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Embryology · Teratology and prenatal diagnosis

Folic acid and neural tube defect prevention !

  • Topic

The neural tube closes in the first month, before many women know they are pregnant: that is why folic acid is started before conception.

Updated 2026-11-01

See it in 3D: Spinal cord · Sacrum

What it is

Folate is essential for DNA synthesis and methylation, and the neural tube grows very fast during week 4 after fertilization. A folic acid supplement before conception and in the first trimester lowers the risk of anencephaly and spina bifida. Because closure happens so early, it is recommended for every woman who could become pregnant, and food fortification reaches those not planning a pregnancy.

Key facts

  • Folic acid is the synthetic form of folate used in supplements and fortified foods.
  • Many countries fortify flour or cereals with folic acid to reach unplanned pregnancies.
  • Maternal hyperthermia in the first month is also linked to neural tube defects.
  • Folate antagonists (methotrexate) and valproate interfere with this pathway.
  • Maternal folate deficiency also causes megaloblastic anaemia.

Structure

  • Folate supplies one-carbon units to build nucleotides (thymidine and purines).
  • It also feeds the methionine cycle, the source of methyl groups for DNA and proteins.
  • Neuroepithelial cells proliferate very fast while the neural folds bend and fuse.

Function

  • Folic acid supplement before conception and through the first trimester for every woman who could become pregnant.
  • A preconception plan with the treating professional when there is a previous neural tube defect, treated epilepsy, diabetes or obesity.
  • Fortification of staple foods as a public health strategy.

Step by step

  1. Week 3: the neural plate thickens over the notochord.
  2. Early week 4: the neural folds rise and fuse, starting in the cervical region.
  3. Around day 25 the cranial neuropore closes; if it fails, anencephaly results.
  4. Around day 28 the caudal neuropore closes; if it fails, spina bifida results.
  5. With enough folate, proliferation and closure happen on time.

Clinical notes

  • Neural tube defects are suspected from high maternal AFP and seen on ultrasound (lemon and banana signs).
  • Open spina bifida can cause leg paralysis, neurogenic bladder and hydrocephalus.

Test yourself

Think of the answer, then tap the question to see it.

Why is folic acid recommended before conception rather than only once pregnancy is confirmed?

Because the neural tube closes in week 4 after fertilization, often before the pregnancy is known.

Which defect results from failed closure of the cranial neuropore, and which from the caudal one?

Cranial: anencephaly; caudal: spina bifida.

Which two drugs raise neural tube defect risk by interfering with folate or its pathway?

Valproate and methotrexate (carbamazepine as well).

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The structures of Durgical's 3D anatomy where it is found.

In Pharmacology

← All of embryology

Educational content on embryonic development; not a guide to prenatal diagnosis or to medicines in pregnancy and no substitute for a health professional's advice. No doses are given.

Sources: About Folic Acid (CDC, 2024); Diabetic Embryopathy (StatPearls Publishing (NCBI Bookshelf), 2023); Langman's Medical Embryology, 13th ed., ch. 9: Birth Defects and Prenatal Diagnosis (Wolters Kluwer, 2015).

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