The Intrauterine Treatment of Open Spinal Dysraphism

Background: Open spinal dysraphism is a congenital malformation that causes major morbidity. Its consequences include sensory and motor impairment as well as bladder- and bowel dysfunction. It is often also associated with prenatal ventriculomegaly, which, in turn, necessitates postnatal treatment with a ventriculoperitoneal shunt in approximately 80% of cases. Prenatal therapy with coverage of neural tube defect can reduce the shunt rate and preserve motor function. In this review, we describe the different surgical procedures and their outcomes.

Methods: This review is based on publications that were retrieved by a selective literature search in the MEDLINE, Web of Science, EMBASE, Scopus, and Cochrane databases, employing pertinent keywords. Studies of all types (except case reports) that were published in English or German in the period 2010–2024 were included.

Results: The randomized, controlled MOMS trial showed that intrauterine surgery for defect closure resulted in less progressive neural tissue damage than postnatal surgery and reduced the need for shunting by approximately half (40% vs. 82%). Since the publication of these results, various prenatal surgical procedures have been established, including hysterotomy-assisted, percutaneous fetoscopic, and laparotomy-assisted fetoscopic closure. The individual surgical methods yield comparable results in terms of motor function and shunt rate. A problem with these procedures is that they increase the likelihood of preterm birth, to an extent that varies from one type of procedure to another.

Conclusion: Prenatal surgery improves motor function and reduces the shunt rate but long-term outcomes beyond adolescence are still lacking. Transparent and interdisciplinary counseling is essential in prenatal communication to inform parents not only about the potential benefits of this treatment, but also about its limitations and risks.

Cite this as
Keil C, Sass B, Schulze M, Köhler S, Axt-Fliedner R, Bedei I: The intrauterine treatment of open spinal dysraphism. Dtsch Arztebl Int 2025; 122: 33–7. DOI: 10.3238/arztebl.m2024.0239

Spinal dysraphism is a severe, rarely fatal, congenital malformation affecting the central nervous system. This neural tube defect is of multifactorial etiology and results from a disturbance of primary or secondary neurulation. Apart from folic acid deficiency, genetic and epigenetic factors play a role; other factors include poorly controlled diabetes mellitus prior to conception, maternal obesity and anticonvulsants (valproic acid) (1). The overall prevalence is approximately 8/10 000 births in Europe, with a live birth rate of 2/10 000. Over the past decades, it has largely remained unchanged and the European rate can be applied to Germany (1, 2).

A distinction is made between isolated and associated neural tube defects. Associated neural tube defects occur with various syndromal and/or genetic disorders, such as trisomy 18/13, CHARGE syndrome and VACTERL association. Furthermore, clefts, cardiac malformations as well as skeletal and renal malformations can occur in this context and have a significant impact on the prognosis of affected children (3, 4).

Neural tube defects can be open or closed. A characteristic feature of open lesions (formerly spina bifida aperta, SBA) is that the nervous tissue is in contact with the intrauterine environment, while closed lesions (formerly spina bifida occulta) are covered by soft tissue and/or skin.

The most common form of open defects is the cystic variant, the myelomeningocele (MMC). With this anomaly, neural tissue (so-called placode) and meninges protrude from the spinal canal. To be distinguished from MMC are flat defects where the placode is at skin level (myeloschisis) (1).

Open neural tube defects are typically associated with a Chiari II malformation where the posterior fossa is too small, resulting in displacement of the cerebellum through the foramen magnum into the cervical spine (so-called hindbrain herniation, HBH), which, in turn, impairs the circulation and absorption of cerebrospinal fluid (CSF) (5).

According to the two-hit hypothesis, the pathogenesis of open spinal dysraphism is as follows: The first ‘hit’ results from the failure of closure of the neural tube and vertebrae during post–conception days 22–28. The direct exposure of the neural structures to the intrauterine environment leads to degeneration, inflammation, and mechanical injury—this represents the second ‘hit’. According to histopathological studies, damage to the exposed spinal cord starts already prior to a gestational age (GA) of 16 weeks and leads to progressive loss of motor neurons. Depending on the location and extent of the injury, this results in sensory and motor impairment of the affected muscle groups, potentially to the point of paraplegia.

The Chiari II malformation can be associated with ventriculomegaly or hydrocephalus, necessitating the implantation of a ventriculoperitoneal shunt (VP shunt) (6, 7).

Other associated complications include disorders of bladder, bowel and sexual function, as well as orthopedic problems (foot deformities, hip dysplasia and kyphosis) (1). If left untreated, infections (meningitis, ventriculitis) or brainstem compression will lead to a fatal outcome. Prenatal or postnatal surgical repair of the defect is therefore crucial. In this review, we provide an insight into the currently available evidence on the prenatal treatment of open spinal dysraphism. This review is based on publications that were retrieved by a selective literature search in the MEDLINE, Web of Science, EMBASE, Scopus, and Cochrane databases, employing pertinent keywords according to the PICO framework (patient, intervention, comparison, outcome). Studies of all types (except case reports) that were published in English or German in the period 2010–2024 were included. The keywords “spina bifida“, “fetal therapy“ and “feto-maternal outcome“ were used.

The diagnosis of open spinal dysraphism

Ultrasound examinations are an integral part of prenatal care, supplemented by fetal magnetic resonance imaging (8). A detailed diagnostic evaluation is essential when preparing for intrauterine therapy (9).

Ultrasound

Characteristic changes are noted at the time of the second antenatal screening visit set by the German Maternity Guidelines between a GA of 18 and 22 weeks; however, first signs may already be visualized in the first trimester. In cross-sectional planes, the fetal head has a small biparietal diameter (BPD) and a characteristic shape (“lemon sign”). The changes of the posterior cranial fossa result in caudal displacement of the cerebellum (“banana sign”). Ventriculomegaly with enlargement of the lateral ventricles may already be noted (10). In the detailed sonographic scan of the spine, the first affected vertebra defines the anatomical level; other aspects described include the position of the vertebral arches and the morphology of the lesion (MMC or myeloschisis) (10, 11).

In order to determine the motor level of the lesion, an ultrasound assessment of fetal movements of the lower limbs is performed and the findings are matched to the individual neurotomes and muscle groups. The motor outcome correlates significantly better with this functional description than does the anatomical level (12). The classification of the findings, especially the distinction between isolated and associated neural tube defects, is crucial for prognostication (13, 14).

Human genetic testing

In addition to diagnostic imaging, fetal karyotyping should be performed, at least if prenatal surgery is considered. Overall, the rate of genetic abnormalities is low in fetuses with isolated neural tube defect; in the case of associated suspicious findings, it is 16% to 25% (4, 15).

Interdisciplinary counseling

Given the broad spectrum of conditions, interdisciplinary counseling of parents (neuropediatrics, neurosurgery, prenatal diagnostics) plays a decisive role. Counseling should be realistic, open-ended and non-directive, providing a clear picture of open spinal dysraphism as a chronic disease with varying degrees of severity. It also needs to include a discussion on pre- or postnatal surgery and termination of pregnancy.

Referral to self-help groups as well as psychosocial support offerings must be an integral part of the discussions (9).

In Germany, a termination of pregnancy is performed in 46% to 86% of cases (4, 16). However, these rates are based on data from individual centers, since structured registries responsible for comprehensive data collection do not exist. Worldwide, a termination of pregnancy is performed in 63% of cases (range 31–97%) (15).

Postnatal surgical treatment

Until the introduction of prenatal therapy, postnatal neurosurgery was the only treatment available and it has remained an important option for some cases even until today.

In addition to restoring normal circulation of cerebrospinal fluid in the area of the malformed spinal cord, postpartum surgery is performed to create a barrier between neural structures and the environment to prevent infectious complications. During the postnatal surgical procedure, residual arachnoid, epidermal and dermal structures are removed, the filum terminale is dissected and a so-called tubularization is performed where the natural folding of the spinal card is surgically recreated in the area of the placode (17).

Long-term observational studies on 117 patients with significant Chiari II malformation, who underwent postnatal surgery, found a high mortality rate of 35% (18). More than 80% of the pediatric patients undergoing postpartum surgery require the placement of a shunt to lessen this severe disease course as well as neurological and intellectual impairments. Of these, 46% have to undergo shunt revision during their first year (5).

In order to prevent infection (meningitis, ventriculitis), the surgical procedure is frequently performed within 48 hours postpartum; however, there is no clear evidence to date to support a better outcome as a result of this approach (19). The “watertight closure” of the infant’s back is absolutely necessary to ensure that cerebellar herniation, CSF circulation impairment and brainstem compression subside (17).

The tethered cord syndrome (TCS) is a well-recognized long-term complication. It is characterized adhesions between neural structures and the surrounding tissue. During the normal growth in length and the associated ascending of the spinal cord in the spinal canal, TCS can result in neurological deficits (motor, sensory) in the lower limbs, back pain or leg pain, scoliosis, and incontinence. Patients with TCS account for 2.8% to 32% of operated patients (17, 20).

Prenatal therapy of open spinal dysraphism

The approach of intrauterine therapy is based on the hypothesis that an early closure of the defect reduces the complications of the second hit. The only randomized trial, the MOMS trial, compared prenatal with postnatal surgery. The results showed a reduction in the postnatal shunt rate as well as improvements in motor function after prenatal therapy. However, an increase in fetomaternal complications was also noted (eTable A) (21, 22).

eTable A

The MOMS trial: child outcome parameters and maternal risks (Adzick et al. 2011 [23])

The surgical procedure is usually performed between 19–26 weeks’ gestation. The inclusion and exclusion criteria were prepared on the basis of the MOMS trial and later modified (eBox) (1). The costs of prenatal surgery are covered by German health insurances.

eBox

Inclusion and exclusion criteria for the intrauterine treatment of open spinal dysraphism, as per the eTable

At present, there are various surgical methods that differ from each other with regard to access and defect closure; these have been modified over time. In addition to the MOMS trial, the available data is drawn from numerous case series of various centers.

Hysterotomy-assisted repair

Surgical access is via a lower abdominal transverse laparotomy with subsequent hysterotomy and repair of the fetal neural tube defect in a manner similar to the postnatal procedure (Figure 1, Figure 4).

Figure 1

Hysterotomy-assisted repair

Figure 4

Schematic representation of three different surgical methods

This surgical procedure was established in the only available randomized clinical trial, the MOMS trial. A total of 183 women were randomized into two groups (antenatal [n = 78] and postnatal [n = 80] surgery). The results showed an advantage of prenatal therapy with a reduction in the postnatal shunt rate (antenatal 31 (40%), postnatal 66 (82%), RR [95% confidence interval] 0.48 [0.36; 0.64]; p<0.001) as well as a decrease in hindbrain herniation and an improvement in motor function. Furthermore, 42% of children who underwent prenatal surgery were able to walk independently by 30 months compared to 21% of children treated with postnatal surgery (p = 0.001); in each of the two groups occurred 2 perinatal deaths. One problem was the rate of premature births (GA of 34.1 versus 37.3 weeks; p ≤ 0.001), another the rate of maternal complications (eTable A) (23).

After the procedure, delivery by caesarean section is required for this and all subsequent pregnancies. The data of the MOMS trial were confirmed in various centers in the following years and the procedure was approved by the FDA. Besides a reduction in the need for shunt placement as well as improvements in motor development, a lower rate of secondary neurosurgical procedures as well as possible positive effects on bladder and bowel dysfunction were observed (20, 24, 25, 26).

The cohort analysis of the Zurich Center, including 148 cases, found a shunt rate of 37% (39/106) at the end of the first year of life. 84% (48/57) of the children who underwent prenatal surgery were able to walk by the age of three years. In only 0.7% (1/106) of cases, no watertight closure of the back was achieved. Perinatal mortality was 0.7% (1/148) with no maternal mortality (27). A systematic analysis of the fetomaternal complication rate by the same working group found a higher birth rate GA >37 weeks (52/145; 36%) compared to MOMS (16/78; 21%) and a lower amnion separation rate. The rates of premature rupture of membranes and placental abruption were comparable (eTable B) (28).

eTable B

Child outcome parameters and maternal risks in hysterotomy-assisted repair (27, 28) and laparotomy-assisted fetoscopic repair (hybrid) (35, 36)

Fetoscopic techniques

Fetoscopic techniques were developed with the goal to minimize the fetomaternal risks associated with hysterotomy-assisted repair while achieving equivalent outcomes in terms of shunt rate and motor function. The two principal techniques are explained below.

Percutaneous fetoscopic repair

This technique employs a strictly percutaneous, fetoscopic approach, with repair of the fetal back using a single or double-layer patch technique depending on surgical preference (Figure 2, Figure 4) (29, 30).

Figure 2

Percutaneous fetoscopic repair

For the fetal long-term outcome with regard to the need for shunt placement as well as motor development, the data obtained were similar to that of the MOMS trial: In the German cohort (n = 71), 32/71 (45%) needed a VP shunt by 12 months; 32/54 (84%) were able to walk by age 30 months. After 30 months, 35/50 (70%) demonstrated normal psychomotor and mental development (31). A multicenter analysis by Lapa et al. produced similar data. In their analysis, 42/103 (40.8%) required a VP shunt by the age of 12 months and 84/103 (81.6%) had learnt to walk by the age of 30 months (30). Both groups demonstrated a low maternal risk without maternal mortality. After this surgical procedure, cesarean section was the mode of delivery for the majority of cases (88–100%) (21).

An increased rate of premature rupture of membranes (43/51; 84%) with associated preterm birth was observed; furthermore, postnatal revision surgery on the fetal back was required in 9.7–28% of cases because no watertight closure had been achieved (eTable C) (30, 31, 32, 33).

eTable C

Child outcome parameters and maternal risks in percutaneous laparoscopic repair

Laparotomy-assisted fetoscopic repair

(“hybrid method”)

This technique combines lower abdominal transverse laparotomy with fetoscopic defect repair via 2 or 3 ports (Figure 3, Figure 4). The transverse laparotomy and subsequent externalization of the uterus allows for optimum placement of the uterine ports, independent of the position of the placenta. In addition, the amnion can be fixed in place using sutures to reduce the rate of premature rupture of membranes (Figure 3, Figure 4). The fetus itself can be manually positioned by transuterine mobilization and retained in optimum position. With the goal of achieving a watertight closure, fetoscopic repair with three layers (Durapatch, muscle and skin coverage) is performed (34).

Figure 3

Laparotomy-assisted fetoscopic repair (hybrid method)

A reduction in premature births was noted, partly due to a reduced rate of premature ruptures of membranes (29/102; 28%) and a higher gestational age at birth (GA 39 weeks). 29/80 (36%) of children received a shunt within the first 12 months, while 38/73 (52.1%) were able to walk by 30 months (eTable B); this method was also approved by FDA (35, 36).

Discussion

Prenatal treatment of open spinal dysraphism demonstrates significant advantages over postnatal treatment with regard to motor function and shunt rate. However, despite these advantages, it is not a curative treatment. Some disease-specific aspects (bladder and bowel dysfunction, sexual dysfunction, secondary neurosurgical/ orthopedic procedures) are only slightly improved and neural functions that have already been lost cannot be restored. Overall, this method of treatment is still in its infancy and continually evolving as the expertise of the centers grows with increasing numbers of cases (37). Worldwide, there has been a noticeable increase in the number of centers offering this therapy, thereby making it more widely available. (38). Direct comparisons between the various surgical methods continue to pose challenges: First, open spinal dysraphism is a rare condition where different constellations of findings with a significant impact on prognosis can already be found prenatally. Furthermore, the cases operated on prenatally represent a pre-selected and heterogeneous patient population.

Time and again, there are calls for randomized controlled trials as advocated by evidence-based medicine, such as the Management of Myelomeningocele (MOMS) trial. In the field of prenatal therapy, however, there are numerous limitations to conducting randomized, controlled trials. These include long recruitment times in the face of ongoing technical advances, the fact that it is a rare condition with heterogeneous findings as well as the frequent reluctance of parents to accept randomization or to participate in a randomized, controlled trial (21).

In addition, the majority of centers are specialized in one surgical method and only few offer different surgical procedures. This makes it more difficult to conduct randomized, controlled trials. In addition, personal preferences and the technical expertise of the medical team can have an impact on randomization (38). Thus, since hardly any data from randomized, controlled trials will become available in the future, data collection and processing by the centers themselves is key. Linking prenatal and postnatal clinical courses and documenting long-term outcomes up to adulthood should be an integral part of the scientific evaluation (9).

Beyond the disease-specific aspects, the diagnosis of spinal dysraphism places a heavy psychological burden on parents and families; it appears that this negative impact is less severe if the children are treated prenatally compared to postnatal treatment. Here, motor development and family resources are predictive (39).

Attention should also be paid to the role mothers play in prenatal treatment: While surgical treatment offers no advantage to them, they bear the risk of procedure-related complications. Thus, interdisciplinary counselling of parents that addresses all aspects of the individual case is of crucial importance. While prenatal therapy can bring about significant improvements in physical independence and a reduction in associated complications, it also requires an in-depth discussion of the condition, the treatment options and the resulting risks.

In the future, advancements in surgical techniques, novel treatment approaches (for example, intrauterine stem cell therapy) and findings of basic research will contribute to a better understanding of the condition and help to optimize treatment (40).

Conflict of interest
The authors declare no conflict of interest.

Manuscript received on 16 May 2024, revised version accepted on 12 November 2024

Translated from the original German by Ralf Thoene, M.D.

Corresponding author
Dr. med. Corinna Nora Keil
UKGM Marburg-Klinik für Gynäkologie und Geburtshilfe
Zentrum für pränatale Diagnostik und fetale Therapie
35043 Marburg, Germany

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