Anatomy and spontaneous closure of the ductus arteriosus

The ductus arteriosus and foramen ovale were described by Galen without understanding their functions. His beliefs in soul localization and spiritization within the left ventricle established religious pneumatology which became a theological need in the Middle Ages. Pulmonary transit was recognized by Servetus and Colombo after the Reformation around 1550. This prompted Harvey’s full understanding of the fetal circulation. Botallo did not describe the ductus arteriosus, but in 1564 redescribed the foramen ovale, making his way into the Nomina Anatomica by mistake. Most authors of the 19th and 20th centuries believed ductal patency to be passive, and postnatal closure to be an active process, explained by mechanical theories. After the discovery of prostaglandins by Bergstrom and Vane, Coceani proved that ductal patency is maintained by the relaxant action of prostaglandins.

Comparison of Follow-Up Length-Matched Single-Center Myelomeningocele Postnatal Closure Cohort to the Management of Myelomeningocele Study (MOMS) Trial Results

<b><i>Objective:</i></b> We sought to compare our large single-institution cohort of postnatal myelomeningocele closure to the 2 arms of the Management of Myelomeningocele Study (MOMS) trial at the designated trial time points, as well as assess outcomes at long-term follow-up among our postnatal cohort. <b><i>Methods:</i></b> A single-institutional retrospective review of myelomeningocele cases presenting from 1995 to 2015 at Children’s Hospital of Pittsburgh was performed. We compared outcomes at 12 and 30 months to both arms of the MOMS trial and compared our cohort’s outcomes at those designated time points to our long-term outcomes. Univariate statistical analysis was performed as appropriate. <b><i>Results:</i></b> One-hundred sixty-three patients were included in this study. All patients had at least 2-year follow-up, with a mean follow-up of 10 years (range 2–20 years). There was no difference in the overall distribution of anatomic level of defect. Compared to our cohort, the prenatal cohort had a higher rate of tethering at 12 months of age, 8 versus 1.8%. Conversely, the Chiari II decompression rate was higher in our cohort (10.4 vs. 1.0%). At 30 months, the prenatal cohort had a higher rate of independent ambulation, but our cohort demonstrated the highest rate of ambulation with or without assistive devices among the 3 groups. When comparing our cohort at these early time points to our long-term follow-up data, our cohort’s ambulatory function decreased from 84 to 66%, and the rate of detethering surgery increased almost 10-fold. <b><i>Conclusions:</i></b> This study demonstrated that overall ambulation and anatomic-functional level were significantly better among our large postnatal cohort, as well as having significantly fewer complications to both fetus and mother, when compared to the postnatal cohort of the MOMS trial. Our finding that ambulatory ability declined significantly with age in this patient population is worrisome for the long-term outcomes of the MOMS cohorts, especially given the high rates of cord tethering at early ages within the prenatal cohort. These findings suggest that the perceived benefits of prenatal closure over postnatal closure may not be as substantial as presented in the original trial, with the durability of results still remaining a concern.

Pediatric neurosurgeons’ views regarding prenatal surgery for myelomeningocele and the management of hydrocephalus: a national survey

OBJECTIVEThe Management of Myelomeningocele Study (MOMS) compared prenatal with postnatal surgery for myelomeningocele (MMC). The present study sought to determine how MOMS influenced the clinical recommendations of pediatric neurosurgeons, how surgeons’ risk tolerance affected their views, how their views compare to those of their colleagues in other specialties, and how their management of hydrocephalus compares to the guidelines used in the MOMS trial.METHODSA cross-sectional survey was sent to all 154 pediatric neurosurgeons in the American Society of Pediatric Neurosurgeons. The effect of surgeons’ risk tolerance on opinions and counseling of prenatal closure was determined by using ordered logistic regression.RESULTSCompared to postnatal closure, 71% of responding pediatric neurosurgeons viewed prenatal closure as either “very favorable” or “somewhat favorable,” and 51% reported being more likely to recommend prenatal surgery in light of MOMS. Compared to pediatric surgeons, neonatologists, and maternal-fetal medicine specialists, pediatric neurosurgeons viewed prenatal MMC repair less favorably (p < 0.001). Responders who believed the surgical risks were high were less likely to view prenatal surgery favorably and were also less likely to recommend prenatal surgery (p < 0.001). The management of hydrocephalus was variable, with 60% of responders using endoscopic third ventriculostomy in addition to ventriculoperitoneal shunts.CONCLUSIONSThe majority of pediatric neurosurgeons have a favorable view of prenatal surgery for MMC following MOMS, although less so than in other specialties. The reported acceptability of surgical risks was strongly predictive of prenatal counseling. Variation in the management of hydrocephalus may impact outcomes following prenatal closure.

Detailed Analysis of Hydrocephalus and Hindbrain Herniation After Prenatal and Postnatal Myelomeningocele Closure: Report From a Single Institution

BACKGROUND The Management of Myelomeningocele Study (MOMS) demonstrated that fetal myelomeningocele (fMMC) closure results in improved hydrocephalus and hindbrain herniation when compared to postnatal closure. OBJECTIVE To report on the outcomes of a single institution's experience in the post-MOMS era, with regard to hydrocephalus absence and hindbrain herniation resolution. METHODS A single-center retrospective study of a subset of post-MOMS patients who underwent fetal/postnatal myelomeningocele closure was performed. Primary outcomes included cerebrospinal fluid (CSF) diversion status and hindbrain herniation resolution. Families were contacted via telephone for outcome information if care was transitioned to outside institutions. Univariate/multivariable analyses were performed using several prenatal and postnatal variables. RESULTS From January 2011 to May 2016, data were reviewed from families of 62 postnatal and 119 fMMC closure patients. In the postnatal group, 80.6% required CSF diversion compared to 38.7% fetal cases (P &lt; .01). Hindbrain herniation resolution occurred in 81.5% fetal repairs compared to 32.6% postnatal (P &lt; .01). In the fetal group, fetal/premature neonatal demise occurred in 6/119 (5.0%) patients. There was a 42.0% decrease (95% CI –55.2 to –28.8) and 48.9% increase (95% CI 33.7 to 64.1) in risk difference for CSF diversion and hindbrain herniation resolution, respectively, in the fetal group. On univariate analysis for both groups, prenatal atrial diameter, frontal–occipital horn ratio, and hindbrain herniation resolution were significantly associated with the absence of clinical hydrocephalus. The treatment of hydrocephalus was significantly delayed in the fetal group compared to the postnatal group (10 mo vs 13.8 d). CONCLUSION This study demonstrates the benefits of fMMC closure with regard to CSF dynamics.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Incidence of Tethered Cord Syndrome in Infants With Myelomeningocele With Prenatal Versus Postnatal Repair

BACKGROUND The incidence of spina bifida (SB) is higher in the developing world as compared to the United States because of folic acid deficiency during pregnancy. Advances in technology have made prenatal repair of myelomeningocele (MM) possible. OBJECTIVE The objective of this guideline was to determine if there is a difference in the rate of development of tethered cord syndrome (TCS) in infants who had prenatal closure compared to infants who had MM repair after birth. METHODS The Guidelines Task Force developed search terms and strategies to search PubMed and Embase for the relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used. Full text articles were reviewed and, when appropriate, included as evidence. RESULTS A total of 261 abstracts were reviewed. Fifty-four full-text articles were selected for further analysis. Three studies met inclusion criteria. CONCLUSION There was Class II evidence from 1 study and Class III evidence from another 2 studies demonstrating that TCS develops in infants with prenatal MM closure at an equal or higher rate than with postnatal closure. There was an increased risk of development of inclusion cysts in infants who underwent in utero closure. Continued surveillance for TCS and/or the development of inclusion cysts in children with prenatal and postnatal closure of MM is indicated (Level II). Differences between prenatal and postnatal repair with respect to the development of TCS and/or inclusion cysts should be considered alongside other relevant maternal and fetal outcomes when deciding upon a preferred method for MM closure. The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-6.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Management of Patients With Myelomeningocele: Whether Prenatal or Postnatal Closure Affects Future Ambulatory Status

BACKGROUND Myelomeningocele (MM) is an open neural tube defect treated by pediatric neurosurgeons with prenatal or postnatal closure. OBJECTIVE The objective of this systematic review was to answer the question: What is the evidence for the effectiveness of prenatal vs postnatal closure of MM regarding short and long-term ambulatory status? Treatment recommendations were provided based on the available evidence. METHODS The National Library of Medicine PubMed database and Embase were queried using MeSH headings and keywords relevant to ambulatory status after prenatal or postnatal closure of MM. Abstracts were reviewed to identify which studies met the inclusion criteria. An evidence table was assembled summarizing the studies and the quality of evidence (Classes I-III). Based on the quality of the literature, a recommendation was rendered (Level I, II, or III). RESULTS One randomized controlled trial (Class II) and 3 retrospective cohort studies (Class III) were included as evidence. Initial ambulatory status depended on anatomic level of the neural tube defect. In the short term, prenatal closure may improve ambulatory status compared to postnatal closure. Spinal cord tethering or dermoid inclusion cyst has been associated with neurologic deterioration in infants closed in utero and after birth. Ambulation may cease in both groups over time. No long-term studies evaluated whether there is a difference in the ability to ambulate upon reaching adulthood. CONCLUSION Prenatal closure of MM may improve ambulatory status in the short term (Level II). Spinal cord tethering in both groups caused deterioration in the ability to walk. Evaluation and treatment of spinal cord tethering may help maintain ambulatory status (Level III). No studies evaluate whether prenatal or postnatal repair provides improved ability to ambulate upon reaching adulthood. The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-3.

Intrauterine closure of myelomeningocele is associated with superior long-term quality of life than postnatal closure: a single-center study

OBJECTIVEThe Management of Myelomeningocele Study (MOMS) established several important benefits of myelomeningocele fetal closure, including decreased need for shunting at 30 months. However, the effects of fetal closure on long-term quality of life (QOL) have not been studied. In this study, the authors aimed to analyze the differences in long-term QOL between children treated with intrauterine repair and those treated with postnatal repair.METHODSCaregivers of children treated with either intrauterine or postnatal closure at a tertiary acute care hospital between 1997 and 2003 were contacted to participate. The Pediatric Quality of Life Inventory (PedsQL 4.0) and a surgical history questionnaire were administered over the phone. Responses to the QOL survey were reverse scored and linearly transformed to a 0–100 scale, with a higher score indicating better QOL. The Mann-Whitney U-test was used to analyze differences in means.RESULTSSeventy-four children had MMC repair between 1997 and 2003. Twenty-three (31%) of the patients’ families responded to the PedsQL 4.0 questionnaire. Of these 23 children, 11 had intrauterine closure and 12 had postnatal closure. The intrauterine group did not differ in age (median [IQR] 17 years [14–17 years] vs 15 years [14–19 years], p = 0.926), sex (27.3% vs 41.7% male, p = 0.469), or lesion level (p = 0.199) from the postnatal group. Fewer patients in the intrauterine group underwent neurosurgical procedures than those in the postnatal group (55.6% vs 100%, p = 0.018). However, of the children receiving neurosurgical procedures, there was no difference in the number of procedures between the intrauterine and postnatal groups (median [IQR] 4 [2–10.5] vs 2.5 [1.75–6.25], p = 0.458). There was no difference in the percentage of children receiving nonneurosurgical procedures between the two groups (100% vs 100%, p > 0.99). Children who underwent intrauterine closure had significantly higher psychosocial health (median [IQR] 70.0 [56.7–83.3] vs 55.0 [42.1–60.0], p = 0.015) as well as total QOL (median [IQR] 56.5 [55.4–81.5] vs 49.5 [32.9–59.0], p = 0.019) than children with postnatal closure. Physical health was not significantly different between the two groups (median [IQR] 62.5 [37.5–78.1] vs 39.1 [18.8–59.4], p = 0.108).CONCLUSIONSRelative to postnatal closure, children who underwent intrauterine closure of MMC demonstrated better long-term QOL as measured by psychosocial and overall QOL metrics. Given that not all medical and socioeconomic confounders were adjusted for due to the low sample size, validation of these results in a larger population and across multiple centers is needed.

Fetal Myelomeningocele Closure: Technical Considerations

Myelomeningocele (MMC) is one of the most common serious congenital malformations. Typically this condition has been treated with closure of the MMC defect shortly after birth. In general, surgery for MMC aims to provide a multilayered closure to provide protection to the neural elements, prevent leakage of spinal fluid and reduce infection risks. A randomized controlled trial, the Management of Myelomeningocele Study (MOMS), has shown that closure during the fetal period can be performed relatively safely and can result in significant benefit to the child. Whereas the surgical technique of prenatal closure of an MMC defect is similar to a postnatal closure, there are some important technical differences. The goal of this paper is to describe the technique of fetal closure of MMC defects, highlight the unique steps that are needed for this surgery and delineate some potential pitfalls.