on maternal alcohol use identified 3 groups of mothers as a function of alcohol use before, during, and after the pregnancy. The majority of mothers (66%) were identified as having low-risk trajectories of alcohol use over the 17-year span. However, 2 groups were in the higher-risk categories, with 23% identified as being in a long-term high-risk trajectory, and 11% in a short-term high-risk trajectory group. Maternal age at first birth predicted membership in a high-risk group: Younger mothers were more likely to be classified into a long-term high-risk alcohol use group. CONCLUSIONS: Younger mothers were more likely to engage in risky drinking early in pregnancy, continuing 6 to 14 years postpartum. These results can help physicians target mothers who are likely to exceed current NIAAA guidelines of abstinence during pregnancy, and no more than 7 drinks per week in the postpartum.

Prenatal tobacco exposure, maternal postnatal nicotine dependence and adolescent risk for nicotine dependence: Birth cohort study.

AIMS: The goals of this study are to determine if there is (a) a threshold effect for prenatal tobacco exposure (PTE) on adolescent risk for nicotine dependence, and (b) an additive effect of PTE and maternal postnatal nicotine dependence on adolescent risk for nicotine dependence. METHODS: Pregnant women were recruited in their 4th or 5th gestational month and asked about cigarette use during the first trimester. Mothers reported on third trimester cigarette use at delivery. Sixteen years post-partum, mothers and offspring reported on current levels of cigarette use (N=784). Nicotine dependence was assessed in both using a modified Fagerström questionnaire. RESULTS: Based on the results of a threshold analysis for PTE, four groups were created: threshold PTE only (10+ cigarettes per day), maternal nicotine postnatal dependence with no-low PTE (0-<10 cigarettes per day), threshold PTE+maternal postnatal nicotine dependence, and a referent group with no-low PTE and no maternal postnatal nicotine dependence. Adolescents in the PTE-only group and the PTE+maternal postnatal nicotine dependence group were significantly more likely to be at risk for nicotine dependence than the offspring from the referent group. However, there was no evidence for an additive effect of maternal postnatal nicotine dependence, and maternal nicotine dependence was not a significant predictor of adolescent risk for nicotine dependence in regression models including prenatal tobacco exposure. CONCLUSIONS: Bivariate analysis revealed a threshold effect for PTE of 10 cigarettes per day. In multivariate analysis, PTE remained significantly related to risk for offspring nicotine dependence, after controlling for maternal postnatal nicotine dependence and other covariates associated with adolescent cigarette use.

Maternal trajectories of cigarette use as a function of maternal age and race.

BACKGROUND: Patterns of smoking vary as a function of age and race. The goals of this study were to identify trajectories of maternal cigarette use over a 17-year span, and to determine if maternal age at first birth and race were associated with smoking trajectories. METHODS: Pregnant women (N=690) were recruited at an urban prenatal clinic. The women (13-42years old; 62% African-American, 38% White) were interviewed about cigarette use during pregnancy and 6, 10, 14, and 16years postpartum. Growth mixture modeling (GMM) was used to identify trajectories. Regressions were used to determine if maternal age at first birth and race predicted trajectory class membership. RESULTS: A GMM of maternal cigarette use delineated 5 groups: none/unlikely to use (33%), decreasing likelihood of use (6%), late desistance (5%), increasing likelihood of use (17%), and chronic use (39%). Women who became mothers at a younger age were more likely to be classified as late desisters or increasingly likely to smoke. White mothers were more likely to be chronic smokers. Different smoking trajectories and predictors of trajectories were identified for the African-American and White mothers. Covariates including prenatal substance use, hostility, education, and economic hardship also differentiated smoking trajectories. CONCLUSIONS: Both prevention and treatment of smoking should be targeted to specific groups by age of first pregnancy and race. Pregnant smokers should be provided with more information and resources to help them avoid cigarettes during pregnancy and maintain abstinence after pregnancy.

Gestational Alcohol Exposure and Other Factors Associated With Continued Teenage Drinking.

Purpose A longitudinal cohort of adolescents who initiated drinking before age 15 were studied to determine which factors distinguished between early initiators who continued to drink (persisters) from those who stopped drinking (desisters). There were 308 early initiators in the total sample (n = 917); 247 were persisters, and 61 were desisters. Method A stepwise discriminant analysis identified differences between the two groups. Considered risk/protective factors were parenting practices, peer drinking, child and maternal depression, child behavior, prenatal alcohol exposure, home environment, and demographic factors. Results Desistence was significantly related to African American race and more parental strictness. Exposure to ≥1 drink/day during pregnancy and high levels of autonomy from parents were significant predictors of persistent drinking. Conclusions Early initiation places adolescents at risk for continued and heavier drinking. Identifying characteristics of those who start early but do or do not continue drinking can inform education programs to better target the most appropriate adolescents.

Early marijuana initiation: The link between prenatal marijuana exposure, early childhood behavior, and negative adult roles.

We investigated the associations among gestational factors including prenatal marijuana exposure (PME), child behavior at age 3, early age of onset of marijuana use (EAOM, <15years), and adult roles at 22years. Participants were drawn from the Maternal Health Practices and Child Development (MHPCD) Project, a longitudinal study of prenatal substance exposure in offspring who have been studied for over 22years since the prenatal phase. Data from the prenatal, birth, 3-, and 22-year phases (N=608) were used in the present study. Age of onset of offspring substance use was determined based on data from the 14-, 16-, and 22-year phases. The subjects were of lower socioeconomic status, 43% were Caucasian and the remaining were African-American, and 48% were males. Early childhood behavior was significantly (p<0.05) related to EAOM after controlling for PME, birth and childhood environmental risk factors, and Conduct Disorder. EAOM was significantly associated with negative adult roles including increased risk of being arrested (p<0.001), lower educational attainment (p<0.001), having a child without being married (p<0.05), and unemployment at 22years (p<0.001). The correlations between PME and negative adult roles and between early childhood behavior and negative adult roles were also statistically significant. Pathway analysis demonstrated that EAOM significantly mediated the associations between PME and fulfillment of adult roles and between early childhood behavior and adult roles. There are a number of intervention points that could be targeted that would have a long-term impact on lowering the probability of EAOM and less success in adult roles.

Developmental pathways from prenatal marijuana exposure to Cannabis Use Disorder in young adulthood.

BACKGROUND: Earlier studies reported an association between prenatal marijuana exposure (PME) and cognitive and behavioral problems in the offspring. A recent publication demonstrated the relation between PME and offspring marijuana use at age 22. There are no reports of the association between PME and Cannabis Use Disorder (CUD) at 22years, the age when use of marijuana and CUD peak. METHODS: Subjects are from the Maternal Health Practices and Child Development Study, a longitudinal study of PME and other exposures during pregnancy. The cohort of mothers and their offspring has been followed since the fourth prenatal month through 22years of age. A path analysis was conducted on 590 mother-child pairs, representing 77% of the birth cohort, to examine potential pathways from PME to CUD in offspring at 22years of age. RESULTS: There is no direct effect of PME on CUD. There are, however, two indirect pathways from PME to CUD. In the first, the pathway from PME to CUD goes through offspring early age of marijuana onset. In the second, offspring depression at age 10 and early age of marijuana onset predict CUD. CONCLUSIONS: Although there is no direct effect of PME on CUD, there are significant indirect pathways from PME to CUD that affect the rate of CUD in the population. Thus, PME, offspring depression, and an early age of marijuana initiation, are significant points for intervention. As marijuana is legalized in more states, the rates of marijuana use will increase significantly, including during pregnancy, and the consequences of the association between PME and CUD will become even more significant from a public health perspective.