Retinal microvasculature and risk of spontaneous abortion in multiethnic Southeast Asian women

Objective: To better understand the underlying pathogenesis of spontaneous abortion that affects 10%-20% of recognized pregnancies. We used retinal imaging to study the role of systemic microvasculature and the risk of spontaneous abortion.

Design: A prospective multiethnic preconception cohort study conducted in Singapore.

Setting: Hospital-based.

Patient(s): A total of 1,032 Southeast Asian women who intended to conceive naturally were screened at study entry, among which 480 women spontaneously conceived within the 12-month observation period. After excluding 24 women who were lost to follow-up, we calculated the spontaneous abortion rate among 456 women. Further, we included 379 women for the final association analysis because 63 women did not undergo preconception retinal imaging examination and 14 had other types of pregnancy loss instead of spontaneous abortion.

Intervention(s): Trained photographers performed retinal examination using a 45-degree nonmydriatic retinal camera at study entry during the preconception screening. Using a semiautomated, computer-based program, we assessed quantitative retinal microvascular measurements, including caliber, fractal dimension, curvature tortuosity, and branching angle. Clinical research coordinators collected information on sociodemographic status, menstrual characteristics, and lifestyle, and assessed blood pressure and anthropometry at study entry.

Main outcome measure(s): We performed a modified Poisson regression model to estimate the relative risk (RR) and 95% confidence interval (CI) for each retinal microvascular feature and its association with spontaneous abortion after adjusting for major confounders such as maternal prepregnancy, body mass index, and previous pregnancy loss history.

Result(s): We reported a spontaneous abortion rate of 13.4% (61 out of 456). Among all retinal microvascular features, retinal arteriolar caliber, retinal arteriolar, and venular curvature tortuosity were associated with a high risk of incident spontaneous abortion. In the regression model, per SD increase in retinal curvature tortuosity was associated with a 25%-34% increased risk of incident spontaneous abortion (arteriolar: unadjusted RR, 1.29 [95% CI, 1.06-1.56] and adjusted RR, 1.26 [1.04-1.53]; venule: unadjusted RR, 1.30 [1.08-1.55] and adjusted RR, 1.34 [1.09-1.64]).

Conclusion(s): Our prospective cohort observed an increased risk of spontaneous abortion among Asian women with more tortuous retinal vessels assessed during the preconception phase. Our results indicate a role of vascular inflammatory and oxidative stress in the pathogenesis of spontaneous abortion.

Clinical trial registration number: ClinicalTrials.gov, NCT03531658.