Long-term outcome of pre- and perinatal management of congenital head and neck tumors and malformations

International Journal of Pediatric Otorhinolaryngology 121 (2019) 164–172

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International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl

Long-term outcome of pre- and perinatal management of congenital head and neck tumors and malformations

T

Karen Beckersa,1, Julie Faesb,1, Jan Deprestb, Pierre R. Delaerea, Greet Hensa, Luc De Catteb, Gunnar Naulaersc, Filip Clausd, Robert Hermansd, Vincent L.M. Vander Poortena,∗ a Otorhinolaryngology, Head & Neck Surgery, University Hospitals Leuven, Belgium and Department of Oncology, Section Head & Neck Oncology, KU Leuven, Kapucijnenvoer 33, 3000, Leuven, Belgium b Department of Obstetrics & Gynaecology and Fetal Medicine, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium c Department of Neonatal Medicine, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium d Department of Radiology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

A R T I C LE I N FO

A B S T R A C T

Keywords: Congenital airway obstruction Ex utero intrapartum treatment Fetoscopy Teratoma Branchial

Introduction: Congenital head and neck pathology may cause direct postnatal airway obstruction. Prenatal diagnosis facilitates safe delivery with pre- and perinatal airway assessment and management and Ex-UteroIntrapartum-Treatment (EXIT) if necessary. Fetoscopic airway evaluation can optimize the selection of patients in need of an EXIT procedure. Methods: Description of 11 consecutive fetuses, born with a potential airway obstruction between 1999 and 2011 and treated at the University Hospitals Leuven, with a long-term follow-up until 2018. An algorithm including fetoscopic airway evaluation is presented. Results: In utero imaging revealed seven teratomas, one fourth branchial pouch cyst, one thymopharyngeal duct remnant, one lymphatic malformation and one laryngeal atresia. A multidisciplinary team could avoid EXIT in eight patients by ultrasonographic (n = 2) or fetoscopic (n = 6) documentation of accessible airways. Three patients needed an EXIT-to-airway-procedure. Neonatal surgery included tracheostomy during EXIT (n = 2) and resection of teratoma (n = 7) or branchiogenic pathology (n = 3). All patients do well at long-term (minimum 54 months) follow-up. Conclusions: Combining prenatal imaging and perinatal fetoscopy, EXIT-procedure and neonatal surgery yields an optimal long-term outcome in these complex patients. Fetoscopy can dramatically reduce the number of EXITprocedures.

1. Introduction Congenital head and neck tumors and malformations may cause direct postnatal upper airway obstruction, asphyxia and death [1]. With the introduction of ultrasound screening programs, congenital head and neck pathology can frequently be diagnosed prenatally and the scenario of postnatal airway obstruction can be prevented. Depending on the origin, obstructive head and neck lesions are classified as extrinsic or intrinsic to the fetal airway [2] (Table 1). Among extrinsic lesions, head and neck teratomas are the most common cause of fetal airway obstruction [3]. Branchial cleft anomalies are the second cause [4]. Nearly 85% arise from the second branchial apparatus [5,6] and only 2–8% from the fourth branchial apparatus, mostly

a typically left sided fourth branchial pouch sinus, that extends from an internal opening in the piriform sinus to the trachea-esophageal groove [4,6]. Third branchial anomalies such as the thymopharyngeal duct remnant cyst are even less frequent [7]. A third common cause of extrinsic airway compression are cervical lymphatic malformations, fluidfilled cystic masses, often localized in the anterior or posterior compartments of the neck [4]. Intrinsic obstruction can result from subglottic stenosis or atresia, tracheal or laryngeal agenesis or webbing, and laryngeal atresia. The latter is the most common cause of complete or near-complete laryngeal or tracheal obstruction, which results in congenital high airway obstruction syndrome (CHAOS) [8]. In these children, karyotyping must be performed, and a decision whether or not to proceed with the

∗

Corresponding author. Otorhinolaryngology, Head and Neck Surgery and department of Oncology, section Head & Neck Oncology, KU Leuven, Belgium, University Hospitals Leuven (Gasthuisberg), Herestraat 49, 3000, Leuven, Belgium. E-mail address: [email protected] (V.L.M. Vander Poorten). 1 Both authors contributed equally to this manuscript. https://doi.org/10.1016/j.ijporl.2019.03.018 Received 3 January 2019; Received in revised form 13 March 2019; Accepted 14 March 2019 Available online 16 March 2019 0165-5876/ © 2019 Published by Elsevier B.V.

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neonatal intubation can be attempted. If the airway is not accessible, strategies to maximize the perinatal time frame for securing the airway are (1) Operation On Placental Support (OOPS) and (2) Ex Utero Intrapartum Treatment (EXIT). In OOPS, the neonate is fully delivered by caesarian section, but the umbilical cord is not clamped, so that the third stage of labor is delayed until the airway is secured. This gives a rather unpredictable extra time window of 5–10 min, and implies a risk of uterine atony and maternal bleeding [13]. A longer and more predictable time frame is obtained via EXIT. This is a technically and logistically much more demanding procedure, where hysterotomy allows for the fetus to be partially delivered (head, neck and one arm) and maintained on placental support for on average 60 min [14]. During this time frame, the airway can be stabilized (EXIT-to-airway) either via intubation, rigid bronchoscopy or tracheostomy, and even partial resection of the obstructive mass can be performed. Once the airway is established, definitive neonatal surgery can then be safely planned. If this does not work, even an EXIT to extracorporeal membrane oxygenation (ECMO) can be established. Our center has developed a large experience in fetoscopy for fetal airway evaluation [15]. This technique allows for safe in utero evaluation of the airway accessibility, and thus enables a better selection of those patients really in need of the cumbersome EXIT procedure. In this paper, we propose an algorithm showing the essential place of fetoscopy in optimizing the use of the EXIT procedure in prenatally diagnosed head and neck lesions that threaten the airway.

Table 1 Causes of fetal airway obstruction (extrinsic and intrinsic). Extrinsic

Intrinsic

Teratoma: cervical, nasopharyngeal, oral Branchial cleft/pouch/arch anomaly: remnant of thymopharyngeal duct, branchial cyst Congenital goiter Lymphatic malformation Micrognathia Thyroglossal duct cyst Neuroblastoma Hamartoma Vascular malformation or tumor Lipoma - lipoblastoma Parotid tumor Solid thyroid tumors Cervical fetus in fetu

Laryngeal atresia Laryngeal stenosis Laryngeal web Laryngeal cyst Tracheal stenosis Tracheal atresia

pregnancy and with the extensive procedure surrounding a safe delivery, must depend on careful balancing of the observed anomalies, the compatibility with life, the postnasal remedies and long-term care needed, in relation to parental coping capacities. Prenatal suspicion of such an anomaly demands referral to a center that is familiar with the accurate prenatal diagnosis of the type of anomaly, as well as with its perinatal and final management. These anomalies may induce secondary problems already in the pre- and perinatal period. First, compromised fetal swallowing can result in polyhydramnios in one third of cases, risking preterm rupture of the membranes and preterm delivery [1]. The use of corticosteroids, tocolysis and in severe cases amniodrainage may be required to optimize the moment and the conditions of delivery [9,10]. Second, elevated intrathoracic pressure due to the mass effect may decrease venous return, causing cardiac failure, fetal and/or placental hydrops and even maternal mirror syndrome [11]. Third, complete airway obstruction can cause airway dilatation distal to the obstruction, with subsequent overgrowth of the lungs, but also fetal hydrops [11]. Finally, spontaneous or iatrogenic bleeding of highly vascularized tumors must be anticipated [12]. For these children, a safe delivery results from a strategy combining in utero airway assessment and adequate peripartal airway management. If in utero airway assessment reveals a freely accessible airway,

2. Material and Methods Our pre- and perinatal strategy is shown in Fig. 1. The prenatal noninvasive workup consists of high definition two- and three-dimensional ultrasound and fetal MRI [8,11]. On ultrasound, a teratoma appear as an asymmetric, well-defined mass with a mixed appearance, with cystic and solid components and typical calcifications in 50%. Cervical lymphatic malformations present as fluid-filled cystic masses [4]. MRI provides good tissue contrast differentiating teratomas and tumors of other consistency and the imaging quality is not influenced by the position of the fetus or the presence of maternal obesity [16]. Obstruction of the fetal airway results in retention of lung fluid and in complete obstruction, the lungs bilaterally hyperexpand, the airways below the obstruction dilate and the diaphragm flattens or inverts, features that

Fig. 1. Diagnostic algorithm of decision-making in the patient with prenatally suspected congenital head and neck pathology with impact on the fetal airway. 165

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Fig. 2. Neonatal teratoma – patient 8: 2a) 2D ultrasound at 29 weeks, encircled is the semi-cystic, semi-solid mass compressing the airway; 2b) 3D ultrasound at 31 weeks; 2c) fetal MRI.

monitoring is critical [20]. Maintenance of the uterine volume is essential to the persistence of uteroplacental circulation. This is obtained by only partial delivery of the fetus (the head and neck, one arm and one shoulder) and simultaneous infusion of high volumes of warmed fluids using a transfusion pump. The fetal torso helps to lock the uterine access [8]. Safe and effective foetoplacental circulation during EXIT has been estimated up to be as long as 60 min [8]. With the infant partially displayed, the airway is established using different techniques, ranging from direct laryngoscopy, rigid bronchoscopy to tracheostomy when needed after partial resection of obstructing masses [3,16]. Once the airway is secured and ventilation is effective, the umbilical cord can be clamped, the infant fully delivered, and tocolysis aborted. Using this strategy, three possible airway situations with corresponding airway management options are identified (Fig. 1). When a patent airway is expected (1), pregnancy continues under ultrasound follow-up, followed by cesarean section or normal induction, depending on the malformation and the relation to the birth canal. When airway patency is questionable (2), pregnancy continues under ultrasound follow-up, and the Leuven strategy is to plan a multidisciplinary team approach (fetal medicine specialists, anesthesiologists, neonatologists and otolaryngologists) to perform a fetoscopic airway assessment immediately preceding elective delivery in the operating room, with everything prepared for an EXIT procedure. This fetoscopy is performed under epidural anesthesia under ultrasound assistance and can reveal two possible airway situations. When fetoscopy shows a patent airway, we can proceed safely with cesarean section or normal induction. When fetoscopy shows an obstructed airway, the EXIT procedure is indicated to maximize the time frame in which to establish an airway, either by EXIT to intubation, EXIT to rigid bronchoscopy (which can help in moving some compressing tumors) and intubation, or EXIT to tracheostomy [25]. When the airway is obviously not patent (3), the EXIT procedure is used to maximize time available to establish an airway by neonatal surgery that can consist of tracheostomy, or of definitive resection of the tumor or malformation [25].

are easily recognized on ultrasound (CHAOS). The condition is often associated with fetal ascites and hydrops, because of impaired venous return to the heart [17,18]. Prenatal MRI confirms these typical ultrasound findings and both methods contribute to determining the level and extent of obstruction and the anticipated optimal endotracheal tube diameter at the moment of attempted airway control around birth [4] (Fig. 2). We introduced the more invasive method of fetoscopy to evaluate the fetal airways in specific patients. Fetoscopic interventions became popular since the introduction of percutaneous endoluminal occlusion of the fetal trachea for severe cases of congenital diaphragmatic hernia (CDH), using a balloon [19]. In these patients, the balloon is most frequently removed at 34 weeks, and in over half of the cases this is done in utero by fetal tracheoscopy. With this experience, we have learned to safely access the fetal airways at different gestational ages under variable technical circumstances, such as the presence of oligohydramnios, at the onset of labour and difficult fetal position [20]. Consequently, we have started to use this technique to explore the fetal airways in fetuses with congenital head and neck pathology. In these instances, when there is doubt about airway accessibility based on the prenatal imaging, we use fetoscopy to guide the decision whether or not to perform an EXIT procedure. The patency of the fetal airway is assessed endoscopically after puncturing the maternal abdomen and the uterus wall. The procedure is typically performed under regional or local anesthesia with sedation and immobilization of the fetus (using curare and fentanyl intramuscularly or via the umbilical cord vessels). A thin walled flexible cannula loaded with a trocar is then inserted in the area of interest under ultrasound guidance. Depending on the position of the fetus, external version might be necessary to enable a safe entrance. The placenta needs to be avoided at all times but anterior placenta is no contraindication, if a placenta free window can be identified. The presence of polyhydramnion might enhance fetal mobility, necessitating prior amniodrainage [20,21]. If during this procedure there is any doubt about the patency of the airways, one can proceed directly, or at a later stage, to a formal EXIT procedure. Fetoscopy can also be used to create airway patency prenatally. Kohl was the first to describe this in a case of Fraser syndrome [22]. In case of cystic obstructive lesions, in utero puncture may reduce or reverse the airway obstruction, and as such avoid an EXIT procedure [4] (Fig. 3). If, following this prenatal diagnostic approach, airway obstruction is anticipated, delivery by EXIT is planned. The EXIT procedure was first described for restoring tracheal patency after earlier surgical clipping to trigger lung growth in severe congenital diaphragmatic hernia (CDH) [19]. The EXIT procedure is performed under general maternal and fetal anesthesia, which also contributes to uterine relaxation [8]. The goal of an EXIT is to maintain uteroplacental circulation by delaying placental separation [20,23,24]. Uterine relaxants, in case of haemorrhage, may cause a decrease in maternal blood pressure, thus intensive

2.1. Patients This study analyzed the pre-, peri-, and direct postnatal management and the long-term follow-up of 11 consecutive cases with prenatal suspicion of head and neck pathology that were managed using the principles described under the “Material and Methods” section (Table 2). Follow-up was performed until 1st May 2018, except for one case (patient 5), which was followed-up till March 2013 (median follow-up 103 months, range 54–214 months). The study was reviewed and approved by the Medical Ethics Committee of the University Hospitals Leuven (Institutional Research Board number S52733) and informed consent was obtained for all patients. 166

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Fig. 3. Fetoscopic evaluation of the fetal airways of patient 8 at 37 weeks of gestation: 3a) Fetoscopic view of fetal epiglottis (star); 3b) Fetoscopic view of fetal glottis (right vocal cord “+”, left vocal cord “-“); 3c) Fetoscopic view of fetal subglottis with narrowed tracheal lumen (right vocal cord “+”, left vocal cord “-“); 3d) Fetoscopically going through the narrowest part of the trachea (star: pars membranacea); 3e) Fetoscopically past the narrowest part of the trachea: arrow indicates towards carina.

3. Results

3.1. Extrinsic obstruction

was an epignathus teratoma originating from the nasopharyngeal roof. A 36 year primigravida was urgently referred because of the fetal diagnosis of an obstructive nasopharyngeal mass and subsequent polyhydramnios at 32 weeks. Because of its obstetrical impact, a semi-elective EXIT-to-tracheostomy procedure had to be performed. Immediately after, the nasopharyngeal mass was partially resected. Pathology showed mature elements such as cartilage, bone, maturating nervous tissue with formation of cerebral cortex and plexus choroideus, intestinal tissue including muscularis propria and Auerbach plexus, retina and pancreatic parenchyma. There were however immature components, consisting of areas of immature neural tissue with formation of primitive neural tubules, but no yolk sac elements were discovered. The alpha FP level quickly diminished in the following days. Postoperatively however, an intraventricular haemorrhage, subdural hematoma and an ischemic lesion in the left parietooccipital region was diagnosed. On day 14, a ventriculo-peritoneal shunt was placed to treat progressive hydrocephaly. Because of an episode of convulsions, with confirmed epileptic activity on electroencephalogram, luminal and diphantoïne were started. On MRI at 8 days of life, residual tumor was observed (15 × 25 × 40 mm) in the roof of the nasopharynx, which extended to the skull base. The residual tumor was resected three weeks after birth, with negative resection margins. Decannulation was possible at the age of 20 months. There remains to date, at the age of 18 years, clear facial dysmorphia, velopharyngeal insufficiency, but normal food and fluid intake. He followed the special education system and this year he will graduate as a baker.

3.1.1. Teratomas 3.1.1.1. Epignathus teratoma (patient 1). In one patient, the teratoma

3.1.1.2. Thyroid teratoma (patient 2, 3, 8, 9, 11). In 5 teratoma patients, the tumor originated in the thyroid tissue. A typical case history

In 11 patients with prenatally suspected head and neck disorders, advanced in utero imaging suggested seven teratomas (5 thyroid teratomas, 1 epignathus teratoma, 1 floor of mouth teratoma), one 4th branchial pouch cyst, one cystic thymopharyngeal duct remnant, one lymphatic malformation and one laryngeal atresia. Median gestational age at diagnosis was 24 weeks (range: 20–35 weeks). In eight patients, an EXIT procedure was avoided by ultrasonography showing a free airway (n = 2) or by perinatal fetoscopic visualization of the carina confirming accessible airways (n = 6) (Fig. 3). Three patients needed an EXIT-to-airway procedure. Neonatal surgery included tracheostomy during the EXIT procedure (n = 2), definitive teratoma resection (n = 7) in the immediate postnatal period and definitive resection of branchiogenic pathology (n = 1). At last follow-up, the patient operated for the 4th branchiogenic pouch cyst is considered cured. All 7 patients with a resected neonatal teratoma are alive without evidence of disease (normal alpha FP and beta HCG levels). However, 1 patient, operated in the neonatal period for a midline thyroid teratoma, presented with a recurrent anterior neck swelling at 10 months of age, which was confirmed as a thyroglossal duct cyst with abcess formation followed by resection via a standard Sistrunk procedure. The patient and procedure details are tabulated in Table 2, in the chronological order in which the patients presented to us.

167

168

28 w

20 w

20 w

24 w

23 w

34 w

35 w

29 w

24 w

20 w

23 w

1

2

3

4

5

6

7

8

9

10

11

neck mass

cystic neck mass

cystic neck mass -polyhydramnios

neck mass - polyhydramnios

cystic mass floor of mouth

CHAOS* - fetal hydrops -polyhydramnios - ascites neck mass

nasopharynx mass polyhydramnios neck mass - polyhydramnios fetal hydrops - pleural effusion neck mass - polyhydramnios fetal hydrops - pleural effusion neck mass

Prenatal US* - fetal MRI

*US: ultrasound. *CHAOS: congenital high airway obstruction syndrome.

Gestational age at diagnosis (weeks)

Patient

FS not performed airway patent FS: airway patent

FS: airway patent

intra-uterine cyst aspiration; FS: airway patent FS: airway patent

FS not performed airway patent FS: airway not patent FS: airway not patent

FS: airway patent

FS: airway patent

FS not available

Fetoscopy (FS)

38 w: spontaneous breathing 37 w: elective cesarean - intubation

37 w: elective cesarean - intubation 34 w: elective cesarean - intubation

37 w: elective cesarean -spontaneous breathing

34 w: EXIT-totracheostomy 36 w: EXIT-tointubation

32 w: EXIT-totracheostomy 34 w: elective cesarean intubation 34 w: elective cesarean intubation 41 w: normal partus

Delivery airway management

4th branchial pouch cyst left sided immature cervical teratoma thyroid isthmus

mature cervical teratoma right thyroid lobe mature cervical teratoma right thyroid lobe

day 10: resection – right thyroidlobectomy day 5: resection - right thyroidlobectomy day 15: resection without thyroidlobectomy day 2: resection without thyroidlobectomy

mature cystic floor of mouth teratoma

mature cervical teratoma left thyroid lobe mature-immature cervical teratoma left thyroid lobe right posterior neck lymphatic malformation laryngeal atresia, treatment in referring tertiary center thymopharyngeal cyst

epignathus mature teratoma

Diagnosis

none: intubated transport and resection abroad in referring center day 14: transoral lasermicroresection

day 0: tracheostomy

day 1: resection - left thyroidlobectomy day 1: resection - left thyroidlobectomy resection at 4 months

day 0: transoral resection

Neonatal surgery University Hospitals Leuven

Table 2 Clinical data of the 11 patients with prenatal diagnosis of head and neck pathology, born at the University Hospitals Leuven.

66 m

77 m

88 m

93 m

93 m

104 m

54 m

108 m

110 m

125 m

214 m

Follow-up (months)

alive and well - no recurrence - normal (para)thyroid function

alive and well - no recurrence - normal (para)thyroid function alive and well - no recurrence - normal (para)thyroid function – conductive hearing loss right ear alive and well

alive and well

neurodevelopmental problems - not decannulated alive and well

Minimal neurodevelopmental problems, deafness right ear - facial dysmorphia alive and well - no recurrence - normal (para)thyroid function alive and well - no recurrence - normal (para)thyroid function alive and well

Status at end of follow-up

K. Beckers, et al.

International Journal of Pediatric Otorhinolaryngology 121 (2019) 164–172

International Journal of Pediatric Otorhinolaryngology 121 (2019) 164–172

K. Beckers, et al.

The baby could be smoothly intubated. The cyst was located on the midline of the floor of mouth, rather anteriorly and superficial. Because of a quickly increasing volume, laser resection was performed at day 14. During this procedure, both submandibular ducts, both lingual nerves and the intrinsic tongue musculature remained intact. The baby was extubated on day 15 and discharged on day 18. The alpha FP level and beta HCG normalized quickly to remain negative. From 3 weeks postoperatively, no functional or aesthetic sequelae persisted. He has a normal mobility of the tongue (Fig. 5) and a completely normal function at the current age of 9 years.

concerns a 30-year old gravida 2 para 1, referred at 34 weeks with polyhydramnios, fetal hydrops and preterm contractions. A cervical mass (57 × 53 × 44 mm) was seen on ultrasound and MRI. It had a mixed appearance and was located at the left neck base, causing tracheal deviation. Doppler measurements of the umbilical and middle cerebral artery were normal, the deepest vertical amniotic fluid pocket was 83 mm. No other abnormalities were detected. The patient had a shortened cervix, delivery seemed imminent. At 34 weeks thus, steroids were administered [26], and we performed a fetoscopic evaluation of the airways, which were patent. We proceeded therefore with a standard Cesarean section and delivered the baby that underwent smooth intubation. The day after, the cervical teratoma was completely excised and found to originate from the left thyroid lobe. Additional left thyroid lobectomy with preservation of the recurrent laryngeal nerve and both parathyroids was performed. The baby was extubated on day 5. The baby was discharged from the hospital in good health on day 25. The alpha FP level remain negative from 4 months onwards (now 3 years of age). The histories of the other 4 prenatally diagnosed thyroid teratomas were quite similar and are summarized in Table 2. In 4 patients, resection required a thyroid lobectomy. In one patient (patient 11) where the tumor originated from the isthmus, no thyroid lobectomy was required. This patient however posed a problem of a cystic anterior neck mass with an infectious syndrome at 10 months of age. Alpha FP and beta HCG remained normal. MR imaging suggested recurrent teratoma versus thyroglossal duct cyst but surgery (Sistrunk procedure) and pathological findings were compatible with the latter diagnosis. Until now, none of the patients with a thyroid lobectomy needed thyroxin substitution, but close pediatric endocinological follow-up will be needed until adulthood. Otherwise all 5 patients are doing very well, develop normally, and have a hardly visible scar, with the exception of one patient (patient 9) who had an extremely large teratoma destroying the strap muscles at birth. She is now 8 years old and is at the moment not bothered by the scar (Fig. 4).

3.1.2. Branchial anomalies 3.1.2.1. Cystic remnant of the thymopharyngeal duct (patient 6). A 39year old gravida 2 para 1 with a diamniotic dichorionic twin pregnancy was referred at 34 weeks, because one fetus was found to have a cystic mass extending from the heart into the left neck. Because of maternal claustrophobia no fetal MRI could be made. There was no polyhydramnios, and the cervix was not shortened. Doppler measurements were normal. At 36 weeks, fetoscopic airway exploration could not demonstrate patency, so that an EXIT was performed at 36.2 weeks. However, on placental circulation and with hyperextension, the trachea could be smoothly intubated. Postnatal MRI confirmed a 84 × 33 × 20 mm cystic remnant of the thymopharyngeal duct. The neonate was extubated on day 1 and discharged in good health on day 8. The thymopharyngeal duct cyst was resected in the referring academic center at 13 weeks. Follow-up now at age of 10 years is uneventful. 3.1.2.2. 4th branchial pouch cyst (patient 10). A 35-year old gravida 2 para 1 was referred at 20 weeks, because the fetus was found to have a cystic mass measuring 11 × 10 × 9 mm anteriorly in the left neck. This finding was confirmed on fetal MRI at 27 weeks. At 35 weeks a connection with the pharynx, opening upon swallowing, was confirmed at ultrasound. At 38 weeks the mass had decreased in size, to measure 3.5 × 3.0 × 4.5 mm without polyhydramnios or airway compromise, and the cervix was not shortened. It was decided to go for a normal vaginal partus and the boy was born at 38.2 weeks of gestational age. The neonate was breathing and feeding normally, but following oral feeding the cyst quickly increased in size to measure at day 10 on MR 4 × 4.1 × 4.6 cm, so surgery was planned at day 14. The cyst was resected, including the sinus tract ending in the apex of the left piriform sinus, preserving the thyroid lobe, the superior and recurrent laryngeal nerve and both the parathyroids. Follow-up now at age of 8 years is uneventful.

3.1.1.3. Floor of mouth teratoma (patient 7). A 36-year old primigravida was referred at 35 weeks because of a potentially obstructive lesion in the fetal mouth. Both ultrasound and MRI described a unilocular cystic mass (44 × 25 × 34 mm) occupying the entire oral cavity, originating from the tongue or the floor of the mouth. The prenatal imaging was suggestive of a foregut duplication cyst. We performed in utero fetoscopy at 37 weeks, which was only possible following transabdominal cyst puncture and aspiration. We thus could demonstrate patent airways, enabling to avoid EXIT and coupled general anesthesia. Labour was induced after the fetoscopic procedure, during which fetal distress prompted a Cesarean section.

3.1.3. Lymphatic malformation (patient 4) A 26-year old gravida 1 para 0 was diagnosed with a fetus with a

Fig. 4. Giant thyroid teratoma at birth with destruction of the strap muscles (4a); aesthetic situation at 8 years of age (4b) in patient 9. 169

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Fig. 5. Patient 7 with good mobility of the tongue after laser resection of floor of mouth teratoma.

Fig. 6. 2D and 3D ultrasound images of lymphatic malformation at 35 weeks of gestation in patient 4.

years of age no problems remain until age of 10 years at this moment.

right sided cystic posterior neck mass with a septation within, at 24 weeks gestational age. At 35 weeks the cystic mass measured 44 × 28 × 40 mm on ultrasound (Fig. 6). There was no obvious polyhydramnios or airway compromise, and the cervix was not shortened. At 41 weeks a normal vaginal partus was induced because of postdatism. The neonate had a right sided posterior neck mass, a left sided branchiogenic appendage, and was breathing freely. Feeding however initially was difficult with aspiration (resulting in aspiration pneumonia at 6 weeks of age) and regurgitation to a degree that nasogastric tube feeding was needed to facilitate normal thriving. An achalasia of the upper esophageal sphincter was diagnosed and the different problems were ascribed to a neural crest developmental disorder. MR at 3 months of age showed increasing diameters (44 × 53 × 64 mm) so the cyst was resected uneventfully with identification and preservation of the accessory nerve. Postoperatively oral feeding gradually resumed and at 3

3.2. Intrinsic obstruction 3.2.1. Laryngeal atresia (patient 5) In a 40-year old gravida 3 para 0, prenatal ultrasound at 23.4 weeks revealed fetal hydrops with polyhydramnios and ascites, suspect of CHAOS. The deepest vertical pocket measured 54 mm at referral and 150 mm at 32.4 weeks. Doppler flow measurements were pathologic, with reversed A-wave in the ductus venosus, pulsatile flow in the umbilical vein and peak systolic velocity in the middle cerebral artery. Fetal MRI confirmed a 4–5 mm discontinuity of the airway at the level of the larynx. Karyotype was normal at that time. In view of the anomalous Dopplers, as well as the risk for spontaneous preterm delivery, corticosteroids were administered. At 32.6 weeks, fetoscopic 170

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stress for the managing team can be obtained.

creation of tracheal patency was attempted at 32.6 weeks but failed. At 34.4 weeks, after amniodrainage under local anesthesia, an elective EXIT was performed under general anesthesia. A tracheostomy was performed. A baby boy was born, with associated prune belly syndrome and imperforated anus. On day 5, the ascites fluid was drained and enteral alimentation was started. Baby and mother were discharged from the hospital in good health on day 12. Surgical correction of the atresia was attempted in the referring tertiary care center. In 2013 decannulation was still not possible. He has a neurodevelopmental disorder with mental retardation, and no speech production. The patient can walk, but feeding is extremely difficult with remaining gastrostomy dependence in 2013. A genetic mozaicism has been diagnosed. This case was lost to follow-up since 2013.

5. Conclusions In patients with congenital head and neck pathology with potential direct postnatal airway obstruction, a strategy combining prenatal imaging, fetoscopic airway exploration and EXIT procedure guarantees a safe airway. Fetoscopic airway evaluation can dramatically reduce the number of (more invasive) EXIT procedures. Subsequent neonatal surgery provides these little ones with long term cure. Especially in patients with teratomas and branchiogenic pathologies, a normal longterm quality of life is to be expected. Declarations of interest

4. Discussion None. The first point this series shows is that in prenatally diagnosed fetal airway obstruction, with the appropriate pre-, peri- and postnatal care, good long-term outcomes can be obtained. Several of these causes of extrinsic as well as intrinsic fetal airway obstruction as listed in Table 1, were observed in the current patient series with long-term follow-up. The majority of our patients was diagnosed with a congenital teratoma (5 thyroid teratomas, 1 epignathus teratoma of the nasopharynx, 1 floor of mouth teratoma), that all could be resected well. Teratomas produce alpha FP and beta HCG, which can be used to monitor the disease, and in all of our patients these markers normalized following resection [27]. However further follow-up of alpha FP is necessary in the next years. Brodsky et al. [28] reviewed in 2017 their 41-year experience with teratoma of the head and neck in 14 neonates. They diagnosed 7 patients prenatally and 7 patients at birth or shortly thereafter, also using ultrasound and MRI imaging. In this series 4 patients underwent an EXIT procedure, with 3 patients requiring intubation and 1 requiring tracheostomy [28]. In the current series, 2 patients had branchiogenic anomalies, one arising from the third and on from the fourth branchial system. The typical pattern of extension of a fourth branchial pouch sinus is nicely demonstrated in our patient. One patient had a lymphatic malformation. Sheikh et al. [29] evaluated in 2015 35 fetuses with cervical masses for long-term outcome, including functional and cosmetic results. EXIT procedure was used in 18 cases. Surgery was performed in 22 of the 25 surviving patients. They observed that children with lymphatic malformation had the highest risk for disfigurement, cranial nerve dysfunction and persistent disease [29]. In our case however, there were no sequelae after surgical resection. Finally, one patient in our series presented with laryngotracheal stenosis and CHAOS syndrome, which is fatal unless emergency tracheostomy can be done at the time of birth. Prenatal diagnosis and planned EXIT delivery dramatically increased the chances for postnatal survival [17,25]. In our patient, although still dependent on a tracheostomy and long-term care, the family has never regretted to have proceeded as was decided prenatally on the basis of extensive counseling and weighing of the many important decisional aspects. The second point we make in this paper is that fetoscopy is an ideal tool to optimize the pre- and perinatal management by identifying which congenital neck masses will necessitate an EXIT procedure or not. In 8 of the 11 cases of our study we performed a fetoscopy. After this fetoscopy, we concluded that the airway was patent in 6 fetuses and non-patent in 2 fetuses. Consequently, an EXIT-procedure was only performed in these 2 cases with non-patent airways during fetoscopy. In 1 patient, a tracheostomy could be safely performed in the time frame provided by the EXIT procedure, in the other the EXIT-procedure maximized the time frame to perform a difficult intubation. In all, the strategy including fetoscopic in-utero evaluation of the airway, allowed us to safely avoid an EXIT-procedure in 6 of the 8 cases. Consequently, a significant reduction in the perinatal risk for mother and child, as well as a significant reduction in costs, logistic burden and

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