Sleep Related Breathing Disorders in Infants with Spina Bifida Repaired Prenatally and Postnatally

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Stark, Kathryn A. Smith, Rachel Y. Wang, Thomas G. Keens, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3390333/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Apr, 2024 Read the published version in Journal of Clinical Sleep Medicine → Version 1 posted You are reading this latest preprint version Abstract Purpose : Recent advances in prenatal repair of myelomeningocele (MMC) have improved outcomes involving different organ systems. There is limited data on respiratory outcomes following prenatal surgical repair. We hypothesize there is no difference in respiratory outcomes between spina bifida (SB) patients who have undergone prenatal versus postnatal repair. Methods: Retrospective study of 46 infants <1 year with SB seen at Children's Hospital Los Angeles from 2004-2022. Demographic data, timing of closure, neonatal course, Chiari II malformation (CIIM), ventriculoperitoneal shunt (VPS), polysomnography (PSG) results, and need for supplemental oxygen were collected. Unpaired t test and Chi-square Test were used to compare results between groups. Results : 31/46 had prenatal repair of MMC; average age at repair was 27 weeks post-conception (PCA). Average age at postnatal repair was 37 PCA. There was no difference in age at PSG. There was no difference in CIIM presence (p=0.61). 60% of patients with postnatal repair and 23% in the prenatal group underwent VPS placement (p=0.01). There was no difference in PSG findings between the two groups: CAI (p=0.11), OAHI (p=0.64), average SpO 2 baseline (p=0.91), average SpO 2 nadir (p=0.17), average PETCO 2 baseline (p=0.87), average PETCO2 maximum (p=0.54). There were no significant differences in the proportion of patients on supplemental O 2 (p=0.25), CSA or OSA between groups. Conclusions: Patients with SB who’ve undergone closure of defect have persistent central apneas, obstructive apneas, and significant hypoxemia. There were no differences in the frequency or severity of sleep-disordered breathing in those with prenatal repair versus postnatal repair. Spina Bifida Sleep-disordered Breathing Polysomnography Surgery What Is Known There is a high prevalence of sleep related breathing disorders in patients with spina bifida. Prenatal surgery has improved outcomes involving mobility and need for VP shunt. What Is New Following prenatal closure of open neural tube defect, infants with spina bifida may have persistent central and obstructive apneas and significant hypoxemia. The timing of closure does not affect the presence and severity of the sleep related breathing disorder. Introduction Spina bifida is a result of failure of fusion of the caudal region of the neural tube during early development resulting in an open spinal canal, with myelomeningocele being the most severe form. Postnatal repair of the neural tube defect, with or without VP shunt placement, is usually done within 48 hours of birth to mitigate associated morbidity [ 1 ]. Prenatal correction of the neural tube defect, typically performed between 26–27 weeks gestation, has become increasingly utilized in this patient population due to improved motor outcomes [ 2 , 3 ], decreased need for CSF diversion treatment of hydrocephalus [ 2 – 4 ], as well as reversal of hindbrain herniation. Sleep related breathing disorders (SRBD) are highly prevalent in patients with myelomeningocele with up to 81% involvement in a cohort who had undergone screening polysomnography [ 5 ]. These SRBD are manifested as obstructive sleep apnea, central sleep apnea, periodic breathing, hypoxemia, and sleep-related hypoventilation [ 4 , 6 – 11 ]. In a study of 20 infants (5 with prenatal repair and 15 with postnatal repair), Shellhaas et al found no difference in apnea hypopnea index between newborns who had prenatal and postnatal repairs [ 12 ]. The primary aim of our study was to describe the prevalence and presentation of SRBD in a large cohort of infants who have undergone repair of their neural tube defects. Specifically, we aimed to compare the polysomnography parameters in those who have had repairs performed prenatally versus postnatally. We hypothesize that there is no difference in the persistence of apneas and hypoxemia in those with prenatal repair compared to those with postnatal repair during the first year of life. Materials and Methods We performed a retrospective chart review of 48 patients with spina bifida seen at Children’s Hospital Los Angeles from 2004 to 2022. Patients with a diagnosis of myelomeningocele and myeloschisis were included if they had a documented polysomnography before 1 year of age. The following data were collected: demographic, medical and surgical history, timing of closure of neural tube defect, neonatal course, and polysomnography (PSG) results. All polysomnograms were performed as part of clinical care. The studies were reviewed and interpreted by physicians board-certified in sleep medicine using the most current American Academy of Sleep Medicine criteria (Version 2.5, 2.6) at the time of the study [ 13 , 14 ]. The following definitions were used to score respiratory events: 1) obstructive apnea as absence or decrease in flow by ≥ 90% for at least 2 breaths associated with respiratory effort; 2) central apnea as absence or decrease in flow by ≥ 90% for at least 20 seconds or breaths with absent respiratory effort with ≥ 3% oxygen desaturation, arousal, or heart rate < 60 beats per minute for 15 seconds; 3) obstructive hypopnea as drop in flow by ≥ 30% in the presence of with snoring, increased inspiratory flattening of the nasal pressure or paradoxical breathing and associated with ≥ 3% oxygen desaturation or arousal; 4) central hypopneas as drop in flow by ≥ 30% in the absence of with snoring, increased inspiratory flattening of the nasal pressure or paradoxical breathing and associated with ≥ 3% oxygen desaturation or arousal; and 5) periodic breathing as ≥ 3 central apneas lasting at least 3 seconds separated by ≤ 20 seconds of normal breathing [ 13 , 14 ]. The recommended normative data are listed in Table 1 . Obstructive apnea severity was classified as mild (1.5 to 5/h), moderate (5–10/h) and severe (> 10/h) [ 15 – 17 ]. After 2019, for infants who had their polysomnogram at ≤ 44 weeks post conceptional age, the total percentage of time spent in obstruction was used to classify the severity of OSA as follows: 5% of TST (severe) [ 18 , 19 ]. Table 1 Recommended polysomnography normative data [ 15 – 17 ] Central apnea index (event/h) < 5/h Obstructive apnea index (event/h) < 1/h Obstructive apnea-hypopnea index (event/h) < 1.5/h Time with SpO2 < 90% (% sleep time) 0 SpO2 nadir (%) 92% Unpaired t tests (equal variances) and Chi-square tests were used to compare results between groups. This study was approved by Institutional Review Board of Children’s Hospital Los Angeles. Results Forty-six infants (under 1 year of age) were studied, 57% female; 31 patients underwent prenatal repair and 15 had postnatal repair. Of the 31 patients with prenatal repair, 17 (55%) were female. The average gestational age at birth was 34 ± 3 weeks post-conception. Post-conceptional age (PCA) at repair was 27 weeks. The average age at PSG was 39 ± 5 weeks PCA. 25/31 (81%) had Chiari Type II Malformation and 7/31 (23%) underwent ventriculoperitoneal shunt placement before 1 year of age (Table 2 ). Table 2 Sleep parameters compared between patients repaired prenatally and patients repaired postnatally Sleep Parameter Prenatal repair (n = 31) Postnatal repair (n = 15) P value Female Gender, (% Female) 55 60 0.74 GA at Birth (weeks) 34 ± 3 (27.6–39.4) 37 ± 2 (31.5–39.5) 0.002 Age at PSG (weeks PCA) 39 ± 5 (34.4–58.4) 42 ± 6 (35.8–56.4) 0.07 Chiari Type II Malformation, % with 81 87 0.61 VP Shunt, % with 23 60 0.01 Central Sleep Apnea, % of patients 71 60 0.46 Obstructive Sleep Apnea, % of patients 97 100 0.48 Require Supplemental O 2 , % of patients 87 73 0.25 CAI, events/hr 12 ± 12 (1.6–50.9) 7 ± 4 (0.5–15.3) 0.11 OAHI, events/hr 22 ± 21(1.4-100.4) 26 ± 28 (2.7-102.5) 0.64 SpO 2 Baseline 95 ± 3 (90–99) 95 ± 2 (92–98) 0.91 SpO 2 Nadir 75 ± 9 (57–90) 79 ± 6 (67–90) 0.17 PETCO 2 Baseline 34 ± 6 (21–46) 34 ± 4 (29–39) 0.87 PETCO 2 max 45 ± 9 (31–63) 46 ± 6 (37–60) 0.54 Of the 15 patients with postnatal repair, 9 (60%) were female. The average gestational age at birth was 37 ± 2 weeks PCA. PCA at repair was 37 weeks. The average age at PSG was 42 ± 6 weeks PCA. 13/15 (87%) had Chiari Type II Malformation and 9/15 (60%) underwent ventriculoperitoneal shunt placement (Table 2 ). There was a significant difference in gestational age at birth between patients repaired prenatally and patients repaired postnatally (p = 0.002); however, there was no significant difference in post-conceptional age at which the PSGs were performed (p = 0.07). Although there was no difference in presence of Chiari Type II Malformation between the two groups (p = 0.61), a higher proportion of patients with postnatal repair required VP shunt placement than those with prenatal repair (p = 0.01) (Table 2 ). In patients repaired prenatally 22/31 (71%) were diagnosed with central sleep apnea (CSA), and 30/31 (97%) were diagnosed with obstructive sleep apnea (OSA). The central apnea index (CAI) was 12 ± 12 events per hour and the obstructive apnea hypopnea index (OAHI) was 22 ± 21 events per hour. 7/31 (23%) had P ET CO 2 max > 50 mmHg; however, none exceeded 50 mmHg for greater than 25% of sleep time. The mean baseline P ET CO 2 level was 34 ± 6 mmHg and mean maximum P ET CO 2 was 45 ± 9 mmHg. 27/31 (87%) were placed on supplemental oxygen during the sleep study. The mean baseline SpO2 on room air was 95 ± 3 percent and mean SpO2 nadir was 75 ± 9 percent (Table 2 ). Of the patients repaired postnatally, 9/15 (60%) were diagnosed with CSA and 15/15 (100%) patients were diagnosed with OSA. The mean CAI was 7 ± 4 events per hour and the mean OAHI was 26 ± 28 events per hour. 4/15 (27%) had P ET CO 2 max > 50 mmHg; however, none exceeded 50 mmHg for greater than 25% of sleep time. The mean baseline P ET CO 2 was 34 ± 4 mmHg and mean maximum P ET CO 2 was 47 ± 6 mmHg. 11/15 (73%) were placed on supplemental oxygen during the sleep study. The mean baseline oxygen saturation on room air was 95 ± 2 percent, and mean oxygen nadir was 79 ± 6 percent. There were no statistically significant differences in the sleep parameters between patients repaired prenatally and patients repaired postnatally, as seen in Table 2 . Twenty eight of 46 infants (22 prenatal and 6 postnatal) who had sleep studies at ≤ 44 weeks PCA were analyzed using Daftary criteria for severity of OSA [ 18 , 19 ]. 22/28 (79%) had moderate to severe and only 6/28 (21%) had normal obstruction. There was no significant difference in OSA severity between those repaired prenatally and patients repaired postnatally (p = 0.75) using these criteria. Discussion The results of our study show that patients with spina bifida who have undergone prenatal closure of their neural tube defects have SRBD with central and obstructive apneas and significant hypoxemia. There were no significant differences in the presentation of SRBD between patients repaired prenatally and postnatally, suggesting that the timing of closure of the defect did not affect the presence and severity of the SRBD. In a normally developing infant, the caudal neuropore usually closes during the third week of gestation. The prevailing theory for the development of the Chiari II malformation in myelomeningocele is due to in utero CSF leakage through the open neural tube defect. This alters the growth and morphology of the fetal brain as a result from caudal traction on the brainstem, herniation of the cerebellar vermis and medulla into the spinal canal, under development of the posterior fossa and a lack of distension in the early cerebral ventricular system. The hindbrain herniation obstructs CSF flow throughout the lower brain stem, leading to ventricular dilation hydrocephalus, syringomyelia, as well as brainstem and upper spinal cord dysfunction [ 20 , 21 ]. The hindbrain herniation aspect of the Chiari II malformation may be related to the pathophysiology of CSA in myelomeningocele, but there remains debate if this is secondary to an abnormal anatomical location of the brainstem or intrinsic process related to brainstem dysplasia [ 22 ]. Furthermore, several post-MOMs Trial groups have published mixed results on the changes in brainstem function after prenatal myelomeningocele surgery [ 4 , 11 ]. We observed no difference in CSA between our pre and postnatal patients and suggest the timing of myelomeningocele repair may not influence the prevalence of CSA when PSG is completed at approximately 40 weeks PCA. Although this could be attributed to the high incidence of Chiari II malformations amongst our population, we acknowledge our data did not contain the granularity to distinguish between hindbrain herniation reversal after prenatal surgery from other common features of Chiari II malformation (for example, a beaked tectum or a large massa intermedia) that are unrelated to SRBD. Further studies are needed to determine if a relationship between hindbrain herniation reversal and CSA exists. In our cohort, OSA was present in all except for one patient and the proportion of patients with OSA was nearly equal in the prenatal and postnatal groups (p = 0.94). This highlights the high prevalence of OSA in infants with spina bifida. Using the Daftary criteria [ 18 , 19 ], 22 of 28 (79%) of patients who were ≤ 44 weeks PCA who had undergone prenatal repair had moderate to severe obstruction. Our findings differ from Waters et al where 20% of their patient population had moderate to severe OSA [ 9 ]. Thus, although a proportion of these infants will have mild OSA or findings considered normal for age, our study supports the need for expectant monitoring with polysomnography. 38/46 (83%) of infants in our cohort required supplemental O 2 during the sleep study. There was no significant difference in the proportion of patients placed on supplemental oxygen between those repaired prenatally and patients repaired postnatally. Our findings differ from Shelhaas et al, where only 4/20 (20%) patients were given supplemental oxygen but are similar to Patel et al, in which 34/42 (80%) of their patients were placed on supplemental oxygen [ 5 , 12 ]. Previous studies show that patients with myelomeningocele have abnormal central and peripheral chemoreceptor function indicating that these infants may not be able to increase their ventilation in response to hypoxia or hypercapnia [ 23 – 25 ]. The inability to respond to hypoxic stimuli exposes these infants to potential detrimental physiologic consequences of hypoxemia; supplemental oxygen can reduce this risk. In addition, supplemental oxygen in infants with OSA has been shown to decrease frequency of obstructive events and improved oxygenation without adverse effect on alveolar ventilation [ 26 ]. 7/31 (23%) of prenatally repaired patients and 9/15 (60%) postnatally repaired patients underwent VP shunt placement (p = 0.01), which is consistent with previous findings that prenatal surgery decreases the need for VP shunt placement [ 2 , 3 ]. However, despite the difference in VP shunt placement, there was no difference in sleep disordered breathing between the two groups. 5/7 (71%) of prenatally repaired patients had PSG after their shunt placement; and 7/9 (77%) of postnatally repaired patients had PSG after their shunt placement. The results of our study show that patients with spina bifida who have undergone prenatal closure of their neural tube defects have central and obstructive apneas and significant hypoxemia equivalent to those who undergo repair after birth. Our findings demonstrate that these differences in the timing of closure of the defect does not affect the presence or severity of the sleep related breathing disorders. The presence of SRBD indicates need for screening and surveillance after birth. Polysomnography remains the most useful tool in identifying and classifying the sleep related breathing disorders and can guide the need and utility of supplemental oxygen as a treatment intervention to optimize the outcome of infants with spina bifida. Our study suggests that infants born with spina bifida should undergo polysomnography, or other equivalent continuous monitoring, prior to discharge to home. Abbreviations CAI: Central apnea index CIIM: Chiari II Malformation MMC: Myelomeningocele MOMs: Management of Myelomeningocele OAHI: Obstructive apnea hypopnea index PCA: post-conceptional age PSG: polysomnography SB: Spina Bifida SRBD: Sleep related breathing Disorders VPS: ventriculoperitoneal shunt Declarations Statements and Declarations The authors have no relevant financial or non-financial interests to disclose. Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Author Contributions: Study conceptualization and design were performed by Katherine Stark, Thomas Keens, Sally Ward, and Iris Perez. Data Collection was performed by Katherine Stark, Kathryn Smith, Alexander Van Speybroeck, and Iris Perez. Analysis of data was performed by Katherine Stark, Kathryn Smith, Rachel Wang, Thomas Keens, Sally Ward, and Iris Perez. Ramen Chmait and Jason Chu critically reviewed the manuscript for important intellectual content. The first draft of the manuscript was written by Katherine Stark, Rachel Wang, Jason Chu, and Iris Perez and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethics Approval: Study was approved by CHLA Institutional Review Board. Consent to Participate: This is an observational study. The CHLA Institutional Review Board has confirmed that no consent to participate is required. References Mitchell LE, Mitchell LE, Adzick NS, et al (2017) Spina bifida Spina bifida. Lancet 6736(March). Adzick NS, Thom EA, Spong CY, et al (2011) A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele. N Engl J Med 364(11). doi: 10.1056/nejmoa1014379 Lapa DA, Chmait RH, Gielchinsky Y, et al (2021) Percutaneous fetoscopic spina bifida repair: effect on ambulation and need for postnatal cerebrospinal fluid diversion and bladder catheterization. Ultrasound Obstet Gynecol 58(4). doi: 10.1002/uog.23658 Grabb, PA, Vlastos, EJ, Lundy, PA, & Partington, MB (2022). Significant brainstem dysfunction in neonates with myelomeningoceles: a comparison of prenatal versus postnatal closure. J Neurosurg Pediatr 29 (5), 497–503. https://doi.org/10.3171/2021.12.PEDS21430 Patel DM, Rocque BG, Hopson B, et al (2015) Sleep-disordered breathing in patients with myelomeningocele. J Neurosurg Pediatr 16(1). doi: 10.3171/2014.11.PEDS14314 Alsaadi MM, Iqbal SM, Elgamal EA, Gozal D (2012) Sleep-disordered breathing in children with Chiari malformation type II and myelomeningocele. Pediatr Int. doi: 10.1111/j.1442-200X.2012.03660.x Bendel-Stenzel E, Linabery AM, Jorgenson A, Ferrara TB, Spaulding AB (2019) Sleep-disordered breathing: an under-recognized problem in infants with myelomeningocele defects regardless of timing of repair. J Perinatol. doi: 10.1038/s41372-019-0433-7 Shellhaas RA, Kenia P V., Hassan F, Barks JDE, Kaciroti N, Chervin RD (2018) Sleep-Disordered Breathing among Newborns with Myelomeningocele. J Pediatr. doi: 10.1016/j.jpeds.2017.10.070 Waters KA, Forbes P, Morielli A, et al (1998) Sleep-disordered breathing in children with myelomeningocele. J Pediatr. doi: 10.1016/S0022-3476(98)70359-2 Davidson Ward SL, Jacobs RA, Gates EP, Hart LD, Keens TG (1986) Abnormal ventilatory patterns during sleep in infants with myelomeningocele. J Pediatr 109(4). doi: 10.1016/S0022-3476(86)80226-8 Fraga MV, Giaccone A, Adzick NS (2018) Respiratory morbidities in late preterm and term infants with myelomeningocele. J Perinatol 38, 1542–1547. https://doi.org/10.1038/s41372-018-0210-z Shellhaas RA, Kenia P V., Hassan F, Barks JDE, Kaciroti N, Chervin RD (2018) Sleep-Disordered Breathing among Newborns with Myelomeningocele. J Pediatr 194. doi: 10.1016/j.jpeds.2017.10.070 Berry R, Albertario C, Harding S (2018) The AASM Manual for the Scoring of Sleep and Associated Events, Rules, Terminology and Technical Specifications. Am Acad Sleep Med Version 2.5. Berry R, Quan S, Abreu A (2020) Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Am Acad Sleep Med. Version 2.6. Katz ES, Mitchell RB, D’Ambrosio CM (2012) Obstructive sleep apnea in infants. Am J Respir Crit Care Med. 185(8). doi: 10.1164/rccm.201108-1455CI Witmans MB, Keens TG, Davidson Ward SL, Marcus CL (2003) Obstructive Hypopneas in Children and Adolescents: Normal Values [3]. Am J Respir Crit Care Med. 168(12). doi: 10.1164/ajrccm.168.12.954 Marcus CL, Omlin KJ, Basinki DJ, et al (1992) Normal polysomnographic values for children and adolescents. Am Rev Respir Dis. 146(5). doi: 10.1164/ajrccm/146.5_Pt_1.1235 Daftary AS, Jalou HE, Shively L, Slaven JE, Davis SD (2019) Polysomnography reference values in healthy newborns. J Clin Sleep Med. 15(3). doi: 10.5664/jcsm.7670 Daftary, A. S., Shively, L., Slaven, J. E., & Jalou, H. E. (2019) Can estimated time in airway obstruction be a useful measure for infant obstructive sleep apnea? Int J Pediatr Otorhinolaryngol 124, 208–209. doi:1016/j.ijporl.2019.06.011 McLone DG, Knepper PA (1989) The cause of Chiari II malformation: A unified theory. Pediatr Neurosci 15(1). doi: 10.1159/000120432 Iskandar BJ, Finnell RH (2022) Spina Bifida. N Engl J Med. 387(5):444–450. doi: 10.1056/NEJMra2116032 Gilbert JN, Jones KL, Rorke LB, Chernoff GF, James HE (1986) Central nervous system anomalies associated with meningomyelocele, hydrocephalus, and the Arnold-Chiari malformation: reappraisal of theories regarding the pathogenesis of posterior neural tube closure defects. Neurosurgery 18(5):559–564. doi: 10.1227/00006123-198605000-00008 Gozal D, Arens R, Omlin KJ, Jacobs RA, Keens TG (1995) Peripheral chemoreceptor function in children with myelomeningocele and Arnold-Chiari malformation type 2. Chest 108(2). doi: 10.1378/chest.108.2.425 Swaminathan S, Paton JY, Davidson Ward SL, Jacobs RA, Sargent CW, Keens TG (1989) Abnormal control of ventilation in adolescents with myelodysplasia. J Pediatr 115(6). doi: 10.1016/S0022-3476(89)80739-5 Ward SL, Nickerson BG, van der Hal A, Rodriguez AM, Jacobs RA, Keens TG (1986) Absent hypoxic and hypercapneic arousal responses in children with myelomeningocele and apnea. Pediatrics 78(1). doi: 10.1542/peds.79.2.313b Brockbank J, Leon-Astudillo C, Che D, et al (2019) Supplemental oxygen for treatment of infants with obstructive sleep apnea. J Clin Sleep Med 15(8). doi: 10.5664/jcsm.7802 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 24 Apr, 2024 Read the published version in Journal of Clinical Sleep Medicine → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Keens","email":"","orcid":"","institution":"Children’s Hospital Los Angeles","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"G.","lastName":"Keens","suffix":""},{"id":236296162,"identity":"1d95310f-43c7-4bc3-ae20-992aa41384fa","order_by":4,"name":"Alexander Speybroeck","email":"","orcid":"","institution":"Children’s Hospital Los Angeles","correspondingAuthor":false,"prefix":"","firstName":"Alexander","middleName":"","lastName":"Speybroeck","suffix":""},{"id":236296163,"identity":"9a13d0ec-4ab8-49df-9a97-d0469b86e3aa","order_by":5,"name":"Ramen H. Chmait","email":"","orcid":"","institution":"Keck School of Medicine of USC","correspondingAuthor":false,"prefix":"","firstName":"Ramen","middleName":"H.","lastName":"Chmait","suffix":""},{"id":236296164,"identity":"dcd14884-13aa-4a72-b894-4839353ca88f","order_by":6,"name":"Sally L. Davidson Ward","email":"","orcid":"","institution":"Children’s Hospital Los Angeles","correspondingAuthor":false,"prefix":"","firstName":"Sally","middleName":"L. Davidson","lastName":"Ward","suffix":""},{"id":236296165,"identity":"0b8da987-20b7-4eb1-b06e-d8573dc77994","order_by":7,"name":"Jason Chu","email":"","orcid":"","institution":"Keck School of Medicine of USC","correspondingAuthor":false,"prefix":"","firstName":"Jason","middleName":"","lastName":"Chu","suffix":""},{"id":236296166,"identity":"1e119fcb-9731-424a-bd99-0bdd176aac76","order_by":8,"name":"Iris A. Perez","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYBACNigtxyDB3AATNCBKizGDBCORWmAgsYFoLXzsZw8+rqioS++f3dj4gbGtTp6BvXmbBF6H8eQlG545w5Y7487BZgnGtsOGDTzHyvBrYcgxk2xs48ndIAFyW9uBBAaJHDP8WvjfmP9s/CeRbiCR2PwD6LAEBvk3BLQAzWRsbDBIAGppA9rCDLSFh5CWd8mSDccSDGfcSGyzSDh32LCNJ63YAp8W+f7cgx8baurk+WckH77xoQzIYD+88QY+LQwMPEjsBAZE5BKpZRSMglEwCkYBNgAAcj9A+9vN3/kAAAAASUVORK5CYII=","orcid":"","institution":"Children’s Hospital Los Angeles","correspondingAuthor":true,"prefix":"","firstName":"Iris","middleName":"A.","lastName":"Perez","suffix":""}],"badges":[],"createdAt":"2023-09-27 01:14:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3390333/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3390333/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.5664/jcsm.11174","type":"published","date":"2024-04-25T00:36:40+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":55337304,"identity":"12617367-22d9-4bef-a98d-06c94cb3c70b","added_by":"auto","created_at":"2024-04-26 00:36:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":252674,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3390333/v1/0ff4850f-fa3a-455b-9e32-d54f9e319a25.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sleep Related Breathing Disorders in Infants with Spina Bifida Repaired Prenatally and Postnatally","fulltext":[{"header":"What Is Known ","content":"\u003cul\u003e\n \u003cli\u003eThere is a high prevalence of sleep related breathing disorders in patients with spina bifida.\u003c/li\u003e\n \u003cli\u003ePrenatal surgery has improved outcomes involving mobility and need for VP shunt.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"What Is New ","content":"\u003cul\u003e\n \u003cli\u003eFollowing prenatal closure of open neural tube defect, infants with spina bifida may have persistent central and obstructive apneas and significant hypoxemia.\u003c/li\u003e\n \u003cli\u003eThe timing of closure does not affect the presence and severity of the sleep related breathing disorder.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eSpina bifida is a result of failure of fusion of the caudal region of the neural tube during early development resulting in an open spinal canal, with myelomeningocele being the most severe form. Postnatal repair of the neural tube defect, with or without VP shunt placement, is usually done within 48 hours of birth to mitigate associated morbidity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Prenatal correction of the neural tube defect, typically performed between 26\u0026ndash;27 weeks gestation, has become increasingly utilized in this patient population due to improved motor outcomes [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], decreased need for CSF diversion treatment of hydrocephalus [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], as well as reversal of hindbrain herniation.\u003c/p\u003e \u003cp\u003eSleep related breathing disorders (SRBD) are highly prevalent in patients with myelomeningocele with up to 81% involvement in a cohort who had undergone screening polysomnography [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These SRBD are manifested as obstructive sleep apnea, central sleep apnea, periodic breathing, hypoxemia, and sleep-related hypoventilation [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In a study of 20 infants (5 with prenatal repair and 15 with postnatal repair), Shellhaas et al found no difference in apnea hypopnea index between newborns who had prenatal and postnatal repairs [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe primary aim of our study was to describe the prevalence and presentation of SRBD in a large cohort of infants who have undergone repair of their neural tube defects. Specifically, we aimed to compare the polysomnography parameters in those who have had repairs performed prenatally versus postnatally. We hypothesize that there is no difference in the persistence of apneas and hypoxemia in those with prenatal repair compared to those with postnatal repair during the first year of life.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e We performed a retrospective chart review of 48 patients with spina bifida seen at Children\u0026rsquo;s Hospital Los Angeles from 2004 to 2022. Patients with a diagnosis of myelomeningocele and myeloschisis were included if they had a documented polysomnography before 1 year of age.\u003c/p\u003e \u003cp\u003eThe following data were collected: demographic, medical and surgical history, timing of closure of neural tube defect, neonatal course, and polysomnography (PSG) results. All polysomnograms were performed as part of clinical care. The studies were reviewed and interpreted by physicians board-certified in sleep medicine using the most current American Academy of Sleep Medicine criteria (Version 2.5, 2.6) at the time of the study [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe following definitions were used to score respiratory events: 1) obstructive apnea as absence or decrease in flow by \u0026ge;\u0026thinsp;90% for at least 2 breaths associated with respiratory effort; 2) central apnea as absence or decrease in flow by \u0026ge;\u0026thinsp;90% for at least 20 seconds or breaths with absent respiratory effort with \u0026ge;\u0026thinsp;3% oxygen desaturation, arousal, or heart rate\u0026thinsp;\u0026lt;\u0026thinsp;60 beats per minute for 15 seconds; 3) obstructive hypopnea as drop in flow by \u0026ge;\u0026thinsp;30% in the presence of with snoring, increased inspiratory flattening of the nasal pressure or paradoxical breathing and associated with \u0026ge;\u0026thinsp;3% oxygen desaturation or arousal; 4) central hypopneas as drop in flow by \u0026ge;\u0026thinsp;30% in the absence of with snoring, increased inspiratory flattening of the nasal pressure or paradoxical breathing and associated with \u0026ge;\u0026thinsp;3% oxygen desaturation or arousal; and 5) periodic breathing as \u0026ge;\u0026thinsp;3 central apneas lasting at least 3 seconds separated by \u0026le;\u0026thinsp;20 seconds of normal breathing [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe recommended normative data are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Obstructive apnea severity was classified as mild (1.5 to 5/h), moderate (5\u0026ndash;10/h) and severe (\u0026gt;\u0026thinsp;10/h) [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. After 2019, for infants who had their polysomnogram at \u0026le;\u0026thinsp;44 weeks post conceptional age, the total percentage of time spent in obstruction was used to classify the severity of OSA as follows: \u0026lt; 2% of TST (normal), 2\u0026ndash;5% of TST (moderate), \u0026gt;\u0026thinsp;5% of TST (severe) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRecommended polysomnography normative data [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral apnea index (event/h)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5/h\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eObstructive apnea index (event/h)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1/h\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eObstructive apnea-hypopnea index (event/h)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1.5/h\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime with SpO2\u0026thinsp;\u0026lt;\u0026thinsp;90% (% sleep time)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSpO2 nadir (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eUnpaired t tests (equal variances) and Chi-square tests were used to compare results between groups.\u003c/p\u003e \u003cp\u003eThis study was approved by Institutional Review Board of Children\u0026rsquo;s Hospital Los Angeles.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eForty-six infants (under 1 year of age) were studied, 57% female; 31 patients underwent prenatal repair and 15 had postnatal repair. Of the 31 patients with prenatal repair, 17 (55%) were female. The average gestational age at birth was 34\u0026thinsp;\u0026plusmn;\u0026thinsp;3 weeks post-conception. Post-conceptional age (PCA) at repair was 27 weeks. The average age at PSG was 39\u0026thinsp;\u0026plusmn;\u0026thinsp;5 weeks PCA. 25/31 (81%) had Chiari Type II Malformation and 7/31 (23%) underwent ventriculoperitoneal shunt placement before 1 year of age (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSleep parameters compared between patients repaired prenatally and patients repaired postnatally\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSleep Parameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrenatal repair (n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePostnatal repair (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale Gender, (% Female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGA at Birth (weeks)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34\u0026thinsp;\u0026plusmn;\u0026thinsp;3 (27.6\u0026ndash;39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37\u0026thinsp;\u0026plusmn;\u0026thinsp;2 (31.5\u0026ndash;39.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at PSG (weeks PCA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39\u0026thinsp;\u0026plusmn;\u0026thinsp;5 (34.4\u0026ndash;58.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42\u0026thinsp;\u0026plusmn;\u0026thinsp;6 (35.8\u0026ndash;56.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChiari Type II Malformation, % with\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVP Shunt, % with\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral Sleep Apnea, % of patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObstructive Sleep Apnea, % of patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRequire Supplemental O\u003csub\u003e2\u003c/sub\u003e, % of patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAI, events/hr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u0026thinsp;\u0026plusmn;\u0026thinsp;12 (1.6\u0026ndash;50.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u0026thinsp;\u0026plusmn;\u0026thinsp;4 (0.5\u0026ndash;15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOAHI, events/hr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22\u0026thinsp;\u0026plusmn;\u0026thinsp;21(1.4-100.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u0026thinsp;\u0026plusmn;\u0026thinsp;28 (2.7-102.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpO\u003csub\u003e2\u003c/sub\u003e Baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95\u0026thinsp;\u0026plusmn;\u0026thinsp;3 (90\u0026ndash;99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95\u0026thinsp;\u0026plusmn;\u0026thinsp;2 (92\u0026ndash;98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpO\u003csub\u003e2\u003c/sub\u003e Nadir\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;9 (57\u0026ndash;90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79\u0026thinsp;\u0026plusmn;\u0026thinsp;6 (67\u0026ndash;90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePETCO\u003csub\u003e2\u003c/sub\u003e Baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34\u0026thinsp;\u0026plusmn;\u0026thinsp;6 (21\u0026ndash;46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u0026thinsp;\u0026plusmn;\u0026thinsp;4 (29\u0026ndash;39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePETCO\u003csub\u003e2\u003c/sub\u003e max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;9 (31\u0026ndash;63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46\u0026thinsp;\u0026plusmn;\u0026thinsp;6 (37\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOf the 15 patients with postnatal repair, 9 (60%) were female. The average gestational age at birth was 37\u0026thinsp;\u0026plusmn;\u0026thinsp;2 weeks PCA. PCA at repair was 37 weeks. The average age at PSG was 42\u0026thinsp;\u0026plusmn;\u0026thinsp;6 weeks PCA. 13/15 (87%) had Chiari Type II Malformation and 9/15 (60%) underwent ventriculoperitoneal shunt placement (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere was a significant difference in gestational age at birth between patients repaired prenatally and patients repaired postnatally (p\u0026thinsp;=\u0026thinsp;0.002); however, there was no significant difference in post-conceptional age at which the PSGs were performed (p\u0026thinsp;=\u0026thinsp;0.07). Although there was no difference in presence of Chiari Type II Malformation between the two groups (p\u0026thinsp;=\u0026thinsp;0.61), a higher proportion of patients with postnatal repair required VP shunt placement than those with prenatal repair (p\u0026thinsp;=\u0026thinsp;0.01) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn patients repaired prenatally 22/31 (71%) were diagnosed with central sleep apnea (CSA), and 30/31 (97%) were diagnosed with obstructive sleep apnea (OSA). The central apnea index (CAI) was 12\u0026thinsp;\u0026plusmn;\u0026thinsp;12 events per hour and the obstructive apnea hypopnea index (OAHI) was 22\u0026thinsp;\u0026plusmn;\u0026thinsp;21 events per hour. 7/31 (23%) had P\u003csub\u003eET\u003c/sub\u003eCO\u003csub\u003e2\u003c/sub\u003e max\u0026thinsp;\u0026gt;\u0026thinsp;50 mmHg; however, none exceeded 50 mmHg for greater than 25% of sleep time. The mean baseline P\u003csub\u003eET\u003c/sub\u003eCO\u003csub\u003e2\u003c/sub\u003e level was 34\u0026thinsp;\u0026plusmn;\u0026thinsp;6 mmHg and mean maximum P\u003csub\u003eET\u003c/sub\u003eCO\u003csub\u003e2\u003c/sub\u003e was 45\u0026thinsp;\u0026plusmn;\u0026thinsp;9 mmHg. 27/31 (87%) were placed on supplemental oxygen during the sleep study. The mean baseline SpO2 on room air was 95\u0026thinsp;\u0026plusmn;\u0026thinsp;3 percent and mean SpO2 nadir was 75\u0026thinsp;\u0026plusmn;\u0026thinsp;9 percent (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOf the patients repaired postnatally, 9/15 (60%) were diagnosed with CSA and 15/15 (100%) patients were diagnosed with OSA. The mean CAI was 7\u0026thinsp;\u0026plusmn;\u0026thinsp;4 events per hour and the mean OAHI was 26\u0026thinsp;\u0026plusmn;\u0026thinsp;28 events per hour. 4/15 (27%) had P\u003csub\u003eET\u003c/sub\u003eCO\u003csub\u003e2\u003c/sub\u003e max\u0026thinsp;\u0026gt;\u0026thinsp;50 mmHg; however, none exceeded 50 mmHg for greater than 25% of sleep time. The mean baseline P\u003csub\u003eET\u003c/sub\u003eCO\u003csub\u003e2\u003c/sub\u003e was 34\u0026thinsp;\u0026plusmn;\u0026thinsp;4 mmHg and mean maximum P\u003csub\u003eET\u003c/sub\u003eCO\u003csub\u003e2\u003c/sub\u003e was 47\u0026thinsp;\u0026plusmn;\u0026thinsp;6 mmHg. 11/15 (73%) were placed on supplemental oxygen during the sleep study. The mean baseline oxygen saturation on room air was 95\u0026thinsp;\u0026plusmn;\u0026thinsp;2 percent, and mean oxygen nadir was 79\u0026thinsp;\u0026plusmn;\u0026thinsp;6 percent. There were no statistically significant differences in the sleep parameters between patients repaired prenatally and patients repaired postnatally, as seen in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eTwenty eight of 46 infants (22 prenatal and 6 postnatal) who had sleep studies at \u0026le;\u0026thinsp;44 weeks PCA were analyzed using Daftary criteria for severity of OSA [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. 22/28 (79%) had moderate to severe and only 6/28 (21%) had normal obstruction. There was no significant difference in OSA severity between those repaired prenatally and patients repaired postnatally (p\u0026thinsp;=\u0026thinsp;0.75) using these criteria.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of our study show that patients with spina bifida who have undergone prenatal closure of their neural tube defects have SRBD with central and obstructive apneas and significant hypoxemia. There were no significant differences in the presentation of SRBD between patients repaired prenatally and postnatally, suggesting that the timing of closure of the defect did not affect the presence and severity of the SRBD.\u003c/p\u003e \u003cp\u003eIn a normally developing infant, the caudal neuropore usually closes during the third week of gestation. The prevailing theory for the development of the Chiari II malformation in myelomeningocele is due to \u003cem\u003ein utero\u003c/em\u003e CSF leakage through the open neural tube defect. This alters the growth and morphology of the fetal brain as a result from caudal traction on the brainstem, herniation of the cerebellar vermis and medulla into the spinal canal, under development of the posterior fossa and a lack of distension in the early cerebral ventricular system. The hindbrain herniation obstructs CSF flow throughout the lower brain stem, leading to ventricular dilation hydrocephalus, syringomyelia, as well as brainstem and upper spinal cord dysfunction [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The hindbrain herniation aspect of the Chiari II malformation may be related to the pathophysiology of CSA in myelomeningocele, but there remains debate if this is secondary to an abnormal anatomical location of the brainstem or intrinsic process related to brainstem dysplasia [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Furthermore, several post-MOMs Trial groups have published mixed results on the changes in brainstem function after prenatal myelomeningocele surgery [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. We observed no difference in CSA between our pre and postnatal patients and suggest the timing of myelomeningocele repair may not influence the prevalence of CSA when PSG is completed at approximately 40 weeks PCA. Although this could be attributed to the high incidence of Chiari II malformations amongst our population, we acknowledge our data did not contain the granularity to distinguish between hindbrain herniation reversal after prenatal surgery from other common features of Chiari II malformation (for example, a beaked tectum or a large massa intermedia) that are unrelated to SRBD. Further studies are needed to determine if a relationship between hindbrain herniation reversal and CSA exists.\u003c/p\u003e \u003cp\u003eIn our cohort, OSA was present in all except for one patient and the proportion of patients with OSA was nearly equal in the prenatal and postnatal groups (p\u0026thinsp;=\u0026thinsp;0.94). This highlights the high prevalence of OSA in infants with spina bifida. Using the Daftary criteria [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], 22 of 28 (79%) of patients who were \u0026le;\u0026thinsp;44 weeks PCA who had undergone prenatal repair had moderate to severe obstruction. Our findings differ from Waters et al where 20% of their patient population had moderate to severe OSA [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Thus, although a proportion of these infants will have mild OSA or findings considered normal for age, our study supports the need for expectant monitoring with polysomnography.\u003c/p\u003e \u003cp\u003e38/46 (83%) of infants in our cohort required supplemental O\u003csub\u003e2\u003c/sub\u003e during the sleep study. There was no significant difference in the proportion of patients placed on supplemental oxygen between those repaired prenatally and patients repaired postnatally. Our findings differ from Shelhaas et al, where only 4/20 (20%) patients were given supplemental oxygen but are similar to Patel et al, in which 34/42 (80%) of their patients were placed on supplemental oxygen [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Previous studies show that patients with myelomeningocele have abnormal central and peripheral chemoreceptor function indicating that these infants may not be able to increase their ventilation in response to hypoxia or hypercapnia [\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The inability to respond to hypoxic stimuli exposes these infants to potential detrimental physiologic consequences of hypoxemia; supplemental oxygen can reduce this risk. In addition, supplemental oxygen in infants with OSA has been shown to decrease frequency of obstructive events and improved oxygenation without adverse effect on alveolar ventilation [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e7/31 (23%) of prenatally repaired patients and 9/15 (60%) postnatally repaired patients underwent VP shunt placement (p\u0026thinsp;=\u0026thinsp;0.01), which is consistent with previous findings that prenatal surgery decreases the need for VP shunt placement [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, despite the difference in VP shunt placement, there was no difference in sleep disordered breathing between the two groups. 5/7 (71%) of prenatally repaired patients had PSG after their shunt placement; and 7/9 (77%) of postnatally repaired patients had PSG after their shunt placement.\u003c/p\u003e \u003cp\u003eThe results of our study show that patients with spina bifida who have undergone prenatal closure of their neural tube defects have central and obstructive apneas and significant hypoxemia equivalent to those who undergo repair after birth. Our findings demonstrate that these differences in the timing of closure of the defect does not affect the presence or severity of the sleep related breathing disorders. The presence of SRBD indicates need for screening and surveillance after birth. Polysomnography remains the most useful tool in identifying and classifying the sleep related breathing disorders and can guide the need and utility of supplemental oxygen as a treatment intervention to optimize the outcome of infants with spina bifida. Our study suggests that infants born with spina bifida should undergo polysomnography, or other equivalent continuous monitoring, prior to discharge to home.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCAI: Central apnea index\u003c/p\u003e\n\u003cp\u003eCIIM: Chiari II Malformation\u003c/p\u003e\n\u003cp\u003eMMC: Myelomeningocele\u003c/p\u003e\n\u003cp\u003eMOMs: Management of Myelomeningocele\u003c/p\u003e\n\u003cp\u003eOAHI: Obstructive apnea hypopnea index\u003c/p\u003e\n\u003cp\u003ePCA: post-conceptional age\u003c/p\u003e\n\u003cp\u003ePSG: polysomnography\u003c/p\u003e\n\u003cp\u003eSB: Spina Bifida\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSRBD: Sleep related breathing Disorders\u003c/p\u003e\n\u003cp\u003eVPS: ventriculoperitoneal shunt\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatements and Declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eFunding: \u003cem\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting Interests:\u0026nbsp;\u003c/em\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions: Study conceptualization and design were performed by Katherine Stark, Thomas Keens, Sally Ward, and Iris Perez. Data Collection was performed by Katherine Stark, Kathryn Smith, Alexander Van Speybroeck, and Iris Perez. Analysis of data was performed by Katherine Stark, Kathryn Smith, Rachel Wang, Thomas Keens, Sally Ward, and Iris Perez. Ramen Chmait and Jason Chu critically reviewed the manuscript for important intellectual content. The first draft of the manuscript was written by Katherine Stark, Rachel Wang, Jason Chu, and Iris Perez and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eEthics Approval: Study was approved by CHLA Institutional Review Board.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent to Participate: \u003cem\u003eThis is an observational study. The CHLA Institutional Review Board has confirmed that no consent to participate is required.\u003c/em\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMitchell LE, Mitchell LE, Adzick NS, et al (2017) Spina bifida Spina bifida. Lancet 6736(March).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdzick NS, Thom EA, Spong CY, et al (2011) A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele. N Engl J Med 364(11). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/nejmoa1014379\u003c/span\u003e\u003cspan address=\"10.1056/nejmoa1014379\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLapa DA, Chmait RH, Gielchinsky Y, et al (2021) Percutaneous fetoscopic spina bifida repair: effect on ambulation and need for postnatal cerebrospinal fluid diversion and bladder catheterization. Ultrasound Obstet Gynecol 58(4). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/uog.23658\u003c/span\u003e\u003cspan address=\"10.1002/uog.23658\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrabb, PA, Vlastos, EJ, Lundy, PA, \u0026amp; Partington, MB (2022). Significant brainstem dysfunction in neonates with myelomeningoceles: a comparison of prenatal versus postnatal closure. J Neurosurg Pediatr \u003cem\u003e29\u003c/em\u003e(5), 497\u0026ndash;503. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3171/2021.12.PEDS21430\u003c/span\u003e\u003cspan address=\"10.3171/2021.12.PEDS21430\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatel DM, Rocque BG, Hopson B, et al (2015) Sleep-disordered breathing in patients with myelomeningocele. J Neurosurg Pediatr 16(1). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2014.11.PEDS14314\u003c/span\u003e\u003cspan address=\"10.3171/2014.11.PEDS14314\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlsaadi MM, Iqbal SM, Elgamal EA, Gozal D (2012) Sleep-disordered breathing in children with Chiari malformation type II and myelomeningocele. Pediatr Int. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1442-200X.2012.03660.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1442-200X.2012.03660.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBendel-Stenzel E, Linabery AM, Jorgenson A, Ferrara TB, Spaulding AB (2019) Sleep-disordered breathing: an under-recognized problem in infants with myelomeningocele defects regardless of timing of repair. J Perinatol. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41372-019-0433-7\u003c/span\u003e\u003cspan address=\"10.1038/s41372-019-0433-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShellhaas RA, Kenia P V., Hassan F, Barks JDE, Kaciroti N, Chervin RD (2018) Sleep-Disordered Breathing among Newborns with Myelomeningocele. J Pediatr. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jpeds.2017.10.070\u003c/span\u003e\u003cspan address=\"10.1016/j.jpeds.2017.10.070\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWaters KA, Forbes P, Morielli A, et al (1998) Sleep-disordered breathing in children with myelomeningocele. J Pediatr. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0022-3476(98)70359-2\u003c/span\u003e\u003cspan address=\"10.1016/S0022-3476(98)70359-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavidson Ward SL, Jacobs RA, Gates EP, Hart LD, Keens TG (1986) Abnormal ventilatory patterns during sleep in infants with myelomeningocele. J Pediatr 109(4). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0022-3476(86)80226-8\u003c/span\u003e\u003cspan address=\"10.1016/S0022-3476(86)80226-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFraga MV, Giaccone A, Adzick NS (2018) Respiratory morbidities in late preterm and term infants with myelomeningocele. J Perinatol 38, 1542\u0026ndash;1547. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41372-018-0210-z\u003c/span\u003e\u003cspan address=\"10.1038/s41372-018-0210-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShellhaas RA, Kenia P V., Hassan F, Barks JDE, Kaciroti N, Chervin RD (2018) Sleep-Disordered Breathing among Newborns with Myelomeningocele. J Pediatr 194. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jpeds.2017.10.070\u003c/span\u003e\u003cspan address=\"10.1016/j.jpeds.2017.10.070\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerry R, Albertario C, Harding S (2018) The AASM Manual for the Scoring of Sleep and Associated Events, Rules, Terminology and Technical Specifications. Am Acad Sleep Med Version 2.5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerry R, Quan S, Abreu A (2020) Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Am Acad Sleep Med. Version 2.6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatz ES, Mitchell RB, D\u0026rsquo;Ambrosio CM (2012) Obstructive sleep apnea in infants. Am J Respir Crit Care Med. 185(8). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1164/rccm.201108-1455CI\u003c/span\u003e\u003cspan address=\"10.1164/rccm.201108-1455CI\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWitmans MB, Keens TG, Davidson Ward SL, Marcus CL (2003) Obstructive Hypopneas in Children and Adolescents: Normal Values [3]. Am J Respir Crit Care Med. 168(12). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1164/ajrccm.168.12.954\u003c/span\u003e\u003cspan address=\"10.1164/ajrccm.168.12.954\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarcus CL, Omlin KJ, Basinki DJ, et al (1992) Normal polysomnographic values for children and adolescents. Am Rev Respir Dis. 146(5). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1164/ajrccm/146.5_Pt_1.1235\u003c/span\u003e\u003cspan address=\"10.1164/ajrccm/146.5_Pt_1.1235\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaftary AS, Jalou HE, Shively L, Slaven JE, Davis SD (2019) Polysomnography reference values in healthy newborns. J Clin Sleep Med. 15(3). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5664/jcsm.7670\u003c/span\u003e\u003cspan address=\"10.5664/jcsm.7670\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaftary, A. S., Shively, L., Slaven, J. E., \u0026amp; Jalou, H. E. (2019) Can estimated time in airway obstruction be a useful measure for infant obstructive sleep apnea? Int J Pediatr Otorhinolaryngol 124, 208\u0026ndash;209. doi:1016/j.ijporl.2019.06.011\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcLone DG, Knepper PA (1989) The cause of Chiari II malformation: A unified theory. Pediatr Neurosci 15(1). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000120432\u003c/span\u003e\u003cspan address=\"10.1159/000120432\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIskandar BJ, Finnell RH (2022) Spina Bifida. N Engl J Med. 387(5):444\u0026ndash;450. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMra2116032\u003c/span\u003e\u003cspan address=\"10.1056/NEJMra2116032\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGilbert JN, Jones KL, Rorke LB, Chernoff GF, James HE (1986) Central nervous system anomalies associated with meningomyelocele, hydrocephalus, and the Arnold-Chiari malformation: reappraisal of theories regarding the pathogenesis of posterior neural tube closure defects. Neurosurgery 18(5):559\u0026ndash;564. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1227/00006123-198605000-00008\u003c/span\u003e\u003cspan address=\"10.1227/00006123-198605000-00008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGozal D, Arens R, Omlin KJ, Jacobs RA, Keens TG (1995) Peripheral chemoreceptor function in children with myelomeningocele and Arnold-Chiari malformation type 2. Chest 108(2). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1378/chest.108.2.425\u003c/span\u003e\u003cspan address=\"10.1378/chest.108.2.425\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSwaminathan S, Paton JY, Davidson Ward SL, Jacobs RA, Sargent CW, Keens TG (1989) Abnormal control of ventilation in adolescents with myelodysplasia. J Pediatr 115(6). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0022-3476(89)80739-5\u003c/span\u003e\u003cspan address=\"10.1016/S0022-3476(89)80739-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWard SL, Nickerson BG, van der Hal A, Rodriguez AM, Jacobs RA, Keens TG (1986) Absent hypoxic and hypercapneic arousal responses in children with myelomeningocele and apnea. Pediatrics 78(1). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1542/peds.79.2.313b\u003c/span\u003e\u003cspan address=\"10.1542/peds.79.2.313b\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrockbank J, Leon-Astudillo C, Che D, et al (2019) Supplemental oxygen for treatment of infants with obstructive sleep apnea. J Clin Sleep Med 15(8). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5664/jcsm.7802\u003c/span\u003e\u003cspan address=\"10.5664/jcsm.7802\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Spina Bifida, Sleep-disordered Breathing, Polysomnography, Surgery ","lastPublishedDoi":"10.21203/rs.3.rs-3390333/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3390333/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: Recent advances in prenatal repair of myelomeningocele (MMC) have improved outcomes involving different organ systems. There is limited data on respiratory outcomes following prenatal surgical repair. We hypothesize there is no difference in respiratory outcomes between spina bifida (SB) patients who have undergone prenatal versus postnatal repair.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Retrospective study of 46 infants \u0026lt;1 year with SB seen at Children's Hospital Los Angeles from 2004-2022. Demographic data, timing of closure, neonatal course, Chiari II malformation (CIIM), ventriculoperitoneal shunt (VPS), polysomnography (PSG) results, and need for supplemental oxygen were collected. Unpaired t test and Chi-square Test were used to compare results between groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: 31/46 had prenatal repair of MMC; average age at repair was 27 weeks post-conception (PCA). Average age at postnatal repair was 37 PCA. There was no difference in age at PSG. There was no difference in CIIM presence (p=0.61). 60% of patients with postnatal repair and 23% in the prenatal group underwent VPS placement (p=0.01).\u003c/p\u003e\n\u003cp\u003eThere was no difference in PSG findings between the two groups: CAI (p=0.11), OAHI (p=0.64), average SpO\u003csub\u003e2\u003c/sub\u003e baseline (p=0.91), average SpO\u003csub\u003e2\u003c/sub\u003e nadir (p=0.17), average PETCO\u003csub\u003e2\u003c/sub\u003e baseline (p=0.87), average PETCO2 maximum (p=0.54). There were no significant differences in the proportion of patients on supplemental O\u003csub\u003e2\u003c/sub\u003e (p=0.25), CSA or OSA between groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Patients with SB who’ve undergone closure of defect have persistent central apneas, obstructive apneas, and significant hypoxemia. There were no differences in the frequency or severity of sleep-disordered breathing in those with prenatal repair versus postnatal repair.\u003c/p\u003e","manuscriptTitle":"Sleep Related Breathing Disorders in Infants with Spina Bifida Repaired Prenatally and Postnatally","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-10-04 19:07:41","doi":"10.21203/rs.3.rs-3390333/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dedec769-5426-4f52-b065-aadffba2e9ba","owner":[],"postedDate":"October 4th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-04-26T00:36:40+00:00","versionOfRecord":{"articleIdentity":"rs-3390333","link":"https://doi.org/10.5664/jcsm.11174","journal":{"identity":"journal-of-clinical-sleep-medicine","isVorOnly":true,"title":"Journal of Clinical Sleep Medicine"},"publishedOn":"2024-04-25 00:36:40","publishedOnDateReadable":"April 25th, 2024"},"versionCreatedAt":"2023-10-04 19:07:41","video":"","vorDoi":"10.5664/jcsm.11174","vorDoiUrl":"https://doi.org/10.5664/jcsm.11174","workflowStages":[]},"version":"v1","identity":"rs-3390333","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3390333","identity":"rs-3390333","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}