A blockbuster medical breakthrough has identified a major cause of miscarriages and multiple birth defects that could change the way women prepare for pregnancy.
Having low levels of a molecule called nicotinamide adenine dinucleotide (NAD) damages embryos in the crucial first weeks of pregnancy when organs start forming, scientists at Victor Chang Cardiac Research Institute reported on Thursday.
The ground breaking study also hit on a simple, potential preventative: vitaminB3 (or niacin) supplements before and during pregnancy could prevent miscarriages and birth defects caused by NAD deficiency.
"The ramifications are likely to be huge," said the study's senior researcher Professor Sally Dunwoodie at the Victor Chang Institute.
"This has the potential to significantly reduce the number of miscarriage and birth defects around the world, and I do not use those words lightly."
The findings were the most significant advancement in pregnancy and birth research in decades, the authors said, comparing the potential implications to the discovery of the link between folate levels and neural tube defects in the 90s.
An estimated 7.9 million babies are born with significant congenital malformations globally each year and roughly one in four women will have at least one miscarriage.
Some 80 per cent of birth defects had no known cause. NAD levels could explain a significant proportion of these malformations, Professor Dunwoodie said.
Professor Sally Dunwoodie from the Victor Chang Cardiac Research Institute who is going to announce a major breakthrough on miscarriage and birth defects on Thursday. Photo: Supplied
How scientists found the cause and a promising preventative
The researchers sequenced the genes of four families who had a history of miscarriages and babies with multiple birth defects, including congenital heart, vertebral, kidney malformations.
They identified two gene mutations that affected the metabolic pathway that produced NAD – crucial for gene development and repair.
"That alone was a huge discovery," Professor Dunwoodie said. "This pathway had never before been associated with birth defects."
The team then mimicked the gene mutations in mice embryos using CRIPSR technology.
"We found that just like the humans these mice had all the same defects," Professor Dunwoodie said.
Both the human babies and mice embryos had NAD deficiency. The researchers realised they could boost NAD levels in embryos by putting niacin in the drinking water of pregnant mice.
"We got rid of the birth defects completely. It's a phenomenal finding," she said.
The possibility of affordable prevention
Publishing their findings in the New England Journal of Medicine, the authors suggested giving women Vitamin B3 (niacin) supplements before and during pregnancy could significantly cut the rate of miscarriages and congenital malformations globally.
Vitamin B3 is typically in meats and green vegetables, and most pregnancy multivitamins contain niacin.
But a recent US study of over 560 women taking pregnancy multivitamins found one third had low levels of vitamin B3 in their first trimester of pregnancy, suggesting pregnant women were either not absorbing enough niacin from the foods they ate, or they may need more niacin than pregnancy supplements provide.
The researchers do not claim to have found the source of all birth defects and miscarriages, or that boosting niacin levels can prevent all malformations.
"The findings might be restricted to families with multiple miscarriages and multiple birth defects, but it could have far broader relevance and affect many more families [at risk of having] babies with just one defect," she said.
"What we now have is the opportunity to do more research … this prevention measure needs to be confirmed in human trials.
The study also highlighted the interplay between genetics and environmental factors that could cause birth defects.
Diabetes, high BMI, inflammatory bowel syndrome, some prescription medications, coeliac disease are among myriad factors that affected the metabolic pathway that produces NAD.
"If you have a [genetic] pathways not working well, environmental factors can provide additional stress, a second hit," Professor Dunwoodie said.
Future hope for babies like Sophia
Sophia was born with a hole in her heart that caused a ventricular septal defect and needed major heart surgery to repair. Photo: Brook Mitchell
Two-year-old Sophia has the type of congenital heart condition this discovery could help prevent, the researchers hope.
Her mother Jackie had not planned her third pregnancy and was diagnosed with gestational diabetes at 27 weeks.
Jackie took all the proper precautions and gave birth with no complications.
"We took her home and we noticed that she was really lethargic and wasn't feeding properly," Jackie said.
After a battery of tests, Jackie and her father Darren were told Sophia had a hole in her heart, a ventricular septal defect.
By the time Sophia was 19 months old, the hole had become so pronounced that it needed to be repair.
"When they told us she had to have surgery were really worried about how she would go, how she would recover," Jackie said.
"She was so little – half the size of other babies her age – and having major surgery.
"Anything to cut the risk of your child having to through something like that I think is great," she said.
Sophia's paediatric cardiac surgeon Professor David Winlaw hoped the discovery would mean fewer patients like Sophia would wind up on his operating table once the findings could be confirmed in human studies.
"This is the most significant breakthrough in understanding the causes of congenital abnormalities that has hit the world of what I do," said Professor Winlaw at the Children's Hospital Westmead and a study co-author.
The findings made a strong case for adding niacin to the official recommendations for supplements in pregnancy alongside folic acid, Professor Winlaw said.
"Though we have a fair bit of work to do before then," Professor Winlaw said, referring to population-based trials.
"We will need to determine the optimal and safe levels of niacin women should take [and which women are most at risk]."