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Original Investigation |

Effect of Gestational Age and Birth Weight on the Risk of Strabismus Among Premature Infants

Shilpa Gulati, MS1; Chris A. Andrews, PhD1; Alexandra O. Apkarian, MD1; David C. Musch, PhD, MPH1; Paul P. Lee, MD, JD1; Joshua D. Stein, MD, MS1
[+] Author Affiliations
1W.K. Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor
JAMA Pediatr. 2014;168(9):850-856. doi:10.1001/jamapediatrics.2014.946.
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Importance  Strabismus causes irreversible vision loss if not detected and treated early. It is unclear whether birth weight (BW) and gestational age (GA) are risk factors for strabismus.

Objective  To estimate the effect of BW and GA on the likelihood of premature infants developing strabismus.

Design, Setting, and Participants  In this longitudinal cohort analysis, we monitored a group of premature children from birth to determine the proportion that developed strabismus and the timing of the first strabismus diagnosis. Multivariable Cox regression analyses assessed the relationships of BW and GA with the development of strabismus. Regression models were adjusted for other risk factors for strabismus, sociodemographic factors, and ocular comorbidities. The analysis included 38 055 otherwise healthy children born prematurely who were enrolled for more than 6 months in a nationwide US managed care network between 2001 and 2011 in communities throughout the United States.

Exposures  Birth weight less than 2000 g or GA of 32 weeks or less.

Main Outcomes and Measures  Hazard ratios (HRs) for strabismus with 95% CIs.

Results  Of 38 055 otherwise healthy children who were born prematurely, 583 received a diagnosis of strabismus later in life. The cumulative incidence of strabismus was 3.0% at 5 years. Controlling for GA and other covariates, infants born with BW less than 2000 g had a 61% increased hazard (HR, 1.61; 95% CI, 1.22-2.13) of developing strabismus. Controlling for BW and other covariates, there was no significant association between strabismus and GA (HR, 0.98; 95% CI, 0.69-1.38). Among premature infants with BW of less than 2000 g, a GA of 32 weeks or less conveyed no additional increased risk for developing strabismus relative to infants born after 32 weeks (HR, 1.27; 95% CI, 0.86-1.88). In contrast, among infants with a GA of 32 weeks or less, BW of less than 2000 g conveyed a 14-fold increase in the risk of strabismus relative to BW of 2000 g or more (HR, 14.39; 95% CI, 1.99-104.14).

Conclusions and Relevance  Independent of GA, very low BW conferred a large increase in strabismus risk among premature infants. In contrast, independent of BW, GA did not significantly affect the risk of strabismus. Updates to existing guidelines in the pediatric and ophthalmic literature should be considered, highlighting the importance of BW rather than GA and alerting clinicians about the need for careful monitoring of premature infants with low BW for strabismus.

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Figure 1.
Cumulative Incidence of Strabismus Among Premature Infants

The cumulative incidence of strabismus estimated by the Kaplan-Meier method for all study participants and for infants in 4 primary exposure groups: very low birth weight, very premature (VLBW, VP [n = 2980]); very low birth weight, mildly premature (VLBW, MP [n = 3591]); mildly low birth weight, mildly premature (MLBW, MP [n = 18 365]); and mildly low birth weight, very premature (MLBW, VP [n = 665]); 95% CIs for each exposure group are indicated with limit lines at 2 and at 4 years. The effect of birth weight (low birth weight increased the incidence of strabismus) was consistent across different levels of gestational age; the effect of gestational age was not consistent.

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Figure 2.
The Hazards of Developing Strabismus According to 2 Key Predictors: Birth Weight (BW) and Gestational Age (GA)

The effect of each primary factor on the risk of strabismus was estimated in a Cox proportional hazards model. Within each panel the models are for the crude effect of the primary factor (BW only), the effect of adjusting for the other main factor in an additive model (BW and GA), effect in a fully adjusted model (BW and GA adjusted), and the effects determined by the adjusted joint exposure model in subgroups defined by the other main factor (mildly premature and very premature). The risk of strabismus was higher for very low birth weight infants vs mildly low birth weight infants in all cases. The effect of GA was negligible after controlling for BW. Two intervals are very wide for the rare combination of mildly low BW and very premature. Black circles indicate hazard ratios and lines, 95% CIs.

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