Differentiation of early first-trimester cranial neural tube defects

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Ultrasound Obstet Gynecol 2014; 43: 711– 714
Published online 30 April 2014 in Wiley Online Library (wileyonlinelibrary.com).
Letters to the Editor
Differentiation of early rst-trimester cranial
neural tube defects
Neural tube defects (NTDs) are one of the most commonly
reported birth defects and are the result of failure of
primary neurulation, the folding and fusion of the neural
plate1. We report on three early rst-trimester cases with
different types of cranial neural tube defects (NTD) not
previously reported in ultrasound studies.
Previously, it was believed that the process of neural
tube closure occurred in a ‘zipper-like’ fashion, starting
at one point and proceeding in both cranial and cau-
dal directions. However, neural tube closure is a more
complex process. More recently, Nakatsu et al. described
three different closure initiation sites of the human neural
tube after studying miscarried embryos2. Following from
this closure model six different types of cranial NTDs
were distinguished, based on location of the closure defect
(Figure S1)2. Survival rates signicantly decreased if the
Figure 1 Case 1. Transvaginal two-dimensional (a) and
three-dimensional (b,c) ultrasound images of an embryo
(crown– rump length, 23 mm) with a cranial neural tube
defect extending from the mesencephalon to the
rhombencephalon, suggestive of a Type IV defect. Note the
abnormal contour of the head.
rhombencephalon, or fourth ventricle, was involved in the
defect (Types III, IV and V) with two-thirds of cases failing
to survive beyond 7 weeks’ gestational age. Embryos with
total dysraphism (Type VI) failed to survive at an even
earlier stage. However, 70% of the embryos with a rostral
defect (Types I and II) did survive beyond 7 weeks.
In Case 1 (crown–rump length (CRL), 23 mm) and
Case 2 (CRL, 13 mm) a cranial defect was seen from
the mesencephalon to the rhombencephalon, suggestive
of Type IV (Figure 1 and Figure S2). In Case 3 (CRL,
14 mm) the neural tube did not close at the parietal region
of the head and most likely represents a Type II cranial
NTD (Figure 2). We concluded that some of the different
types of cranial NTDs can be diagnosed in vivo using
high-frequency two- and three-dimensional transvaginal
ultrasound during the early rst trimester of pregnancy.
Increasing awareness of the existence of different types
of cranial NTDs is important in beginning to unravel the
etiology of the development of NTDs. If good documen-
tation exists the different types of cranial NTDs might
Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd. LET TE R S TO THE E DI T OR

712 Letters to the Editor
Figure 2 Case 3. Transvaginal two-dimensional (a) and
three-dimensional (b) ultrasound images of an embryo
(crown– rump length, 14 mm) with a cranial neural tube defect
visible at the partietal region of the head, suggestive of a Type II
defect.
be linked to different genetic pathways or environmental
factors3. However, since the moment of demise in the
majority of cases appears to be before 10 weeks’ gestation,
detection remains a challenge.
The existence of different types of cranial NTDs is a
rather recent insight and the implications for counseling
are not yet well understood. Understanding the cause of
these malformations might contribute to determination
of increased risks in couples and development of new pre-
vention strategies. The in vivo detection of cranial NTDs
raises the question whether these women are at increased
risk for recurrence of NTD. If so, in a subsequent preg-
nancy, an increased dosage of supplemental folic acid
is indicated and additional ultrasound examinations are
recommended.
In conclusion, different types of cranial NTDs can be
diagnosed using transvaginal ultrasound examination in
early pregnancy. Detection of these NTDs is of particular
importance in beginning to understand etiology, in devel-
oping prevention strategies, in counseling patients and in
initiating new research projects.
Acknowledgments
This research was nancially supported by Erasmus Trust-
fonds, Erasmus MC Vriendenfonds, Meindert de Hoop
Foundation and Fonds NutsOhra.
L. Baken*†, N. Exalto†, B. Benoit‡, P. J. van der Spek§,
E. A. P. Steegers† and I. A. L. Groenenberg†
†Department of Obstetrics and Gynaecology, Division
of Obstetrics and Prenatal Medicine, Erasmus MC,
University Medical Centre Rotterdam, Rotterdam,
The Netherlands; ‡Department of Obstetrics and
Gynecology, Princess Grace Hospital, Monaco;
§Department of Bioinformatics, Erasmus MC,
University Medical Centre Rotterdam, Rotterdam,
The Netherlands
*Correspondence.
(e-mail: l.baken@erasmusmc.nl)
DOI: 10.1002/uog.13292
References
1. Copp AJ. Neurulation in the cranial region– normal and abnor-
mal. JAnat2005; 207: 623–635.
2. Nakatsu T, Uwabe C, Shiota K. Neural tube closure in humans
initiates at multiple sites: evidence from human embryos and
implications for the pathogenesis of neural tube defects. Anat
Embryol (Berl) 2000; 201: 455– 466.
3. Detrait ER, George TM, Etchevers HC, Gilbert JR, Vekemans
M, Speer MC. Human neural tube defects: developmental biol-
ogy, epidemiology, and genetics. Neurotoxicol Teratol 2005; 27:
515– 524.
SUPPORTING INFORMATION ON THE
INTERNET
The following supporting information may be
found in the online version of this article:
Figure S1 Different types of cranial neural tube
defects in human embryos (as reported by
Nakatsu et al.2).
Figure S2 Transvaginal two-dimensional and
three-dimensional ultrasound images of an
embryo (at crown–rump lengths 13 mm and
17 mm) with a cranial neural tube defect
extending from the mesencephalon to the
rhombencephalon (suggestive of Type IV neural
tube defect).
Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd. Ultrasound Obstet Gynecol 2014; 43: 711– 714.