Puberty and Growth in Patients with Pediatric Intestinal Failure

Background: Children with pediatric intestinal failure (PIF) are at risk for nutritional deficits and growth failure. While these morbidities may impact pubertal development, the natural history of puberty in this population is unknown. The aims of this study were to define the timing of puberty and characterize the pubertal growth spurt in children with PIF.

Methods: A retrospective review was performed of patients treated at an intestinal rehabilitation program during the years 2014-2020. Children with PIF (parenteral nutrition dependence >60 days), age >8 years, and diagnosis of short bowel syndrome before age 8 years were included. Pubertal onset was defined as achievement of Tanner stage 2 and was compared to published norms using a one-sample t-test. Peak height velocity (PHV) and age at PHV were compared to the CDC 50th percentile height curves using a one-sample t-test. Generalized estimating equations (GEE) were used to create a cubic model for height velocity, stratified by sex.

Results: This study included 110 patients (55% male) with PIF. Median age at most recent follow-up was 12.2 (IQR 10.4,14.4) years. Female patients reached pubertal onset at a slightly younger though not statistically different age than the published standards (10.45±1.81 vs. 11.15 years, p=0.13). Male patients reached pubertal onset at a significantly younger age than the published standards (12.41±1.80 vs. 13.44 years, p=0.014). This is represented graphically in Figure 1. For females, the mean PHV (8.09±2.36 cm/yr) was not significantly different compared to CDC values of 7.37 cm/yr (p=0.23), but the patients achieved their PHV at a significantly younger age compared to the CDC norms (10.70±1.06 vs. 11.71 years, p=0.001). For males, the mean PHV (9.27±2.56 cm/yr) was significantly higher than the CDC values (7.91 cm/yr, p=0.038), and the patients achieved their PHV at a significantly younger age compared to the CDC norms (12.31±2.14 vs. 13.38 years, p=0.049). The GEE model for height velocity is depicted graphically in Figure 2. Twenty-two patients (20%) had an average height-for-age Z score less than -2 at most recent follow-up.

Conclusion: Patients with pediatric intestinal failure have normal or early onset of puberty and achieve peak height velocity at a significantly younger age when compared to established norms. Despite their robust pubertal growth spurt, there remains a high incidence of short stature in this cohort, with 1 in 5 children having height-for-age Z scores less than -2 at most recent follow-up. While timing and pubertal growth seem to be relatively maintained in pediatric intestinal failure patients, these findings do reinforce the importance of ongoing attention to nutritional rehabilitation to optimize prepubertal linear growth and height potential.