Risk factors in children with optic nerve hypoplasia and septo-optic dysplasia

To identify the risk factors for optic nerve hypoplasia (ONH) and septo-optic dysplasia (SOD).

A retrospective, population-based study with case-control design was undertaken using the Population Research Data Repository at the Manitoba Center for Health Policy in Manitoba, Canada. Cases were 111 patients (63 males, 48 females; age range 1-35 years [mean 11 years 6 months, SD 7 years 2 months]) with ONH and SOD diagnosed from 1990 to 2019, matched to 555 unrelated population-based controls (315 males, 240 females; age range 1-35 years [mean 11 years 6 months, SD 7 years 2 months]) on year of birth, sex, and area of residence. Additionally, 75 cases (46 males, 29 females; age range 2-35 years [mean 12 years 6 months, SD 7 years 2 months]) with ONH and SOD were matched one-on-one with sibling controls (40 males, 35 females; age range 0-33 years [mean 11 years 7 months, SD 7 years 10 months], the rest did not have siblings). Several antenatal maternal risk factors associated with ONH and SOD were tested for their association with case and control group membership using adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from a multivariate conditional logistic regression model. The outcome was the risk of developing ONH and SOD.

Maternal age at conception (OR = 0.91, 95% CI = 0.86-0.96), primigravida (OR = 3.39, 95% CI = 1.92-6.01), and smoking (OR = 2.86, 95% CI = 1.61-5.05) were independently associated with ONH and SOD in the cohort matched to unrelated controls (p < 0.001). In the sibling cohort, smoking was an important risk factor (OR = 3.65, 95% CI = 1.2-11.1, p = 0.02).

Unmodifiable and modifiable antenatal maternal risk factors are associated with ONH and SOD. Our investigation suggests that several risk factors reported in previous studies may have been due to confounding bias and that maternal smoking during pregnancy is the main modifiable risk factor associated with ONH and SOD.

Historically, many antenatal risk factors have been associated with optic nerve hypoplasia (ONH) and septo-optic dysplasia (SOD). Population-based data with matched controls for potential confounding bias are lacking. Young maternal age at conception, primigravida, and smoking during pregnancy are the main risk factors for ONH and SOD using a population-based, case-control design.