In children with CAH, developmental difficulties can emerge as early as infancy and broaden across domains throughout their lifespan.In a cross-sectional study, children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency show distinct developmental challenges at different ages.
“[In our study,] infants and toddlers with CAH tend to have more trouble with movement skills, while school-age children have more trouble with thinking and everyday life skills,” the investigators said. “These differences may start earlier in life than we once thought, and they could be related to having the condition itself.”
Infants, toddlers
Infants and toddlers showed gross motor skills below the normative mean (Bayley-4*; 27th percentile, 8.2 vs 10; p=0.03), which, according to the researchers, may have stemmed from programming effects from birth. [Horm Res Paediatr 2026;doi:10.1159/000550902]
They added that these results were “largely unanticipated”, in view of evidence showing increased muscle strength in older patients with hyperandrogenism. [Gynecol Endocrinol 2015;31:237-242; Psychoneuroendocrinology 2009;34:249-258]
“However, gross motor skills require more than muscle strength alone, encompassing larger movements with coordination and balance … [Hence,] other affected developmental abilities may contribute to the lower gross motor skills seen in very young children with CAH,” the researchers said.
Children
Children showed decreased overall auditory working memory (WISC-V** Digit Span Total; 27th percentile, 8.2 vs 10; p=0.01) and nonverbal learning skills (WRAML-2*** Design Memory; 21st percentile, 7.6 vs 10; p=0.02) compared with the normative mean.
Parents reported significantly lower overall motor skills on composite scoring (Vineland-3#; 26th percentile, 90.3 vs 100; p=0.006), with fine motor skills lower than the normative mean (27th percentile, 13.2 vs 15; p=0.001). They also reported lower overall adaptive behaviour skills on composite scoring (Vineland-3; 30th percentile, 92.2 vs 100; p=0.004), with communication skills lower than the normative mean (27th percentile, 90.7 vs 100; p=0.006).
In a sensitivity analysis excluding children on puberty blockers, the primary working memory outcome remained significantly lower than the normative mean (WISC-V Digit Span Backward, 8.3 vs 10; p=0.04).
Children with CAH have smaller hippocampal and prefrontal cortex regions, which are part of the auditory working memory network. [J Clin Endocrinol Metab 2020;105:1098-1111; J Neurosci 2016;36:4492-4505] However, the association between brain structure and auditory working memory skills in these patients has yet to be fully elucidated, the researchers noted.
“[A]daptive behaviour skills are the practical and social skills required to live independently every day … [L]ower adaptive skills observed at home could be related to lower cognitive and motor skills in young children with CAH,” they said.
Early developmental screening warranted
The cohort included 13 infants and toddlers (≤3.5 years) and 21 children (3.5–11.9 years; Tanner II, n=4; Tanner III, n=3). All Tanner children were on puberty blockers. Most participants (n=28) had salt-wasting CAH, while the rest had simple-virilizing CAH.
The researchers acknowledged limitations, including the small sample size, the lack of comprehensive measurement of general intellectual functioning, and the limited sensitivity of some neuropsychological instruments used in the study.
“Despite these limitations, this study provides initial exploratory, clinically relevant data on neurodevelopment in young children with CAH and lays the groundwork for future larger-scale investigations,” they said.
“[The findings show that] developmental difficulties appear to emerge as early as infancy in CAH and can then broaden across domains throughout the patient lifespan,” the researchers said. “Our findings … highlight the potential need for early developmental screening in these at-risk patients.”
The researchers called for future studies from infancy through adulthood to shed light on the developmental trajectory of children with CAH.