Micro-Surgical Treatment of Fetal Myelomeningocele

Abstract

Introduction Myelomeningocele (MMC) is the most common malformation of the central nervous system compatible with life. We will report the results obtained with the prenatal closure of MMC at the Instituto Estadual do Cérebro Paulo Niemeyer (IECPN).

Objectives Clinical outcome of fetuses undergoing intrauterine MMC repair by the Peralta mini-hysterotomy. Monitor the reduction of Arnold-Chiari II secondary to MMC, reduction of hydrocephalus and also motor development in these children.

Methods Descriptive study of 26 cases with intrauterine MMC repair by mini-hysterotomy, or Peralta technique, performed at the IECPN from December 2017 to February 2020.

Results Between December 2017 and February 2020, 26 pregnant women with children with MMC were operated on using Peralta technique. Fetuses were born at an average gestational age of 34.2 weeks and 8% were born before 30 weeks of gestation. The average birth weight was 2096g. It was possible to observe a significant reduction in the occurrence of Arnold-Chiari II in these patients, as well as an evident improvement in motor function in the neurological examination of these babies at the end of the first month of life, where 20 of 23 babies had active movement in the lower limbs.

Discussion This study demonstrates the correction of fetal MMC through a mini-hysterotomy of 2.5 to 3.5 cm, developed in order to reduce maternal and fetal mortality. This mini-hysterotomy technique is not a minimally invasive procedure, as it is based on open surgery for the treatment of fetal MMC, as recommended by the Management of Myelomeningocele Study (MOMS).

Resumo

Introdução Mielomeningocele (MMC) é a malformação mais comum do sistema nervoso central compatível com a vida. Nós relataremos os resultados obtidos com o fechamento pré-natal da MMC no Instituto Estadual do Cérebro Paulo Niemeyer (IECPN).

Objetivos Desfecho clínico dos fetos submetidos a correção intrauterina de MMC por mini-histerotomia de Peralta. Monitorar a redução de Arnold-Chiari II secundária à MMC, redução da hidrocefalia e também o desenvolvimento motor nessas crianças.

Métodos Estudo descritivo de 26 casos com correção intrauterina de MMC por mini-histerotomia ou técnica de Peralta realizadas no IECPN no período entre dezembro de 2017 a fevereiro de 2020.

Resultados Entre dezembro de 2017 a fevereiro de 2020, 26 gestantes com filhos portadores de MMC, foram operadas utilizando-se a técnica de Peralta. Os fetos nasceram com uma idade gestacional média de 34,2 semanas e 8% nasceram antes das 30 semanas de gestação. O peso médio ao nascer foi de 2096 gramas. Foi possível observarmos uma significativa redução na ocorrência de Arnold-Chiari II nestes pacientes, bem como uma evidente melhora da função motora no exame neurológico destes bebês ao final do primeiro mês de vida, aonde 20 de 23 bebês apresentavam movimentação ativa nos membros inferiores.

Discussão Este estudo demonstra a correção da MMC fetal através de uma mini-histerotomia de 2,5 à 3,5cm, desenvolvida com o intuito de reduzir a mortalidade materna e fetal. Esta técnica de mini-histerotomia não é um procedimento minimamente invasivo, pois é baseada na cirurgia aberta para o tratamento da MMC fetal, como preconiza o estudo Management of Myelomeningocele Study (MOMS).

Keywords

myelomeningocele - fetal surgery - spina bifida - Arnold Chiari II - hydrocephalus

Palavras-chave

mielomeningocele - cirurgia fetal - espinha bífida - Arnold Chiari II - hidrocefalia

Introduction

Spina bifida or spinal dysraphism is characterized by a defect in the closure of the neural tube at a certain point in the spine. Spina bifida can be opened when there is exposure of the spinal cord and nerve roots through a skin defect. Spina bifida occulta, or closed spina bifida, however, does not expose the central nervous system, with the defect being covered by intact skin. Myelomeningocele (MMC), or open spina bifida, is the most frequent congenital alteration of the central nervous system compatible with life, occurring due to a defect in the closure of the neural tube, in the first four weeks of pregnancy, during primary neurulation.[1] It is characterized by the presence of a hernial sac, most often in the lumbosacral region, containing the spinal cord, nerve roots and cerebrospinal fluid, and is generally associated with Arnold-Chiari II malformation. Hydrocephalus is always present in MMC and approximately 80% of patients who are treated in the postnatal period require peritoneal ventricle shunt (PVD)[2] [3]. This malformation occurs at a rate of approximately 0.7 to 0.8 per 1000 live births in the USA; in Brazil, there is an incidence of 1 to 2 cases per 1000 live births. The neural plate found in the center of the MMC (placode) corresponds to the dysplastic medullary neural tissue that did not close during the embryonic period. A median groove can be viewed longitudinally and corresponds to the central canal of the spinal cord, open dorsally. Associated with protrusion of the meninges and, dorsally, of the placode, the formed hernial sac contains cerebrospinal fluid. The most frequent location of MMC is in the lumbosacral region.[1] [4] [5]

Most children who are born with MMC have the Arnold-Chiari II malformation concomitantly, which presents a low implantation of the torcula and straight sinus, associated with a lower displacement of the IV ventricle, bulb, and lower portion of the cerebellum. This malformation is commonly associated with hydrocephalus.[6] Both the Chiari II malformation and hydrocephalus impose on these children a need for constant follow-up and monitoring for the rest of their lives.

Ultrasonography performed during pregnancy in women with fetuses with MMC has demonstrated a progressive evolution of the Chiari II malformation and hydrocephalus in these fetuses. Another detail observed during the serial performance of the ultrasounds is a progressive worsening the fetuses affected by MMC have in relation to the motor function in the lower limbs. This worsening could be attributed to the exposure of nervous tissue, placode and roots, to the neurotoxic action of amniotic fluid, as well as the absence of posterior vertebral elements as a result of the neural plate closure defect, between the 19^th and 25^th day of gestation during primary neurulation (two-hit hypothesis).[7] [8] [9]

After conducting the prospective, randomized, controlled, multicenter MOMS trial,[4] it became evident that the prenatal surgical treatment for the repair of MMC would significantly improve the quality of life of these children, with important regression of the Chiari II malformation, reduced need for placement of PVD, and improvement of motor sensory parameters in all the fetuses.[4] [5] [7] [10] [11] [12] [13] Regarding the functions of the urinary tract, the neurogenic bladder continues to be present, but the occurrence of urinary tract infections in patients treated in the prenatal period is lower than in children who received postnatal treatment.[14] Another very important observation was seen in Toronto where, after the beginning of fetal treatment for repair of MMC, combined with the good postoperative results evidenced in these children, there has been a reduction in the optional termination of pregnancy in fetuses with MMC, considering that in Canada the termination of pregnancies in the face of congenital malformations is allowed by law.[15]

Methods

This study was approved by the IRB with the number 32112920.2.00008110 version 3.

Descriptive study of 26 cases with intrauterine MMC repair by mini-hysterotomy or the Peralta technique performed at the Instituto Estadual do Cérebro Paulo Niemeyer (IECPN) from December 2017 to February 2020.

Epidemiology / Etiology

Epidemiological studies have revealed a wide variation in the prevalence of MMC based on ethnicity, race, temporal and geographical trends. Spinal dysraphism occurs at approximately 0.7 to 0.8 per 1000 live births in the USA; in Brazil there is an incidence of 1 to 2 cases per 1000 live births, and underdeveloped countries have a slightly higher incidence.[1] [8] [16] [17]

It is recognized that MMC has a complex etiologic basis with genetic and environmental predisposing factors. The genetic influence is evidenced by the presence of recurrence within families (5% for the second child, 10% for the third child, and 25% for a fourth child of the same couple)[18], ethnic groups, and an increased risk in genes involving the folate metabolism and other cellular processes.[19] Other maternal conditions implicated as risk factors are obesity and diabetes.[15] A body mass index (BMI) greater than 30 seems to double the risk of conceiving children with dysraphism,[4] as well as the presence of febrile illness in the early stages of pregnancy. The mean BMI of our series was 27.8 ([Table 1]). Maternal intake of anticonvulsants, such as valproate and carbamazepine, during the pre-conception period is also a widely recognized risk factor. Folic acid supplementation is recommended for women of childbearing age at least 3 months before conception, as it is known that women with a diet low in folic acid (vitamin B9) have a greater chance of having children affected by the disease.[1] [4] [20] In our series, it was observed that the majority of pregnant women with a lower level of education did not use folic acid supplements, while patients with a higher level of education used this medication more ([Chart 1]).

Table 1 Data from patients operated on at IECPN compared to data chosen from the MOMS study

Characteristics	IECPN Fetal Surgery	MOMS Fetal Surgery
Fetal gender: female – %	56%	45%
GA – weeks	26.5	23.6
Maternal age – years	29.8	29.3
Married – %	39.1%	94%
BMI	27.8	25.9
Smoker – %	29%	6%
Nulliparous	14.6%	42%
Previous uterine surgery – %	16%	14%
GUS injury level – % Thoracic	0%	4%
L1–L2	13%	27%
L3–L4	53.5%	38%
L5–S1	34.1%	19%

Abbreviations: BMI, body mass index; GA, gestational age. IECPN, Instituto Estadual do Cerebro Paulo Niemeyer; MOMS, management of myelomeningocele study. Source: Data from patients of the IECPN and MOMS study; GUS, gestational ultrasound.

Chart 1 Correlation between patients who used folic acid and schooling. We evidenced that among the mothers with complete higher education, 6 used folic acid and 1 did not use it. Regarding those with incomplete higher education, 1 used folic acid and 3 did not. Eleven patients with elementary education did not use folate and one did. The chart shows how higher levels of education are related to the use of folic acid.

Inclusion Criteria for Fetal Surgery

Inclusion criteria are: single pregnancy, gestational age between 19 and 27 weeks and 6 days, MMC level between T1 and S1, evidence of Arnold-Chiari II malformation, absence of fetal chromosomal alteration, absence of other fetal malformations, absence of fetal scoliosis greater than 30%, absence of a previous history of prematurity or cervix smaller than 25 mm during pregnancy, absence of serious maternal disease that may increase surgical risk, and absence of positive maternal serology for HIV or hepatitis B and C.[2] [4] [13] [21] [22]

Diagnose

Currently, the diagnosis of MMC is made with ultrasound (2D or 3D) between the 12^th and 14^th week, which has a sensitivity of 80 to 90%. The diagnosis is made through the presence of indirect signs such as ventriculomegaly, lemon sign (scalloping of the frontal bones), banana sign (inversion of the cerebellum curvature) and obliteration of the cisterna magna (Chiari malformation type II). Direct signs are best detected in the axial plane, where the U- or C-shaped vertebrae can be visualized, due to the absence of the dorsal arches, and the interruption of the skin contour with or without the meningocele. The spinal examination also includes the location of the medullary cone, which varies according to the gestational age; typically, the medullary cone ends at L4 between the 13^th and 18^th week; in L3 around the 19^th and 36^th week, and L2 after the 36^th week.[22] [23] Although the image quality is currently excellent, some characteristics are still difficult to accurately assess, including the size of the placode and the extent of normal skin around the lesion. Ultrasound can also be used to assess the degree of involvement of the lower limbs in the fetus, including the presence of congenital clubfoot. The presence of active movement of the lower limbs indicates a good prognosis, and must be distinguished from involuntary movements, sometimes present in fetuses with open dysraphism.[23]

Ventriculomegaly is present in 70 to 90% of fetuses with MMC. It is assessed at the level of the ventricular atrium of the lateral ventricle in the axial plane of the fetus's head at the level of the thalamus and is considered abnormal if greater than 10 mm. The prevalence of ventriculomegaly increases along with the gestational age. Generally, there is a correlation between the severity of ventriculomegaly, its onset gestational age, and the severity of malformation of the posterior fossa. It is important to note that the ventricles may be asymmetrically dilated.[22] It is in the postnatal period that the need for hydrocephalus treatment is evaluated, either by placing a shunt or performing an endoscopic third ventriculostomy.[19] [24]

Prenatal magnetic resonance imaging (MRI) is very useful to evaluate more specific details of the malformation, details that are important, but not essential in the evaluation for fetal surgery. T2 weighted images (T2WI), including single-shot fast spin-echo, or half-fourier acquisition single-shot turbo spin-echo (HASTE) with 2 to 4 mm cuts, are sufficient for diagnosis. There is no need to use gadolinium.[22] [25]

Other malformations be associated with MMC are hydrocephalus (80%), Chiari II, disorderly cortical migration (92%), hypoplasia or aplasia of the cranial nerve nuclei (20%), fusion of the thalamus (16%), agenesis of the corpus callosum (12%), complete or partial agenesis of the olfactory tract or bulb (18%), dysplasias or abnormalities of the corpus callosum and heterotopias of the gray matter (19%).[18]

The presence of Chiari malformation type II occurs in almost all children with MMC who received postnatal treatment, according to the theory of Mc Lone and Kepper,[26] due to a cerebrospinal fluid fistula caused by the presence of spinal malformation, which reduces pressure in the ventricle and, consequently, originates a smaller posterior fossa, with the tentacle in a lower position. When the cerebellar primordium begins to grow, herniation occurs through the cervical vertebral canal, below the foramen magnum. Symptoms related to Chiari malformation type II are determined by the degree of descent of the cerebellum into the vertebral canal and include sialorrhea, inspiratory stridor, weak crying, and respiratory failure, among others.[27]

The level of MMC is an important predictive factor in the ability to walk. Patients with lesions at the sacral level are able to walk 100% of the time. However, patients with the lesion at the level of L3 or above will need a wheelchair to move around.[28] Most of the patients in our series had a lesion between levels L3 and L4 ([Table 1]). Approximately 84% of children with neurogenic bladders have altered bowel control and severe chronic constipation.[18] The quality of their social life will depend on the degree of functional loss (difficulty walking, fecal and urinary incontinence).

Surgical Treatment

Classically, MMC repair is performed shortly after birth with the postnatal repair of the lesion. However, studies show that spinal cord injury in MMC occurs before birth, both due to an abnormality in the development of the neural tube during the embryonic period, and the chronic exposure of this nervous tissue to the intrauterine environment (amniotic fluid, trauma to the wall of the uterus, and hydrodynamic pressure on nervous tissue without the protection of normal skin), which worsen the neurological lesion. This theory is called two-hit hypothesis.[12] Some studies on the histological evaluation of these spinal closure defects show that the nervous tissue exposed directly to the amniotic fluid (spinal cord, meninges, and nerve roots) presents different degrees of loss of neural tissue, at the same time as the less exposed portions (ventral and dorsal horns, especially of the proximal portions of the lesion) have a normal histological aspect. Additionally, several observational studies have shown that most fetuses with MMC with movements in the lower limbs in ultrasound exams do not present the same motor function soon after birth. This theory (two-hit hypothesis) led to the initiation of studies for intrauterine treatment of MMC, in order to improve the prognosis by reducing environmental factors.[4] [10] [16] [22] [29] [30]

The first experimental studies on intrauterine closure of MMC were carried out in the mid-1980s, in primates. Initial animal studies showed that coverage of lesions similar to dysraphism in the intrauterine period preserved neurological function and reversed cerebellar herniation to varying degrees.[24] [31] [32] The repair of the defect in human fetuses started in 1997 with Bruner et al.,[31] and the initial studies corroborated with the previous results, and still reported the reduction of the need to use shunts for hydrocephalus. Since then, several techniques have been developed, and since 2004 the intrauterine repair of MMC has been recommended. Before then, there was no standardization as to the indications and techniques used. In 2011, a randomized clinical trial was conducted in the USA, called MOMS (Management of Myelomeningocele Study),[3] [7] [30] the results of which were published in the New England Journal of Medicine in 2011. In this study, 183 pregnant women whose fetuses had MMC were randomized for intrauterine treatment (MMC repair through hysterotomy) or for postnatal treatment (control group). The main criteria for inclusion of patients in this study were: gestational age between 19 and 27 weeks, MMC with a higher level of injury between T1 (first thoracic vertebra) and S1 (first sacral vertebra), absence of other serious fetal malformations or chromosomal abnormalities, presence of Chiari II, and absence of severe tortuosity in the fetal spine. The repair of the defect in the fetus was done through a body hysterotomy of 6 to 10 cm in length, in order to allow adequate exposure of the fetal lesion so that the neurosurgeon could perform the classical MMC layered closure surgery. The results were extremely promising. There was a significant reduction in the need to install ventriculoperitoneal shunts in the fetal surgery group (40%) in relation to children operated after birth (82%), and it improves global neurological and motor scores of infants. In the 30^th month follow-up of these children, there was a significant increase in the chance of walking without using orthoses and a significant improvement in intellectual development, when compared to the group of children who were operated after birth.[3] [6] [7]

Despite the favorable results for the child, fetal surgery was accompanied by some controllable, but not negligible, maternal complications. The most frequently observed were premature rupture of ovular membranes (PTROM, 46%), premature labor (PTL, 38%), complete or partial dehiscence of the hysterotomy observed at the time of pregnancy resolution (30%), chorioamniotic separation (26%), need for maternal blood transfusion at delivery (9%), acute pulmonary edema (6%) after fetal surgery, and placental abruption (6%) during fetal surgery. These complications ended up somewhat limiting the spread of fetal surgery for MMC worldwide.[3] [4] [5] [30]

In order to minimize the access necessary for the repair of fetal dysraphism and, therefore, to reduce maternal morbidity, some groups have tested the endoscopic approach. However, the neurological results after these apparently less invasive procedures are still not well known, and the rates of PTROM, PTL and fetal/neonatal scar dehiscence requiring postnatal reoperation are still high.[13] [33] [34]

Considering that adverse maternal results are the biggest concerns regarding the intrauterine approach to fetal repair of spinal dysraphism, a technical innovation was described in 2016 in order to minimize these complications. This new technique is described as mini-hysterotomy, or the Peralta technique,[20] and consists of a modification of the classical open surgery for the treatment of fetal MMC, in which the same multilayer repair of the spinal defect is performed through a 2.5 to 3.5 cm hysterotomy. This technique is the one we have been using at the IECPN, since December 2017.

The Peralta Mini-Hysterotomy

The surgery is performed with the pregnant woman in the supine position, under general anesthesia; an enlarged Pfannestiel incision is made with subsequent exteriorization of the uterus from the abdominal cavity. The fetus is gently moved by ultrasound-guided external manipulation, so that the spinal defect is located against the uterine wall in the region where the placenta is not located. Thereafter, a 2.5 to 3.5 cm hysterotomy is performed, at least 2 cm from the placental edge ([Fig. 1]). The amniotic membrane is sutured in the inner layer of the myometrium and then the neonatal Ankeney retractor is introduced, which is fixed with the help of the Leyla retraction system, in order to keep the uterine walls separate and expose the malformation ([Fig. 2]). Then, the repair of MMC is performed by the neurosurgery team. During this part, the fetus is monitored by the obstetric team.[20]

Fig. 1 Mini-hysterotomy (Peralta technique).

Fig. 2 The neonatal Ankeney retractor is introduced, which is fixed with the help of the Leyla retraction system, in order to keep the uterine walls separate and expose the malformation.

From the neurosurgical point of view, the goal of the treatment of MMC is to remove the malformed hernial sac, protect the exposed nervous system by creating a barrier between the spinal canal and the outside, preventing trauma and protecting the central nervous system against the aggressive action of the amniotic fluid, in addition to restoring the cerebrospinal fluid medium around the malformed spinal cord, thereby preserving motor and sensory functions.

In fetal surgery, neurosurgical steps are similar to those of postnatal surgery. With the aid of the surgical microscope, the placode is identified ([Fig. 3]), then separated from the surrounding epithelium ([Fig. 4] and [Fig. 5]). The junction between the placode and the skin is variable, usually a translucent tissue extends from each side of the placode to the medial side of the skin, and this is the entry point for the surgical repair. This layer represents the primitive arachnoid pia and should be incised close to the skin, as the placode is very fragile; thereafter, the circumferential incision is continued, allowing complete mobilization of the placode, which is closed with PDS 7.0 sutures, bringing the edges together (pia-to-pia) ([Fig. 6]). The dura mater is often transparent and has characteristics of the arachnoid of older children. It is present along the vertebral canal and extends laterally beyond the vertebral canal, being lost in the subcutaneous tissue. The junction between the dura and the dermis can be seen by slightly elevating the skin. At this point, a small incision is made and the dura mater is dissected in a circumferential manner, separating the dorsal fascia. After the 22^nd week, the dura mater becomes more substantial and easier to handle. After its complete dissection, it is sutured with a continuous stitch with PDS 6.0 ([Fig.7A], [Fig.7B], [Fig.7C]). When the dural closure is completed, the fetal skin is closed in a single plane, also with continuous stitch with PDS 5.0 ([Fig. 8]). The dissection of the muscular plane and fascia is not performed due to bleeding and reduced surgical time. The elevation of the skin and separation of the adjacent subcutaneous tissue does not present any major difficulties. Once the primary closure is performed, the postnatal result is very good. Finally, it should be taken into account that the fetuses' skin can break with a harsher movement, despite its great elasticity.

Fig. 3 The placode is identified after the Ankeney retractor has been introduced.

Fig. 4 The neural placode is circumferentially dissected. The neural groove can be seen, which would represent the central canal of the spinal cord.

Fig. 5 The dorsal roots can be seen after arachnoid incision.

Fig. 6 Reconstruction of the spinal cord with micro sutures (pia-to-pia) with PDS 7.0.

Fig. 7 (A) Circumferential dissection of the dura. (B) After complete circumferential dissection of the dura, we can see the muscle fascia (open arrow). (C) Tight dural closure with PDS 6.0 (running sutures).

Fig. 8 The fetal skin is closed in a single plane, also with continuous stitch with PDS 5.0.

After the injury is closed, the obstetrics team continues to close the uterus and abdominal wall. A Nelaton probe is then inserted into the amniotic cavity in the opposite direction to the location of the placenta, then the uterine wall is closed in layers, bringing the edges of the hysterotomy closer together. During this closure, warm saline is instilled in the amniotic cavity, in an amount sufficient to involve the entire fetus (monitored by ultrasound), always giving fetal vitality. Right after the hysterotomy is closed and the Nelaton tube is removed, the peritoneal cavity is cleaned, and the hemostasis and pelvic viscera are reviewed. Then, the uterus is hydrated with saline inside the peritoneal cavity and the overlying layers of the abdominal wall are closed.

The follow-up of these babies in the postnatal period includes an initial observation of the MMC scar, being necessary to reoperate in cases of cerebrospinal fluid fistula; monitoring of ventriculomegaly, assessing the need or not for surgical treatment, and monitoring of bladder dysfunction with assessment of the possible need for vesical catheterization. These children subsequently require the monitoring of a multidisciplinary team: pediatrician, neurosurgeon, neurologist, geneticist, orthopedist, urologist, physiotherapist, and psychological support ([Table 2]).

Table 2 Observed results of skeletal muscle characteristics. And exam evaluating the reflexes presented in the first month of life, performed by a neonatologist

Skeletal muscle characteristics no. (%)	Yes	No
Anatomical defect of the lower limbs	10 (43)	13 (56.5)
Unilateral clubfoot	2 (8.6)	20 (86.9)
Bilateral clubfoot	8 (35)	13 (56)
Neonatal neurological examination: Normal +	15 (65.2)	8 (34.7)
Abolished tendon bone reflexes	2 (8.6)	21 (91.3)
Active movements of the lower limbs	20 (86.9)	3 (13)

Note: The most common anatomical defect was clubfoot. Most patients had a normal motor neurological exam for their age.

Regarding maternal complications,[35] we observed two cases of placental abruption, two cases of preeclampsia and one case of uterine rupture. Regarding fetal complications, we had two deliveries under 30 weeks and one perinatal death ([Table 3]).

Table 3 Results showing maternal complications, comparing the two groups, MOMS / IECPN

Maternal – fetal complications (%)	IECPN	MOMS
Oligo amnio	1 (4)	16 (21)
DPP	2 (8.6)	36 (46)
Chorioamnionitis	1 (4)	2(3)
Placenta previa	1 (4)	5 (6)
Gestational diabetes	2 (8.6)	4 (5)
Pre-eclampsia	2 (8.6)	3(4)
Uterine rupture	1 (4)	1 (1)
Fetal complications
Repair dehiscence	1 (4)	10 (13)
Gestational age at birth (weeks)
< 30	2 (8)	10 (13)
30–34	11 (47)	26 (33)
35–36	6 (26)	26 (33)
> 37	5 (22)	16 (21)
Mean birth weight (grams)	2,096	2,383
Perinatal death	1 (4)	2 (3)

Abbreviations: DPP, premature placental abruption; IECPN, Instituto Estadual do Cerebro Paulo Niemeyer; MOMS, management of myelomeningocele study. Notes: Perinatal death at the IECPN was related primarily to intrauterine infection, and secondarily to premature birth evolving to the newborn's respiratory distress syndrome. Low birth weight and premature birth are risk factors for fetal complications. At IECPN, the uterine opening is 2.5 to 3.0 cm in diameter, which is one of the causes of different values between the variables of DPP and oligo amnio.

Of the 23 children in our series, aged 12 months, only 5 needed treatment for hydrocephalus, and 12 of the 23 children aged 12 months did not have Chiari II malformation ([Table 4]).

Table 4 Comparative data of the results in the first 12 months of life of patients operated on fetal myelomeningocele, between IECPN and MOMS study

Primary results of children at 12 months of age
Results	IECP patients (n = 23)	MOMS patients (n = 73)
Placement of PVD / TVE – no. (%)	5 (26.5)	31 (40)
No evidence of FP herniation – no. (%)	12 (63)	25 (36)
Decompression FP for Chiari II – no. (%)	0	1 (1)
PVD infection – no. (%)	2 (10)	5 (6)

Abbreviations: FP, posterior fossa; IECPN, Instituto Estadual do Cerebro Paulo Niemeyer; MOMS, management of myelomeningocele study; PVD, peritoneal ventricle shunt; TVE, third ventriculostomy endoscopy.

Discussion

Surgical treatment for fetal MMC has been widely indicated regarding the postnatal treatment.[13] Fetal surgery, whether made by microscopy or endoscopically, requires a coordinated effort of several specialists, including from the nursing staff, neonatologists, obstetricians, pediatric surgeons, anesthesiologists with maternal-fetal experience, neurosurgeons, radiologists, geneticists, and psychologists, which makes the IECPN a qualified and complete hospital to perform this type of procedure in Rio de Janeiro, Brazil.

The resources necessary to start a program dedicated to fetal surgery need to be known and no details should be ignored. A multidisciplinary team with experience to carry out patient evaluation is essential to perform procedures, as well as appropriate postoperative follow-up. Hospitals where fetal surgeries are performed most often generate very high costs, but it is essential that they have multidisciplinary and qualified teams to perform fetal surgery.

The main trial conducted in 2011, MOMS, started in a developed country, with more favorable technology and physical means to carry out the study, yet Brazil already performed this type of surgery with excellent and favorable results, being one of the countries with a high number of surgeries and positive outcomes.[22] [36] [37]

Lunet et al.,[38] suggest that the non-use of folic acid is dependent on some demographic and socioeconomical factors, especially in cases of women with less education, single mothers, without prenatal monitoring, becoming more vulnerable to malformations of the neural tube.[39] Barbosa et al. showed that the level of education and higher number of prenatal consultations are directly linked to the use of folate, and a higher education level corresponds to a higher use of folic acid and lower incidence of children with neural tube defects. [40] In our series, we have noted that patients with more education were the ones who used folic acid the most during prenatal care; this shows that the socioeconomic and educational parameter is directly linked with one of the main factors of closure of the neural tube.

Not only does the fetus present potential risks from intrauterine fetal surgery, but the mother's health can also be threatened. The mother undergoes two laparotomy surgeries, one for MMCf correction and another to perform the c-section at the appropriate moment to interrupt the pregnancy. In our study, we noted that we were able to perform the procedure in several patients with more than one pregnancy and previous C-section without causing maternal complications for this group of pregnant women. It is not necessary to exclude women with previous c-sections. Our school adopts the Peralta mini-hysterotomy (uterine opening of 2.5–3.5 cm)[20], with more maternal favorable outcomes compared to the MOMS study.

In our series we have noted a total of 16% of women with previous uterine surgeries, which is similar to the results in the MOMS study (14%). Nulliparity between the 2 centers had a difference of almost 30%, IECPN (14.6%) vs MOMS.[35] [41] Placental abruption occurred in 8% of our patients, while at MOMS placental abruption occurred in 42% of pregnant women; we believe that this great difference is due to the use of the Peralta technique, which is related to less postoperative maternal complications.

Within the expected outcomes for patients who need shunt, only 26% of our patients, all of which were over 11 months old, underwent internal ventricular shunt or third ventriculostomy endoscopy (TVE). A surgery performed with gestational age within the stipulated time (19–25.6 weeks) minimizes the risk of reduced posterior fossa and descent of the brain stem by the foramen magnum (Chiari II), which is one of the physical mechanisms that favor hydrocephalus when surgery is performed in the postnatal period.[33]

Hydrocephalus tends to progress in patients with MMC during pregnancy, which is why operating earlier in pregnancy, when hydrocephalus is less evident, reduces the possible need for postnatal procedure for ventriculoperitoneal shunt placement. This was suggested by Bruner et al., who showed that the intrauterine repair after 26 weeks of age conferred much less benefit than the surgery performed between 20 and 24 weeks.[17] [33]

McLone (1983) commented that up to 32% of patients with MMC observed and corrected in the postnatal period presented the Arnold-Chiari II malformation.[41] [42] It is currently known that this malformation is seen in 80 to 100% of patients with MMC who are operated in the postnatal period.[43] Stevenson (2004) observed that patients with Arnold-Chiari II, sometimes had such prominent deformities and bony angulations posterior fossa decompression was required in patients up to 2 years old to decompress the bulb and release cerebral spinal fluid (CSF) flow,[44] a situation not observed in our study of cases at the IECPN.

Conclusion

Microsurgery provides better results when compared to patients treated after birth. We have observed that prenatal surgery for the treatment of MMC provides a decreased occurrence of hydrocephalus, resulting in a decrease in the need to place a peritoneal ventricular shunt. We also proved an important reduction in the occurrence of Chiari II, which was proved through gestational ultrasound and, in some cases, fetal MRI. Finally, we have also proved that the use of the Peralta technique results in more independent children, due to a better motor sensory function, when compared to the newborns submitted to traditional postnatal closure.

Conflict of Interests

The authors have no conflict of interests to declare.

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Publication History

Received: 10 June 2020

Accepted: 06 April 2022

Article published online:
10 October 2023