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BACKGROUND: This study investigated the effects of moderate prenatal alcohol exposure on learning and memory in 14-year-old adolescents. The Children's Memory Scale was used to assess learning and memory function in the verbal/auditory and visual/spatial domains. In addition, both short- and long-term memory function were assessed. METHODS: Data were collected as part of the Maternal Health Practices and Child Development Project, a longitudinal study including 580 children and their mothers. Women were assessed during each trimester of pregnancy and with their children from birth to 16 years of age. At age 14, memory function was evaluated using the Children's Memory Scale, an assessment tool that measures learning and immediate and delayed memory function in the verbal and visual-spatial domains. RESULTS: Prenatal alcohol exposure during the first trimester predicted deficits in learning, short-term memory, and long-term memory, specifically in the verbal domain. Deficits in performance were specific to learning and memory of word-pairs. In addition, deficits in memory were mediated by learning performance. CONCLUSIONS: Results demonstrated that prenatal alcohol exposure lead to deficits in encoding processes as indicated by deficits in verbal learning. Initial deficits in acquisition were responsible for deficits in immediate and delayed recall of verbal information in children who were exposed to alcohol during pregnancy but did not have fetal alcohol syndrome. [ABSTRACT FROM AUTHOR]

Alcohol use across pregnancy causes growth and other abnormalities in the offspring. Confirmation of pregnancy leads some women to discontinue alcohol use and other women to continue use. The study discussed in this article assessed alcohol use at the first and third trimesters and at delivery for 393 pregnant African American women in an urban area. At the first trimester, 118 women were moderate to heavy drinkers (one or more drinks per day), compared with 38 women who were at delivery. Socioenvironmental and psychological differences were identified for both women who reduced consumption and women who continued. An understanding of continued drinkers' vulnerability to factors that influence their drinking behaviors demands the development of appropriate, early, and effective intervention strategies. Social welfare implications are discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Growth deficits are among the cardinal features for the diagnosis of fetal alcohol syndrome. Growth deficits have also been noted among those who were exposed to alcohol prenatally but who do not have fetal alcohol syndrome. Few studies have observed subjects past early and middle childhood, however, to evaluate the longer-term effects of prenatal alcohol exposure on growth in adolescence. This is a report of the effects of alcohol exposure during gestation on the size of the offspring at 14 years of age. METHODS: Women were recruited in their fourth prenatal month. These women were interviewed in the fourth and seventh months of pregnancy and at delivery. The women and their children were seen when the offspring were 14 years of age. RESULTS: Growth deficits associated with prenatal alcohol exposure were identified among the offspring at 14 years of age. Weight, height, head circumference, and skinfold thickness continued to be significantly affected by prenatal alcohol exposure after controlling for other significant predictors of size. These effects exhibited a dose-response pattern, and significant effects were found at levels below one drink per day. For example, first trimester alcohol exposure predicted weights of 152 lbs for the offspring of abstainers, 149 lbs for the offspring of light drinkers (>0 and <0.2 drinks per day), 143 lbs for the offspring of moderate drinkers (>0.2 and <0.89 drinks per day), and 136 lbs for the offspring of heavy drinkers (>0.89 drinks per day). CONCLUSIONS: Prenatal alcohol exposure continues to affect size at age 14 years in this cohort of children followed since their fourth month of gestation. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is an immunoinflammatory disease of the esophagus attributable to a complex interaction between genetic and environmental factors. While several genetic risk variants have been linked with EoE, we report a novel association between B-cell lymphoma/leukemia 11B genetic mutation in a child with dysmorphic facies, developmental delays, atopic comorbidities, and difficult-to-treat EoE. After a prolonged course of EoE and multiple esophagogastroduodenoscopies with biopsies, this patient achieved clinical and histologic remission on a combination of swallowed topical steroids and high-dose proton pump inhibitor (PPI) therapy. However, her EoE relapsed when we attempted to wean her off PPI, and it was finally controlled after adding PPI back to her regimen. This report underscores the importance of genetic testing in patients with unusual clinical features and difficult-to-treat EoE. Relevant to real-world clinical practice, this case also raises the question of the treatment goals in children with EoE and underlying genetic mutation(s)., Competing Interests: Girish Hiremath serves as a consultant to Bristol Myers Squibb, Regeneron, and Sanofi. Other authors declare no conflict of interest., (© 2024 The Author(s). JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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., (© 2024 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

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., (© 2024 Research Society on Alcohol.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (© 2021 by the Research Society on Alcoholism.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Breast cancer brain metastases (BM) affect younger women disproportionally, including those lacking estrogen receptor (ER), progesterone receptor, and HER2 (known as triple-negative breast cancer; TNBC). Previous studies in preclinical models showed that pre-menopausal levels of estradiol (E2) promote TNBC-BM through incompletely understood mechanisms involving reactive astrocytes. Herein, a novel mechanism involving E2-dependent upregulation of brain-derived neurotrophic factor (BDNF) in astrocytes, and subsequent activation of tumor cell tropomyosin kinase receptor B (TrkB), is identified. E2 increased experimental BM of TNBC 4T1BR5 and E0771 cells by 21 and 3.6 fold, respectively, compared to E2-depleted mice. ERα +  reactive astrocytes were found at early and late stages of BM, and E2 upregulated BDNF in ER + reactive astrocytes in vitro and in vivo. TrkB was expressed in TNBC brain-trophic cell lines, BM-patient-derived xenografts, and breast cancer BM. Conditioned media from E2-treated astrocytes (CM-E2) activated TrkB and downstream AKT, ERK, and PLC-γ signaling in TNBC cells, increasing their invasiveness and tumor-initiating capability in vitro. The promotion of BM by E2-activated astrocytes was found to be more complex, involving feedback loops and other receptor tyrosine kinases. In 4T1BR5 cells, there was a positive feedback loop whereby astrocytic BDNF induced cancer cell BDNF translation. Upregulation of cancer cell BDNF was required to promote full invasiveness of 4T1BR5 in response to CM-E2, and was observed in brain metastatic cells in E2-treated mice in vivo. Moreover, the non-competitive BDNF/TrkB inhibitor ANA-12 reduced E2-induced 4T1BR5 BM to levels similar to OVX mice. BDNF also activated EGFR in TrkB + EGFR + TNBC cells, suggesting that E2 action through astrocytes activates redundant pathways promoting BM. These findings have important therapeutic implications, as they provide a rationale to use E2-depletion therapies or TrkB inhibitors to prevent or delay development of BM in younger women.

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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 Δ 9 -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., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) often leads to substantial adverse cognitive and health outcomes, including permanent disability and death. Preventing these outcomes requires attenuation of the secondary biochemical damage that follows the initial biomechanical insult, but a clinically proven pharmacotherapeutic capable of such has not been identified. In fact, the heterogeneous nature of TBI and the complexity of secondary injury cascades suggest a polytherapeutic approach that targets multiple pathways might be necessary. We and others have reported that 17β-estradiol (E2) is neuroprotective in models of central nervous system injury. Although E2 is neuroprotective and favorably modulates several key components of secondary injury, it does not effectively block the destructive excitotoxic cascade. Thus, administering E2 in combination with a second drug that targets excitotoxicity, such as the FDA-approved uncompetitive NMDA receptor antagonist memantine hydrochloride, may provide additional benefits. Here, we assessed the neuroprotective potential of an acutely administered intravenous bolus dose of a combination of memantine and E2 after induction of experimental TBI in the clinically relevant lateral fluid percussion model. Our results indicate that the combination of these drugs conferred neuroprotection by increasing neuronal survival and decreasing neuronal degeneration in the hippocampus and cortex ipsilateral to injury. Furthermore, administration of this combination improved vestibulomotor deficits and modestly reduced anxiety. We conclude that further investigation of the neuroprotective potential of memantine administered with E2 is warranted., (Published by Elsevier Ltd.)

Brain metastases are an increasing burden among breast cancer patients, particularly for those with HER2 + and triple negative (TN) subtypes. Mechanistic insight into the pathophysiology of brain metastases and preclinical validation of therapies has relied almost exclusively on intracardiac injection of brain-homing cells derived from highly aggressive TN MDA-MB-231 and HER2 + BT474 breast cancer cell lines. Yet, these well characterized models are far from representing the tumor heterogeneity observed clinically and, due to their fast progression in vivo , their suitability to validate therapies for established brain metastasis remains limited. The goal of this study was to develop and characterize novel human brain metastasis breast cancer patient-derived xenografts (BM-PDXs) to study the biology of brain metastasis and to serve as tools for testing novel therapeutic approaches. We obtained freshly resected brain metastases from consenting donors with breast cancer. Tissue was immediately implanted in the mammary fat pad of female immunocompromised mice and expanded as BM-PDXs. Brain metastases from 3/4 (75%) TN, 1/1 (100%) estrogen receptor positive (ER + ), and 5/9 (55.5%) HER2 + clinical subtypes were established as transplantable BM-PDXs. To facilitate tracking of metastatic dissemination using BM-PDXs, we labeled PDX-dissociated cells with EGFP-luciferase followed by reimplantation in mice, and generated a BM-derived cell line (F2-7). Immunohistologic analyses demonstrated that parental and labeled BM-PDXs retained expression of critical clinical markers such as ER, progesterone receptor, epidermal growth factor receptor, HER2, and the basal cell marker cytokeratin 5. Similarly, RNA sequencing analysis showed clustering of parental, labeled BM-PDXs and their corresponding cell line derivative. Intracardiac injection of dissociated cells from BM-E22-1, resulted in magnetic resonance imaging-detectable macrometastases in 4/8 (50%) and micrometastases (8/8) (100%) mice, suggesting that BM-PDXs remain capable of colonizing the brain at high frequencies. Brain metastases developed 8-12 weeks after ic injection, located to the brain parenchyma, grew around blood vessels, and elicited astroglia activation characteristic of breast cancer brain metastasis. These novel BM-PDXs represent heterogeneous and clinically relevant models to study mechanisms of brain metastatic colonization, with the added benefit of a slower progression rate that makes them suitable for preclinical testing of drugs in therapeutic settings.

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., (Copyright © 2017 by the Research Society on Alcoholism.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., Competing Interests: All authors declare that they have no conflicts of interest., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (© 2015 Society for Public Health Education.)

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., (© 2014 John Wiley & Sons Ltd.)

Background: Recent data suggest that children of mothers who are obese before pregnancy, or who gain too much weight during pregnancy, may be at an increased risk of cognitive impairments., Methods: Mother-infant dyads enrolled in a birth cohort study in Pittsburgh, Pennsylvania (1983-1986), were followed from early pregnancy to 14 years postpartum (n=574). Math, reading and spelling achievements were assessed at ages 6 and 10 years using the Wide Range Achievement Test-Revised, and at age 14 years using the Wechsler Individual Achievement Test Screener. Self-reported total GWG was converted to gestational age-standardised z-scores. Generalised estimating equations were used to estimate the effects of GWG and pre-pregnancy body mass index (BMI) on academic achievement at 6, 10 and 14 years, while adjusting for maternal race, child sex, parity, employment, family income, maternal intelligence, maternal depression, pre-pregnancy BMI (in GWG models only) and the home environment., Results: The mean (SD) BMI was 23.4 (5.7) kg/m(2) and the mean (SD) GWG reported at delivery was 14.4 (5.9) kg. There was a significant non-linear association between pre-pregnancy BMI and an offspring's academic achievement. At 6, 10 and 14 years, an offspring's academic scores were inversely associated with pre-pregnancy BMI beyond 22 kg/m(2). High GWG (>1 SD) was associated with approximately 4-point lower reading (adjusted β (adjβ) -3.75, 95% CI -7.1 to -0.4) and spelling scores (adjβ -3.90, 95% CI -7.8 to -0.2), compared with GWG -1 to +1 SD., Conclusions: Future studies in larger and socioeconomically diverse populations are needed to confirm maternal weight and weight gain as causal determinants of a child's academic skills, and whether this effect persists into adulthood., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

We examined direct and indirect pathways between adverse environmental exposures during gestation and childhood and drinking in mid-adolescence. Mothers and their offspring (n=917 mother/child dyads) were followed prospectively from second trimester to a 16-year follow-up assessment. Interim assessments occurred at delivery, 6, 10, and 14years. Adverse environmental factors included gestational exposures to alcohol, tobacco, and marijuana, exposures to childhood maltreatment and violence, maternal psychological symptoms, parenting practices, economic and home environments, and demographic characteristics of the mother and child. Indirect effects of early child behavioral characteristics including externalizing, internalizing activity, attention, and impulsivity were also examined. Polytomous logistic regression analyses were used to evaluate direct effects of adverse environmental exposures with level of adolescent drinking. Structural equation modeling (SEM) was applied to simultaneously estimate the relation between early adversity variables, childhood characteristics, and drinking level at age 16 while controlling for significant covariates. Level of drinking among the adolescent offspring was directly predicted by prenatal exposure to alcohol, less parental strictness, and exposures to maltreatment and violence during childhood. Whites and offspring with older mothers were more likely to drink at higher levels. There was a significant indirect effect between childhood exposure to violence and adolescent drinking via childhood externalizing behavior problems. All other hypothesized indirect pathways were not significant. Thus most of the early adversity measures directly predicted adolescent drinking and did not operate via childhood behavioral dysregulation characteristics. These results highlight the importance of adverse environmental exposures on pathways to adolescent drinking., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 β: 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 β: -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., (© 2015 American Society for Nutrition.)

Background: Becoming a mother is a developmental transition that has been linked to desistance from substance use. However, timing of motherhood may be a key determinant of cannabis use in women, based on preliminary evidence from teenage mothers. The goal of this study was to identify trajectories of maternal cannabis use, and to determine if maternal age was associated with different trajectories of use., Methods: This prospective study examined 456 pregnant women recruited at a prenatal clinic, ranging in age from 13 to 42 years. The women were interviewed about their cannabis use 1 year prior to pregnancy and during each trimester of pregnancy, and at 6, 10, 14, and 16 years post-partum., Results: A growth mixture model of cannabis use reported at each time point clearly delineated four groups: non/unlikely to use, decreasing likelihood of use, late desistance, and increasing likelihood/chronic use (Lo-Mendell-Rubin adjusted LRT test statistic=35.7, p<.001). The youngest mothers were least likely to be in the "non/unlikely to use" group. Younger maternal age also differentiated between late desistance and increasing likelihood/chronic use, versus decreasing likelihood of use post-partum., Conclusions: This is the first study to demonstrate that younger mothers are more likely to use cannabis across 17 years, including later desistance post-partum and increasing/chronic use. Other substance use and chronic depressive symptoms were also associated with more frequent use. These findings have implications for both prevention and treatment of cannabis use in mothers., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: We examined the association between gestational weight gain (GWG) and offspring obesity at age 36 months., Methods: Mother-infant dyads (n = 609) were followed from a first study visit (mean [standard deviation]: 18.8 [2.7] weeks gestation) to 36 months postpartum. Total GWG over the entire pregnancy was defined as excessive or non-excessive according to the 2009 Institute of Medicine guidelines. Four mutually exclusive categories of excessive or non-excessive GWG across early (conception to first study visit) and late (first study visit to delivery) pregnancy defined GWG pattern. Body mass index (BMI) z-scores ≥95th percentile of the 2000 Centers for Disease Control (CDC) references defined offspring obesity at 36 months. Multivariable log-binomial models adjusted for pre-pregnancy BMI and breastfeeding were used to estimate the association between GWG and childhood obesity risk., Results: Nearly half of the women had total excessive GWG. Of these, 46% gained excessively during both early and late pregnancy while 22% gained excessively early and non-excessively late, and the remaining 32% gained non-excess weight early and excessively later. Thirteen per cent of all children were obese at 36 months. Excessive total GWG was associated with more than twice the risk of child obesity (adjusted risk ratio [95% confidence interval]: 2.20 [1.35, 3.61]) compared with overall non-excessive GWG. Compared with a pattern of non-excessive GWG in both early and late pregnancy, excessive GWG in both periods was associated with an increased risk of obesity (2.39 [1.13, 5.08])., Conclusions: Excessive GWG is a potentially modifiable factor that may influence obesity development in early childhood., (© 2014 World Obesity.)

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.

Background: Studies have demonstrated that an early age of onset of marijuana use (EAOM) is associated with a higher risk of developing psychotic symptoms (PS) compared to initiating marijuana use at a later age or not at all. Research has also found that prenatal marijuana exposure (PME) predicts EAOM. This report evaluates the relationships among PME, EAOM, and PS., Method: Subjects were initially interviewed in their fourth prenatal month. Women and offspring who completed the birth assessment (n = 763) were selected for follow-up. Women and their offspring were followed until the offspring were 22 years of age: 596 offspring were evaluated. At age 22, PS were assessed in the offspring with the Diagnostic Interview Schedule using DSM-IV criteria. Analyses controlled for significant covariates including other prenatal substance exposures, race, gender, and offspring substance use at 22 years., Results: PME and EAOM significantly predicted increased rates of PS at 22 years controlling for other significant covariates. The direct effect of PME on PS was marginally significant (p = 0.06) when EAOM was entered into the model and other covariates were fixed. In the mediation analysis, EAOM did not significantly mediate the association between PME and PS, controlling for significant covariates, nor was the indirect pathway significant when structural equation modeling was used. The total effect of the direct and indirect pathways was significant., Conclusions: In addition to EAOM, PME may also play a role in the association between marijuana use and the development of PS. This could highlight a new area for prevention.

The associations between prenatal cocaine exposure (PCE) and adolescent behavior, cognitive development, and physical growth were examined in 219 15-year-olds who have participated in a longitudinal study since their fourth gestational month. During the first trimester, 42% of the women used cocaine, with use declining across pregnancy. At the 15-year follow-up, the caregivers were, on average, 43 years old, had 13 years of education, and 50% were African American. First trimester PCE was not associated with global cognitive development or with measures of learning and memory. First trimester PCE was significantly related to adolescent-reported delinquent behavior, poorer problem solving and abstract reasoning, and reduced weight, height, and head circumference at 15 years. These results were significant after other factors that affect these domains were controlled in regression analyses. In addition, exposure to violence partially mediated the effect of PCE on delinquent behavior. These adolescent domains are important because they are predictors of poorer adult functioning., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Studies have reported effects of prenatal marijuana exposure (PME) on cognitive and behavioral outcomes. An earlier publication from this study found that PME predicted early onset of marijuana use and frequency of marijuana use at age 14. No study has reported the effects of PME on marijuana use in young adulthood. This is a developmental period when substance use peaks, and by which, initiation of substance use has largely occurred., Methods: Subjects were from a longitudinal cohort. Women were interviewed initially in their fourth prenatal month and women and their offspring were followed through 22 years. Significant covariates of offspring marijuana use at 22 years were identified and controlled for using ordinal logistic regression., Results: PME predicted marijuana use in the offspring at 22 years after controlling for significant covariates. Prenatal alcohol exposure, offspring race, gender, and age were also significant predictors, but family history of substance abuse or disorder, and sociodemographic and psychological characteristics of the mother and offspring were not. This association was not moderated by gender or race., Conclusions: PME is associated with subsequent marijuana use in young adulthood after considering the effects of other significant factors. These findings have important implications for public health given the recent trend toward legitimization of marijuana use., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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.