Prenatal Drug Exposure Research Articles

The moderating role of attachment on the association between childhood maltreatment and adolescent dating violence

Approximately 20% of female and 10% of male adolescents report violence in their dating relationships and there is a significant association between dating violence in adolescence and later perpetration of intimate partner violence (IPV) in adulthood. Identification of factors associated with dating violence can inform intervention and prevention efforts. This study was designed to examine the associations of early childhood maltreatment experience and involvement in adolescent dating violence. It also aimed to identify the moderating effect of insecure attachment styles on these associations.One hundred fifty adolescent who participated in a larger longitudinal study on prenatal drug exposure participated in this study. Participants completed self-report measures of childhood maltreatment at a standard follow-up visit between the ages of 15–19 years. Approximately 18 month later, they completed questionnaires on their attachment styles and level of dating violence perpetration and victimization.Hierarchical regression modeling revealed a significant main effect for childhood abuse but not insecure attachment on perpetration and victimization of dating violence. Avoidant attachment significantly moderated the relationship between childhood abuse exposure and dating violence: For adolescents who reported an avoidant attachment style, an increase in the level of experienced childhood maltreatment predicted significantly higher increases in victimization by dating violence, compared to those did not have avoidant attachment.Results suggest adolescents with child maltreatment history and avoidant attachment styles may be at higher risk for involvement in dating violence and support intervention efforts for fostering attachment relationship to attenuate the association between early exposures to maltreatment and involvement in dating violence later.

POMME cohort valuable tool to assess prenatal drug exposure

POMME cohort valuable tool to assess prenatal drug exposure

Early Postnatal Stress Impairs Cognitive Functions of Male Rats Persisting Until Adulthood.

Methamphetamine (MA) is the most abused “hard” illicit drug in the Czech Republic. Drugs abused during pregnancy are not hazardous merely to the mother, but also to developing fetuses. The offspring of drug-addicted mothers are also often exposed to perinatal stressors that may impair brain development of affected progeny. The present study examines the effect of perinatal stressors and drug exposure on cognitive function in male progeny. In the present study, rat mothers were divided into three groups according to drug treatment during pregnancy: controls (C); saline (SA, s.c., 1 ml/kg); MA (s.c., 5 mg/ml/kg). Litters were divided into two groups according to postnatal stressors: non-stressed controls (N); Maternal separation (MS). For evaluation of learning and memory, adult male progeny were tested in the Morris Water Maze (MWM). Our results revealed no significant effects caused by prenatal drug or prenatal stress exposure. On the other hand, chronic postnatal stress, mediated by MS, significantly impaired learning on the Place Navigation test. In addition, MS was associated with changes in search strategies on the Place Navigation, Probe, and Memory Recall tests. Specifically, postnatal stress increased thigmotaxis, indicating less awareness of the hidden platform. In conclusion, the present study provides evidence that exposure to early postnatal stress significantly impairs cognitive functions of male rats, which persists into adulthood.

Cortisol reactivity and weight gain among adolescents who vary in prenatal drug exposure.

Low inhibitory control is linked with weight gain among youth. Inhibitory problems are associated with disruption to the hypothalamic-pituitary-adrenal axis cortisol response. Increased cortisol predicts appetite and weight gain (though may be gender specific). This study hypothesized that cortisol reactivity explains the association between inhibition and weight gain while considering the moderating factors of early stressors to the hypothalamic-pituitary-adrenal axis (e.g. prenatal-drug exposure) and gender. Adolescents with prenatal-drug exposure (n=76) and non-exposed comparison adolescents (NE; n=61) completed the Conner's Continuous Performance Test and provided salivary cortisol samples. BMI z-score were measured at the initial and 12-month follow-up evaluations. A bootstrapped moderated mediation analysis was conducted to test for conditional indirect effects of cortisol reactivity. Lower inhibition was associated with increased cortisol reactivity among youth who were NE, and increased cortisol reactivity was associated with weight gain among girls. Cortisol reactivity mediated the relation between inhibition and BMI z-score change for the girls in the group who was NE. Increased cortisol reactivity may play a mechanistic role in predicting weight gain among non-prenatally drug-exposed girls. Cortisol reactivity may be a biomarker for targeted interventions to improve biological regulation and ultimately health risk among girls.

HPLC Method for Quantification of Caffeine and Its Three Major Metabolites in Human Plasma Using Fetal Bovine Serum Matrix to Evaluate Prenatal Drug Exposure.

Caffeine is recognized as the first-line therapeutic agent for apnea of prematurity. The dosage regimen is 10 mg/kg loading dose and 2.5 mg/kg maintenance dose. However, the plasma concentration achieved, not always, is therapeutically useful. It makes necessary to increase the doses to reach plasma concentration up to 30 or 35 μg/mL or even higher to attain therapeutic effect. To study why neonates have these differences, and whether these effects are linked to prenatal caffeine exposure, we had to develop an analytical method for an accurate measurement of caffeine and metabolites concentration. The analysis was carried out using fetal bovine serum (FBS) as biological matrix in a high-performance liquid chromatography with an ultraviolet detector method. This method allows acceptable chromatographic resolution between analytes in 15 minutes. It was validated and proved to be linear in the 0.1–40 µg/mL range for caffeine, paraxanthine, theobromine, and theophylline in the same chromatographic analysis. Accuracy for quality control samples for intra- and interday assays was ranged from 96.5 to 105.2% and 97.1 to 106.2%. Precision had CV no more than 10% in all concentration levels for all analytes. No differences were observed between quantification in human and FBS. This method was applied to quantify plasma drug concentration in mothers and their newborns in a Mexican northeast population. In our study, we confirmed self-reported caffeine maternal intake in 85.2% (n=23); meanwhile, in their newborn's plasma, it was detected only in 78% (n=21). Caffeine plasma concentrations in mother and newborn had a linear relationship, and no differences were observed between groups (mothers versus children). These results suggest that our analytical method and substitution of biological matrix was linear, precise, and accurate for caffeine quantification and could be used for measuring prenatal exposure and let us to study, in the future, concentration differences observed during apnea clinical treatment.

Testing the programming of temperament and psychopathology in two independent samples of children with prenatal substance exposure.

Prenatal programming models have rarely been applied to research on children with prenatal substance exposure, despite evidence suggesting that prenatal drug exposure is a form of stress that impacts neurodevelopmental outcomes and risk for psychopathology. Utilizing data from two longitudinal multisite studies comprising children prenatally exposed to substances as well as a nonexposed comparison group (Maternal Lifestyle Study, n = 1,388; Infant Development, Environment, and Lifestyle study, n = 412), we tested whether early phenotypic indicators of hypothesized programming effects, indexed by growth parameters at birth and infant temperament, served as a link between prenatal substance exposure and internalizing and externalizing behavior at age 5. Latent profile analysis indicated that individual differences in reactivity and regulation for infants prenatally exposed to substances was best characterized by four temperament profiles. These profiles were virtually identical across two independent samples, and demonstrated unique associations with adjustment difficulties nearly 5 years later. Results of path analysis using structural equation modeling also showed that increased prenatal substance exposure was linked to poorer growth parameters at birth, profiles of temperamental reactivity in infancy, and internalizing and externalizing behavior at age 5. This pathway was partially replicated across samples. This study was among the first to link known individual-level correlates of prenatal substance exposure into a specific pathway to childhood problem behavior. Implications for the developmental origins of a child's susceptibility to psychopathology as a result of intrauterine substance exposure are discussed.

Maternal methamphetamine exposure causes cognitive impairment and alteration of neurodevelopment-related genes in adult offspring mice

Prenatal drug exposure altered cognitive function in individuals, and may also impact their offspring's susceptibility to cognitive impairment. The high incidence of methamphetamine (METH) abuse among adolescents and women of childbearing age elevates the importance to determine the influence of maternal METH exposure on cognitive functions in the descendants. We hypothesized that maternal METH exposure affects cognitive behavior in offspring mice by disrupting gene expression associated with neural development. Here, female C57BL/6 mice were exposed to intermittent escalating doses of METH or saline from adolescence to adulthood, and then continued through pregnancy. Interestingly, male but not female offspring exhibited impaired short-term recognition memory and long-term spatial memory retention in novel object recognition and Morris water maze test respectively. Additionally, maternal METH exposure altered neurodevelopmental genes in both male and female offspring, and 12 differentially expressed genes between male and female were observed in the HPC and NAc regions. These differentially expressed genes are involved in neurogenesis, axon guidance, neuron migration and synapse of neural development circuits. Our observations suggest that maternal METH exposure induced differential expression patterns of neurodevelopment-related genes in the HPC and NAc of male and female mice, which may underlie the different cognitive behavior phenotypes in both genders.

The Policy to Practice Gap: Factors Associated With Practitioner Knowledge of CAPTA 2010 Mandates for Identifying and Intervening in Cases of Prenatal Alcohol and Drug Exposure

This article describes results from a state-wide survey of social services professionals ( n = 259) regarding knowledge of the Child Abuse Prevention and Treatment Act Reauthorization of 2010 (CAPTA), clinically based markers of prenatal substance exposure (PSE), and appropriate child protection responses following a PSE referral. Few respondents were aware of CAPTA, and knowledge of clinical markers of PSE and appropriate child protective services responses to prenatal exposure varied according to substance type (alcohol or drugs). Regression models revealed that fewer years in practice and fewer annual drug referrals predicted more drug-exposure knowledge. Fewer years in practice and awareness of CAPTA predicted more alcohol-exposure knowledge. Policy implementation strategies are needed to increase the likelihood that CAPTA achieves its desired intent, particularly with professionals who have been in the field longer and may be less open to changing practice behaviors.

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.

Ectopic neurogenesis induced by prenatal antiepileptic drug exposure augments seizure susceptibility in adult mice

Epilepsy is a neurological disorder often associated with seizure that affects ∼0.7% of pregnant women. During pregnancy, most epileptic patients are prescribed antiepileptic drugs (AEDs) such as valproic acid (VPA) to control seizure activity. Here, we show that prenatal exposure to VPA in mice increases seizure susceptibility in adult offspring through mislocalization of newborn neurons in the hippocampus. We confirmed that neurons newly generated from neural stem/progenitor cells (NS/PCs) are integrated into the granular cell layer in the adult hippocampus; however, prenatal VPA treatment altered the expression in NS/PCs of genes associated with cell migration, including CXC motif chemokine receptor 4 (Cxcr4), consequently increasing the ectopic localization of newborn neurons in the hilus. We also found that voluntary exercise in a running wheel suppressed this ectopic neurogenesis and countered the enhanced seizure susceptibility caused by prenatal VPA exposure, probably by normalizing the VPA-disrupted expression of multiple genes including Cxcr4 in adult NS/PCs. Replenishing Cxcr4 expression alone in NS/PCs was sufficient to overcome the aberrant migration of newborn neurons and increased seizure susceptibility in VPA-exposed mice. Thus, prenatal exposure to an AED, VPA, has a long-term effect on the behavior of NS/PCs in offspring, but this effect can be counteracted by a simple physical activity. Our findings offer a step to developing strategies for managing detrimental effects in offspring exposed to VPA in utero.

Treating Neonatal Abstinence Syndrome in a Rural Hospital: Lessons Learned

ObjectiveOur level 1 nursery and pediatric unit in a rural hospital adopted a family-centered, symptom-based oral morphine weaning protocol for neonatal abstinence syndrome (NAS) in 2009. Length of stay (LOS), treatment duration (TD), and hospital charges for infants treated for NAS were then compared to published data in neonatal intensive care units (NICUs) nationwide. MethodsThe electronic medical records of infants born January 1, 2011, to April 1, 2017, whose discharge diagnosis included an ICD-9 or ICD-10 code for NAS or prenatal drug exposure were paired with maternal electronic medical record and reviewed. TD was calculated by subtracting the last day morphine was provided from the day it was started, and LOS was calculated by subtracting the discharge date from the date of birth. Infant characteristics, maximum Finnegan score, breastfeeding, discharge disposition, maternal demographics, prenatal use of drugs or medications, and toxicology results were abstracted. Predictors of TD and LOS were analyzed, and hospital charges were enumerated. ResultsChart review identified 167 infants with prenatal drug exposure, 33 of whom were treated for NAS. Median TD for infants with NAS was 18 days (range, 9–37 days) compared to 15 days (range, 9–25 days) in NICUs. Median LOS for infants treated for NAS was 22 days (range, 12–41 days) compared to 20 days (range, 12–32 days) in NICUs, but hospital charges were less. Maternal prenatal use of cocaine (P = .016) predicted LOS. ConclusionsFamily-centered NAS treatment in a rural hospital lasted 2 to 3 days longer than in NICUs, largely as a result of social issues; however, hospital charges were less.

Long-term Outcome after Prenatal Drug Exposure

Although prenatal exposure to opioids, cannabinoids and cocaine is a frequent problem, only scarce data have been published on the long-term outcome in affected children and adolescents. While opioid-exposed children up to the age of 2 years show a reduced motor developmental pattern, data from meta-analyses up to adolescence show a strong trend for reduced performance with regard to cognitive function and behavior. Follow-up data after intrauterine cannabinoid exposure indicate reduced cognitive and reading abilities as well as abnormal findings in complex planning tests. Externalizing pathologies have been observed more frequently in boys. Prenatal cocaine exposure results in reduced cognitive and verbal development up to adolescence; however, differences are small but significant in meta-analyses. Interpretation of follow-up data with partially contradictory results may reflect methodological differences and a number of modifying co-factors, e.g., social conditions during the childhood period. These data should encourage further primary and secondary preventive attempts.

Blood lead levels and longitudinal language outcomes in children from 4 to 12 years

ObjectivesIn this study, the authors aimed to examine the association of a range of blood lead levels on language skills assessed at 4, 6, 10 and 12 years of age using a prospective longitudinal design controlling for potential confounding variables including maternal vocabulary, caregiver’s psychological distress and symptomatology, child’s race and prenatal drug exposure. MethodsThe participants (N = 278) were a subsample of a large longitudinal study that examined the association of prenatal drug exposure on children who were followed prospectively from birth and assessed for receptive and expressive language skills at 4, 6, 10 and 12 years of age. Blood lead levels were determined at 4-years of age by atomic absorption spectrometry. A mixed model approach with restricted maximum likelihood procedures was used to assess the association of lead on language outcomes. ResultsLongitudinal mixed model analyses suggested a negative effect of lead exposure on both receptive and expressive language, with the adverse outcomes of lead exposure appearing to become more prominent at 10 and 12 years. Higher caregiver vocabulary was positively associated with child’s language scores whereas caregiver psychological distress appeared to negatively affect language scores. Prenatal drug exposure was not related to the effects of lead on language skills. ConclusionsThese findings suggest that elevated blood lead levels occurring early in life may be associated with poorer language skills at older ages. A language rich environment may minimize the negative influence of early lead exposure on language skills, with psychological distress seemingly exacerbating the negative outcome.

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.

Birth outcomes after inadvertent use of category X drugs contraindicated in pregnancy: Where is the real risk?

Öztürk Z, Ölmez E, Gürpınar T, Vural K. Birth outcomes after inadvertent use of category X drugs contraindicated in pregnancy: Where is the real risk? Turk J Pediatr 2018; 60: 298-305. Drugs contraindicated in pregnancy are medicines that should be avoided by pregnant women, since they carry a concern for teratogenicity or there is no indication for their use during pregnancy. It does not mean that exposures to these drugs always cause harm. The aim of the present study was to investigate the risk of adverse outcomes following maternal exposure to the drugs contraindicated in pregnancy. We retrospectively analyzed prenatal drug exposure records of the pregnant patients referred to the clinical pharmacology consultation service in a tertiary-level university hospital from January 2007 until December 2012. Exposures to category X drugs (CXD) contraindicated in pregnancy were evaluated. After the expected date of delivery, we collected data about pregnancy complications and the outcomes. For comparison the women in the exposed group (N=52) were matched with a control group (N=162) of pregnant women without teratogenic exposure. We observed only one baby born with a birth defect (congenital cryptorchidism) in CXD group (2.6%) and four in control group (RR 0.91; 95% CI 0.10- 7.94). The rates of adverse pregnancy outcomes including miscarriage, preterm birth and congenital abnormality were not significantly different from controls. However, the rate of elective termination of pregnancy was higher in women exposed to CXD while pregnant (RR 2.54; 95% CI 1.11- 5.80, p = 0.027). Contraceptive failure and unintended pregnancy are the reasons for inadvertent drug exposure and choosing abortion. The high perception of teratogenic risk among pregnant women may cause terminations of pregnancies. Individual risk assessment and avoiding the phrase `CXD` or `contraindicated in pregnancy` in counseling may help to reduce maternal concerns about medication use in pregnancy.

Adolescent cannabis use and brain systems supporting adult working memory encoding, maintenance, and retrieval

Given prior reports of adverse effects of cannabis use on working memory, an executive function with a protracted developmental course during adolescence, we examined associations between developmental patterns of cannabis use and adult working memory (WM) processes. Seventy-five adults with longitudinal assessments of cannabis use (60 with reported use, 15 with no reported use) and prenatal drug exposure assessment completed a spatial WM task during fMRI at age 28. All subjects passed a multi-drug urine screen on the day of testing and denied recreational drug use in the past week. A fast event-related design with partial trials was used to separate the BOLD response associated with encoding, maintenance, and retrieval periods of the WM task. Behavioral results showed that subjects who began using cannabis earlier in adolescence had longer reaction times (RT) than those with later initiation. Cannabis age of onset was further associated with reduced posterior parietal cortex (PPC) encoding BOLD activation, which significantly mediated age of onset WM RT associations. However, cannabis age of onset brain-behavior associations did not differ between groups with a single reported use and those with repeated use, suggesting age of onset effects may reflect substance use risk characteristics rather than a developmentally-timed cannabis exposure effect. Within repeated cannabis users, greater levels of total cannabis use were associated with performance-related increases in dorsolateral prefrontal cortex (DLPFC) activation during maintenance. This pattern of significant results remained unchanged with inclusion of demographic and prenatal measures as covariates. Surprisingly, however, at the group level, cannabis users generally performed better than participants who reported never using cannabis (faster RT, higher accuracy). We extend previous investigations by identifying that WM associations with cannabis age of onset may be primary to PPC stimulus encoding activity, while the amount of cannabis use is associated with DLPFC maintenance processes. Poorer performance of participants who reported never using cannabis and the consistency of cannabis age of onset associations across single and repeated users limit interpretation of direct developmental effects of cannabis on WM in adulthood.

Does prenatal methamphetamine exposure induce sensitization to drugs in adulthood?

Behavioral sensitization is defined as augmented psychomotor activity, which can be observed after drug re-administration following withdrawal of repeated drug exposure. It has been shown that abuse of one drug can lead to increased sensitivity to certain other drugs. This effect of developed general drug sensitivity is called cross-sensitization and has been reported between drugs with similar as well as different mechanisms of action. There is growing evidence that exposure to drugs in utero not only causes birth defects and delays in infant development, but also impairs the neural reward pathways, in the brains of developing offspring, in such a way that it can increase the tendency for drug addiction later in life. This review summarizes the results of preclinical studies that focused on testing behavioral cross-sensitization, after prenatal Methamphetamine exposure, to drugs administered in adulthood, with both similar and different mechanisms of action. Traditionally, behavioral sensitization has been examined using the Open field or the Laboras Test to record locomotor activity, and the Conditioned Place Preference and Self-administration test to examine drug-seeking behavior. However, it seems that prenatal drug exposure can sensitize animals not only to the locomotor-stimulating and conditioning effects of drugs, but may also be responsible for modified responses to various drug effects.

Interventions and programs that support the health and development of infants with prenatal alcohol and/or drug exposure in foster care: a scoping review protocol.

The objective of this scoping review is to identify and describe caregiving interventions and program elements that support the health and development of infants with prenatal alcohol and/or drug exposure in foster care.

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.

Are changes in excitability in the hippocampus of adult male rats induced by prenatal methamphetamine exposure or stress?

Prenatal stress and drug exposure induce permanent alterations of the brain. Even though different brain structures are involved, alterations almost always refer to the hippocampus. The aim of this study was to investigate the excitability of hippocampal slices in low-magnesium epilepsy model of prenatally methamphetamine (MA, 5mg/kg sc.) or saline (sc., stress model) exposed animals in adult male rats. The second aim was to investigate, if a low dose of MA (1ml/kgs.c.) administered in adulthood changes the hippocampal activity of these animals. Adult Wistar male rats were divided into groups according to their prenatal treatment (C − naïve control; Sa − saline; MA − MA administration). One half of the animals was treated with a challenge dose of MA (1mg/kg sc.) 45min before hippocampal slices were cut. The activity of 350μ thick transversal slices of CA1 hippocampi was recorded (latencies of the first epileptiform discharge and the regular epileptiform activity) and evaluated in ACSF with low-magnesium concentration. Effects of prenatal exposure: The highest excitability was found in the Sa (prenatally stressed) group in respect to C and MA groups. This group developed also the highest number of seizure-like events. In addition, the prenatally MA treated group had also higher excitability than C group. Effects of the MA challenge dose: The challenge dose decreased the excitability of prenatally SA- exposed group. To conclude, even a mild prenatal stress significantly increases hippocampal excitability in adulthood and a challenge dose of MA is able to dampen it.