Aug 01, · Abstract. Recent studies have documented that an increasing number of women of childbearing age are using licit and illicit substances. Although statistical data are insufficient, there are indications that approximately 1 in 10 infants may have been exposed to illicit drugs in utero. The Office of Applied Studies National Household Survey 1 revealed that % of women of Cited by: 70 Trauma-exposed Infants and Toddlers: A Review of Impacts and Evidence-Based Interventions Alysse Melville Abstract: Infants and toddlers are exposed to abuse and neglect at disproportionate rates compared to other children, setting a trajectory for disrupted developmental processes and increased vulnerability to future traumatic exposure We undertook a systematic review of the literature to examine the long-term effects of prenatal marijuana exposure on neuropsychological function in children aged years. Methods: Primary research publications were searched from Medline, Embase, PsychInfo, CINAHL EbscoHost, Cochrane Library, Global Health and ERIC (). Eligible articles documented neuropsychological
Try out PMC Labs and tell us what you think. Learn More. Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates among other drugs produce alterations in neurodevelopmental trajectory, article review on drug exposed infants.
We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies.
Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose—response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, article review on drug exposed infants, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.
Given the crucial roles for the major protein targets of drugs of abuse in shaping brain development Bhide, ; Bonnin and Levitt, article review on drug exposed infants, ; Frederick and Stanwood, ; Hohmann, ; Kater and Lipton, ; Lauder, ; Money and Stanwood, ; Stanwood and Levitt,it should not be surprising that fetal drug exposures have been linked to a wide variety of brain deficits, article review on drug exposed infants.
In this review, we will focus on: 1 what is currently known about the likely pattern of substance use among pregnant or article review on drug exposed infants of childbearing age; 2 the cellular and molecular pathways by which prenatal drug exposure may influence structural and functional brain development; 3 current studies on outcomes of exposed individuals across various areas of functioning neurobiology, physical growth, intelligence, executive functioning, behavior, and psychopathology ; 4 reviews of current experimental animal models, article review on drug exposed infants, and 5 current limitations in understanding and potential avenues for future research.
Thus, beyond the specific developmental article review on drug exposed infants of article review on drug exposed infants drugs, there are additional common factors that can produce deficits in neurodevelopmental trajectories. Recent data suggest that nearly 25 million Americans aged 12 or older are current illicit drug users; this estimate represents 9.
Current illicit drug use among pregnant women aged 15—44, has remained constant at 5. In fact, the pattern of rates of article review on drug exposed infants illicit drug use among young adolescent females has grown to where they are now more likely than males in their age group to be current non-medical users of psychoactive drugs. Legal drugs such as alcohol and nicotine also represent a significant hurdle regarding unintended effects on the fetus. The NSDUH also found that among pregnant women aged 15—44, the prevalence of reported current alcohol and cigarette usage rates has not changed substantially in the past decade.
This greatly complicates translatability to humans. Rodents mice, rats and lagomorphs rabbits are born relatively early, as compared with humans, and thus those offspring must be treated with drugs postnatally if the aim is to model third trimester human exposure Figure 1. However, article review on drug exposed infants, this omits the transplacental transfer that is inherent in human fetal drug exposure. Major neurodevelopmental events across species.
Schematic diagram that aligns human brain development with several animal models monkey, rabbit, rat, and mouse often used in studies of fetal drug exposure. Note in particular that the rodent equivalent of third trimester fetal development occurs postnatally. Moreover, drugs can alter fetal development through a wide variety of mechanisms Figure 2.
For example, if the drug crosses the placenta and the vast majority of drugs of abuse do crossthen it can directly act on its molecular target in the fetus. These effects would include altering placental secretory activity or uteroplacental blood flow, for example. And although it is beyond our scope to review it here, it has recently become clear that paternal exposures, to drugs such as cocaine, during spermatogenesis, can also influence offspring brain development and neurobehavioral development through epigenetic mechanisms, at least in animal models Killinger et al; Rodgers et al; Vassoler et al This topic is thus extremely complicated; nevertheless, we will do our best to review both animal models and clinical and imaging data from longitudinal human cohorts following fetal exposure to specific drugs of abuse.
Biological targets of fetal drug exposures. Drugs of abuse not only target the developing fetal brain directly, but can exert effects through a variety of organs with the mother, including the uterus, placenta, heart, lungs, and brain.
Methamphetamine METH is metabolized in rat and human livers to the main metabolites, amphetamine, and 4-hydroxymethamphetamine Caldwell et alprenatal amphetamine exposure discussed below.
Due to the addition of a methyl group, METH has a higher lipophilicity than amphetamine, allowing more rapid transport of the drug across the blood—brain barrier Barr et al METH has a high potential for abuse and addiction compared with other amphetamine-type stimulants, affecting the serotonin 5-HT plasma membrane transporter SERT and activating the psychological reward system by triggering a cascade of the massive release of dopamine DA in the brain.
This release of DA occurs by multiple mechanisms including: binding to reuptake transporter DATthe displacement of vesicles and inhibition of monoamine oxidase, and enhancing DAT-mediated reverse transport of DA transport across the plasma membrane Scott et al These targets of METH appear by mid-gestation in the fetal brain Bhide, ; Frederick and Stanwood, ; Malanga and Kosofsky, ; Money and Stanwood, The use of METH in the United States and in other parts of the world still remains a serious public health concern.
According to the United Nations, 1. There are few studies that have surveyed the prevalence of METH use among pregnant women. The only large-scale investigation to report METH prevalence for pregnant women has been the Infant Development, Environment, and Lifestyle IDEAL study. Despite the fact that METH has been utilized by pregnant women for many years, article review on drug exposed infants, relatively little is known about the effects of METH during early infancy and even less is known about the long-term effects.
The most common effects noted in newborns indicate that METH use is associated with growth restriction, decreased weight, length, and head circumference Little et al; Nguyen et al; Smith et al; Smith et alb. Echoencephalography has revealed congenital anomalies in exposed neonates include cardiac anomalies, cranial abnormalities, and abnormal brain development closely resembling those in ill, asphyxiated infants Dixon and Bejar, Mild withdrawal symptoms have also been noted in newborns Oro and Dixon, ; Smith et al, although these symptoms are not as common.
In animal models, increased DNA article review on drug exposed infants and postnatal functional deficits in motor coordination were documented in neonatal METH-exposed mice Jeng et al Several recent studies have examined the effects of METH exposure on childhood growth patterns and behavior after birth.
Focusing on physical growth patterns, Zabaneh et al found children exposed prenatally to METH have a modest decrease in height during the first 3 years of life with no observed difference in weight, head circumference, or weight-for-length trajectories.
Prenatal METH exposure also is associated with significantly reduced caudate nucleus volume and cortical thickness increases in perisylvian and orbital—frontal cortices Derauf et alarticle review on drug exposed infants, ; Zabaneh et al Diffusion tensor imaging DTI suggests lower diffusion and higher fractional anisotropy in METH-exposed children at 3—4 years of age, indicating that fetal METH may alter white matter tracts Cloak et al Furthermore, the METH-exposed children performed significantly worse on a visual motor integration task, which correlated with lower myoinositol in the thalamus Chang et al In another magnetic resonance imaging MRI study on children ranging from 3 to 16 years of age, exposed children scored lower on measures of visual motor integration, attention, verbal memory, and long-term spatial memory.
There were no differences among the groups in motor skills, short delay spatial memory, or measures of nonverbal intelligence. Despite comparable whole brain volumes in each group, the METH-exposed children appeared to have subtle but significant decreases in size or volume in certain brain regions, including the putamen, globus pallidus, and hippocampus.
These reductions correlated with poorer sustained attention and delayed verbal memory Chang et al It is important to note that although the study had an impressive article review on drug exposed infants range, sample sizes were limited.
Concentrating on long-term motor skills after birth, Smith et al observed a subtle METH exposure effect on fine motor performance at 1 year, with the poorest performance observed in the most heavily exposed children.
However, by 3 years of age, no differences in fine motor performance were observed. These findings suggest METH exposure has modest motor effects in the first year of life, but that this may be mostly resolved by 3 years of age.
The IDEAL study found that prenatal METH exposure was associated with child externalizing behavioral problems at 5 years and parenting stress and psychological symptoms experienced by primary caregivers were associated with increased child behavioral problems; indicating these effected children may have more difficulties negotiating the increasing complex academic and social demands of school-age children LaGasse et al; Twomey et al Animal models may give us insight and provide correlation to these studies examining the effects of prenatal METH exposure and if these effects will remain into adulthood.
Results from mouse exposure to METH during a time period equivalent to the third trimester of human fetal gestation see Figure 1 impaired weight gain, reduced novel location recognition, and impaired novel object recognition in both male and female mice during adolescence. In rats, article review on drug exposed infants, neonatal exposure to METH produces deficits in latency and memory in a Morris water maze Vorhees et al Both prenatal and neonatal exposure also caused impaired spatial learning Slamberova et alarticle review on drug exposed infants, ; Williams et alb ; Williams et ald ; Williams et aland neonatal exposure altered the adrenal response to a forced swim stressor, suggesting that the adrenal output during learning may contribute to the spatial learning deficits Williams et ala.
Rats exposed to METH in utero showed changes in the mesolimbic dopaminergic system and were more sensitive to the administration of the acute dose of METH in adulthood Bubenikova-Valesova et article review on drug exposed infants This indicates that offspring exposed to METH in utero could be more sensitive to METH and potentially to other psychostimulants Bubenikova-Valesova et al Although relatively little is known about the effects of METH during early infancy or the following long-term effects, recently there have been studies attempting to examine children exposed to METH in utero.
Further studies are important to aid in prevention programs and treatment for these individuals. Comparing the effects of prenatal METH exposure on infant and childhood growth between the United States and New Zealand demonstrated that the effects of prenatal METH differed across countries Abar et al In the study, the prenatal METH-exposed children in New Zealand fared better than exposed children in the United States. In addition, according to the United Nations, 1.
This reported use is at higher levels than the global average of 0. These studies suggest that the United States needs improved prevention programs, better pre- and postnatal treatments, and caregiver support for this exposed population. The users are either legally prescribed AMPHs for medical reasons or are nonmedical users.
Although ADHD is less common in females than males, a significant percentage of women of childbearing age are thus likely prescribed AMPH or other stimulants as a treatment for ADHD. The prevalence of women of childbearing age using non-medical AMPH is currently unknown, and even less is known about the frequency of use during pregnancy. Further studies are required to determine the true frequency of illegal AMPH-exposed pregnant and lactating women, so that appropriate care can be provided for mother and her family.
After prenatal exposure, AMPH has been detected in human umbilical cord Jones et al, plasma Dearlove and Betteridge,and placenta as early as the first trimester Joya et al The cellular actions of AMPH are nearly identical to METH see section aboveincluding increasing the levels of norepinephrine NEDA, and 5-HT in the synaptic cleft via transporter reuptake inhibition.
This increased availability allows the monoamines to act upon post-synaptic receptors. The use of AMPHs during pregnancy increases the risk of adverse effects on the outcome of pregnancy, such as placental hemorrhage Figure 2. This is mediated, at least in part, by stimulation of contractions in the uterus and by targeting NET and SERT in the human placenta Cordeaux et al; Ramamoorthy et al These actions have been hypothesized to contribute to preterm labor associated with AMPH exposure Cordeaux et al Animal studies revealed at a prepubertal age, an enhancement of D1 receptors in the dorsal striatum and nucleus accumbens NAc and a decrement of the D3 receptors in NAc, olfactory tubercle, and the article review on drug exposed infants of Calleja.
In contrast, article review on drug exposed infants, at a postpubertal age, the authors instead measured an increase in the levels of DAT in the NAc and striatum, and a decrease article review on drug exposed infants D2 receptor expression in the NAc shell.
In addition, acute AMPH induces a marked decrease in locomotor activity in rats following prenatal AMPH exposure Flores et al These developmental and behavioral changes in animal models associated with in utero AMPH exposure provide insights to the mechanisms causing changes in affective, behavioral, and cognitive outcomes in exposed children. A meta-analysis of 10 studies of low-to-moderate risk of bias submits that AMPH exposure in pregnancy is associated with higher odds of preterm birth, low birth weight, and small size for gestational age Ladhani et al Birth weight as a continuous variable was also found to be significantly lower among exposed women.
Gestational age, however, was not found to be significantly different Ladhani et al The most extensive follow-up data on affective, behavioral, and cognitive outcomes following prenatal AMPHs are provided by Swedish researchers who tracked a cohort of 65 AMPH-exposed children from birth to age They reported in children with continuous AMPH exposure throughout gestation, a variety of adverse physical, cognitive, emotional, and social effects, including increased prevalence of ADHD, aggression, and learning difficulties attributed to deficits in attention, memory, and motivation Eriksson et al; Eriksson et al Furthermore, a relationship between head circumference at birth and at 1 year of age predicted language and mathematics proficiency at 14 years of age Eriksson et al As with its parent drug METH, further studies on prenatal AMPH exposure is needed to better understand effects from prescribed AMPHs or non-medical users Oei et al It acts as a powerful releasing agent of 5-HT, NE, and DA and also acts as a reuptake inhibitor of their high-affinity transporters de la Torre et al; Rudnick and Wall, MDMA is actively transported through the plasma membrane and can then inhibit the vesicular monoamine transporter, resulting in increased concentrations of 5-HT, NE, article review on drug exposed infants, and DA in the cytoplasm.
MDMA can also directly bind a number of receptors with moderate affinity, including α 2-adrenergic adrenaline and 5-HT2A receptors de la Torre et al A single MDMA injection to pregnant rat dams results in MDMA transfer into the fetal compartment Campbell et al However, emerging data also suggests key roles for maternal and placental 5-HT in regulating brain development Bonnin et al; Bonnin and Levitt, Figure 2.
In the United States, data from the National Survey on Drug Use and Health estimate that about 6. Although data from pregnant women was not presented, the prevalence of at least once in lifetime Ecstasy use in saw a significant increase from past-year use, and past-year use for eighth through twelfth graders remained stable UNODC,
Dr. Bergeron speaks on drugs and pregnancy
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We undertook a systematic review of the literature to examine the long-term effects of prenatal marijuana exposure on neuropsychological function in children aged years. Methods: Primary research publications were searched from Medline, Embase, PsychInfo, CINAHL EbscoHost, Cochrane Library, Global Health and ERIC (). Eligible articles documented neuropsychological Aug 01, · Abstract. Recent studies have documented that an increasing number of women of childbearing age are using licit and illicit substances. Although statistical data are insufficient, there are indications that approximately 1 in 10 infants may have been exposed to illicit drugs in utero. The Office of Applied Studies National Household Survey 1 revealed that % of women of Cited by: 70 Trauma-exposed Infants and Toddlers: A Review of Impacts and Evidence-Based Interventions Alysse Melville Abstract: Infants and toddlers are exposed to abuse and neglect at disproportionate rates compared to other children, setting a trajectory for disrupted developmental processes and increased vulnerability to future traumatic exposure
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