title: The fetal cleft palate: III. Ultrastructural and functional analysis of palatal development following in utero repair of the congenital model.
abstract: The role of fetal surgery in the management of congenital anomalies and intrauterine abnormalities is appropriately restricted on the basis of feasibility and risk-to-benefit analyses of intrauterine intervention. Recently, the authors demonstrated that in utero cleft palate repair of the congenital caprine model is technically feasible and results in scarless healing of the mucoperiosteum and velum, with subsequent development of a potentially functional bilaminar palate with distinct oral and nasal mucosal layers, following single-layer repair of the fetal mucoperiosteal flaps. A slight indentation at the site of repair was the only remaining evidence of a cleft. At 6 months of age, normal palatal architecture, including that of mucosal, muscular, and glandular elements, was seen grossly and histologically. The present work investigated the ultrastructural and functional aspects of the palate following in utero cleft repair to determine what benefits might be derived from fetal intervention. Six goats pregnant with twins were gavaged twice daily for 10 days (gestational days 32 to 41; term, 145 days) with dry, ground Nicotiana glauca plant delivering between 2.4 and 14 mg/kg per day of anabasine, doses that were adjusted in response to mater-nal toxicity. At 85 days' gestation, six fetuses underwent in utero palatoplasty using a modified von Langenbeck technique with elevation of bilateral mucoperiosteal flaps and lateral relaxing incisions. A single-layer repair of the mucoperiosteal flaps was performed using interrupted 6-0 Vicryl sutures. Six fetuses remained as unrepaired clefted controls. Six months after in utero palatoplasty, each group of goats underwent nasoendoscopy to evaluate palatal function; two unclefted 6-month-old goats served as controls. Subsequently, soft palate muscle was harvested from each of the goats and was evaluated by light and electron microscopy. Velar muscle was also harvested from the unclefted control goats and was similarly studied. Nasoendoscopy demonstrated functional palates capable of dynamic velopharyngeal closure following in utero cleft repair; this motion was similar to that observed in unclefted animals. Unrepaired clefted goats did not demonstrate any evidence of velar motion or velopharyngeal closure. Soft palate muscle from this group demonstrated evidence of myofibril degeneration, atrophy, and loss compared with unclefted control velar muscle. Ultrastructural changes included sarcomere "scalloping, " partial Z-line degeneration and loss, and progressive I-band degeneration and loss. Repaired clefted soft palate muscle was remarkably similar to unclefted control muscle. Significantly less myofibril, Z-line, and I-band degeneration and loss were observed with minimal evidence of sarcomere scalloping. In utero cleft palate repair results in a functional soft palate with restoration of ultrastructural architecture of the velum. These findings were attributed to reconstitution of the velar muscular sling, which is disrupted during the clefting process and remains abnormally inserted into the posterior edge of the palatal bone and along the bony cleft. Although repaired velar muscle does demonstrate some evidence of ultrastructural change compared with control muscle, these findings are significantly less pronounced than those observed in the unrepaired clefted muscle.
authors.affiliation: Department of Plastic Surgery, Division of Biology and Medicine, Brown University School of Medicine, Rhode Island Hospital, Hasbro Children's Hospital, 2 Dudley Street-Suite 380, Providence, R.I. 02905, USA. scalpels@aol.com
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weinzweig
authors.forename: Kip E
authors.initials: KE
authors.lastname: Panter
authors.forename: Anthony
authors.initials: A
authors.lastname: Spangenberger
authors.forename: James S
authors.initials: JS
authors.lastname: Harper
authors.forename: Robert
authors.initials: R
authors.lastname: McRae
authors.forename: Lee E
authors.initials: LE
authors.lastname: Edstrom
mesh_terms: D000818:Animals; D002972:Cleft Palate / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D005315:Fetal Diseases / Q000601:surgery; D005333:Fetus / Q000601:surgery*; D006041:Goats; D008855:Microscopy, Electron, Scanning; D010159:Palate / Q000254:growth & development* / Q000503:physiopathology; D010160:Palate, Soft / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D010609:Pharyngeal Muscles / Q000503:physiopathology / Q000648:ultrastructure; D011247:Pregnancy