Effect of gestational age and birth weight on the risk of strabismus among premature infants

Abstract

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.

Figure 1. Selection of premature infants

Plan participants who were enrolled for at least six-months, born prematurely, and were not chronically ill were eligible for this study. Those with missing covariates (birth weight, gestational age, race, sex, residency, household net worth, delivery method, retinopathy of prematurity, other ocular conditions) were excluded from some analyses.

Figure 2. Cumulative incidence of strabismus among premature infants

The cumulative incidence of strabismus estimated by Kaplan-Meier for all study participants and for infants in four primary exposure groups: Very low birth weight, very premature (LBW, VP; n=2980), Very low birth weight, mildly premature (LBW, MP; n=3591), Mildly low birth weight, mildly premature (MLBW, MP; n=18365), and Mildly low birth weight, very premature (MLBW, VP; n=665). 95% confidence intervals for each exposure group are shown at two and at four years. The effect of birth weight (low birth weight increases incidence of strabismus) is consistent across different levels of gestational age; the effect of gestational age is not.

Figure 3. The hazard of developing strabismus according to two key predictors: birth weight and gestational age

The effect of each primary factor on strabismus risk was estimated in a Cox proportional hazard model and is displayed in five different scenarios. Within each panel (birth weight (BW) on left, gestational age (GA) on right), from left to right the models are for (1) the crude effect of the primary factor, (2) the effect adjusting for just the other main factor in an additive model, (3) the effect in a fully adjusted model, (4–5) the effects determined by the adjusted joint exposure model in subgroups defined by the other main factor. The risk of strabismus is higher for very low birth weight infants vs. mildly low birth weight infants in all cases. The effect of gestational age is negligible after controlling for birth weight. Two intervals are very wide for the rare combination of Mildly Low BW and Very Premature.