medwireNews: US researchers have created age- and sex-adjusted growth charts for use in children with classic congenital adrenal hyperplasia (CAH), reflecting the distinct patterns of height and weight among patients versus the general population.
“The CAH-specific growth charts depict these differences at key stages of growth and development and provide a way to track these differences in relation to the CDC [Centers for Disease Control and Prevention] reference growth charts”, say Kyriakie Sarafoglou (University of Minnesota Masonic Children’s Hospital, Minneapolis) and colleagues.
“It is especially important as new therapies become available for providers to have a way to evaluate these new treatment options specifically in relation to growth attainment expectations at defined nodal points of classic CAH”, they explain in The Journal of Clinical Endocrinology & Metabolism.
The team collated data from two clinical cohorts in Minnesota on 515 children (54% girls) with a confirmed diagnosis of classic salt-wasting (67%) or simple virilising (33%) 21-hydroxylase-deficient CAH. Age at diagnosis was a median 0.1–0.5 months for girls and 0.2–48.0 months for boys.
The patients attended 8692 clinic appointments between the ages of 0 and 20 years. The majority (63.5%) of patients were treated with standard hydrocortisone and fludrocortisone therapy during their growth years, while 12.8% also received a gonadotropin-releasing hormone (GnRH) analogue, 10.4% an aromatase inhibitor, and 4.2% growth hormone. A further 11.1% received a combination of standard therapy plus GnRH analogue with aromatase inhibitor and/or growth hormone.
The children were considered to have reached adult height at a bone age of 15 years in girls or 17 years in boys, Sarafoglou et al say.
The CAH growth charts were generated using the Lamda-Mu-Sigma modelling method and then overlaid on the CDC 2000 growth charts between birth and age 36 months and between ages 2–20 years. Nodal point analysis was used to compare the CAH and CDC cohorts at 4-year intervals. In addition, BMI classifications were noted for each cohort at ages 4, 8, 12, 16 and 20 years
The authors report that the CAH patients showed significant differences compared with the CDC reference cohort with regard to height, weight and BMI-for-age over the full growth period.
Among girls, the CAH patients had comparable median height to the general population at age 4 and 8 years but were shorter thereafter so that at age 20 years, they were 5 cm shorter (158 vs 163 cm). Boys with CAH were taller than their peers in the general population at age 8 and 12 years but shorter at ages 16 and 20 years, with again a 5-cm median difference at the last time point (171 vs 176 cm).
The researchers also found that the children with CAH had weight and BMI percentile scores above those of their peers in the general population. For example, girls with CAH weighed an average 5 kg more than those without CAH at every point from age 8 years and this was “even more pronounced in boys”, they say.
Moreover, from age 2–12 years, the 50th CAH-specific BMI-for-age percentile was above the CDC BMI 85th percentile for both boys and girls, “suggesting that patients with CAH would be classified as overweight during these periods”, the authors comment.
They highlight the “importance of classifying overweight/obesity status in children with CAH using the CAH-specific charts” by citing a case study of a boy with simple virilising CAH who was diagnosed at age 3 years and 11 months with tall stature and a bone age of 9 years. On the CDC chart, he was considered obese throughout childhood, with a BMI consistently above the 95th percentile, but when using the CAH-specific chart, he was obese only up to age 5 years, after which he was overweight and below the 85th percentile until age 18 years.
Indeed, the researchers emphasise that the CDC charts were more likely than the CAH-specific charts to classify children with CAH as overweight or obese across all age, sex and BMI categories. For example, 37% of girls with CAH were considered overweight at age 4 years with the CDC BMI chart versus 4% of girls with the CAH chart, with corresponding rates in boys of 30% versus 8%.
They suggest that this overestimation of BMI using the CDC charts may be “driven by tall stature due to growth acceleration and advanced bone age, even in the presence of increased lean body mass.”
In addition, adiposity rebound – the BMI nadir after peak BMI at age 1 year – occurred earlier in girls and boys with CAH than the general population, at 3.3 and 3.9 years versus 5.0–6.0 years, respectively, and there were significant differences in the timing of adiposity rebound within the CAH cohort depending on sex and type of CAH.
“Our study showed that at incremental time points throughout childhood, children with CAH collectively follow specific differences in growth trajectories than unaffected children”, Sarafoglou et al summarise.
“These variations highlight the need for CAH-specific charts to assist in clinical management, appraisal of growth trajectories and to assess the impact of new therapies.”
By Lynda Williams
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