Dec. 02, 2011

Reduced Growth and Delayed Puberty in Children with Lupus

A longitudinal PRINTO study on growth and puberty in juvenile lupus erythematosus
Rygg M, Pistorio A, Ravelli A, Maghnie M, Di Iorgi N, Bader-Meunier B, Da Silva C, Roldan-Molina R, Barash J, Dracou C, Laloum SG, Jarosova K, Deslandre CJ, Koné-Paut I, Garofalo F, Press J, Sengler C, Tauber T, Martini A, Ruperto N; for the Paediatric Rheumatology International Trials Organisation (PRINTO). Annals of the Rheumatic Diseases. 2011 Oct 13. [epub ahead of print]

What is the topic?

Children represent about 15%-20% of all people with lupus. Lupus in children tends to manifest more severely and can result in the need for more aggressive treatments. As a result, children with lupus can be faced with unique challenges, including reduced height and delayed puberty. These effects may rise due to disease activity, side effects of drug treatments, and/or the presence of diseases other than lupus. 

Delayed growth and puberty can cause damage, affect quality of life, and add to the burden of coping with the disease. Relatively few studies have addressed the effects of lupus and/or its treatments on growth and development in children. 

What did the researchers hope to learn?

The researchers hoped to learn about the effects of lupus and/or its treatments on multiple indicators or growth and development in children. 

Who was studied?

The study included 331 children with lupus. 

How was the study conducted?

Patients were included in the study if they were younger than 18 years of age, had active lupus, and had body measurement data available at enrollment and at follow-up visits (at months 6, 14, and 26).

At each visit, height (cm) and weight (kg) were measured and body mass index (BMI) was calculated. Height measurements were adjusted according to chronological age (months) and the average height of both parents (called the “adjusted height”). Drug treatments for lupus were documented for each child. 

Growth failure (reduction in adjusted height), height deflection (a reduced rate of growth, as indicated by adjusted height over time), and several aspects of the development of secondary sexual characteristics were assessed for each child according to specific criteria. 
For statistical purposes, children were classified according to age at disease onset as follows: pre-pubertal (< 8 years), peri-pubertal (8-13 years), and post-pubertal (> 13 years). 

What did the researchers find?

Most of the children included in the study were girls. The children entered the study at an average age of 14 years old after having been diagnosed with lupus an average of two years prior, and having an average of six months’ worth of disease activity. At study entry, about 26% of the children were taking cyclophosphamide, about 17% were taking azathioprine, and fewer than 10% were taking either methotrexate or ciclosporin A. All 331 of the children were taking steroids. 

Growth failure at study entry was observed in about 17% of girls and 22% of boys, with no further increases during the study and with no gender differences. Height deflection was most evident at the 6-month follow-up and remained significantly impaired in 21% of females and 46% of males at the end of the study. At the end of the study (after the 26-month follow-up), a significant reduction in adjusted height (as compared to study entry) was observed in both boys and girls, but was more pronounced in boys. For both boys and girls, BMI increased significantly (as compared to study entry) and peaked at the 6-month follow-up and remained significantly increased at the end of the study. 

When the children were separated into groups according to age at disease onset, some additional trends emerged. Using these classifications, the effect of age of disease onset or disease duration on adjusted height was not significant in boys. Pre-pubertal girls (who had lupus at <8 years of age), however, showed significant reduction in adjusted height at study entry and for each of the follow-up visits for up to 26 months. Peri-pubertal girls (who acquired lupus at ages 8-13 years old) showed a significant but less pronounced reduction in adjusted height at study entry, which was most pronounced at the 14-month follow-up. Post-pubertal females (> 13 years old) showed normal adjusted height at study entry and throughout the rest of the study. 

When the children were separated into groups according to both how long they had lupus and age at disease onset, there were again no significant effects on adjusted height in boys. However, in this analysis, girls who had lupus for at least a year and were diagnosed prior to age 12 showed significant reduction in adjusted height when compared to girls who had lupus for at least a year and were diagnosed after age 12 (the latter showed normal adjusted height). 

At the end of the study, there was significantly more growth failure and height deflection in girls with age of disease onset < 12 years as compared to > 12 years. For boys with age of disease onset <14 years of age, the pattern was the same. There was a significant association among growth failure at study entry, age at first study visit, and cumulative steroid dose. 

Data from a subset of girls (147 out of 276) were used to evaluate effects on pubertal characteristics. About 15% of girls showed delayed pubertal onset. About 22% of the girls showed delayed or absent menarche (first menstrual cycle). Irregular menses or suspension of periods after initiation of menses was found in 46% of girls. For boys, 24% showed delayed pubertal onset. 

What were the limitations of the study?

Cumulative doses of steroids being taken by the children with lupus was estimated by pediatric rheumatologists, as were indications of sexual maturation. In addition, parents of children with lupus self-reported their heights. Lastly, height measurements were not standardized. 

What do the results means for you?

There were no differences among children with lupus in terms of disease characteristics or treatments according to gender or age of onset. Girls who acquired lupus before age 12 had significant reductions in growth, especially after having lupus for at least a year. In males, there were no significant associations among disease characteristics at study entry, treatments, growth failure, or pubertal delay. 

The significant increases in BMI observed in both genders at the 6-month follow-up visit are likely due to high doses of steroids being used at study entry. The children most at risk of impaired height or pubertal development were being treated with a >400 mg/kg cumulative dose of steroids.


Related Stories

Research News | May. 16, 2012

Predictors of Bone Density Changes in Children with Lupus

The researchers hoped to learn about the long-term outcomes of bone mass density (BMD) in children newly diagnosed with lupus.

Research News | Feb. 17, 2012

Reduced Bone Density in Newly Diagnosed Children with Lupus

The researchers hoped to learn about the prevalence of low bone mineral density (BMD), as well as to identify risk factors for its development, in a large cohort of newly diagnosed children and adolescents with lupus.