Prenatal Methamphetamine Research Articles

Neurocognitive and neurodevelopmental impact of prenatal methamphetamine exposure: A comparison study of prenatally exposed children with nonexposed ADHD peers

ABSTRACTPrenatal methamphetamine exposure has become an increasingly pervasive concern, especially in rural-based populations and populations of lower socioeconomic status. While research has begun to highlight the effects of prenatal methamphetamine exposure, the long-term impact of this exposure remains an under-investigated topic. This study attempts to investigate the neurocognitive and neurodevelopmental effects of prenatal methamphetamine exposure by comparing the index and full-scale IQ scores on the WISC-IV between a sample of clinically referred children prenatally exposed to methamphetamine (N = 80) and a sample of clinically referred nonexposed children diagnosed with ADHD (N = 44). Children prenatally exposed to methamphetamine showed significantly lower scores on all WISC-IV domains when compared to peers with ADHD. When taking into account polysubstance exposure to alcohol, these differences remained statistically significant, with the exception of the Processing Speed Index (PSI); children reported to have been prenatally exposed to methamphetamine and to alcohol (PME) remained below ADHD peers on all other WISC-IV index scores. Within the prenatally exposed sample, regression analyses indicated that age was a significant negative predictor of PSI scores. Overall findings suggest that prenatal methamphetamine exposure is associated with a notable cognitive impact independent of polysubstance exposure to alcohol, and that the impact of this exposure on processing speed skills may become more pronounced with age.

Mapping of the prenatal and postnatal methamphetamine effects on D1-like dopamine, M1 and M2 muscarinic receptors in rat central nervous system

Methamphetamine (MA) is worldwide known drug with high potential for addiction that causes dopamine, noradrenaline and serotonin release. MA is also able to increase acetylcholine levels in adult rodents. The aim of this study was to map changes in D1-like dopamine receptors (DR), M1 and M2 muscarinic receptors (MR), and the total number of MR (M1-M5 MR) in the CNS of rats exposed to MA prenatally and in adulthood. Rat mothers were exposed to MA (5mg/kg s.c.) or saline during the entire gestation period and their male offspring were administered in adulthood with single MA (1mg/kg) or saline injection. Thus, the animals were divided into 4 groups: prenatally MA-exposed rats treated with saline (MA/S) or MA (MA/MA) in adulthood and prenatally saline-exposed rats treated with saline (S/S) or MA (S/MA) in adulthood. One hour after the acute treatment animals were sacrificed and their brains were removed. The numbers of M1, M2, total MR, and D1-DR were measured by autoradiography. The main effect was detected in the hippocampus with the most affected M1 MR. D1-DR were decreased in motor cortex and substantia nigra. M1MR were decreased in caudate-putamen, dorsal hippocampus, CA1, CA3 and dentate gyrus (DG). M2MR were decreased in DG only. Total number of MR was moreover decreased in dorsal hippocampus, CA1, CA3 and DG. Our results have shown different patterns of changes in DR and MR, suggesting a pilot role of M1 MR in the CNS changes induced by prenatal and adult MA exposure.

Prenatal methamphetamine exposure is associated with corticostriatal white matter changes in neonates.

Diffusion tensor imaging (DTI) studies have shown that prenatal exposure to methamphetamine is associated with alterations in white matter microstructure, but to date no tractography studies have been performed in neonates. The striato-thalamo-orbitofrontal circuit and its associated limbic-striatal areas, the primary circuit responsible for reinforcement, has been postulated to be dysfunctional in drug addiction. This study investigated potential white matter changes in the striatal-orbitofrontal circuit in neonates with prenatal methamphetamine exposure. Mothers were recruited antenatally and interviewed regarding methamphetamine use during pregnancy, and DTI sequences were acquired in the first postnatal month. Target regions of interest were manually delineated, white matter bundles connecting pairs of targets were determined using probabilistic tractography in AFNI-FATCAT, and fractional anisotropy (FA) and diffusion measures were determined in white matter connections. Regression analysis showed that increasing methamphetamine exposure was associated with reduced FA in several connections between the striatum and midbrain, orbitofrontal cortex, and associated limbic structures, following adjustment for potential confounding variables. Our results are consistent with previous findings in older children and extend them to show that these changes are already evident in neonates. The observed alterations are likely to play a role in the deficits in attention and inhibitory control frequently seen in children with prenatal methamphetamine exposure.

Prenatal methamphetamine exposure is associated with reduced subcortical volumes in neonates

ObjectivesPrenatal exposure to methamphetamine is associated with a range of neuropsychological, behavioural and cognitive deficits. A small number of imaging studies suggests that these may be mediated by neurostructural changes, including reduced volumes of specific brain regions. This study investigated potential volumetric changes in the brains of neonates with prenatal methamphetamine exposure. To our knowledge no previous studies have examined methamphetamine effects on regional brain volumes at this age. Study designMothers were recruited antenatally and interviewed regarding methamphetamine use during pregnancy. Mothers in the exposure group reported using methamphetamine≥twice/month during pregnancy; control infants had no exposure to methamphetamine or other drugs and minimal exposure to alcohol. MRI scans were performed in the first postnatal month, following which anatomical images were processed using FreeSurfer. Subcortical and cerebellar regions were manually segmented and their volumes determined using FreeView. Pearson correlations were used to analyse potential associations between methamphetamine exposure and regional volumes. The associations between methamphetamine exposure and regional volumes were then examined adjusting for potential confounding variables. ResultsMethamphetamine exposure was associated with reduced left and right caudate and thalamus volumes. The association in the right caudate remained significant following adjustment for potential confounding variables. ConclusionsOur findings showing reduced caudate and thalamus volumes in neonates with prenatal methamphetamine exposure are consistent with previous findings in older exposed children, and demonstrate that these changes are already detectable in neonates. Continuing research is warranted to examine whether reduced subcortical volumes are predictive of cognitive, behavioural and affective impairment in older children.

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.

Cognitive outcomes in prenatal methamphetamine exposed children aged six to seven years

BackgroundMethamphetamine use among pregnant women has become a significant problem. Research delineating the cognitive outcomes of prenatal methamphetamine exposure (PME) in early childhood is limited, however. The aim of this study was to examine effects of PME on cognition in six-to-seven-year-old children. MethodsPME children (n=23) and unexposed controls (n=22) completed a battery of neurocognitive tests, which included the Kaufman Assessment Battery for Children, Boston Naming Test, Beery Developmental Test of Visual-Motor Integration, and Grooved Pegboard Test. ResultsIndependent samples t-tests revealed that PME children scored significantly worse than controls on the measures of IQ, learning and memory, confrontation naming, visual-motor integration, and fine motor coordination. Hierarchical regression analyses that included potential confounding sociodemographic, co-exposure and anthropometric variables confirmed that PME impacts negatively on cognitive performance. ConclusionsThe study confirms that PME has deleterious effects on cognition in several broad cognitive domains, likely by altering underlying brain circuitry in development. These effects may be particularly pronounced at the time when children enter formal schooling. Extended follow-ups into late childhood might help elucidate the developmental trajectory of cognitive dysfunction in PME, and subsequent effects on everyday functioning.

Trans-generational neurochemical modulation of methamphetamine in the adult brain of the Wistar rat.

Chronic methamphetamine (METH) abuse has been shown to elicit strong neurotoxic effects. Yet, with an increasing number of children born to METH abusing mothers maturing into adulthood, one important question is how far do the neurotoxic effects of METH alter various neurotransmitter systems in the adult METH-exposed offspring. The purpose of this study was to investigate long-term trans-generational neurochemical changes, following prenatal METH exposure, in the adult Wistar rat brain. METH or saline (SAL-control animals) was administered to pregnant dams throughout the entire gestation period (G0-G22). At postnatal day 90, dopamine, serotonin, glutamate and GABA were measured in the adult brain before (baseline) and after a METH re-administration using in vivo microdialysis and liquid chromatography/mass spectrometry. The results show that METH-exposure increased basal levels of monoamines and glutamate, but decreased GABA levels in all measured brain regions. Acute challenge with METH injection in the METH-exposed group induced a lower increase in the monoamine system relative to the increase in the GABAergic and glutamatergic system. The data show that prenatal METH exposure has strong effects on the monoaminergic, GABAergic and glutamatergic system even when exposure to METH was limited to the prenatal phase. Toxicological effects of METH have therefore longer lasting effects as currently considered and seem to affect the excitatory-inhibitory balance in the brain having strong implications for cognitive and behavioral functioning.

Differential behavioral effects of nicotine in adult male and female rats with a history of prenatal methamphetamine exposure

The goal of the current study was to assess the effects of prenatal methamphetamine (MA)/saline exposure on nicotine-induced stimulant and aversive effects in both male and female adult rats. The aversive effects of nicotine were assessed using the nicotine-induced conditioned taste aversion model (0.4mg/kg, base), while the stimulant effects of nicotine were measured by assessing changes in spontaneous locomotor activity after subcutaneous administration of different doses of nicotine (0, 0.1 & 0.4mg/kg, base). The aversive effects of nicotine were significantly decreased in male, but not in female rats with a history of prenatal MA exposure compared to respective saline controls. No influence of prenatal MA exposure was observed on nicotine-induced increase in locomotor activity in either male or female rats. In conclusion, males with a history of prenatal MA exposure may be more vulnerable to nicotine addiction due to a decrease in nicotine-induced aversive effects.

Effect of Prenatal Methamphetamine Exposure on Blood Pressure and Vascular Function in Adult Male and Female Offspring

Hypertension and endothelial dysfunction are commonly associated with cardiovascular disease. Methamphetamine (meth) use is a widespread societal problem, with ~4.7% of the US population having tried meth at least once. Meth use during pregnancy can have deleterious developmental and behavioral consequences for offspring, including delayed development of gross motor skills and decreased memory. Although prenatal meth exposure reportedly causes increased cardiac ischemia in females, there exists very little additional data on the cardiovascular consequences of prenatal meth exposure in adult offspring. The aims of this study were to therefore test whether prenatal meth exposure increases blood pressure and impairs endothelial function in adult offspring, and whether this is influenced by gender. Pregnant female Sprague Dawley rats (8 wk old) were treated with either saline or methamphetamine (5 mg/kg/d sc, once daily) from gestational day 1 until pups were born. Male and female pups were weaned at 3 weeks of age and blood pressure (using tail cuff plethysmography) and vascular function (using myography) assessed after rats were 8 weeks old. Systolic blood pressure (SBP) was increased in male offspring prenatally exposed to meth (SBP = 151±2 mmHg, n=11) vs saline (141±3 mmHg, n=11, P<0.05 vs meth). SBP was similar in female offspring prenatally exposed to meth (SBP = 128±5 mmHg, n=7) and saline (SBP = 125±4 mmHg, n=8, P>0.05 vs meth). In males, endothelium‐dependent relaxation (assessed via relaxation responses to acetylcholine [ACh]) in second‐order mesenteric resistance arteries was impaired by prenatal meth exposure (pEC50: meth‐exposed = −7.5±0.06, n=5; saline‐exposed = −8.0±0.1, n=6; P<0.05). Prenatal meth exposure had no effect on responses to ACh in females (pEC50: meth‐exposed = −7.8±0.05, n=5; saline‐exposed = −8.1±0.08, n=5; P>0.05). Vasorelaxation responses to the endothelium‐independent agonist DEA NONOate, and phenylephrine‐induced vasoconstriction were not influenced by prenatal meth exposure in either gender. These data suggest that prenatal exposure to methamphetamine increases blood pressure and causes endothelial dysfunction in adult male offspring, whereas female offspring prenatally exposed to methamphetamine are protected against an increase in blood pressure and endothelial dysfunction. Prenatal methamphetamine exposure may therefore increase risk of cardiovascular disease in males.Support or Funding InformationRaabe College of Pharmacy, Ohio Northern University

Increasing Consumption of Crystal Meth in Saxony and its Risks for Mother and Child - Experiences at a Level I Perinatal Center from a Pediatric Viewpoint

Over the past several years, the number of first-time users of methamphetamine considerably increased within the Free State of Saxony. This number also, and especially, includes women of child-bearing age and young mothers. A supportive intervention aimed at reducing the effects of drug abuse should begin in a timely way - during pregnancy at latest, but better before it. To develop an optimal care protocol for both the mother and her child, more knowledge regarding the personal conditions of the women as well as the specific features of later child development after prenatal methamphetamine exposure (PME) is vital. In this study, the data of 129 women and their newborns with PME who were admitted to a Level-1 perinatal center between 2007 and 2015 were analyzed. At delivery, two-thirds of the women were aged 20-30 years. Only 48% attended their first preventive examination in pregnancy within the first 12 weeks. Their children subsequently presented with heterogeneous withdrawal symptoms, and pathological findings of the heart, urogenital and central nervous system. The present data aims to sensitize pediatric and obstetric health professionals to the need for timely and adequate care and support. A pathway model of detoxification treatment for mother and child - "The Dresden Crystal Path" - is presented. It combines public and voluntary youth welfare organizations, public health authorities, a public drugs advisory service as well as medical care facilities. Moreover, it describes the coordination of different medical subspecialties such as pediatrics, obstetrics/gynecology and psychiatry.

Methamphetamine Consumption during Pregnancy – Effects on Child Health

Methamphetamine abuse during pregnancy represents an emerging health care problem. The consequences are not only of relevance to the pregnant women, but also their unborn child. It is associated with an increased risk of preeclampsia and hypertension, fetal demise, preterm delivery, and intrauterine growth restriction. The deleterious effects of prenatal methamphetamine exposure on the developing fetal brain may lead to long-term neuro-developmental and behavioral problems.Given the current evidence, abuse of methamphetamine during pregnancy must be of utmost concern to health care professionals and to policy-makers. As it has been described for neonatal abstinence syndrome, a multi-professional team is required to improve care of affected women and families. A multi-disciplinary approach is needed, including good prenatal care of pregnant women, perinatal care by specialized obstetricians and neonatologists, and psychiatric treatment by an addiction specialist. Furthermore, families should be integrated into appropriate social support networks.For the development of a structured support program for pregnant women with methamphetamine consumption, methamphetamine use disorder should be considered as a disease that requires medical treatment as well as psychological and social support. The pregnancy should be considered as a window of opportunity to provide the required help.

Does effect from developmental methamphetamine exposure on spatial learning and memory depend on stage of neuroontogeny?

Psychostimulants, including methamphetamine (MA), have neurotoxic effect, especially, if they are targeting CNS during its critical periods of development. The present study was aimed to examine cognitive changes after prenatal and neonatal MA treatment in combination with chronic MA exposure in adulthood of male rats. Eight groups of male rats were tested in adulthood: males whose mothers were exposed to MA (5 mg/kg) or saline (SA, 1 ml/kg) during the first half of gestation period (GD 1-11), the second half of gestation period (GD 12-22) and neonatal period (PD 1-11). In addition, we compared indirect neonatal application via the breast milk with the group of rat pups that received MA or SA directly by injection (PD 1-11). Males were tested in adulthood for cognitive changes in the Morris Water Maze (MWM). MWM experiment lasted for 12 days: Learning (Day 1-6), Probe test (Day 8) and Retrieval Memory test (Day 12). Each day of the MWM animals were injected with MA (1 mg/kg) or SA (1 ml/kg). Prenatal MA exposure did not induce changes in learning abilities of male rats, but neonatal exposure to MA leads to an increase search errors and latencies to find the hidden platform. Prenatal and also neonatal MA exposure impaired cognitive ability to remember the position of the platform in Retrieval Memory test in adulthood. Animals exposed to the prenatal treatment within the second half of gestation (ED 12-22) swam longer, slower and spent more time to find the hidden platform in Retrieval Memory test than animals exposed throughout other periods. The present study demonstrated that stage of development is crucial for determination the cognitive deficits induced by prenatal or neonatal MA exposure.

Sex-Specific Alterations of White Matter Developmental Trajectories in Infants With Prenatal Exposure to Methamphetamine and Tobacco

Methamphetamine is a common illicit drug used worldwide. Methamphetamine and/or tobacco use by pregnant women remains prevalent. However, little is known about the effect of comorbid methamphetamine and tobacco use on human fetal brain development. To investigate whether microstructural brain abnormalities reported in children with prenatal methamphetamine and/or tobacco exposure are present at birth before childhood environmental influences. A prospective, longitudinal study was conducted between September 17, 2008, and February 28, 2015, at an ambulatory academic medical center. A total of 752 infant-mother dyads were screened and 139 of 195 qualified neonates were evaluated (36 methamphetamine/tobacco exposed, 32 tobacco exposed, and 71 unexposed controls). They were recruited consecutively from the community. Prenatal methamphetamine and/or tobacco exposure. Quantitative neurologic examination and diffusion tensor imaging performed 1 to 3 times through age 4 months; diffusivities and fractional anisotropy (FA) assessed in 7 white matter tracts and 4 subcortical brain regions using an automated atlas-based method. Of the 139 infants evaluated, 72 were female (51.8%); the mean (SE) postmenstrual age at baseline was 41.5 (0.27) weeks. Methamphetamine/tobacco-exposed infants showed delayed developmental trajectories on active muscle tone (group × age, P < .001) and total neurologic scores (group × age, P = .01) that normalized by ages 3 to 4 months. Only methamphetamine/tobacco-exposed boys had lower FA (group × age, P = .02) and higher diffusivities in superior (SCR) and posterior corona radiatae (PCR) (group × age × sex, P = .002; group × age × sex, P = .01) at baseline that normalized by age 3 months. Only methamphetamine/tobacco- and tobacco-exposed girls showed persistently lower FA in anterior corona radiata (ACR) (group, P = .04; group × age × sex, P = .01). Tobacco-exposed infants showed persistently lower axial diffusion in the thalamus and internal capsule across groups (P = .02). Prenatal methamphetamine/tobacco exposure may lead to delays in motor development, with less coherent fibers and less myelination in SCR and PCR only in male infants, but these abnormalities may normalize by ages 3 to 4 months after cessation of stimulant exposure. In contrast, persistently less coherent ACR fibers were observed in methamphetamine/tobacco- and tobacco-exposed girls, possibly from increased dendritic branching or spine density due to epigenetic influences. Persistently lower diffusivity in the thalamus and internal capsule of all tobacco-exposed infants suggests aberrant axonal development. Collectively, prenatal methamphetamine and/or tobacco exposure may lead to delayed motor development and white matter maturation in sex- and regional-specific manners.

Refining the Understanding of the Effects of Prenatal Methamphetamine and Tobacco Exposure on the Developing Brain

Refining the Understanding of the Effects of Prenatal Methamphetamine and Tobacco Exposure on the Developing Brain

Prenatal exposure: The effects of prenatal cocaine and methamphetamine exposure on the developing child.

Prenatal substance use remains a significant issue in the United States. Initial reports regarding prenatal cocaine and methamphetamine exposure suggested profound adverse effects on child development. However, subsequent prospective, longitudinal investigations have found more subtle effects. What follows is a brief review of the health, growth, behavioral, and intellectual outcomes for children exposed to prenatal cocaine and prenatal methamphetamine. Factors that may mitigate or intensify subtle adverse effects manifested in exposed children will also be discussed. Birth Defects Research (Part C) 108:142-146, 2016. © 2016 Wiley Periodicals, Inc.

How various drugs affect anxiety-related behavior in male and female rats prenatally exposed to methamphetamine

Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the drugs.

Sex-Dependent Changes in Striatal Dopamine Transport in Preadolescent Rats Exposed Prenatally and/or Postnatally to Methamphetamine.

Methamphetamine (MA) is the most commonly used psychostimulant drug, the chronic abuse of which leads to neurodegenerative changes in the brain. The global use of MA is increasing, including in pregnant women. Since MA can cross both placental and haematoencephalic barriers and is also present in maternal milk, children of chronically abused mothers are exposed prenatally as well as postnatally. Women seem to be more vulnerable to some aspects of MA abuse than men. MA is thought to exert its effects among others via direct interactions with dopamine transporters (DATs) in the brain tissue. Sexual dimorphism of the DAT system could be a base of sex-dependent actions of MA observed in behavioural and neurochemical studies. Possible sex differences in the DATs of preadolescent offspring exposed to MA prenatally and/or postnatally have not yet been evaluated. We examined the striatal synaptosomal DATs (the activity and density of surface expressed DATs and total DAT expression) in preadolescent male and female Wistar rats (31-35-day old animals) exposed prenatally and/or postnatally to MA (daily 5mg/kg, s.c. to mothers during pregnancy and lactation). To distinguish between specific and nonspecific effects of MA on DATs, we also evaluated the in vitro effects of lipophilic MA on the fluidity of striatal membranes isolated from preadolescent and young adult rats of both sexes. We observed similar changes in the DATs of preadolescent rats exposed prenatally or postnatally (MA-mediated drop in the reserve pool but no alterations in surface-expressed DATs). However, prenatal exposure evoked significant changes in males and postnatal exposure in females. A significant decrease in the activity of surface-expressed DATs was found only in postnatally exposed females sensitized to MA via prenatal exposure. MA applied in vitro increased the fluidity of striatal membranes of preadolescent female but not male rats. In summary, DATs of preadolescent males are more sensitive to prenatal MA exposure via changes in the reserve pool and those of preadolescent females to postnatal MA exposure via the same mechanism. The combination of prenatal and postnatal MA exposure increases the risk of dopaminergic deficits via alterations in the activity of surface-expressed DATs especially in preadolescent females. MA-mediated changes in DATs of preadolescent females could be still enhanced via nonspecific disordering actions of MA on striatal membranes.

School-Aged Outcomes following Prenatal Methamphetamine Exposure: 7.5-Year Follow-Up from the Infant Development, Environment, and Lifestyle Study

To assess the relationship between prenatal methamphetamine exposure (PME) and behavior problems at age 7.5 years and the extent to which early adversity mediated this relationship. The multicenter, longitudinal Infant Development, Environment, and Lifestyle study enrolled 412 mother-infant pairs at 4 sites. Methamphetamine-exposed participants (n = 204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched participants (n = 208) denied methamphetamine use and had a negative meconium screen. At the 7.5-year follow-up, 290 children with complete Child Behavior Checklist data and an early adversity index score were available for analysis (n = 146 exposed). PME was significantly associated with an increased early adversity index score (P < .001) and with increased externalizing, rule-breaking behavior, and aggressive behavior (P < .05). Early adversity was also associated with higher externalizing behavior scores. Early adversity significantly mediated the relationship between PME and behavioral problems. After adjusting the mediation model for sex, prenatal tobacco, alcohol, and marijuana exposures, and study site, the association of PME with early adversity remained significant. Though PME is associated with behavioral problems, early adversity may be a strong determinant of behavioral outcome for children exposed to methamphetamine in utero. Early adversity significantly mediated the relationship between PME and behavioral problems.

Does route of methamphetamine exposure during pregnancy have an impact on neonatal development and behaviour in rat offspring?

Many preclinical studies have aimed to elucidate the effects of methamphetamine (MA) exposure during pregnancy on the offspring in recent years. However, the severity of effects on the neonate may be related to the subcutaneous (sc) route of administration of the drug that is often employed (88% of preclinical studies) and consequently the delivered dose that the foetus is exposed to. To date there is a paucity of comparative studies investigating different routes of administration for MA during pregnancy and it is not known how these different routes compare when it comes to neonatal outcome. Thus, the aim of this study was to determine if the route of administration of MA (oral gavage or sc injection) during pregnancy at a pharmacological dose affects the magnitude of neurodevelopmental and behavioural effects in the resultant rat offspring. Pregnant Sprague-Dawley dams (n=10 dams/group) received MA (3.75mg/kg) or control (distilled water) via oral gavage or sc injection from gestation day 7–21. A range of well-recognised neurodevelopmental parameters were examined in the offspring. When administered sc, MA significantly reduced maternal weight gain and altered maternal behaviour; mothers spent less time in the nest with pups and spent less time nursing compared to controls. Significant impairments in neurodevelopmental parameters were evident in both MA treatment groups. Somatic development such as pinna unfolding, fur appearance and eye opening were all delayed after MA exposure but these impairments were more pronounced in the MA sc group. Other somatic parameters such as ano-genital distance and body length were only impeded by sc MA. Behavioural development in the surface righting, inclined plane and forelimb grip tests were also altered for both MA treatment groups. This study demonstrates that prenatal MA can have a profound effect on neonatal outcome, but this can be exacerbated if given via the subcutaneous route, as well as producing additional effects not seen with the oral gavage route. Consequently, the route of administration should be considered when interpreting preclinical studies investigating prenatal MA exposure.

Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts.

Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg·kg(-1)·day(-1)) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated end-diastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cε expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart.