Association of Infantile Hemangiomas and Retinopathy of Prematurity: Analysis of the Multicenter KID

Abstract

Introduction: Retinopathy of prematurity (ROP) and infantile hemangiomas (IHs) both have similar proposed pathophysiological mechanisms. IH is more common in preterm than term infants. Hypoxia-induced mediators like vascular endothelial growth factor have been found elevated in children with hemangiomas. The aim of our study was to determine if there is an association between ROP and IH in preterm infants and to investigate racial/ethnic and gender differences of ROP and IHs in this cohort.

Methods: We accessed the national multicenter Kids' Inpatient Database (KID) Healthcare Cost and Utilization Project (HCUP) including admissions at age ≤28 days. Eligible infants were identified by using ICD-9 codes of ROP and IH in infants with gestational age (GA) ≤32 weeks and/or birth weight ≤1,500 g during the years 2003, 2006, 2009, and 2012. A weight-based analysis was performed using SAS Enterprise Guide 7.1 for complex sample design.

Results: In the cohort of 1,068,502 eligible infants, the prevalence of IH was 4.7 per 1,000 preterm admissions (<32 weeks). ROP prevalence was 16% for GA ≤26 weeks, 12.5% for GA 27-30 weeks, and 2.7% for GA 31-32 weeks. IH was significantly higher in infants with ROP; this relationship was consistent among all stages of ROP. Regression analysis showed that females are at increased risk of IH with ROP compared to males (adjusted odds ratio [aOR]: 2.00 [1.85-2.56]). White non-Hispanic premature infants had an increased risk of IH with concomitant ROP compared to both African American (aOR: 3.9 [2.63-4.76]) and Hispanic (aOR: 1.2 [1.14-1.38]) infants. However, African American infants had an increased risk of ROP compared to white non-Hispanic infants (aOR: 1.16 [1.07-1.14]). These genders and racial/ethnic disparities were consistent among GA categories.

Conclusions: To our knowledge, this is the largest cohort based on a national multicenter database comparing an association between ROP and IH. A strong association between ROP and IH may suggest similar risk factors and/or pathophysiology. A further role of genetic factors could explain racial/ethnic differences in both conditions despite similar pathogenesis. These findings may open up new bases of research for management and prevention strategies.

Keywords: Gender; Infantile hemangioma; Premature infant; Race; Retinopathy of prematurity.

Fig. 1

Cohort extraction.

Fig. 2

Forrest plot of IH by regression analysis. aOR (95% CI) of IH in infants with ROP controlled for GA, race, gender, and other congenital anomalies.