• American College of Obstetricians and Gynecologists (ACOG). Neural tube defects. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2003 Jul. 11 p. (ACOG practice bulletin; no. 44). [81 references]

This is the current release of the guideline.

This guideline updates a previous version: American College of Obstetricians and Gynecologists (ACOG). Neural tube defects. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2001 Mar.

Neural tube defects, including:

• Cranial defects (anencephaly, exencephaly, encephalocele, and iniencephaly)
• Spinal defects (spina bifida, meningocele, meningomyelocele, myeloschisis, holorachischisis, and craniorachischisis)

Diagnosis
Management
Prevention
Risk Assessment
Screening

Medical Genetics
Neurological Surgery
Neurology
Obstetrics and Gynecology
Pediatrics
Preventive Medicine

Physicians

• To aid practitioners in making decisions about appropriate obstetric and gynecologic care
• To provide guidelines on screening for and primary prevention of neural tube defects and for management of delivery of fetuses with neural tube defects

• Pregnant women diagnosed with fetal neural tube defects
• Fetuses and newborn infants with neural tube defects

Diagnosis/Screening

1. Maternal serum alpha-fetoprotein (MSAFP) evaluation
2. Amniocentesis
3. Ultrasound

Management

1. Delivery at a facility with personnel capable of handling all aspects of neonatal complications
2. Fetal surgery (considered but not recommended)

Prevention

Periconceptional folic acid supplementation

• Risk factors for neural tube defects
• Effectiveness of periconceptional folic acid supplementation for preventing neural tube defects
• Predictive value of serum alpha-fetoprotein levels in screening for neural tube defects

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

The MEDLINE database, the Cochrane Library, and the American College of Obstetricians and Gynecologists' (ACOG's) own internal resources and documents were used to conduct a literature search to locate relevant articles published between January 1985 and January 2003. The search was restricted to articles published in the English language. Priority was given to articles reporting results of original research, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document.

Guidelines published by organizations or institutions such as the National Institutes of Health and the American College of Obstetricians and Gynecologists were reviewed, and additional studies were located by reviewing bibliographies of identified articles.

Not stated

Weighting According to a Rating Scheme (Scheme Given)

Studies were reviewed and evaluated for quality according to the method outlined by the U.S. Preventive Services Task Force.

I Evidence obtained from at least one properly designed randomized controlled trial

II-1 Evidence obtained from well-designed controlled trials without randomization

II-2 Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group

II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.

III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

Review of Published Meta-Analyses
Systematic Review

Not stated

Expert Consensus

Analysis of available evidence was given priority in formulating recommendations. When reliable research was not available, expert opinions from obstetrician-gynecologists were used. See also the "Rating Scheme for the Strength of Recommendations" field regarding Grade C recommendations.

Based on the highest level of evidence found in the data, recommendations are provided and graded according to the following categories:

Level A - Recommendations are based on good and consistent scientific evidence.

Level B - Recommendations are based on limited or inconsistent scientific evidence.

Level C - Recommendations are based primarily on consensus and expert opinion.

A formal cost analysis was not performed and published cost analyses were not reviewed.

Practice Bulletins are validated by two internal clinical review panels composed of practicing obstetrician-gynecologists generalists and sub-specialists. The final guidelines are also reviewed and approved by the American College of Obstetricians and Gynecologists (ACOG) Executive Board.

The grades of evidence (I-III) and levels of recommendations (A-C) are defined at the end of the "Major Recommendations."

The following recommendations are based on good and consistent scientific evidence (Level A):

• Periconceptional folic acid supplementation is recommended because it has been shown to reduce the occurrence and recurrence of neural tube defects (NTDs).
• For low-risk women, folic acid supplementation of 400 micrograms per day currently is recommended because nutritional sources alone are insufficient. Higher levels of supplementation should not be achieved by taking excess multivitamins because of the risk of vitamin A toxicity.
• For women at high risk of NTDs or who have had a previous pregnancy with an NTD, folic acid supplementation of 4 mg per day is recommended.
• Maternal serum alpha-fetoprotein (AFP) evaluation is an effective screening test for NTDs and should be offered to all pregnant women.

The following recommendations are based on limited or inconsistent scientific evidence (Level B):

• Women with elevated serum alpha-fetoprotein levels should have a specialized ultrasound examination to further assess the risk of NTDs.
• The fetus with an NTD should be delivered at a facility that has personnel capable of handling all aspects of neonatal complications

The following recommendations are based primarily on consensus and expert opinion (Level C):

• The ideal dose for folic acid supplementation has not been appropriately evaluated in prospective clinical studies. A 400 microgram supplement currently is recommended for women capable of becoming pregnant.
• The route of delivery for the fetus with an NTD should be individualized because data are lacking that any one route provides a superior outcome.

Definitions:

Grades of Evidence

I Evidence obtained from at least one properly designed randomized controlled trial

II-1 Evidence obtained from well-designed controlled trials without randomization

II-2 Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group

II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.

III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

Levels of Recommendations

Level A - Recommendations are based on good and consistent scientific evidence.

Level B - Recommendations are based on limited or inconsistent scientific evidence.

Level C - Recommendations are based primarily on consensus and expert opinion.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Overall Benefits

Appropriate diagnosis, management, and prevention of neural tube defects

Benefits of Folic Acid

A double-blind, placebo-controlled, randomized trial showed that periconceptional folic acid supplementation decreased the risk of a first occurrence of a neural tube defect. The efficacy of periconceptional folic acid supplementation for preventing both recurrence and occurrence of neural tube defects has since been confirmed by many other studies.

• Risks of folic acid supplementation. The risks of higher levels of folic acid supplementation are believed to be minimal. Folic acid is considered nontoxic even at very high doses and is rapidly excreted in the urine. There have been concerns that supplemental folic acid could mask the symptoms of pernicious anemia and thus delay treatment. However, folic acid cannot mask the neuropathy typical of this diagnosis. Currently, 12% of patients with pernicious anemia present with neuropathy alone. With folic acid supplementation, this proportion may be increased, but there is no evidence that initiating treatment after the development of a neuropathy results in irreversible damage. A small number of women taking seizure medication (diphenylhydantoin, aminopterin, or carbamazepine) may have lower serum drug levels and experience an associated increase in seizure frequency while taking folic acid supplement. Monitoring drug levels and increasing the dosage as needed may help to avert this complication.
• Some over-the-counter multivitamin supplements and most prenatal vitamins contain 400 micrograms of folic acid. Higher levels of supplementation should be achieved by taking an additional folic acid supplement and not by taking excess multivitamins. In particular, vitamin A is potentially teratogenic at high doses, and pregnant women should not take more than the 5,000 IU per day, which is typically found in one multivitamin/mineral supplement.

These guidelines should not be construed as dictating an exclusive course of treatment or procedure. Variations in practice may be warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice.

An implementation strategy was not provided.

Getting Better
Staying Healthy

Effectiveness

• American College of Obstetricians and Gynecologists (ACOG). Neural tube defects. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2003 Jul. 11 p. (ACOG practice bulletin; no. 44). [81 references]

Not applicable: The guideline was not adapted from another source.

2001 (revised 2003 Jul)

American College of Obstetricians and Gynecologists - Medical Specialty Society

American College of Obstetricians and Gynecologists (ACOG)

American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics

Not stated

Not stated

This is the current release of the guideline.

This guideline updates a previous version: American College of Obstetricians and Gynecologists (ACOG). Neural tube defects. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2001 Mar.

None available

None available

This summary was completed by ECRI on February 4, 2004. The information was verified by the guideline developer on July 26, 2004.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.