Associations Between Fetal Growth Trajectories and the Development of Myopia by 20 Years of Age

Abstract

Purpose: To evaluate the contribution of genetic and early life environmental factors, as reflected by fetal anthropometric growth trajectories, toward the development of myopia during childhood and adolescence.

Methods: This analysis included 498 singleton Caucasian participants from the Raine Study, a pregnancy cohort study based in Western Australia. Serial fetal biometric measurements of these participants were collected via ultrasound scans performed at 18, 24, 28, 34, and 38 weeks' gestation. At a 20-year follow-up, the participants underwent a comprehensive ophthalmic examination, including cycloplegic autorefraction and ocular biometry measurements. Using a group-based trajectory modeling approach, we identified groups of participants with similar growth trajectories based on measurements of fetal head circumference (HC), abdominal circumference, femur length (FL), and estimated fetal weight (EFW). Differences between trajectory groups with respect to prevalence of myopia, axial length (AL), and corneal radius of curvature measured at the 20-year follow-up were evaluated via logistic regression and analysis of variance.

Results: Prevalence of myopia was highest among participants with consistently short or consistently long FLs (P = 0.04). There was also a trend toward increased prevalence with larger HC in late gestation, although not at a statistically significant level. Trajectory groups reflecting faster HC, FL, or EFW growth correlated with significantly flatter corneas (P = 0.03, P = 0.04, and P = 0.01, respectively) and a general, but not statistically significant, increase in AL.

Conclusions: Environmental or genetic factors influencing intrauterine skeletal growth may concurrently affect ocular development, with effects persisting into adulthood.

Figure 1.

Study population flowchart. “Sufficient numbers of ultrasound measurements” was defined as least one fetal biometric parameter measured around at least four of the nominal time points during gestation. “Sufficient measurements” of a specific fetal growth parameter for inclusion in the corresponding trajectory model was defined as measurements of that fetal growth parameter around at least four of the nominal time points during gestation. The one participant removed on the basis of ophthalmic history was specifically excluded due to a history of keratoconus.

Figure 2.

Plots of the trajectory groups (estimated mean trajectories with 95% confidence intervals). (A) The five-group head circumference trajectory model (n = 439). (B) The four-group abdominal circumference trajectory model (n = 490). (C) The five-group femur length trajectory model (n = 496). (D) The six-group estimated fetal weight trajectory model (n = 429).

Figure 3.

Ophthalmic characteristics of participants in the trajectory groups of each model. (A) Head circumference model. (B) Abdominal circumference model. (C) Femur length model. (D) Estimated fetal weight model. Each panel presents the prevalence of myopia (top), mean axial length (middle), and corneal radius of curvature (bottom) for each model group. Bars represent 95% confidence intervals calculated in a one-way analysis of variance. For myopia, P < 0.05 in the femur length model and P > 0.05 in all other models; for axial length, P > 0.05 in all models; and for corneal radius of curvature, P > 0.05 in the abdominal circumference model and P < 0.05 in all other models.