Deep diving into miscarriage’s clue: Scientists discovered significant metabolic dysregulation tied to repetitive pregnancy loss.
Scientists explored a chief metabolic aberration that could be a cause for recurrent miscarriage in women.
The research unearthed how the body uses vitamin B3 and the role of cell molecule, Nicotinamide Adenine Dinucleotide (NAD) as crucial in rising miscarriage.
The discoveries made by researchers from Victor Chang Cardiac Research Institute, University of Sydney, and the Royal Hospital for Women. The findings were published in the journal Human Reproduction.(1✔ ✔Trusted Source
Identification of potential NAD-related biomarkers of recurrent miscarriage risk
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NAD is the main coenzyme responsible for cell health, energy, and DNA repair. Three specific metabolites produced as excretion products in NAD salvage pathway are found be elevated in women who experienced continual miscarriage.
The study offers new avenues for developing tests and treatment options for analyzing miscarriage and women’s health.
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A Deeper Metabolic Imbalance Linked to Recurrent Miscarriage
Analysing blood, plasma, and urine samples from 88 women with and without a history of recurrent miscarriage (two or more consecutive losses), the team found distinct changes in three NAD-related metabolites in those who had experienced repeated losses. These differences occurred regardless of vitamin B3 supplementation, suggesting a deeper metabolic imbalance may be involved.
“Every miscarriage is heartbreaking,” said Dr. Cuny. “Our goal is to understand the biology behind them, so that in time, fewer families have to go through such loss.”
This new research builds on Professor Dunwoodie’s 2017 discovery that low NAD levels cause birth defects and miscarriage, which are prevented by vitamin B3 supplementation in mouse models.
This led to the theory that insufficient NAD levels might be linked to some cases of miscarriage.
More Complex Metabolism Than Previously Thought
However, in women, the story appears more complex. Rather than NAD being simply “too low,” this new study shows changes in how vitamin B3 is metabolised may also play a key role – revealing that the pathway’s impact on reproduction might be more varied than previously thought.
Building on these findings, the team has now been awarded a Australian Government Medical Research Future Fund Grant to continue this line of investigation. The new three-year project will commence in February 2026.
Working in partnership with women who have experienced miscarriage and their clinicians, the study will investigate NAD levels and related metabolites among women with and without a history of recurrent miscarriage.
The Ultimate Goal: Diagnostic Tests and Prevention
Next Steps in Clinical Exploration of NAD and Recurrent Miscarriage:
- Identify NAD-related biomarkers that may indicate elevated miscarriage risk
- Examine how timing and number of miscarriages correspond to NAD metabolite levels
- Assess the impact of diet and nutritional supplements on NAD metabolism
- Explore other clinical factors that may interact with NAD metabolism and recurrent miscarriage risk
The study will involve women from three groups – those with recurrent miscarriage, those currently experiencing recurrent miscarriage, and those with no history of miscarriage – recruited from the Royal Hospital for Women and Nepean Hospital.
Each participant will provide blood and urine samples and complete a detailed health and lifestyle questionnaire.
Researchers hope this work will ultimately lead to a diagnostic test to identify women at risk of recurrent miscarriage and improve understanding of the biological mechanisms involved, so that in time some future losses might be prevented.
Reference:
- Identification of potential NAD-related biomarkers of recurrent miscarriage risk – (https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf195/8307317)
Source-Eurekalert