Study examines folic acid dose and bleeding risk in pregnancy

Taking 800 micrograms or more of folic acid per day may increase some women’s risk of vaginal bleeding in early pregnancy, according to a new study from Flinders University, but a GP expert has warned of nuances in the findings.
 
For the study, researchers analysed data from more than 2400 first-time mothers, comparing two cohorts recruited before and after Australia introduced mandatory folic acid fortification of bread-making flour in September 2009.
 
Women recruited after fortification were much more likely to be taking high-dose supplements and had higher folate levels overall.
 
The data revealed that women taking 800 micrograms or more of folic acid per day were more likely to report spotting and mild bleeding during the first 16 weeks of pregnancy.
 
In pregnancies carrying a boy, the risk of vaginal bleeding was more than double compared with women who did not take folic acid supplements.
 
Researchers emphasised that the findings ‘do not challenge the well-established benefits of folic acid’ in preventing serious birth defects, but suggest ‘more may not always be better’.
 
RACGP NSW&ACT Chair Dr Rebekah Hoffman agrees that ‘every pregnant person should be recommended to have a folic and iodine supplement’.
 
However, she told newsGP there are nuances to the findings.
 
‘When we talk about standard dosing, we’re talking about 400 to 500 micrograms, so that’s what we would recommend every patient have to reduce their risk,’ Dr Hoffman said.
 
‘But when we’re talking about high dose, if there’s a high risk of neural tube defects, it’s five milligrams.’
 
Researchers say the findings highlight the importance of ensuring supplementation levels are appropriate in an era when most women also receive folic acid through fortified foods.
 
The study’s senior author, Professor Claire Roberts, said the recommended daily dose of about 400 micrograms ‘may be sufficient for most women’ in countries where food fortified with folic acid is available.
 
‘We need further research to understand the biological mechanisms behind these associations and to determine whether supplementation guidelines should be refined,’ she said.
 
Dr Hoffman said the study is a reminder for GPs to check in with their pregnant patients about what supplements they might be taking.
 
‘It’s a really lovely takeaway from this; making sure we’re asking all the questions, making sure that they bring in every supplement that they’re taking,’ she said.
 
‘Quite often our patients don’t consider these to be medications, or don’t think that the GP wants to know about the vitamins that they’re taking; whereas in fact we absolutely really do want to know to make sure that they’re on the right thing and there’s no interactions with either other vitamins or other medications.’
 
Professor Roberts said the findings also point to a previously unrecognised interaction between folic acid intake, a baby’s sex, and pregnancy health.
 
‘This is the first study to show that the relationship between folic acid supplementation and vaginal bleeding appears to differ depending on whether a woman is carrying a boy or girl,’ she said.
 
Of the women in the study who experienced vaginal bleeding, those carrying boys were also more likely to give birth earlier than women who did not experience bleeding.
 
The researchers said fetal sex ‘is known to influence pregnancy outcomes‘.
 
‘This is thought to be because of fetal sex-specific genetic differences that likely explain fetal sex differences in placental gene expression,’ they wrote. 
 
Dr Hoffman suggests the reasons for the bleeding may not be causative, but ‘correlative’.
 
‘It might be that there’s another reason that with boy fetuses there is more likely to be vaginal bleeding,’ she said.
 
‘They’re so early in the pregnancy at that point in time that they might get some spotting or some bleeding. It’s even before any genitalia have presented themselves.’
 
Professor Roberts said that while the study’s findings should not discourage mothers-to-be from taking folic acid supplements, it should be done in consultation with their GP or other healthcare provider.
 
Dr Hoffman agrees, adding that pregnant females are an ‘under-researched population’.
 
‘That’s what’s nice about these studies, they often ask more questions than they answer, and it really shows that we need more research in this space,’ she said.
 
‘We know that females and pregnant females have significantly less funding into research and significantly lower historical levels of research as well, so I definitely encourage more funding in this space.’
 
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