Definitions of the levels of the recommendations (A, B, C, U) and classification of the evidence (Class I-IV) are provided at the end of the "Major Recommendations" field.
What is the role of diagnostic testing of children with microcephaly?
Data from 6 Class III studies (2 computed tomography [CT], 2 magnetic resonance imaging [MRI], 2 CT/MRI of 292 children with microcephaly found diagnostic yields ranging from 43% to 80%. In 2 studies, children with severe microcephaly (<-3 SD) were more likely (i.e., 75%, 80%) to have an abnormal MRI than those with milder microcephaly. MRI detected brain abnormalities typically beyond the sensitivity of computed tomography (CT).
Neuroimaging may be considered useful in identifying structural causes in the evaluation of the child with microcephaly (Level C).
Genetic etiologies may be found in 15.5% (Class II, n = 58) to 53.3% (Class III, n = 30) of children with microcephaly. MRI studies may detect specific malformations associated with well described genetic conditions.
Specific targeted genetic testing may be considered in the evaluation of the child with microcephaly in order to determine a specific etiology (Level C).
The prevalence of metabolic disorders among children with microcephaly is unknown. Based on prior analysis of studies of children with global developmental delay (GDD), it is likely 1% to 5%.
There is insufficient evidence to support or refute obtaining metabolic testing on a routine basis for the evaluation of the newborn or infant with microcephaly (Level U).
What neurologic disorders are associated with microcephaly?
Children with microcephaly are more likely to have epilepsy, particularly epilepsy that is difficult to treat. Certain microcephaly syndromes are associated with a much higher prevalence of epilepsy. There are no systematic studies regarding electroencephalogram (EEG) testing of children with microcephaly with and without epilepsy.
- Because children with microcephaly are at risk for epilepsy, physicians may consider educating caregivers of children with microcephaly on how to recognize clinical seizures (Level C).
- There are insufficient data to support or refute obtaining a routine EEG in a child with microcephaly (Level U).
Cerebral Palsy (CP)
CP is a common disability in children with microcephaly. Microcephaly, particularly of postnatal onset and identifiable etiology, is more common in children with CP.
- Because children with microcephaly are at risk for CP, physicians and other care providers may consider monitoring them for early signs so that supportive treatments can be initiated (Level C).
- Because children with CP are at risk for developing acquired microcephaly, serial HC measurements should be followed (Level A).
Microcephaly is commonly found in developmentally and cognitively impaired children. Children with microcephaly are at a higher risk for mental retardation and there is a correlation between the degree of microcephaly and the severity of cognitive impairment.
Because children with microcephaly are at risk for developmental disability, physicians should periodically assess development and academic achievement to determine whether further testing and rehabilitative efforts are warranted (Level A).
Ophthalmologic and Audiologic Disorders
Ophthalmologic disorders are more common in children with microcephaly but the frequency, nature, and severity of this involvement has not been studied. Data on the prevalence of audiologic disorders in children with microcephaly have not been reported.
Screening for ophthalmologic abnormalities in children with microcephaly may be considered (Level C).
Classification of Recommendations
Level A = Established as effective, ineffective, or harmful (or established as useful/predictive or not useful/predictive) for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies.*)
Level B = Probably effective, ineffective, or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified population. (Level B rating requires at least one Class I study or two consistent Class II studies.)
Level C = Possibly effective, ineffective, or harmful (or possibly useful/predictive or not useful/predictive) for the given condition in the specified population. (Level C rating requires at least one Class II study or two consistent Class III studies.)
Level U = Data inadequate or conflicting; given current knowledge, treatment (test, predictor) is unproven.
*In exceptional cases, one convincing Class I study may suffice for an "A" recommendation if: 1) all criteria are met, 2) the magnitude of effect is large (relative rate improved outcome >5 and the lower limit of the confidence interval is >2).
Classification of Evidence for the Rating of a Screening Article
Class I: A statistical, population-based sample of patients studied at a uniform point in time (usually early) during the course of the condition. All patients undergo the intervention of interest. The outcome, if not objective, is determined in an evaluation that is masked to the patients' clinical presentations.
Class II: A statistical, non-referral-clinic-based sample of patients studied at a uniform point in time (usually early) during the course of the condition. Most patients undergo the intervention of interest. The outcome, if not objective, is determined in an evaluation that is masked to the patients' clinical presentations.
Class III: A sample of patients studied during the course of the condition. Some patients undergo the intervention of interest. The outcome, if not objective, is determined in an evaluation by someone other than the treating physician.
Class IV: Studies not meeting Class I, II or III criteria including consensus, expert opinion or a case report.