Effects Of Prenatal Drug Exposure Research Articles

Co-occurrence of Psychopathology Problems in At-Risk Adolescents.

No known studies have investigated co-occurrence of psychopathology problems in adolescents with biologic and/or environmental susceptibility, including prenatal drug exposure. This study identified comorbidity patterns of psychopathology problems by utilizing data from urban, primarily African American, youth, majority of whom were at heightened risk for exposure to drugs in utero. The roles of Research Domain Criteria (RDoC)-informed behavioral constructs of the Negative Valence (irritability) and Social Process Systems (social disinhibition) as antecedents of the comorbidity patterns were further examined. Lastly, the predictive validity of the identified patterns was evaluated in relation to emerging adulthood outcomes. Participants were 358 urban adolescents, primarily African Americans, drawn from a 21-year prospective birth-cohort study of the effects of prenatal drug exposure. Psychopathology problems were assessed at age 15. Irritability and social disinhibition were self-reported at age 12. Emerging adulthood outcomes were measured at age 21. Latent class modeling indicated four patterns: Normative (57%), substance-use (SU; 24%), mental-health-problems-without-substance-use (MH; 11%), and substance-use-and-other-mental-health-problems (SUMH; 7%). Higher irritability increased the odds of developing the MH pattern, whereas higher social disinhibition increased the odds of developing the SU pattern. The odds of manifesting the SUMH pattern were higher for children with higher irritability. For children with higher social disinhibition, the odds of manifesting the SUMH pattern were higher at a trend level. Adolescent comorbidity patterns were differentially associated with problematic tobacco and marijuana use and clinically relevant mental health problems in emerging adulthood, and completion of high school education. Peri-pubertal identification of individual differences in irritability and social disinhibition may mitigate the emergence of adolescent psychopathology, which could influence emerging adulthood adjustment in this at-risk population.

Independent and Interactive Effects of Prenatal Drug Exposure and Childhood Trauma on Emotion Reactivity in Youth

Development of emotion regulation may inform predisposition or resilience to affective psychopathologies. While small cohort studies have identified prenatal drug exposure (PDE) and childhood trauma (CT) as factors that impact such development, a large-scale assessment of their interactive impact is warranted. Using data from the ABCD Study, we hypothesize that PDE and CT independently and interactively will be associated with altered activity of neural substrates underlying emotion processing in children exposed to PDE and CT.

Behavioral and Gene Regulatory Responses to Developmental Drug Exposures in Zebrafish.

Developmental consequences of prenatal drug exposure have been reported in many human cohorts and animal studies. The long-lasting impact on the offspring—including motor and cognitive impairments, cranial and cardiac anomalies and increased prevalence of ADHD—is a socioeconomic burden worldwide. Identifying the molecular changes leading to developmental consequences could help ameliorate the deficits and limit the impact. In this study, we have used zebrafish, a well-established behavioral and genetic model with conserved drug response and reward pathways, to identify changes in behavior and cellular pathways in response to developmental exposure to amphetamine, nicotine or oxycodone. In the presence of the drug, exposed animals showed altered behavior, consistent with effects seen in mammalian systems, including impaired locomotion and altered habituation to acoustic startle. Differences in responses seen following acute and chronic exposure suggest adaptation to the presence of the drug. Transcriptomic analysis of exposed larvae revealed differential expression of numerous genes and alterations in many pathways, including those related to cell death, immunity and circadian rhythm regulation. Differential expression of circadian rhythm genes did not correlate with behavioral changes in the larvae, however, two of the circadian genes, arntl2 and per2, were also differentially expressed at later stages of development, suggesting a long-lasting impact of developmental exposures on circadian gene expression. The immediate-early genes, egr1, egr4, fosab, and junbb, which are associated with synaptic plasticity, were downregulated by all three drugs and in situ hybridization showed that the expression for all four genes was reduced across all neuroanatomical regions, including brain regions implicated in reward processing, addiction and other psychiatric conditions. We anticipate that these early changes in gene expression in response to drug exposure are likely to contribute to the consequences of prenatal exposure and their discovery might pave the way to therapeutic intervention to ameliorate the long-lasting deficits.

Alterations in Excitatory and Inhibitory Synaptic Development Within the Mesolimbic Dopamine Pathway in a Mouse Model of Prenatal Drug Exposure.

The rise in rates of opioid abuse in recent years in the United States has led to a dramatic increase in the incidence of neonatal abstinence syndrome (NAS). Despite improved understanding of NAS and its acute symptoms, there remains a paucity of information regarding the long-term effects of prenatal exposure to drugs of abuse on neurological development. The primary goal of this study was to investigate the effects of prenatal drug exposure on synaptic connectivity within brain regions associated with the mesolimbic dopamine pathway, the primary reward pathway associated with drug abuse and addiction, in a mouse model. Our secondary goal was to examine the role of the Ca+2 channel subunit α2δ-1, known to be involved in key developmental synaptogenic pathways, in mediating these effects. Pregnant mouse dams were treated orally with either the opioid drug buprenorphine (commonly used in medication-assisted treatment for substance use patients), gabapentin (neuropathic pain drug that binds to α2δ-1 and has been increasingly co-abused with opioids), a combination of both drugs, or vehicle daily from gestational day 6 until postnatal day 11. Confocal fluorescence immunohistochemistry (IHC) imaging of the brains of the resulting wild-type (WT) pups at postnatal day 21 revealed a number of significant alterations in excitatory and inhibitory synaptic populations within the anterior cingulate cortex (ACC), nucleus accumbens (NAC), and medial prefrontal cortex (PFC), particularly in the buprenorphine or combinatorial buprenorphine/gabapentin groups. Furthermore, we observed several drug- and region-specific differences in synaptic connectivity between WT and α2δ-1 haploinsufficient mice, indicating that critical α2δ-1-associated synaptogenic pathways are disrupted with early life drug exposure.

Effect of Prenatal Drug Exposure on White Matter Development in Adolescents

Effect of Prenatal Drug Exposure on White Matter Development in Adolescents

Are patients of a large paediatric nephrology department an appropriate population to investigate long-term effects of prenatal drug exposure in a retrospective approach?

Are patients of a large paediatric nephrology department an appropriate population to investigate long-term effects of prenatal drug exposure in a retrospective approach?

Effects of Prenatal Drug Exposure on Children’s Working Memory: A Systematic Review

Effects of Prenatal Drug Exposure on Children’s Working Memory: A Systematic Review

Prenatal drug exposure and neurodevelopmental programming of glucocorticoid signalling.

Prenatal neurodevelopment is dependent on precise functioning of multiple signalling pathways in the brain, including those mobilised by glucocorticoids (GC) and endocannabinoids (eCBs). Prenatal exposure to drugs of abuse, including opioids, alcohol, cocaine and cannabis, has been shown to not only impact GC signalling, but also alter functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Such exposures can have long-lasting neurobehavioural consequences, including alterations in the stress response in the offspring. Furthermore, cannabis contains cannabinoids that signal via the eCB pathway, which is linked to some components of GC signalling in the adult brain. Given that GCs are frequently used in pregnancy to prevent complications of prematurity, and also that rates of cannabis use in pregnancy are increasing, the likelihood of foetal co-exposure to these compounds is high and may have additional implications for long-term neurodevelopment. Here, we present a discussion of GC signalling and the HPA axis, as well as the effects of prenatal drug exposure on these pathways and the stress response, and we explore the interactions between GC and EC signalling in the developing brain and potential for neurodevelopmental consequences.

S63. Effects of Prenatal Drug Exposure on Amygdala-mPFC Connectivity During the First Year of Life

S63. Effects of Prenatal Drug Exposure on Amygdala-mPFC Connectivity During the First Year of Life

Pharmacoepidemiology in pregnancy

Taking a medication is usually a challenge for a pregnant woman as the beneficial drug effect on the mother has to be considered regarding its potential adverse effects, not only for her but also for her unborn child. As medication use is common in pregnant women, by chance or necessity, it gives the opportunity to evaluate the consequences of prenatal drug exposure in real life through pharmacoepidemiological studies. This paper provides an overview of data sources, study designs and data analysis methods that can be used for pregnancy medication safety studies. In the future, the implementation of responsive international networks may be the keystones of drug evaluation in pregnancy.

A Monoclonal Antibody against 6-Acetylmorphine Protects Female Mice Offspring from Adverse Behavioral Effects Induced by Prenatal Heroin Exposure.

Escalating opioid use among fertile women has increased the number of children being exposed to opioids during fetal life. Furthermore, accumulating evidence links prenatal opioid exposure, including opioid maintenance treatment, to long-term negative effects on cognition and behavior, and presses the need to explore novel treatment strategies for pregnant opioid users. The present study examined the potential of a monoclonal antibody (mAb) targeting heroin's first metabolite, 6-acetylmorphine (6-AM), in providing fetal protection against harmful effects of prenatal heroin exposure in mice. First, we examined anti-6-AM mAb's ability to block materno-fetal transfer of active metabolites after maternal heroin administration. Next, we studied whether maternal mAb pretreatment could prevent adverse effects in neonatal and adolescent offspring exposed to intrauterine heroin (3 × 1.05 mg/kg). Anti-6-AM mAb pretreatment of pregnant dams profoundly reduced the distribution of active heroin metabolites to the fetal brain. Furthermore, maternal mAb administration prevented hyperactivity and drug sensitization in adolescent female offspring prenatally exposed to heroin. Our findings demonstrate that passive immunization with a 6-AM-specific antibody during pregnancy provides fetal neuroprotection against heroin metabolites, and thereby prevents persistent adverse behavioral effects in the offspring. An immunotherapeutic approach to protect the fetus against long-term effects of prenatal drug exposure has not been reported previously, and should be further explored as prophylactic treatment of pregnant heroin users susceptible to relapse.

Adult consequences of prenatal drug exposure.

Maternal drug use is not new but over the last few decades, the number of mothers using drugs of addiction has escalated to epidemic levels. These drugs are both legal (e.g. prescription medication) and illegal (e.g. heroin) and all will cross the placental barrier into the developing infant. The most immediate and obvious consequence of intra-uterine drug exposure is newborn withdrawal or the Neonatal Abstinence Syndrome (NAS) which is now, with prompt recognition and treatment, an uncommon cause of neonatal death. Thousands (if not millions) of adults most likely would have had a history of passive drug exposure during gestation and the outcomes of these people are unknown. Most are physically healthy and do not need extra medical attention but the effects of prenatal drug exposure may be subtle and extensive. Drug-use disorders are accompanied by a myriad of other adverse problems, including poverty, mental and physical health problems and inadequate parenting ability that may compound the negative effects of drugs. Emerging data suggest that vulnerability to health and neurocognitive issues are pervasive and long-lasting as are lifestyle issues. This review will address current evidence in this area and highlight the knowledge gaps that must be addressed in order to optimise the outcomes for this vulnerable and marginalised but rapidly expanding population of adults.

Long-term effects of prenatal drug exposure on the neural correlates of memory at encoding and retrieval

The objective of the current study was to examine what stage of memory (encoding or retrieval) may be compromised in adolescents with a history of prenatal drug exposure (PDE) and how the effects of PDE on memory ability are substantiated at the neural level. To achieve this goal, we examined memory performance and associated brain activations in adolescents with and without a history of PDE via event-related fMRI during encoding and retrieval. Consistent with previous studies, we found that PDE subjects remembered fewer items than community comparison subjects. However, there were no differences in behavior after adjusting for correct rejections (i.e., d′). Novel extensions of previous work are findings that PDE is associated with changes in brain activation during memory encoding but not during retrieval. These results suggest that less optimal memory performance often observed in adolescents with a history of PDE may result from variations in encoding rather than retrieval processes.

Prenatal exposure to recreational drugs affects global motion perception in preschool children

Prenatal exposure to recreational drugs impairs motor and cognitive development; however it is currently unknown whether visual brain areas are affected. To address this question, we investigated the effect of prenatal drug exposure on global motion perception, a behavioural measure of processing within the dorsal extrastriate visual cortex that is thought to be particularly vulnerable to abnormal neurodevelopment. Global motion perception was measured in one hundred and forty-five 4.5-year-old children who had been exposed to different combinations of methamphetamine, alcohol, nicotine and marijuana prior to birth and 25 unexposed children. Self-reported drug use by the mothers was verified by meconium analysis. We found that global motion perception was impaired by prenatal exposure to alcohol and improved significantly by exposure to marijuana. Exposure to both drugs prenatally had no effect. Other visual functions such as habitual visual acuity and stereoacuity were not affected by drug exposure. Prenatal exposure to methamphetamine did not influence visual function. Our results demonstrate that prenatal drug exposure can influence a behavioural measure of visual development, but that the effects are dependent on the specific drugs used during pregnancy.

ATTENTION FUNCTIONING IN CHILDREN WITH PRENATAL DRUG EXPOSURE.

Children born to drug abusers are exposed to teratogenic influences on intrauterine brain development and undergo postnatal withdrawal. We investigated the interplay of different domains and levels of attention functioning in 24 prenatally exposed and 25 nonexposed children who were 5 to 6 years old. Assessment included parent ratings and neuropsychological and electrophysiological methods. Exposed children had a higher prevalence of attention deficit hyperactivity symptoms, tended to have poorer performance in an attention test battery, and showed EEG alterations in P3 and N2c. Findings suggest long-term effects of prenatal drug exposure on specific domains and on different levels of attention functioning.

Poor actigraphic and self-reported sleep patterns predict delinquency and daytime impairment among at-risk adolescents

ObjectiveTo evaluate associations between actigraphic sleep patterns, subjective sleep quality, and daytime functioning (ie, sleepiness, symptoms of depression, and delinquency and other conduct problems) in at-risk adolescents. DesignProspective, observational cohort study. SettingProvidence, RI, predominantly home and school and 2 visits to the Brown Center for the Study of Children at Risk. ParticipantsA diverse group of low-income 13-year-olds (n = 49) with and without prenatal drug exposure. InterventionsNone. MeasurementsActigraphy, sleep diaries, and sleep and health questionnaires. ResultsAbove and beyond the effects of prenatal drug exposure and postnatal adversity, actigraphic daytime sleep was a significant predictor of daytime sleepiness and delinquency. Subjective sleep quality was a significant predictor of daytime sleepiness, delinquency, and depressive symptoms. Later bed times predicted increased delinquency. ConclusionsThere was a unique effect of actigraphic daytime sleep duration, subjective nighttime sleep quality, and bedtime on daytime functioning (ie, sleepiness, symptoms of depression, and delinquency and other conduct problems) of at-risk adolescents. In these vulnerable youth, these problematic sleep patterns may contribute to feeling and behaving poorly. Intervention studies with at-risk teens should be conducted to further explore the role of these sleep parameters on daytime functioning.

Prenatal drug exposure affects neonatal brain functional connectivity.

Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala-frontal, insula-frontal, and insula-sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala-frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention.

Prenatal drug exposure to illicit drugs alters working memory-related brain activity and underlying network properties in adolescence

The persistence of effects of prenatal drug exposure (PDE) on brain functioning during adolescence is poorly understood. We explored neural activation to a visuospatial working memory (VSWM) versus a control task using functional magnetic resonance imaging (fMRI) in adolescents with PDE and a community comparison group (CC) of non-exposed adolescents. We applied graph theory metrics to resting state data using a network of nodes derived from the VSWM task activation map to further explore connectivity underlying WM functioning. Participants (ages 12–15years) included 47 adolescents (27 PDE and 20 CC). All analyses controlled for potentially confounding differences in birth characteristics and postnatal environment. Significant group by task differences in brain activation emerged in the left middle frontal gyrus (BA 6) with the CC group, but not the PDE group, activating this region during VSWM. The PDE group deactivated the culmen, whereas the CC group activated it during the VSWM task. The CC group demonstrated a significant relation between reaction time and culmen activation, not present in the PDE group. The network analysis underlying VSWM performance showed that PDE group had lower global efficiency than the CC group and a trend level reduction in local efficiency. The network node corresponding to the BA 6 group by task interaction showed reduced nodal efficiency and fewer direct connections to other nodes in the network. These results suggest that adolescence reveals altered neural functioning related to response planning that may reflect less efficient network functioning in youth with PDE.

Methodological Issues in Assessing the Impact of Prenatal Drug Exposure.

Prenatal drug exposure is a common public health concern that can result in perinatal complications, birth defects, and developmental disorders. The growing literature regarding the effects of prenatal exposure to specific drugs such as tobacco, alcohol, cocaine, and heroin is often conflicting and constantly changing. This review discusses several reasons why the effects of prenatal drug exposure are so difficult to determine, including variations in dose, timing, duration of exposure, polydrug use, unreliable measures of drug exposure, latent or “sleeper” effects, genetic factors, and socioenvironmental influences. In addition to providing research guidelines, this review also aims to help clinicians and policy makers to identify the strengths and weaknesses in studies investigating the effects of prenatal drug exposure. This knowledge may be used to make better informed decisions regarding the appropriate treatment for pregnant, drug-dependent women and their children.

Do Prenatally Methamphetamine-Exposed Adult Male Rats Display General Predisposition to Drug Abuse in the Conditioned Place Preference Test?

Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.