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Kids born to mothers with diabetes might see eye problems by early adulthood, a new study suggested.

In a nationwide cohort study of Danish mother-offspring pairs, children who were prenatally exposed to diabetes had a 39% increased risk for developing high refractive error in the eyes by age 25 (HR 1.39, 95% CI 1.28-1.51, P<0.001), according to Yongfu Yu, PhD, MSc, of Aarhus University in Denmark, and colleagues.

Compared with offspring unexposed to diabetes, kids born to mothers with diabetes had an overall 0.72% higher cumulative incidence difference (95% CI 0.51-0.94%).

This included mothers with type 1 diabetes, type 2 diabetes, and gestational diabetes, the authors explained in .

However, the risk for developing this common eye problem, which prevents the eye from properly focusing images on the retina, was highest for offspring born to mothers with type 2 diabetes:

• Type 2 diabetes: HR 1.68 (95% CI 1.36-2.08, P<0.001)
• Type 1 diabetes: HR 1.32 (95% CI 1.15-1.51, P<0.001)
• Gestational diabetes: HR 1.37 (95% CI 1.21-1.55, P<0.001)

When looking at the varying risks for a few of the specific types of high refractive error -- hypermetropia, myopia, and astigmatism -- exposure to diabetes in utero was associated with significantly increased risks for all three of these eye conditions. Specifically, there was a 37% increased risk for offspring developing hypermetropia, a 34% increased risk for myopia, and a 58% increased risk for astigmatism.

Pregnancy complications only seemed to magnify this association as well, as offspring born to mothers who experienced diabetes-related complications during pregnancy saw more than a twofold increased risk for high refractive error (HR 2.05, 95% CI 1.60-2.64, P<0.001). Not surprisingly, this risk only increased if the mother experienced two or more complications during pregnancy.

Identified through ICD-10 codes in the Danish National Patient Registry, these complications included diabetic coma, ketoacidosis, and diabetes with kidney, ophthalmic, neurological, circulatory, unspecified, or multiple complications.

Yu's group offered some possible reasons for the association between maternal diabetes and eye problems in their offspring, such as maternal elevated serum glucose levels, which may lead to hyperglycemia in the fetus from the placenta, inducing both vascular endothelial dysfunction and neuropathy. "This may result in the leakage or breakdown of the blood-ocular barrier endothelial system, in turn leading to aqueous humor osmotic pressure changes and subsequent RE [refractive error] after birth," they wrote.

Another possible explanation for this link may stem from increased oxidative stress and inflammatory responses to hyperglycemia in the utero, leading to eye damage. Reinforcing this idea, Yu's group pointed out that infants born to mothers specifically with gestational or pregestational diabetes had significantly lower pericentral macular retinal variables and a higher risk of superior segmental optic nerve hypoplasia.

The authors also noted that "hypermetropia occurred more frequently in childhood and myopia was more frequent in adolescence and young adulthood. This difference might be due to the natural process of emmetropisation, which could correct most hyperopia in early infancy over time. In addition, the increasing years and intensity of school education could increase the risk of myopia from early childhood to young adulthood."

For this analysis, they drew upon data from 2,470,580 individuals from Denmark who were born from 1977 to 2016. Among this group, 2.3% (n=56,419) were prenatally exposed to some form of diabetes, including 0.9% exposed to type 1 diabetes, 0.3% to type 2 diabetes, and 1.1% to gestational diabetes.

Rates of diabetes drastically increased over the past few decades, as only 0.4% of mothers in 1977 had some form of diabetes versus 6.5% in 2016. Mothers with diabetes tended to be older, well-educated, live alone, and have a higher parity versus mothers free of diabetes.

Over the course of a 25-year follow-up, a total of 553 offspring to mothers with diabetes developed high refractive error (0.93 per 1,000 person-years) versus 19,695 of those born to mothers free of diabetes (0.42 per 1,000 person-years).

"As many REs in young children are treatable, early identification and intervention can have a lifelong positive impact," the researchers underscored. "Therefore, although the 39% increased risk is a relatively low effect size, from a public health perspective, considering the high global prevalence of REs, any tiny improvement in this low-risk preventable factor will contribute to a huge reduction in absolute incidence of REs."

One place to start tackling this problem is investing in early ophthalmological screening for offspring of mothers with diabetes, particularly for those who experienced diabetes-related complications, Yu and colleagues recommended. This intervention should likewise be paired with glucose control in mothers with diabetes during pregnancy to mitigate risk.

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