Fetal Myelomeningocele Research Articles

Anesthesia for In Utero Repair of Myelomeningocele

Recently published results suggest that prenatal repair of fetal myelomeningocele is a potentially preferable alternative when compared to postnatal repair. In this article, the pathology of myelomeningocele, unique physiologic considerations, perioperative anesthetic management, and ethical considerations of open fetal surgery for prenatal myelomeningocele repair are discussed. Open fetal surgeries have many unique anesthetic issues such as inducing profound uterine relaxation, vigilance for maternal or fetal blood loss, fetal monitoring, and possible fetal resuscitation. Postoperative management, including the requirement for postoperative tocolysis and maternal analgesia, are also reviewed. The success of intrauterine myelomeningocele repair relies on a well-coordinated multidisciplinary approach. Fetal surgery is an important topic for anesthesiologists to understand, as the number of fetal procedures is likely to increase as new fetal treatment centers are opened across the United States.

Corrección intrauterina de mielomeningocele: experiencia del programa de medicina y terapia fetal del Hospital Universitario Virgen del Rocío

The most frequent form of spina bifida is myelomeningocele. There is no optimal postnatal treatment for this defect. In addition to the motor or sensory deficits, which depend on the location of the lesion, the defect is usually associated with Chiari ii malformation in affected children. Myelomeningocele has high mortality and, in up to 80% to 90% of patients, can be accompanied by hydrocephalus, which causes severe neurocognitive impairment and requires the patient to be shunted for survival. Intrauterine repair of fetal malformations employing open access through hysterotomy has become a therapeutic option due to improved anesthetic and surgical techniques and instrumentation, which have allowed this type of intervention to become relatively frequent. Anesthetic treatment should focus on both the mother and fetus and the hemodynamic factors regulating placental flow, uterine dynamics, blood loss and fetal well-being must remain well-controlled. Within our Program for Fetal Medicine and Therapy, 21 open fetal interventions have been performed: 17 EXIT procedures and 4 procedures for the intrauterine correction of fetal myelomeningocele. We describe our experience of the intrauterine repair of fetal myelomeningocele through open fetal surgery.

Fetal Myelomeningocele Repair: A New Standard of Care

Myelomeningocele, also known as spina bifida, is one of the most common congenital anomalies of the central nervous system and the most common open, prenatally repaired birth defect. The Management of Myelomeningocele Study (MOMS), which compared the results of prenatal and postnatal myelomeningocele repair, found prenatal surgery to be much more effective than postnatal surgery. During surgery, the surgeon makes a hysterotomy and repairs the fetal myelomeningocele without removing the fetus from the uterus. After the repair is completed, the surgeon closes the uterus. The obstetric team monitors the mother closely with a goal of performing a cesarean delivery at 37 weeks' gestation. The fetal surgery nursing team used innovative simulation teaching methods to establish and maintain fetal surgery team member competence, resulting in a successful program with good outcomes.

Maternal, Fetal, and Neonatal Care in Open Fetal Surgery for Myelomeningocele

Fetal myelomeningocele closure (fMMC) was demonstrated in a randomized, prospective clinical trial to improve outcomes for children diagnosed prenatally. Complex care of the maternal/fetal dyad undergoing fetal surgery requires a well-coordinated multidisciplinary team. Nurses in many roles are essential members of the team that cares for these women across the continuum. In this article we discuss the care of the woman, fetus, and family from initial contact through the discharge of the neonate.

Long-Term Urological Impact of Fetal Myelomeningocele Closure

Long-Term Urological Impact of Fetal Myelomeningocele Closure

Fetal Spine Findings on MRI and Associated Outcomes in Children With Open Neural Tube Defects

The purpose of this study is to determine the relationship between abnormal fetal spine findings on MRI and adverse outcomes in children with open neural tube defects. This was a review of pregnancies complicated by myelomeningocele referred for fetal MRI from 2001 to 2007 and followed postnatally at a spina bifida treatment center. MRI scans were reviewed to determine lesion level (T-L2, L3-4, or L5-S), interpediculate distance (≤ 10 or > 10 mm), vertebral segment span, and presence or absence of covering membrane. Ambulation was assessed in children 3 years old or older. Bladder dysfunction was termed as high-risk if renal damage was present or if urodynamic studies indicated increased risk for renal damage. Statistical analyses included chi-square, Mantel-Haenszel test for trend, and logistic regression. MRI was performed in 36 pregnancies with fetal myelomeningocele at a mean (± SD) of 27 ± 6 weeks, with subsequent delivery at 38 ± 1 week. Outcomes were assessed at 3.2 years (range, 2.4-5.1 years), and 23 children were 3 years old or older. Higher lesion level was associated with dysphagia: T-L2, 50%; L3-4, 45%; and L5-S, 13% (p < 0.05). The absence of covering membrane was associated with scoliosis (36% vs 0% with membrane present) and with high-risk bladder dysfunction (71% vs 36%; both p < 0.05). Higher lesion level, larger segment span, and interpediculate distance greater than 10 mm were associated with full-time wheelchair use (all p < 0.05). In fetuses with myelomeningoceles, higher and larger lesions on MRI were significantly associated with full-time wheelchair use. High lesion level was associated with dysphagia. The absence of a covering membrane was associated with scoliosis and high-risk bladder dysfunction.

Long-Term Urological Impact of Fetal Myelomeningocele Closure

Between 1997 and 2002 a large number of fetal myelomeningocele closures were performed at our institution. Previously early reports showed little improvement in neonatal bladder function after fetal back closure. We evaluated the long-term urological impact of this procedure. Using a combination of retrospective review and survey questionnaire we reviewed the records of 28 patients in whom fetal myelomeningocele closure was done at our institution between 1997 and 2002. The areas addressed included medical management for neurogenic bladder and bowel, need for lower urinary tract reconstruction and functional bladder assessment by videourodynamics. Parameters after fetal myelomeningocele closure were compared to those of 33 age and sex matched patients with myelomeningocele who underwent standard postnatal closure. We reviewed the records of 28 patients after fetal myelomeningocele closure. At a mean age of 9.6 years 23 used clean intermittent catheterization to manage the bladder, 24 required a bowel regimen to manage constipation and 6 underwent lower urinary tract reconstruction with enterocystoplasty and a catheterizable bladder channel. Videourodynamics performed in 14 patients at a mean age of 7.4 years revealed decreased bladder capacity in 71%, detrusor overactivity in 35% and increased detrusor pressure in 25%. Compared to age and sex matched children who underwent postnatal closure we noted no significant differences in bladder management, urinary tract surgery or urodynamics. Neurogenic bowel and bladder management continues to be a significant issue for patients after fetal myelomeningocele closure. After fetal surgery patients should be followed closely, similar to patients who undergo postnatal closure.

Preschool Neurobehavioral Outcome following Fetal Myelomeningocele Surgery

Objective: It was the aim of this study to assess the prevalence of preschool neurobehavioral problems in children following fetal myelomeningocele (fMMC) surgery. Methods: Prior to the Management of Myelomeningocele Study, 30 fMMC patients underwent a standardized neurodevelopmental examination at 5 years of age. The prevalence of behavioral problems was assessed by the Child Behavior Check List (CBCL), which includes a total problem score and 2 broad-band indices (internalizing and externalizing problems). fMMC children were classified as having normal, at-risk or clinically significant scores based on calculated T scores. Results: Twenty-two (73%) fMMC families completed the evaluation. Mean age at delivery following fMMC surgery was 35.5 ± 1.6 weeks. The prevalence of ‘at-risk’ or ‘clinically significant’ scores for internalizing, externalizing and total behavioral problems was similar to general population norms. No difference in overall internalizing (p = 0.19), externalizing (p = 0.54) and total behavioral (p = 0.18) scores was found between non-shunted and shunted fMMC children. However, shunted fMMC children were more likely to experience anxiety and depressive (p = 0.02), pervasive developmental (p = 0.03) and withdrawn (p = 0.06) behavior. Oppositional defiant, attention deficit and hyperactivity problems were not found. No correlation was found between overall neurodevelopmental outcome and abnormal CBCL scores. Conclusions: fMMC surgery and subsequent preterm delivery is not associated with increased behavioral problems, impaired social interactions and restricted behavior patterns. Shunted fMMC children were more likely to have scores in the ‘at-risk’ or ‘clinically significant’ range for multiple CBCL subindices. Early detection of behavioral problems following fMMC surgery provides an opportunity for targeted and timely intervention enabling affected fMMC children to be socially successful.

Fetal myelomeningocele surgery: preschool functional status using the Functional Independence Measure for children (WeeFIM)

To study preschool functional status in children following fetal myelomeningocele (fMMC) surgery. Prior to the NICHD-MOMS trial, 30 fMMC underwent standardized neurodevelopmental examination at 5 years of age. Functional status was determined with the Functional Independence Measure (WeeFIM), which assesses self-care, mobility, and cognitive independence. Evaluations were completed in 26 (87%). Mean cognitive (93.0 ± 21.9), self-care (66.5 ± 23.9), mobility (82.3 ± 19.5), and total (77.9 ± 20.3) functional quotient of fMMC children were significantly lower than age-matched population norms (P < 0.01). Complete caregiver independence was achieved by 22 (84%), 10 (38%), 16 (62%), and 15 (58%) fMMC children for cognition, self-care, mobility, and total functional outcome, respectively. Cognitive, mobility, and total independence were higher in non-shunted than shunted fMMC children (P = 0.02, P = 0.02, and P < 0.01, respectively) and in fMMC children with average neurodevelopmental scores (P < 0.001, P = 0.01, and P < 0.01, respectively). Self-care independence tended to be higher in the non-shunted group and in fMMC children with normal neurodevelopmental outcome (P = 0.07 and P = 0.09, respectively). The majority of fMMC children achieved cognitive and mobility independence, but continue to require significant assistance in self-care. Non-shunted and fMMC children with normal neurodevelopmental outcome were more likely to be independent in daily living activities. Better understanding of the extent of functional limitations following fMMC surgery will allow for more effective early interventions geared toward maximizing independence in everyday tasks in all environments.

The Relationship of Seizure Activity and Chronic Epilepsy in Early Infancy and Short-Term Neurodevelopmental Outcome Following Fetal Myelomeningocele Closure

We explored the relationship between seizure activity (SA) and/or chronic epilepsy (CE) and short-term neurodevelopmental outcomes following fetal myelomeningocele (fMMC) surgery. Retrospective databases and a parental questionnaire focusing on common complications of hindbrain herniation associated with MMC were used to determine the incidence of seizures following fMMC surgery. The Bayley Scales of Infant Development II was used to evaluate the neurocognitive outcomes. The available 3-year outcome data were used for analysis. 54 children underwent fMMC closure at our institution between 1998 and 2003. 48 (89%) families participated. The shunt rate was 50% (n=24). Seizures developed in 8/48 (17%) children, 2 (8%) non-shunted and 6 (25%) shunted (P=0.07). Of those six, 3 developed CE. Neurodevelopmental scores in the average range were found in both non-shunted and 3 shunted fMMC children. The remaining 3 shunted toddlers had CE and significant neurodevelopmental delays. Of those, 2 had severe intracranial hemorrhage and one developed frequent apneic spells in combination with epilepsy. The incidence of seizures in fMMC children was similar to previously reported data of postnatally repaired MMC patients. SA alone without CE was not associated with a worse neurocognitive outcome. The occurrence of severe acquired intracranial injury and CE, however, appeared to be correlated with adverse neurocognitive outcome following fMMC surgery.

Preschool neurodevelopmental outcome of children following fetal myelomeningocele closure

We sought to investigate the preschool neurodevelopmental outcomes of children following fetal myelomeningocele (fMMC) surgery. Prior to the Management of Myelomeningocele Study trial, 54 children underwent fMMC closure at our institution. Thirty (56%) returned at 5 years of age for standardized neurocognitive examination. Scores were grouped as high-average, average, mildly delayed, and severely delayed by SD intervals. Mean verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full intelligence quotient (FIQ) scores were within normal population range. High-average or average scores for VIQ, PIQ, FIQ, and processing speed were found in 93%, 90%, 90%, and 60%, respectively. Mean FIQ and processing speed of nonshunted children were significantly higher than for those who required shunt placement (P=.02 and P=.01, respectively). Mean VIQ and PIQ tended to be higher in nonshunted fMMC children (P=.05). The majority of fMMC children in this highly selective population had average preschool neurodevelopmental scores. fMMC children who did not require shunt placement were more likely to have better scores.

Supratentorial Abnormalities in the Chiari II Malformation, IV

The sonographic diagnosis of fetal myelomeningocele (MMC) has improved mainly because the diagnostic focus has shifted from observation of the spinal abnormality to observation of cranial abnormalities. We describe an abnormality in the position of the occipital horn in fetuses with MMC. The occipital horn appears to be too posterior in location when compared to healthy fetuses. We searched for all cases in which fetal MMC was sonographically detected from 1999 to 2009. Random controls from normal pregnancies were identified. We then measured the shortest distance of the edge of the occipital horn to the occipital bone in fetuses with MMC compared to healthy fetuses. Only fetuses with MMC who had normal-size ventricles were included. A total of 91 fetuses with MMC were identified. Twenty-six fetuses had a normal ventricle size. The gestational age range in this cohort was 18 weeks 5 days to 30 weeks 0 days. The comparison group of 39 healthy fetuses all had normal ventricles and had a gestational age range of 18 weeks 3 days to 35 weeks 2 days. After adjusting for gestational age, the statistical analysis showed that fetuses with MMC had significantly shorter measured distances from the posterior edge of the occipital horn to the occipital bone than healthy fetuses (P = .003). The occipital horn both appears to be and measures closer to the occipital bone in fetuses with MMC compared to healthy fetuses.

In utero meconium passage in fetuses and newborns with myelomeningocele

The authors retrospectively investigated whether midgestational fetal myelomeningocele (fMMC) repair alters intrauterine meconium exposure. Prior to the National Institutes of Health Management of Myelomeningocele Study, 54 fetuses underwent fMMC repair at the authors' institution. Forty-six fMMC sacs were available for pathological examination and 53 MMC sacs from postnatally repaired MMCs (pMMCs) were available for comparison. The presence and distribution of meconium were blindly evaluated using a grading system defined as follows: absent (no meconium present), mild (<10 meconium-positive histiocytes [MPHs]/hpf), moderate (10-25 MPHs/hpf), and severe (>25 MPHs/hpf). Hall's bile stain was used to confirm meconium and Prussian blue and Fontana Masson stains to exclude hemosiderin and melanin, respectively. Compared to pMMCs (79%), meconium histiocytosis was less prevalent in fMMC sacs (57%; p=0.017). Meconium staining was completely absent in 43% of the fMMC sacs. Mild meconium histiocytosis was found in 35% fMMC and 61% pMMC sacs (p=0.035). There was no statistical difference between groups with moderate and severe meconium histiocytosis. Meconium passage in MMCs can occur early in fetal life. Fetal MMC repair may reduce the duration of meconium exposure, thereby potentially limiting the toxic injury to the vulnerable neural elements.

Lower Extremity Neuromotor Function and Short-Term Ambulatory Potential following in utero Myelomeningocele Surgery

Objective: To evaluate lower extremity neuromotor function (LENF) and short-term ambulatory potential following fetal myelomeningocele (fMMC) closure. Methods: Retrospective chart review of 54 children that underwent fMMC closure at our institution prior to the NIHCD-MOMS trial. Neonatal LENF was compared to predicted function based on spinal lesion level assigned by prenatal ultrasound. Ambulatory status was classified as independent walkers (walks without assistive appliances), assisted walker (requires walking aid), and non-ambulatory (wheelchair bound). Results: Thoracic, lumbar, and sacral level lesions were present in 4, 44 and 6 fMMC infants, respectively. 31/54 of fMMC children (57.4%; median: 2 levels, range: 1–5) had better than predicted, 13/54 (24.1%) same as predicted and 10/54 (18.5%; median: 1 level, range: 1–2) worse than predicted LENF at birth. At a median follow-up age of 66 months (36–113), 37/54 (69%) walk independently, 13/54 (24%) are assisted walkers, and 4/54 (7%) are wheelchair dependent. The strongest factors predicting a lower likelihood to walk independently were higher-level lesion (>L4, p = 0.001) and the development of clubfoot deformity after fetal intervention (p = 0.026). Despite the observed improved ambulatory status, structured evaluation of coordinative skills revealed that the majority of independent ambulators and all children that require assistive devices to walk experience significant deficits in lower extremity coordination. Conclusions: We observed that fMMC surgery in this highly selective population results in better than predicted LENF at birth and short-term ambulatory status. However, fMMC toddlers continue to demonstrate deficits in movement coordination that are characteristic for children with spina bifida.

Supratentorial Abnormalities in the Chiari II Malformation, II

The sonographic diagnosis of fetal myelomeningocele has improved mainly because the diagnostic focus has shifted from observation of spinal manifestations to observation of cranial abnormalities. Intracranial diagnostic criteria rely on abnormalities in the posterior fossa. We describe abnormalities in tectal morphologic characteristics that, although well described on magnetic resonance imaging, have received little attention in the sonographic literature. This study analyzed the frequency of this observation and technical aspects that improve its visualization. From a database of obstetric sonograms, we identified all cases of sonographically detected myelomeningocele. The search covered the years 1999 to 2007. We retrospectively reviewed the fetal intracranial findings with special attention to elongation or "beaking" of the tectum. A total of 89 fetuses were identified. The mean and median gestational ages were 22 weeks 4 days and 22 weeks 2 days, respectively. Of the 89 cases, 59 (66%) had an abnormal tectal shape. The abnormality was seen in 77% of cases judged to be suboptimally visualized and 62% of cases with good visualization. Tectal abnormalities were seen equally well in fetuses before and after 24 weeks. Finally, tectal abnormalities were seen more frequently as the severity of posterior fossa findings increased. Tectal morphologic alteration is a common supratentorial feature of the Chiari II malformation on prenatal sonography both before and after 24 weeks' gestation. Its frequency increases with the severity of posterior fossa abnormalities. Therefore, it may be useful as a supratentorial indicator of both the presence and, potentially, the severity of the Chiari II malformation.

1A2-L03 ワイヤ駆動を用いた胎児外科手術用パッチスタビライザの開発

The clinical target of this study is intrauterine patch coverage of fetal myelomeningocele. The collagen patch is supposed to be stabilized onto the fragile fetal tissue during the laser fixation process. In this study, a patch-stabilizer using wire driven mechanism has been developed for precise force control on the patch without damaging fetal tissue. The diameter of the patch-stabilizer's shaft is 2.4[mm] and the stabilizing part holds collagen patch with diamond shape mechanism using wire driven. The patch-stabilizer is moved by the ball screw to stabilize the collagen patch and the stabilizing force is estimated with the wires tension. In this paper, the wires tension is controlled less than 0.4[N] and the stabilizing force is small enough to stabilize the collagen patch onto the fetal tissue.

Reversal of Hindbrain Herniation after Maternal-fetal Surgery for Myelomeningocele Subsequently Impacts on Brain Stem Function

The aim of our study was to delineate whether the reversal of hindbrain herniation (HH) following fetal myelomeningocele (fMMC) closure subsequently reduces the incidence and severity of HH-associated brainstem dysfunction (BSD). Prior to the NIH-sponsored Management of Myelomeningocele Study (MOMS) trial, 54 children underwent fMMC closure at our institution. Forty-eight (89%) families participated in a structured survey focusing on HH-associated BSD (e.g., apnea, neurogenic dysphagia [ND], gastro-esophageal reflux disease [GERD], neuro-ophthalmologic disturbances [NOD]). Median age at follow-up was 72 months (range: 46-98). Fifty-percent required shunting. HH-related symptoms were completely absent in 15 (63%) non-shunted and 10 (42%) shunted children (P=0.15). No HH-related death occurred and none developed severe persistent cyanotic apnea. ND was reported in 2 (8%) non-shunted and 9 (38%) shunted infants (P=0.03). Mild GERD (medically managed) developed in 2 (8%) without and 6 (25%) with shunt placement (P=0.24). NOD was found in 6 (25%) and 13 (54%) of non-shunted and shunted children, respectively (P=0.07). The majority of fMMC children developed no or only mild BSD at follow-up. Our data support the hypothesis that neurodevelopmental deficits associated with MMC are at least partially acquired and that reversal of HH following fMMC surgery may help to reduce the incidence and severity of BSD.

Intradural inclusion cysts following in utero closure of myelomeningocele: clinical implications and follow-up findings

The goal in this study was to evaluate the incidence and clinical implications of the development of cutaneously derived intradural inclusion cysts (ICs) following fetal myelomeningocele (fMMC) closure. Retrospective databases and responses to a parental questionnaire were reviewed to determine the incidence, clinical presentation, and outcomes of fMMCs in children in whom ICs developed at follow-up. Prior to the National Institutes of Health (NIH)-sponsored Management of Myelomeningocele Study (MOMS), 54 patients underwent fMMC closure at the authors' institution. Sixteen (30%) presented with symptomatic tethered cord syndrome (TCS) at a median age of 27 months (range 4-93 months). Ten (63%) of the 16 (19% of the total) developed TCS in association with an intradural IC. In 9 (90%) of 10 patients, the IC was seen on preoperative MR imaging, and in 1 it was found during surgery. Four additional children (7% of the total) with evidence of an IC on surveillance MR imaging are currently asymptomatic at 94, 84, 60, and 60 months of age, respectively. All but 1 (an L-3 level lesion) IC developed in infants with L-4 and L-5 defects. After cyst removal, 6 children are asymptomatic at a median follow-up of 36 months (range 12-63 months). Following IC removal, 4 children lost normal bladder function and now require clean intermittent catheterization, and 1 lost normal leg function and now requires a walking aid for ambulation. Histologically, 8 lesions were dermoid, 1 was an epidermoid, and 1 was a mixed dermoid-epidermoid IC. Three patients developed another IC and required its removal at 24, 39, and 51 months, respectively. One required another tethered cord release within 57 months after IC removal. Cutaneously derived intradural ICs can develop following fMMC surgery. Deterioration of bladder function, risk of recurrence, and loss of lower-extremity function appear to be the most important long-term complications of IC in children with fMMCs. The ongoing NIH-sponsored MOMS may help determine whether children with fMMC are at increased risk of IC development compared with children treated with postnatal MMC closure. Parents seeking fMMC closure should be informed about the possibility of IC formation and the potential clinical consequences.

Supratentorial Abnormalities in the Chiari II Malformation, I

The sonographic diagnosis of fetal myelomeningocele has improved dramatically over the past 20 years, mainly because the diagnostic focus has shifted from observation of the spinal abnormality to observation of cranial abnormalities. We describe an abnormality in the shape of the occipital horn that has received scant attention in the sonographic literature. The abnormality is a misshapen occipital horn that is "pointed" rather than rounded. This study analyzed the frequency of this observation and technical aspects that improve its visualization. From a database of obstetric sonograms, we searched for all cases in which open fetal myelomeningocele was sonographically detected. The search covered the period from 1999 to 2007. We then retrospectively reviewed the fetal intracranial findings in each case, with special attention to the contour of the occipital horn of the lateral ventricle. A total of 89 fetuses were identified. The mean and median gestational ages were 22 weeks 4 days and 22 weeks 2 days, respectively. Of the 89 cases, 62 (70%) had an occipital horn with a pointed shape. This abnormality was better seen in cases judged to be well visualized and in cases in which digital video clips were available for review. The abnormality was more frequently seen in fetuses at less than 24 weeks' gestation and in fetuses without ventriculomegaly. Finally, it was seen as commonly among fetuses with mild posterior fossa deformations as in those with more severe distortions. The occipital point is a common supratentorial feature of the Chiari II malformation. It is seen more commonly in fetuses at less than 24 weeks and in fetuses with normal-sized ventricles. As well, it is seen as commonly among fetuses with mild posterior fossa deformations as in those with more severe distortions. Therefore, its usefulness is enhanced as an observation in the armamentarium of cranial findings for detection of fetal myelomeningocele.

Scanning electron microscopy of fetal murine myelomeningocele reveals growth and development of the spinal cord in early gestation and neural tissue destruction around birth

Background Previous studies demonstrated that the spinal cord within a fetal myelomeningocele (MMC) lesion suffers progressive destruction during gestation. This study aims at elucidating thispathophysiologic feature on a cellular and ultrastructural level in a model of genetically determinedMMC. Methods Curly tail/loop tail mouse fetuses at various gestational stages and neonates were analyzed electron-microscopically to document time-point and nature of neural tissue development and pathologic alterations within the MMC. Results At embryonic day (E) 8.5 and E9.5, round cells displaying multiple microvilli covered the entire region of interest, and some specimens showed initial stages of neurulation. At E10.5, neurulation was terminated in normal animals, whereas the neural placode remained unfolded in MMC fetuses and became distinguishable from adjacent epidermal layers. At E15.5, an apparently normal differentiation was found. Until this time-point, there was no tissue damage or inflammation. Thereafter, increasingly severe tissue alterations were identified with ongoing gestation leading to almost complete loss of neural tissue at birth. Conclusion We show here in fetal mice with MMC that, apart from absent neurulation, growth and development of the otherwise perfectly intact exposed spinal cord appear normal in early gestation, whereas later, the unprotected neural tissue is progressively destroyed.