Reliability of Variables of Consonant Production and Velopharyngeal Competence in 10-year-olds with Cleft Palate Using Multiple Raters.

OBJECTIVE: To assess the reliability of speech data and speech-related quality indicators in the Swedish quality registry for cleft lip and palate (CLP) at 10 years of age. DESIGN: Retrospective study. SETTING: University hospitals. PARTICIPANTS: One hundred twenty-one 10-year-olds with unilateral or bilateral CLP. MAIN OUTCOME MEASURES: Six independent raters reassessed audio recordings for comparison with registry data. For calculation of agreement, the single measures intraclass correlation coefficient (ICC) was used for percentage of consonants correct (PCC) and non-oral speech errors, quadratic weighted kappa for velopharyngeal competence (VPC), and percentage agreement and kappa for quality indicators. The results of the three to four raters with the highest intra-rater and inter-rater reliability were used for comparison with registry data. RESULTS: There was excellent agreement between registry data and reassessments for PCC (ICC, 0.93) and percentage of non-oral errors (ICC, 0.80). For VPC, one rater and registry data had good agreement (k, 0.704); the remaining cases had fair agreement (k, 0.476-0.554). The percentage agreement between registry data and reassessments for quality indicators ranged from fair to excellent. When calculated with kappa, agreement was good to excellent (mean of all k values, 0.67-0.70). CONCLUSIONS: The CLP registry variables PCC and percentage of non-oral errors and the quality indicators without non-oral speech errors and competent/marginally incompetent velopharyngeal function are reliable for use in clinical audits and research of 10-year-olds. The three-tier ratings of VPC have weaker reliability but can still be useful in more detailed analyses if interpreted with caution.

Congenital diaphragmatic hernia and cleft lip and palate: looking for a common genetic etiology.

PURPOSE: Congenital diaphragmatic hernia (CDH) and cleft lip and/or palate (CL/P) are inborn closure defects. Genetic factors in and outcomes for patients with both anomalies (CDH+CL/P) remain unclear. We aimed to investigate associated genetic aberrations, prevalence of, and outcomes for, CDH+CL/P. METHODS: Data from Congenital Diaphragmatic Hernia Study Group (CDHSG) registry were collected. CL/P prevalence in CDH patients was determined. Genetic abnormalities and additional malformations in CDH+CL/P were explored. Patient characteristics and outcomes were compared between CDH+CL/P and isolated CDH (CDH-) using Fisher's Exact Test for categorical, and t-test or Mann-Whitney U-test for continuous, data. p < 0.05 was considered statistically significant. RESULTS: Genetic anomalies in CDH+CL/P included trisomy 13, 8p23.1 deletion, and Wolf-Hirschhorn syndrome (4p16.3 deletion). CL/P prevalence in CDH was 0.7%. CDH+CL/P had lower survival rates than CDH-, a nearly fourfold risk of death within 7 days, were less supported with extracorporeal life support (ECLS), had higher non-repair rates, and survivors had longer length of hospital stay. CONCLUSION: Genetic anomalies, e.g. trisomy 13, 8p23.1 deletion, and Wolf-Hirschhorn syndrome, are seen in patients with the combination of CDH and orofacial clefts. CL/P in CDH patients is rare and associated with poorer outcomes compared to CDH-, influenced by goals of care decision-making.

Central Auditory Processing Abilities in Children with Non-Syndromic Cleft Lip/and Palate-a Behavioural Study.

The present study aimed to assess the central auditory processing abilities and working memory in children with non-syndromic cleft lip and palate (NSCLP) and to compare with the developed normative and craniofacially normal peers. Sixteen NSCLP children aged 7 to 12 years and fifteen craniofacially normal peers were recruited in this study. Speech perception in noise Kannada (SPIN-K), gap detection threshold (GDT), dichotic consonant-vowel (DCV), and masking level difference (MLD) tests were administered to assess various central auditory processing abilities. Working memory abilities were assessed by using forward-digit span and backward-digit span tests. The results showed significant differences in SPIN-K, dichotic CV, GDT, forward digit, and backward digit span scores between children with NSCLP and craniofacially normal peers. Thus, it can be concluded from the present study that children with NSCLP have a risk of developing auditory processing deficits. To conclude, assessment of central auditory processing abilities in children with NSCLP is recommended.

Risk of self-harm ideation in mothers of children with orofacial cleft defects: the Japan environment and children's study.

Introduction: Cleft lip and/or palate (CL/P), the most prevalent congenital anomaly, has been associated with higher rates of child maltreatment. In particular, the presence of cleft lip has more of an impact on external appearance and may increase the risks of negative health outcomes such as parental postpartum depression; however, this concept remains controversial. Item #10 of the Edinburgh Postpartum Depression Scale is the assessment of parental self-harm ideation, and its presence in postpartum mothers merits risk assessments as an emergent issue that may affect the health of both mothers and infants. This study focused on the impact of CL/P on maternal self-harm ideation. Methods: Of 100,300 live births from a nationwide birth cohort in Japan, 238 mothers of infants with CL/P [186 children born with cleft lip (CL ± P) and 52 born with isolated cleft palate (CP)] were included in the analyses. The prospective association of children with CL/P and maternal self-harm ideation, which were acquired using item #10 in the Edinburgh Postpartum Depression Scale at 1 and 6 months postpartum, was examined using binomial logistic regression analyses after multiple imputations and with adjustments for several maternal (age at delivery, smoking habit, and alcohol intake) and child-related (sex and prevalence of other congenital diseases) variables. Results: The prevalence of self-harm ideation in 238 mothers of infants with CL/P at 1 and 6 months were 14.7% (35/238) and 18.8% (45/238) [8.2% (8,185/100,062) and 12.9% (12,875/100,062) in the control group], respectively. The odds ratio (95% confidence interval) for maternal self-harm ideation increased with CL/P prevalence [1.80 (1.22-2.65) and 1.47 (0.98-2.18)] at 1 and 6 months of age, respectively. After stratified by the prevalence of cleft lip, we found significant differences in the CL ± P group but not in the CP group. Furthermore, persistent self-harming ideation was associated with a higher risk in the CL ± P group [2.36 (1.43-3.89)]. Conclusion: CL/P, particularly cleft lip, which is more noticeable externally, was associated with an increased prevalence of maternal self-harm ideation. The findings in this study indicate some potential benefits of increasing support for mothers who have infants with CL/P.

Three-dimensional Analysis of Presurgical Nasoalveolar Molding Outcomes in Patients with Unilateral Cleft Lip and Palate: A Preliminary Study Using LED Surface Scanning Technology.

OBJECTIVES: Presurgical infant orthopedic appliances, such as presurgical nasoalveolar molding (PNAM) devices, are used to attain optimal conditions for primary repair of the lip and nose (PRoLN) in patients with cleft lip. We aimed to analyze the three-dimensional (3D) outcomes of PNAM using an LED surface scanner. METHODS: Fifteen patients with unilateral cleft lip and palate (CLP) were included in this study and treated using a PNAM device. The patients' faces were digitized pre- and post-PNAM using an Artec Space Spider scanner, and the scanned data were analyzed using 3D software (Geomagic Control X and ANSYS SpaceClaim). The columellar angle (CA), nostril curvature (NC) on the affected (NC_A) and unaffected (NC_U) sides, gap of cleft lip (GCL), alar width (AW), and nasal tip angle (NTA) were measured. RESULTS: CA increased significantly by 10.00° and NC_A by 0.030 mm-1 (p<0.001). GCL decreased by 4.98 mm2 on average and NC_U by 0.015 mm-1 (p=0.029 and 0.046, respectively). AW also decreased by approximately 1.22 mm pre- and post-treatment (p=0.002), and NTA, which shows a lateral profile, decreased by approximately 3.32° (p=0.002). CONCLUSIONS: This study confirmed the orthopedic benefits of PNAMd treatment through 3D analysis using an LED surface scanner. Further studies involving a larger number of participants are warranted to study the effects of PNAM and analyze longitudinal changes in patients with CLP. CLINICAL SIGNIFICANCE: This study shows that PNAM effectively corrects columellar deviation and nostril shape in patients with unilateral cleft lip, with 3D scanners enhancing primary lip and nose repair outcomes.

A Comparative Effectiveness Study of Speech and Surgical Outcomes: Study Overview.

AIMS: To provide an overview of the Cleft Outcomes Research NETwork (CORNET) and the CORNET Speech and Surgery study. The study is (1) comparing speech outcomes and fistula rate between two common palate repair techniques, straight-line closure with intra-velar veloplasty (IVVP) and Furlow Double-Opposing Z-palatoplasty (Furlow Z-plasty); (2) summarizing practice variation in the utilization of early intervention speech-language (EI-SL) services; and (3) exploring the association between EI-SL services and speech outcomes. DESIGN: Prospective, longitudinal, observational, comparative effectiveness, multi-center. SITES: Twenty sites across the United States. PARTICIPANTS: One thousand two hundred forty-seven children with cleft palate with or without cleft lip (CP ± L). Children with submucous cleft palate or bilateral sensorineural severe to profound hearing loss were excluded from participation. INTERVENTIONS: Straight-line closure with IVVP or Furlow Z-plasty based on each surgeon's standard clinical protocol. MAIN OUTCOME MEASURE(S): The primary study outcome is perceptual ratings of hypernasality judged from speech samples collected at 3 years of age. Secondary outcomes are fistula rate, measures of speech production, and quality of life. The statistical analyses will include generalized estimating equations with propensity score weighting to address potential confounders. CURRENT PROGRESS: Recruitment was completed in February 2023; 80% of children have been retained to date. Five hundred sixty two children have completed their final 3-year speech assessment. Final study activities will end in early 2025. CONCLUSIONS: This study addresses long-standing questions related to the effectiveness of the two most common palatoplasty approaches and describes CORNET which provides an infrastructure that will streamline future studies in all areas of cleft care.

Presurgical Nasoalveolar Molding and Columella Lengthening for Early Unilateral Cleft Lip and Palate Rehabilitation: A Comprehensive Clinical Case Report.

Aim and background: In presurgical infant orthopedics, nasoalveolar molding (NAM) therapy has gained more popularity worldwide in treating patients with cleft lip and palate because of its soft tissue nasal corrections in addition to the alignment and close approximation of the cleft alveolar segments, which gives better postsurgical stability and esthetics with minimal tissue tension and scar formation to the patients.The clinical case report aims to show the better post-NAM results, which had helped to gain better postsurgical results in terms of stability and aesthetics in hard and soft tissues. Case description: This clinical report presents the case of a 9-day-old female patient reported in the Department of Orthodontics and Dentofacial Orthopedics at Sharad Pawar Dental College and Hospital with nonsyndromic complete left-sided unilateral cleft lip and palate with a defect size of 13 mm, which was treated with a presurgical nasoalveolar molding (PNAM) appliance. NAM therapy takes advantage of circulating maternal estrogen, bringing pliability to the cartilage cells for presurgical cartilage molding. This has resulted in the closure of the alveolar defect from 13 mm to <2 mm in the present case, with nasal symmetry restoration due to nasal stent within 12 weeks of active treatment; hence, the postsurgical esthetics are maintained. Conclusion: NAM therapy remained beneficial and had significant aesthetic results in reducing the cleft defect size. Because of this, it gained a big surgical advantage in reducing tissue tension, primary stability, and scar formation. Clinical significance: By reducing the cleft defect size of the dysplastic maxillae, which brings the lip segments and alveolar segments closer to each other, it thus reduces the defect size for primary lip and palate repair. This serves as the biggest advantage for maxillofacial and plastic surgeons to maintain the posttreatment results with redefined aesthetics and symmetry. How to cite this article: Taori KP, Niranjane P, Kamble R. Presurgical Nasoalveolar Molding and Columella Lengthening for Early Unilateral Cleft Lip and Palate Rehabilitation: A Comprehensive Clinical Case Report. Int J Clin Pediatr Dent 2024;17(8):955-961.

Enhancing Surgical Outcomes: Presurgical Nasoalveolar Molding for Unilateral Cleft Lip, Alveolus, and Palate in Infants-A Progressive Clinical Report.

This case report describes the successful application of presurgical nasoalveolar molding (PNAM) in the treatment of a neonate with Veau's class III cleft lip and palate of the left side. PNAM, a noninvasive method, effectively reduced the cleft deformity (from 10 mm pretreatment to 1 mm post-NAM), improved nasal esthetics, and minimized the need for extensive surgical interventions and better surgical outcomes. The treatment involved precise impression procedures, custom-made appliances, and weekly modifications to achieve optimal results. The comprehensive approach resulted in favorable esthetic outcomes, reduced scar formation, and improved lip symmetry, demonstrating the potential of PNAM as a valuable adjunctive therapy in cleft lip and palate management. How to cite this article: Yadav L, Mattu N, Yadav N, et al. Enhancing Surgical Outcomes: Presurgical Nasoalveolar Molding for Unilateral Cleft Lip, Alveolus, and Palate in Infants-A Progressive Clinical Report. Int J Clin Pediatr Dent 2024;17(8):951-954.

Case report: Artificial thymic organoids facilitate clinical decisions for a patient with a TP63 variant and severe persistent T cell lymphopenia.

Pathogenic variants in the transcription factor TP63 are associated with clinically overlapping syndromes including ectrodactyly-ectodermal dysplasia clefting (EEC) and ankyloblepharon-ectodermal defects-cleft lip/palate (AEC). T cell lymphopenia has rarely been described in individuals with TP63 variants and the cause of the T cell defect is unclear. Here, we present a case of a female infant born with TP63-related syndrome and profound T cell lymphopenia, first uncovered through newborn screening. Flow cytometry analysis revealed low CD4+ naïve T cells and nearly absent CD8+ T cells with intact B and NK cell compartments. A de novo heterozygous pathogenic variant c.1040 G>A (C347Y) in exon 8 of TP63 was identified. An artificial thymic organoid system, to assess the intrinsic ability of the patient's hematopoietic cells to develop into T cells, was performed twice using separate peripheral blood samples. Ex vivo T cell differentiation was evident with the artificial organoid system, suggesting that a thymic stromal cell defect may be the cause of the T cell lymphopenia. Consistent with this, interrogation of publicly available data indicated that TP63 expression in the human thymus is restricted to thymic epithelial cells. Based on these data, congenital athymia was suspected and the patient received an allogenic cultured thymus tissue implant (CTTI). This is the first report of suspected congenital athymia and attempted treatment with CTTI associated with TP63 variant. At 9 months post-implant, peripheral lymphocyte analysis revealed measurable T cell receptor excision circles and presence of CD4+ recent thymic emigrants suggestive of early thymopoiesis. She will continue regular monitoring to ensure restoration of T cell immunity.

Bridging Gaps in Health Literacy for Cleft Lip and Palate: The Role of Artificial Intelligence and Interactive Educational Materials.

OBJECTIVE: Our goal is to address the health literacy gap concerning cleft lip and palate using artificial intelligence (AI), specifically OpenAI's ChatGPT-4, to enhance the readability of patient educational materials (PEMs). Additionally, we aim to explore the integration of interactive educational materials into these resources. DESIGN: A cross-sectional study. SETTING: Websites of craniofacial teams approved by the American Cleft Palate-Craniofacial Association (ACPA). PATIENTS/PARTICIPANTS: PEMs collected from these websites. INTERVENTIONS: First, we examined the PEMs for interactive educational content such as videos, photos, case examples, and audio clips. Subsequently, we used the WebFX online readability calculator and Grammarly to evaluate the texts' readability and clarity. After that, we used ChatGPT-4 to simplify the PEM texts to a 6th-grade reading level and re-evaluated their readability and clarity. MAIN OUTCOME MEASURE(S): Readability levels (grade level) and clarity scores of PEMs before and after AI modification, and the presence of interactive educational content. RESULTS: Initial evaluations using the Flesch-Kincaid Grade Level formula showed that the texts were written at a median 9th-grade reading level. Modifications using ChatGPT-4 significantly improved readability, achieving a median 6th-grade level and enhanced clarity. Only 27% of the websites featured interactive educational content, indicating a gap in utilizing educational enhancements. CONCLUSION: The use of AI improved the readability and clarity of patient educational materials, aligning with recommended standards. However, the underutilization of interactive tools suggests a need for broader integration of these resources to optimize patient education and engagement.

A Rorschach Test.

Unexpectedly intersecting her path with a person with a congenital anomaly gives the writer an opportunity to reflect on her own understanding of patients outside the medical perimeter that ultimately influences her point of view during the hospital encounter.

Association of rs8670 Polymorphism in the MSX1 Gene With Non-Syndromic Cleft Lip With or Without Cleft Palate in Malay Population.

OBJECTIVE: This study aimed to investigate the association between variants present in the MSX1 gene and the risk of developing non-syndromic cleft lip with or without cleft palate (NSCL±P) among individuals of Malay ethnicity in Malaysia. MATERIALS AND METHODS: This case-control study involved 89 patients with NSCL±P and 100 healthy control subjects. Polymerase chain reaction (PCR) was performed on both exon 1 and exon 2 of the MSX1 gene using four pairs of primers. The amplification products were then subjected to denaturing high-pressure liquid chromatography for initial screening, and the presence of a heteroduplex peak was validated using direct sequencing analysis to detect the single-nucleotide polymorphism. RESULTS: Five previously known variations (c.-36G>A, p.Ala30Ala, p.Ala34Gly, p.Gly110Gly, and rs8670: C>T) were detected within the MSX1 gene in both NSCL±P patients and controls.A significant association was found between the rs8670: C>T variant and NSCL±P (p = 0.017; OR: 0.368; 95% CI: 0.152 - 0.893), with this particular single-nucleotide polymorphism present in 20% (20) among controls and 7.9% (7) of the NSCL±P cases. CONCLUSIONS: Our data showed a lower incidence of the rs8670: C>T polymorphism among NSCL±P cases compared to control in this Malay population. However, since this variant is located in the 3'UTR, it could potentially impact the stability of MSX1 mRNA.

Cleft lip and palate and periconception COVID-19 infection in five arab countries.

BACKGROUND: Little is known about factors associated with the severity of cleft lip with or without cleft palate (CL/P) especially during the COVID-19 pandemic with its dramatic changes. OBJECTIVES: The aim of this multi-national study is to measure the association between CL/P severity, COVID-19 infection, and fear of COVID-19 in five Arab countries. METHODS: This cross-sectional study took place in major governmental hospitals in five Arab countries from November 2020 to April 2023. Participants were infants born with CL/P and their mothers who were in their 1st trimester during the COVID-19 pandemic. Clinical examination was carried out, and CL/P cases were grouped according to phenotype: cleft lip and palate (CLP) versus cleft lip (CL), cleft extension (incomplete versus complete), and site (unilateral versus bilateral) to assess severity. Information on maternal COVID-19 infection and fear of COVID-19 were gathered. RESULTS: The study recruited 273 CL/P infants. Maternal COVID-19 infection during one-month pre-gestation and 1st trimester was significantly associated with higher odds of CL/P severity (AOR = 2.707; P = 0.002) than mothers without the COVID-19 infection. Using supplements during pregnancy showed a protective effect (AOR = 0.573; P = 0.065). CONCLUSION: Mothers infected with COVID-19 before and during pregnancy had more than twofold higher odds of having an infant with a more severe CL/P phenotype.

[Single nucleotide polymorphism heritability of non-syndromic cleft lip with or without cleft palate in Chinese population].

OBJECTIVE: To delve into the intricate relationship between common genetic variations across the entire genome and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). METHODS: Utilizing summary statistics data from genome-wide association studies (GWAS), a thorough investigation to evaluate the impact of common variations on the genome were undertook. This involved assessing single nucleotide polymorphism (SNP) heritability across the entire genome, as well as within specific genomic regions. To ensure the robustness of our analysis, stringent quality control measures were applied to the GWAS summary statistics data. Criteria for inclusion encompassed the absence of missing values, a minor allele frequency ≥1%, P-values falling within the range of 0 to 1, and clear SNP strand orientation. SNP meeting these stringent criteria were then meticulously included in our analysis. The SNP heritability of NSCL/P was calculated using linkage disequilibrium score regression. Additionally, hierarchical linkage disequilibrium score regression to partition SNP heritability within coding regions, promoters, introns, enhancers, and super enhancers were employed, and the enrichment levels within different genomic regions using LDSC (v1.0.1) software were further elucidated. RESULTS: Our study drew upon GWAS summary statistics data obtained from 806 NSCL/P trios, comprising a total of 2 418 individuals from the Chinese population. Following rigorous quality control procedures, 490 593 out of 492 993 SNP were deemed suitable for inclusion in SNP heritability calculations. The observed SNP heritability of NSCL/P was 0.55 (95%CI: 0.28-0.82). Adjusting for the elevated disease pre-valence within our sample, the SNP heritability scaled down to 0.37 (95%CI: 0.19-0.55) based on the prevalence observed in the general Chinese population. Notably, our enrichment analysis unveiled significant enrichment of SNP heritability within enhancer regions (15.70, P=0.04) and super enhancer regions (3.18, P=0.03). CONCLUSION: Our study sheds light on the intricate interplay between common genetic variations and the risk of NSCL/P in the Chinese population. By elucidating the SNP heritability landscape across different genomic regions, we contribute valuable insights into the genetic basis of NSCL/P. The significant enrichment of SNP heritability within enhancer and super enhancer regions underscores the potential role of these regulatory elements in shaping the genetic susceptibility to NSCL/P. This paves the way for further research aimed at uncovering novel genetic pathogenic factors underlying NSCL/P pathogenesis.

Quality of Life and Psychosocial Outcomes Among Children With Cleft Differences.

Introduction Velopharyngeal insufficiency (VPI) and craniofacial differences can lead to diminished speech and swallowing function resulting in communication and social challenges throughout childhood. To monitor changes in patients' psychosocial health and velopharyngeal function, the Pediatric Symptom Checklist (PSC) and Velopharyngeal Insufficiency Effects on Life Outcomes (VELO) survey tools can be utilized. This study aimed to investigate the relationship between VPI quality-of-life outcomes and psychosocial disturbances through a comparative analysis of PSC and VELO parental surveys among children followed by a craniofacial team. Methods A retrospective chart review was completed using data from a single, multidisciplinary cleft and craniofacial team. Previously completed parental survey responses between 2010 and 2022 were collated and results were analyzed using a Spearman's rank correlation test (rs). Results There were 89 subjects who completed both surveys on the same day (n = 148 survey pairs (s)). Patients aged three to five years old (s = 88) had a mean VELO of 17.9 (0-65) and a mean PSC of 7.9 (0-27), while patients aged six to eight years old (s = 60) had a mean VELO of 16.6 (0-74) and a mean PSC of 12.0 (0-37). The strongest correlation observed for both age groups was between the total PSC and VELO Speech Limitations sub-scores (three to five years old: rs = 0.537, p < 0.001; six to eight years old: rs = 0.330, p = 0.010). Similarly, children in the six- to eight-year-old group with cleft lip and palate showed a correlation between the total PSC and VELO Speech Limitations (rs = 0.583, p < 0.001). Conclusion This study suggests a relationship between PSC and VELO scores among children ages three to eight years old with cleft differences and demonstrates that specific domains within the VELO questionnaire should be considered as being associated with a higher risk for psychosocial impairment. Specifically, higher VELO Speech Limitations sub-scores may portend a greater risk for poor psychosocial outcomes supporting the importance of early interventions in this group.

Considering the Environmental Impact of Cleft Lip and Palate Surgery.

OBJECTIVE: We sought to calculate the waste generated by cleft lip and palate (CL/P) procedures and to increase awareness of the environmental impact of our speciality. DESIGN: Waste from 5 CL/P procedures was categorised into 5 streams and weighed. A carbon calculator tool was used to convert weight of waste in to estimated carbon emission over a 12-month period. SETTING: The study was carried out in a university teaching hospital. PATIENTS AND PARTICIPANTS: This was an assessment of the waste produced from 5 paediatric CL/P procedures. MAIN OUTCOME MEASURES: Weight of waste produced as result of CL/P procedures, measured in kilograms (kg); weight of CO2, measured in kg. RESULTS: We found that 768.5 kg of surgical waste was generated by CL/P procedures at our centre annually. This equates to 2653 kg of CO2. CONCLUSIONS: This study serves as a reminder of surgeons' responsibility to oversee how the waste we produce is disposed of.

Hospital-based Costs to the National Health Service (UK) for Children and Adolescents Born with Cleft from Birth to 20 Years.

OBJECTIVE: The primary aim was to assess the cost (£) to the National Health Service (NHS) of hospital treatment for individuals born with bilateral cleft lip and palate (BCLP), unilateral cleft lip and palate (UCLP), and cleft palate (CP), from birth to 20 years. The secondary aim was to assess the number of scheduled clinical outpatient and inpatient/outpatient surgical visits for this cohort. DESIGN: Retrospective micro-costing analysis. SETTING: Patients treated within the South West of England Cleft Service (UK). PATIENTS: Twenty-three case-notes of children born with cleft (5 BCLP; 10 UCLP; 8 CP) were identified from birth up to and including secondary alveolar bone graft (ABG), and a second group of 23 hospital case-notes (3 BCLP; 10 UCLP; 10 CP) were identified, post-ABG to 20 years. RESULTS: Mean costs from birth to ABG were £17,004 (BCLP), £11,620 (UCLP), and £6137 (CP), and post-ABG to 20 years were £9,463, £7,945, and £3,816, respectively. The largest costs were for staff. Repeat surgery had a significant impact on costs. The mean number of clinical outpatient visits for BCLP, UCLP, and CP were 140, 110 and 83 respectively and 8, 6 and 2 for inpatient/outpatient surgical visits, respectively. CONCLUSIONS: Costs for provision of cleft care by the NHS are significant. The greatest costs were incurred with care for patients with BCLP. Patients were expected to attend many appointments, with BCLP experiencing the most visits. Engagement with quality improvement programmes to minimise repeat surgery, and remote consultation for certain appointments, to reduce the patient burden are recommended.

A Bibliometric Analysis of 100 Top-cited Articles on Cleft Orthodontics.

OBJECTIVE: This bibliometric study seeks to provide a comprehensive overview of the 100 most frequently cited articles in the domain of cleft orthodontics. The analysis will reveal key influential publications, collaborative author networks, and identify prevailing research themes within the field. METHOD: The studies related to Orthodontics in the realm of cleft lip and palate (CLP) were retrieved from the Scopus database on 30th August 2024 using key terms. The results obtained were sorted in descending order of citations and the 100 top-cited articles were hand-filtered. RStudio software version 4.2.0 and Bibliometrix R-package was used for performing scientometrics involving co-citation, co-occurrence, collaboration and co-word analyses, bibliographic coupling and network mapping. RESULTS: A total of n = 3984 articles were retrieved from which top-100 cited articles were filtered. These documents were published during 1950-2019 with peak production in 1997. The United States and the Netherlands were the most prolific countries involved in the given research. The majority of the highly referenced articles pertained to alveolar bone grafting, and treatment outcomes being the second common focus followed by Infant and early orthopedics (Naso-alveolar moulding, Maxillary Protraction) and facial growth during the given period. CONCLUSIONS: Thematic mapping depicted bone grafting, alveoloplasty (infant orthopedics) and maxillofacial development as the more developed core topics than the psychology and self-perception of patients with CLP. Recent research trends have shifted towards three-dimensional assessment methods.

Research Trends in Presurgical Infant Orthopaedic Treatment in Patients with Cleft Lip and Palate: A Bibliometric Analysis of 100 Most-Cited Articles.

OBJECTIVE: To assess research trends and publication patterns of literature related to presurgical infant orthopaedics (PSIO) through a bibliometric analysis of the top 100 most-cited articles. MATERIAL AND METHODS: The top 100 most-cited articles were identified in the Web of Science (WoS) database using search terms related to PSIO on April 23, 2024, without any restrictions to study design, publication date and language. Standard information about each study was extracted. Citations from WoS, Scopus and PubMed databases were compared. The level of evidence for each article included was assessed. Association between different variables was calculated using Spearman's correlation coefficient with statistical significance set at p < 0.05. Visual analysis of the author's keyword co-occurrence, co-authorship analysis of authors, and citation analysis of journals and authors were performed using VOSviewer. RESULTS: Top cited articles were published from 1994 to 2020, with total individual database citations being WoS (n = 5378), Scopus (n = 6184) and PubMed (n = 10 450). Eleven articles were considered classic articles. Cleft Palate and Craniofacial Journal (Impact Factor = 1.1) had a maximum number of articles and citations. Two hundred eighty-five individuals contributed to top-cited articles, with 62 corresponding authors from 19 countries. A maximum number of authors were affiliated with universities in the United States. The most common keyword used was "nasoalveolar molding (n = 24)", "cleft palate (n = 16)", and "infant orthopedics (n = 16)". The study design of the majority of articles was retrospective and follow-up studies (level 3; n = 53). A weak negative correlation was observed between citation metrics and both the publication year (P < 0.01) and the level of evidence (P < 0.01). CONCLUSION: This analysis recognises the contributions of experts and offers valuable insights into trends that have shaped the development and evidence related to PSIO research. Future research should focus on integrating advanced technologies, conducting longitudinal studies, fostering collaboration, and emphasizing patient-centred outcomes.

Organotin exposure and DNA methylation in non-syndromic cleft lip and palate: Integrating findings from case-control studies and animal experiments.

Human exposure to organotin is common but little is known about the adverse pregnancy outcomes. This study aimed to explore the association between organotin exposure and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P) and to explore the underlying mechanism. Placental samples (109 NSCL/P cases and 128 controls) were analyzed for 8 organotin concentrations, and subsequent animal experiments were conducted by administering tributyltin (TBT) during critical developmental periods. DNA methylation BeadChip analysis (12 NSCL/P and 12 controls), bisulfite Sequencing analysis (3 NSCL/P and 3 controls mice), and RNA sequencing were performed to explore epigenetic mechanisms. Logistic regression, LASSO regression, support vector machine, random forest, and mediation effect analysis were utilized to identify key genes related to TBT and NSCL/P. Only tributyltin met the detection criteria for further analysis among 8 compounds. The median levels of TBT in cases (8.93 ng/g) were statistically significantly higher than those in controls (5.33 ng/g). Excessive TBT exposure in maternal placenta was associated with an increased risk of NSCL/P (OR = 6.44, 95 % CI, 2.91-14.25) in humans, showing a dose-response relationship (p for trend <0.05). 288 differentially methylated CpG sites in 129 genes were identified between cases and controls. Tributyltin was associated with FGFR2 and SCD hypomethylation, which were identified as potential key genes associated with NSCL/P. Mediation analysis suggested that DNA methylation of FGFR2 and SCD may mediate the impact of TBT on NSCL/P occurrence. TBT exposure during the critical period in mice (GD8.5-GD15.5) can induce progeny NSCL/P. Altered FGFR2 and SCD hypomethylation and gene expression observed in response to TBT exposure in fetal mice. Excessive TBT exposure was associated with increased risks of human NSCL/P. TBT exposure can induce NSCL/P in fetal mice. FGFR2 and SCD were implicated in NSCL/P pathogenesis, potentially mediated by DNA methylation alterations.