Role of First-Trimester Ultrasound Screening for Central Nervous System Anomalies: A Single Center Study

Abstract

Objective

To evaluate potential sonographic features and a standardized protocol for ultrasound screening of different central nervous system (CNS) malformations in the first trimester and their follow up.

Methods

This was a single center prospectively collected data with retrospective analysis evaluating first-trimester scans for CNS malformations with standardized protocols performed between July 2017 and July 2023 involving 5,612 pregnancies. Follow-up at second and third trimester scans and post natal details were noted.

Results

We suspected or confirmed 36 cases with CNS abnormalities in 5,612 first trimester scans. Among those, 9 cases of exencephaly, 6 alobar holoprosencephaly, 2 isolated occipital encephalocele, 1 isolated hydrocephalus, 1 amniotic band syndrome, and 3 cases of open spina bifida were confirmed in first trimester scans. Three cases of Blake's pouch cyst, 2 cases of vermian hypoplasia, 1 with Dandy–Walker malformation, 1 with trisomy 21 (T21), one trisomy 18 (T18), 1 Meckel–Gruber syndrome, and 1 Joubert syndrome were suspected in first trimester scans and confirmed on follow up scans. Corpus callosal agenesis, corpus callosal dysgenesis, vein of Galen aneurysm, lobar holoprosencephaly, closed spinal dysraphism, and a massive cerebral hemorrhage and fetal infection were detected in second- and third trimester scans, which were normal at first trimester anomaly screening scan. With standard CNS planes, 69% of fetal CNS malformations were detected in our study. The sensitivity of our study was 69.7%, and the specificity was 99.89%.

Conclusion

Most of the major CNS abnormalities can be detected early in pregnancy. The first trimester is an ideal time for detection of CNS parameters, which is feasible and efficient and does not require any additional investigation time. Some CNS abnormalities manifest later in gestation and are not detected in the first trimester scan.

 

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Keywords

first trimester anomaly scan - CNS anomalies - posterior fossa anomalies - Meckel–Gruber syndrome - Joubert syndrome

Introduction

Central nervous system (CNS) abnormalities are the largest group of fetal abnormalities and have a prevalence of 1 per 1,000 live births.[1] CNS malformations account for approximately 75% of intrauterine fetal deaths and approximately 40% infant deaths, which needs early detection.[2] Assessing the CNS anomalies in the first trimester is challenging due to significant brain development throughout gestation.[3] [4] First trimester evaluation is only possible with a good knowledge of normal neuroembryology and quality equipment, and needs an experienced hand. Some of the abnormalities show direct signs in first trimester scan, but some may show only indirect markers which need to be confirmed on follow up scans. Fetal nuchal translucency (NT) is a crucial marker in first trimester scans for screening fetal aneuploidy and structural abnormalities.[5] [6] Advancements in ultrasound technology have made fetal anatomical assessments more feasible.[7]

The early scans with standard examination planes have a 100% detection rate of anencephaly, alobar holoprosencephaly, and large cephaloceles.

Detailed anatomical screening can improve the detection rate of most CNS abnormalities. CNS abnormalities detectable by prenatal ultrasound can be categorized into six groups:

• Developmental anomalies (like neural tube defects [NTDs] and neuronal migration disorder).

• Posterior fossa issues (such as Dandy–Walker malformation and Chiari-11 malformation).

• Ventricular problems (including aqueductal stenosis).

• Midline disorders (like holoprosencephaly and callosal agenesis).

• Vascular anomalies (like vein of Galen malformations).

• Miscellaneous conditions (including hydranencephaly, porencephaly, intracranial hemorrhage, and tumors).

 

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Methods

This was a single center study. Data were collected from 5,612 pregnant women who visited our center from 2017 to 2023 for a NT scan at 11 to 14 weeks. All continued pregnancies were followed up with scans at 20 to 24 weeks and 34 to 38 weeks. Data were analyzed retrospectively to detect CNS anomalies from first trimester scans, their progression, prognosis during subsequent scans, and postnatal follow up by hospital records and some by telephone calls. For suspicious findings for CNS malformations in the first trimester anomaly scan (FTAS), we performed an additional scan at 16 to 18 weeks for follow up. A high resolution ultrasound machine, General Electronics Voluson E8, with a convex probe of 1–5 MHz and a high resolution transducer of 2–9 MHz was used. The routine standard anatomical planes in evaluating the fetal brain in the first trimester were the midsagittal view of the brain, and axial views with transventricular, caudothalamic planes. In suspicious cases, extended axial and coronal views were performed. The planes on coronal view were the frontal, transcaudate, transthalamic, and occipital planes. Color mapping was also included in needed cases. Evaluation was done routinely by transabdominal approach. If necessary, the transvaginal approach was performed with patient's consent. A thorough anatomical assessment was performed at 20 to 24 weeks of gestation as per International Society of Ultrasound in Obstetrics and Gynecology guidelines,[8] followed by growth scan, which was performed between 34 to 38 weeks of gestation.

 

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Results

By using standard protocols, for CNS anomalies in the first trimester noted a detection rate of 69% in our study.

We diagnosed 9 cases of exencephaly ([Fig. 1]), 6 alobar holoprosencephaly ([Fig. 2]), 2 isolated occipital encephaloceles, and 1 amniotic band syndrome ([Fig. 3]). Obliterated or reduced Intracranial translucency (IT) was noted in four cases, out of which three were associated with open spina bifida ([Fig. 4]). Remaining one case on further follow up scans at 18, 24, and 34 weeks showed no spinal or posterior fossa abnormalities with normal postnatal outcome. One fetus with isolated hydrocephalus ([Fig. 5]) on follow up scan at 20 weeks showed absent corpus callosum, and pregnancy was terminated. A total of 13 cases with dilated IT were found in the first trimester scan ([Table 1]). Isolated dilated IT with three fluid filled spaces were noted in six cases, which on follow up at 18 to 20 weeks showed normal posterior fossa in three cases. The other three cases turned out to be Blake's pouch cyst ([Fig. 6]) with normal outcome in two cases and one was associated with an aberrant right subclavian artery, which was confirmed as trisomy 21 and terminated. Isolated dilated IT with two anechoic spaces was found in three cases, of which two cases were vermian hypoplasia ([Fig. 7]), and one Dandy–Walker malformation ([Fig. 8]) was diagnosed on follow up scans. Dilated IT with other associated findings were noted in four cases.

Fig. 1 Fetus of 11 Weeks 4 days in sagital view with absent cranial bones and cephalic dysmorphism-Anencephaly.

Fig. 2 13 weeks 5 days fetal axial view showing absent falx with mono-ventricle -Alobar holoprosencephaly.

Fig. 3 Amniotic band syndrome with parietal encephalocele at 13 to 14 weeks.

Fig. 4 (A) Sonographic features of Chiari-II malformation at 13 weeks 1 day fetus on midsagittal view showing thickened and posteriorly displaced brainstem (BS), compressed fourth ventricle (4V), with consequent collapse of cisterna magna. (B) In axial transthalamic view, third ventricle and aqueduct of Sylvius are barely visible (“dry brain”) and midbrain is displaced backwards, with aqueduct pushed close to occipital bone (“crash sign”). (C) Transvaginal approach of spine demonstrating the kyphoscoliosis with spinal defect.

Fig. 5 (A) First-trimester ultrasound images of a fetus with hydrocephalus: enlarged cerebral ventricles with shrunk choroid plexus (axial view). (B) Mid-sagittal view at 20 weeks 3 days showing absent corpus callosum.

Table 1 Outcomes of fetuses with dilated intracranial translucency in the first trimester

Number of cases	Posterior fossa fluid-filled spaces	Associated anomalies at 11–14 weeks	Follow-up sonography	Outcome
3	3	Isolated	Normal	Normal
2	3	Isolated	Blake's pouch cyst	Normal
1	3	Isolated	Blake's pouch cyst with ARSA	Trisomy 21
1	2	Isolated	Dandy–Walker malformation	Aborted at 20 weeks
2	2	Isolated	Vermian hypoplasia	Aborted at 22–23 weeks
1	3	Increased NT, DV reversal	Increased NF	Confirmed as T21 Aborted at 18–19 weeks
1	2	Micrognathia, increased NT	Confirmed the findings	Confirmed as T18 Aborted at 18 weeks
1	2	Occipital encephalocele, polycystic kidneys, tricuspid atresia, and polydactyly	Confirmed the findings at 12–13 week scan	Suspected Meckel–Gruber syndrome Aborted at 15–16 weeks
1	2	Nil	Polycystic kidneys, molar tooth sign	Confirmed as Joubert syndrome and aborted at 20–21 weeks.

Abbreviations: ARSA, aberrant right subclavian artery; DV, ductus venosus; NF, nuchal fold; NT, nuchal translucency.

Fig. 6 (A) Blake's pouch cyst at 12 weeks' gestation, on mid-sagittal view the fourth ventricle was enlarged with three fluid-filled spaces. (B) Follow-up scan at 20 weeks showing mild rotation of normal vermis. (C) Confirmed the 2D findings on TUI. (D) Normal vermis with open fourth ventricle on 3D. 2D, two-dimensional; 3D, three-dimensional; TUI, tomographic ultrasound imaging.

Fig. 7 (A) At 12 to 13 weeks fetus with enlarged intracranial translucency with two fluid-filled spaces. (B) Follow up at 20 weeks gestation confirming as inferior vermian hypoplasia with rotation of vermian noted. (C) Open fourth ventricle with elevated tentorium confirming the 2 D findings.

Fig. 8 (A) On midsagittal view, the ratio between brainstem (BS) thickness and BS-to-occipital bone distance (BSOB) is reduced and only two rather than three parallel anechoic spaces are seen with increased NT. (B) Significant rotation of a small cerebellar vermis (the BS-vermis angle was >45 degrees) with an enlarged posterior fossa - Dandy walker malformation. (C) 3D reconstruction confirming the findings of 2D. NT, nuchal translucency.

First case of dilated IT was associated with increased NT and ductus venosus a wave reversal further karyotyping was done confirmed as T21 and later aborted. Second case with micrognathia and increase NTwas confirmed as T18 ([Fig. 9]) by ammiocentesis. The third case which was associated with polydactyly, congenital heart disease, and polycystic kidneys, was suspected as Meckel–Gruber syndrome at 10 to 11 weeks ([Fig. 10]) and confirmed at 12 to 13 weeks. The patient refused invasive testing and was aborted at 15 to 16 weeks. The fourth case with occipital encephalocele and polycystic kidneys on follow up scan showed a positive molar tooth sign, suggestive of Joubert syndrome ([Fig. 11]), which was also confirmed at another center and terminated. We could not diagnose 5 cases of corpus callosal agenesis, 1 case of callosal dysgenesis, 1 case of fetal intracranial hemorrhage, 2 cases of vein of Galen aneurysm, 2 cases of lobar holoprosencephaly, 1 case of fetal infection, and 1 case of closed spinal dysraphism in the first trimester, these were picked up in follow up scans.

Fig. 9 Trisomy 18. (A) Sagittal view showing dilated IT with two anechoic spaces, micrognathia and increased NT. (B) 3D confirming the findings. IT, intracranial translucency; NT, nuchal translucency.

Fig. 10 Meckel–Gruber syndrome suspected at 10 to 11 weeks and confirmed at 12 to 13 weeks. (A) Occipital encephalocele at 12 to 13 weeks. (B) Polycystic kidneys. (C and D) Tricuspid atresia. (E) Polydactyly.

Fig. 11 Joubert syndrome. (A) Sagittal view at 12 to 13 weeks showing dilated IT with two fluid-filled spaces in posterior fossa. (B) Polycystic kidneys at 15 to 16 weeks. (C) At 20 weeks, molar tooth sign. IT, intracranial translucency.

 

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Discussion

Previously, only severe CNS malformations were detected in first trimester scans. Subtle findings in intracranial structures like NT, brainstem (BS), BS-to-BS occipital bone (BSOB) ratio, IT and cisterna magna were associated with CNS malformations in early pregnancy.[9] [10] [11] Posterior fossa anomalies were associated with absent or change in position of choroid plexus of fourth ventricle.[12] [13] [14] The suspicious signs of Chiari-II malformation in the first trimester scan are the lower position of torcular Herophili with increased BS–tentorium angle.[15] Increased BS/BSOB ratio, decreased IT, obliterated cisterna magna in sagittal view, and elongated choroid plexus on axial view are described as the “dried up brain” sign and downward displacement of midbrain and aqueduct is known as crash sign in the FTAS. Th dried up brain sign was a reliable and reproducible sonographic marker of OSB.[16] An increased open spina bifida (OSB) detection rate of 15 to 60% was achieved by including the posterior fossa cystic spaces in the first trimester CNS evaluation.[17] Open spinal dysraphism and posterior fossa cystic malformations are suspected in the absence of choroid bar.[18] Higher displacement of torcular Herophili, increased IT, small BS–tentorium angle (BS and straight sinus become parallel),[19] ponto–vermian angle >100, and aqueduct of Sylvius smaller than usual are the suspicious findings in Dandy–Walker malformation in the first trimester.[20] As per Lachmann et al,[21] an increased ratio between the diencephalon and the falx diameter is noted in callosal agenesis. Callosal agenesis in the first trimester may possibly be excluded on color Doppler by demonstrating the pericallosal artery.[1] [22] [23] [24]

On standard protocols, we found two thirds of CNS anomalies in first trimester, with poor prognosis, leading to a higher rate of abortion. Our study has shown a 100% detection rate of exencephaly–anencephaly sequence, alobar holoprosencephaly, and occipital encephaloceles, as previously reported. In our study, 76.9% of posterior cranial fossa anomalies and 75% of OSB cases were diagnosed. The sensitivity of our study was 69.7%, and the specificity was 99.89%, with a positive predictive value of 83% and a negative predictive value of 99.7%. In our study, the detection rate was 69%, with an accuracy of 99%. Our study showed a similar or slightly lower detection rate than some other recent studies[25] and somewhat higher than some other published data.[26] [27] [28] Regarding OSB, the detection rate was lower than those obtained by some of the researchers.[29] [30] Fetal CNS anomalies diagnosed in the first and second trimesters in our study resulted in abortion rates of 49 and 51% ([Figs. 12] [13] [14]).

Fig. 12 First trimester scan result.

Fig. 13 Follow-up scan result.

Fig. 14 Number of CNS anomalies in the first trimester that are terminated. CNS, central nervous system.

Several CNS anomalies, including agenesis of the corpus callosum, vein of Galen aneurysmal malformation, intracerebral hemorrhage, intracranial infection, lobar holoprosencephaly, and closed spinal dysraphism, were undetected in the first trimester and picked up on follow up scans ([Fig. 15]).

Fig. 15 CNS anomalies undetected in the first trimester that are diagnosed on follow-up scans. CNS, central nervous system.

 

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Conclusion

The present study has emphasized the different types of fetal CNS anomalies that need to be identified based on a standard first trimester CNS ultrasound protocol, which can provide parents with crucial medical options and the possibility of safer abortion. IT evaluation during first trimester ultrasound is a valuable screening marker for early detection of NTD and posterior fossa abnormalities. Abnormal IT may also be associated with aneuploidy. Presence of an echogenic line formed by the choroid plexus of the fourth ventricle known as choroid bar helps differentiate the more benign from the pathological ones.

 

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Conflict of Interest

None declared.

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Publikationsverlauf

Artikel online veröffentlicht:
17. Juli 2025