Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 2. Surgical results.

BACKGROUND: Longstanding uncertainty surrounds the selection of surgical protocols for unilateral cleft lip and palate, and randomised trials have only rarely been performed. The Scandcleft Project consists of three trials commenced in 1997 involving ten centres in Denmark, Finland, Norway, Sweden, and the UK. Three groups of centres tested a newly-defined common technique for palatal repair (Arm A) against their local protocols (Arms B, C, D). Arm A was familiar to most of the surgeons in Trial 1, but not to the surgeons in the other Trials. AIM: To evaluate surgical events and complications of the 448 (293 boys, 155 girls) patients with complete unilateral cleft lip and palate (UCLP) enrolled in the three trials. METHOD: The three trials were carried out in parallel in adherence with a fully developed, ethically approved protocol. Operative time, bleeding, complications, and major dehiscence during and after both primary surgeries were recorded by the surgeon. Rates of fistula and surgery for velopharyngeal incompetence (VPI) were assessed until the youngest patient of the study had reached the age of 9 years. Pearson Chi-square statistical analysis was used to compare the outcomes. RESULTS: No significant differences in bleeding, infection, anaesthetic complications or length of hospital stay between the different arms were found for Trial 1. However, in Trials 2 and 3 there were more airway problems in Arm A than with the traditional local protocols (Arms C or D). In Trial 3 fistula and VPI surgery rates were also higher in Arm A. CONCLUSIONS: The results do not provide statistical evidence that any technique is better than others, but indicate that surgery was more problematic for surgeons who were still gaining experience with an unfamiliar surgical protocol. TRIAL REGISTRATION: ISRCTN29932826.

A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.

BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project. METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes. RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years. CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series. TRIAL REGISTRATION: ISRCTN29932826.

Superiorly based pharyngeal flap for treatment of velopharyngeal insufficiency in patients with 22q11.2 deletion syndrome.

BACKGROUND: There are no previous blinded studies for comparison of preoperative versus postoperative perceptual speech assessments when using a pharyngeal flap for treating velopharyngeal insufficiency (VPI) in patients diagnosed with 22q11.2 deletion syndrome. The aim of the study was to evaluate the effect of superiorly based pharyngeal flap surgery on speech in these patients using blinded judgments of experienced speech therapists. METHODS: A retrospective study of 12 consecutive patients who had undergone pharyngeal flap surgery for treatment of VPI between 2002 and 2009 was conducted. Seven girls and 5 boys between 4 and 15 (median, 6) years old at the time of surgery were included in the study. Six patients were born with a submucous cleft palate (including 2 occult), and 1 patient, with an overt cleft palate. The remaining 5 patients had no signs of a palatal pathology. All palatal clefts had been repaired before pharyngeal flap surgery except in 2 patients with occult submucous cleft palate. Preoperative and postoperative audio recordings were blinded for scoring independently by 3 senior speech therapists. RESULTS: There was a significant improvement in hypernasality (P = 0.002), audible nasal emission (P = 0.033), weak pressure consonants (P = 0.008), and speech intelligibility (P = 0.021) after pharyngeal flap surgery. Hyponasality did not develop significantly with surgery. One patient was diagnosed with obstructive sleep apnea. CONCLUSIONS: Superiorly based pharyngeal flap resulted in a significant speech improvement in 12 consecutive patients with 22q11.2 deletion syndrome having VPI.

Speech and magnetic resonance imaging results following autologous fat transplantation to the velopharynx in patients with velopharyngeal insufficiency.

OBJECTIVE: To measure velopharyngeal closure with magnetic resonance imaging (MRI) and to evaluate speech when treating velopharyngeal insufficiency (VPI) with autologous fat transplantation to the velopharynx. PATIENTS: Nine patients were recruited. Six patients had undergone cleft palate repair and subsequently developed VPI. Three were noncleft patients of which one had developed VPI after nasopharyngeal cancer treatment; another patient had developed VPI after combined adenotonsillectomy, and a third patient had VPI of unknown etiology. MAIN OUTCOME MEASURE: Preoperative and 1-year postoperative MRIs were obtained during vocal rest and during phonation. Data measured were the velopharyngeal distance in the sagittal plane and the velopharyngeal gap area in the axial plane. Preoperative and 1-year postoperative audio recordings were blinded for scoring independently by three senior speech therapists. RESULTS: When comparing preoperative and 1-year postoperative MRI during phonation we found a significant reduction of the median velopharyngeal distance from 4 to 0 mm (p = .011), and a significant reduction of the median velopharyngeal gap area from 42 to 34 mm(2) (p = .038). Nasal turbulence improved significantly (p = .011). Hypernasality/hyponasality and audible nasal emission did not change significantly. CONCLUSIONS: Autologous fat transplantation to the velopharynx resulted in a significant reduction of the velopharyngeal distance and the velopharyngeal gap area during phonation, as measured by MRI. This was in accordance with a significant improvement in nasal turbulence. However, hypernasality and audible nasal emission did not change significantly and could not be correlated to the MRI findings.

Pharyngoplasty after primary repair of clefts of the secondary palate.

Our aim was to identify factors associated with the incidence of pharyngoplasty in patients with clefts of the secondary palate (CP). We studied 351 children born between 1968 and 1999 with CP alone, who had their primary operation at the Department of Plastic Surgery, Rikshospitalet University Hospital, Oslo, Norway. Data were collected retrospectively from the archives of the Oslo Cleft Team. During the study period 1968-2007, 68 children (19%) had a pharyngoplasty to improve their speech. Mean follow up time from the primary operation was 16 years (range 2-37). The estimated incidence of pharyngoplasty at 5, 7, 10, and 15 years after the primary operation was 9%, 12%, 14%, and 15%, respectively. Thirty-one (46%) of the pharyngoplasties were done more than seven years after the primary palatal repair. Children with total clefts of the secondary palate had a pharyngoplasty more often than children with clefts of the soft palate alone (7 years incidence: 11 (42%) compared with 22 (10%), p<0.001). Sex, age at time of primary operation, and surgeon's experience were not significantly associated with the necessity for pharyngoplasty. Our study suggested that the necessity for pharyngoplasty is related to the severity of clefts, and duration of observation.

Palatal fistulas after primary repair of clefts of the secondary palate.

Our aim was to assess whether severity of cleft, age at the time of repair, and the operating surgeon's experience contributed to the development of fistulas in patients with clefts of the secondary palate. We studied 814 children born between 1960 and 1999 with clefts of the secondary palate who had had their primary operation at the Department of Plastic Surgery, Rikshospitalet University Hospital, Oslo, Norway. Data were collected retrospectively from the archives of the Oslo Cleft Team. Palatal fistulas developed in 36 patients (4%), among whom 17 patients required correction (2% of the total). The incidence of fistulas was not related to sex. Patients with clefts of the hard and soft palate developed fistulas more often than patients with clefts of the soft palate only (8% compared with 1%, p<0.001). Patients with submucous cleft palates developed fistulas significantly more often than patients with clefts of the soft palate only (5% compared with 1%, p=0.02). Among patients with clefts of the hard and soft palate, the incidence of fistulas increased significantly with increasing age at the time of palatal closure (p=0.005). The incidence decreased significantly the more experienced the operating surgeon was for treating clefts of the hard and soft palate (p<0.001) but not for submucous clefts. Among patients with clefts of the hard and soft palate who had the palate closed at 14 months of age or later, the incidence of fistulas decreased from 21% when the operating surgeon had little experience to 0 when the surgeon had much experience. The incidence of fistulas was related to severity of cleft, age at palatal closure, and the operating surgeon's experience.

Prevalence of major anatomic variations in oral clefts.

BACKGROUND: The authors describe morphologic variations of oral clefts in a large population-based sample, especially variations in severity and laterality. The authors present 3616 cleft cases treated in Norway for oral clefts between 1967 and 1998. METHODS: Classification of cleft morphology was based on clefting in 9 anatomical focal areas. A three-digit coding system provides a total of 63 possible cleft combinations. Their distribution in the population is presented as a whole and stratified by the baby's sex and the presence of accompanying malformations. The relative proportion of cleft types is illustrated in modified striped Y Kernahan diagrams. RESULTS: Clefts of the lip or palate are more severe when both cleft types are present. Among babies with cleft lip, 18 percent of lips were severe (i.e., complete cleft of the primary palate) in the absence of cleft palate, compared with 81 percent severe when cleft palate was also present. Similarly, among babies with cleft palate, 40 percent were severe (complete cleft of the secondary palate) in the absence of cleft lip, compared with 93 percent when cleft lip was also present. The more severe the cleft lip, the more likely that the baby had an accompanying cleft palate. Girls were more likely to have severe clefts, as were patients who had other types of congenital disabilities. Although cleft lip was more frequent on the left side, clefts were not more severe on the left side. In bilateral cleft lip, the severity was similar on both sides. CONCLUSION: The authors' data provide a population-based reference for common and rare variants of oral clefts.

Patient-reported outcomes after breast reconstruction with deep inferior epigastric perforator flaps.

We assessed patient-reported outcomes in 34 women who had had their breasts reconstructed with a deep inferior epigastric perforator (DIEP) flap, and compared them with those of 24 patients who were waiting for breast reconstruction. Both groups completed the Short Form 36 (SF-36) questionnaire. The DIEP flap group also assessed their preoperative conditions retrospectively and completed a study-specific questionnaire. The DIEP group reported higher SF-36 mental health scores after the operation than before, but no difference on other SF-36 scales. There was no difference on any SF-36 scale between patients who had had DIEP flaps and those waiting for reconstruction. Most of the DIEP group was satisfied with their bodies, the appearance of their breasts after reconstruction, and would have chosen operation again. In conclusion, there was little improvement in generic health-related quality of life after reconstruction with a DIEP flap. However, patients' satisfaction was high after the procedure.

Green urine after surgical treatment of pressure ulcer.

We describe a 58-year-old man who developed green urine after operation on a pressure ulcer. The discolouration disappeared gradually after two days. We think that the use of methylene blue dye during the revision of the wounds and the use of the sedative propofol could have caused it.

Folic acid supplements and risk of facial clefts: national population based case-control study.

OBJECTIVE: To explore the role of folic acid supplements, dietary folates, and multivitamins in the prevention of facial clefts. DESIGN: National population based case-control study. SETTING: Infants born 1996-2001 in Norway. PARTICIPANTS: 377 infants with cleft lip with or without cleft palate; 196 infants with cleft palate alone; 763 controls. MAIN OUTCOME MEASURES: Association of facial clefts with maternal intake of folic acid supplements, multivitamins, and folates in diet. RESULTS: Folic acid supplementation during early pregnancy (> or =400 microg/day) was associated with a reduced risk of isolated cleft lip with or without cleft palate after adjustment for multivitamins, smoking, and other potential confounding factors (adjusted odds ratio 0.61, 95% confidence interval 0.39 to 0.96). Independent of supplements, diets rich in fruits, vegetables, and other high folate containing foods reduced the risk somewhat (adjusted odds ratio 0.75, 0.50 to 1.11). The lowest risk of cleft lip was among women with folate rich diets who also took folic acid supplements and multivitamins (0.36, 0.17 to 0.77). Folic acid provided no protection against cleft palate alone (1.07, 0.56 to 2.03). CONCLUSIONS: Folic acid supplements during early pregnancy seem to reduce the risk of isolated cleft lip (with or without cleft palate) by about a third. Other vitamins and dietary factors may provide additional benefit.

Prevalence of duplications and deletions of the 22q11 DiGeorge syndrome region in a population-based sample of infants with cleft palate.

The prevalence of duplications and deletions of the 22q11.2 (DiGeorge syndrome) region was studied among babies born in Norway with open cleft palate without cleft lip (cleft palate only, CPO). During a 5-year period (1996-2001), there were 245 live births with CPO that were referred for surgery. DNA was available from 174 cases with overt cleft palate. DNA copy number was analyzed with the multiplex ligation-dependent probe amplification (MLPA) technique, and an unambiguous result was obtained in 169 (97%) of the samples. We found no 22q11.2 duplications, and one known, and two previously undiagnosed cases with 22q11.2 deletions. All three del22q11-syndrome cases also had heart malformations, which represent one-third of the 10 babies with heart malformations in our study population. The prevalence of del22q11-syndrome among babies with cleft palate with or without additional malformations was 1 of 57 (1.8%). Because the prevalence of CPO in the 35 22q11.2 duplication cases published was 20%, we also investigated if dup22q11-testing was warranted in this group. However, no 22q11.2 duplications were found, indicating that the duplication cases ascertained so far might not be representative of the dup22q11-group as a whole. We conclude that neither del22q11 nor dup22q11 testing is warranted in babies with overt cleft palate as the only finding.

Skin burned by contact with flagstones made of cement.

Chemical burns account for few admissions to burns units. A well-known but rare cause is wet cement. We present a case where a man had a full-thickness skin burn after contact with flagstones made of cement.

Computed tomography of alveolar bone grafts 20 years after repair of unilateral cleft lip and palate.

The aim of this study was to estimate the clinical condition and amount of remaining grafted bone 20 years after final repair of unilateral cleft lip and palate. Eighteen consecutive patients had computed tomograms (CT) and clinical examination 20 years or more after secondary bone grafting which had been done at ages of 7-11 years. The images were obtained with a spiral CT with 1 mm collimation, and reconstructed as three-dimensional volumes with reformatted cut planes. The area of grafted bone was measured in a plane perpendicular to the curved axis of the alveolar arch and compared with the area corresponding section through the non-cleft side. The clinical examination showed satisfactory results in all. CT indicated a mean cross sectional area of 97 mm2 on the cleft side compared with 157 mm2 on the non-cleft side. The bone mass was significantly less on the grafted cleft side (p < 0.001), but the functional results were satisfactory.

Cleft palate, transforming growth factor alpha gene variants, and maternal exposures: assessing gene-environment interactions in case-parent triads.

We have previously reported a threefold risk of cleft palate only (CPO) among children homozygous for the less common allele A2 at the TaqI marker site of the transforming growth factor alpha gene (TGFA) (Jugessur et al. [2003a] Genet. Epidemiol. 24:230-239). Here we assess possible interaction between the child's TGFA TaqI A2A2 genotype and maternal cigarette smoking, alcohol consumption, use of multivitamins and folic acid. This was done by comparing the strength of genetic associations between strata of exposed and unexposed case-parent triads. We also looked for possible gene-gene interaction with the polymorphic variant C677T of the folic acid-metabolizing gene MTHFR. We analyzed a total of 88 complete CPO triads selected from a population-based study of orofacial clefts in Norway (May 1996-1998). No evidence of interaction was observed with either smoking or alcohol use. The risk associated with two copies of the A2 allele at TGFA TaqI was strong among children whose mothers did not use folic acid (relative risk=4.5, 95% confidence interval=1.3-15.7), and was only marginal among children whose mothers reported using folic acid (RR=1.4, 95% CI=0.2-12.7). Although the interaction between the child's genotypes at TGFA TaqI and MTHFR-C677T was not statistically significant, the effect of the TGFA TaqI A2A2 genotype appeared to be stronger among children with either one or two copies of the T-allele at C677T (RR=4.0, 95% CI=1.1-13.9) compared to children homozygous for the C-allele (RR=1.7, 95% CI=0.2-15.7). In conclusion, we find little evidence of interaction between the child's genotypes at TGFA TaqI and various exposures for cleft palate, with the possible exception of folic acid intake.

Exploring the effects of methylenetetrahydrofolate reductase gene variants C677T and A1298C on the risk of orofacial clefts in 261 Norwegian case-parent triads.

Folic acid and the methylenetetrahydrofolate reductase (MTHFR) gene have both been implicated in the etiology of orofacial clefts. The authors selected 261 case-parent triads (173 cases with cleft lip with or without cleft palate (CL/P) and 88 cases with cleft palate only (CPO)) from a Norwegian population-based study of orofacial clefts (May 1996-1998). A case-parent triad design was used to examine whether MTHFR variants C677T and A1298C, and their haplotypes, are risk factors for orofacial clefts. Among CL/P cases, the child's genotype at C677T or A1298C did not influence the risk. However, children of mothers carrying the C677T variant allele had a lower risk of CL/P. For CPO, children carrying the C677T variant allele had about a twofold increased risk, whereas the mother's genotypes did not contribute to the risk. The haplotype-based transmission/disequilibrium test showed that except for 677T/1298A (p = 0.06), none of the other haplotypes showed evidence of excess transmission to the offspring. The authors also explored interaction of C677T with maternal use of folic acid among children with CPO. Surprisingly, the risk associated with the child's carrying either CT or TT was higher (fourfold) when the mother used folic acid. These findings suggest a possible role of MTHFR and folic acid in the causation of orofacial clefts, but the strength and direction of these effects remain to be clarified.