Identification of potential NAD-related biomarkers of recurrent miscarriage risk

This Australian prospective pilot study investigated whether women with a history of recurrent miscarriage have differences in nicotinamide adenine dinucleotide (NAD)-related metabolites that could potentially be detected in blood, plasma or urine. The study included 88 non-pregnant women aged 20–40 years: 37 with a history of recurrent miscarriage and 51 without. Researchers measured NAD and related metabolites and examined whether particular metabolic patterns were associated with recurrent miscarriage.

Women with a history of recurrent miscarriage had higher concentrations of several products of the NAD salvage pathway, particularly 1-methylnicotinamide (1MNA), 2PY and 4PY, across blood, plasma and urine samples. Plasma 1MNA remained associated with recurrent miscarriage after accounting for maternal age. A predictive model combining age with 1MNA, 2PY and 4PY achieved an area under the receiver operating characteristic curve (AUROC) of 0.89.

The findings suggest that differences in NAD metabolism may be associated with recurrent miscarriage and that some NAD-related metabolites could have potential as biomarkers. However, this was a small, single-hospital pilot study and the metabolites were measured after the participants’ pregnancies. The findings therefore need to be replicated and validated in larger studies before these markers could have a role in clinical care.

Authors: Hartmut Cuny, Antonia W Shand, Jennifer Goth, Delicia Z Sheng, Tamarah Tossey, Ella M M A Martin, Alena Sipka, Olga Aleshin, Francisco J Schneuer, Natasha Nassar, Sally L Dunwoodie
Publication date: 31 October 2025
Journal: Human Reproduction, Volume 40, Issue 12, pages 2247–2259
Link to paper: https://doi.org/10.1093/humrep/deaf195