Researchers at the Victor Chang Cardiac Research Institute, in collaboration with the University of Sydney and the Royal Hospital for Women, have made significant strides in understanding the biology of recurrent miscarriage. This condition, which impacts approximately one in fifty couples attempting to conceive, has been a source of heartache for many families. The study, led by Dr. Hartmut Cuny and Professor Sally Dunwoodie, focuses on the metabolism of vitamin B3 (niacin) and its relationship with a crucial molecule known as NAD (Nicotinamide adenine dinucleotide).
The research involved analyzing blood, plasma, and urine samples from 88 women, some with a history of recurrent miscarriage and others without. The team discovered notable changes in three NAD-related metabolites among those who had experienced repeated losses. These findings indicate that metabolic differences exist regardless of vitamin B3 supplementation, suggesting a more complex imbalance that could contribute to miscarriage.
Implications of the Findings
Published in the journal Human Reproduction, the results provide new insights into how NAD metabolism and inflammation may influence pregnancy health. The research aims to enhance understanding of miscarriage and potentially lead to methods for identifying women at risk, as well as new treatment avenues. Dr. Cuny stated, “Every miscarriage is heartbreaking. Our goal is to understand the biology behind them, so that in time, fewer families have to go through such loss.”
This study builds on earlier work by Professor Dunwoodie, who in 2017 identified that low NAD levels could lead to birth defects and miscarriage, which vitamin B3 supplementation could prevent in mouse models. The current research indicates a shift in perspective; rather than solely focusing on low NAD levels, it suggests that variations in how the body metabolizes vitamin B3 may also play a critical role.
Future Research Directions
In light of these findings, the research team has received funding from the Australian Government Medical Research Future Fund to further investigate this area. The three-year project, set to commence in February 2026, aims to explore NAD levels and related metabolites among women with varying histories of miscarriage. The study will focus on identifying NAD-related biomarkers that could indicate an elevated risk for miscarriage, examining how the timing and number of miscarriages correlate with these metabolite levels, and assessing the role of diet and nutritional supplements on NAD metabolism.
Participants will include women from three groups: those with recurrent miscarriage, those currently undergoing recurrent miscarriage, and those with no history of miscarriage. Each participant will provide blood and urine samples while completing a comprehensive health and lifestyle questionnaire.
The researchers are hopeful that their work will ultimately lead to a diagnostic test for identifying women at risk of recurrent miscarriage. By improving the understanding of the biological mechanisms involved, they aim to prevent future losses and support families facing this challenging experience.
The study, titled “Identification of potential NAD-related biomarkers of recurrent miscarriage risk,” can be found in the journal Human Reproduction with the DOI: 10.1093/humrep/deaf195.
