Prenatal Screening SOGC

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SOGC CLINICAL PRACTICE GUIDELINE

No. 314, October 2014 (Replaces No. 261, July 2011)

Prenatal Screening, Diagnosis, and Pregnancy


Management of Fetal Neural Tube Defects
This clinical practice guideline has been prepared by
the Genetics Committee, reviewed by Family Physician
Advisory and Diagnostic Imaging Committees, and
approved by the Executive and Council of the Society of
Obstetricians and Gynaecologists of Canada.
PRIMARY AUThOR

Abstract
Objective: To provide obstetrical and genetic health care practitioners
with guidelines and recommendations for prenatal screening,
diagnosis, and obstetrical management of fetal open and closed
Options: This review includes prenatal screening and diagnostic
including maternal serum alpha fetoprotein screening, ultrasound,
fetal magnetic resonance imaging, and amniocentesis.

SOGC GENETICS COMMITTEE

Outcomes: To improve prenatal screening, diagnosis, and obstetrical

Francois Audibert, MD, Montreal QC


Evidence: Published literature was retrieved through searches

Lola Cartier, MSc, CCGC, Montreal QC

neural tube defects, alpha fetoprotein, ultrasound scan, magnetic


reviews, randomized control trials/controlled clinical trials, and
observational studies published in English from 1977 to 2012.
Searches were updated on a regular basis and incorporated in

practice guideline collections, clinical trial registries, and national


health care practitioners was also reviewed.
Values:
criteria described in the Report of the Canadian Task Force on
.
SPECIAL CONTRIBUTOR

This review will provide health


care practitioners with a better understanding of the available
risks associated with each technique to allow evidenced-based
management.

Key words: prenatal screening, congenital anomalies, neural tube


defects, alpha fetoprotein, ultrasound scan, magnetic resonance

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

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SOGC CLINICAL PRACTICE GUIDELINE

Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive health Care
A. There is good evidence to recommend the clinical preventive action
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization

B. There is fair evidence to recommend the clinical preventive action

more than one centre or research group


D. There is fair evidence to recommend against the clinical preventive action
places with or without the intervention. Dramatic results in
E. There is good evidence to recommend against the clinical preventive
action
III:

Opinions of respected authorities, based on clinical experience,


descriptive studies, or reports of expert committees
decision-making

Preventive Health Care.109


on Preventive Health Care.109

RECOMMENDATIONS
Screening Evaluation
abnormalities including open/closed neural tube defects

estimated risk of recurrence, and prediction of long-term


neonatal and childhood outcomes of open/closed neural tube

anatomical ultrasound with detailed fetal intracranial and spinal

of

closed neural tube defects screening should be discontinued


with the limited clinical exceptions of pregnant women with a
2
or when geographical

screening, maternal serum alpha fetoprotein can be used as a


4. Positive screening results for open/closed neural tube defect
referral to appropriate experienced providers for genetic review,

Diagnostic Evaluation
5. If the second trimester screening fetal ultrasound indicates a
probable diagnosis of neural tube defects, the women should be
for a more detailed ultrasound examination looking for the
6. Prenatal magnetic resonance imaging can be considered as
an additional fetal imaging technique if further detailed fetal

maternalfetal medicine, and pediatric neurosurgical counselling

Pregnancy Management
10. Following the detection of an isolated open/closed neural tube
management options after diagnostic and genetic testing results
are available. Options should include information about
or fetal contraindications for prenatal repair at 2026 weeks
prognosis, and

request. For an encephalocele, individualized counselling is

Invasive Prenatal Diagnostic Methods


considered in selected MMC vertex presentation cases that have

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Prenatal Screening, Diagnosis, and Pregnancy Management of Fetal Neural Tube Defects

oral folic acid supplementation of 5 mg within a multivitamin


preparation should be recommended to the female partner,

INTRODUCTION

CNTDs are congenital abnormalities or


malformations of the neuraxis. Structural
developmental malformations can affect the thoracic,
is declined, fetal magnetic resonance imaging should be
considered to better evaluate fetal abnormalities either in
utero or after postnatal death. If genetic studies have not
been completed prior to the termination, at the minimum,

not performed. This procedure will maximize information for

Pregnancy Follow-up
14. Follow-up consultation is recommended when postnatal genetic
and pathologic studies are complete, to provide the woman with

presumed folic acid-sensitive open/closed neural tube defect

(anencephaly or encephalocele). Secondary co-anomalies


(disruption or deformation) can involve the lower limb,
bowel, bladder, cerebellum, and cerebral cortex or cerebral
ventricles (for myelomeningocele).13 The human neural
tube normally closes during the 3rd and 4th weeks of
embryonic development (correlating with 56 weeks
gestation from LMP).
The primary method of preventing the majority of
OCNTDs is with increased red blood cell folate by
supplementation, but this increased maternal folate
strategy must occur before conception and continue
new cell production during rapid cell division.46
This biological folic acid factor is important because
embryogenesis has certain folic acid-sensitive anomalies

ABBREVIATIONS

trimester development. With the introduction of folic


acid supplementation (19911992), there has been a

AFP

alpha fetoprotein

FPR

false positive rate

LMP

last menstrual period

MC

meningocele

MRI

magnetic resonance imaging

MSAFP

maternal serum alpha fetoprotein

of OCNTDs in Canada. This reduction and new clinical


prenatal surgical outcomes for OCNTD highlighted the
need for new clinical care protocols and recommendations
to be developed for prenatal screening, diagnosis, and
management of OCNTDs.
Since the introduction of ONTD screening methods in the
1970s, the total number of reported cases has increased,
most likely because of advances in prenatal screening and
early detection.2,714 A decrease in birth prevalence is the
result of both primary prevention, in the form of folic
prevention methods (prenatal screening and termination
of an affected pregnancy).4,6,13,14

OR

odds ratio

RCT

randomized controlled trial

OCNTD screening and diagnosis are carried out by


MSAFP measurement, fetal imaging techniques (ultrasound
imaging and MRI), and amniocentesis. It is recommended
that prenatal screening be offered and undertaken in the
second trimester between 15 and 22 weeks gestation to
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maximize testing accuracy, achieve a low FPR, and allow


optimal management of affected pregnancies.4,10,1527
Factors that have been reported to affect the accuracy
and interpretation of OCNTD screening results include
type of NTD malformation, gestational age, maternal
weight, maternal insulin-dependent diabetes, multiple
gestations, ethnicity, environmental factors (prescription
and non-prescription medications), and concurrent fetal
anomalies.1,9,13,17,22
Early prenatal screening for ONTD gives parents and
health care practitioners the ability to evaluate the anomaly
and the overall health of the fetus during the second
trimester. This guideline focuses on NTD screening,
diagnosis, and post-diagnostic pregnancy management.
GENETICS OF NTD

In humans, the neural tube closes between 21 to 28 days


of embryonic development, and abnormal closure is
characterized by the improper fusion of the neural tube in
the developing embryo.1,2,7 NTD prevalence ranges from 1
in 300 to 1 in 1000 pregnancies and is affected by ethnic,
genetic, and dietary factors, with the highest NTD rates in
the United Kingdom and the United States and the lowest
rates in Japan.9,10,2831
Certain chronic maternal medical conditions will increase the
risk of NTDs, including poorly controlled maternal insulindependent diabetes (OR 11.5), antiepileptic medications
(valproic acid, carbamazepin), therapy with folic acid
antagonists, and maternal obesity (OR 3.5).2831
NTDs are described by their anatomical location and
neural content type as follows:

16.3% incidence.3337 Syndromes or sequences associated with


NTDs include amniotic band syndrome, cloacal extrophy,
limb body wall complex, OEIS (omphalocele, extrophy,
imperforate anus, spinal) syndrome, cerebrocostomandibular
syndrome, and caudal regression.38 Other syndromic
OCNTDs are associated with single gene disorders such as
(cranial ONTD and holoprosencephaly) genes. Other single
gene disorders reported include Waardenburg syndrome and
Curarino syndrome.38
There are reports of gene mutations or alterations of gene
expression leading to ONTDs, such as polymorphisms
or SNPs in genes responsible for folate transport, the
methionine/homocysteine metabolic cycle, methylation,
and nucleotide biosynthesis. Rare mechanisms contributing
autoantibodies to the folate receptors, and infertility or
assisted reproductive technology therapy.3942
NON-INVASIVE NTD SCREENING TEChNIQUES
Ultrasound Screening

Ultrasound is the non-invasive screening modality of choice


for the detection of fetal anomalies including NTDs because
4,21,22,43,44

The current generation of ultrasound machines allow for


highly detailed fetal imaging. National screening policy
documents cite detection rates of approximately 68% to
94% for NTDs,9,22,4547 with EUROCAT reporting a 68%
48
and British
Columbia an 86% detection rate (19971999).4

4. inencephaly/craniorachischisis (abnormal skull and


upper spine development) 1.5%.32

A second trimester screening ultrasound should be offered


to all pregnant women, as recommended in a number of
SOGC guidelines43,49,50 for the detection of congenital
anomalies from 18 to 22 weeks gestation, avoiding the
need for a second trimester MSAFP screening test.15,43,45,47,48
Ultrasound is recommended routinely in all second trimester
pregnancies and is a more effective screen for OCNTD
(improved sensitivity with lower FPR although more
expensive) than MSAFP screening, and diagnostically it is
safer than amniocentesis which carries the risk of infection
or spontaneous abortion.9,11,45,47,5153 In addition, ultrasound
has the major advantage of screening for multiple congenital
anomalies at a single ultrasound imaging visit. The factors
that may affect ultrasound screening for NTDs include

Seventy percent of NTDs related to genetic abnormalities


are isolated, non-syndromic anomalies or malformations,
and with current genetic knowledge, are considered to have
a multi-factorial inheritance. Chromosomal abnormalities
associated with an apparently isolated NTD have a 2.4% to

of fetuses, and maternal BMI. Other factors to consider


are parental ethnicity, at risk maternal medication use,
maternal diabetic status, and personal, pregnancy, and family
histories.1,15,43,5461 In a fetus with an OCNTD, features visible
by ultrasound in the second trimester include anencephaly

93% ONTDs (neural placode at the base of the NTD)


and 7% CNTDs (MC = dural sac only; MMC = neural
elements attached to the dural sac);
2. anencephaly (closure failure of caudal NT folds
causing failure of brain development) 40%;
3. encephalocele (outpouching of the brain through a
bony skull defect; occipital is most common, with
anterior and lateral locations) 8.5%; and

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Prenatal Screening, Diagnosis, and Pregnancy Management of Fetal Neural Tube Defects

dysmorphology), open spinal anomalies (abnormal skull


shape [lemon sign], abnormal appearance and possible
increased width of the cerebral ventricles, abnormal
appearance of the posterior fossa/cerebellum [banana sign],
and abnormal or incomplete appearance of the posterior
vertebral arches in thoracic, lumbar, or sacral locations),
and closed spinal anomalies (with the possible absence of
the lemon and banana signs and a thick appearing MMC
sac protruding from the posterior vertebral opening).
Abnormal lower limb movement and positioning of the
foot or feet may also be present.43,49,50 Preliminary research
for NTD at 11 to 13 weeks gestation, assessing structural
developmental variation, such as the absence of intracranial
translucency, decreased frontomaxillary facial angle, partial
or complete cisterna magna obliteration (brainstem diameter
decreased intracranial CSF volume.
NTD imaging should be conducted under a research
protocol at the present time.
6165

The experience of the sonographer and up-to-date and


well-maintained equipment are important in screening
evaluation.7,15 The importance of these factors is
highlighted in the recent publication from the rural areas
of China,7 where researchers found that ultrasound did not
meet its full potential as a method of secondary screening
of NTDs; ultrasound was a satisfactory screening method,
but NTD detection rate was low. This study did not report
that ultrasound was a poor method for screening, but
rather that the ultrasound screening skills of the user were
not optimal for the detection of NTD anomalies.7

contrast and spatial resolution, and single-shot rapid


acquisition with relaxation enhancements for decreasing
fetal movement effects,22,6971 there is no established
standard imaging reference because MRI is not used as a
screening modality.22,67,70,72
by MRI emphasizes the importance of correct imaging
methods and radiologic interpretation. Many new
techniques under development are already commonly
used in the neonatal period, when anatomical structures
order to use them safely during pregnancy.6670 Operator
interpretation of the MRI requires a thorough knowledge
of normal and abnormal fetal anatomy. As the option
of fetal NTD surgery becomes available in perinatal
CNS evaluation.70,73,74
MRI is considered safe for the fetus, but there are
hypothetical concerns about teratogenesis and acoustic
damage.67,70 While additional fetal MRI research with
neonatal follow-up is needed, an SOGC Diagnostic
Imaging Committee Guideline75 reports that fetal MRI is
safe at 1.5 tesla magnet exposure during the second and
third trimesters.
Ultrasound has the advantage over MRI of easier patient
access to imaging services; it is not hampered by fetal
movement, it is less expensive than MRI, and it provides
good spatial resolution. MRI, however, is not limited by
contrast, and performs well regardless of oligohydramnios,
maternal obesity, or fetal lie.22,27,70,73,74

Fetal MRI

Obstetric application of MRI began approximately 20 years


ago, 10 years after its discovery and initial use.66,67 The main
use of fetal MRI is as an adjunct to the primary ultrasound
detail could be obtained for management planning and
counselling.6870 Fetal MRIs are usually conducted between
the late second and early third trimesters, between 23 and
32 weeks gestation.21,59,70 This gestational age allows for
optimal imaging of the entire fetal brain and subarachnoid
space15,21,67,71; however, late gestation MRI can delay
decisions regarding pregnancy management, including
termination of pregnancy.
The use of fetal MRI, primarily known for its superior
brain imaging capabilities, has now been expanded to
detect non-CNS abnormalities.22,27,67,70 Although there
have been many advances in MRI technology such as the
use of T2-weighted sequences, which allow for better

additional anomalies,76 but its expense, lack of a standard


of reference for imaging, and limited availability are factors
that continue to favour ultrasound as the imaging choice
for the detection of OCNTDs.77,78
Maternal serum AFP

MSAFP screening was once considered the gold standard


of prenatal ONTD screening, but with advances in
technology, research, and knowledge, MSAFP screening
now has limited value when reliable second trimester
ultrasound (screening and diagnostic) is available. Since
the mid-1970s, non-invasive MSAFP has been used for the
detection of ONTDs.10,11,19,27,51,79 MSAFP levels rise early
in the pregnancy, and ONTD screening was optimized
to discern normal from abnormal MSAFP results in the
second trimester between 15 and 18 weeks gestation.14,15,18,45
MSAFP levels are measured in multiples of the median,
using unaffected pregnancies of the same gestational age as
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SOGC CLINICAL PRACTICE GUIDELINE

the control value.11,14,18 To interpret results, it is important


to correctly identify the gestational age, number of fetuses,
maternal ethnicity, and maternal weight. Furthermore, such
factors as a personal or family history of OCNTD, any
maternal at risk for NTD medications (epilepsy control
[valproic acid, carbamazepine] or folate antagonists), or
certain chronic medical conditions, such as diabetes, must
be taken into consideration.14,18 First trimester MSAFP
(11 to 13 gestational weeks) levels in normal pregnancies
are affected by maternal race, weight, smoking status, and
method of contraception (oral birth control).46
Second trimester MSAFP detects 71% to 90% of NTDs,
with an FPR of 1% to 3% percent.11,14,18 Elevated levels
of MSAFP can be associated with other conditions, such
as fetal skin disorders, abdominal wall defects, fetal demise,
fetal nephrosis, and pregnancies at an increased risk for
placenta-related adverse events.14,17,19 First trimester MSAFP
10%,55 and it is not recommended of NTD screening.
A detailed fetal structural ultrasound at 18 to 22
gestational weeks and amniocentesis (AFAFP, AFAChE,
and chromosome karyotype analysis) is recommended as
a diagnostic follow-up with an elevated second trimester
MSAFP level (screen-positive result).
A second trimester detailed ultrasound (at 18 to 22 gestational
weeks) is recommended as the standard of care for all
pregnancies to determine the approximate gestational age,
(not usually detected by MSAFP screening), or screen for
other congenital anomalies.43,49,50 Earlier ultrasound imaging
for dating or evaluating the pregnancy may be required, based
on clinical care factors as determined by the primary obstetrical
provider. First trimester dating by crownrump length has a
3 to 5 day standard deviations for estimating the gestational
age, compared to the 7 day standard deviations for the 18
to 22 gestational weeks ultrasound.
Many recent retrospective studies have shown that
with present screening approaches and new technology
measuring MSAFP is no longer practical for the detection
selecting women for diagnostic testing, such as ultrasound
or amniocentesis.14,16,19,20,51,79

Recommendations
Screening Evaluation

1. The primary screening test for the detection


of fetal structural abnormalities including
open/closed neural tube defects (anencephaly,
anatomical ultrasound with detailed fetal
intracranial and spinal imaging and
assessment. (II-2A)
2. The primary use of maternal serum alpha
fetoprotein for open/closed neural tube defects
screening should be discontinued with the limited
clinical exceptions of pregnant women with a pre2
or when
geographical or clinical access factors limit timely
and good quality ultrasound screening at 18 to
22 weeks gestation. (II-2A)
3. When used as a component in maternal serum
genetic aneuploidy screening, maternal serum
alpha fetoprotein can be used as a secondary
screening tool in the second trimester. (II-2A)
4. Positive screening results for open/closed neural
tube defect (ultrasound maternal serum alpha
fetoprotein) require timely referral to appropriate
experienced providers for genetic review,
diagnosis, and counselling. (II-2A)
Diagnostic Evaluation

5. If the second trimester screening fetal ultrasound


indicates a probable diagnosis of neural tube
defects, the women should be referred to a tertiary
or regional centre with ultrasound expertise for a
more detailed ultrasound examination looking for
the features associated with a neural tube defect
sequence. (II-2A)
6. Prenatal magnetic resonance imaging can
be considered as an additional fetal imaging
technique if further detailed fetal central nervous
system assessment is required for diagnostic or
management counselling. (II-2A)
INVASIVE PRENATAL DIAGNOSTIC
METhODS (NTD SCREENING/TESTING)
Amniocentesis

AFP from the fetal yolk sac initially and subsequently

MSAFP screening for ONTDs is less costly than ultrasound


or amniocentesis,11,52 but its cost advantage must be weighed
detect closed NTDs, and the requirement of further testing
that includes detailed second trimester ultrasound when
second trimester screening MSAFP levels are elevated.
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only AFP is present in maternal blood.5,14,17,80 Elevated


levels of AFAFP and AFAChE are present is fetuses
14,18,80

Prenatal Screening, Diagnosis, and Pregnancy Management of Fetal Neural Tube Defects

An amniocentesis is most often performed for the


detection of chromosomal aneuploidy or genetic
the detection of NTDs.18,23,74,8184 The procedure is
usually conducted between the 15th and 20th gestational
weeks.6,17,45,8588
karyotype, chromosomal microarray, and AFAFP and
AFAChE levels. When amniocentesis is performed with a
suspicion of OCNTD, the information from the karyotype,
chromosomal microarray, AFAFP, and the AFAChE levels
with counselling regarding prognosis.
If amniocentesis is being performed for aneuploidy
AChE is not routinely required.
aneuploidy still require a routine second trimester screening
ultrasound for fetal congenital anomalies, including NTD
screening if a complete ultrasound anatomic assessment is
Risks associated with amniocentesis include spontaneous
abortion (estimated procedural risk of 0.5% to 1.0%
added to the no-procedure background spontaneous risk
of pregnancy loss), post-procedure spotting, infections,
rupture of membranes, and fetal damage or loss.48,8688
Amniocentesis for genetic testing is especially important
when considering prenatal or postnatal repair of congenital
fetal genetic factors is important as these factors may
interfere with the neonatal outcome.73,74,8183
Although an amniocentesis is an important diagnostic
option for high-risk pregnancies in the detection of
chromosomal abnormalities and ONTDs, amniocentesis
should not be used as a method for laboratory NTD
(AFAFP, AFAChE) screening because of the risks and cost
associated with the test.
Recommendations
Invasive Prenatal Diagnostic Methods

amniocentesis (following the ultrasound detection

risk of recurrence, and prediction of long-term


neonatal and childhood outcomes of open/closed
neural tube defect for family counselling. (II-2A)
8. When a routine diagnostic amniocentesis indicates
only a risk
anomalies, it is not necessary to take an amniotic
fetoprotein and acetylcholinesterase testing to
screen for open neural tube defects. (II-2E)
an open/closed neural tube defect (isolated or in a
more complex multiple-anomaly grouping) requires
referral for comprehensive genetic, maternalfetal
medicine, and pediatric neurosurgical counselling
for complete patient-focused care. (II-2A)
PREGNANCY MANAGEMENT
Counselling Information for
Continuing Pregnancies

Counselling should be based on the recognition of the


personal impact that a physical or mental disability could
have on a child and its family.
One of the major questions a family asks when their fetus
is given an isolated, non-syndromic, non-chromosomal
myelomeningocele diagnosis is What will the quality
of life be for my child? Krl et al. reported a followup study of 33 children (19 female; 14 male) with a
myelomeningocele at ages 5 to 20 years. They were
evaluated in 2 age groups: 5 to 12 (n = 17) and 13 to
20 (n = 16) using the Health-Related Quality of Life in
study reported good, very good, and average QoL in
64%, 30%, and 6% of participants respectively. None
of the participants felt their QoL was poor. Issues of
visual perception in the younger group and ambulation
in the older group were related to lower QoL scores. The
vast majority of children had a history of good specialist
care. The most common medical issues were related to
hydrocephalus and neurogenic bladder.89
In a larger study of 119 patients with hydrocephalus and
MMC, Barf et al. reported a near equal overall QoL in the
study group (76%) as in an age-matched peer group (72%),

suspected open/closed neural tube defect),


should be evaluated for a fetal karyotype (and, if
indicated and available, a chromosomal microarray),

life, but less satisfaction with their sex lives and abilities to

acetylcholinesterase. These test results will allow


comprehensive evaluation of the etiology, estimated

In a retrospective cohort study Hunt and Oakeshott reported


on 117 open MMC patients. The cohort had had 54%

that the severity of disease and the level of the lesion had
little bearing on self-reported QoL.90

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SOGC CLINICAL PRACTICE GUIDELINE

mortality and, at evaluation, had an average age of 35 years.


Among the survivors, 40% were independent in activities
of daily living, meeting medical needs, transportation, and
continence care.91
Bowman et al. reported a 25-year follow-up of 118
MMC patients in which 75% lived to early adult age, 85%
had high school or college education, 80% were able to
maintain social bladder continence with catheterization,
90% reported acceptable levels of bowel continence,
and 86% of long-term survivors were shunt-dependent.
childhood or early adulthood was an unrecognized shunt
malfunction.92
For more complete counselling knowledge, the health
care provider could consider an economic assessment of
the cost of continuing care for the MMC patient. Yi et al.
reported across all.93 The lifetime direct medical costs for
being for inpatient care, treatment at initial diagnosis in
childhood, and co-morbidities in adult life. The caregiver
Continuing Pregnancy Surveillance
and Method of Delivery

Pregnancy surveillance and delivery recommendations


for fetuses with OCNTDs are controversial because
increased pregnancy termination has limited the study of
the MMC delivery model for more than 2 decades. The
ACOG Practice Bulletin94 reports that most pregnancies
complicated by MMC will deliver with appropriate lung
maturity at term, and there is no evidence that antenatal
fetal heart rate testing for an MMC indication improves
outcome. It is recognized that anomalous fetuses frequently
interpret.95
Serial ultrasounds for fetal growth, head size, and
ventricular size may be helpful in continued prognosis
counselling and delivery planning. The fetus should be
delivered at a centre with a level III NICU and pediatric
neurosurgery services.90 A latex-free delivery and surgical
repair plan should be considered because individuals with
MMC are at an increased risk of developing a severe and
life-threatening allergy to latex.96
The mode of delivery for an MMC-affected fetus with a vertex
presentation remains controversial. There are no RCTs, but at
least 5 studies representing a total of 400 patients suggested
vaginal delivery does not adversely affect neonatal outcome,
and one large study of 200 patients suggested Caesarean
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sections as a safer method of delivery for the MMC-affected


fetus.97102 Breech presentation is common in the MMCaffected fetus as a result of decreased lower limb neurologic
function and megacephaly, and hence requires delivery by
Caesarean section.
Prenatal in Utero Repair of MMC

The Randomized Trial of Prenatal versus Postnatal Repair


of Myelomeningocele74 showed that prenatal fetal surgery
for MMC reduced the need for ventricular peritoneal
shunting (40% vs. 82%) and showed improved lower limb
motor outcomes at 30 months of age. However, the surgery
was associated with maternal and fetal risks. Additional
improvement in the child composite score for mental
development and motor function at 30 months of age was
score: prenatal surgery [n = 64] 148.6 57.5; postnatal
surgery [n = 70] 122.6 57.2; P = 0.007). Improved
hindbrain herniation at 12 months and ambulation at 30
months was also reported. This landmark study provides
an important treatment option for parents because it clearly
surgery, albeit at the cost of increased maternal risks for
the index and subsequent pregnancies.74 An accompanying
editorial counselled caution regarding the initiation of this
new prenatal treatment in multiple fetal therapy/treatment
centres and emphasized that most women who expressed
an interest in the experimental trial were either ineligible or
declined to participate, with only 15% of screened women
participating in the study.103 A legal and ethical opinion that
drew attention to prioritizing the fetus stated that:
unlike a born child, a fetus is not a patient in the real
sense, but only a metaphor. However, it would be
unethical if a care provider, without the womans
informed consent, promoted the interests of the
fetus over those of the woman.104
When considering the consent to fetal surgery
the parents have clear legal responsibilities to provide
or consent to their born childrens necessary medical
care but the maternal duties to fetuses in utero are
not generally recognized.104
Regarding whether this study was research or a therapeutic
innovation they stated that:
the research component of the study was not in
the prenatal surgical and postnatal management
of each child but in the systematic control of
each case according to the research protocol and
the retrospective comparative review for all the
outcome data.104

Prenatal Screening, Diagnosis, and Pregnancy Management of Fetal Neural Tube Defects

Their conclusion was that women, diagnosed with a fetal


MMC and where open fetal surgery is available, will have to
be informed of this treatment option.104 This prenatal repair
option needs therefore to be presented to families in Canada
as part of the informed consent process because although it is
not available here, it is available in the United States.104
Postnatal Repair of MMC

The decision to perform postnatal repair is the most likely


clinical scenario in Canada for the MMC fetus or neonate
because only mothers who have travelled to in utero MMC
treatment centres in the United States will have received in
utero MMC repair.
The postnatal group in the Randomized Trial of Prenatal
74
is used
as the clinical outcome for comparison because the RCT
study was done in selected Childrens Hospital facilities
with organized and comprehensively controlled pediatric
neurosurgery services. The placement of a shunt within the
group (82%, compared to prenatal group 40%; P = 0.001).
Other abnormal cranial and brain features were higher in the
postnatal group than in the prenatal repair group (degree of
hindbrain herniation, P = 0.001; brainstem kinking, P = 0.001;
abnormal location of the 4th ventricle, P = 0.002).
lower with postnatal repair than with prenatal repair, but this
was mainly due to differences in motor function between the
spinal anatomical levels of the defects (P = 0.001); the Bayley
(P
independently with prenatal repair and 21% with postnatal
repair (relative risk 2.01 ([95% CI 1.163.48]; P = 0.01).
lower WeeFIM scores for self-care (P = 0.02) and mobility
(P = 0.003), but not for cognitive ability (P = 0.67).
Immediate postnatal care for MMC is required whether
the birth was by Caesarean section or vaginal delivery.
Neonatology specialists should attend in the labour
room for MMC protection and care, probable neonatal
prematurity (less than 37 weeks gestation), and planning
and performing subsequent primary neurosurgical MMC
closure within 24 hours of delivery, especially if the MMC
is open or the MMC sac was ruptured at delivery
Termination of Pregnancy

Over the last 3 decades an estimated 70% to 80% of


women and couples with a fetus affected by OCNTD have
chosen termination of the pregnancy.4,105,106

For families choosing to terminate a pregnancy because of


an MMC, anencephaly, or encephalocele, the health care
provider should discuss fetal autopsy and chromosomal
provide important information about the etiology for
the NTD and the recurrence risk.107 Measures to prevent
recurrence, including maternal supplementation with 5 mg
of preconception folic, are recommended in subsequent
pregnancies because folic acid supplementation has
been shown in an RCT to reduce the isolated recurrence
risk of NTD by 72%, with a resulting reduction of the
non-supplementation prevalence rate of 3% to a post
supplementation recurrence rate of 1%.5,108
Recommendations
Pregnancy Management

10. Following the detection of an isolated open/closed


neural tube defect, families should be offered a
choice of 3 obstetrical care management options
after diagnostic and genetic testing results are
available. Options should include information about
prenatal myelomeningocele repair and prognosis (if
there are no maternal or fetal contraindications for
prenatal repair at 2026 weeks gestation), postnatal
myelomeningocele surgical repair and prognosis,
and pregnancy termination with autopsy. Because
anencephaly is a lethal condition, pregnancy with
anencephaly may be interrupted at any gestational
age on the womans request. For an encephalocele,
individualized counselling is recommended because
of the possibly unique circumstances of the
anomaly. (II-2A)
11. Caesarean section is the most common method of
delivery for a fetus with a myelomeningocele (MCC)
in either vertex or breech presentation, but is it
with intrapartum fetal heart rate monitoring can be
considered in selected MMC vertex presentation
cases that have no macrocephaly related to
gestational age and a small or no MMC sac. (II-2A)
12. Delivery management for a fetus with complex
multiple anomalies including a neural tube defect
will need to be individually determined by the
multidisciplinary health care providers at the
anticipated delivery centre based on the differential
testing results, prenatal care requirements, anticipated
neonatal morbidity or mortality, and family
consultation and requests. (III-A)
13. Autopsy is recommended for all cases of prenatal
and postnatal open/closed neural tube defect
(isolated or complex) following either termination

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SOGC CLINICAL PRACTICE GUIDELINE

of pregnancy or prenatal/postnatal death.


Induction of labour may be the preferred method
for pregnancy termination, allowing for a more
complete autopsy evaluation of the fetal central
nervous system. If autopsy is declined, fetal
magnetic resonance imaging should be considered
to better evaluate fetal abnormalities either in utero
or after postnatal death. If genetic studies have
not been completed prior to the termination, at
the minimum, chromosomal karyotyping and/or
chromosomal microarray should be considered or
encouraged, even if a full autopsy is not performed.
This procedure will maximize information for
postnatal review and counselling. (II-2A)
Pregnancy Follow-up

14. Follow-up consultation is recommended when


postnatal genetic and pathologic studies are
complete, to provide the woman with information
related to the etiology, risk of recurrence,
recurrence prevention, and the possible impact on
other family members of the congenital isolated or
complex anomaly. (II-2A)
15. When a previous pregnancy history is complicated
by a presumed folic acid-sensitive open/closed
neural tube defect (i.e., no karyotype, chromosomal
etiology) for either member of the couple, or
if either member of the couple planning the
pregnancy is personally affected with an isolated
neural tube disorder, oral folic acid supplementation
of 5 mg within a multivitamin preparation should
be recommended to the female partner, starting at
least 3 months prior to pregnancy conception and

Although it may be cost effective, the MSAFP screen


can detect only open NTDs; it has poor sensitivity and
used as an adjunct to ultrasound when more detail of the
CNS is required or when fetal therapy is being considered.
MRI is more expensive and is not as readily available as
ultrasound; further research is necessary to ensure its
reported safety and to allow the creation of reference
standards.
Amniocentesis is an invasive diagnostic procedure that
is accurate in the detection of ONTDs and in analyses
for chromosomal or genetic abnormalities. With the use
of ultrasound for guidance, amniocentesis performed
by experienced hands, can greatly reduce the risks of
miscarriage, infection, and harm to the fetus. However,
although amniocentesis has a greater than 99% detection
rate for ONTD, it is neither cost effective nor necessary
for the detection of ONTD unless performed for the
Improved prenatal screening and diagnosis will enable
mothers or couples to obtain precise information about
detected anomalies so they can make informed decisions
about whether to continue or interrupt the pregnancy and
what their options are for fetal or postnatal repair.
Our current knowledge and experience indicates that
pregnant woman should be offered 2 prenatal screening
approaches:
1. risk screening for fetal aneuploidy and fetal anomalies,
using a combination of non-invasive techniques that
includes ultrasound (fetal anatomic and structural
detail) and
2. maternal serum testing for placental biochemical

SUMMARY

NTDs occur early in embryologic development, secondary


to failure of fusion of the neural groove and formation
of the neural tube. NTDs include malformations or
disruptions in the lower spine and upper cranium and
occur in approximately 1 in 1000 live births. There are
2 methods of prevention: primary prevention with

trimester screening approaches) or for placental cellfree fetal DNA (for future direct fetal molecular DNA
screening or diagnostic testing).
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