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.

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 and Postnatal Maternal Trajectories of Cigarette Use Predict Adolescent Cigarette Use.

INTRODUCTION: The goal of this study was to identify maternal patterns of prenatal and postnatal cigarette smoking associated with adolescent smoking. We hypothesized that maternal use at multiple time points, especially at later assessments when the offspring were adolescents, would predict offspring use. METHODS: Pregnant women (N = 456: ages 13-42) were recruited from a prenatal clinic and interviewed during pregnancy and at delivery, providing data on cigarette use (any/none) for the first and third trimesters. Mothers were re-assessed at 6, 10, 14, and 16 years postpartum. Offspring reported cigarette use at age 16. Covariates included maternal race, age, education, family income, child age, parenting behavior, and other maternal and child substance use. RESULTS: A growth mixture model revealed five patterns of tobacco use: infrequent/nonuse (39%), postpartum quitters (5%), later quitters (7%), increasing likelihood of being smokers (17%), and chronic users (32%). Offspring of postpartum quitters and the increasing likelihood of being smokers groups were more likely to use cigarettes, compared to adolescents of mothers from the infrequent/nonuse group, controlling for significant covariates. CONCLUSIONS: This is the first study to examine trajectories of maternal cigarette use from pregnancy to 16 years postpartum, linking prenatal and postnatal patterns of maternal use to use in adolescent offspring. Our findings highlight the risk associated with prenatal exposure, because mothers who used during pregnancy but quit by 6 years postpartum still had offspring who were 3.5 times more likely to smoke than non/infrequent users. IMPLICATIONS: This is the first study to examine trajectories of maternal cigarette use from the prenatal period to 16 years postpartum, and to link prenatal and postnatal patterns of use to use in adolescent offspring. We identified two long-term patterns of maternal cigarette use that were associated with offspring smoking at age 16, including one where offspring were exposed prenatally, but much less likely to be exposed to maternal cigarette use postpartum. Our findings highlight the risk associated with prenatal exposures for cigarette use in offspring, even if mothers quit in the postpartum.

Childhood maltreatment and the risk of pre-pregnancy obesity and excessive gestational weight gain.

The objective of this study was to estimate whether maternal history of childhood maltreatment was associated with pre-pregnancy obesity or excessive gestational weight gain. Pregnant women (n = 472) reported pre-pregnancy weight and height and gestational weight gain and were followed up to 16 years post-partum when they reported maltreatment on the Childhood Trauma Questionnaire (CTQ). CTQ score ranged from no maltreatment (25) to severe maltreatment (125). Prenatal mental health modified the association between CTQ score and maternal weight (P < 0.15), and thus stratified models are presented. After adjusting for race, prenatal tobacco, marijuana and alcohol use, a one standard deviation (1 SD) increase in CTQ score was associated with a 45% increase in the risk of pre-pregnancy obesity among the 141 women with elevated anxiety (≥75th percentile on the State Trait Anxiety Inventory) [relative risk, RR (95% confidence interval, CI): 1.45 (1.12, 1.88)], but was not associated among less anxious (<75th percentile) women [RR (95% CI): 1.10 (0.81, 1.51)]. Risk of excessive gestational weight gain was higher [adjusted RR (95% CI): 1.21 (1.07, 1.37)] with every 1 SD increase in CTQ score for anxious women. No association was observed for less anxious women [adjusted RR (95% CI): 0.89 (0.78, 1.02)]. Prenatal depression similarly modified the association between maltreatment and weight gain. Factors such as psychological status and traumatic experiences in early childhood may contribute to pre-pregnancy obesity and excessive gestational weight gain.

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.

Gestational Weight Gain and Offspring Longitudinal Growth in Early Life.

BACKGROUND: Excessive gestational weight gain (GWG) increases the risk of childhood obesity, but little is known about its association with infant growth patterns. AIM: The aim of this study was to examine the association between GWG and infant growth patterns. METHODS: Pregnant women (n = 743) self-reported GWG at delivery, which we classified as inadequate, adequate or excessive based on the current guidelines. Offspring weight-for-age z-score (WAZ), length-for-age z-score (LAZ (with height-for-age (HAZ) in place of length at 36 months)) and body mass index z-score (BMIZ) were calculated at birth, 8, 18 and 36 months using the 2006 World Health Organization growth standards. Linear mixed models estimated the change in z-score from birth to 36 months by GWG. RESULTS: The mean (SD) WAZ was -0.22 (1.20) at birth. Overall, WAZ and BMIZ increased from birth to, approximately, 24 months and decreased from 24 to 36 months, while LAZ/HAZ decreased from birth through 36 months. Excessive GWG was associated with higher offspring WAZ and BMIZ at birth, 8 and 36 months, and higher HAZ at 36 months, compared with adequate GWG. Compared with the same referent, inadequate GWG was associated with smaller WAZ and BMIZ at birth and 8 months. CONCLUSION: Excessive GWG may predispose infants to obesogenic growth patterns, while inadequate GWG may not have a lasting impact on infant growth.

Gestational diabetes diagnostic methods (GD2M) pilot randomized trial.

To test the feasibility of conducting a pragmatic randomized controlled trial (RCT) comparing the International Association of Diabetes in Pregnancy Study Groups (IADPSG) versus Carpenter-Coustan diagnostic criteria for gestational diabetes (GDM), and to examine patient and provider views on GDM screening. A single-blinded pragmatic pilot RCT. Participants with a singleton pregnancy between 24 and 28 weeks gestation received a 50 g oral glucose challenge test and if the value was <200 mg/dL were randomized to either the 2 h 75 g OGTT using the IADPSG criteria or the 3 h 100 g OGTT using the Carpenter-Coustan criteria. Primary outcome was the feasibility of randomization and screening. Secondary outcomes included patient and provider views (or preferences) on GDM testing. Sixty-eight women were recruited, 48 (71 %) enrolled and 47 (69 %) were randomized. Participants in both study arms identified the main challenges to GDM testing to be: drinking the glucola, fasting prior to testing, waiting to have blood drawn, and multiple venipuntures. Women in both study arms would prefer the 2 h 75 g OGTT or whichever test is recommended by their doctor in a future pregnancy. Physicians and nurse midwives endorsed screening and were comfortable with being blinded to the GDM testing strategy and results values. Both pregnant women and providers value GDM screening, and pregnant women can be recruited to a blinded, randomized GDM screening trial with minimal attrition and missing data.

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.

The association between prenatal alcohol exposure and behavior at 22 years of age.

BACKGROUND: Prenatal alcohol exposure (PAE) affects central nervous system development, growth, and morphology at higher exposure levels. Little is known about the effects of PAE at lower exposure levels or in young adults. Research on children with higher levels of PAE has shown that PAE predicts behavior problems. The question remains whether these effects are permanent or ameliorated by maturation into adulthood. METHODS: These data are from a longitudinal study of PAE. Mothers were recruited from a prenatal clinic and interviewed during their fourth prenatal month, seventh month, and delivery. In the postpartum, mothers and offspring were seen at 8 and 18 months, and 3, 6, 10, 14, 16, and 22 years. RESULTS: At 22 years, PAE significantly predicted behavior as measured with the adult self-report. These findings were significant controlling for covariates. Exposure at each trimester predicted increased behavior problems on the Total Score, Internalizing, Externalizing, Attention, and Critical Items scales. Use across pregnancy predicted a higher rate of behavior problems compared to no use and use in the first trimester only. CONCLUSIONS: The effects were dose-response and significant at each trimester of pregnancy. However, duration across pregnancy was a better predictor than drinking during the first trimester only. Binge drinking was not a better predictor of outcome compared to average daily volume (ADV), and within categories of ADV, binge drinking did not predict more problems than nonbinge drinking. Thus, there is no safe level or safe time during pregnancy for women to drink. These data demonstrate that the effects of PAE, even at low to moderate levels, extend into young adulthood and are most likely permanent.

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.

Prenatal cigarette smoke exposure and early initiation of multiple substance use.

INTRODUCTION: Earlier studies have shown a relation between prenatal cigarette smoke exposure (PCSE) and offspring initiation of tobacco use. No prior study has examined the association between PCSE and early initiation of multiple substances (EIMS) including marijuana and alcohol in addition to tobacco. We investigated the association between PCSE and multiple substance use during adolescence. METHODS: Pregnant women attending an urban prenatal clinic were selected to participate in the prospective longitudinal study based on their substance use. This study is based on the 16-year follow-up phase and consists of 579 mother-offspring dyads. The women were of lower socioeconomic status, 54% were Black, and 53% reported smoking cigarettes. 52% of the offspring were female. EIMS is a measure of the number of substances initiated prior to age 16 by the adolescents; it ranged from 0 (no initiation, N = 166) to 3 (all, N = 162). RESULTS: Adolescents exposed to tobacco during first trimester of gestation were 1.4 times more likely to initiate multiple substances by age 16 than the nonexposed group. PCSE was a significant predictor of EIMS after controlling for other prenatal exposures, home environment, and demographic characteristics, using ordinal polytomous logistic regression. Other risk factors of EIMS were maternal and adolescent depression, less strict and less involved parenting, offspring attention problems, and lack of participation in a youth club. CONCLUSIONS: There is a significant relation between PCSE and adolescent's EIMS.

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.

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.

Validity of recall of tobacco use in two prospective cohorts.

This project studied the convergent validity of current recall of tobacco-related health behaviors, compared with prospective self-report collected earlier at two sites. Cohorts were from the Oregon Research Institute at Eugene (N = 346, collected 19.5 years earlier) and the University of Pittsburgh, Pennsylvania (N = 294, collected 3.9 years earlier). Current recall was examined through computer-assisted interviews with the Lifetime Tobacco Use Questionnaire from 2005 through 2008. Convergent validity estimates demonstrated variability. Validity estimates of some tobacco use measures were significant for Oregon subjects (age at first cigarette, number of cigarettes/day, quit attempts yes/no and number of attempts, and abstinence symptoms at quitting; all P < 0.03). Validity estimates of Pittsburgh subjects' self-reports of tobacco use and abstinence symptoms were significant (P < 0.001) for all tobacco use and abstinence symptoms and for responses to initial use of tobacco. These findings support the utility of collecting recalled self-report information for reconstructing salient lifetime health behaviors and underscore the need for careful interpretation.

Developmental consequences of prenatal tobacco exposure.

PURPOSE OF REVIEW: This paper reviews results from published, in press, and conference proceedings from 2007 and 2008 that link in-utero tobacco exposure to neurodevelopmental outcomes in exposed offspring. RECENT FINDINGS: Prenatal tobacco exposure (PTE) affected speech processing, levels of irritability and hypertonicity, attention levels, ability to self-regulate, need to be handled, and response to novelty preference in infants. In early childhood, PTE effects were mostly behavioral outcomes including activity and inattention and externalizing behaviors, including conduct disorder and antisocial behavior. In adolescents, PTE predicted increased attention deficit hyperactivity disorder, modulation of the cerebral cortex and white matter structure, and nicotine addiction. Several studies found moderating effects with PTE and genetic susceptibilities including dopamine transporter, serotonergic synaptic function, and monomine oxidase pathways. Other studies suggested that environmental and genetic factors might be more important than the direct teratological effects of PTE. SUMMARY: The majority of studies reviewed were prospective and tobacco exposure was quantified biologically. Most demonstrated a direct association between PTE and neurodevelopmental outcomes. More work is needed to examine multifactorial influences. Effects of PTE on the offspring appear to be moderated by genetic variability, neurobehavioral disinhibition, and sex.