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Brief Report
September 5, 2019

Association of Weight Gain Acceleration With Risk of Retinopathy of Prematurity

Sila Bal, MD, MPH1; Gui-shuang Ying, PhD2; Lauren Tomlinson, BS1; et al Gil Binenbaum, MD, MSCE1,2; for the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study Group
Author Affiliations
  • 1Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
  • 2Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
JAMA Ophthalmol. 2019;137(11):1301-1305. doi:10.1001/jamaophthalmol.2019.3447
Key Points

Question  Is fast weight gain acceleration, a surrogate for change in serum insulinlike growth factor 1 level, associated with a higher risk of severe retinopathy of prematurity (ROP)?

Findings  In this secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity study including 6835 infants undergoing ROP examinations at 29 North American hospitals, except in infants with the slowest early postnatal weight gain, increasing late weight gain acceleration was associated with increasing risk of severe ROP up to a threshold, beyond which risk fell.

Meaning  Although early slow weight gain is associated with an increased risk of ROP, the association appears more complex than previously thought, since the timing and rate of weight gain acceleration may also affect the risk of severe ROP.


Importance  Early slow postnatal weight gain, a surrogate for low insulinlike growth factor 1 (IGF-1) levels, is predictive of retinopathy of prematurity (ROP). While low IGF-1 levels inhibit retinal vessel growth, a later rise theoretically activates vascular endothelial growth factor, causing neovascularization. Rate of rise of IGF-1 level is represented by weight gain acceleration (WGA) and may be used to evaluate risk of ROP.

Objective  To evaluate whether faster WGA during a later postnatal period is associated with a higher, rather than lower, risk of severe ROP.

Design, Setting, and Participants  This secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) study included 6835 infants undergoing ROP examinations from 29 hospitals in North America from January 2006 to June 2012. Data were analyzed from September to December 2016.

Main Outcomes and Measures  Early weight gain rate (WGR) during 29 to 33 weeks’ postmenstrual age and late WGA during 34 to 38 weeks’ postmenstrual age were determined using linear regression of daily weight measurements and changes in daily weight measurements, respectively. The primary outcome was the association of late WGA with severe ROP.

Results  Of the 6835 included infants, the mean (SD) birth weight was 1086 (357) g, and the mean (SD) gestational age was 27.9 (2.5) weeks. Risk of severe ROP increased with increasing late WGA up to about the 80th percentile of WGA. After adjusting for birth weight and gestational age, among infants in the lowest early WGR tertile, there was no association of late WGA with severe ROP, and among infants in the moderate and highest early WGR tertiles, the moderate WGA tertiles had the highest risk of ROP (moderate early WGR tertile: adjusted odds ratio, 1.38; 95% CI, 0.98-1.94; highest early WGR tertile: adjusted odds ratio, 1.63; 95% CI, 1.02-2.60).

Conclusions and Relevance  Although much attention has been paid to the association of slow weight gain with ROP, the association may be more complex than appreciated. These findings suggest that low early WGR is associated with severe ROP regardless of subsequent WGA, but if early WGR is moderate or high, subsequent rapid rises in WGR are associated with increasing risk of severe ROP. If validated in additional cohorts, this finding may affect potential therapies, such as the timing of IGF-1 supplementation.

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