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Open neural tube defects: Risk factors, prenatal screening and diagnosis

Open neural tube defects: Risk factors, prenatal screening and diagnosis



 Open neural tube defects (NTDs) are relatively common congenital anomalies that develop when a portion of the neural tube fails to close normally during the third and fourth weeks after conception (the fifth and sixth weeks of gestation). The resulting defect may involve the vertebrae, spinal cord, cranium, and/or brain.  The two most common NTDs are spina bifida (a spinal cord defect) and anencephaly (a brain defect).

Two key advances related to open NTDs have occurred in recent decades:

  • Folic acidfortification of commonly consumed foods (e.g., bread, flour, cornmeal, rice, pasta) and administration of folic acid supplements have been shown to prevent occurrence/recurrence of most open NTDs.
  • Maternal serum (blood test) and sonographic screening (ultrasound) programs have led to identification of most affected pregnancies, allowing parents to make decisions about pregnancy management.


Folate deficiency — Most isolated NTDs appear to be caused by folate deficiency, likely in combination with genetic or other environmental risk factors.

Genetic factors — Although no specific genes have been identified, genetic factors have been implicated.

Fever — Elevation of maternal core temperature from a febrile illness or other source (e.g., hot tub, sauna) in the first trimester may be associated with an increased risk of congenital anomalies, especially NTDs, or miscarriage.

Pregestational diabetes — Poorly controlled pregestational diabetes mellitus, inclusive of type 2 diabetes, has been associated with NTDs.

Obesity — Obese women have almost a twofold increase in risk of NTDs. This is particularly a concern because of the limitations of fetal imaging as a woman’s body mass index increases.



Rationale for prenatal screening — Screening and early diagnosis of affected pregnancies allows couples the option of pregnancy termination or an opportunity to prepare for the birth of an affected child.

Screening tests — The two approaches to NTD screening are ultrasound examination and measurement of maternal serum alpha-fetoprotein (MSAFP) – Blood Test.

Alpha-fetoprotein — Alpha-fetoprotein is a fetal-specific globulin, synthesized by the fetal yolk sac, gastrointestinal tract, and liver.   During a baby’s development, some AFP passes through the placenta and into the mother’s blood. An AFP test measures the level of AFP in pregnant women during the second trimester of pregnancy (Approximately 16 weeks).


 Supplemental folic acid is a safe and effective treatment for prevention of NTDs.



Stephanie Dukhovny, MD

Louise Wilkins-Haug, MD, PhD

Section Editors:

Deborah Levine, MD

Lynn L Simpson, MD

Deputy Editor:

Vanessa A Barss, MD, FACOG

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2022. | This topic last updated: Nov 30, 2021.