In the current issue of Anesthesia & Analgesia, Flick and colleagues1 report on the association between neuraxial labor analgesia for vaginal delivery and childhood learning disabilities (LDs). LDs are a significant public health concern, affecting at least 5%, or 2.5 million United States (U.S.) children attending public schools.2 Approximately one half of all students receiving special education in the U.S. are diagnosed as having LDs.3 According to the federal definition,
The term “specific learning disability” means a disorder in one or more of the psychological processes involved in understanding or in using language, spoken or written, which may manifest itself in an imperfect ability to listen, speak, read, write, spell, or to do mathematical calculations. The term does not include children who have LD which are primarily the result of visual, hearing, or motor handicaps, or mental retardation, or emotional disturbance, or of environmental, cultural, or economic disadvantage.4
As is stated in this definition, there are many different types of LDs, all of which interfere with learning and functioning in school or at work.5,6 The most prevalent is reading disability, commonly called dyslexia. Other common LDs are dyscalculia, a learning disorder related to math, and dysgraphia, a learning disorder related to handwriting. Attention disorders, executive function disorders, and social skills deficits are increasingly recognized as types of LDs. A child may have more than one type of LD, each with a different level of severity. Each child with an LD thus requires an intervention tailored to his or her specific needs, including individualized help in a regular classroom setting, adjunctive therapies, an individualized education plan, and specialized school placement. In addition to specific educational interventions, other components of an effective LD intervention plan may include psychosocial support at home and school and, for some, psychotropic medication to address attention or mood issues. LDs are typically diagnosed when children reach an age when academic expectations are clear, and a significant “gap” appears between those expectations and the child's performance.
A typical age at which children are diagnosed with LDs is 8 years, although some children are diagnosed as young as 5 to 6 years, and others as old as 16 years. The assessment typically includes intellectual assessment (e.g., IQ testing and evaluation of skills component to learning, such as memory and attention), as well as achievement testing using measures that have been norm-referenced to reflect current geographic, sociodemographic, and parent-education levels in the U.S. Testing for LDs also includes evaluation of behavior, social–emotional functioning, sensory function, and other factors that may interfere with learning. This information is necessary to rule out other explanations for a child's inability to master the academic information expected at his or her age grade in school, and thus to allow for an appropriate deployment of educational resources to address the issues.
LEARNING DISABILITY AS AN OUTCOME WITHIN THE CURRENT STUDY
With their examination of the associations of neuraxial analgesia exposure during labor and delivery and children's subsequent learning disabilities, the report by Flick and colleagues1 offers an important public health investigation towards understanding the impact of labor and delivery variables on children's neurodevelopmental outcomes. A strength of this work, as well as earlier research by this team, is the use of state-wide information on the use of labor analgesia in this cohort and subsequently diagnosed LDs. Within the state of Minnesota, where this research was conducted, 3 different methods for diagnosing LDs were used, reflecting the considerable variation in how the “gap” between educational expectations and achievement is defined. In the Flick et al. study,1 one set of Minnesota schools used the state-required regression formula for identifying LD, defined as an achievement score at least 1.75 standard deviations below the scores on individually administered tests of cognitive ability. A slightly different approach used in a second set of schools within this study was to adjust the required difference in scores according to the age range of the child. Within this approach, younger children were permitted to show a smaller discrepancy between tested intelligence and achievement than were older children for an LD to be diagnosed, under the assumption that there is greater variation in educational outcomes as children experience additional years of education. A third approach, used by another subset of Minnesota schools, was simply to define LD as low achievement independently of cognitive ability, under the assumption that children's cognitive abilities are at least within the low-average range. This latter approach is more consistent with contemporary standards and legislation that hold schools accountable for educating children to generally accepted age guidelines.5 The varied practices used in Minnesota to diagnoses LDs reflect the heterogeneity of LD evaluative approaches that currently exist within the U.S. All are efforts to define “unexpected underachievement” in a uniform and objective manner.
None of the approaches used by Flick et al.1 to define LD explicitly examines exclusionary factors for LD, such as sensory impairments, or emotional, cultural, or economic barriers, that are included within the federal definition of LD. By using only existing information on intellectual and academic achievement testing, apparently without reference to actual LD determinations made by local educational teams that would have presumably considered exclusionary factors (such as sensory impairment, social–emotional difficulties, weak academic instruction, non-English language proficiency, or cultural differences, as listed within the federal guidelines), Flick and colleagues may have inadvertently overestimated the numbers of children with LDs in this study. However, because the diagnosis of LD is itself subject to such local variation in its application, and to conduct a study of this scale requires more consistency in its approach than may exist in actual practice, Flick and colleagues have taken an approach that at least uses intelligence and academic achievement data in a systematic manner to establish the LD study outcome. However, the LD outcomes in this study are not entirely consistent with either the federal guidelines for LD or contemporary clinical practices in LD determination.
ALTERNATIVE APPROACHES TO STUDYING ANESTHESIA/ANALGESIA AND LEARNING DISABILITIES
Several different methodological approaches can be used to characterize the association between anesthesia/analgesia and the risk of LDs. Each has its strengths and weaknesses. Among the most important issues to consider are study design, selection of a control group, and potential confounding variables.
An ambidirectional observational cohort study, in which the outcomes of children who received anesthesia/analgesia in a defined period in the past (e.g., younger than 3 years) are compared with the outcomes of those who did not, has the advantages of being an efficient and relatively economical strategy.7 One disadvantage of this study design is that receipt of anesthesia or analgesia is never randomized, confounding any resulting associations. Another disadvantage is that the anesthesia or analgesia was titrated to clinical need, resulting in a range of exposures across patients. A third disadvantage is residual confounding, that is, confounding that remains either because a bona fide confounder was not measured or was measured poorly. Residual confounding is particularly problematic if a study is conducted using medical record data only.1,8,9 The use of in-person data collection addresses this limitation, particularly if siblings are used as controls, because siblings share the same family environment (e.g., the PANDA study, described by Sun et al.7).
A prospective design has the advantage of affording the opportunity to collect data on potential confounders contemporaneously. Furthermore, if children with the same medical condition are randomized to receive general or regional anesthesia, or different types of analgesia, the potential for confounding by indication and by differential postexposure experiences is further reduced, increasing the likelihood that any association identified between the randomized variable (i.e., type of anesthesia) and the primary outcome is causal. The ongoing General Anesthesia Study (GAS) involving children undergoing inguinal hernia repair (Davidson et al.10) is an example of a study using a randomized design. The primary disadvantage of such a study is that a long period of follow-up is required to assess an outcome such as LD, because infant assessments tend to have limited predictive validity. Thus, the duration and cost of a prospective study such as GAS will generally be considerably greater than that of a retrospective study such as PANDA. Also, there is no untreated control group in the GAS study, and thus the study can provide only an estimate of the relative risk rather than absolute safety of alternative anesthesia or analgesia strategies.
No single approach can be considered the “best” for evaluating the risk of anesthesia neurotoxicity in children. The weight-of-evidence from studies that use diverse approaches will provide the strongest basis for drawing inferences about the magnitude of the neurodevelopmental risk associated with children's early exposure to anesthesia and analgesia. Given the incidence of LD and associated costs of specialized education plans for children with LDs, continued research into the long-term effects of anesthesia toxicity on children's learning and development is essential.
Name: Jerilynn Radcliffe, PhD.
Contribution: This author helped write the manuscript.
Attestation: Jerilynn Radcliffe approved the final manuscript.
Name: David C. Bellinger, PhD.
Contribution: This author helped write the manuscript.
Attestation: David C. Bellinger approved the final manuscript.
1. Flick RP, Lee K, Hofer RE, Beinborn CW, Hambel EM, Klein MK, Gunn PW, Wilder RT, Katusic SK, Schroeder DR, Warner DO, Sprung J. Neuraxial labor analgesia for vaginal delivery and its effects on childhood learning disabilities. Anesth Analg 2011;112:1424–31
2. Pierangelo R, Guilani G. Learning Disabilities: A Practical Approach to Foundations, Assessment, Diagnosis, and Teaching.San Antonio: Merrill, 2006
3. President's Commission on Excellence in Special Education. A New Era: Revitalizing Special Education for Children and Their Families. Washington DC: U.S. Department of Education, 2002
4. U. S. Office of Education. Assistance to states for education for handicapped children: Procedures for evaluating specific learning disabilities. Federal Register 1977;42:65,082–5
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