SOGC CLINICAL PRACTICE GUIDELINE

It is the Society of Obstetrician and Gynaecologists of Canada (SOGC) policy to review the content 5 years after publication, at which
time the document may be revised to reflect new evidence or archived.

No. 410, January 2021 (Replaces No. 314, October 2014)

Guideline No. 410: Prevention, Screening,

Diagnosis, and Pregnancy Management for
Fetal Neural Tube Defects
The English document is the original version. In the event of any Subject Category: Genetics
discrepancy between the English and French content, the English
2019 SOGC Genetics Committee: Francois Audibert (co-chair),
version prevails.
Jo-Ann Brock, June C. Carroll, Shannon Dwinnell, Catriona
This clinical practice guideline was prepared by the author and
Hippman, Sylvie Langlois, Nanette Okun (co-chair), Chisty
overseen by the SOGC Genetics Committee. It was reviewed by

e-Pouliot, R. Douglas Wilson, Karen Wou,
Pylypjuk, Karine Valle
the SOGC Family Physician Advisory and the Medico-Legal and
and Rhonda Zwingerman
Ethics Committees, and approved by the SOGC Guideline Man-
agement and Oversight Committee and the SOGC Board of Disclosures: Statements were received from the author. No
Directors. relationships or activities were disclosed.
This clinical practice guideline supersedes No. 314, published in
The authors have indicated that they meet the journal’s
October 2014.
requirements for authorship.
R. Douglas Wilson, MD, Calgary, AB
Keywords: spina bifida; neural tube defects; myelomeningocele;
Tim Van Mieghem, MD, Toronto, ON prenatal diagnosis; fetal surgery; neural tube defect prevention;
neural tube defect screening; neural tube defect diagnosis; neural
Sylvie Langlois, MD, Vancouver, BC tube defect management

Paige Church, MD, Toronto, ON Corresponding Author; doug.wilson@albertahealthservices.ca

RECOMMENDED CHANGES IN PRACTICE

J Obstet Gynaecol Can 2020;000(000):1−16
1. Clinical evidence supports the use of the first-trimester (12 to
https://doi.org/10.1016/j.jogc.2020.11.003 14 weeks gestation) and routine second-trimester (18 to 22
weeks gestation) sonographic examination for screening and
© 2020 The Society of Obstetricians and Gynaecologists of Canada/La
diagnosis of fetal neural tube defects. Prompt diagnosis of a
Société des obstétriciens et gynécologues du Canada. Published by
fetal neural tube defect is important for treatment decision-
Elsevier Inc. All rights reserved.

This document reflects emerging clinical and scientific advances as of the publication date and is subject to change. The information is not meant
to dictate an exclusive course of treatment or procedure. Institutions are free to amend the recommendations. The SOGC suggests, however,
that they adequately document any such amendments.
Informed consent: Everyone has the right and responsibility to make informed decisions about their care together with their health care
providers. In order to facilitate this, the SOGC recommends that health care providers provide patients with information and support that is
evidence-based, culturally appropriate, and personalized.
Language and inclusivity: This document uses gendered language in order to facilitate plain language writing but is meant to be inclusive of all
individuals, including those who do not identify as a woman/female. The SOGC recognizes and respects the rights of all people for whom the
information in this document may apply, including but not limited to transgender, non-binary, and intersex people. The SOGC encourages
healthcare providers to engage in respectful conversation with their patients about their gender identity and preferred gender pronouns and to
apply these guidelines in a way that is sensitive to each person’s needs.
Copyright: The contents of this document, in whole or in part, cannot be reproduced in any form without prior written permission of the publisher
of the Journal of Obstetrics and Gynaecology Canada.
Weeks Gestation Notation: The authors follow the World Health Organization’s notation on gestational age: the first day of the last menstrual
period is day 0 (of week 0); therefore, days 0 to 6 correspond to completed week 0, days 7 to 13 correspond to completed week 1, etc.

000 JOGC 000 2020  1

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SOGC CLINICAL PRACTICE GUIDELINE
making, especially with the recent availability of fetal surgical
repair for myelomeningocele (open spina bifida).
2. Enhanced genetic evaluation and diagnosis through molecular
technology (i.e., chromosomal microarray, fetal exome
sequencing) allows for improved identification of etiology as
well as genetic counselling for fetal neural tube defects.
3. A randomized controlled trial of prenatal surgical repair of
myelomeningocele (Management of Myelomeningocele
Study) showed that prenatal surgery improves a range of
outcomes. Since the trial was completed in 2016, additional
fetal therapy centres have begun to offer this intervention, with
evaluation, process, and maternal and neonatal outcomes
comparable to those in the trial.
4. There is enhanced evaluation and ongoing support for
children and adolescents with myelomeningocele (open spina
bifida) malformations that were repaired prenatally or
neonatally.
5. There is enhanced evidence for protocols to prevent neural
tube defects that maximize the folic acid dosage, optimize
gestational timing based on the mother’s risk category, and
minimize risk of overusing folic acid.
KEY MESSAGES
 PREVENT fetal neural tube defects with appropriate maternal
and paternal genetic evaluation and counselling to take an
appropriate dosage of folic acid supplementation.
 SCREEN to identify fetal neural tube defects with directed
first- and second-trimester sonography.
 DIAGNOSE using primary sonography (and secondary
magnetic resonance imaging, if required) and amniocentesis
(analysis of amniotic fluid amniocytes with chromosomal
microarray and exome sequencing, and amniotic fluid alpha
fetoprotein testing).
 COUNSEL on treatment options, comprising fetal repair,
postnatal repair, and pregnancy termination. Options should
be offered to and discussed with patients after
myelomeningocele (open spina bifida) or other neural tube
defects are diagnosed.
 EDUCATE patients concerning the benefits of long-term
follow-up and management for children and adolescents with
myelomeningocele (open spina bifida) or other neural tube
defects.
ABSTRACT
Objective: 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.
Options: 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
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subsequent pregnancies: prevention and screening options and
counselling.
Outcomes: The research on and implementation of fetal surgery for
prenatally diagnosed myelomeningocele has added a significant
treatment option to the previous o (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.
Evidence: 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 multivita-
min 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 contin-
ues (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 sup-
plementation 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 breast-
feeding 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 concep-
tion and until 12 weeks gestation. From 12 weeks gestation, contin-
ued 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 diag-
nostic 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 screen-
ing tool for open/closed neural tube defects, in limited clinical indica-
tions, 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 component of maternal serum cell-free placental DNA for aneu-
ploidy screening, maternal serum alpha fetoprotein can also be used
as a secondary screening tool in the second trimester (strong,
moderate).
8. Positive screening 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 man-
agement counselling (strong, high).
9. Prenatal MRI can be considered if further detailed assessment of
the fetal central nervous system is required for diagnostic or man-
agement 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 test-
ing, as considered appropriate after assessment of fetal anomalies
and family history, with amniotic fluid alpha fetoprotein and amni-
otic fluid acetylcholinesterase, if required by protocols for fetal sur-
gery decisions (strong, high).
11. For fetuses with myelomeningocele or other spina bifida anoma-
lies, 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 avail-
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Fetal Neural Tube Defects
able, families should be offered a choice of 3 obstetrical care man-
agement options. In the absence of specific contraindications, fam-
ilies should be given information about the following options:
prenatal surgical repair of myelomeningocele and prognosis, post-
natal 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 neurologi-
cal benefits associated with cesarean delivery. Therefore, intrapar-
tum 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 myelomeningo-
cele (isolated or complex) and other neural tube defects, to provide
optimal counselling for the current pregnancy and future pregnan-
cies, as well as neural tube defect risk assessment for future preg-
nancies (strong, high).
Subsequent Pregnancies
16. Daily oral supplementation with 4.0 to 5.0 mg of folic acid in a multi-
vitamin supplement containing vitamin B12 should be recom-
mended 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 micro-
array, 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 preg-
nancies (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 pla-
cental 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).
000 JOGC 000 2020  3
SOGC CLINICAL PRACTICE GUIDELINE
INTRODUCTION
his guideline for the management of fetal neural tube
T defects (NTDs) highlights the genetic aspects, preven-
tion, screening, diagnosis, and maternity care management
for the affected and subsequent pregnancies, with a focus
on myelomeningocele (MMC), since prenatal surgical
repair for this condition has recently become available.
NTDs are congenital abnormalities of the neural axis. The
human neural tube normally closes during the third to
fourth weeks of embryonic development (corresponding
to 5 to 6 weeks gestation, based on the last menstrual
period),1-5 and NTDs result from the failed closure of this
tube.
In NTDs, the primary structural malformation affects the
spine (most commonly in lumbar or thoracic locations)
and/or the cranium. NTD variations are described by their
anatomical location and neural content as follows6:
1. Spina bifida (closure failure of rostral neural tube folds)
is a commonly used term for approximately 50% of
NTDs. The majority of spina bifida cases (93%) are
“open” NTDs, in which the neural elements are
exposed at the level of the skin. A minority (7%) are
“closed” NTDs that are covered by skin. There are two
types of open spina bifida. In a meningocele, only the
dural sac is herniated. In MMC, the neural elements are
both attached to the dural sac and herniated into the
dural sac. MMC is the only spinal anomaly for which
fetal surgery is indicated.
2. Acrania, exencephaly, and anencephaly make up
approximately 40% of NTDs. In these malformations,
the upper part of the neural tube fails to close, causing
progressive destruction of the brain.
3. Encephalocele accounts for 8.5% of NTDs and
involves outpouching of the brain through a bony skull
defect; occipital location is most common, with anterior
and lateral locations seen less frequently.
4. Iniencephaly and craniorachischisis are the rarest forms
(accounting for 1.5% of NTDs), involving both the
skull and upper spine.
ABBREVIATIONS
AF-AChE amniotic fluid acetylcholinesterase
AFAFP amniotic fluid alpha fetoprotein
MMC myelomeningocele
MSAFP maternal serum alpha fetoprotein
NTDs Neural tube defects
4  000 JOGC 000 2020
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In cases of MMC, secondary co-anomalies appear progres-
sively during fetal development as a result of chronic
trauma to the exposed neural elements and leaking of cere-
brospinal fluid. Following birth, these secondary anomalies
present as muscle weakness or paralysis, bowel dysfunc-
tion, genitourinary dysfunction, cerebellar herniation
(Chiari malformation, type II), and hydrocephalus.
Since the last version of this guideline, Prenatal Screening,
Diagnosis, and Pregnancy Management of Fetal Neural Tube
Defects,7 significant progress has been made in genetic test-
ing for and treatment of fetal MMC. In this revised ver-
sion, we will discuss NTD epidemiology, genetic aspects,
prevention, screening, diagnosis, counselling, and obstetric
management of pregnancies affected by a fetal NTD, as
well as considerations for subsequent pregnancies. The
Society of Obstetricians and Gynaecologists of Canada
(SOGC) “Guideline No. 324: Pre-conception Folic Acid
and Multivitamin Supplementation for the Primary and
Secondary Prevention of Neural Tube Defects and Other
Folic Acid-Sensitive Congenital Anomalies” is another
valid guideline source.8
EPIDEMIOLOGY AND GENETIC RISK FACTORS FOR
NEURAL TUBE DEFECTS
The prevalence of NTDs ranges from 1 in 300 to 1000
pregnancies in populations without folic acid food fortifi-
cation or supplementation and varies by ethnic, genetic,
and dietary factors. The highest NTD rates are seen in the
United Kingdom and United States, while the lowest rates
occur in Japan.9-12 In Canada, the rate of non-chromo-
somal NTDs was 4.4 per 10 000 births, which increased
from 3.6 to 4.6 per 10 000 births from 2004 to 2015. How-
ever, this increase over time reflected an increase in spina
bifida alone. The prevalence was higher in young mothers
(age <30 y), and those with type 2 diabetes, chronic illness,
or substance use disorder.13 Data from the province of
Alberta show the total prevalence of spina bifida (2001 to
2015) at 0.37 per 1000 births, with the prevalence of an
isolated MMC (no other malformations) at 0.21 per 1000
births.14 Most MMC cases are isolated, but urinary tract
and congenital heart defects are the most frequently co-
occurring anomalies. NTDs are reportedly more common
in female than in male fetuses, with lumbosacral lesions
having a male-to-female ratio of 0.94:1 for isolated lesions,
1.24:1 for lesions with associated anomalies, and 0.65:1 for
lesions associated with a chromosomal anomaly.15, 16 The
etiology of the vast majority of NTDs are proposed to be
multifactorial, but specific abnormal chromosomal etiolo-
gies are reported in 2% to 16% of cases.1, 17-21 The most

common chromosomal anomalies observed in MMCs are
trisomy 13, trisomy 18, triploidy.20, 22-31
The prevalence of a genetic variation (full aneuploidy, par-
tial aneuploidy, microduplication/deletion) for MMC (iso-
lated or multiple anomalies) is summarized in Appendix
B.20, 22-31 Earlier reports did not have the advantage of
current cytogenetic molecular testing methods or high-res-
olution sonography, meaning that fetuses with isolated
NTDs may have been grouped with fetuses with associated
anomalies for analysis. The latter explains the wide variabil-
ity in the incidence of abnormal genetic results, varying
between 4.4% and 17.3%, even in cohorts of cases of “iso-
lated” MMC. More recent studies, however, have identified
genetic anomalies in fewer than 3% of fetuses without
associated anomalies.1, 32 Certain pathogenic variants in
single genes are associated with a predisposition for
NTDs. These include genes affecting folate metabolism
(folate transport, the methionine/homocysteine metabolic
cycle, methylation, and nucleotide biosynthesis), as well as
novel genes associated with familial NTDs identified by
whole exome sequencing.33-38 Mechanisms that contribute
to NTDs include epigenetic modifications, maternal auto-
antibodies to folate receptors, and the use of assisted
reproductive technologies, but these mechanisms are
rare.33-38
Syndromes and sequences associated with NTDs include
amniotic band syndrome, cloacal exstrophy, limb-body
wall complex, omphalocele, exstrophy, imperforate anus,
spinal syndrome (omphalocele-exstrophy-imperforate
anus-spinal defects), cerebrocostomandibular syndrome,
and caudal regression syndrome.38 Other syndromic
NTDs are associated with single-gene disorders, such as
mutations in the VANGL1 (caudal regression) and the
VANGL2 (cranial open NTDs and holoprosencephaly)
genes, Waardenburg syndrome, and Currarino syndrome.39
Certain chronic medical conditions in the mother can
increase the risk of NTDs through disruptive developmen-
tal processes, such as poorly controlled type 2 or gesta-
tional diabetes (odds ratio [OR] 11.5), epilepsy (because of
antiepileptic medications such as valproic acid and carba-
mazepine), therapy with folic acid antagonist medications,
and obesity (OR 3.5).7
Diet and micronutrients play an important role in the etiol-
ogy of NTDs. The most common factor is folic acid
(folate). Folate (or vitamin B9) is an essential dietary nutri-
ent found in leafy vegetables, grains, avocados, beans, dairy
products, and meat. A biological and functional summary
of folic acid interactions is provided in Sarmah et al.40
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Fetal Neural Tube Defects
Recent studies have reported that low levels of vitamin B12
may be an independent risk factor for NTDs. There is a
biological premise for this possibility, because folic acid
and vitamin B12 are interlinked metabolically. Vitamin B12
is a complex, water-soluble vitamin required for proper
red blood cell formation, cell metabolism, neurological
function, and DNA synthesis. Most over-the-counter mul-
tivitamin tablets have both folic acid (0.4 to 1.0 mg) and
vitamin B12 (12 to 21.6 mg) in the formulation (but it is
always important to check amounts).41, 42 The recom-
mended B12 intake is 2.4 mg for adults in Canada and the
U.S.
In subsequent pregnancies for a couple who had a previ-
ous pregnancy affected by a fetal NTD, the recurrence rate
varies depending on the primary etiology of the NTD
(folic acid−dependent, non-folic acid−dependent, or
teratogen exposure). The historic recurrence risk for non-
chromosomal NTDs is estimated at 2% to 4% if there was
previously one affected sibling or parent. This estimate is
for a population with a prevalence of NTDs of 1 per 1000
and no food fortification or supplementation with folic
acid; the prevalence of recurrence can be reduced to 1%
with folic acid supplementation.8
PREVENTION
Maternal folic acid supplementation and folic acid food
fortification (via flour-based products) in certain countries,
including Canada, have reduced the incidence of NTDs.4,
43-45
The 2015 SOGC guideline “Pre-conception Folic
Acid and Multivitamin Supplementation for the Primary
and Secondary Prevention of Neural Tube Defects and
Other Folic Acid Sensitive Congenital Anomalies” summa-
rizes the available evidence.8 Folic acid, ideally in combina-
tion with vitamin B12 or in a multivitamin supplement,
reduces the incidence of NTDs as well as certain other
congenital anomalies, such as heart defects, urinary tract
anomalies, oral facial clefts, and limb defects.46
Folic acid supplementation has been shown to influence
the distribution of NTD subtypes. In one study using a
large population-based registry of congenital anomalies,
proportionally fewer cases of cervical and thoracic spina
bifida and more cases of lumbar/sacral spina bifida were
found in the group receiving optimal folic acid supplemen-
tation (anencephaly 34%, cervical/thoracic 6%, lumbar/
sacral spina bifida 51%, encephalocele 9%), regardless of
the presence of the main NTD risk factors.47
In a population with adequate food fortification, the incidence
of folic acid deficiency is low, and mothers of most infants
000 JOGC 000 2020  5
SOGC CLINICAL PRACTICE GUIDELINE
with NTDs do not have clinical folate deficiency.48,49
Canadian data have shown that the percentage of women of
childbearing age (15 to 45 years) with red blood cell folate
concentrations below 906 nmol/L—the threshold associated
with increased NTD prevalence—was only 7% in 2013, a
dramatic drop from 40% in 2006.49
The SOGC and the American College of Obstetricians and
Gynecologists (ACOG) support the pre-conception inter-
pregnancy care model for folic acid supplementation,
counselling, and planning.50,51 They recommend promot-
ing the following for all women of child-bearing age,
regardless of whether they are planning a pregnancy:8,52
 A diet high in folate should be encouraged, but, because
dietary intake is not enough to reach red blood cell folate
levels associated with maximal protection against NTDs,
a daily multivitamin containing 0.4 mg of folic acid is
needed for women of reproductive age who could
become pregnant and who have no risk factors for folic
acid−sensitive birth anomalies.
 Higher intake of folic acid is required for women with
risk factors, including
○ a previous pregnancy affected by an NTD for the
women or her partner
○ personal or partner family history of NTDs
○ personal or family history of other folic acid−related
congenital anomalies (e.g., cardiac, urinary-tract, or
limb-reduction defects; oral-facial clefting)
○ pre-pregnancy diabetes (type 1or 2)
○ use of kidney dialysis
○ gastrointestinal malabsorption conditions (e.g.,
inflammatory bowel disease, celiac disease, history of
gastric bypass surgery)
○ use of antiepileptic or other folate-inhibiting
medications
○ advanced liver disease or alcohol use disorder
The SOGC “Guideline No. 324: Pre-Conception Folic
Acid and Multivitamin Supplementation for the Primary
and Secondary Prevention of Neural Tube Defects and
Other Folic Acid−Sensitive Congenital Anomalies”
defines 3 NTD risk groups (low, moderate, and high) that
require different amounts of folic acid supplementation for
prevention:8
 Low risk (daily oral multivitamin supplement containing
0.4 to 0.6 mg folic acid) for women if they and their
male partner have no personal or family history of folic
acid−sensitive birth defects
 Moderate risk (daily oral multivitamin supplement con-
taining 1.0 mg folic acid) for women with one or more
6  000 JOGC 000 2020
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of the following maternal factors (1 to 5 listed below) or
male partner with the following factors (1 or 2 listed
below):
1. Personal or family history of other folic acid−sensi-
tive anomalies
2. Family history of NTD in first- or second-degree
relative
3. Diabetes (type 1 or 2)
4. Use of teratogenic medications such as antiepileptic
and cholestyramine medications
5. Gastrointestinal malabsorption conditions
 High risk (daily oral multivitamin with added folic acid
supplementation to total 4 mg folic acid or prescription
of 5 mg of folic acid) for women if they or their male
partner have a personal history of an NTD or previous
pregnancy affected by an NTD.
SCREENING FOR NEURAL TUBE DEFECTS
Sonography
Sonographic imaging is the non-invasive screening modal-
ity of choice for the detection of fetal anomalies, including
NTDs, because of its safety, cost efficiency, and sensitiv-
ity.46,53-59 The current generation of sonographic equip-
ment allows for highly detailed fetal imaging.
It is recommended that routine sonographic prenatal
screening be offered to all pregnant women in the second
trimester between 18 and 22 weeks gestation to maximize
testing accuracy, achieve low false-positive rates, and allow
optimal management of affected pregnancies.
Certain factors have been reported to affect the accuracy
and interpretation of NTD screening results, including the
type of NTD malformation, gestational age, maternal
weight, maternal type 1 diabetes, maternal multiple gesta-
tions, maternal ethnic background, environmental factors
(such as prescription and non-prescription medications),
and concurrent fetal anomalies.7, 8
In a fetus with an NTD, features visible by sonography in
the second trimester include anencephaly (the absence of
the cranial vault and significant facial dysmorphology),
abnormal skull shape with flattened temporal bones
(“lemon sign”), abnormal appearance of the cerebral ven-
tricles and ventriculomegaly, herniation of the cerebellum
(Chiari malformation, “banana sign”) with the obliteration
of the cisterna magna, and abnormal or incomplete appear-
ance of the posterior vertebral arches. In cases of rachischi-
sis, the skin defect may be difficult to observe, and closed
spinal anomalies usually do not present with the

intracranial signs. Abnormal lower-limb movement and
abnormal positioning of one or both feet may be present
but are variable.54
When an NTD is detected, an attempt should be made to
assess the spinal vertebral level of the lesion, lower limb
deformities, and the presence of hindbrain herniation, ven-
triculomegaly, or associated anomalies, as these features
will have an impact on prenatal counselling and expected
health outcomes.
For women undergoing first-trimester sonographic screen-
ing for aneuploidy, a basic review of anatomical structures
should be performed as part of the screening. This review
would allow detection of virtually all cases of anencephaly.
In the first trimester, the striking finding of anencephaly is
the absence of the skull bones, which should normally be
ossified after 11 weeks gestation. Often, part of the brain is
still present, but appears splayed and abnormal in shape,
with the appearance of exencephaly (sequence for acrania-
exencephaly-anencephaly).60, 61
Observational studies have shown that open spina bifida
can be detected at 11 to 13 weeks gestation. First-trimester
screening for this condition can be done by assessing intra-
cranial translucency, biparietal diameter, frontomaxillary
facial angle, cisterna magna obliteration, and volume of
intracranial cerebrospinal fluid.62-68 Assessment of intra-
cranial translucency in the mid-sagittal plane has gained the
most support, but large studies of sensitivity (true-positive
rates) and false-positive rates are still lacking. Moreover,
first-trimester screening for spina bifida requires higher
levels of sonography operator expertise, thereby limiting its
availability.
Maternal Serum Alpha Fetoprotein
While sonography is the primary screening tool, second-tri-
mester maternal serum alpha fetoprotein (MSAFP) detects
71% to 90% of NTDs, with a false-positive rate of 1% to
3%.8 Elevated levels of MSAFP can be associated with
other conditions, such as fetal skin disorders, abdominal
wall defects, fetal death, fetal nephrosis, and pregnancies at
an increased risk for placenta-related adverse events.8 By
contrast, first-trimester MSAFP screening detects 50% of
NTDs, with a false-positive rate of 10%, and is not recom-
mended for NTD screening. MSAFP has limited use in
population screening at the present time. The only appro-
priate indications are pre-pregnancy body mass index ≥35
kg/m2 or unavailability of timely and good-quality sono-
graphic screening at 18 to 22 weeks gestation due to geo-
graphic factors or lack of clinical access.8
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Fetal Neural Tube Defects
Magnetic Resonance Imaging
MRI is not a screening test for NTDs but can be used as
an adjunct to sonography to assist with further manage-
ment planning and counselling.69-78 Fetal MRI is usually
conducted after 20 weeks gestation, as this gestational age
allows for optimal imaging of the fetal brain and subarach-
noid space. However, the later gestational age for the MRI
imaging can delay decisions regarding pregnancy manage-
ment. MRI exposure is considered safe for the fetus,
assuming that the use of contrast agent is avoided.79, 80
Further Management Following a Positive Screening
Test
Positive screening for an NTD by either sonography or
MSAFP should trigger timely referral to experienced pro-
viders for confirmation, further diagnostic workup, and
pregnancy management counselling.7
GENETIC TESTING
Genetic testing should be offered when any major congeni-
tal anomaly (isolated or multiple) is identified, but espe-
cially when considering prenatal or postnatal repair of
congenital anomalies, as identifying additional fetal genetic
factors may contribute to neonatal morbidity and out-
comes.
The joint SOGC−Canadian College of Medical Geneticists
“Guideline No. 348: Update on Prenatal Screening for
Fetal Aneuploidy, Fetal Anomalies, and Adverse Pregnancy
Outcomes” recommends clinicians offer invasive fetal
diagnostic testing with rapid aneuploidy detection if a fetal
structural abnormality is identified. If the rapid aneuploidy
result is normal or inconclusive, the clinician should con-
tinue to microarray analysis, regardless of previous screen-
ing results.81
If structural anomalies, including central nervous system
anomalies, are found, non-invasive prenatal testing is sub-
optimal because of its limited scope and the risk of false-
positive and false-negative results.82, 83
The prevalence of abnormal microarray results depends on
whether other anomalies are identified by sonography (e.g.,
isolated or multiple anomalies, growth restriction, still-
birth).84-88
If the clinical suspicion of an underlying genetic condition
is high after detailed fetal imaging and family history
assessment, yet microarray results are normal, fetal exome
sequencing can be considered. Sequencing should be
offered in a multidisciplinary prenatal setting that includes
000 JOGC 000 2020  7
SOGC CLINICAL PRACTICE GUIDELINE
providers with expertise in medical genetics, and should
follow patient counselling and informed consent.89-91
An amniocentesis is performed to detect chromosomal
aneuploidy or genetic mutations in both the fetal cell
amniocytes and the amniotic fluid.92, 93 The amniocentesis
is usually conducted between 15 and 20 weeks gestation.
Fetal cell amniocytes can be analyzed by chromosomal
microarray (with or without exome sequencing). Measure-
ment of amniotic fluid alpha fetoprotein (AFAFP) and
amniotic fluid acetylcholinesterase (AF-AChE) levels is
considered optional for diagnosis but is required for some
protocols for fetal surgery decisions. AFAFP is produced
initially from the fetal yolk sac and, later in fetal develop-
ment, from the fetal liver, whereas AF-AChE is specifically
derived from fetal neural tissue. These proteins are not
normally found in amniotic fluid, except in the presence of
a breach in skin integrity (AF-AFP) or an open NTD (AF-
AChE).93 When amniocentesis is performed for a sus-
pected NTD, the information from the karyotype, chro-
mosomal microarray, AF-AFP, and the AF-AChE levels
can assist with the diagnosis of the specific type of NTD
and with counselling regarding prognosis.
When an amniocentesis is performed for an increased risk
of aneuploidy, but no NTD is suspected on sonography,
amniotic fluid analysis for AFAFP and AChE is not
recommended.93
In women who undergo first-trimester chorionic villus
sampling for the detection of fetal aneuploidy, second-tri-
mester sonography is still required to detect fetal congeni-
tal anomalies, including NTDs.93 There are no published
studies of amniocentesis in cohorts with MMC only that
can guide risk assessment. Therefore, in counselling,
maternity care providers should use the published risks
associated with amniocentesis and chorionic villus sam-
pling, including:
 spontaneous abortion
 post-procedure spotting
 infections
 rupture of membranes
 fetal injury or death93-96
FURTHER PREGNANCY CARE
Identifying a pregnancy with a fetal NTD should trigger
timely referral to a specialized, multidisciplinary team for
comprehensive counselling, typically involving clinical
geneticists and genetic counsellors, maternal-fetal medicine
specialists, neonatologists, and neurosurgeons.7 Counsel-
ling should be individualized, with discussion of the
8  000 JOGC 000 2020
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etiology of the NTD, the expected natural history from
childhood to adolescence to adulthood, and the available
management options for a complex pregnancy. Transfer of
obstetrical care as well as social service counselling and
support may be required.
Anencephaly
Because anencephaly is incompatible with long-term post-
natal survival, pregnancy termination should be offered,
regardless of gestational age. Counselling for continuing
pregnancies should indicate that there is an increased risk
of polyhydramnios and antepartum or intrapartum fetal
death. Delivery may be more complex at later gestational
ages due to the labour mechanics associated with the lack
of a presenting part or abnormal cranial volume for vertex
presentaion. Only neonatal comfort care should be pro-
vided when the infant is born alive.97, 98
Encephalocele
With an encephalocele, individualized counselling is rec-
ommended, as the morbidity of this central nervous sys-
tem anomaly depends on the specific characteristics of the
lesion.7 Counselling for delivery and postnatal manage-
ment should take into account the extent and location of
the encephalocele, the presence of herniated brain tissue,
as well as any associated anomalies or genetic syndrome in
the fetus. A pediatric neurosurgical consultation should be
offered and initiated prenatally.
Spina Bifida
Prenatal counselling should be guided by the level of the
spinal lesion, the presence or absence of skin covering the
lesion, and associated structural or genetic anomalies. After
counselling, pregnant women should be offered the option
of expectant prenatal care with postnatal surgical repair,
prenatal fetal surgical repair, or termination of pregnancy.
1. Routine Prenatal Care and Postnatal Surgical Repair
Antenatal Considerations
In fetuses with an isolated MMC, the risk of fetal death is
not significantly increased, and most pregnancies will con-
tinue to term. Serial sonograms for fetal growth, head size,
and ventricular size may be helpful in delivery planning.
The fetus should be delivered at a centre with a level III
neonatal intensive care unit and pediatric neurosurgery
services, since the neonate will require surgery within the
first 24 hours of life.99 A latex-free delivery and surgical
repair plan is recommended, because infants with MMC
are at an increased risk of developing a severe and life-
threatening allergy to latex.99

There continues to be controversy concerning the mode of
delivery for an fetus with an MMC, with a vertex presenta-
tion, without macrocephaly, with a small meningocele sac,
and with non-fixed lower limb positioning.100-105 However,
a recent systematic review and meta-analysis showed that
routine delivery by cesarean was not associated with
improved neurological outcomes among fetuses with open
NTDs (MMC).106 Hence, in most centres, the mode of
delivery depends on the usual obstetric indications, except
for fetuses who have undergone fetal surgical repair, as
these cases should all be delivered by cesarean.
Postnatal Considerations
Immediately following birth, the lesion should be covered,
to prevent ascending infection and ongoing trauma, and
should be closed surgically within the first 24 hours. Given
the hydrocephalus and Chiari type II malformation often
associated with MMC, about 60% to 80% of infants will
need ventriculoperitoneal shunting or third ventriculos-
tomy within the first 6 months of life to decrease intracra-
nial pressure (Appendix C). Shunt revisions are required in
45% to 50% of cases.107, 108 The risk of perinatal death in
recently studied cohorts is less than 5%.108, 109
In neonates with bladder dysfunction, intermittent clean
bladder catheterization should be initiated neonatally to
prevent reflux and infections. A study of 5250 patients
with spina bifida found that 22.4% had had bladder conti-
nence surgery, 92.6% used some form of bladder manage-
ment, and 45.8% reported bladder continence at a mean
follow-up age of 16.6 years.110 Sexual dysfunction has
been reported in both men and women in approximately
50% of cases.111, 112
Motor and sensory function depend on the level of the
lesion, and counselling must be individualized. The prena-
tal upper vertebral level, defined by sonography, agrees
with postnatal imaging within one vertebral level in 81% of
cases and within two vertebral levels in 85% of cases.113 In
general, 20% to 30% of those affected achieve autono-
mous ambulation, and 32% to 45% require the use of a
wheelchair. Children are more likely to be ambulatory if
they did not need a ventriculoperitoneal shunt, if the lesion
is at a lower vertebral level, or if they do not have a history
of hip or knee contracture release surgery.108, 114
Developmental outcomes in infants with spina bifida are
typically good, and most children will be able to attend a
traditional school program. However, the risk of low IQ or
global delay at school age ranges between 15% and
20%.107, 108 Quality of life is typically self-reported as good
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Fetal Neural Tube Defects
to very good in 75% to 90% of patients,115, 116 but close
mental health follow-up, obesity prevention, and appropri-
ate transition into adult care are required to ensure contin-
ued well-being. Appropriate social participation and
healthy relationships, including managing their personal
reproductive risks are also important.117-122
2. Prenatal Fetal Surgical Repair
Both human and animal studies have shown that the
hydrocephalus and loss of motor function in the lower
limbs seen at birth in babies with MMC are progressive
findings that originate in the second and third trimester of
pregnancy.109 As a consequence, in utero closure of the
defect can prevent secondary in utero trauma to the central
nervous system. Following extensive pre-clinical experi-
mentation, the Management of Myelomeningocele ran-
domized trial of prenatal versus postnatal surgical repair of
MMC malformations clearly demonstrated that prenatal
repair reduced the need for ventriculoperitoneal shunting
(40% in the prenatal surgical repair group versus 82% in
the postnatal repair group) and improved lower limb func-
tion, compared with postnatal repair.109, 123-125 Moreover,
improvement in hindbrain herniation was seen at 12
months of age, and independent ambulation at 30 months
was more common in children who underwent prenatal
surgical repair than those with postnatal repair (42%
vs.21%). A systematic review and meta-analysis compared
the neurodevelopmental outcomes in children with MMC
surgically repaired prenatally versus postnatally. Six studies
met the systematic review inclusion criteria, and 2 were
used for the meta-analysis. Neurodevelopmental assess-
ments were carried out in 213 children 14 to 53 months of
age. The risk of neurodevelopmental impairment in infants
with MMC was similar between the groups with prenatal
surgical repair and postnatal repair, in spite of an increased
risk of prematurity in the group with prenatal repair.126
The Management of Myelomeningocele study also identi-
fied risks associated with the surgery, including preterm
pre-labour rupture of membranes; preterm birth (mean
gestational age at delivery 34 to 35 weeks); maternal blood
transfusion; and residual extensive uterine scarring, which
may affect subsequent pregnancies.127, 128 Indeed, the risk
of uterine dehiscence and/or rupture in subsequent preg-
nancies may be as high as 30%,128 and cases of invasive
placentation have been reported.127 A recent meta-analysis
shows that maternal complications occur in 20.9% of open
fetal surgeries and that serious maternal complications are
reported in up to 4.5%.129
Finally, all pregnancies in which open fetal surgery has been
performed should be delivered by pre-labour cesarean at
000 JOGC 000 2020  9
SOGC CLINICAL PRACTICE GUIDELINE

37 weeks gestation at the latest, to prevent rupture of the Box 1. 2011−2018 data from the North American Fetal
hysterotomy scar. Therapy Network (NAFTNet) consortium registry
Maternal age 29.4 years (range 18−45)
Risks and benefits of this prenatal intervention should be
Ethnic group White 75%
considered in each case individually, and pregnant women
Hispanic 9%
in whom a fetal MMC has been diagnosed should be
informed of this treatment option.130 African-American 3%
Other 13%

Follow-up data from the North America Fetal Therapy Gravidity G1 29%

Network Consortium Registry show that the outcomes BMI 27.4 kg/m2 (range 18−39 kg/m2)

reported in the Management of Myelomeningocele study Fetal sex Female 51%

have been reproduced outside of the trial protocol and Lesion MMC 74%
have been achieved in other centres (Box 1).131 Since June Myeloschisis 25%
2016, prenatal fetal surgical repair of MMC has been avail- Other 1%
able in Toronto at the Ontario Fetal Centre (http://www. MMC anatomic level T 11−12 3%
ontariofetalcentre.ca). This option should be presented L 1−3 49%
to families in Canada as part of the informed consent pro- L 4−5 46%
cess. S 1−2 2%
Pre-operative lateral ventricle, width Right 10.4 mm
To minimize the morbidity associated with the large hyster- (range 3.5−21 mm)

otomy performed during open fetal MMC surgical repair, a Left 11 mm

(range 3−25 mm)
number of groups have been using a fetoscopic approach.
GA at surgery 24.1 weeks (range 20.6−26.4
Appendix D provides a summary of the results of these weeks)
groups and their outcomes compared with the Manage- Lesion closure Standard repair 62%
ment of Myelomeningocele study, which is currently the Patch 28%
gold standard.109, 132-136 As well, this approach has been Operative complications 9%
systematically reviewed.137 These treatments remain exper- Maternal complications Pulmonary edema <1%
imental, as the surgical technique has not yet been stan- Obstetrical complications PTL 31%
dardized and data on long-term outcomes are lacking. PROM 30%
Appendix E provides a summary of surgical technical out- Oligohydramnios 15%
comes for the fetoscopic approach compared with the Chorioamniotic membrane
open MMC surgical repair approach. separation 13%
Chorioamnionitis 4%
A systematic review of maternal and obstetric complica- Placental Abruption 3%
tions following prenatal MMC surgical repair analyzed data Delivery data GA 34.3 weeks (range
from 11 studies.138 Overall rates of obstetrical complica- 22.6−37.6 weeks)

tions (both open surgical and fetoscopic techniques) were Birth weight 2405 g (range
421−3740 g)
reported as chorioamniotic membrane separation 66%, oli-
Hysterotomy:
gohydramnios 13%, placental abruption 5%, chorioamnio-
Intact 67%
nitis 3%, and non-intact hysterotomy scar 22%. Rates of
Thin 27%
maternal complications were reported as pulmonary
Dehiscence 6%
edema (3%) and blood transfusion at delivery (3%). Early
preterm delivery at <30 weeks was 10% for the feto- Postnatal outcomes Perinatal loss 3%
Maternal transfusion 2%
scopic approach and 12% for open fetal surgical repair,
MMC revision 3%
and mean gestational age at delivery was 36.0 weeks for
CSF diversion by 12 months
fetoscopy and 34.5 weeks for open fetal surgical repair. 42% (at average of 25 weeks
Only the risk of spontaneous rupture of membranes was 6 months)
increased with fetoscopy versus open surgery (OR 4.2; Independent ambulation 52%
95% CI 2.51−7.04).138 Clean intermittent catheterization at
3 years of age 55%
While there is an identified benefit for the child in terms of Source: Adapted from Society for Maternal-Fetal Medicine abstract summary.131
central nervous system outcomes after fetal MMC surgical BMI: body mass index; CSF: cerebrospinal fluid; GA: gestational age; MMC: mye-
repair, there is added morbidity from possible premature lomeningocele; PROM: premature rupture of membranes; PTL: preterm labour.

10  000 JOGC 000 2020

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delivery, and this morbidity and cost burden have recently
been evaluated.139 The ethical, legal, and social issues for
fetal MMC surgical repair have been reviewed by Radic
et al.140 There are ethical issues for the mother and fetus,
involving informed consent and equipoise, and identifying
who is the patient or research participant. There are justice
issues related to access to care, as well as safety issues for
new centres involving their ability to follow existing recom-
mendations to provide competent care.
3. Termination of Pregnancy
Over the last 3 decades, an estimated 70% to 80% of
women with a fetus affected by NTD have chosen preg-
nancy termination,1, 41, 42, 141, 142 but this decision is
strongly influenced by geographic variables, legislation, as
well as cultural and personal beliefs. For families choosing
to terminate a pregnancy due to spina bifida, including
MMC, the health care provider should discuss fetal
autopsy and genetic testing, as autopsy findings may pro-
vide important information about the etiology of the NTD
and the risk of recurrence. Induction of labour is the pre-
ferred method of pregnancy termination, allowing for a
more complete autopsy evaluation of the fetal central ner-
vous system. If autopsy is declined, fetal MRI, either in
utero or after postnatal death, should be considered to bet-
ter evaluate fetal abnormalities. If genetic studies have not
been completed before the termination, they should be
considered or encouraged, even if a full autopsy is not per-
formed. Such genetic studies should include, at a mini-
mum, a chromosomal evaluation (chromosomal
microarray and or fetal exome sequencing if multiple mal-
formations, not disruptions, are present). Following induc-
tion of labour and vaginal delivery of a fetus affected with
a MMC, clinical photography can be an important option
if no autopsy is undertaken. These measures will maximize
information about the fetus for use in postnatal review and
counselling.
CONCLUSION
Fetal NTDs are common congenital malformations and
are largely preventable, since a large proportion are associ-
ated with folic acid deficiency. Randomized controlled tri-
als, for both primary and recurrence prevention of a NTD,
have established appropriate dosages of folic acid supple-
mentation. Most recommendations to reduce the risk of
spina bifida involve pre-conception oral folic acid supple-
mentation, regardless of whether national folic acid food
fortification programs exist.
National NTD prevention strategies, prenatal NTD screening
processes, prenatal NTD diagnostic testing, and pregnancy
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Fetal Neural Tube Defects
management options for pre- and post-conception NTD sce-
narios (including spina bifida and MMC) are important
issues for maternity care providers to understand.
If an isolated fetal spina bifida defect is diagnosed, patients
should be referred to specialized centres for further imag-
ing as well as genetic, obstetrical, and surgical counselling
and management. After an informed consent discussion,
patients should be offered prenatal fetal surgical repair for
an MMC, postnatal surgical repair for MMC or other spina
bifida, and pregnancy termination with postnatal follow-up
and counselling regarding future pregnancies.
GUIDELINE TOOLKIT
SOGC members can visit the Guideline Resource Kit web-
page on sogc.org to find complementary tools and resour-
ces and to participate in accredited continuing professional
development activities.
SUPPLEMENTARY MATERIAL
Supplementary material can be found in the online ver-
sion of this article, at https://doi.org/10.1016/
j.jogc.2020.11.003.
REFERENCES
1. AlRefai A, Drake J, Kulkarni AV, Connor KL, Shannon P, Toi A, et al.
Fetal myelomeningocele surgery: Only treating the tip of the iceberg.
Prenat Diagn 2019;39:10–5. Available from: https://www.ncbi.nlm.nih.
gov/pubmed/30536580.
2. Copp AJ, Adzick NS, Chitty LS, Fletcher JM, Holmbeck GN, Shaw GM.
Spina bifida. Nat Rev Dis Primers 2015;1:15007.. Available from: https://
www.ncbi.nlm.nih.gov/pubmed/27189655.
3. Frey L, Hauser WA. Epidemiology of neural tube defects. Epilepsia
2003;44(Suppl 3):4–13. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/12790881.
4. Gucciardi E, Pietrusiak MA, Reynolds DL, Rouleau J. Incidence of neural
tube defects in Ontario, 1986-1999. CMAJ 2002;167:237–40. Available
from: https://www.ncbi.nlm.nih.gov/pubmed/12186167.
5. Savvidou M, Jauniaux E. Prenatal spina bifida: what has changed in
diagnosis and management. BJOG 2019;126:329.. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/30632690.
6. Ghi T, Pilu G, Falco P, Segata M, Carletti A, Cocchi G, et al. Prenatal
diagnosis of open and closed spina bifida. Ultrasound Obstet Gynecol
2006;28:899–903. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/17086581.
7. Wilson RD, Sogc Genetics C, Special C. Prenatal screening, diagnosis, and
pregnancy management of fetal neural tube defects. J Obstet Gynaecol
Can 2014;36:927–39. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/25375307.
8. Wilson RD, Genetics C, Wilson RD, Audibert F, Brock JA, Carroll J, et al.
Pre-conception Folic Acid and Multivitamin Supplementation for the
Primary and Secondary Prevention of Neural Tube Defects and Other
000 JOGC 000 2020  11
SOGC CLINICAL PRACTICE GUIDELINE
Folic Acid-Sensitive Congenital Anomalies. J Obstet Gynaecol Can
2015;37:534–52. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/26334606.
9. Prevalence of neural tube defects in 20 regions of Europe and the impact
of prenatal diagnosis, 1980-1986. EUROCAT Working Group. J
Epidemiol Community Health 1991;45:52–8. Available from: https://
www.ncbi.nlm.nih.gov/pubmed/2045746.
10. Bamforth FJ. Laboratory screening for genetic disorders and birth defects.
Clin Biochem 1994;27:333–42. Available from: https://www.ncbi.nlm.nih.
gov/pubmed/7867213.
11. Cameron M, Moran P. Prenatal screening and diagnosis of neural tube
defects. Prenat Diagn 2009;29:402–11. Available from: https://www.ncbi.
nlm.nih.gov/pubmed/19301349.
12. Cuckle HS, Wald NJ, Cuckle PM. Prenatal screening and diagnosis of
neural tube defects in England and Wales in 1985. Prenat Diagn
1989;9:393–400. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/2668917.
13. Liu S, Evans J, MacFarlane AJ, Ananth CV, Little J, Kramer MS, et al.
Association of maternal risk factors with the recent rise of neural tube
defects in Canada. Paediatr Perinat Epidemiol 2019;33:145–53.
14. Lowry RB, Bedard T, MacFarlane AJ, Crawford S, Sibbald B,
Agborsangaya BC. Prevalence rates of spina bifida in Alberta, Canada:
2001-2015. Can we achieve more prevention? Birth Defects Res
2019;111:151–8. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/30561844.
15. Kallen B, Cocchi G, Knudsen LB, Castilla EE, Robert E, Daltveit AK,
et al. International study of sex ratio and twinning of neural tube defects.
Teratology 1994;50:322–31. Available from: https://www.ncbi.nlm.nih.
gov/pubmed/7716740.
16. Rittler M, Lopez-Camelo J, Castilla EE. Sex ratio and associated risk
factors for 50 congenital anomaly types: clues for causal heterogeneity.
Birth Defects Res A Clin Mol Teratol 2004;70:13–9. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/14745890.
17. Drugan A, Johnson MP, Dvorin E, Moody J, Krivchenia EL, Schwartz D,
et al. Aneuploidy with neural tube defects: another reason for complete
evaluation in patients with suspected ultrasound anomalies or elevated
maternal serum alpha-fetoprotein. Fetal Ther 1989;4:88–92. Available
from: https://www.ncbi.nlm.nih.gov/pubmed/2484814.
18. Harmon JP, Hiett AK, Palmer CG, Golichowski AM. Prenatal ultrasound
detection of isolated neural tube defects: is cytogenetic evaluation
warranted? Obstet Gynecol 1995;86:595–9. Available from: https://www.
ncbi.nlm.nih.gov/pubmed/7675386.
19. Hume RF Jr., Drugan A, Reichler A, Lampinen J, Martin LS, Johnson MP,
et al. Aneuploidy among prenatally detected neural tube defects. Am J
Med Genet 1996;61:171–3. Available from: https://www.ncbi.nlm.nih.
gov/pubmed/8669447.
€
20. Kanit H, Ozkan €
AA, Oner SR, Ispahi C, Endrikat JS, Ertan K.
Chromosomal abnormalities in fetuses with ultrasonographically detected
neural tube defects. Clin Dysmorphol 2011;20:190–3.
21. Kennedy D, Chitayat D, Winsor EJ, Silver M, Toi A. Prenatally diagnosed
neural tube defects: ultrasound, chromosome, and autopsy or postnatal
findings in 212 cases. Am J Med Genet 1998;77:317–21. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/9600743.
22. Canda MT, Demir N, Bal FU, Doganay L, Sezer O. Prenatal diagnosis of a
22q11 deletion in a second-trimester fetus with conotruncal anomaly,
absent thymus and meningomyelocele: Kousseff syndrome. J Obstet
Gynaecol Res 2012;38:737–40. Available from: https://www.ncbi.nlm.nih.
gov/pubmed/22380655.
12  000 JOGC 000 2020
Downloaded for Mahasiswa FK UKDW 02 (mhsfkdw02@gmail.com) at Duta Wacana Christian University from ClinicalKey.com by Elsevier on November 27, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
23. Chen CP. Chromosomal abnormalities associated with neural tube defects
(I): full aneuploidy. Taiwan J Obstet Gynecol 2007;46:325–35. Available
from: https://www.ncbi.nlm.nih.gov/pubmed/18182338.
24. Chen CP. Chromosomal abnormalities associated with neural tube defects
(II): partial aneuploidy. Taiwan J Obstet Gynecol 2007;46:336–51.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/18182339.
25. Chen CP, Chen CY, Chern SR, Wu PS, Chen SW, Lai ST, et al. Molecular
cytogenetic characterization of a duplication of 15q24.2-q26.2 associated
with anencephaly and neural tube defect. Taiwan J Obstet Gynecol
2017;56:550–3. Available from: https://www.ncbi.nlm.nih.gov/pubmed/
28805617.
26. Chen CP, Chen YJ, Chern SR, Tsai FJ, Lin HH, Lee CC, et al. Prenatal
diagnosis of mosaic 1q31.3q32.1 trisomy associated with occipital
encephalocele. Prenat Diagn 2008;28:865–7.
27. Ekin A, Gezer C, Taner CE, Ozeren M, Ozer O, Koc A, et al.
Chromosomal and structural anomalies in fetuses with open neural tube
defects. J Obstet Gynaecol 2014;34:156–9. Available from: https://www.
ncbi.nlm.nih.gov/pubmed/24456437.
28. Lurie IW, Novikova IV, Tarletskaya OA, Lazarevich AA, Gromyko OA.
Distal 13q monosomy and neural tube defects. Genet Couns
2016;27:177–86. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/29485808.
29. Preiksaitiene E, Benusiene E, Ciuladaite Z, Sliuzas V, Mikstiene V,
Kucinskas V. Recurrent fetal syndromic spina bifida associated with
3q26.1-qter duplication and 5p13.33-pter deletion due to familial balanced
rearrangement. Taiwan J Obstet Gynecol 2016;55:410–4. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/27343325.
30. Sepulveda W, Wong AE, Fauchon DE. Fetal spinal anomalies in a first-
trimester sonographic screening program for aneuploidy. Prenat Diagn
2011;31:107–14. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/20734349.
31. Yazici LE, Malatyalioglu E, Sakinci M, Tosun M, Bildircin FD, Ogur G,
et al. Chromosomal anomalies and additional sonographic findings in
fetuses with open neural tube defects. Arch Gynecol Obstet
2012;286:1393–8. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/22836815.
32. Aguilera S, Soothill P, Denbow M, Pople I. Prognosis of spina bifida in the
era of prenatal diagnosis and termination of pregnancy. Fetal Diagn Ther
2009;26:68–74. Available from: https://www.ncbi.nlm.nih.gov/pubmed/
19752521.
33. Alfarra HY, Alfarra SR, Sadiq MF. Neural tube defects between folate
metabolism and genetics. Indian J Hum Genet 2011;17:126–31. Available
from: https://www.ncbi.nlm.nih.gov/pubmed/22345982.
34. Aneji CN, Northrup H, Au KS. Deep sequencing study of the MTHFR
gene to identify variants associated with myelomeningocele. Birth Defects
Res A Clin Mol Teratol 2012;94:84–90. Available from: https://www.ncbi.
nlm.nih.gov/pubmed/22241680.
35. De Marco P, Merello E, Cama A, Kibar Z, Capra V. Human neural tube
defects: genetic causes and prevention. Biofactors 2011;37:261–8.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/21674647.
36. De Marco P, Merello E, Rossi A, Piatelli G, Cama A, Kibar Z, et al. FZD6
is a novel gene for human neural tube defects. Hum Mutat 2012;33:384–
90. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22045688.
37. Lemay P, De Marco P, Traverso M, Merello E, Dionne-Laporte A,
Spiegelman D, et al. Whole exome sequencing identifies novel
predisposing genes in neural tube defects. Mol Genet Genomic Med
2019;7:e00467.. Available from: https://www.ncbi.nlm.nih.gov/pubmed/
30415495.

38. Wang XW, Luo YL, Wang W, Zhang Y, Chen Q, Cheng YL. Association
between MTHFR A1298C polymorphism and neural tube defect
susceptibility: a metaanalysis. Am J Obstet Gynecol 2012;206. 251 e1-
7Available from: https://www.ncbi.nlm.nih.gov/pubmed/22265089.
39. Chen CP. Syndromes, disorders and maternal risk factors associated with
neural tube defects (IV). Taiwan J Obstet Gynecol 2008;47:141–50.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/18603497.
40. Sarmah S, Muralidharan P, Marrs JA. Common congenital anomalies:
Environmental causes and prevention with folic acid containing
multivitamins. Birth Defects Res C Embryo Today 2016;108:274–86.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/27718306.
41. Molloy AM. Should vitamin B(12) status be considered in assessing risk of
neural tube defects? Annals of the New York Academy of Sciences
2018;1414:109–25. Available from: https://pubmed.ncbi.nlm.nih.gov/
29377209 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887889/.
42. O'Malley EG, Reynolds CME, Cawley S, Woodside JV, Molloy AM,
Turner MJ. Folate and vitamin B12 levels in early pregnancy and maternal
obesity. Eur J Obstet Gynecol Reprod Biol 2018;231:80–4. Available
from: https://www.ncbi.nlm.nih.gov/pubmed/30336308.
43. Boulet SL, Yang Q, Mai C, Kirby RS, Collins JS, Robbins JM, et al. Trends
in the postfortification prevalence of spina bifida and anencephaly in the
United States. Birth Defects Res A Clin Mol Teratol 2008;82:527–32.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/18481813.
44. De Wals P, Tairou F, Van Allen MI, Uh SH, Lowry RB, Sibbald B, et al.
Reduction in neural-tube defects after folic acid fortification in Canada. N
Engl J Med 2007;357:135–42. Available from: https://www.ncbi.nlm.nih.
gov/pubmed/17625125.
45. Van Allen MI, Boyle E, Thiessen P, McFadden D, Cochrane D, Chambers
GK, et al. The impact of prenatal diagnosis on neural tube defect (NTD)
pregnancy versus birth incidence in British Columbia. J Appl Genet
2006;47:151–8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/
16682757.
46. Roberts N, Bhide A. Ultrasound prenatal diagnosis of structural
abnormalities. Obstetrics, Gynaecology & Reproductive Medicine
2007;17:1–8. Available from: http://www.sciencedirect.com/science/
article/pii/S1751721406001679.
47. Bergman JE, Otten E, Verheij JB, de Walle HE. Folic acid
supplementation influences the distribution of neural tube defect subtypes:
A registry-based study. Reprod Toxicol 2016;59:96–100. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/26627544.
48. van Gool JD, Hirche H, Lax H, De Schaepdrijver L. Folic acid and
primary prevention of neural tube defects: A review. Reprod Toxicol
2018;80:73–84. Available from: https://www.ncbi.nlm.nih.gov/pubmed/
29777755.
49. Shere M, Kapur BM, Koren G. Folate status of women in Toronto:
Implications of folate fortification and supplementation. Can J Public
Health 2016;106:e509–13. Available from: https://www.ncbi.nlm.nih.
gov/pubmed/26986912.
50. Wilson RD. Woman's Pre-Conception Evaluation: Genetic and Fetal Risk
Considerations for Counselling and Informed Choice. J Obstet Gynaecol
Can 2018;40:935–49. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/29032069.
51. Obstetric Care Consensus No. 8 Summary: Interpregnancy Care. Obstet
Gynecol 2019;133:220–5. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/30575670.
52. Lamers Y, MacFarlane AJ, O'Connor DL, Fontaine-Bisson B.
Periconceptional intake of folic acid among low-risk women in Canada:
summary of a workshop aiming to align prenatal folic acid supplement
composition with current expert guidelines. Am J Clin Nutr
Downloaded for Mahasiswa FK UKDW 02 (mhsfkdw02@gmail.com) at Duta Wacana Christian University from ClinicalKey.com by Elsevier on November 27, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
Fetal Neural Tube Defects
2018;108:1357–68. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/30541097.
53. Cargill Y, Morin L. No. 223-Content of a Complete Routine Second
Trimester Obstetrical Ultrasound Examination and Report. J Obstet
Gynaecol Can 2017;39. e144-e9Available from: https://www.ncbi.nlm.
nih.gov/pubmed/28729106.
54. Coleman BG, Langer JE, Horii SC. The diagnostic features of spina bifida:
the role of ultrasound. Fetal Diagn Ther 2015;37:179–96. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/25341807.
55. Driscoll DA, Gross SJ, Professional Practice Guidelines C. Screening for
fetal aneuploidy and neural tube defects. Genet Med 2009;11:818–21.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/19915395.
56. Kokalj TS, Rejc B, Gersak K. Incidence and prevention of neural tube
defects in Slovenia. Eur J Obstet Gynecol Reprod Biol 2011;156:119–20.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/21300428.
57. Lu QB, Wang ZP, Gong R, Sun XH, Gao LJ, Zhao ZT. Investigation of
ultrasound screening efficiency for neural tube defects during pregnancy in
rural areas of China. Public Health 2011;125:639–44. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/21872896.
58. Nevo O, Brown R, Glanc P, Lim K. No. 352-Technical Update: The Role
of Early Comprehensive Fetal Anatomy Ultrasound Examination. J
Obstet Gynaecol Can 2017;39:1203–11. Available from: https://www.
ncbi.nlm.nih.gov/pubmed/29197487.
59. Norem CT, Schoen EJ, Walton DL, Krieger RC, O'Keefe J, To TT, et al.
Routine ultrasonography compared with maternal serum alpha-
fetoprotein for neural tube defect screening. Obstet Gynecol
2005;106:747–52. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/16199631.
60. Van den Hof MC, Smithies M, Nevo O, Oullet A. No. 375-Clinical
Practice Guideline on the Use of First Trimester Ultrasound. J Obstet
Gynaecol Can 2019;41:388–95. Available from: https://www.ncbi.nlm.
nih.gov/pubmed/30784569.
61. Salomon LJ, Alfirevic Z, Da Silva Costa F, Deter RL, Figueras F, Ghi T,
et al. ISUOG Practice Guidelines: ultrasound assessment of fetal biometry
and growth. Ultrasound Obstet Gynecol 2019;53:715–23. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/31169958.
62. Chaoui R, Benoit B, Mitkowska-Wozniak H, Heling KS, Nicolaides KH.
Assessment of intracranial translucency (IT) in the detection of spina
bifida at the 11-13-week scan. Ultrasound Obstet Gynecol 2009;34:249–
52.
63. Engels AC, Joyeux L, Brantner C, De Keersmaecker B, De Catte L, Baud
D, et al. Sonographic detection of central nervous system defects in the
first trimester of pregnancy. Prenat Diagn 2016;36:266–73. Available
from: https://www.ncbi.nlm.nih.gov/pubmed/26732542.
64. Fong KW, Toi A, Okun N, Al-Shami E, Menezes RJ. Retrospective review
of diagnostic performance of intracranial translucency in detection of open
spina bifida at the 11-13-week scan. Ultrasound Obstet Gynecol
2011;38:630–4. Available from: https://www.ncbi.nlm.nih.gov/pubmed/
21404357.
65. Lachmann R, Chaoui R, Moratalla J, Picciarelli G, Nicolaides KH.
Posterior brain in fetuses with open spina bifida at 11 to 13 weeks. Prenat
Diagn 2011;31:103–6.
66. Lachmann R, Picciarelli G, Moratalla J, Greene N, Nicolaides KH.
Frontomaxillary facial angle in fetuses with spina bifida at 11-13 weeks'
gestation. Ultrasound Obstet Gynecol 2010;36:268–71.
67. Loureiro T, Ushakov F, Montenegro N, Gielchinsky Y, Nicolaides KH.
Cerebral ventricular system in fetuses with open spina bifida at 11-13
weeks' gestation. Ultrasound Obstet Gynecol 2012;39:620–4.
000 JOGC 000 2020  13
SOGC CLINICAL PRACTICE GUIDELINE
68. Scheier M, Lachmann R, Petros M, Nicolaides KH. Three-dimensional
sonography of the posterior fossa in fetuses with open spina bifida at 11-
13 weeks' gestation. Ultrasound Obstet Gynecol 2011;38:625–9.
69. Al-Mukhtar A, Kasprian G, Schmook MT, Brugger PC, Prayer D.
Diagnostic pitfalls in fetal brain MRI. Semin Perinatol 2009;33:251–8.
70. Cannie M, Jani J, Dymarkowski S, Deprest J. Fetal magnetic resonance
imaging: luxury or necessity? Ultrasound in Obstetrics & Gynecology
2006;27:471–6. Available from: https://obgyn.onlinelibrary.wiley.com/
doi/abs/10.1002/uog.2776.
71. Coakley FV, Glenn OA, Qayyum A, Barkovich AJ, Goldstein R, Filly RA.
Fetal MRI: a developing technique for the developing patient. AJR Am J
Roentgenol 2004;182:243–52.
72. Girard N, Chaumoitre K, Chapon F, Pineau S, Barberet M, Brunel H.
Fetal Magnetic Resonance Imaging of Acquired and Developmental Brain
Anomalies. Seminars in Perinatology 2009;33:234–50. Available from:
http://www.sciencedirect.com/science/article/pii/S0146000509000329.
73. Glenn OA, Cuneo AA, Barkovich AJ, Hashemi Z, Bartha AI, Xu D.
Malformations of cortical development: diagnostic accuracy of fetal MR
imaging. Radiology 2012;263:843–55. Available from: https://pubmed.
ncbi.nlm.nih.gov/22495681 https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC3359515/.
74. Hosny IA, Elghawabi HS. Ultrafast MRI of the fetus: an increasingly
important tool in prenatal diagnosis of congenital anomalies. Magnetic
Resonance Imaging 2010;28:1431–9. Available from: http://www.
sciencedirect.com/science/article/pii/S0730725X1000216X.
75. Ljubic A, Cetkovi
c A, Novakov Mikic A, Stamenkovic JD, Jovanovic I,
Opincal T, et al. Ultrasound vs MRI in Diagnosis of Fetal and Maternal
Complications. Donald School Journal of Ultrasound in Obstetrics and
Gynecology 2011;5:231–42.
76. Pugash D, Brugger PC, Bettelheim D, Prayer D. Prenatal ultrasound and
fetal MRI: the comparative value of each modality in prenatal diagnosis.
Eur J Radiol 2008;68:214–26.
77. Saleem SN, Said A-H, Abdel-Raouf M, Elkattan EA, Zaki MS, Madkour
N, et al. Fetal MRI in the evaluation of fetuses referred for sonographically
suspected neural tube defects (NTDs): Impact on diagnosis and
management decision. Neuroradiology 2009;51:761–72.
78. Sohn YS, Kim MJ, Kwon JY, Kim YH, Park YW. The usefulness of fetal
MRI for prenatal diagnosis. Yonsei Med J 2007;48:671–7.
79. Patenaude Y, Pugash D, Lim K, Morin L, Lim K, Bly S, et al. The use of
magnetic resonance imaging in the obstetric patient. J Obstet Gynaecol
Can 2014;36:349–63.
80. Ray JG, Vermeulen MJ, Bharatha A, Montanera WJ, Park AL. Association
Between MRI Exposure During Pregnancy and Fetal and Childhood
Outcomes. Jama 2016;316:952–61.
81. Armour CM, Dougan SD, Brock JA, Chari R, Chodirker BN, DeBie I,
et al. Practice guideline: joint CCMG-SOGC recommendations for the use
of chromosomal microarray analysis for prenatal diagnosis and assessment
of fetal loss in Canada. J Med Genet 2018;55:215–21. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/29496978.
82. Beulen L, Faas BHW, Feenstra I, van Vugt JMG, Bekker MN. Clinical
utility of non-invasive prenatal testing in pregnancies with ultrasound
anomalies. Ultrasound Obstet Gynecol 2017;49:721–8.
83. Al Toukhi S, Chitayat D, Keunen J, Roifman M, Seaward G, Windrim R,
et al. Impact of introduction of noninvasive prenatal testing on uptake of
genetic testing in fetuses with central nervous system anomalies. Prenat
Diagn 2019;39:544–8.
84. Charan P, Woodrow N, Walker SP, Ganesamoorthy D, McGillivray G,
Palma-Dias R. High-resolution microarray in the assessment of fetal
14  000 JOGC 000 2020
Downloaded for Mahasiswa FK UKDW 02 (mhsfkdw02@gmail.com) at Duta Wacana Christian University from ClinicalKey.com by Elsevier on November 27, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
anomalies detected by ultrasound. Aust N Z J Obstet Gynaecol
2014;54:46–52.
85. Reddy UM, Page GP, Saade GR, Silver RM, Thorsten VR, Parker CB,
et al. Karyotype versus microarray testing for genetic abnormalities after
stillbirth. N Engl J Med 2012;367:2185–93.
86. Sun L, Wu Q, Jiang SW, Yan Y, Wang X, Zhang J, et al. Prenatal Diagnosis
of Central Nervous System Anomalies by High-Resolution Chromosomal
Microarray Analysis. Biomed Res Int 2015;2015:426379.
87. Tonni G, Palmisano M, Perez Zamarian AC, Rabachini Caetano AC,
Santana EFM, Peixoto AB, et al. Phenotype to genotype characterization
by array-comparative genomic hydridization (a-CGH) in case of fetal
malformations: A systematic review. Taiwan J Obstet Gynecol
2019;58:15–28.
88. Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, et al.
Chromosomal microarray versus karyotyping for prenatal diagnosis. N
Engl J Med 2012;367:2175–84.
89. Best S, Wou K, Vora N, Van der Veyver IB, Wapner R, Chitty LS.
Promises, pitfalls and practicalities of prenatal whole exome sequencing.
Prenat Diagn 2018;38:10–9.
90. Wou K, DeBie I, Carroll J, Brock JA, Douglas Wilson R. Fetal Exome
Sequencing on the Horizon. J Obstet Gynaecol Can 2019;41:64–7.
91. Joint Position Statement from the International Society for Prenatal
Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and
the Perinatal Quality Foundation (PQF) on the use of genome-wide
sequencing for fetal diagnosis. Prenat Diagn 2018;38:6–9.
92. Nizard J. Amniocentesis: technique and education. Curr Opin Obstet
Gynecol 2010;22:152–4.
93. Wilson RD, Gagnon A, Audibert F, Campagnolo C, Carroll J. Prenatal
Diagnosis Procedures and Techniques to Obtain a Diagnostic Fetal
Specimen or Tissue: Maternal and Fetal Risks and Benefits. J Obstet
Gynaecol Can 2015;37:656–68.
94. Alfirevic Z, Navaratnam K, Mujezinovic F. Amniocentesis and chorionic
villus sampling for prenatal diagnosis. Cochrane Database Syst Rev
2017;9:Cd003252.
95. Bakker M, Birnie E, Robles de Medina P, Sollie KM, Pajkrt E, Bilardo
CM. Total pregnancy loss after chorionic villus sampling and
amniocentesis: a cohort study. Ultrasound Obstet Gynecol 2017;49:599–
606.
96. Beta J, Zhang W, Geris S, Kostiv V, Akolekar R. Procedure-related risk of
miscarriage following chorionic villus sampling and amniocentesis.
Ultrasound Obstet Gynecol 2019;54:452–7.
97. Obeidi N, Russell N, Higgins JR, O'Donoghue K. The natural history of
anencephaly. Prenat Diagn 2010;30:357–60.
98. Al-Obaidly S, Thomas J, Abu Jubara M, Al Ibrahim A, Al-Belushi M,
Saleh N, et al. Anencephaly and obstetric outcome beyond the age of
viability. J Perinat Med 2018;46:885–8.
99. Bowman RM, McLone DG, Grant JA, Tomita T, Ito JA. Spina bifida
outcome: a 25-year prospective. Pediatr Neurosurg 2001;34:114–20.
100. Bensen JT, Dillard RG, Burton BK. Open spina bifida: does cesarean
section delivery improve prognosis? Obstet Gynecol 1988;71:532–4.
101. Cochrane D, Aronyk K, Sawatzky B, Wilson D, Steinbok P. The effects of
labor and delivery on spinal cord function and ambulation in patients with
meningomyelocele. Childs Nerv Syst 1991;7:312–5.
102. Hill AE, Beattie F. Does caesarean section delivery improve neurological
outcome in open spina bifida? Eur J Pediatr Surg 1994;4(Suppl 1):32–4.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/7766550.

103. Luthy DA, Wardinsky T, Shurtleff DB, Hollenbach KA, Hickok DE,
Nyberg DA, et al. Cesarean section before the onset of labor and
subsequent motor function in infants with meningomyelocele diagnosed
antenatally. N Engl J Med 1991;324:662–6. Available from: https://www.
ncbi.nlm.nih.gov/pubmed/1994249.
104. Merrill DC, Goodwin P, Burson JM, Sato Y, Williamson R, Weiner CP.
The optimal route of delivery for fetal meningomyelocele. Am J Obstet
Gynecol 1998;179:235–40. Available from: https://www.ncbi.nlm.nih.
gov/pubmed/9704793.
105. Sakala EP, Andree I. Optimal route of delivery for meningomyelocele.
Obstet Gynecol Surv 1990;45:209–12.
106. Tolcher MC, Shazly SA, Shamshirsaz AA, Whitehead WE, Espinoza J,
Vidaeff AC, et al. Neurological outcomes by mode of delivery for fetuses
with open neural tube defects: a systematic review and meta-analysis.
BJOG 2019;126:322–7. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/29924919.
107. Sileo FG, Pateisky P, Curado J, Evans K, Hettige S, Thilaganathan B.
Long-term neuroimaging and neurological outcome of fetal spina bifida
aperta after postnatal surgical repair. Ultrasound Obstet Gynecol
2019;53:309–13. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/30663167.
108. Masini L, De Luca C, Noia G, Caruso A, Lanzone A, Rendeli C, et al.
Prenatal diagnosis, natural history, postnatal treatment and outcome of
222 cases of spina bifida: experience of a tertiary center. Ultrasound
Obstet Gynecol 2019;53:302–8. Available from: https://www.ncbi.nlm.
nih.gov/pubmed/30288814.
109. Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson
MP, et al. A randomized trial of prenatal versus postnatal repair of
myelomeningocele. N Engl J Med 2011;364:993–1004. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/21306277.
110. Liu T, Ouyang L, Thibadeau J, Wiener JS, Routh JC, Castillo H, et al.
Longitudinal Study of Bladder Continence in Patients with Spina Bifida in
the National Spina Bifida Patient Registry. J Urol 2018;199:837–43.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/29132982.
111. Choi EK, Ji Y, Han SW. Sexual Function and Quality of Life in Young
Men With Spina Bifida: Could It Be Neglected Aspects in Clinical
Practice? Urology 2017;108:225–32. Available from: https://www.ncbi.
nlm.nih.gov/pubmed/28366704.
112. Choi EK, Kim SW, Ji Y, Lim SW, Han SW. Sexual function and qualify of
life in women with spina bifida: Are the women with spina bifida satisfied
with their sexual activity? Neurourol Urodyn 2018;37:1785–93. Available
from: https://www.ncbi.nlm.nih.gov/pubmed/29521435.
113. Matuszewski L, Perdriolle-Galet E, Clerc-Urmes I, Bach-Segura P, Klein
O, Masutti JP, et al. [Prenatal diagnosis of neural tube defects: Correlation
between prenatal and postnatal data]. J Gynecol Obstet Hum Reprod
2017;46:291–6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/
28403928.
114. Dicianno BE, Karmarkar A, Houtrow A, Crytzer TM, Cushanick KM,
McCoy A, et al. Factors Associated with Mobility Outcomes in a National
Spina Bifida Patient Registry. Am J Phys Med Rehabil 2015;94:1015–25.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/26488146.
115. Krol M, Sibinski M, Stefanski M, Synder M. [Assessment of life quality in
children with spina bifida]. Chir Narzadow Ruchu Ortop Pol 2011;76:52–
5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21850999.
116. Barf HA, Post MW, Verhoef M, Jennekens-Schinkel A, Gooskens RH,
Prevo AJ. Life satisfaction of young adults with spina bifida. Dev Med
Child Neurol 2007;49:458–63. Available from: https://www.ncbi.nlm.nih.
gov/pubmed/17518933.
117. Fischer N, Church P, Lyons J, McPherson AC. A qualitative exploration of
the experiences of children with spina bifida and their parents around
Downloaded for Mahasiswa FK UKDW 02 (mhsfkdw02@gmail.com) at Duta Wacana Christian University from ClinicalKey.com by Elsevier on November 27, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
Fetal Neural Tube Defects
incontinence and social participation. Child Care Health Dev
2015;41:954–62. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/26010416.
118. Heller MK, Gambino S, Church P, Lindsay S, Kaufman M, McPherson
AC. Sexuality and Relationships in Young People With Spina Bifida and
Their Partners. J Adolesc Health 2016;59:182–8. Available from: https://
www.ncbi.nlm.nih.gov/pubmed/27222355.
119. McPherson AC, Leo J, Church P, Lyons J, Chen L, Swift J. An
environmental scan of weight assessment and management practices in
paediatric spina bifida clinics across Canada. J Pediatr Rehabil Med
2014;7:207–17. Available from: https://www.ncbi.nlm.nih.gov/pubmed/
25260504.
120. McPherson AC, Swift JA, Peters M, Lyons J, Joy Knibbe T, Church P, et al.
Communicating about obesity and weight-related topics with children with
a physical disability and their families: spina bifida as an example. Disabil
Rehabil 2017;39:791–7. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/27015588.
121. McPherson AC, Swift JA, Yung E, Lyons J, Church P. The assessment of
weight status in children and young people attending a spina bifida
outpatient clinic: a retrospective medical record review. Disabil Rehabil
2013;35:2123–31. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/23510013.
122. Shepard CL, Doerge EJ, Eickmeyer AB, Kraft KH, Wan J, Stoffel JT.
Ambulatory Care Use among Patients with Spina Bifida: Change in Care
from Childhood to Adulthood. J Urol 2018;199:1050–5. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/29113842.
123. Tulipan N, Wellons JC 3rd, Thom EA, Gupta N, Sutton LN, Burrows PK,
et al. Prenatal surgery for myelomeningocele and the need for
cerebrospinal fluid shunt placement. J Neurosurg Pediatr 2015;16:613–20.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/26369371.
124. Clayton DB, Tanaka ST, Trusler L, Thomas JC, JCt Pope, Adams MC,
et al. Long-term urological impact of fetal myelomeningocele closure. J
Urol 2011;186:1581–5. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/21862080.
125. Johnson MP, Bennett KA, Rand L, Burrows PK, Thom EA, Howell LJ,
et al. The Management of Myelomeningocele Study: obstetrical outcomes
and risk factors for obstetrical complications following prenatal surgery.
Am J Obstet Gynecol 2016;215. 778 e1- e9Available from: https://www.
ncbi.nlm.nih.gov/pubmed/27496687.
126. Inversetti A, Van der Veeken L, Thompson D, Jansen K, Van Calenbergh
F, Joyeux L, et al. Neurodevelopmental outcome of children with spina
bifida aperta repaired prenatally vs postnatally: systematic review and
meta-analysis. Ultrasound Obstet Gynecol 2019;53:293–301. Available
from: https://www.ncbi.nlm.nih.gov/pubmed/30520204.
127. Goodnight WH, Bahtiyar O, Bennett KA, Emery SP, Lillegard JB, Fisher
A, et al. Subsequent pregnancy outcomes after open maternal-fetal surgery
for myelomeningocele. Am J Obstet Gynecol 2019;220. 494 e1-
e7Available from: https://www.ncbi.nlm.nih.gov/pubmed/30885769.
128. Wilson RD, Lemerand K, Johnson MP, Flake AW, Bebbington M, Hedrick
HL, et al. Reproductive outcomes in subsequent pregnancies after a
pregnancy complicated by open maternal-fetal surgery (1996-2007). Am J
Obstet Gynecol 2010;203. 209 e1-6Available from: https://www.ncbi.
nlm.nih.gov/pubmed/20537307.
129. Sacco A, Van der Veeken L, Bagshaw E, Ferguson C, Van Mieghem T,
David AL, et al. Maternal complications following open and fetoscopic
fetal surgery: A systematic review and meta-analysis. Prenat Diagn
2019;39:251–68. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/30703262.
130. Dickens BM, Cook RJ. Legal and ethical issues in fetal surgery. Int J
Gynaecol Obstet 2011;115:80–3. Available from: https://www.ncbi.nlm.
nih.gov/pubmed/21839453.
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SOGC CLINICAL PRACTICE GUIDELINE
131. Moldenhauer JS, Bahtiyar O, Benett KA, Emery SP, Lillegard JB, Fischer
A, et al. 213: Fetal myelomeningocele closure: outcomes from the fMMC
consortium registry sponsored by NAFTNet. Am J Obstet Gynecol 2019:
S154.
132. Belfort MA, Whitehead WE, Shamshirsaz AA, Bateni ZH, Olutoye OO,
Olutoye OA, et al. Fetoscopic Open Neural Tube Defect Repair:
Development and Refinement of a Two-Port, Carbon Dioxide
Insufflation Technique. Obstet Gynecol 2017;129:734–43. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/28277363.
133. Blumenfeld YJ, Belfort MA. Updates in fetal spina bifida repair. Curr
Opin Obstet Gynecol 2018;30:123–9. Available from: https://www.ncbi.
nlm.nih.gov/pubmed/29489502.
134. Degenhardt J, Schurg R, Winarno A, Oehmke F, Khaleeva A, Kawecki A,
et al. Percutaneous minimal-access fetoscopic surgery for spina bifida
aperta. Part II: maternal management and outcome. Ultrasound Obstet
Gynecol. 2014;44:525–31. Available from: https://www.ncbi.nlm.nih.
gov/pubmed/24753062.
135. Kohl T. Percutaneous minimally invasive fetoscopic surgery for spina
bifida aperta. Part I: surgical technique and perioperative outcome.
Ultrasound Obstet Gynecol. 2014;44:515–24. Available from: https://
www.ncbi.nlm.nih.gov/pubmed/24891102.
136. Pedreira DA, Zanon N, Nishikuni K, Moreira de Sa RA, Acacio GL, Chmait
RH, et al. Endoscopic surgery for the antenatal treatment of
myelomeningocele: the CECAM trial. Am J Obstet Gynecol 2016;214. 111
e1- e11Available from: https://www.ncbi.nlm.nih.gov/pubmed/26386383.
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137. Lapa DA. Endoscopic fetal surgery for neural tube defects. Best Pract Res
Clin Obstet Gynaecol 2019;58:133–41. Available from: https://www.ncbi.
nlm.nih.gov/pubmed/31350160.
138. Licci M, Guzman R, Soleman J. Maternal and obstetric complications in
fetal surgery for prenatal myelomeningocele repair: a systematic review.
Neurosurg Focus 2019;47:E11.. Available from: https://www.ncbi.nlm.
nih.gov/pubmed/31574465.
139. Riddle S, Huddle R, Lim FY, Stevenson C, Dean K, Sparling K, et al.
Morbidity and cost burden of prenatal myelomeningocele repair. J Matern
Fetal Neonatal Med 2019:1–7. Available from: https://www.ncbi.nlm.nih.
gov/pubmed/31345076.
140. Radic JAE, Illes J, McDonald PJ. Fetal Repair of Open Neural Tube
Defects: Ethical, Legal, and Social Issues. Camb Q Healthc Ethics
2019;28:476–87. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/31298194.
141. Barry S. Quality of life and myelomeningocele: an ethical and evidence-
based analysis of the Groningen Protocol. Pediatr Neurosurg
2010;46:409–14. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/21540616.
142. Boyd PA, Devigan C, Khoshnood B, Loane M, Garne E, Dolk H, et al.
Survey of prenatal screening policies in Europe for structural
malformations and chromosome anomalies, and their impact on detection
and termination rates for neural tube defects and Down's syndrome.
BJOG 2008;115:689–96. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/18410651.
 Fetal Neural Tube Defects

APPENDIX A

Table 1 and 2

Table 1. Key to Grading of Recommendations, Assessment, Development and Evaluation Quality of Evidence
Strength of Recommendation Definition
Strong High level of confidence that the desirable effects outweigh the undesirable effects (strong recommendation
for) or the undesirable effects outweigh the desirable effects (strong recommendation against)
Conditional (weak)a Desirable effects probably outweigh the undesirable effects (weak recommendation for) or the undesirable
effects probably outweigh the desirable effects (weak recommendation against)
Quality of Evidence Definition
High High level of confidence that the true effect lies close to that of the estimate of the effect
Moderate Moderate confidence in the effect estimate:
The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially
different
Low Limited confidence in the effect estimate:
The true effect may be substantially different from the estimate of the effect
Very low Very little confidence in the effect estimate:
The true effect is likely to be substantially different from the estimate of effect
a
Do not interpret conditional (weak) recommendations to mean weak evidence or uncertainty of the recommendation.
Adapted from GRADE Handbook (2013), Table 5.1.

Table 2. Implications of Strong and Conditional (Weak) Recommendations, by Guideline User

Perspective Strong Recommendation Conditional (Weak) Recommendation
“We recommend that. . .” “We suggest. . .”
“We recommend to not. . .” “We suggest to not. . .”

Authors The net desirable effects of a course of action
outweigh the effects of the alternative course of
action.
Patients Most individuals in the situation would want the
recommended course of action, while only a small
proportion would not.
Clinicians Most individuals should receive the course of
action. Adherence to this recommendation
according to the guideline could be used as a
quality criterion or performance indicator.
Policy makers The recommendation can be adapted as policy in
most settings.
Adapted from GRADE Handbook (2013), Table 6.1.
It is less clear whether the net desirable consequences
of a strategy outweigh the alternative strategy.
The majority of individuals in the situation would want
the suggested course of action, but many would not.
Recognize that patient choices will vary by
individual and that clinicians must help patients arrive
at a care decision consistent with the patient’s values
and preferences.
The recommendation can serve as a starting point for
debate with the involvement of many stakeholders.

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SOGC CLINICAL PRACTICE GUIDELINE

APPENDIX B

Genetic copy number variants reported in myelomeningocele (MMC)

Order of frequency (highest to lowest)

MMC with additional
Gestational stage; study Isolated MMC Undesignated anomalies
Embryonic: surgical abortion, missed
abortion, therapeutic abortion (full
aneuploidy)
Chen CP. Chromosomal abnormalities  triploidy
associated with neural tube defects (I):  trisomy 13
full aneuploidy. Taiwan J Obstet Gynecol.  trisomy 18
2007;46(4):325-335.  45,X (Turner Syndrome)
 trisomy 14
 trisomy 16
Fetal
Full aneuploidy
Chen CP. Chromosomal abnormalities Overall range 4.4%−17.3%:
associated with neural tube defects (I):  trisomy 18
full aneuploidy. Taiwan J Obstet Gynecol.  trisomy 13
2007;46(4):325-335.  triploidy
 trisomy 9
 trisomy 21
 trisomy 7
 trisomy 8
 trisomy 14
 trisomy 15
 trisomy 16
 mosaic trisomy 5, 11, 20
 45,X
 tetraploidy
Kanit H, Ozkan AA, Oner SR, Ispahi C,  7% (7/100) 29% (2/7):
Endrikat JS, Ertan K. Chromosomal  structural (4)
 trisomy 18 (1)
abnormalities in fetuses with ultrasono-  triploidy (1)
 45,X (1)
graphically detected neural tube defects.  trisomy 18 (1)
Clinical Dysmorphology 2011; 20:  trisomy 21 (1)
190-193.
Yazici LEE, Malatyalioglu E, Sakinci M, 0/60
Tosun M. Bildircin FD, Ogur G, Karayel M.
Chromosomal anomalies and additional
sonographic findings in fetuses with
open neural tube defects. Arch Gynaecol
Obstet 2012; 286: 1393-1398
Ekin A, Gezer C, Taner CE, Ozeren M, 0/44 9% (2/22):
Ozer O, Koc A, Gezer NS. Chromosomal  trisomy 18
and structural anomalies in fetuses with  trisomy 13
open neural tube defects. J Obstet
Gynecol 2014; 34(2): 156-159
Full aneuploidy (first trimester)
Sepulveda w, Wong AE, Fauchon DE. 0/7 1/1 (trisomy 18)
Fetal spinal anomalies in a first-trimester
sonographic screening program for
aneuploidy. Prenat Diagn 2011; 31: 107-
114
Partial aneuploidy
Chen CP. Chromosomal No estimate for the frequency
Abnormalities Associated with Neural of dup or del is available;
tube Defects (II): Partial Aneuploidy Tai- each chromosome (1 to 22)
wan J Obstet Gynecol 2007; 46(4): 336- has been reported

(continued)

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 Fetal Neural Tube Defects

(Continued)
Order of frequency (highest to lowest)
MMC with additional
Gestational stage; study Isolated MMC Undesignated anomalies
351.
Chen CP, Chen YJ, Chern SR, Tsai
FJ, Lin HH, Lee CC, Wang W. Prenatal
diagnosis of mosaic 1q31.3q32.1 trisomy
associated with occipital encephalocele.
Prenat Diagn 2008; 28: 865-867.
Chen CP, Chen CY, Chern SR, Wu
PS, Chen SW, Lai ST, et al. Molecular
cytogenetic characterization of a duplica-
tion of 15q24.2-q26.2 associated with
anencephaly and neural tube defect.
Taiwanese J Obstet Gynecol 2017; 56:
550-553.
Preiksaitiene E, Benusiene E, Ciula-
daite Z, Sliuzas V, Mikstiene V, Kucinskas
V. Recurrent fetal syndromic spina bifida
associated with 3q26.1-qter duplication
and 5p13.33-pter deletion due to familial
balanced rearrangement. Taiwanese J
Obste Gynecol 2016; 55: 410-414.
Lurie IVV, Novikova IV, Tarletskaya
OA, Lazarevich AA, Gromyko OA. Distal
13q monosomy and neural tube defects.
Genet Couns 2016; 27(2): 177-86.
Canda MT, Demir N, Bal FU, Doganay
L, Sezer O. Prenatal diagnosis of a 22q11
deletion in a second-trimester fetus with
conotruncal anomaly, absent thymus,
and meningomyelocele: Kousseff syn-
drome. J Obstet Gynaecol Res 2012; 38
(4): 737-740.
Preiksaitiene et al. 201630, Lurie et al.
201631

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SOGC CLINICAL PRACTICE GUIDELINE

APPENDIX C

Postnatal spina bifida repair follow-up

Rate, %
No. of patients
with postnatal Ambulation, GI bladder QoL
Study N SB repair VP shunt good function function IQ >70 assessment
Sileo FG, Pateisky P, Curado J, 241 75 64 46 44 85
Evans K, Hettige S, Thilagana-
than. Long-term neuroimaging
and neurological outcome of
fetal spina bifida aperta after
postnatal surgical repair. Ultra-
sound Obstet Gynecol 2019; 53:
309-313.
Masini L, De Luca C, Noia G, Lan- 222 157 60 50 38 80
zone A, Rendell C, Ausili E,
Massimi L, Tamburrini G, Api-
cella M, De Santis. Prenatal
diagnosis, naturel history, post-
natal treatment and outcome of
222cases of spina bifida: experi-
ence of a tertiary center. Ultra-
sound Obstet Gynecol 2019; 53:
302-308.
Adzick NS, Thom EA, Spong CY, 80 80 82 21 (at 30 mo)
Brock JW, Burrows PK, Johnson
MP, et al. A randomized trial of
prenatal versus postnatal repair
of myelomeningocele. N Engl J
Med 2011; 364(11): 993-1004.
Rintoul NE, Sutton LN, Hubbard 297 297 81 Function worse than
AM, Cohen B, Melchionni J, predicted by radio-
Pasquariello PS, Adzick NS. A logical level
new look at myelomeningoceles:
functional level, vertebral level,
shunting, and the implications
for fetal intervention. Pediatrics
2002; 109(3): 409-13.

l M, Sibin
Kro
ski M, Stefanski M, 33 33
Synder M. Assessment of life  very good (60)
quality in children with spina
bifida. M.Chir Narzadow Ruchu  good (30)
Ortop Pol 2011; 76:52−5.
Barf HA, Post MW, Verhoef M, 119 119 Comparable to
Jennekens-Schinkel A, Goosk- control (76 vs. 72)
ens RH, Prevo AJ. Life satisfac-
tion of young adults with spina
bifida. Dev Med Child Neurol
2007; 49:458−63.
Hunt GM, Oakeshott P. Outcome 117 117 40 40
in people with open spina bifida
at age 35: prospective commu-
nity-based cohort study. BMJ
2003; 326:1365−6.
Bowman RM, McLone DG, Grant 118 118 86 90 80
JA, Tomita T, Ito JA. Spina bifida
outcome: a 25-year prospective.
Pediatr Neurosurg 2001; 34:114-
120.
GI: gastrointestinal; QoL: quality of life; RCT: randomized controlled trial; VP: ventriculoperitoneal.

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 Fetal Neural Tube Defects

APPENDIX D

Comparison among fetoscopic approaches for fetal surgical repair of myelomeningocele

Study; approach
Belfort MA, Whitehead Pedreira DA, Zanon Kohl T. percutaneous Adzick NS, Thom EA,
WE, Shamshirsaz AA, N, Nishikuni K, et al. minimally invasive Spong CY, Brock JW,
et al. Fetoscopic Open Endoscopic surgery fetoscopic surgery for Burrows PK, Johnson
Neural Tube Defect for the antenatal spina bifida aperta. MP, et al. A
Repair: Development treatment of Part 1: surgical randomized trial of
and Refinement of a myelomeningocele: technique and prenatal versus
Two-Port, Carbon the CECAM trial. Am J perioperative postnatal repair of
Dioxide Insufflation Obstet Gynecol. outcome. Ultrasound myelomeningocele. N
Technique. Obstet 2016;214(1):111. Obstet Gynecol 2014; Engl J Med 2011; 364
Gynecol. 2017;129 e1-111.e11. 44: 515-24. (11): 993-1004.
(4):734-743. Degenhardt J, Schurg
R, Winarno A,
Oehmke F, Khaleeva
A, Kawecki A, et al.
Percutaneous
minimal-access
fetoscopic surgery for
spins bifida aperta.
Part II; maternal
management and
outcome. Ultrasound
Obstet Gynecol 2014;
44: 525-31.
Fetoscopic with Percutaneous Percutaneous Uterine hysterotomy
maternal laparotomy fetoscopic fetoscopic with maternal
laparotomy
Cases, no. 10 10 51 78
Incomplete repair 0 2 1 0
Maternal outcome
Placental abruption 0 1 0 5
Chorioamnionitis 0 0 3 2
Oligohydramnios 1 4 7 16
Chorioamniotic membrane separation 2 4 2 20
PROM 1 10 43 36
Vaginal delivery 6 0 0 0
Uterine thinning 0 0 0 27
Fetal neonatal outcome
Mean § SD GA at birth, wk 38.5 § 1.2 32.4 § 1.9 32.9 § 2.7 34.1 § 3.1
PTB <30 wk 0 1/9 6 10/78
RDS 0 0 NA 16/77
Additional repair 0 2/7 NA 2/77
Hindbrain reversal 6 6/7 NA 25/70
Ventricular surgery <12 mo 2 3/7 NA 31/77
CM decompression 0 0 NA 1/77
PNM 0 2/10 4/51 2/78
CM: Chiari malformation; GA: gestational age; PNM: perinatal mortality; PROM: premature rupture of membranes; PTB: preterm birth; RDS: respiratory distress
syndrome.

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SOGC CLINICAL PRACTICE GUIDELINE
APPENDIX E
Table. Summary of technical outcomes of fetal myelomeningocele repair
Study
Pan ET, Pallapati J, Krueger A,
et al. Evaluation and Disposition
of Fetal Myelomeningocele
Repair Candidates: A Large
Referral Center Experience.
Fetal Diagn Ther. 2020;47
(2):115-122.
Joyeux L, De Bie F, Danzer E,
et al. Learning curves of open
and endoscopic fetal spina
bifida closure: systematic review
and meta-analysis. Ultrasound
Obstet Gynecol. 2020;55
(6):730-739.
Zarutskie A, Guimaraes C, Yepez
M, Torres P, Shelly A, Sagi-
Haghpeykar H, Lee W, et al.
Prenatal brain imaging for pre-
dicting need for postnatal hydro-
cephalus treatment in fetuses
that had neural tube defect
repair in utero. Ultrasound
Obstet Gynecol 2019; 53
(3):324-334
Flanders TM, Heuer GG, Madsen
PJ, et al. Detailed Analysis of
Hydrocephalus and Hindbrain
Herniation After Prenatal and
Postnatal Myelomeningocele
Closure: Report From a Single
Institution. Neurosurgery.
2020;86(5):637-645.
Sanz Cortes M, Torres P, Yepez
M, et al. Comparison of brain
microstructure after prenatal
spina bifida repair by either lapa-
rotomy-assisted fetoscopic or
open approach. Ultrasound
Obstet Gynecol. 2020;55(1):
87-95.
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Topic
Fetal MMC evaluation and
disposition
Learning curve for open vs.
fetoscopic MMC repair
Prenatal CNS imaging and post-
natal shunt
Detailed analysis of hydrocepha-
lus and hindbrain herniation
Brain micro-structure following
MMC repair
Design
Single-centre cohort study
(2013−2018) of 204 referrals
Systematic review and meta-
analysis of 17 studies with low
and moderate risks of bias
Retrospective cohort study of 50
fetuses with MMC
Retrospective single-centre
cohort study (2011−2016) of
MMC repair
Retrospective cohort study of
57 fetuses with MMC
Outcomes and conclusions
175 patients were evaluated
 80 (46%) qualified for MMC
repair
○ 17 declined the option
○ 57 (32%) had MMC repair
& 37 (65%) fetoscopic repair
& 20 (35%) open repair
Competency was achieved for:
 Standard hysterotomy after 35
consecutive cases
 Mini-hysterotomy predicted at
>57 cases
 Percutaneous two-layer
approach predicted at >56
cases
Competency was not reached
after 28 and 81 consecutive cases
for exteriorized uterus and percu-
taneous single layer fetoscopy,
respectively
 18 were treated with fetoscopic
approach
 32 were treated with open
repair
 17 required hydrocephalus
treatment (HT)
Persistence of hindbrain hernia-
tion on MRI at 6 weeks after repair
independently predicted the need
for HT better than sonography or
other MRI-derived measurements.
Outcomes for
 62 postnatal repairs
 119 fetal repairs
○ CSF diversion 81% (postna-
tal) vs. 39% (fetal)
○ HB herniation resolution
33% (postnatal) vs. 82%
(fetal)
○ Hydrocephalus treatment at
14 days (postnatal) vs. 10
months (fetal)
○ Fetal or neonatal death 0
(postnatal) vs. 5% (6) (fetal)
Fetal repair improved CSF
dynamics.
 27 were treated with fetoscopic
approach
 30 were treated with open
repair
After 1 year of age, there were no
differences between techniques
for ventriculomegaly or apparent
diffusion coefficient values from
selected CNS lobes.Uterine car-
bon dioxide (CO2) insufflation was
associated with CNS effects.
(continued)

(Continued)
Study
Sanz-Cortes M, Davila J, Torres P,
Yepez M, Lee W, Guimaraes CV,
Sangi-Haghpeykar H, et al.
Does fetoscopic or open repair
for spina bifida affect fetal and
postnatal growth? Ultrasound
Obstet Gynecol 2019; 53(3):
314-323.
Kassir E, Belfort MA, Shamshirsaz
AA, Sanz-Cortes M, Whitehead
WE, Espinoza J Doppler
changes in umbilical artery and
ductus venosus during feto-
scopic prenatal surgical repair of
myelomeningocele. Ultrasound
Obstet Gynecol 2019; 53(3):
335-339.
Sanz-Cortes M, Castro E, Shar-
han D, Torres P, Yepez M, Espi-
noza J, Shamshirsaz AA, et al.
Amniotic membrane and placen-
tal histopathological findings
after open and fetoscopic prena-
tal neural tube defect repair. Pre-
nat Diagn 2019; 39(4): 269-279.
Seaman RD, Cassady CI, Yepez
Donado MC, et al. Postoperative
imaging following fetal open
myelomeningocele repair: The
clinical utility of magnetic reso-
nance imaging and sonographic
amniotic fluid volumes in detect-
ing suspected hysterotomy scar
dehiscence. Prenat Diagn.
2020;40(1):66-70.
Kohn JR, Rao V, Sellner AA, et al.
Management of Labor and
Delivery After Fetoscopic Repair
of an Open Neural Tube Defect.
Obstet Gynecol. 2018;131
(6):1062-1068.
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Topic
Fetal growth following MMC
repair
Fetal vascular change during
fetal MMC repair
Amniotic membrane and placen-
tal histopathological findings
after fetal MMC repair
Post-operative imaging after
open MMC repair
Labour and delivery care follow-
ing fetoscopic MMC repair
Design
Retrospective cohort study of 66
fetuses with MMC
Retrospective cohort study of 35
cases of fetoscopic MMC
repair
Retrospective cohort study of 43
fetuses compared with healthy
controls
Retrospective cohort study of 31
cases of open repair of MMC
Retrospective cohort study
(2014−2018) of fetoscopic
repair of MMC in 34 fetuses
Fetal Neural Tube Defects
Outcomes and conclusions
 32 were treated with fetoscopic
approach
 34 were treated with open
repair
No significant differences in
growth or in other fetal or postnatal
outcomes were identified; the
study supports use of CO2 for
fetoscopic repair.
15 cases had data from colour
Doppler sonography.
Transient Doppler abnormalities
of the umbilical artery, but no
significant changes in the ductus
venosus, were seen during feto-
scopic MMC repair. The clinical
significance of the transient and
intermittent abnormalities is
unclear.
 17 were treated with fetoscopic
approach
 26 were treated with open
repair
 18 healthy controls
No differences were identified
between fetal repair techniques,
individually or compared with con-
trols. No detrimental effects were
found of the use of heated and
humidified CO2 gas for uterine
insufflation.
At cesarean delivery
 21 cases of hysterotomy scars
were identified as intact
 10 cases of hysterotomy scars
were identified as non-intact
○ 6 very thin scar
○ 4 dehiscence
Routine post-operative MRI at 6
weeks post-MMC repair failed to
identify any of the 10 cases. Ret-
rospective review of Amniotic
Fluid Index (AFI) measurements
identified decrease in mean AFI
for the 10 cases with non-intact
finding.The combination of uterine
contractions and significantly
decreased AFI may indicate non-
intact scarring in the index preg-
nancy involving fetal MMC repair.
 17 vaginal deliveries (50%) at a
mean GA of 381 weeks
 17 cesarean deliveries (50%) at
a mean GA of 371 weeks
 62% were term deliveries
 26% involved labour
○ 20 spontaneous labour
○ 6 induced labour
○ 17 vaginal deliveries
○ 9 urgent cesarean deliveries
Following fetoscopic MMC repair,
a trial of labour, the use of low-
dose oxytocin, and vaginal deliv-
ery outcomes are reassuring.
(continued)
000 JOGC 000 2020  16.e7
SOGC CLINICAL PRACTICE GUIDELINE

(Continued)
Study
Parizi JLG, Leal da Cruz M,
Andrade MC, et al. A Compara-
tive Analysis of Bladder Pattern
of Patients who Underwent In
Utero Versus Postnatal Myelo-
meningocele Repair. J Urol.
2020;203(1):194-199.
Cools M, Northam W, Goodnight
W, Mulvaney G, Elton S, Quin-
sey C. Thirty-day medical and
surgical readmission following
prenatal versus postnatal myelo-
meningocele repair. Neurosurg
Focus. 2019;47(4):E14.
AFI: Amniotic Fluid Index; CNS: central nervous system; CO2: carbon dioxide; CSF: cerebrospinal fluid; GA: gestational age; HB: hindbrain; HT = hydrocephalus treat-
ment; MMC: myelomeningocele; MRI: magnetic resonance imaging.
Topic
Bladder function in patients fol-
lowing fetal vs. postnatal repair
of MMC
Hospital re-admission following
fetal vs. postnatal repair of
MMC
Design
Retrospective cohort study of
174 fetuses
Retrospective cohort study
(2011−2017) of 58 fetuses
Outcomes and conclusions
High-risk bladder pattern following
MMC repair
 56% of 88 fetuses undergoing
fetal repair
 50% of 86 fetuses undergoing
postnatal repair
○ 46% of 38 in subgroup of
fetuses treated <12 months
postnatally
Fetal repair did not improve uro-
logical parameters compared to
postnatal repair.
 24 treated with fetal repair
 34 treated with postnatal repair
Fetuses treated with fetal repair
had fewer readmissions at 30 and
60 days and at 1 year than those
treated with postnatal repair.
Those treated with fetal repair had
lower requirements for CSF diver-
sion at 1 year of age and were
older, with larger body mass, at
the time of CSF diversion than
those treated with postnatal repair.

16.e8  000 JOGC 000 2020

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