Children treated with recombinant human growth hormone (rhGH) were found to be at increased risk for cardiovascular events during early adulthood, according to a study published in JAMA Pediatrics.

In this nationwide population-based cohort study, Swedish treated with rhGH (n=3408) between 1985 and 2010 were included. Health outcomes were prospectively collected through 2014. Each child was matched for sex, year of birth, and geographic region with 15 control individuals (n=50,036) from the Swedish Total Population Register.

The average age for beginning rhGH therapy was 9.3±3.2 years, the median follow-up time was 14.9 years (range, 0-25 years), and the average age at the study conclusion was 25.1±8.2 years.

In total, 1809 cardiovascular events were observed, corresponding to 25.6 events per 10,000 person-years (py; 95% CI, 21.6-30.4) among patients and 22.6 events per 10,000 py (95% CI, 21.5-23.7) among control individuals.


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Patients had higher rates of all cardiovascular events than control individuals (adjusted hazard ratio [aHR], 1.69; 95% CI, 1.30-2.19), and this risk was further elevated in women vs men (aHR, 2.05; 95% CI, 1.31-3.20 vs aHR, 1.55; 95% CI, 1.12-2.13, respectively).

Patients who received rhGH for small for gestational age (SGA) had the highest risk for cardiovascular events (aHR, 1.97; 95% CI, 1.28-3.04), followed by those treated for growth hormone deficiency (GHD; aHR, 1.66; 95% CI, 1.21-2.26) and idiopathic short stature (ISS; aHR, 1.55; 95% CI, 1.01-2.37).

Patients who were exposed to rhGH therapy for longer periods of time had increased risk for cardiovascular events (3-6 years: aHR, 1.58; 95% CI, 1.10-2.28; ³7 years: HR, 2.08; 95% CI, 1.35-3.20; P =.01). Patients with the largest cumulative dose of rhGH (³4500 mg) were at increased risk for all cardiovascular disease (aHR, 2.05; 95% CI, 1.18-3.55).

A total of 167 severe cardiovascular events were observed. Patients were at increased risk for severe events compared with control individuals (aHR, 2.27; 95% CI, 1.01-5.12). This risk was more prevalent among women (aHR, 3.65; 95% CI, 0.84-16.08) than men (HR, 1.92; 95% CI, 0.72-5.11).

Study limitations include the fact that some conditions which caused these children to be prescribed rhGH therapy may also be associated with increased risk for cardiovascular complications. It remains unclear to which extent the therapy or the underlying condition may be driving these observations.

These data suggest that rhGH therapy during childhood for SGA, GHD, or ISS may be associated with an increased risk for cardiovascular events during early adulthood. The increased risk was amplified among women.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Tidblad A, Bottai M, Kieler H, et al. Association of childhood growth hormone treatment with long-term cardiovascular morbidity. JAMA Pediatr. 2020;e205199. doi:10.1001/jamapediatrics.2020.5199