Scientists discovered why folate (a B vitamin) is so important for preventing birth defects of the brain and spinal cord. When the body doesn’t have enough folate, a protein called KDM5A stops working properly. This causes certain genes to turn on too much, leading to problems with how the brain develops. Researchers found this pattern in lab cells, animal models, and actual brain samples from babies born with these defects. This discovery could help doctors develop new ways to prevent these serious birth defects beyond just taking folate vitamins.

The Quick Take

  • What they studied: How low folate levels cause birth defects of the brain and spinal cord by changing how genes are controlled inside cells
  • Who participated: Mouse cells in labs, zebrafish embryos, mouse models with birth defects, and brain tissue samples from babies born with these defects
  • Key finding: When folate is low, a protein called KDM5A becomes less active, which allows certain ‘growth’ genes to stay turned on too much, causing brain development problems
  • What it means for you: This research suggests that folate works by controlling how genes are turned on and off. While folate supplements are already recommended for pregnant women, this discovery might lead to new treatments that work in a similar way. However, this is early-stage research and more studies are needed before any new treatments become available.

The Research Details

Researchers used multiple approaches to understand how folate prevents birth defects. They studied cells grown in the lab that didn’t have enough folate, watched how zebrafish embryos developed when a specific protein was removed, and examined brain tissue from mice and humans with birth defects. They used special techniques to look at which genes were turned on or off and how the instructions for making proteins were being controlled. This multi-layered approach helped them trace the problem from the molecular level (inside cells) all the way to actual birth defects in living organisms.

Using multiple study types—from cells to animals to human tissue—makes the findings more convincing. When researchers see the same problem happening in different systems, it suggests they’ve found something real and important. This approach also helps identify potential targets for new treatments.

The study used advanced scientific techniques (ChIP and Cut&Tag) that are considered reliable for studying how genes are controlled. The researchers tested their findings in multiple systems (cells, fish, mice, and human tissue), which strengthens their conclusions. However, this is laboratory and animal research, so results may not directly apply to humans yet. The study was published in a peer-reviewed journal, meaning other scientists reviewed it before publication.

What the Results Show

The main discovery is that when folate levels are low, a protein called KDM5A doesn’t work properly. Normally, KDM5A acts like an eraser, removing chemical marks from genes that tell the cell to turn them on. When KDM5A isn’t working, these marks stay on the genes, keeping them turned on too much. Specifically, genes involved in the Wnt pathway (a system that controls how the brain develops) stayed too active. The researchers found this pattern in lab cells without enough folate, in zebrafish embryos missing the KDM5A protein, and in brain tissue from babies born with neural tube defects. This suggests that the KDM5A protein is a key control point that folate helps regulate.

The researchers also discovered that another protein called PAX2 controls whether KDM5A gets made. When folate is low, PAX2 reduces KDM5A production, which starts the whole chain of problems. This identifies another potential point where treatment could intervene. The findings were consistent across different types of cells and organisms, suggesting this is a fundamental biological process.

Scientists have known for decades that folate prevents birth defects, but they didn’t understand exactly how. Previous research showed that abnormal Wnt pathway activation causes these defects, but nobody knew what role folate played in controlling this pathway. This study fills that gap by showing that folate works by helping control a protein (KDM5A) that manages how active the Wnt genes are. This is a significant advance in understanding the mechanism.

This research was primarily done in laboratory cells and animal models. While the findings in human brain tissue are encouraging, they don’t prove that the same mechanism causes defects in human pregnancies. The study doesn’t show whether increasing KDM5A activity would actually prevent birth defects in humans. Additionally, the exact role of other factors that might influence this process wasn’t fully explored. More research in humans would be needed to develop new treatments based on these findings.

The Bottom Line

Current medical guidance remains unchanged: pregnant women and women planning pregnancy should take folate supplements as recommended by their doctor (typically 400 micrograms daily). This research suggests that folate’s protective effect works through a specific molecular mechanism, but it doesn’t change current prevention strategies. In the future, this research might lead to new treatments, but those are not yet available. Confidence level: High for continuing current folate recommendations; Low for any new treatments at this time.

This research is most relevant to pregnant women, women planning pregnancy, and healthcare providers. It’s also important for researchers developing new treatments for birth defects. People with a family history of neural tube defects should discuss folate supplementation with their doctor. This research doesn’t directly apply to people who aren’t pregnant or planning pregnancy, though understanding how folate works is scientifically interesting to everyone.

Folate’s protective effect works throughout pregnancy, with the critical period being before and during the first month of pregnancy when the brain and spinal cord are forming. If new treatments based on this research are eventually developed, they would likely take 5-10 years to reach patients. For now, taking folate supplements as recommended provides the best current protection.

Want to Apply This Research?

  • Track daily folate intake (in micrograms) and prenatal vitamin compliance. Set a daily reminder to take folate supplements at the same time each day and log completion. For women planning pregnancy, track folate intake for at least 3 months before conception.
  • If using a health app, set up a daily notification to take your folate supplement. Create a simple checklist in the app to mark off each day you take your vitamin. If you’re planning pregnancy, use the app to track when you start supplementation so you know you’ve had adequate folate before conception.
  • Monitor consistency of folate supplement use over weeks and months. Track any pregnancy-related milestones and correlate with supplement adherence. Share supplement compliance data with your healthcare provider during prenatal visits to ensure adequate folate intake throughout pregnancy.

This research describes laboratory and animal studies exploring how folate prevents birth defects. While the findings are scientifically interesting, they represent early-stage research and do not change current medical recommendations. Pregnant women and women planning pregnancy should continue to take folate supplements as recommended by their healthcare provider. This article is for educational purposes and should not replace medical advice. If you have questions about folate supplementation or birth defect prevention, consult with your doctor or healthcare provider. Do not make changes to your supplement routine based solely on this research summary.