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A Systematic Review

Ihor Hrytsiuk, MB, ChB; Ruth Gilbert, MD, MSc(Epid), FRCPCH; Stuart Logan, MB, ChB, MSc(Epid), FRCPCH; Sima Pindoria, MSc(Med Stats); Charles G. D. Brook, MD, FRCP, FRCPCH

Arch Pediatr Adolesc Med. 2002;156:485-491.

Objective  To determine the effect of levothyroxine sodium starting dose on cognitive development, growth, or behavior in children with congenital hypothyroidism identified by neonatal screening.

Design  Systematic review of cohort studies. Two analyses were performed: a between-study comparison of mean starting dose with mean developmental score and an analysis of the within-study effects of starting dose on cognitive development, growth, or behavior.

Results  The between-study comparison (14 cohort studies based on 1321 patients) found that the standardized mean IQ or developmental quotient scores ranged from 90 to 115 but were not associated with the mean starting dose of levothyroxine (P = .48). The within-study comparison of 4 cohort studies (based on 558 patients) that reported the effect of the starting dose of levothyroxine on cognitive development found no consistent effects. There was weak evidence for an effect of starting dose on growth (1 study) and on behavior problems (1 study).

Conclusions  The evidence for an effect of starting dose of levothyroxine on cognitive development, growth, or behavior is too weak to justify recommendations in favor of high- or standard-dose regimens. More reliable information, based on a randomized controlled trial of starting dose or a meta-analysis of the individual patient data currently available, is required to inform treatment policies.

From the Department of Paediatric Endocrinology, the Middlesex Hospital, University College London (Drs Hrytsiuk and Brook); Systematic Reviews Training Unit, Department of Paediatric Epidemiology and Biostatistics, Institute of Child Health (Drs Gilbert and Logan and Mr Pindoria), London, England.

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