Prenatal assessment and pregnancy outcomes of foetal low-lying conus medullaris using 3D ultrasound

With advances in ultrasound technology and the growing understanding of foetal disorders, the implementation of prenatal ultrasound for foetal central nervous system (CNS) examination has become increasingly important. The International Society of Ultrasound in Obstetrics and Gynaecology (ISUOG) has recently updated its guidelines on foetal central nervous system ultrasound, suggesting that the conus medullaris helps determine the normality of the lumbosacral spine [1] and can help to detect neural tube defects. The most common neural tube defects are spina bifida and meningocele [2, 3] and closed spinal dysraphism. These are associated with lipoma, diastematomyelia, epidermoid cysts, and dermoid cysts [4].

A low-lying conus medullaris (CM) refers to the condition with conus medullaris below L3 (excluding L3), regardless of gestational age [1]. It could lead to some clinical symptoms, such as motor and sensory dysfunction of lower extremities, urination and defecation function disturbance. As a result, diagnosing "low-lying CM by prenatal ultrasound has become increasingly necessary in recent years. There are few studies on the correlation between ultrasonic manifestations during pregnancy and postnatal pregnancy outcomes. This study aimed to provide our experience and clinical outcomes of foetuses prenatally diagnosed with low-lying conus medullaris.

In our study, 24.3% (9/37) of low-lying CM were complicated with spine abnormality (3 cases of open spina bifida and 6 cases of tethered cord syndrome). When the CM was between L4 and L5, its AUS to predict spinal dysraphism was 0.877, with a sensitivity of 66.7% and a specificity of 96%.

Between the 3rd and 4th week of embryogenesis, the CNS develops from the neural plate, followed by progressive folding, closure of the neural tube and separation from the ectoderm. On the 27^th day after fertilisation, the caudal end of the neural tube closes. By day 38, the caudal segment eventually becomes the end of the conus medullaris, the terminal filament, and the terminal ventricle (a local expansion of the central canal of the conus medullaris) [7]. The CM refers to a structure at the lower end of the spinal cord, which tapers to a cone-like shape. During the first three months of embryonic development, the spine is almost equal in length to the spinal cord. Then the spine extends caudally and grows faster than the spinal cord. Since the upper end of the spinal cord is attached to the medulla oblongata, it visually seems that the spinal cord is moving upward compared to the spine [8]. Consequently, the positions of the conus medullaris and its corresponding vertebral bodies change throughout pregnancy.

Lu et al. found that the foetal CM rose rapidly to the L3 level by 21 weeks and then rose slowly to L2-L3 by 28 weeks, according to data from 828 normal foetuses at 17–39 weeks gestation. Despite the large sample, this study may not reflect the accurate level of the foetal spinal conus due to inaccurate findings from prenatal two-dimensional (2D) ultrasound [9]. Arthurs et al. performed post-mortem MRI on 84 foetuses that died between 14 and 41 weeks of gestation. In their study, 84.2% of foetal CM was located at L4/5 or above, 22.8% were at or above the L3 before 20 weeks gestation, 50.7% were at L3 by 26 weeks, and 94.8% were at L3 by the time of birth [10].

Since The normal range of CM position has not reached a consensus, we defined a low-lying CM as being below L3, according to the ISUOG guidelines, which do not consider the upward shift of the CM with gestational age [1]. Zalel et al. conducted a prospective study that recorded the CM position in 110 normal foetuses throughout pregnancy (13–40 weeks). The team found that all foetuses' CM was at L3-L4 between 13 and 18 weeks gestation. For example, 97% were at L2-L3 between 19 and 24 weeks, and 100% were above L3 between 25 and 42 weeks [11]. In China, Li et al. also analysed 282 normal foetuses from 20 to 26 weeks of gestation and concluded that 95.5% of foetuses' CM were at L3 and above [12]. Additionally, Perlitz et al. summarised the location of the CM in 110 normal foetuses from 20 to 24 weeks of gestation. He found that 93% of foetuses' CM was above L3 and that the location of the CM did not differ with gestational age, maternal age, or foetal sex [13]. The above conclusions proved that our study's definition of low-lying conus medullaris as below L3 (excluding L3) was evidence-based.

Perlitz et al. mentioned the need for vigilance when the conus medullaris was below L3 [13]. In Li et al.'s study, the CM position of ten foetuses with spinal dysraphism was below the L3 level [12]. Our study collected data from 37 foetuses with conus medullaris below L3. Among them, 10 (27.0%) foetuses' CM was located between L3 and L4, and they had no spinal anomalies eventually. Of the 27 foetuses with CM at L4 and below, three had open spinal dysraphism, and six had closed spinal dysraphism. According to the ROC analysis, if the position of conus medullaris was at L3.75, the sensitivity and specificity to predict spinal defect were 100% and 63%, respectively. Likewise, if the position of conus medullaris was at L4.25, the sensitivity and specificity to predict spinal defect were 66.7% and 96.4%. Hence, we assume that conus medullaris at L4 and below is more suggestive of a spine defect. Nevertheless, more data should be collected to reach a more decisive conclusion.

Tethered cord syndrome is a neurological injury caused by fixation of the caudal end of the spinal cord by a hypertonic fatty infiltrated terminal filament, which in turn triggers neurological symptoms corresponding to the lower segment of the spinal cord [14]. Tethered spinal cord syndrome may occur as an isolated lesion or be associated with other lesions such as lipomas, dermal sinuses, fatty infiltration of the terminal filaments, and caudal degeneration. This study confirmed six infants with tethered cord syndrome postnatally (four isolated and two with dermal sinus and lipoma, respectively). Postnatal neurosurgical consultation and early neonatal surgery will reduce the risk of neurological injury [15].

We found no evidence of a clear correlation between an isolated foetal low-lying conus medullaris and chromosomal anomalies. Several genetic syndromes involve low-lying conus medullaris, such as Pallister–Killian syndrome [16] and Russell–Silver syndrome [17]. However, these are sporadic case reports, and the genetic syndromes always involve multiple structural anomalies. Our study identified only one case of gene abnormality according to the result of an amniocentesis performed for advanced maternal age. The clinical significance of the single-copy-number variants was not clear. The foetal conus medullaris position rose to the L3 level during this woman's pregnancy follow-up, but the patient and family chose to terminate the pregnancy because of the genetic abnormality.

However, there are a few limitations to our study. Firstly, this was a retrospective analysis with a relatively small sample. Secondly, we focused on the short-term outcomes of the infants, thereby needing further follow-up for long-term neurological development and function.

The second trimester finding of low CM is associated with spinal defects, mainly open spinal dysraphism and closed spinal dysraphism/tethered cord syndrome. Careful assessment of the fetal spine should be considered especially when the location of CM is lower than L4.