Search Results (9)

Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral problem in children. Multiple risk factors, including prenatal substance exposure, have been associated with this disorder. Objectives: We determined (1) the rate of ADHD in children with prenatal cocaine exposure (PCE) as compared to those non-exposed, (2) the association of ADHD with the infant’s sex, race, and birth weight, maternal age and education, and other known risk factors, and factors that may mediate the relationship between these risk factors and ADHD. Methods: This was a secondary analysis of data from the Maternal Lifestyle Study for a long-term follow-up. ADHD was defined as any diagnosis of attention deficit, hyperactivity disorder, or the combination, from the National Institute of Mental Health Diagnostic Interview Schedule for Children (NIMH DISC) administered to children, ages 11 or 14 years. The main exposure variable was PCE. Independent variables included infant and maternal characteristics, caretaker psychopathology, and maternal–child conflict. Mediators evaluated were the child’s impulsivity at 4 years of age and attention problems at 5 years from the Child Behavior Checklist. Results: Path analysis revealed that the effects of risk variables, including PCE, were mediated through the child’s attention problems at age 5 years. Child’s impulsivity, which was significantly associated with attention problems, was also a mediator between PCE and ADHD. Male sex had a direct path to ADHD. Conclusions: Our findings lend support to early screening before 4 years of age in children with PCE or other risk factors for ADHD. Behavioral interventions provided during early childhood may mitigate the later diagnosis or severity of ADHD. Full article

Substance use during pregnancy is an increasingly important yet under-recognized threat to maternal and child health. This narrative review synthesizes the current evidence available on the epidemiology, pathophysiology, clinical management, and policy landscape of prenatal exposure to alcohol, tobacco, opioids, benzodiazepines, cocaine, cannabis, methamphetamines, and other synthetic drugs. All major psychoactive substances readily cross the placenta and can remain detectable in breast milk, leading to a shared cascade of obstetric complications (hypertensive disorders, placental abruption, pre-term labor), fetal consequences (growth restriction, structural malformations), and neonatal morbidities such as neonatal abstinence syndrome and sudden infant death. Mechanistically, trans-placental diffusion, oxidative stress, inflammatory signaling, and placental vascular dysfunction converge to disrupt critical neuro- and cardiovascular developmental windows. Early identification hinges on the combined use of validated screening questionnaires (4 P’s Plus, CRAFFT, T-ACE, AUDIT-C, TWEAK) and matrix-specific biomarkers (PEth, EtG, FAEE, CDT), while effective treatment requires integrated obstetric, addiction, and mental health services. Medication for opioid use disorders, particularly buprenorphine, alone or with naloxone, confers superior neonatal outcomes compared to methadone and underscores the value of harm-reducing non-punitive care models. Public-health strategies, such as Mexico’s “first 1 000 days” framework, wrap-around clinics, and home-visiting programs, demonstrate the potential of multisectoral interventions, but are hampered by structural inequities and punitive legislation that deter care-seeking. Research gaps persist in polysubstance exposure, culturally tailored therapies, and long-term neurodevelopmental trajectories. Multigenerational, omics-enabled cohorts, and digital longitudinal-care platforms represent promising avenues for closing these gaps and informing truly preventive perinatal health policies. Full article

Clinical and animal studies suggest that multiple brain systems are involved in mediating reward-motivated and related emotional behavior including the consumption of commonly used drugs and palatable food, and there is evidence that the repeated ingestion of or exposure to these rewarding substances may in turn stimulate these brain systems to produce an overconsumption of these substances along with co-occurring emotional disturbances. To understand this positive feedback loop, this review focuses on a specific population of hypothalamic peptide neurons expressing melanin-concentrating hormone (MCH), which are positively related to dopamine reward and project to forebrain areas that mediate this behavior. It also examines neurons expressing the peptide hypocretin/orexin (HCRT) that are anatomically and functionally linked to MCH neurons and the molecular systems within these peptide neurons that stimulate their development and ultimately affect behavior. This report first describes evidence in animals that exposure in adults and during adolescence to rewarding substances, such as the drugs alcohol, nicotine and cocaine and palatable fat-rich food, stimulates the expression of MCH as well as HCRT and their intracellular molecular systems. It also increases reward-seeking and emotional behavior, leading to excess consumption and abuse of these substances and neurological conditions, completing this positive feedback loop. Next, this review focuses on the model involving embryonic exposure to these rewarding substances. In addition to revealing a similar positive feedback circuit, this model greatly advances our understanding of the diverse changes that occur in these neuropeptide/molecular systems in the embryo and how they relate, perhaps causally, to the disturbances in behavior early in life that predict a later increased risk of developing substance use disorders. Studies using this model demonstrate in animals that embryonic exposure to these rewarding substances, in addition to stimulating the expression of peptide neurons, increases the intracellular molecular systems in neuroprogenitor cells that promote their development. It also alters the morphology, migration, location and neurochemical profile of the peptide neurons and causes them to develop aberrant neuronal projections to forebrain structures. Moreover, it produces disturbances in behavior at a young age, which are sex-dependent and occur in females more than in males, that can be directly linked to the neuropeptide/molecular changes in the embryo and predict the development of behavioral disorders later in life. These results supporting the close relationship between the brain and behavior are consistent with clinical studies, showing females to be more vulnerable than males to developing substance use disorders with co-occurring emotional conditions and female offspring to respond more adversely than male offspring to prenatal exposure to rewarding substances. It is concluded that the continued consumption of or exposure to rewarding substances at any stage of life can, through such peptide brain systems, significantly increase an individual’s vulnerability to developing neurological disorders such as substance use disorders, anxiety, depression, or cognitive impairments. Full article

Background: Polysubstance use, particularly combining opioids with stimulants such as cocaine, is rising among individuals with substance use disorders. This practice aims to balance cocaine’s stimulant effects with opioids’ sedative effect, potentially decreasing adverse outcomes. We hypothesized that concurrent exposure to cocaine and opioids would reduce the risk of neonatal opioid withdrawal syndrome (NOWS) compared to opioid use alone. Methods: This analysis draws from an ongoing prospective study of maternal substance use (SUD) at Regional One Health’s perinatal center in Memphis, TN, and included mothers and their infants born between 2018 and 2022. Maternal SUD was identified via screening questionnaires, urine toxicology, or umbilical cord tissue analysis. Participants were grouped into using (a) opioids with cocaine (OwC) and (b) opioids without cocaine (OwoC). Univariate and regression analyses were conducted to assess the risk of NOWS. Results: A total of 353 infants were born to 342 mothers, with 31% (110/353) of the infants born to women who used cocaine along with opioids. While maternal demographics were similar, the OwC group had significantly lower rates of prenatal care, chronic pain history, and MOUD enrollment (p = 0.03). Infants in the OwC group had significantly higher rates of NOWS (p < 0.01), longer hospital stays (p < 0.01), and 6.5 times greater odds of developing NOWS (p < 0.001). NOWS was associated with an average 15-day increase in the length of stay for term infants (95% CI: 11.2, 18.8; p < 0.001). Conclusions: Contrary to our hypothesis, our study highlights the significant impact of maternal cocaine use on the increased likelihood of NOWS and extended hospital stays for affected infants. Full article

Infantile occult exposure to cocaine in domestic environments represents a complex clinical and medico-legal problem, which can be associated with abuse and neglect and with potential short- and long-term health risks for children. The authors present a retrospective study on 764 children under 14 years old who accessed the Emergency Department of IRCCS Meyer from 2016 to 2023 and were included in the GAIA (Child and Adolescent Abuse Group) protocol for suspected maltreatment and abuse, and for which a urine toxicology analysis was performed. The aim is to discuss the medico-legal implications and highlight the need for a thorough evaluation and management of such situations. Urine screening tests for substances of abuse (e.g., cocaine, opiates, etc.) were performed with an EMIT^® Siemens VIVA-E drug testing system (Siemens, Newark DE) in 124 cases for which the child’s clinical condition raised suspicion of intoxication, or the family context indicated distress or substance abuse dependency. The screening results revealed the presence of cocaine and its main metabolite, benzoylecgonine, in the urine of 11 children. In one case, a single girl was brought to the Emergency Department by staff from the facility where she and her mother were staying. In most of the cases, children were brought to the Emergency Department by their parents who accessed the Emergency Department due to various clinical manifestations (drowsiness, agitation, seizures, hypotonia, diarrhea, vomiting, etc.), except for one case of eye trauma suspected to be caused by abuse or neglect by one of the parents. Three of the children did not have signs or symptoms attributable to substance exposure, whilst eight of the cases presented some of the symptoms associated with occult infant exposure to cocaine, such as neurological manifestations, seizures, gastrointestinal symptoms, and respiratory depression. The probable mode of intake was mostly through breastfeeding and continuous environmental exposure due to domestic contamination or inhalation of “crack”. In the case of a 12-hour-old infant, there was probable prenatal in utero exposure. All the children were hospitalized, some for medical reasons and others solely as a precautionary measure for proper care. In all cases, a report was made to the Prosecutors as required by the Italian Penal Code, as well as to the Court of Minor. The study highlighted the importance of a multidisciplinary approach involving pediatricians, social workers, and forensics, as well as close collaboration with the relevant authorities, as the Gaia service at IRCCS Meyer offers. The occasional detection of cocaine in cases that showed no suspicion of intoxication led to a modification of the procedure and the development of a standardized protocol at IRCCS Meyer both in terms of prevention and in the detection and interception of hidden cases, in order to intervene early and initiate the necessary care pathways (secondary prevention). This protocol includes routine toxicological urine testing in all suspected or confirmed cases of child abuse, not just in those where symptoms might suggest a suspicion of intoxication. Full article

Children and youths diagnosed with FASD may experience a range of adverse health and social outcomes. This cross-sectional study investigated the characteristics and outcomes of children and youths diagnosed with FASD between 2015 and 2018 at the Sunny Hill Centre in British Columbia, Canada and examined the relationships between prenatal substance exposures, FASD diagnostic categories, and adverse health and social outcomes. Patient chart data were obtained for 1187 children and youths diagnosed with FASD and analyzed. The patients (mean age: 9.7 years; range: 2–19) had up to 6 physical and 11 mental health disorders. Prenatal exposure to other substances (in addition to alcohol) significantly increased the severity of FASD diagnosis (OR: 1.18): the odds of FASD with sentinel facial features (SFF) were 41% higher with prenatal cigarette/nicotine/tobacco exposure; 75% higher with exposure to cocaine/crack; and two times higher with exposure to opioids. Maternal mental health issues and poor nutrition also increase the severity of FASD diagnosis (60% and 6%, respectively). Prenatal exposure to other substances in addition to alcohol significantly predicts involvement in the child welfare system (OR: 1.52) and current substance use when adjusted for age (aOR: 1.51). Diagnosis of FASD with SFF is associated with an increased number of physical (R² = 0.071, F (3,1183) = 30.51, p = 0.000) and mental health comorbidities (R² = 0.023, F (3,1185) = 9.51, p = 0.000) as compared to FASD without SFF adjusted for age and the number of prenatal substances. Screening of pregnant women for alcohol and other substance use, mental health status, and nutrition is extremely important. Full article

Fetal alcohol spectrum disorder (FASD) is a set of conditions resulting from prenatal alcohol exposure (PAE). FASD is estimated to affect between 2% and 5% of people in the United States and Western Europe. The exact teratogenic mechanism of alcohol on fetal development is still unclear. Ethanol (EtOH) contributes to the malfunctioning of the neurological system in children exposed in utero by decreasing glutathione peroxidase action, with an increase in the production of reactive oxygen species (ROS), which causes oxidative stress. We report a case of a mother with declared alcohol abuse and cigarette smoking during pregnancy. By analyzing the ethyl glucuronide (EtG, a metabolite of alcohol) and the nicotine/cotinine in the mother’s hair and meconium, we confirmed the alcohol and smoking abuse magnitude. We also found that the mother during pregnancy was a cocaine abuser. As a result, her newborn was diagnosed with fetal alcohol syndrome (FAS). At the time of the delivery, the mother, but not the newborn, had an elevation in oxidative stress. However, the infant, a few days later, displayed marked potentiation in oxidative stress. The clinical complexity of the events involving the infant was presented and discussed, underlining also the importance that for cases of FASD, it is crucial to have more intensive hospital monitoring and controls during the initial days. Full article

Cocaine use disorder has been reported to cause transgenerational effects. However, due to the lack of standardized biomarkers, the effects of cocaine use during pregnancy on postnatal development and long-term neurobiological and behavioral outcomes have not been investigated thoroughly. Therefore, in this study, we examined extracellular vesicles (EVs) in adult (~12 years old) female and male rhesus monkeys prenatally exposed to cocaine (n = 11) and controls (n = 9). EVs were isolated from the cerebrospinal fluid (CSF) and characterized for the surface expression of specific tetraspanins, concentration (particles/mL), size distribution, and cargo proteins by mass spectrometry (MS). Transmission electron microscopy following immunogold labeling for tetraspanins (CD63, CD9, and CD81) confirmed the successful isolation of EVs. Nanoparticle tracking analyses showed that the majority of the particles were <200 nm in size, suggesting an enrichment for small EVs (sEV). Interestingly, the prenatally cocaine-exposed group showed ~54% less EV concentration in CSF compared to the control group. For each group, MS analyses identified a number of proteins loaded in CSF-EVs, many of which are commonly listed in the ExoCarta database. Ingenuity pathway analysis (IPA) demonstrated the association of cargo EV proteins with canonical pathways, diseases and disorders, upstream regulators, and top enriched network. Lastly, significantly altered proteins between groups were similarly characterized by IPA, suggesting that prenatal cocaine exposure could be potentially associated with long-term neuroinflammation and risk for neurodegenerative diseases. Overall, these results indicate that CSF-EVs could potentially serve as biomarkers to assess the transgenerational adverse effects due to prenatal cocaine exposure. Full article

Background: The accurate assessment of fetal exposure to psychoactive substances provides the basis for appropriate clinical care of neonates. The objective of this study was to identify maternal socio-demographic profiles and risk factors for prenatal exposure to drugs of abuse by measuring biomarkers in neonatal matrices. Methods: A prospective, observational cohort study was completed. Biomarkers of fetal exposure were measured in meconium samples. The mothers were interviewed using a questionnaire. Univariate and multivariate logistic regression analyses were performed. Results: A total of 372 mothers were included, 49 (13.2%) testing positive for psychoactive substances use: 24 (49.0%) for cannabis, 11 (22.5%) for ethyl glucuronide, six (12.2%) for cocaine, and in eight (16.3%) more than one psychoactive substance. Mothers who consumed any psychoactive substance (29.7 ± 6.6 years) or cannabis (27.0 ± 5.7 years) were younger than non-users (32.8 ± 6.2 years, p < 0.05). Cocaine (50.0% vs. 96.9%, p < 0.05) and polydrug users (37.5% vs. 96.9%, p < 0.05) showed a lower levels of pregnancy care. Previous abortions were associated with the use of two or more psychoactive substances (87.5% vs. 37.8%, p < 0.05). Single-mother families (14.3% vs. 2.5%, p < 0.05) and mothers with primary level education (75.5% vs. 55.1%, p < 0.05) presented a higher consumption of psychoactive substances. Independent risk factors that are associated with prenatal exposure include: maternal age < 24 years (odds ratio: 2.56; 95% CI: 1.12–5.87), lack of pregnancy care (odds ratio: 7.27; 95%CI: 2.51–21.02), single-mother families (odds ratio: 4.98; 95%CI: 1.37–8.13), and active tobacco smoking (odds ratio: 8.13; 95%CI: 4.03–16.43). Conclusions: These results will allow us to develop several risk-based drug screening approaches to improve the early detection of exposed neonates. Full article