Hebrew University team finds how folic acid prevents spinal and brain birth defects

Doctors have advised women for decades to take folic acid, vitamin B9, before and in early pregnancy because it sharply reduces the risk of neural tube defects such as spina bifida and anencephaly. Exactly how it protects the embryo, however, has remained unclear. A study published in PNAS and announced by the Hebrew University of Jerusalem on 10 August 2026 offers a large part of the answer.

The work was led by Prof. Abraham Fainsod and his MD-PhD student Tamir Edri at the Hebrew University's Faculty of Medicine, with Prof. José António Belo of NOVA Medical School in Lisbon and an international team. Early in development, a flat sheet of cells called the neural plate folds up and its edges join like a zipper to form the neural tube, which becomes the brain and spinal cord. The researchers found that folic acid helps switch on a gene called ALDH1L1. The enzyme it encodes turns a vitamin A-derived molecule, retinaldehyde, into retinoic acid, a signal that tells developing cells when to grow, what to become and when to stop dividing.

Using frog embryos, a standard model for early development, the team created embryos whose neural tubes failed to close and treated them with folic acid, which helped many of them develop normally. When ALDH1L1 was knocked out, the protection disappeared. With too little retinoic acid, future nervous-system cells multiplied too fast and the neural plate became abnormally large; folic acid brought growth back toward normal only when the enzyme was working. The researchers also showed that the human version of ALDH1L1 can make retinoic acid and that the pathway is active in mammalian cells. In the embryos, small amounts of vitamin A boosted the effect of low-dose folic acid, though the authors stress that excess vitamin A is itself harmful in pregnancy.

The authors suggest that faults in this pathway could help explain why folic acid prevents many but not all neural tube defects, while cautioning that much more research is needed to confirm the mechanism in human pregnancy.