Evaluation of the normal ratio of fetal brain choroidal plexus size to fetal head size at 11 to 13 weeks of gestation to obtain useful sonographic markers in spina bifida rule out

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MEDICAL SCIENCE l ANALYSIS ARTICLE
Medical Science, 26, ms374e2351 (2022) 1 of 6
Evaluation of the normal ratio
of fetal brain choroidal plexus
size to fetal head size at 11 to 13
weeks of gestation to obtain
useful sonographic markers in
spina bifida rule out
Tahereh Ghasemi1, Ayda Roostaee2, Zeinab Safarpour
Lima2, Ladan Younesi Asl2*
ABSTRACT
Background: Early detection of open spina bifida (OSB) with ultrasound at 11
to 13 weeks of gestation is considered useful, but no information has been
provided on the size and shape of the choroid plexus. Therefore, the aim of
this study was to determine the normal ratio of the size of the choroid plexus
of the fetal brain to the size of the fetal head at 11 to 13 weeks of gestation to
rule out spina bifida. Material and Methods: Aimed to measure cervical
transparency (NT: nuchal transparency) during the first trimester of
pregnancy and at 11 to 13 weeks of gestation, the pregnant women who has
only one fetus were screened and then were checked using E8 or E10
ultrasound machine. Our study was performed during April 2020 to
December 2021. Results: The results of our study on 203 embryos are
consisting of normal values of crown-rump length (CRL), biparietal diameter
(BPD), the length of Choroid plexus (CPL), head area (HA), head
circumference (HC), and choroid plexus area (CP-A). Evaluating the ratio of
these indicators shows a significant positive correlation between CPA and
other indexes include CRL, BPD, HC and HA (p<0.001). Additionally,
significant positive correlations between CPL and others include BPD and HC,
(p<0.001) and negative correlations between CRL and CPL/OFD and between
CRL and CP-A/HA (p<0.05) was seen. Conclusion: With respect to these result
it seems that these indicators can be used to distinguish healthy infants.
Keywords: Fetal brain choroidal plexus, Gestation, Sonographic markers,
Spina bifida
1. INTRODUCTION
Spina bifida occulta (SBO) is a childhood spinal development disease and that
last into adulthood if it doesn't heal on its own. This disorder, which affects 1
Medical Science
pISSN 2321–7359; eISSN 2321–7367
To Cite:
Ghasemi T, Roostaee A, Safarpour-Lima Z, Younesi-Asl L. Evaluation of
the normal ratio of fetal brain choroidal plexus size to fetal head size at
11 to 13 weeks of gestation to obtain useful sonographic markers in spina
bifida rule out. Medical Science 2022; 26:ms374e2351.
doi:
Authors’ Affiliation:
1Department of Radiology, School of Medicine, Shahid Akbar-Abadi
Hospital, Iran University of Medical Sciences, Tehran, Iran
2Shahid Akbarabadi Clinical Development Unit (ShACRDU), Iran
University of Medical Sciences, Tehran, Iran
*Corresponding author
Ladan Younesi Asl, Shahid Akbarabadi Clinical Development Unit
(ShACRDU), Iran University of Medical Sciences,
Tehran, Iran
Email: ladanyoonesi@yahoo.com
Peer-Review History
Received: 11 June 2022
Reviewed & Revised: 14/June/2022 to 09/September/2022
Accepted: 18 September 2022
Published: 20 September 2022
Peer-review Method
External peer-review was done through double-blind method.
URL: https://www.discoveryjournals.org/medicalscience
This work is licensed under a Creative Commons Attribution 4.0
International License.
Copyright © 2022 Discovery Scientific Society.
DISCOVERY
SCIENTIFIC SOCIETY

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in 1000 newborns, is characterized by a defect in the formation of the posterior arch (Garne et al., 2005, Khoshnood et al., 2015).
Although the diagnostic importance of this illness has been recorded in the first trimester, nearly 60% of cases were detected with
open spina bifida (OSB) by ultrasound at this period, and in the second trimester generally newborns were at second for OSB
(Syngelaki et al., 2019). As a result, current research has demonstrated the importance of ultrasound-derived indicators in the
screening of OSB cases (Chen et al., 2017). The diagnostic signs include the non visualization of the fourth ventricular choroid
plexus (CP) and intracranial translucency (IT) (Chen et al., 2017).
The choroid plexus grows in tandem with the brain's ventricles, adapting and specializing to form a blood-brain barrier and aid
to continual creation of cerebrospinal fluid (CSF). Between the weeks 11 and 13 of pregnancy, this structure comprises of two highly
echogenic forms that fill the fetus' lateral ventricles (Sepulveda & Won, 2013). During the first trimester of pregnancy, changes in
the choroid plexus display a "butterfly" sign which is the most sensitive marker for diagnosing structural brain problems such
acrania and holoprosencephaly (Sepulveda & Won, 2013). Besides, its size is different from the lateral ventricles and has been linked
to aneuploidy and has been used as a measure of ventriculomegaly in early pregnancy (Loureiro et al., 2012 and Manegold-Brauer
et al., 2017). During the weeks 11 and 13 of gestation, OSB is associated with the increment of the CP length ratio to frontal occipital
diameter (OFD) in fetuses. They revealed a reduction in lateral ventricular fluid volume and the choroid plexus (CP) occupied the
whole headspace as a "dry brain" marker (Chaoui et al., 2020).
Other signs of this marker include the leakage of cerebrospinal fluid leaking and CP progression into the lateral ventricles.
Based on their data, nearly 80% of fetuses with OSB had a CP-to-OFD ratio more than two standard deviations of predicted mean
(Chaoui et al., 2020). In the study of Kalafat et al., (2021) through investigating the optimal mean ratio of chorionic plexus to occipito
frontal diameter ratio, a positive predictive value of 90.9% was reported. Due to the availability of this method, further research
should be considered to corroborate these and other markers.
Consequently, the present study was aimed to specify the normal ratio of fetal choroid plexus to head size between the weeks 11
to 13 of gestation to make appropriate sonographic markers to make precise decisions about spina bifida.
2. MATERIAL AND METHODS
Our study is a cross-sectional study in which the pregnant women with single fetuses who referred for their routine screening
during the first trimester of pregnancy to measure the thickness of the nuchal translucency (NT: nuchal translucency) during April
2020 to December 2021. Embryos were examined using a high-resolution voluson E8 or E10 ultrasound machine with a
transabdominal-vaginal ultrasound during the weeks 11 and 13 of gestation.
Crown-rump length (CRL), head circumference (HC), choroid plexus area (CP-A), choroid plexus length (CP-L), fetal head area
(HA): head area and occipitofrontal diameter (OFD) were measured. The ellipse function of the ultrasound system was used to
measure CP-A, HC, and HA in this investigation. For any of CP tissues, their longest length was considered and choroid plexus
length was calculated as their mean.
Statistical analysis
The data was analyzed by SPSS and graph pad prism software. Descriptive statistics were expressed as mean and standard or
median deviation (distance between quartiles) for quantitative variables and absolute and relative frequency for qualitative
variables. Pearson or Spearman correlation test was used to examine the relationship between variables and linear regression was
used to examine the effect of variables on the response.
Ethical consideration
All data were confidential and were only used for scientific research. The data was kept private, and only the researchers can access
the information of participants. Moreover, participation in this research was voluntary, and prior to participation, each participant
was provided written consent. The data analysis and publication process did not require any identifiable personal information. This
research was approved by Iran University of medical science with code IR.IUMS.FMD.REC.1399.213.
3. RESULTS
Descriptive statistics obtained from a study of 203 infants at 11-13 weeks of gestation, were recorded. Accordingly, (table 1),
Crown-rump length (CRL), was between 50 mm to 79 mm with a mean of 60.78 ± 5.61 mm. Head circumference (HC) and fetal head
area (HA) were measured in fetuses aged 11 to 13 weeks and ranged from 55 to 91 mm with a mean of 70.96 mm and 226 to 672 mm
with a mean of 383.43 mm, respectively.

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Table 1 Descriptive Statistics associated with sonographic
marker for screening of open spina bifida
Minimum
Maximum
Statistic
Statistic
Mean±SD
CRL
50.00
79.00
60.78±5.61
BPD
15.50
31.00
19.07±2.27
HC
55.00
91.00
70.96±7.06
Cp area Rt
39.00
111.00
62.75±12.51
CP area Lt
37.00
101.00
63.84±12.84
CPA total
78.00
208.00
126.39±24.05
HA
226.00
672.00
383.43±75.61
CP-A/HA
0.23
0.44
0.33±0.04
CP Length Rt
9.60
18.40
12.83±1.52
CP Length Lt
9.00
20.00
12.94±1.63
CPL mean
9.65
19.00
12.89±1.51
OFD
17.40
23.40
23.64±14.64
CP-L/OFD
0.45
0.73
0.57±0.06
Valid N
(listwise)
The size of the plexus choroid in these embryos was measured using two different indicators: choroid plexus area (CP-A) and
choroid plexus length (CP-L). The choroid plexus area index (CP-A) was 78 to 208 mm, with an average of 126.39 mm, and the
choroid plexus length (CP-L) was 9.65 to 19 mm, with an average of 12.89 mm. In 11 to 13 weeks of gastation, the occipitofrontal
diameter (OFD) of the fetuses varied from 17.4 to 23.4, with an average of 23.64. CP-A/HA and CP-L/OFD, two of the most essential
indices for diagnosing brain abnormalities, were evaluated, with CP-A/HA ranging from 0.23-0.44 and a mean of 0.33 and CP-
L/OFD ranging from 0.45-0.73 and a mean of 0.57.
Figure 1 Scatter plots for specifying the correlations between crown-rump length (CRL), occipito frontal diameter (OFD), the length
of Choroid plexus (CPL), head area, and choroid plexus area (CP-A).

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Figure 2 Scatter plots of correlations between the length of Choroid plexus (CPL), head area and occipitofrontal diameter (OFD),
choroid plexus area (CP-A), and head area (HA).
Figure 3 Scatter plots of correlations between crown-rump length (CRL), choroid plexus area (CP-A), the length of Choroid plexus
(CPL), head area and occipito frontal diameter (OFD), head circumference (HC) and head area (HA).

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As observed in figure 1, by examining the correlation between CPL and OFD, CPL and CRL and between CP-A and CRL, the
significant positive correlation was observed. Therefore, increasing OFD and CRL has led to a significant increase in CPL. Si milarly,
higher CP-A levels were observed in healthy infants with larger CRLs. According to figure 2, increase in HA and OFD led to a
significant increase in choroid plexus indices such as CPA and CPL and a significant positive correlation was observed between
them. By examining the correlation between fetal size indices, BPD, CRL and HC with CP-A/HA and CP-L/OFD indices, a
significant negative correlation was observed between them (p<0.05) (Figure 3).
4. DISCUSSION
Compared to healthy embryos, open Spina bifida embryos have a smaller OFD and BPD, as well as a longer mean CP length and a
higher mean CP length to OFD or BPD ratio (Kalafat et al., 2021). In this study, 203 healthy fetuses between the ages of 11-13 weeks
who underwent first trimester screening including nuchal translucency and nasal bone ultrasound were studied. Comparing the
data from our study with other related reports demonstrated that fetuses between the weeks 11 and 13 had approximately the same
CRLs, OFD, BPD and CPL. In our investigation, a rise in CRL was related with a large increase in CP-A and a significant drop in
CP-L/OFD and CP-A/HA, similar to another study (Chaoui et al., 2020). In our study, HC and BPD indices, likewise directly
associated to CRL, were found to be adversely correlated with CP-L/OFD and CP-A/HA, similar to CRL.
The size of the CP-A, CP-A/HA, and CP-L/OFD ratios in OSB fetuses faced a dramatical increase compared to the normal
population. At 11-13 weeks of pregnancy, the choroid plexus (CP) nearly entirely fills the fetus' lateral ventricles as a pair of
enormous hypercogenic structures. Previous research has focused on CPs and their natural form during early pregnancy, called as
the "butterfly sign," which aids in the diagnosis of alobar holoprosencephaly (Sepulveda and Wong, 2013). Availability of
asymmetry in CP tissues between the left and right sides has been described explained as a normal variety (Abu-Rustum et al.,
2013). This index was not explored in our research, but it appears to be beneficial by evaluating it and identifying its standard limit
in normal fetuses’ vs OSB cases. In addition, comparing CP size to lateral ventricular size has revealed aneuploidy and
ventriculomegaly (Loureiro et al., 2012; Manegold-Brauer et al., 2016). However, because normal fetuses were screened and the
gestational age was 11-13 weeks, these markers were not explored in our study. Studying this index, on the other hand, looks to be
a useful technique to figure out OSB.
The most probable reason for changes in CP-head size in fetuses with OSB is a temporary decrease in cerebrospinal fluid in the
brain ventricular system of affected fetuses between the weeks 11-13. As a result of the spinal deformity's leak, the head is relatively
tiny (Karl et al., 2012; Khalil et al., 2013; Bernard et al., 2012). We showed changes in lateral ventricular CP levels in this study and
then we advised to measure them for a precise objective assessment. If so, various indicators in this study include CRL, BPD, HC,
CP area right, CP area left, CPA total, HA, CPA/HA, CP length right, CP length left, CPL mean, OFD, CPL/OFD was analyzed. We
verified the predictive utility of mean CP length relative to OFD in a quite large set of pregnancies. In addition, other indicators
investigated in this study can also be taken into account.
5. CONCLUSION
Examining the indicators of this study along with other similar studies, and the changes in these indicators that occur in fetuses
with OSB, it seems that these indicators can be used to distinguish healthy infants from infants with OSB. Furthermore, numerous
signs must be evaluated at the same time and referenced.
Acknowledgement
We thank the participants who were all contributed samples to the study.
Author Contributions
All authors contributed to the design of the study, as well as data collection and analysis, and the writing of the manuscript. All
authors read and approved the final manuscript
Ethical approval
The study was approved by the Medical Ethics Committee of Iran. (Ethical approval code: IR.IUMS.FMD.REC.1399.213).
Funding
This study has not received any external funding.

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Conflicts of interest
The authors declare that there are no conflicts of interests.
Data and materials availability
All data associated with this study are present in the paper.
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