Congenital malformation affects a significant number of babies worldwide, with approximately 3% of live-born infants affected each year. In Australia alone, this amounts to around 9,000 babies and their families facing the challenges posed by these conditions annually. Sadly, congenital malformation stands as the leading cause of non-infectious infant death, surpassing even chronic childhood diseases like autism, cancer, and type 1 diabetes.

Despite its prevalence, the causes of congenital malformation largely remain a mystery, stemming from a complex interplay of genetic and environmental factors. Identifying these causes is critical for prevention and may offer insights into prognosis and treatment.

St Vincent’s Clinic Research Foundation proudly supported the pioneering research led by Professor Sally Dunwoodie AO, aimed at understanding and addressing congenital malformation. Dunwoodie’s team discovered that mutations in two genes, KYNU and HAAO, caused NAD deficiency and cases of congenital malformation and miscarriage. Our funding enabled exploration into two crucial areas: identifying additional gene mutations linked to NAD synthesis in humans with congenital malformation and modelling these and the efficacy of vitamin B3 as a preventative in mice. These avenues of research shed light on the extent to which NAD deficiency contributes to birth defects and miscarriage.

Building on this research, Professor Dunwoodie’s team is conducting a world-first clinical study investigating the levels of NAD, vitamin B3 and related molecules in women, in pregnancy, and in those with adverse pregnancy outcomes. Their groundbreaking work has already provided hope for affected families, with mothers taking vitamin B3 supplements to prevent further cases of birth defects and miscarriage.

For those already affected by gene mutations that disrupt NAD synthesis, low NAD levels may impact growth and development, highlighting the importance of clinically directed vitamin B3 supplementation. While the broader implications of NAD deficiency, birth defects and miscarriage remain unclear, this research represents a crucial step in understanding their significance.

Moreover, with evidence suggesting the involvement of additional genes in NAD synthesis, vitamin B3 supplements could offer a personalized and cost-effective preventative measure for affected families.

This research underscores the power of understanding genetic and environmental factors in disease, offering hope for prevention and improved outcomes for affected families.