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Congenital nasal pyriform aperture stenosis: Analysis of twenty cases at a single institution
International Journal of Pediatric Otorhinolaryngology 126 (2019) 109608
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Congenital nasal pyriform aperture stenosis: Analysis of twenty cases at a single institution
T
Gopi B. Shaha,*, Allison Ordemanna, Shiva Darama, Emily Romana, Tim Boothb, Romaine Johnsona, Yin Xib, Ron Mitchella a b
Department of Otolaryngology, University of Texas Southwestern Medical Center, 2001 Inwood Road, 6th & 7th Floors, Dallas, TX, 75390, USA Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390, USA
ARTICLE INFO
ABSTRACT
Keywords: Pyriform Aperture Stenosis Congenital Maternal diabetes
Objectives: Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of neonatal respiratory distress that is difficult to treat. The primary objective of this study was to identify factors that predict the need for initial and revision surgery for CNAPS. The secondary objective is to identify risk factors in maternal history associated with the development of CNPAS. Methods: Infants with CNPAS between 2010 and 2017 were identified by ICD- 9 and 10 codes. Demographics, maternal history, anatomic features on imaging and medical and/or surgical management were reviewed. Frequencies, means and standard deviations were calculated. A p-value < .05 was considered significant. Results: Twenty infants were included. All underwent flexible nasal endoscopy with inability to pass the scope in either nostril in 65% of infants. Nineteen had a CT scan and 13 had a MRI with midline defects in 76.3% and 53.8%, respectively. Solitary central mega-incisor was present in 65%. Half underwent surgical intervention at a mean age of 74.8 days, with 90% requiring revision surgery. There was no difference in pyriform aperture distance in the surgical and non-surgical patient subgroups (5.4 mm and 5.2 mm, p = .6 respectively). No specific variables were predictive of need for initial or revision surgery. Maternal diabetes mellitus (MDM) was found in 55% of mothers of infants with CNPAS. Conclusion: Pyriform aperture distance was not a predictor of surgical intervention. MRI should be considered in all infants with CNPAS as the rate of intracranial complications is high. MDM may be a risk factor for CNPAS.
1. Introduction First described in 1988, congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of neonatal nasal obstruction and respiratory distress [1–3]. Infants can be asymptomatic, or present with episodes of cyclical cyanosis during feeding and failure to thrive [4,5]. CNPAS is caused by overgrowth of the nasal process of the maxilla which decreases the pyriform aperture, the most narrow opening of the bony nasal airways [1,6]. CNPAS can exist as an isolated anomaly or with other craniofacial or intracranial malformations including solitary central mega-incisor (CMI) and holoprosencephaly [6–8]. Pyriform aperture width (PAW) of less than 11 mm on CT is diagnostic of CNPAS [4]. Treatment can be medical or surgical, the latter usually via a sublabial approach [5,9]. There is no standard surgical approach and revision surgery is common due to nasal scarring. Maternal diabetes mellitus (MDM) is known to double the rate of
congenital anomalies including congenital heart disease, genitourinary, gastrointestinal and musculoskeletal anomalies [10,11]. Other studies suggest that hyperglycemia during pregnancy may lead to orofacial clefts, facial deformities and defects in neural tube closure [12,13]. Given the high incidence of congenital anomalies, including craniofacial and neural tube defects in these infants, MDM may be a risk factor for CNPAS. The primary objectives of this study is to identify factors that predict the need for primary and revision surgery. The secondary objective is to look for the prevalence of MDM in infants with CNPAS. 2. Methods Infants with a diagnosis of CNPAS were included in the study. The University of Texas Southwestern Medical Center institutional review board approved and exempted the study from consent because of its retrospective design. All patients under 18 years of age with a diagnosis
* Corresponding author. Department of Otolaryngology, University of Texas Southwestern Medical Center, 2350 North Stemmons Freeway, F6.211, Dallas, TX, 75207, USA. E-mail addresses: [email protected], [email protected] (G.B. Shah).
https://doi.org/10.1016/j.ijporl.2019.109608 Received 18 December 2018; Received in revised form 24 July 2019; Accepted 24 July 2019 Available online 26 July 2019 0165-5876/ © 2019 Elsevier B.V. All rights reserved.
International Journal of Pediatric Otorhinolaryngology 126 (2019) 109608
G.B. Shah, et al.
of CNPAS between 2010 and 2017 were identified by ICD-9 and 10 codes 748.0 and Q30.0 respectively. Exclusion criteria were: age 18 years and older, no diagnosis of CNPAS or no available imaging studies. The following were collected from the electronic medical records (Epic® production): age at diagnosis (days), gestational age (weeks), sex, race, birth weight (kilograms), APGAR scores at 1 and 5 min, history of a neonatal intensive care unit (NICU) stay, cardiac, renal, intracranial, craniofacial, laryngotracheal and pulmonary comorbidities. Maternal history (age at delivery, method of delivery, social history, medical history and specifically MDM, hypertension, and obesity) was recorded. Maternal diabetes mellitus (MDM) was defined as pre-pregnancy diabetes mellitus and gestational diabetes mellitus and was obtained from the problem list. Symptoms at presentation such as noisy breathing, poor feeding or weight gain; oxygen requirements, cyanosis and the ability to pass a 2.5 mm flexible endoscope were recorded. Computed tomography (CT) findings were recorded including pyriform aperture distance, choanal measurements, presence of central megaincisor. Pyriform aperture and choanal width measurements were taken at the narrowest bony aperture of each using an axial CT scan showing the entire nasal cavity from pyriform aperture to choanal opening. Intracranial or skull base abnormalities on magnetic resonance imaging (MRI) were also recorded. Medical management such as the use of topical steroids and surgical treatment (sublabial or endonasal approach and use of stents), outcomes and complications were recorded. Infants underwent surgical treatment if they could not be discharged from the ICU or were readmitted for difficulty breathing during feeding and poor weight gain, signs of sleep disordered breathing or episodes of cyanosis or apneas. Categorical data is presented as number and percentages and continuous data as mean and standard deviation. Given the small sample size, Fisher's exact test was used to compare infants born to mothers with diabetes (MDM group) or without diabetes (non-MDM group) and infants who underwent surgery (surgical group) versus no surgery (nonsurgical group). Paired 2-sample t-test was used to compare continuous data between groups: MDM group versus non-MDM group and surgical versus non-surgical groups. A p-value of < .05 was considered significant.
and non-surgical subgroup or the MDM and non-MDM. Six infants had dacrocystoceles, 5 of whom were in the MDM group and 4 required surgery. MRI abnormalities (defined as CMI and/or other midline abnormalities as part of the holoprosencephaly spectrum) were noted in approximately 75% of infants. Thirteen (65%) infants had a solitary central mega-incisor (CMI). Midline abnormalities were more common in the surgical versus non-surgical group (71% versus 33%). Over half (53%) of infants had other midline abnormalities including subependymal cysts, posterior fossa epidermoids, hypoplastic internal carotid arteries, dilated medullary veins, absent septum pellucidum, dorsal diencephalic fusion, aqueductal stenosis, hydrocephalus, ectopic neurohypophysis, dysplastic corpus callosum, and hypoplastic brainstem, pituitary, optic nerves and olfactory nerves. Medical management included saline, a short course of neosynephrine drops and nasal steroids in the form of aerosolized nasal steroid spray, or antibiotic/steroid drops, specifically ciprofloxacin 0.3%/dexamethasone 0.1% otic suspension drops. Medical management continued for an average of 100 days (range 4–366 days). A comparison of infants undergoing surgical versus medical management as well as those born to mothers with and without MDM is summarized in Table 1. The diagnosis of CNPAS in the non-surgical group was made at an average of 113 days and in the surgical group at 17 days. Ten infants (50%) underwent surgical repair. Eight of 10 female infants underwent surgical repair; 2 of 10 male infants underwent surgical repair. Males were less likely to have surgical repair. APGAR at 1 min was higher in the surgical group versus the non-surgical group. Average age at surgery was 74.8 days. Nine (90%) had stents at time of surgery usually for not being able to pass a 3.5 or 4.0 endotracheal tube on either side of the nose. The average length of time for stent placement was 7.3 days. A total of 9 (90%) of infants required revision surgery due to intranasal synechiae. Six infants had no more than 2 surgeries; 2 infants had 4 and 1 infant had 8 revisions. None of the infants had a tracheostomy. The infant who did not require revision had stents placed for 2 days. Surgery was slightly more common in the infants in the MDM group than in the infants in non-MDM (54.6% versus 44.4%).
3. Results
We present 20 infants with CNPAS in whom half were treated surgically. The measurements of the pyriform aperture and choana were similar in those infants who did have surgical intervention compared to those who did not. This finding is in agreement with several other studies that have also shown no difference in pyriform aperture width between infants managed surgically and medically [2,4,5,14]. This suggests that factors other than nasal airway narrowing influence whether a patient requires surgery. For example, the surgical group had an earlier average age of CNPAS diagnosis that suggests tone, medical comorbidities or ability to coordinate suck may play a role in these earlier diagnosed infants. Moreover, an initial trial of medical management including saline, nasal steroids and nasal decongestants is recommended and used universally [4,15]. Seventy-five percent of the infants had abnormalities on MRI of which more than half were intracranial. In addition to holoprosencephaly, other intracranial abnormalities include microcephaly and hypoplasia of olfactory bulbs, corpus callosum and pituitary. This is consistent with findings in a radiologic review of 40 CNPAS infants in whom 16 (40%) had hypothalamic-pituitary abnormalities [7]. Furthermore, pituitary abnormalities in CNPAS has been reported in 20% of infants [7,16]. The high incidence of intracranial abnormalities in infants with CNPAS suggests that an MRI of the brain should be performed routinely as part of the work-up. Gonik and Lin both hypothesized that the presence of several comorbidities may result in the need for surgical intervention [2,14]. This, coupled with the high incidence of midline intracranial abnormalities in infants with CNPAS presented in this series may explain the high rate of primary and revision surgery in this report compared to
4. Discussion
Twenty-one infants had a diagnosis of CNPAS. One infant was excluded due to a lack of CT or MRI resulting in a study population of 20. Demographics is shown in Table 1. There were 10 females (50%); mean age at diagnosis was 65 days (range 1–906 days) and mean birth weight was 3.1 kg (range 2.2–3.9 kg). Eighty percent were Caucasian (n = 9) or Hispanic (n = 7). Sixteen infants (80%) were full term and 4 were born at gestational age 34–36 weeks. Average APGAR at 1 and 5min was 7.3 and 8.4. Genetic testing was done in 3 of the 20 infants with microarray anomaly revealed in 2. None of the infants had adrenal suppression. Average maternal age at time of delivery was 28 years (range 18–35 years). MDM was noted in 11 (55%) mothers; six mothers (30%) had obesity and/or hypertension. Of the 10 infants born to mothers with MDM, 6 were male and 4 were female. Of the 10 infants born to mothers without MDM, 4 were male and 6 were female. There was no difference in sex of the infant born to mothers with or without MDM. Eighteen infants had a neonatal intensive care unit (NICU) stay, with an average of 28 days. Most common symptoms at presentation were nasal congestion, noisy breathing (recorded as stridor and stertor), difficulty feeding and respiratory distress. A pediatric flexible 2.5 mm scope could not be passed on either side of the nose in 13 infants (65%). In 4 infants (20%) the scope could only be passed on one side, and in 3 (15%) infants it was passed on both sides. Table 2 illustrates imaging findings of the study population. CT and MRI imaging was obtained in 95% and 85% of patients, respectively. Pyriform aperture distance averaged 5.3 mm for all of the patients; there was no difference pyriform aperture distance between the surgical 2
International Journal of Pediatric Otorhinolaryngology 126 (2019) 109608
G.B. Shah, et al.
Table 1 Demographics of infants with congenital pyriform aperture stenosis (CNPAS) comparing those born to mothers with and without Maternal Diabetes Mellitus (MDM) and those infants with and without surgical intervention. Variable (units)
Overall, n(%)
MDMa n(%)
Non-MDMa n(%)
P value
Surgical patients n(%)
Non-surgical patients n(%)
P value
Male Race Caucasian Hispanic Black Middle Eastern Unknown
10 (50)
6 (55)
4 (44)
0.5
2 (20)
8 (80)
0.01
9 7 2 1 1
4 6 1 0 0
5 1 1 1 1
0.3 0.06 0.07 0.05 0.05
6 3 1 0 0
3 4 1 1 1
0.2 0.5 0.8 0.5 0.5
Age at diagnosis (days) Gestational age (weeks) APGARb (1 min) APGARb (5 min) Birth weight(kg) c NICU length of stay (days) Maternal age at delivery (year)
(45) (35) (10) (5) (5)
(36) (55) (9) (0) (0)
(56) (11) (11) (11) (11)
Overall (n=20) Mean
MDMa (n = 11) Mean (SD)
Non-MDMa (n = 9) Mean (SD)
65 38 7 8 3 28 28
100 (267) 37 (1) 7 (3) 8 (2) 3 (0.4) 35 (27) 29 (4)
22 (27) 39 (2) 8 (1) 9 (1) 3 (0.5) 20 (26) 27 (6)
0.2 1 0.9 1 0.5 0.1 0.2
(60) (30) (10) (0) (0)
(30) (40) (10) (10) (10)
Surgical patients (n = 10) Mean (SD)
Non-surgical patients (n = 10) Mean (SD)
17 (15) 38 (1.1) 8 (1) 9 (1) 3 (0.5) 34 (31) 28 (4)
113 (280) 38 (2) 6 (3) 8 (2) 4 (0.5) 22 (21) 27 (56)
0.9 0.5 0.02 0.06 1 0.2 0.5
SD- Standard Deviation. P Value-significance set at < 0.05. a MDM-Maternal Diabetes Mellitus. b APGAR-Activity Pulse Grimace Appearance Respiration. c NICU- Neonatal Intensive Care Unit.
previous studies [4,14]. The studies that did describe revision surgery also noted higher rates in infants with craniofacial anomalies [4,14]. The most common anomaly associated with CNPAS is a form of holoprosencephaly spectrum, with solitary central mega-incisor (CMI) being the least severe and most common manifestation. CMI was present in 65% of patients in this study, consistent with other reported series but did not predict a need for surgical correction in keeping with previous reports [2,5,17,18]. However, we did find that almost a third of infants had dacrocystoceles that were more common in those treated surgically and likely due to the combined narrowing effect of the two conditions. An association between MDM and CNPAS, to our knowledge, has not been previously reported. In this study, over half of the infants were born to mothers with MDM. It is important to note that MDM is associated with increased rates of structural congenital anomalies, including congenital heart defects and orofacial clefts, so an association with CNPAS is not surprising [11,12,19]. The presence of MDM did not predict the severity of CNPAS in terms of nasal widths or the need for
surgical intervention. However, we feel it is an important and a potential etiologic factor, as better control of MDM may influence the development of CNPAS. In addition, clinicians may be able to identify CNPAS as an important differential diagnosis in infants of MDM who present with cyclical cyanosis or nasal obstruction. Finally maternal obesity may increase the risk of neural tube defects in infants [20]; obesity was found in 30% of the mothers in our study and would be another potential area in need of research. The strengths of this study include the large sample size, given the overall low incidence of CNPAS, and the documentation of maternal medical history which allowed us to study associations with CNPAS. Our study was limited by its retrospective nature and our inability to access maternal records. Multi-institutional studies or a meta-analysis are needed for pooled outcome analysis and the subsequent establishment of the most efficacious treatment for CNPAS as well as to determine if there is a significant risk of CNPAS in an infant born to a mother with MDM. We were unable to distinguish between pre-pregnancy diabetes mellitus and gestational diabetes mellitus or the severity
Table 2 Imaging characteristics of patients with congenital pyriform aperture stenosis (CNPAS) comparing those with and without Maternal Diabetes Mellitus (MDM) and those patients with and without surgical intervention. Imaging Findings
Overall (n = 20) n (%)
MDM (n = 11) n(%)
Non-MDM (n = 9) n (%)
CTa scan obtained MRIb obtained MRIᶧ abnormal
19 (95) 17 (85) 10 (76)
11 (100) 11 (100) 7 (79)
8 (89) 6 (67) 3 (75)
Median central incisor (Y) Dacrocystoceles on CT
13 (65) 6 (30)
9 (82) 5 (45.5)
4 (44) 1 (11.1)
Mean (SD)
Mean (SD)
Mean (SD)
199 (250) 5.3 (1.4)
151 (306) 5.1 (1.7)
31 (31) 5.4 (1.0)
b
Age MRI done (days) PA width (mm)
P values
Surgical patients (n = 10) n (%)
Non-surgical patients (n = 10) n (%)
0.1
10 (100) 10 (100) 5 (71)
9 (90) 7 (70) 5 (83)
0.1 0.1
6 (60) 4 (40)
7 (70) 2 (20)
Mean (SD)
Mean (SD)
77 (179) 5.2 (1.0)
154 (338) 5.4 (1.8)
0.1 0.7
P value significance set at < 0.05. ∧ PA-measurement of pyriform aperture width. a CT – computed tomography. b MRI- magnetic resonance imaging. 3
P values
0.2 0.3
0.7 0.6
International Journal of Pediatric Otorhinolaryngology 126 (2019) 109608
G.B. Shah, et al.
of MDM as we did not have access to maternal medical records. A detailed review of maternal medical record may be helpful to determine if the time of diagnosis of diabetes, before or at the onset of pregnancy, and the severity of MDM affects the incidence or severity of CNPAS in the infant.
[7] S. Guilmin-Crépon, C. Garel, C. Baumann, et al., High proportion of pituitary abnormalities and other congenital defects in children with congenital nasal pyriform aperture stenosis, Pediatr. Res. 60 (4) (2006) 478–484, https://doi.org/10.1203/ 01.pdr.0000238380.03683.cb. [8] F. Lo, Y. Lee, S. Lin, E. Shen, J. Huang, K. Lee, Solitary maxillary central incisor and congenital nasal pyriform aperture stenosis, Eur. J. Pediatr. 157 (1) (1998) 39–44, https://doi.org/10.1007/s004310050763. [9] V.S. Merea, A.H. Lee, D.L. Peron, E.H. Waldman, E. Grunstein, CPAS: surgical approach with combined sublabial bone resection and inferior turbinate reduction without stents, The Laryngoscope 125 (6) (2015) 1460–1464, https://doi.org/10. 1002/lary.25001. [10] E. Zhao, Y. Zhang, X. Zeng, B. Liu, Association between maternal diabetes mellitus and the risk of congenital malformations: a meta-analysis of cohort studies, Drug Discov Ther 9 (4) (2015) 274–281, https://doi.org/10.5582/ddt.2015.01044. [11] S. Liu, J. Rouleau, J. León, R. Sauve, K. Joseph, J. Ray, Impact of pre-pregnancy diabetes mellitus on congenital anomalies, Canada, 2002–2012, Health Promotion and Chronic Disease Prevention in Canada, vol. 35, 2015, pp. 79–84, , https://doi. org/10.24095/hpcdp.35.5.01 5. [12] I.K. Trindade-Suedam, L.M. Kostrisch, L.A. Pimenta, C.A. Negrato, S.B. Franzolin, AS Junior Trindade, Diabetes mellitus and drug abuse during pregnancy and the risk for orofacial clefts and related abnormalities, Rev Lat Am Enfermagem 24 (2016) e2701, , https://doi.org/10.1590/1518-8345.0815.2701. [13] T.C. Hrubec, M.R. Prater, K.A. Toops, et al., Reduction in diabetes-induced craniofacial defects by maternal autoimmune stimulation, Birth Defect Res B Dev Reprod Tpxicol 77 (1) (2006) 1–9. [14] N.J. Gonik, J. Cheng, M. Lesser, M.J. Shikowitz, L.P. Smith, Patient selection in congenital pyriform aperture stenosis repair - 14 year experience and systematic review of literature, Int. J. Pediatr. Otorhinolaryngol. 79 (2) (2015) 235–239, https://doi.org/10.1016/j.ijporl.2014.12.016. [15] M. Devambez, A. Delattre, P. Fayoux, Congenital nasal pyriform aperture stenosis: diagnosis and management, Cleft Palate-Craniofacial J. 46 (3) (2009) 262–267, https://doi.org/10.1597/07-182.1. [16] S.C. Chen, H. McDevitt, W.A. Clement, et al., Early identification of pituitary dysfunction in congenital pyriform aperture stenosis: recommendations based on experience in a single centre, Horm Res. Paediatr. 83 (2015) 302–310. [17] V. Visvanathan, D.M. Wynne, Congenital pyriform aperture stenosis: a report of 10 cases and literature review, Int. J. Pediatr. Otorhinolaryngol. 76 (2012) 28–30. [18] T. Van Den Abbeele, J.M. Triglia, M. Francois, et al., Congenital nasal pyriform aperture stenosis: diagnosis and management of 20 cases, Ann. Otol. Rhinol. Laryngol. 110 (2001) 70–75. [19] H.H. Chou, M.J. Chiou, F.W. Liang, L.H. Chen, T.H. Lu, C.Y. Li, Association of maternal chronic disease with risk of congenital heart disease in offspring, CMAJ (Can. Med. Assoc. J.) 188 (17–18) (2016) E438–E446. [20] K.J. Stothard, P.W. Tennant, R. Bell, et al., Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis, J. Am. Med. Assoc. 301 (2009) 636–650.
5. Conclusion CNPAS is initially treated medically though many infants may require surgery. Pyriform aperture width does not predict the need for surgical management in infants with CNPAS; factors including neurological comorbidities may contribute to the need for surgery and even revision surgery. MRI imaging for midline intracranial abnormalities should be considered in all patients given the high likelihood of abnormalities (76%). MDM may be a risk factor for developing CNPAS. Disclosure None of the authors have anything to disclose. References [1] O. Brown, C. Myer, S. Manning, Congenital nasal pyriform aperture stenosis, The Laryngoscope 99 (1) (1989) 86–91, https://doi.org/10.1288/00005537198901000-00016. [2] K. Lin, K. Lee, C. Yang, L. Hsieh, C. Su, F. Sun, The natural course of congenital nasal pyriform aperture stenosis, The Laryngoscope 126 (10) (2016) 2399–2402, https:// doi.org/10.1002/lary.25873. [3] T. Serrano, L. Pfeilsticker, V. Silva, et al., Newborn nasal obstruction due to congenital nasal pyriform aperture stenosis, Allergy& Rhinology. 7 (1) (2016) 37–41, https://doi.org/10.2500/ar.2016.7.0146. [4] A. Losken, F.D. Burstein, J.K. Williams, Congenital nasal pyriform aperture stenosis: diagnosis and treatment, Plast. Reconstr. Surg. 109 (5) (2002) 1506–1511 discussion 1512. [5] R. Wormald, A. Hinton-Bayre, P. Bumbak, S. Vijayasekaran, Congenital nasal pyriform aperture stenosis 5.7 mm or less is associated with surgical intervention: a pooled case series, Int. J. Pediatr. Otorhinolaryngol. 79 (11) (2015) 1802–1805, https://doi.org/10.1016/j.ijporl.2015.07.026. [6] E. Sesenna, M. Leporati, B. Brevi, G. Oretti, A. Ferri, Congenital nasal pyriform aperture stenosis: diagnosis and management, Ital. J. Pediatr. 38 (1) (2012) 28, https://doi.org/10.1186/1824-7288-38-28.
4
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Congenital nasal pyriform aperture stenosis: Analysis of twenty cases at a single institution
T
Gopi B. Shaha,*, Allison Ordemanna, Shiva Darama, Emily Romana, Tim Boothb, Romaine Johnsona, Yin Xib, Ron Mitchella a b
Department of Otolaryngology, University of Texas Southwestern Medical Center, 2001 Inwood Road, 6th & 7th Floors, Dallas, TX, 75390, USA Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390, USA
ARTICLE INFO
ABSTRACT
Keywords: Pyriform Aperture Stenosis Congenital Maternal diabetes
Objectives: Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of neonatal respiratory distress that is difficult to treat. The primary objective of this study was to identify factors that predict the need for initial and revision surgery for CNAPS. The secondary objective is to identify risk factors in maternal history associated with the development of CNPAS. Methods: Infants with CNPAS between 2010 and 2017 were identified by ICD- 9 and 10 codes. Demographics, maternal history, anatomic features on imaging and medical and/or surgical management were reviewed. Frequencies, means and standard deviations were calculated. A p-value < .05 was considered significant. Results: Twenty infants were included. All underwent flexible nasal endoscopy with inability to pass the scope in either nostril in 65% of infants. Nineteen had a CT scan and 13 had a MRI with midline defects in 76.3% and 53.8%, respectively. Solitary central mega-incisor was present in 65%. Half underwent surgical intervention at a mean age of 74.8 days, with 90% requiring revision surgery. There was no difference in pyriform aperture distance in the surgical and non-surgical patient subgroups (5.4 mm and 5.2 mm, p = .6 respectively). No specific variables were predictive of need for initial or revision surgery. Maternal diabetes mellitus (MDM) was found in 55% of mothers of infants with CNPAS. Conclusion: Pyriform aperture distance was not a predictor of surgical intervention. MRI should be considered in all infants with CNPAS as the rate of intracranial complications is high. MDM may be a risk factor for CNPAS.
1. Introduction First described in 1988, congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of neonatal nasal obstruction and respiratory distress [1–3]. Infants can be asymptomatic, or present with episodes of cyclical cyanosis during feeding and failure to thrive [4,5]. CNPAS is caused by overgrowth of the nasal process of the maxilla which decreases the pyriform aperture, the most narrow opening of the bony nasal airways [1,6]. CNPAS can exist as an isolated anomaly or with other craniofacial or intracranial malformations including solitary central mega-incisor (CMI) and holoprosencephaly [6–8]. Pyriform aperture width (PAW) of less than 11 mm on CT is diagnostic of CNPAS [4]. Treatment can be medical or surgical, the latter usually via a sublabial approach [5,9]. There is no standard surgical approach and revision surgery is common due to nasal scarring. Maternal diabetes mellitus (MDM) is known to double the rate of
congenital anomalies including congenital heart disease, genitourinary, gastrointestinal and musculoskeletal anomalies [10,11]. Other studies suggest that hyperglycemia during pregnancy may lead to orofacial clefts, facial deformities and defects in neural tube closure [12,13]. Given the high incidence of congenital anomalies, including craniofacial and neural tube defects in these infants, MDM may be a risk factor for CNPAS. The primary objectives of this study is to identify factors that predict the need for primary and revision surgery. The secondary objective is to look for the prevalence of MDM in infants with CNPAS. 2. Methods Infants with a diagnosis of CNPAS were included in the study. The University of Texas Southwestern Medical Center institutional review board approved and exempted the study from consent because of its retrospective design. All patients under 18 years of age with a diagnosis
* Corresponding author. Department of Otolaryngology, University of Texas Southwestern Medical Center, 2350 North Stemmons Freeway, F6.211, Dallas, TX, 75207, USA. E-mail addresses: [email protected], [email protected] (G.B. Shah).
https://doi.org/10.1016/j.ijporl.2019.109608 Received 18 December 2018; Received in revised form 24 July 2019; Accepted 24 July 2019 Available online 26 July 2019 0165-5876/ © 2019 Elsevier B.V. All rights reserved.
International Journal of Pediatric Otorhinolaryngology 126 (2019) 109608
G.B. Shah, et al.
of CNPAS between 2010 and 2017 were identified by ICD-9 and 10 codes 748.0 and Q30.0 respectively. Exclusion criteria were: age 18 years and older, no diagnosis of CNPAS or no available imaging studies. The following were collected from the electronic medical records (Epic® production): age at diagnosis (days), gestational age (weeks), sex, race, birth weight (kilograms), APGAR scores at 1 and 5 min, history of a neonatal intensive care unit (NICU) stay, cardiac, renal, intracranial, craniofacial, laryngotracheal and pulmonary comorbidities. Maternal history (age at delivery, method of delivery, social history, medical history and specifically MDM, hypertension, and obesity) was recorded. Maternal diabetes mellitus (MDM) was defined as pre-pregnancy diabetes mellitus and gestational diabetes mellitus and was obtained from the problem list. Symptoms at presentation such as noisy breathing, poor feeding or weight gain; oxygen requirements, cyanosis and the ability to pass a 2.5 mm flexible endoscope were recorded. Computed tomography (CT) findings were recorded including pyriform aperture distance, choanal measurements, presence of central megaincisor. Pyriform aperture and choanal width measurements were taken at the narrowest bony aperture of each using an axial CT scan showing the entire nasal cavity from pyriform aperture to choanal opening. Intracranial or skull base abnormalities on magnetic resonance imaging (MRI) were also recorded. Medical management such as the use of topical steroids and surgical treatment (sublabial or endonasal approach and use of stents), outcomes and complications were recorded. Infants underwent surgical treatment if they could not be discharged from the ICU or were readmitted for difficulty breathing during feeding and poor weight gain, signs of sleep disordered breathing or episodes of cyanosis or apneas. Categorical data is presented as number and percentages and continuous data as mean and standard deviation. Given the small sample size, Fisher's exact test was used to compare infants born to mothers with diabetes (MDM group) or without diabetes (non-MDM group) and infants who underwent surgery (surgical group) versus no surgery (nonsurgical group). Paired 2-sample t-test was used to compare continuous data between groups: MDM group versus non-MDM group and surgical versus non-surgical groups. A p-value of < .05 was considered significant.
and non-surgical subgroup or the MDM and non-MDM. Six infants had dacrocystoceles, 5 of whom were in the MDM group and 4 required surgery. MRI abnormalities (defined as CMI and/or other midline abnormalities as part of the holoprosencephaly spectrum) were noted in approximately 75% of infants. Thirteen (65%) infants had a solitary central mega-incisor (CMI). Midline abnormalities were more common in the surgical versus non-surgical group (71% versus 33%). Over half (53%) of infants had other midline abnormalities including subependymal cysts, posterior fossa epidermoids, hypoplastic internal carotid arteries, dilated medullary veins, absent septum pellucidum, dorsal diencephalic fusion, aqueductal stenosis, hydrocephalus, ectopic neurohypophysis, dysplastic corpus callosum, and hypoplastic brainstem, pituitary, optic nerves and olfactory nerves. Medical management included saline, a short course of neosynephrine drops and nasal steroids in the form of aerosolized nasal steroid spray, or antibiotic/steroid drops, specifically ciprofloxacin 0.3%/dexamethasone 0.1% otic suspension drops. Medical management continued for an average of 100 days (range 4–366 days). A comparison of infants undergoing surgical versus medical management as well as those born to mothers with and without MDM is summarized in Table 1. The diagnosis of CNPAS in the non-surgical group was made at an average of 113 days and in the surgical group at 17 days. Ten infants (50%) underwent surgical repair. Eight of 10 female infants underwent surgical repair; 2 of 10 male infants underwent surgical repair. Males were less likely to have surgical repair. APGAR at 1 min was higher in the surgical group versus the non-surgical group. Average age at surgery was 74.8 days. Nine (90%) had stents at time of surgery usually for not being able to pass a 3.5 or 4.0 endotracheal tube on either side of the nose. The average length of time for stent placement was 7.3 days. A total of 9 (90%) of infants required revision surgery due to intranasal synechiae. Six infants had no more than 2 surgeries; 2 infants had 4 and 1 infant had 8 revisions. None of the infants had a tracheostomy. The infant who did not require revision had stents placed for 2 days. Surgery was slightly more common in the infants in the MDM group than in the infants in non-MDM (54.6% versus 44.4%).
3. Results
We present 20 infants with CNPAS in whom half were treated surgically. The measurements of the pyriform aperture and choana were similar in those infants who did have surgical intervention compared to those who did not. This finding is in agreement with several other studies that have also shown no difference in pyriform aperture width between infants managed surgically and medically [2,4,5,14]. This suggests that factors other than nasal airway narrowing influence whether a patient requires surgery. For example, the surgical group had an earlier average age of CNPAS diagnosis that suggests tone, medical comorbidities or ability to coordinate suck may play a role in these earlier diagnosed infants. Moreover, an initial trial of medical management including saline, nasal steroids and nasal decongestants is recommended and used universally [4,15]. Seventy-five percent of the infants had abnormalities on MRI of which more than half were intracranial. In addition to holoprosencephaly, other intracranial abnormalities include microcephaly and hypoplasia of olfactory bulbs, corpus callosum and pituitary. This is consistent with findings in a radiologic review of 40 CNPAS infants in whom 16 (40%) had hypothalamic-pituitary abnormalities [7]. Furthermore, pituitary abnormalities in CNPAS has been reported in 20% of infants [7,16]. The high incidence of intracranial abnormalities in infants with CNPAS suggests that an MRI of the brain should be performed routinely as part of the work-up. Gonik and Lin both hypothesized that the presence of several comorbidities may result in the need for surgical intervention [2,14]. This, coupled with the high incidence of midline intracranial abnormalities in infants with CNPAS presented in this series may explain the high rate of primary and revision surgery in this report compared to
4. Discussion
Twenty-one infants had a diagnosis of CNPAS. One infant was excluded due to a lack of CT or MRI resulting in a study population of 20. Demographics is shown in Table 1. There were 10 females (50%); mean age at diagnosis was 65 days (range 1–906 days) and mean birth weight was 3.1 kg (range 2.2–3.9 kg). Eighty percent were Caucasian (n = 9) or Hispanic (n = 7). Sixteen infants (80%) were full term and 4 were born at gestational age 34–36 weeks. Average APGAR at 1 and 5min was 7.3 and 8.4. Genetic testing was done in 3 of the 20 infants with microarray anomaly revealed in 2. None of the infants had adrenal suppression. Average maternal age at time of delivery was 28 years (range 18–35 years). MDM was noted in 11 (55%) mothers; six mothers (30%) had obesity and/or hypertension. Of the 10 infants born to mothers with MDM, 6 were male and 4 were female. Of the 10 infants born to mothers without MDM, 4 were male and 6 were female. There was no difference in sex of the infant born to mothers with or without MDM. Eighteen infants had a neonatal intensive care unit (NICU) stay, with an average of 28 days. Most common symptoms at presentation were nasal congestion, noisy breathing (recorded as stridor and stertor), difficulty feeding and respiratory distress. A pediatric flexible 2.5 mm scope could not be passed on either side of the nose in 13 infants (65%). In 4 infants (20%) the scope could only be passed on one side, and in 3 (15%) infants it was passed on both sides. Table 2 illustrates imaging findings of the study population. CT and MRI imaging was obtained in 95% and 85% of patients, respectively. Pyriform aperture distance averaged 5.3 mm for all of the patients; there was no difference pyriform aperture distance between the surgical 2
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Table 1 Demographics of infants with congenital pyriform aperture stenosis (CNPAS) comparing those born to mothers with and without Maternal Diabetes Mellitus (MDM) and those infants with and without surgical intervention. Variable (units)
Overall, n(%)
MDMa n(%)
Non-MDMa n(%)
P value
Surgical patients n(%)
Non-surgical patients n(%)
P value
Male Race Caucasian Hispanic Black Middle Eastern Unknown
10 (50)
6 (55)
4 (44)
0.5
2 (20)
8 (80)
0.01
9 7 2 1 1
4 6 1 0 0
5 1 1 1 1
0.3 0.06 0.07 0.05 0.05
6 3 1 0 0
3 4 1 1 1
0.2 0.5 0.8 0.5 0.5
Age at diagnosis (days) Gestational age (weeks) APGARb (1 min) APGARb (5 min) Birth weight(kg) c NICU length of stay (days) Maternal age at delivery (year)
(45) (35) (10) (5) (5)
(36) (55) (9) (0) (0)
(56) (11) (11) (11) (11)
Overall (n=20) Mean
MDMa (n = 11) Mean (SD)
Non-MDMa (n = 9) Mean (SD)
65 38 7 8 3 28 28
100 (267) 37 (1) 7 (3) 8 (2) 3 (0.4) 35 (27) 29 (4)
22 (27) 39 (2) 8 (1) 9 (1) 3 (0.5) 20 (26) 27 (6)
0.2 1 0.9 1 0.5 0.1 0.2
(60) (30) (10) (0) (0)
(30) (40) (10) (10) (10)
Surgical patients (n = 10) Mean (SD)
Non-surgical patients (n = 10) Mean (SD)
17 (15) 38 (1.1) 8 (1) 9 (1) 3 (0.5) 34 (31) 28 (4)
113 (280) 38 (2) 6 (3) 8 (2) 4 (0.5) 22 (21) 27 (56)
0.9 0.5 0.02 0.06 1 0.2 0.5
SD- Standard Deviation. P Value-significance set at < 0.05. a MDM-Maternal Diabetes Mellitus. b APGAR-Activity Pulse Grimace Appearance Respiration. c NICU- Neonatal Intensive Care Unit.
previous studies [4,14]. The studies that did describe revision surgery also noted higher rates in infants with craniofacial anomalies [4,14]. The most common anomaly associated with CNPAS is a form of holoprosencephaly spectrum, with solitary central mega-incisor (CMI) being the least severe and most common manifestation. CMI was present in 65% of patients in this study, consistent with other reported series but did not predict a need for surgical correction in keeping with previous reports [2,5,17,18]. However, we did find that almost a third of infants had dacrocystoceles that were more common in those treated surgically and likely due to the combined narrowing effect of the two conditions. An association between MDM and CNPAS, to our knowledge, has not been previously reported. In this study, over half of the infants were born to mothers with MDM. It is important to note that MDM is associated with increased rates of structural congenital anomalies, including congenital heart defects and orofacial clefts, so an association with CNPAS is not surprising [11,12,19]. The presence of MDM did not predict the severity of CNPAS in terms of nasal widths or the need for
surgical intervention. However, we feel it is an important and a potential etiologic factor, as better control of MDM may influence the development of CNPAS. In addition, clinicians may be able to identify CNPAS as an important differential diagnosis in infants of MDM who present with cyclical cyanosis or nasal obstruction. Finally maternal obesity may increase the risk of neural tube defects in infants [20]; obesity was found in 30% of the mothers in our study and would be another potential area in need of research. The strengths of this study include the large sample size, given the overall low incidence of CNPAS, and the documentation of maternal medical history which allowed us to study associations with CNPAS. Our study was limited by its retrospective nature and our inability to access maternal records. Multi-institutional studies or a meta-analysis are needed for pooled outcome analysis and the subsequent establishment of the most efficacious treatment for CNPAS as well as to determine if there is a significant risk of CNPAS in an infant born to a mother with MDM. We were unable to distinguish between pre-pregnancy diabetes mellitus and gestational diabetes mellitus or the severity
Table 2 Imaging characteristics of patients with congenital pyriform aperture stenosis (CNPAS) comparing those with and without Maternal Diabetes Mellitus (MDM) and those patients with and without surgical intervention. Imaging Findings
Overall (n = 20) n (%)
MDM (n = 11) n(%)
Non-MDM (n = 9) n (%)
CTa scan obtained MRIb obtained MRIᶧ abnormal
19 (95) 17 (85) 10 (76)
11 (100) 11 (100) 7 (79)
8 (89) 6 (67) 3 (75)
Median central incisor (Y) Dacrocystoceles on CT
13 (65) 6 (30)
9 (82) 5 (45.5)
4 (44) 1 (11.1)
Mean (SD)
Mean (SD)
Mean (SD)
199 (250) 5.3 (1.4)
151 (306) 5.1 (1.7)
31 (31) 5.4 (1.0)
b
Age MRI done (days) PA width (mm)
P values
Surgical patients (n = 10) n (%)
Non-surgical patients (n = 10) n (%)
0.1
10 (100) 10 (100) 5 (71)
9 (90) 7 (70) 5 (83)
0.1 0.1
6 (60) 4 (40)
7 (70) 2 (20)
Mean (SD)
Mean (SD)
77 (179) 5.2 (1.0)
154 (338) 5.4 (1.8)
0.1 0.7
P value significance set at < 0.05. ∧ PA-measurement of pyriform aperture width. a CT – computed tomography. b MRI- magnetic resonance imaging. 3
P values
0.2 0.3
0.7 0.6
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of MDM as we did not have access to maternal medical records. A detailed review of maternal medical record may be helpful to determine if the time of diagnosis of diabetes, before or at the onset of pregnancy, and the severity of MDM affects the incidence or severity of CNPAS in the infant.
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5. Conclusion CNPAS is initially treated medically though many infants may require surgery. Pyriform aperture width does not predict the need for surgical management in infants with CNPAS; factors including neurological comorbidities may contribute to the need for surgery and even revision surgery. MRI imaging for midline intracranial abnormalities should be considered in all patients given the high likelihood of abnormalities (76%). MDM may be a risk factor for developing CNPAS. Disclosure None of the authors have anything to disclose. References [1] O. Brown, C. Myer, S. Manning, Congenital nasal pyriform aperture stenosis, The Laryngoscope 99 (1) (1989) 86–91, https://doi.org/10.1288/00005537198901000-00016. [2] K. Lin, K. Lee, C. Yang, L. Hsieh, C. Su, F. Sun, The natural course of congenital nasal pyriform aperture stenosis, The Laryngoscope 126 (10) (2016) 2399–2402, https:// doi.org/10.1002/lary.25873. [3] T. Serrano, L. Pfeilsticker, V. Silva, et al., Newborn nasal obstruction due to congenital nasal pyriform aperture stenosis, Allergy& Rhinology. 7 (1) (2016) 37–41, https://doi.org/10.2500/ar.2016.7.0146. [4] A. Losken, F.D. Burstein, J.K. Williams, Congenital nasal pyriform aperture stenosis: diagnosis and treatment, Plast. Reconstr. Surg. 109 (5) (2002) 1506–1511 discussion 1512. [5] R. Wormald, A. Hinton-Bayre, P. Bumbak, S. Vijayasekaran, Congenital nasal pyriform aperture stenosis 5.7 mm or less is associated with surgical intervention: a pooled case series, Int. J. Pediatr. Otorhinolaryngol. 79 (11) (2015) 1802–1805, https://doi.org/10.1016/j.ijporl.2015.07.026. [6] E. Sesenna, M. Leporati, B. Brevi, G. Oretti, A. Ferri, Congenital nasal pyriform aperture stenosis: diagnosis and management, Ital. J. Pediatr. 38 (1) (2012) 28, https://doi.org/10.1186/1824-7288-38-28.
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