Neurobehavioral assessments of school-aged children with a history of prenatal methamphetamine, nicotine, and alcohol exposure revealed pronounced dysfunction in executive function and a slight reduction in spatial memory. Parental ratings were clinically significant on the Global Executive Composite as well as both the Behavioral Regulation and Metacognition Indexes, which indicate substantial difficulties in everyday tasks, including working memory, impulse control, setting goals, flexibility, and emotional control, both at home and at school. As prenatal amphetamine exposure was also associated with an increased likelihood of being behind a grade in school (Cernerud et al. 1996
), the identified impairments are likely contributing factors to the academic success of children so exposed. Although the ratings of exposed children that were and were not living with a biologically related family member were both elevated, there was also some evidence to indicate that the executive function profile was more problematic when the BRIEF was completed by a non-biologically related caregiver. One possibility is that the children placed in the care of an adoptive parent are more severely affected by their early developmental history and show more difficulties with behavioral regulation and working memory. This could result from a heavier pattern of drug abuse among women that subsequently lose child custody. A second possibility is that adoptive parents have a tendency to rate their children’s behavior more extremely than do biological parents. Importantly, the BRIEF has been frequently employed in other research with adopted children (Groza et al. 2004; Jacobs et al. 2010
; Lawson et al. 2007). For example, Lawson and colleagues (2007) obtained BRIEF ratings of adoptive children made by their parents and their teachers. Although no formal statistical comparison was made in this report, examination of the means reveals that scores were generally concordant across raters for girls, but higher (more problematic) for boys for parental ratings. Further, the higher negativity ratings of children with a methamphetamine history, particularly those made by the non-biologically related parents, would support the second explanation. The elevated negativity is also cause for some concern as maternal methamphetamine use may result in a stigmatization of these children which could diminish parental expectations.
Exposed children exhibited very subtle deficits in spatial function as measured by Memory Island. Exposed children navigated around the virtual island more slowly on the first target visible trial. Interestingly, a prior study determined that speed on this trial shows a marked progression with age (Piper, Acevedo, McGinness, & Raber, unpublished observations). This finding, in conjunction with earlier investigations that revealed abnormalities copying a geometric pattern (Chang et al. 2004
), suggests prenatal exposure may cause developmental delays in visual-motor integration. With the exception of this transient speed difference, performance was generally similar for both groups during the eight consecutively conducted visible and hidden trials of Memory Island, indicating that spatial learning was unaffected. However, unlike the unexposed group, exposed children did not spend significantly more time in the target relative to non-target quadrants during the probe trial which is indicative of a reduction in spatial memory. Early developmental exposure to recreational drugs alters dendritic morphology in the hippocampus (González-Burgos et al. 2006
; Roy & Sabherwal, 1998
; Williams et al. 2004
), a structure that is integral to spatial function (Bird & Burgess, 2008
). This finding with Memory Island extends upon a large body of preclinical research with early developmental methamphetamine exposure and water-maze assessments in adulthood (Golub et al. 2005
; Siegel et al. 2010
; Williams et al. 2003
) and highlights the utility of a translational approach.
An interesting and novel finding from this investigation was that the frequency of an ADHD diagnosis was four-fold more common in the exposed group. Prior cross-sectional studies have identified as much as a three-fold increase in the rates of ADHD in children exposed prenatally to alcohol or nicotine, and this association appears to be dose dependent (Banerjee et al. 2005; Huizink & Mulder, 2006
). It should also be emphasized that the parents and guardians of children diagnosed with ADHD were instructed to, if possible, base their evaluations on those times when their child was not under the influence of any cognitive enhancing drugs. The vast majority of the participants diagnosed with ADHD had received methylphenidate or other similar drug therapies prior to behavioral testing in this investigation. The question of whether pharmacotherapies for ADHD can improve neurobehavioral function, particularly spatial performance, has received some attention. Methylphenidate-naïve children diagnosed with ADHD showed an improvement in visual-spatial working memory and on some measures of motor speed following acute methylphenidate (Kempton et al. 1999
). Similarly, amphetamine increased the spatial span in children with ADHD (Alloway et al. 2009
). Exposed ADHD+ children did slightly, albeit non-significantly, better on the Memory Island probe trial than did exposed ADHD− children. Together, the ability of ADHD medications to improve neurobehavioral function in exposed children warrants additional research.
Although maternal ratings revealed clear abnormalities in executive function, several behavioral assessments that might be anticipated to corroborate this dysfunction (e.g., CPT, Dot Location, Spatial Span, or WASI) were unaffected. The present data suggests that some elements of the more global experiences of the parent ratings may be manifested in their child’s behavior in the virtual world created by Memory Island. Further, our qualitative impression is that some of the exposed children were much more challenging to test (e.g., requiring more breaks), especially in the latter half of the 2.5 hour session, which provides some verification for the parental BRIEF reports. Additional evidence and detailed explanations for the previously documented disassociation between laboratory based measures and parent ratings of executive function may be found elsewhere (Bodnar et al. 2007
; Mcauley et al. 2010
The postnatal environment of a child living with a biological mother who uses methamphetamine is likely to be non-optimal (Messina et al. 2010). Women who use drugs during pregnancy have high rates of psychiatric disorders as well as histories of emotional and/or sexual abuse, and their home environments often include domestic violence (Datner et al. 2007
; Kissin et al. 2001
; Medrano et al. 1999
; Paz et al. 1999). Any one of these factors could adversely influence the cognitive development of a child. Animal researchers can easily cross-foster exposed pups onto non-methamphetamine–treated dams (Hrubá et al. 2009
). A somewhat analogous practice is also occurring clinically as approximately two-thirds of the exposed children were currently residing in homes that did not include the biological mother. Clearly, the existence of group differences between exposed and unexposed children on ratings of executive function, largely independent of the rater, indicates that the prenatal environment may be a key determinant of these outcomes. As it has been estimated that as many as half of the children that entered the foster care system in the state of Oregon have a parent who uses methamphetamine (Oregon DHS, 2007
), these findings may be particularly relevant for foster-care providers and adoptive families. Although the inclusion of adopted children in this study offers some pronounced limitations (e.g. note the smaller N on some measures in where selected information on maternal substance use was unavailable from the adoptive mother), the inclusion of children living with both adoptive and biological parents is, overall, a novel aspect and strength of this report. Alternatively, children that are subsequently adopted may be subject to several influences (e.g. prenatal stress, neglect/abuse) in conjunction with maternal substance abuse which could adversely impact neurodevelopment. It should therefore be emphasized that prior investigations of executive function in adoptive children have been completed. Despite the many challenges facing adoptive children, there is often a tremendous resilience as well. Only 11% of international adoptees met the criteria for problems in executive function by the age of four (Jacobs et al. 2010
). One could conceivably argue the key time period in prior investigations of methamphetamine exposed children (Chang et al. 2004
) could be postnatal, rather than prenatal. Overall, incorporation of adopted children that are living in homes that are more similar to unexposed children, although raising some complexities, also allows for greater specificity of the origins of any group differences and provides an important contribution to the larger literature on early developmental methamphetamine (Golub et al. 2005
; Lagasse et al. 2010
; Lu et al. 2009
; Meyer & Piper, 2010
; Smith et al. 2001
; Sowell et al. 2010
Some clear limitations of this cross-sectional investigation as well as future directions should be noted. First, because women who use methamphetamine during pregnancy tend to concurrently abuse other recreational drugs (Chang et al. 2004
; Paz et al. 2009
; Smith et al. 2001
), it is exceedingly difficult, if not impossible, to obtain a sample of women who use methamphetamine exclusively. Other substances, including recreational drugs and/or the chemicals used in manufacturing methamphetamine (Messina et al. 2010) acting alone or in combination with methamphetamine, or early developmental factors might have contributed to the neurobehavioral profile observed. Children with Fetal Alcohol Syndrome show pronounced impairments in both executive function and spatial learning and memory in a virtual water-maze (Hamilton et al. 2003
, Schonfeld et al. 2006
). However, the present study did not include children with either mental retardation or Fetal Alcohol Syndrome. Although not yet a common practice in this research area (Chang et al. 2004
; Dixon & Bejar, 1989
; Lagasse et al. 2010
; Paz et al. 2009
; Smith et al. 2001
), based on the present outcomes, more reports that include a separate group of polysubstance users who do not abuse methamphetamine are warranted (Lu et al. 2009
; Sowell et al. 2010
; Roussotte et al. 2010) as, without this separate group, the present data only implies that methamphetamine is a component teratogen in these children. As women that exclusively use methamphetamine during pregnancy are virtually non-existent and standard research ethics preclude controlled maternal administration, preclinical studies (Golub et al. 2005
; Siegel et al. 2010
; Slamberová et al. 2005
; Williams et al. 2003
) are crucial as such reports will allow more satisfactory inferences regarding causality and specificity.
Second, children with an ADHD diagnosis and who received drug therapies were included in the sample. It is tempting to speculate, as some parents did, that methylphenidate and other cognitive enhancing drugs provide clear benefits for these children. Therefore, it is possible that stimulant medications obscured some behavioral deficits that would have been identified in a drug-free state. A within-subjects design in which exposed children are assessed on and off drug therapy is needed to evaluate this hypothesis. Notably, an earlier cross-sectional report excluded children with ADHD and, in general, obtained complementary results (Chang et al. 2004
). The length of testing (2.5 hours) may have resulted in fatigue and, thus, may not accurately assess the children's cognitive abilities. Additional research is ongoing with a more focused emphasis on objective measures of executive function (e.g. with the Tower of London test).
Third, and perhaps foremost, the majority of exposed children were not currently living with their biological mothers. In these instances, retrospective identification (which always much be interpreted cautiously even when completed by the biological mother) of methamphetamine use during pregnancy came from other sources including the biological father, grandparents, laboratory analyses, maternal reports contained within the medical records obtained from the antenatal period, birth certificates, or other legal documents from the mother’s incarceration or custody hearing. More specifically, urine analysis positive for amphetamines for either the biological mother during pregnancy or the neonate was available for 52.6% (10/19) of adopted participants. Although inclusion of both ADHD+ and adopted children increases the generalizability of results, detailed information about the precise timing and extent of maternal drug use was unavailable for some adopted children (note reduced N on some measures on due to unavailable information). On the other hand, as such a sizeable number of children exposed prenatally to methamphetamine in Oregon are adopted (Oregon DHS, 2007
), we strongly believe that these families are worthy of systematic investigation while simultaneously keeping in mind the substantial caveats this group presents. Additional neurobehavioral studies of adoptive children without a prenatal exposure history are needed and are ongoing. Finally, the current study did not evaluate or screen for attachment issues which may be a concern in this population. As the living situations of exposed children were often rather complex, e.g., sometimes involving multiple transitions between foster care placements, adoptive parents, grandparents, as well as the biological mother, a larger sample will be needed to provide subgroup analyses to further determine the extent that an optimal postnatal context can mitigate against the sequelae of the prenatal history.
In conclusion, this study, in conjunction with many others, shows that there may be persistent neurological consequences of in utero
methamphetamine exposure (Chang et al. 2004
; Chomchai et al. 2004
, Lagasse et al. 2004; Smith et al. 2001
). This underlines the need for greater educational strategies to minimize maternal stimulant abuse and further development of specially tailored child interventions for neurobehavioral remediation in children exposed in utero
to recreational drugs including methamphetamine.