Developmental outcomes after early surgery for complex congenital heart disease: a systematic review and meta-analysis

Abstract

Aim: (1) To systematically review the literature on developmental outcomes from infancy to adolescence of children with complex congenital heart disease (CHD) who underwent early surgery; (2) to run a meta-regression analysis on the Bayley Scales of Infant Development, Second Edition Mental Developmental Index and Psychomotor Developmental Index (PDI) of infants up to 24 months and IQs of preschool-aged children to adolescents; (3) to assess associations between perioperative risk factors and outcomes.

Method: We searched pertinent literature (January 1990 to January 2019) in PubMed, Embase, CINAHL, and PsycINFO. Selection criteria included infants with complex CHD who had primary surgery within the first 9 weeks of life. Methodological quality, including risk of bias and internal validity, were assessed.

Results: In total, 185 papers met the inclusion criteria; the 100 with high to moderate methodological quality were analysed in detail. Substantial heterogeneity in the group with CHD and in methodology existed. The outcome of infants with single-ventricle CHD was inferior to those with two-ventricle CHD (respectively: average scores for PDI 77 and 88; intelligence scores 92 and 98). Perioperative risk factors were inconsistently associated with developmental outcomes.

Interpretation: The literature on children undergoing surgery in early infancy suggests that infants with a single ventricle are at highest risk of adverse developmental outcomes.

Figure 1

Meta‐analyses of Bayley Psychomotor Developmental Index (PDI) and Mental Developmental Index (MDI). Forest plots of (a) PDI, (b) MDI. The studies are listed by the author’s last name and year, and ranked according to methodological quality (high at the top). The black boxes indicate the means, the lines the confidence intervals (CIs), and the dotted lines the prediction intervals. The black diamond indicates the estimated means from the random‐effects (RE) meta‐analysis. Heterogeneity remained: (PDI: τ ² =49.47 [p<0.001], I ² =94%; MDI: τ ² =34.03 [p<0.001]). I ² =89%). (c) Bubble plot regression graph of the association between surgery era and mean PDI of the individual studies. The symbol sizes are related to the weights of the studies in the analysis; larger diamonds indicate larger/more precise studies. Based on the meta‐regression RE model with adjustment for age, the predicted average mean PDI as a function of the covariate period (with age fixed at 21mo) is also added to the plot (line) with 95% CI (dotted lines). Surgery era code is indicated as the median year of the surgery period. (d) Bubble plot regression graph of the association between assessment age of the infant and MDI. For explanation, see the description of (c).

Figure 2

Meta‐analyses of IQ scores. (a–c) Forest plots of full‐scale IQ, verbal IQ, and performance IQ respectively. The studies are listed by the author’s last name and year, and ranked according to methodological quality (high at the top). The black boxes indicate the means, the lines the confidence intervals, and the dotted lines the prediction intervals. The black diamond indicates the estimated means from the random‐effects (RE) meta‐analysis. Heterogeneity remained: (full‐scale IQ: τ ²=9.21 [p<0.001], I ²=70.3%; verbal IQ: τ ² =11.2 [p<0.001], I ²=75.7%; performance IQ: τ ²=14.1 [p<0.001], I ² =80.4%). (d–f) Bubble plot regression graphs of the association between assessment age of the child and full‐scale IQ, verbal IQ, and performance IQ respectively. (g–i) Bubble plot regression graphs of the association between surgery era and full‐scale IQ, verbal IQ, and performance IQ respectively. For explanation, see the description of Figure 1.