Through a teratological lens: A narrative review of exposure to stress and drugs of abuse during pregnancy on neurodevelopment.

Teratological research shows that both prenatal stress and prenatal substance exposure have a significant impact on neurodevelopmental outcomes in children. Using human research, the purpose of this narrative review is to explore the degree to which these exposures may represent complex prenatal and postnatal risks for the development of cognition and behavior in children. An understanding of the HPA axis and its function during pregnancy as well as the types and operationalization of prenatal stress provide a context for understanding the direct and indirect mechanisms by which prenatal stress affects brain and behavior development. In turn, prenatal substance exposure studies are evaluated for their importance in understanding variables that indicate a potential interaction with prenatal stress including reactivity to novelty, arousal, and stress reactivity during early childhood. The similarities and differences between prenatal stress exposure and prenatal substance exposure on neurodevelopmental outcomes including arousal and emotion regulation, cognition, behavior, stress reactivity, and risk for psychopathology are summarized. Further considerations for teratological studies of prenatal stress and/or substance exposure include identifying and addressing methodological challenges, embracing the complexity of pre-and postnatal environments in the research, and the importance of incorporating parenting and resilience into future studies.

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

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

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

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

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.

An examination of the association between prenatal cocaine exposure and brain activation measures of arousal and attention in young adults: An fMRI study using the Attention Network Task.

Prenatal drug exposure, including cocaine, alcohol, marijuana, and tobacco, is associated with deficits in behavioral regulation and attention. Using fMRI, the objective of this study was to characterize the association between prenatal cocaine exposure (PCE) and the underlying neural substrates associated with behavioral outcomes of attention. Forty-seven young adults were recruited for this study from the ongoing Maternal Health Practices and Child Development (MHPCD) Project, a longitudinal study of the effects of PCE on growth, behavior, and cognitive function. Three groups were compared: 1) prenatal exposure to cocaine, alcohol, marijuana, and tobacco (CAMT, n = 15), 2) prenatal exposure to alcohol, marijuana, and tobacco (AMT, n = 17), and 3) no prenatal exposure to drugs (Controls, n = 15). Subjects were frequency matched on gender, race, handedness, and 15-year IQ. This study used the theoretical model proposed by Posner and Peterson (1990), which posits three dissociable components of attention: alerting, orienting, and executive attention. Subjects completed a functional MRI (fMRI) scan while performing the Attention Network Task, a validated neuroimaging measure of the 3-network model of attention. Behavioral and fMRI data revealed no associations between PCE and task accuracy, speed of processing, or activation in key brain regions associated with each of the attention networks. The results of this study show that any subtle differences in brain function associated with PCE are not detectable using the ANT task and fMRI. These results should be interpreted in the context of other studies that have found associations between PCE and arousal with emotionally arousing stimuli, compared to this study that found no associations using emotionally neutral stimuli.

School achievement in 14-year-old youths prenatally exposed to marijuana.

The relation between prenatal marijuana exposure (PME) and school achievement was evaluated in a sample of 524 14-year-olds. Women were recruited during pregnancy and assessed, along with their offspring, at multiple phases from infancy to early adulthood. The sample represents a low-income population. Half of the adolescents are male and 55% are African American. School achievement was assessed with the Wechsler Individual Achievement Test (WIAT) Screener (Psychological Corporation, 1992). A significant negative relation was found between PME and 14-year WIAT composite and reading scores. The deficit in school achievement was mediated by the effects of PME on intelligence test performance at age 6, attention problems and depression symptoms at age 10, and early initiation of marijuana use. These findings suggest that the effects of PME on adolescent achievement are mediated by the earlier negative effects of PME on child characteristics. The negative impact of these characteristics on adolescent achievement may presage later problems in early adulthood.

Effects of prenatal cigarette smoke exposure on neurobehavioral outcomes in 10-year-old children of adolescent mothers.

In this prospective study, adolescent mothers (mean age=16; range=12-18; 70% African-American) were interviewed about their tobacco use during pregnancy. When their children were ten, mothers reported on their child's behavior and the children completed a neuropsychological battery. We examined the association between prenatal cigarette smoke exposure (PCSE) and offspring neurobehavioral outcomes on data from the 10-year phase (n=330). Multivariate regression analyses were conducted to test if PCSE predicted neurobehavioral outcomes, adjusting for demographic characteristics, maternal psychological characteristics, prenatal exposure to other substances, and exposure to environmental tobacco smoke. Independent effects of PCSE were found. Exposed offspring had more delinquent, aggressive, and externalizing behaviors (CBCL). They were more active (Routh, EAS, and SNAP) and impulsive (SNAP) and had more problems with peers (SNAP). On the Stroop test, deficits were observed on the more complex interference task that requires both selective attention and response inhibition. The significant effects of PCSE on neurobehavioral outcomes were found for exposure to as few as 10 cigarettes per day. Most effects were found from first trimester PCSE exposure. These results are consistent with results from an earlier assessment when the children were age 6, demonstrating that the effects of prenatal tobacco exposure can be identified early and are consistent through middle childhood.

Effects of prenatal tobacco, alcohol and marijuana exposure on processing speed, visual-motor coordination, and interhemispheric transfer.

Deficits in motor control are often reported in children with prenatal alcohol exposure (PAE). Less is known about the effects of prenatal tobacco exposure (PTE) and prenatal marijuana exposure (PME) on motor coordination, and previous studies have not considered whether PTE, PAE, and PME interact to affect motor control. This study investigated the effects of PTE, PAE, and PME as well as current drug use on speed of processing, visual-motor coordination, and interhemispheric transfer in 16-year-old adolescents. Data were collected as part of the Maternal Health Practices and Child Development Project. Adolescents (age 16, n=320) participating in a longitudinal study of the effects of prenatal substance exposure on developmental outcomes were evaluated in this study. The computerized Bimanual Coordination Test (BCT) was used to assess each domain of function. Other important variables, such as demographics, home environment, and psychological characteristics of the mother and adolescent were also considered in the analyses. There were significant and independent effects of PTE, PAE, and PME on processing speed and interhemispheric transfer of information. PTE and PME were associated with deficits in visual-motor coordination. There were no interactions between PAE, PTE, and PME. Current tobacco use predicted deficits in speed of processing. Current alcohol and marijuana use by the offspring were not associated with any measures of performance on the BCT.

Body size and intelligence in 6-year-olds: are offspring of teenage mothers at risk?

OBJECTIVES: Children born to teenage mothers are at risk for more physical and cognitive problems than those born to adult mothers. Our objective was to examine differences in size and intelligence between two cohorts of offspring born to adolescent (n = 357) and adult mothers (n = 668) who attended the same prenatal clinic. METHODS: Two prospective study cohorts assessed children from gestation through age 6 years. The adult cohort was studied in the mid-1980's and the teen cohort was evaluated in the mid-1990's. Both samples were of low socio-economic status. The same study design and measures allowed us to adjust for the covariates of size and IQ. RESULTS: Offspring of adolescent mothers had a significantly smaller mean head circumference (5 mm) (HC) and higher body mass index (BMI) than offspring of adult mothers. Offspring of adolescent mothers scored significantly lower than the offspring of adult mothers on the Stanford-Binet (SBIS) composite score (4 points), and the quantitative (6.2 points), verbal reasoning (4.8 points), and short-term memory (3.9 points) area scores. Additional predictors of child IQ were maternal IQ, home environment, race, and number of siblings. When child HC was entered into our final regression model for the SBIS, maternal age and HC significantly predicted the composite score, the verbal reasoning, and short-term memory area scores. A 1 cm decrease in HC predicted a 1 point decrease in the SBIS composite score. CONCLUSIONS: Compared to offspring of adult women, children of adolescent mothers have lower mean scores on cognitive measures, smaller head circumference, and higher BMI. These differences were significant after adjusting for differences between the two groups. Adolescent mothers and their children would benefit from interventions such as parenting support, education about nutritional needs, and advice on enriching the environments of their children.

Verbal and visuospatial learning and memory function in children with moderate prenatal alcohol exposure.

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.