Research uncovers new molecular and immune insights into recurrent miscarriage causes - Video

A new study sheds light on a hidden cause of recurrent miscarriage, offering hope for affected couples worldwide. Researchers at the Victor Chang Cardiac Research Institute, University of Sydney, and Royal Hospital for Women investigated whether disturbances in vitamin B3 (niacin) metabolism might explain why some pregnancies end in repeated loss.

Their work, published in Human Reproduction, reveals complex alterations in NAD metabolism in women with recurrent miscarriage, opening new pathways for diagnosis and treatment.

The study analyzed blood, plasma, and urine samples from 88 women, including those with two or more consecutive miscarriages and healthy controls. Using ultra-high performance liquid chromatography paired with tandem mass spectrometry, the team quantified 25 NAD-related metabolites. Sophisticated statistical analyses, including partial least-squares discriminant analysis and machine learning, identified three key metabolites—1-methylnicotinamide (1MNA) and its derivatives-differing significantly between groups. These changes were independent of vitamin B3 supplementation, suggesting fundamental metabolic disruptions. Elevated plasma 1MNA levels correlated with a 2% higher miscarriage risk per unit increase.

Building on earlier discoveries that low NAD levels cause developmental defects in mice, this research reveals a more nuanced picture in humans involving altered vitamin B3 metabolism rather than simple deficiency. The study’s methodological strength lies in its multi-sample design, advanced metabolomic profiling, and robust statistical approach, enhancing confidence in findings despite modest sample size.

With funding secured for a three-year longitudinal follow-up starting in 2026, researchers will explore NAD biomarkers, dietary impacts, and other clinical factors in larger cohorts, including women currently experiencing miscarriages. Ultimately, this work aims to develop predictive tests and targeted interventions to reduce recurrent pregnancy loss, offering tangible hope for families.

This discovery dramatically advances our molecular understanding of miscarriage risk, heralding new precision medicine approaches to protect maternal and fetal health.

REFERENCE: Cuny, H., et al. (2025). Identification of potential NAD-related biomarkers of recurrent miscarriage risk. Human Reproduction. doi: 10.1093/humrep/deaf195. https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf195/8307317