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Authors: Iona Novak, Catherine Morgan
Journal: JAMA Pediatrics (2018)

In Reply We thank Parikh for his excellent points and deeply appreciate his efforts to refine advanced magnetic resonance imaging (MRI) biomarkers toward multivariable prediction models in high-income contexts.Our clinical practice guideline 1 was developed from the combined body of best-available evidence, sourced using a systematic review method, and organized by panel consensus using the GRADE framework.We did not review single articles in isolation to avoid selection and reporting bias.Furthermore, we examined multiple causal pathways to cerebral palsy, not just the preterm population as cited by Parikh, which affects the denominator value used for interpreting data.We agree that the Hintz et al 2015 MRI case series of SUPPORT trial participants cited by Parikh makes an important contribution to the literature for the extremely preterm population.We wish to make important distinctions between 1 preterm article by Hintz et al vs the collective body of published evidence, which explains the different risk ratios and predictive values in our article. 1First, Hintz et al examined the composite risk for developmental delay (motor and cognitive) and cerebral palsy, whereas we reviewed risk for cerebral palsy only.Second, Hintz and colleagues examined all forms of moderate to severe white matter injury (eg, Grade 3 intraventricular hemorrhage, which has a low predictive value for cerebral palsy), whereas we specifically focused on MRI findings of damage to the motor tracts (eg, cystic periventricular leukomalasia, periventricular hemorrhage/ intraventricular hemorrhage involving the motor tracts, and basal ganglia thalamic injury in term infants and stroke including motor tracts), which have higher predictive values for cerebral palsy.The Constantinou et al general movements study referred to by Parikh was included within the systematic reviews we analyzed.The strength of 1 article therefore cannot be compared with systematic reviews that included the 1 article.The Spittle et al study referred to by Parikh could not be cited because it was published after the extraction dates of our included systematic reviews.Nevertheless, the Spittle et al article provides important additional research data that confirms, not negates, the findings of our systematic review in the preterm population.Notably, the research sample of Spittle et al included 5 of 99 children with cerebral palsy, indicating a 5% prevalence estimate for cerebral palsy, whereas meta-analysis population estimates are higher, ranging between 6% and 14%. 2 An increase in 1 to 2 cases of cerebral palsy in the Spittle et al sample by chance could have substantially affected the sensitivity and specificity calculations in either direction.Studies with the highest sensitivity and specificity examined in our guideline had large samples; advance trained general movements raters; predictions from the more accurate "fidgety period"; and studied prediction of cerebral palsy rather than composite disability end points.Numerous references support the complementary role of MRI and general movements for the prediction of cerebral palsy in both the preterm 3 and full-term 4 group.We agree that MRI and general movements are significantly correlated.Importantly, we have not mathematically collapsed these correlated data to develop a flawed combined risk index.Rather we, and others 5 have recommended both tests be conducted, and where the data are congruent, the clinician can have higher confidence that the clinical picture might be cerebral palsy, not another developmental delay.