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Update on Prenatal Diagnosis and Fetal Surgery for Myelomeningocele

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Update on Prenatal Diagnosis and Fetal Surgery for Myelomeningocele Review Arch Argent Pediatr 2021;119(3):e215-e228 / e215 Update on prenatal diagnosis and fetal surgery for myelomeningocele César Meller, M.D.a, Delfina Covini, M.D.b, Horacio Aiello, M.D.a, Gustavo Izbizky, M.D.a, Santiago Portillo Medina, M.D.c and Lucas Otaño, M.D.a ABSTRACT This powered research in two A seminal study titled Management of critical areas. On the one side, prenatal Myelomeningocele Study, from 2011, demonstrated that prenatal myelomeningocele defect repaired myelomeningocele diagnosis within before 26 weeks of gestation improved the therapeutic window became a neurological outcomes; based on this study, fetal mandatory goal; therefore, research surgery was introduced as a standard of care efforts on screening strategies were alternative. Thus, prenatal myelomeningocele diagnosis within the therapeutic window became intensified, especially in the first a mandatory goal; therefore, research efforts on trimester. On the other side, different screening strategies were intensified, especially fetal surgery techniques were assessed in the first trimester. In addition, different fetal to improve neurological outcomes and surgery techniques were developed to improve neurological outcomes and reduce maternal reduce maternal risks. The objective risks. The objective of this review is to provide an of this review is to provide an update update on the advances in prenatal screening and on the advances in prenatal screening diagnosis during the first and second trimesters, and diagnosis and in fetal surgery for and in open and fetoscopic fetal surgery for myelomeningocele. myelomeningocele. Key words: myelomeningocele, fetal therapies, spina bifida, fetoscopy, antenatal care. EPIDEMIOLOGY The prevalence of spina bifida http://dx.doi.org/10.5546/aap.2021.eng.e215 varies markedly worldwide based on ethnic and geographic To cite: Meller C, Covini D, Aiello H, Izbizky G, characteristics.8,9 In Argentina, since et al. Update on prenatal diagnosis and fetal surgery for myelomeningocele. Arch Argent Pediatr 2021; the implementation of the law for 119(3):e215-e228. flour fortification with folic acid, spina bifida prevalence decreased approximately 60 %. Nowadays, it a. Department of Obstetrics. is approximately 1 in every 2000 live 10 b. Department of INTRODUCTION births. Its prevalence during Imaging Studies. Until 2011, prenatal screening pregnancy is higher and decreases c. Department and diagnosis strategies regarding towards the end due to intrauterine of Pediatric Neurosurgery. myelomeningocele were aimed at death caused by this disease, 11 Hospital Italiano providing appropriate counseling to especially in syndromic cases. de Buenos Aires, parents based on prognosis so that Most myelomeningocele cases occur Autonomous City they were aware of management as a single defect. Some abnormalities of Buenos Aires, Argentina. options, either adequate obstetric are considered part of the disease follow-up and delivery in a center spectrum and, therefore, it is still E-mail address: with neonatal surgery availability considered an isolated defect, such as César H. Meller, M.D.: or, depending on local laws, an ventriculomegaly, Arnold-Chiari II cesar.meller@ abortion.1,2 A seminal study titled malformation, hypoplasia of the corpus hospitalitaliano.org.ar Management of Myelomeningocele callosum, and talipes equinovarus.2,10-12 3 Funding: Study (MOMS) demonstrated that None. prenatal myelomeningocele repair PRENATAL SCREENING before 26 weeks of gestation improved AND DIAGNOSIS OF Conflict of interest: neurological outcomes; based on this MYELOMENINGOCELE None. study, fetal surgery was introduced Prenatal spina bifida detection Received: 9-29-2020 to standard of care alternatives for has increased in recent decades, Accepted: 11-12-2020 myelomeningocele management.2,4-7 and it is now possible to do it in the e216 / Arch Argent Pediatr 2021;119(3):e215-e228 / Review first trimester. The European Surveillance of It may be technically difficult to find them, such Congenital Anomalies (EUROCAT) reported, as when the fetus is back-to-back (with the spine for the 2012-2017 period, a prenatal sensitivity away from the probe) or with the spine against close to 90 %, i.e., in approximately 10 % of cases, the placenta or uterus. Therefore, it is critical to be ultrasounds were wrongly classified as normal aware of the indirect signs of spina bifida, which (false negative result).13 In turn, in regions with had been described in the 1980s and became the fewer resources, such as Latin America, prenatal true pillars of myelomeningocele screening.22 detection is not as common and it is done at a 1.b. Assessment of intracranial signs of more advanced gestational age.8,14 spina bifida: indirect cranial signs work for In the 1970s, spina bifida was diagnosed by screening and help to diagnose spina bifida. ultrasound in the prenatal period for the first They include, during the second trimester, a time15 and maternal blood alpha-fetoprotein smaller biparietal diameter (BPD) and head levels were added to second trimester screening circumference, flattened or concave frontal bones tests.16 The biochemistry panel is practically (“lemon sign”), ventriculomegaly, obliteration not used anymore; screening and diagnosis are of the cisterna magna, and visualization of currently usually done in the second trimester cerebellar abnormalities, including the absence and, more recently, also during the 11-14-week of cerebellum in the posterior fossa, a small ultrasound.17-19 cerebellum or anterior concave shape (“banana sign”) (Figure 3).23 In fetus with myelomeningocele 1. Second-trimester ultrasound at less than 24 weeks of gestation, the “lemon 1.a. Direct spinal assessment: this is done sign” is almost invariably present (98 %), and the as part of a routine, detailed ultrasound around “banana sign” is observed in 70-80 % of cases; week 18-24. The International Society of however, in fetuses with an older gestational Ultrasound in Obstetrics & Gynecology (ISUOG) age, the “lemon sign” is uncommon and, in suggests re-assessing the spine using axial, the posterior fossa, the most common finding sagittal, and coronal sections (Figure 1).20,21 is an absent cerebellum due to the downward The direct signs of spina bifida aperta include displacement through the foramen magnum.11,23,24 visualizing the bone defect and the sac protrusion A smaller head size, with a BPD or head (meningocele or myelomeningocele) (Figure 2). circumference below the 5th percentile, also FIGURE 1. a) Sagittal section, b) axial section, c) coronal section, and d) 3D reconstruction of a normal spine at 20 weeks of gestation Update on prenatal diagnosis and fetal surgery for myelomeningocele / e217 tends to normalize towards the third trimester,11 difficult.26 Therefore, intracranial indirect signs whereas ventriculomegaly (atrium > 10 mm) have been described. tends to progress throughout gestation, both in 2.b. Assessment of intracranial signs: fetuses receiving routine treatment and those while measuring nuchal translucency (NT), undergoing prenatal surgery.11,25 it is possible to assess whether the posterior fossa is normal (Figure 4). Our group recently 2. First-trimester ultrasound published a bibliographic review of spina bifida 2.a. Direct spinal assessment: although it is aperta detection in the first trimester, which possible to make a prenatal diagnosis based on provided details on the multiple intracranial direct visualization at 11-14 weeks, it is extremely indirect signs described, both in mid-sagittal and FIGURE 2. Direct signs of spina bifida aperta. a) Sagittal section and b) axial section showing a spinal defect through which the meningeal sac protrudes (arrows). c) Coronal section showing the separation of lateral processes of lumbar vertebrae FIGURE 3. a) Transverse section of the cephalic pole showing the posterior fossa of a normal fetus at 21 weeks of gestation: note the skull ovoid shape, the anterior complex made up of the anterior horns of the lateral ventricles and the cavum septum pellucidum (CSP) and, in the posterior fossa, the butterfly-shaped cerebellum and the presence of the cisterna magna. b) Twenty-week fetus with lumbosacral spina bifida aperta: ventriculomegaly (*) and concave frontal bone (thin arrows) shaping the skull in a particular manner (lemon sign). c) Image of posterior fossa of a 20-week fetus with myelomeningocele: obliteration of the cisterna magna caused by an abnormal cerebellum position and shape, showing posterior convexity (thick arrows), known as the banana sign. e218 / Arch Argent Pediatr 2021;119(3):e215-e228 / Review axial sections.26 The assessment of the posterior of brain structures.37,38 fossa may detect abnormalities such as reduced These signs have a variable performance or absent intracranial translucency (or fetal across studies and among observers.26 However, fourth ventricle)17,27 or cisterna magna,17,27,28 or using the same mid-sagittal section of the NT an abnormal relationship between the brainstem and while examining the posterior fossa “at and the distance between the brainstem and first sight,” it may be possible to detect most the occipital bone (Figure 5). This space may myelomeningocele cases.24,26 be analyzed based on measurements or by simply looking at the 4 echogenic lines defining PRENATAL DIAGNOSTIC EVALUATION the 3 hypoechoic spaces.26-27,29-31 Abnormalities OF MYELOMENINGOCELE in axial sections include observation of the If myelomeningocele is suspected in the “lemon sign;”27,32 reduced BPD33,34 and its prenatal
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