Guideline No. 410: Prevention, Screening, Diagnosis, and Pregnancy Management for Fetal Neural Tube Defects

Published:November 16, 2020DOI:



      This revised guideline is intended to provide an update on the genetic aspects, prevention, screening, diagnosis, and management of fetal neural tube defects.

      Target population

      Women who are pregnant or may become pregnant. Neural tube defect screening should be offered to all pregnant women.


      For prevention: a folate-rich diet, and folic acid and vitamin B12 supplementation, with dosage depending on risk level. For screening: second-trimester anatomical sonography; first-trimester sonographic screening; maternal serum alpha fetoprotein; prenatal magnetic resonance imaging. For genetic testing: diagnostic amniocentesis with chromosomal microarray and amniotic fluid alpha fetoprotein and acetylcholinesterase; fetal exome sequencing. For pregnancy management: prenatal surgical repair; postnatal surgical repair; pregnancy termination with autopsy. For subsequent pregnancies: prevention and screening options and counselling.


      The research on and implementation of fetal surgery for prenatally diagnosed myelomeningocele has added a significant treatment option to the previous options (postnatal repair or pregnancy termination), but this new option carries an increased risk of maternal morbidity. Significant improvements in health and quality of life, both for the mother and the infant, have been shown to result from the prevention, screening, diagnosis, and treatment of fetal neural tube defects.

      Benefits, harms, and costs

      The benefits for patient autonomy and decision-making are provided in the guideline. Harms include an unexpected fetal diagnosis and the subsequent management decisions. Harm can also result if the patient declines routine sonographic scans or if counselling and access to care for neural tube defects are delayed. Cost analysis (personal, family, health care) is not within the scope of this clinical practice guideline.


      A directed and focused literature review was conducted using the search terms spina bifida, neural tube defect, myelomeningocele, prenatal diagnosis, fetal surgery, neural tube defect prevention, neural tube defect screening, neural tube defect diagnosis, and neural tube defect management in order to update and revise this guideline. A peer review process was used for content validation and clarity, with appropriate ethical considerations.

      Validation Methods

      The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations).

      Intended Audience

      Maternity care professionals who provide any part of pre-conception, antenatal, delivery, and neonatal care. This guideline is also appropriate for patient education.

      RECOMMENDATIONS (GRADE ratings in parentheses)

      • Prevention
      • 1
        Women with a low risk for neural tube defects or other folic acid–sensitive congenital anomalies, whose male partner also has a low risk, require a diet of folate-rich foods and a daily oral multivitamin supplement containing 0.4 mg folic acid and vitamin B12 for at least 2 to 3 months before conception, throughout the pregnancy, and for 4 to 6 weeks postpartum or as long as breastfeeding continues (strong, moderate).
      • 2
        Women with a moderate risk for neural tube defects or other folic acid–sensitive congenital anomalies, or whose male partner has a moderate risk, require a diet of folate-rich foods and daily oral supplementation with a multivitamin containing 1.0 mg folic acid and vitamin B12, beginning at least 3 months before conception. Women should continue this regime until 12 weeks gestation (strong, high). From 12 weeks gestation, continued daily supplementation should consist of a multivitamin with 0.4 to 1.0 mg folic acid throughout the pregnancy and for 4 to 6 weeks postpartum or as long as breastfeeding continues (strong, moderate).
      • 3
        Women at high risk for neural tube defects or with a male partner with a neural tube defect affecting himself or his children require a diet of folate-rich foods and daily oral supplementation with 4.0 to 5.0 mg folic acid and vitamin B12 for at least 3 months before conception and until 12 weeks gestation. From 12 weeks gestation, continued daily supplementation should consist of a multivitamin with 0.4 to 1.0 mg of folic acid throughout the pregnancy and for 4 to 6 weeks postpartum or as long as breastfeeding continues (strong, high).
      • Screening
      • 4
        The primary screening technology used to detect fetal structural abnormalities, including open and closed neural tube defects (i.e., anencephaly, encephalocele, myelomeningocele, and other spina bifida malformations), is second-trimester anatomical sonography with detailed fetal intracranial and spinal imaging (strong, moderate).
      • 5
        First-trimester sonographic neural tube defect screening and diagnostic techniques are available and recommended, especially for women with moderate- or high-risk factors. Sonography providers and units providing this first-trimester service must demonstrate appropriate training, expertise, and evidence of follow-up and audit of first-trimester sonographic anomalies (strong, moderate).
      • 6
        Maternal serum alpha fetoprotein can be used as a primary screening tool for open/closed neural tube defects, in limited clinical indications, for pregnant women if their geographical location or their clinical factors (such as a pre-pregnant body mass index ≥35 kg/m2) limit timely and high-quality sonographic screening at 18 to 22 weeks gestation (strong, moderate).
      • 7
        As a complement to maternal serum cell-free placental DNA for aneuploidy screening, maternal serum alpha fetoprotein can be used as a secondary screening tool in the second trimester (strong, moderate).
      • 8
        Positive screening on imaging for an open or closed neural tube defect (sonography with or without maternal serum alpha fetoprotein) requires timely referral to experienced providers for confirmation, genetic/etiologic investigation and diagnosis, and pregnancy management counselling (strong, high).
      • 9
        Prenatal MRI can be considered if further detailed assessment of the fetal central nervous system is required for diagnostic or management counselling (strong, high).
      • Genetic Testing
      • 10
        Following the sonographic detection of fetal anomalies, including confirmed or suspected open or closed neural tube defects, if a diagnostic amniocentesis is performed, the amniotic fluid specimen should be evaluated for fetal genetic abnormalities. The evaluation should consist of chromosomal microarray and other genetic testing, as considered appropriate after assessment of fetal anomalies and family history, with amniotic fluid alpha fetoprotein and amniotic fluid acetylcholinesterase, if required by protocols for fetal surgery decisions (strong, high).
      • 11
        For fetuses with myelomeningocele or other spina bifida anomalies, fetal exome sequencing may be considered, but only after multidisciplinary counselling and after appropriate criteria for molecular genetic sequencing are met (strong, moderate).
      • Pregnancy Management if the Fetus Has Myelomeningocele
      • 12
        Once an isolated open or closed neural tube defect is detected, and diagnostic and genetic testing results (if applicable) are available, families should be offered a choice of 3 obstetrical care management options. In the absence of specific contraindications, families should be given information about the following options: prenatal surgical repair of myelomeningocele and prognosis, postnatal surgical repair of myelomeningocele and prognosis, and pregnancy termination with autopsy (strong, high).
      • 13
        Both cesarean and vaginal delivery are an option for a fetus with a myelomeningocele when the fetus is in a vertex presentation. A systematic review and meta-analysis did not identify any neurological benefits associated with cesarean delivery. Therefore, intrapartum care should be individualized based on head size, myelomeningocele lesion size, lower limb position, and mobility considerations (conditional, low).
      • 14
        If prenatal myelomeningocele surgical repair is conducted, a pre-labour cesarean delivery should be performed at 37 weeks at the latest, to prevent possible rupture of the hysterotomy scar during labour (strong, high).
      • 15
        Following either termination of pregnancy or prenatal/postnatal death, autopsy should be offered for all cases of myelomeningocele (isolated or complex) and other neural tube defects, to provide optimal counselling for the current pregnancy and future pregnancies, as well as neural tube defect risk assessment for future pregnancies (strong, high).
      • Subsequent Pregnancies
      • 16
        Daily oral supplementation with 4.0 to 5.0 mg of folic acid in a multivitamin supplement containing vitamin B12 should be recommended for the mother, starting at least 3 months before conception and throughout the first trimester, when either member of the couple has had an isolated neural tube defect or a previous pregnancy that involved a presumed folic acid–sensitive open or closed neural tube defect (i.e., no karyotype, chromosomal microarray, or identified single-gene disorder) (strong, high).
      • 17
        First-trimester sonographic neural tube defect screening can be offered when imaging expertise is available, to allow for early fetal anatomical assessment in subsequent moderate- or high-risk pregnancies (strong, moderate).
      • 18
        Subsequent pregnancy planning after prenatal surgical repair of a myelomeningocele requires (strong, high):
        • pre-conception counselling
        • appropriate daily oral supplementation with 4.0 to 5.0 mg folic acid daily starting 3 months before conception and continuing until 12 weeks gestation
        • sharing with the parents the risk of uterine rupture, estimated at 11%–14%, and the associated risk of fetal death of 2%–4%
        • first-trimester sonographic neural tube defect screening
        • a detailed second-trimester sonographic fetal, uterine, and placental location evaluation because of increased risk of placenta accreta
        • counselling that delivery will be by repeat cesarean delivery because of the risk of uterine rupture (either scheduled at 36 weeks gestation or on an emergency basis between 26 and 37 weeks gestation).



      AF-AChE (amniotic fluid acetylcholinesterase), AFAFP (amniotic fluid alpha fetoprotein), MMC (myelomeningocele), MSAFP (maternal serum alpha fetoprotein), NTD (neural tube defect)
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