Cognitive outcome in congenital central hypothyroidism: a systematic review with meta-analysis of individual patient data

in European Journal of Endocrinology

Correspondence should be addressed to N Zwaveling-Soonawala; Email:
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To provide an overview of cognitive and motor outcome, and quality of life (QoL) in patients with congenital central hypothyroidism (CH-C).


Systematic review with individual patient data (IPD) meta-analysis.


OVID MEDLINE, EMBASE and PsycInfo were searched from inception to June 11th, 2019. Studies in patients with CH-C, either isolated or with multiple pituitary hormone deficiency (MPHD), were included if CH-C patients could be separated from any additional patient groups. Primary outcomes were full-scale intelligence quotient (FSIQ) and motor outcome; secondary outcome was QoL. Following data-extraction, one-stage IPD meta-analysis was performed, fitting a linear mixed model with FSIQ as dependent variable. Random intercepts were fitted for each study.


Six studies measuring FSIQ were eligible for meta-analysis, comprising 30 CH-C patients (20 males; 27 MPHD patients). FSIQ range was wide (64–123). Mean weighted FSIQ was 97 (95% CI: 88–105). Twenty-seven percent had an FSIQ below 85 (≥1 s.d. below norm score), and 10% below 70 (≥2 s.d. below norm score). There was no significant association between FSIQ and sex or age. Age at treatment initiation was available from three studies only, thus impeding a reliable analysis of this parameter. Motor outcome and QoL were each studied in one study; no quantitative analyses could be performed for these outcomes.


A wide range in FSIQ scores was observed in CH-C patients. Results should be interpreted with caution, because included patients mainly had MPHD and age at treatment initiation was unknown for the majority of patients.

Supplementary Materials

    • Supplementary file 1. Search strategy
    • Supplementary file 2. Newcastle-Ottawa Scale, adapted for quality assessment of cross-sectional studies for the systematic review “Cognitive outcome in congenital central hypothyroidism: a systematic review with meta-analysis of individual patient data”
    • Supplemental File 3.Studyselectionprocessforprimaryoutcomemotor function, reportedusingthePRISMA IPD flow diagram. Abbreviations: CH, congenitalhypothyroidism; CH-T, congenitalhypothyroidism of thyroidal origin; IPD, individualpatientdata.
    • Supplementary table 1. Overview of eligible studies unable to provide Individual Patient Data (IPD)
    • Supplementary Table 2. Risk of bias assessment of studies reporting on primary outcome full- scale intelligence quotient


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