Effect of Sustained Interventions from Infancy to Toddlerhood in Children with Cleft Lip and Palate for Preventing Early Childhood Caries.

The study aimed to evaluate the effectiveness of sustained interventions in children with cleft lip and palate (CLP) for preventing early childhood caries (ECC). This prospective, nonrandomized interventional cohort study was conducted in infants aged 0-12 months with congenital CLP. Interventions were given to parents/primary caregivers in the form of combined oral health-care measures (sterile wet gauze piece, finger brush, toothbrush, and toothpaste) by a motivational interviewing approach. Education of primary caregivers on oral hygiene was provided by audiovisual aids and demonstration. Reinforcement of the prescribed regimen was done through daily short message services in caregivers' preferred language and bimonthly telephone calls. Participants were followed up for 9-32 months from the time of recruitment, with a mean period of 18.3 ± 5.1 months. Rates of dental caries were represented as prevalence rates, incidence density, and transitional probability. The distribution of the International Caries Detection and Assessment System (ICDAS) scores on different tooth surfaces affected in the intervention group was compared descriptively with that of the age- and sex-matched historical control groups. On analysis of surface-wise distribution of the ICDAS scores in the intervention group (n = 1,919), 1.2% (n = 24) had noncavitated lesions (ICDAS codes 1 and 2), 0.88% (n = 17) had cavitated lesions (ICDAS codes 3-6), and 0.26% (n = 5) had both cavitated and noncavitated lesions (ICDAS codes 1-6). The incidence density of caries-affected children observed at the first and last follow-ups was 1.2 persons/100 person-months and 1.3 persons/100 person-months of observation, respectively. The incidence density of new caries-affected tooth surfaces at the first and last follow-ups was 0.163 surfaces/100 surface-months and 0.062 surfaces/100 surface-months, respectively. Maxillary first molars had the maximum transition from sound to the cavitated lesion (11.5%), followed by maxillary incisors from sound to noncavitated (7.5%) at the last follow-up. Based on the newly developed assessment criteria in our study, sustained interventions proved to be significantly effective in preventing ECC in children with CLP.

Maternal Vitamin B12 Status and Risk of Cleft Lip and Cleft Palate Birth Defects in Tamil Nadu State, India.

BACKGROUND AND OBJECTIVE: The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B12 and low folate status are each associated with an increased risk of isolated cleft lip with or without cleft palate (CL±P) in a case-control study in Tamil Nadu state, India. METHODS: Case-mothers of CL±P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B12, methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured at that time. Logistic regression analyses estimated associations between nutrient biomarkers and case-control status. RESULTS: Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B12 (OR = 2.48, 95% CI, 1.02-6.01) and high versus low plasma MMA, an indicator of poor B12 status (OR = 3.65 95% CI, 1.21-11.05). Case-control status was not consistently associated with folate or tHcy levels. Low vitamin B12 status, when defined by a combination of both plasma vitamin B12 and MMA levels, had an even stronger association with case-mothers (OR = 6.54, 95% CI, 1.33-32.09). CONCLUSIONS: Mothers of CL±P children in southern India were 6.5 times more likely to have poor vitamin B12 status, defined by multiple biomarkers, compared to control-mothers. Further studies in populations with diverse nutritional backgrounds are required to determine whether poor maternal vitamin B12 or folate levels or their interactions are causally related to CL±P.

A Comparative Study of Two Infant Feeding Tools: The Nifty Cup and The Paladai.

OBJECTIVE: The World Health Organization recommends that infants unable to feed directly at the breast in low resource settings be cup fed with hand expressed breastmilk. No standard feeding cup exists. The aim of this study was to evaluate the design of the Nifty cup, a newly designed feeding cup, as compared to the paladai and to assess acceptability among mothers and health care providers. METHODS: This study was conducted at Sri Ramachandra Medical Center and Research Institute in Chennai. Eligible caregivers were primary caregivers of infants who were less than 12 mo old, born prematurely or with an oral cleft, and who were fed by cup. Health care providers who prescribed cup feeding for infants at least 4 times in the past year were also eligible. Caregivers and health care providers fed each infant with a paladai and a Nifty cup. They completed an interviewer-administered survey. The design and acceptability parameters of the Nifty cup were compared to those of paladai using a Wilcoxon signed rank test. RESULTS: Forty three caregivers and 28 health care providers were enroled. Among caregivers, the Nifty cup as compared to the paladai was less problematic on most parameters including spillage, regurgitation, difficulty in use, and duration of feeding (all p-values <0.01). Findings were similar for health care providers. CONCLUSIONS: The Nifty cup is a promising feeding cup for feeding infants with breastfeeding difficulties to support growth and nutrition.

Burden of Care: Management of Cleft Lip and Palate.

Burden of care has become a commonly used terminology in healthcare in the recent years. Burden of care is the balance how much patients and families commit to their time, compromise quality of life, undergo multiple interventions, and take risks weighing against the benefits the patients and families receive. Cleft lip and palate, congenital anomaly, demands a long-term and interdisciplinary care. These children are at high risk of various treatment/intervention episodes increasing the burden of care. This subject has been widely discussed with many other diseases and health conditions at national, international meetings, and World Health Organization as well. We bring out some facts and practices affecting the burden of care in cleft lip and palate.

The refinement of the median tubercle of cleft lip.

AIM: Repair of cleft lip aims to bring symmetry and provide normal aesthetics for the lip. Several techniques have been employed; however, the finer aspect of median lip tubercle has not been emphasised in cleft lip repair. MATERIALS AND METHODS: We have modified cleft lip repair, both unilateral and bilateral, preserving all the tissues of the median tubercle to provide normal-looking median tubercle of the lip. The modified technique was carried out by a single surgeon on 322 cases of unilateral cleft lip and 68 cases of bilateral cleft lip. Follow-up was done for 1-3 years on these children to evaluate the outcome. RESULTS: The evaluation showed excellent results in more than 80% of patients in unilateral cleft lip repair, on 1-3 years of follow-up; 20% had acceptable results. Of 68 patients with bilateral cleft lip, none had any complication, and excellent results were obtained in 70%. Result was rated acceptable in 30%; 15% may need revision surgery for white roll and vermilion adjustment. CONCLUSION: We present the technique of reconstructing a normal-looking median tubercle in cleft lip repair. The technique was modified based on the study of normal upper lip and embryology of cleft lip, with emphasis on creating better median tubercle of the lip.

IRF6 rs2235375 single nucleotide polymorphism is associated with isolated non-syndromic cleft palate but not with cleft lip with or without palate in South Indian population / Polimorfismo de nucleotídeo único do gene IRF6 rs2235375 está associado com à fenda palatina isolada não sindrômica, mas não com fenda labial com ou sem fenda palatina em população do sul da Índia

Abstract Introduction Transcription factors are very diverse family of proteins involved in activating or repressing the transcription of a gene at a given time. Several studies using animal models demonstrated the role of transcription factor genes in craniofacial development. Objective We aimed to investigate the association of IRF6 intron-6 polymorphism in the non-syndromic cleft lip with or without palate in a South Indian population. Methods 173 unrelated nonsyndromic cleft lip with or without cleft palate patients and 176 controls without clefts patients were genotyped for IRF6 rs2235375 variant by allele-specific amplification using the KASPar single nucleotide polymorphism genotyping system. The association between interferon regulatory factor-6 gene intron-6 dbSNP208032210:g.G>C (rs2235375) single nucleotide polymorphism and non-syndromic cleft lip with or without palate risk was investigated by chi-square test. Results There were significant differences in genotype or allele frequencies of rs2235375 single nucleotide polymorphism between controls and cases with non-syndromic cleft lip with or without palate. IRF6 rs2235375 variant was significantly associated with increased risk of non-syndromic cleft lip with or without palate in co-dominant, dominant (OR: 1.19; 95% CI 1.03-2.51; p = 0.034) and allelic models (OR: 1.40; 95% CI 1.04-1.90; p = 0.028). When subset analysis was applied significantly increased risk was observed in cleft palate only group (OR dominant: 4.33; 95% CI 1.44-12.97; p = 0.005). Conclusion These results suggest that IRF6 rs2235375 SNP play a major role in the pathogenesis and risk of developing non-syndromic cleft lip with or without palate.

Resumo Introdução Fatores de transcrição constituem uma família de proteínas muito diversa envolvida na ativação ou repressão da transcrição de um gene, em um determinado momento. Vários estudos usando modelos animais demonstraram o papel dos genes do fator de transcrição no desenvolvimento craniofacial. Objetivo Nosso objetivo foi investigar a associação do polimorfismo IRF6 intron-6 na fenda labial não sindrômica com ou sem fenda palatina em uma população do sul da Índia. Método Um total de 173 pacientes com fenda labial não sindrômica com ou sem fenda palatina e 176 controles sem fendas foram genotipados para a variante IRF6 rs2235375 por amplificação alelo-específica utilizando o sistema KASPar de genotipagem de polimorfismo de nucleotídeo único. A associação entre o polimorfismo de nucleotídeo único Fator 6 Regulatório do Interferon (IRF6) intron-6 dbSNP208032210:g.G>C (rs2235375) e o risco de fenda labial não sindrômica com ou sem fenda palatina foi investigado pelo teste qui-quadrado. Resultados Houve diferenças significativas nas frequências de genótipos ou alelos do rs2235375 SNP entre controles e casos com fenda labial não sindrômica com ou sem fenda palatina. A variante IRF6 rs2235375 foi significativamente associada ao aumento do risco de fenda labial não sindrômica com ou sem fenda palatina em modelos codominantes, dominantes (OR: 1,19; IC 95%: 1,03-2,51; p = 0,034) e alélicos (OR: 1,40; IC 95%: 1,04-1,90; p = 0,028). Quando a análise do subgrupo foi realizada, um risco significativamente aumentado foi observado no grupo Fenda Palatina Isolada (OR dominante: 4,33; IC 95%: 1,44-12,97; p = 0,005). Conclusões Esses resultados sugerem que o polimorfismo de nucleotídeo único IRF6 rs2235375 desempenha um papel importante na patogênese e no risco de desenvolvimento de fenda labial não sindrômica com ou sem fenda palatina.

IRF6 rs2235375 single nucleotide polymorphism is associated with isolated non-syndromic cleft palate but not with cleft lip with or without palate in South Indian population.

INTRODUCTION: Transcription factors are very diverse family of proteins involved in activating or repressing the transcription of a gene at a given time. Several studies using animal models demonstrated the role of transcription factor genes in craniofacial development. OBJECTIVE: We aimed to investigate the association of IRF6 intron-6 polymorphism in the non-syndromic cleft lip with or without palate in a South Indian population. METHODS: 173 unrelated nonsyndromic cleft lip with or without cleft palate patients and 176 controls without clefts patients were genotyped for IRF6 rs2235375 variant by allele-specific amplification using the KASPar single nucleotide polymorphism genotyping system. The association between interferon regulatory factor-6 gene intron-6 dbSNP208032210:g.G>C (rs2235375) single nucleotide polymorphism and non-syndromic cleft lip with or without palate risk was investigated by chi-square test. RESULTS: There were significant differences in genotype or allele frequencies of rs2235375 single nucleotide polymorphism between controls and cases with non-syndromic cleft lip with or without palate. IRF6 rs2235375 variant was significantly associated with increased risk of non-syndromic cleft lip with or without palate in co-dominant, dominant (OR: 1.19; 95% CI 1.03-2.51; p=0.034) and allelic models (OR: 1.40; 95% CI 1.04-1.90; p=0.028). When subset analysis was applied significantly increased risk was observed in cleft palate only group (OR dominant: 4.33; 95% CI 1.44-12.97; p=0.005). CONCLUSION: These results suggest that IRF6 rs2235375 SNP play a major role in the pathogenesis and risk of developing non-syndromic cleft lip with or without palate.

Transmission analysis of TGFB1 gene polymorphisms in non-syndromic cleft lip with or without cleft palate.

OBJECTIVES: Transforming growth factor beta1 (TGF-ß1) plays a significant role in craniofacial development. Previous linkage studies reported that the TGF-ß1-locus at 19q13.1 harbour predisposing genes for non-syndromic oral clefts. In the present study case parents triads were evaluated to find the transmission effects of genetic variants in TGF- ß1 towards non-syndromic cleft lip or palate (NSCL/P). METHODS: Using allelic discrimination method148 families (case-parent triads) were assessed for single nucleotide polymorphisms (SNPs) in TGF-ß1 gene. The SNPs were checked for mendelian errors and Hardy-Weinberg equilibrium (HWE). Transmission disequilibrium test and haplotype frequencies were estimated. RESULTS: The TGF-ß1 SNPs showed very low minor allele frequencies (MAFs) and observed heterozygosity (Hobs). The transmission disequilibrium test (TDT) and parent-of-origin likelihood ratio tests (PO-LRT) were not significant for any of the SNPs tested. Strong linkage disequilibrium (r2 = 0.722) was found between rs1800469 and rs1800470 SNPs. Haplotype analysis ignoring parent of origin showed strong evidence of excess transmission but it is not significant (p-value = 0.293). CONCLUSION: Transmission of minor alleles were not observed from either parent indicating that the TGF-ß1 gene polymorphisms by themselves do not confer risk for non-syndromic oral clefts but, rather, modify the stability and the activation process of TGF-ß1. As the number of families included in the study are less, results must be considered still preliminary and require replication using more families.

Association of TFAP2A gene polymorphism with susceptibility to non-syndromic cleft lip with or without palate risk in south Indian population.

The aetiology of non-syndromic cleft lip with or without cleft palate (NSCL/P) is complex involving multiple interacting genes and environmental factors. The primary objective of the present study was to investigate the role of TFAP2A gene single nucleotide polymorphisms (SNPs) in the pathogenesis of NSCL/P. In this study, 173 unrelated NSCL/P patients and 176 controls without clefts were genotyped with TFAP2A rs1675414 (Exon 1), rs3798691 (Intron 1), and rs303050 (Intron 4) variants by allele-specific amplification using the KASPar SNP genotyping system. The method of multifactor dimensionality reduction (MDR) was used to analyze gene-gene interactions. TFAP2A polymorphisms are not found to be associated with non-syndromic cleft lip with or without cleft palate (NSCL/P) at either the genotype or allele levels. No linkage disequilibrium (LD) was found between TFAP2A variants. MDR analysis did not show a significant effect of the TFAP2A gene polymorphisms on susceptibility to NSCL/P (p > 0.05). These results suggest that the analyzed variations in TFAP2A gene might not be associated with NSCL/P pathogenesis in south Indian population.

Best Practices for the Diagnosis and Evaluation of Infants With Robin Sequence: A Clinical Consensus Report.

IMPORTANCE: Robin sequence (RS) is a congenital condition characterized by micrognathia, glossoptosis, and upper airway obstruction. Currently, no consensus exists regarding the diagnosis and evaluation of children with RS. An international, multidisciplinary consensus group was formed to begin to overcome this limitation. OBJECTIVE: To report a consensus-derived set of best practices for the diagnosis and evaluation of infants with RS as a starting point for defining standards and management. EVIDENCE REVIEW: Based on a literature review and expert opinion, a clinical consensus report was generated. FINDINGS: Because RS can occur as an isolated condition or as part of a syndrome or multiple-anomaly disorder, the diagnostic process for each newborn may differ. Micrognathia is hypothesized as the initiating event, but the diagnosis of micrognathia is subjective. Glossoptosis and upper airway compromise complete the primary characteristics of RS. It can be difficult to judge the severity of tongue base airway obstruction, and the possibility of multilevel obstruction exists. The initial assessment of the clinical features and severity of respiratory distress is important and has practical implications. Signs of upper airway obstruction can be intermittent and are more likely to be present when the infant is asleep. Therefore, sleep studies are recommended. Feeding problems are common and may be exacerbated by the presence of a cleft palate. The clinical features and their severity can vary widely and ultimately dictate the required investigations and treatments. CONCLUSIONS AND RELEVANCE: Agreed-on recommendations for the initial evaluation of RS and clinical descriptors are provided in this consensus report. Researchers and clinicians will ideally use uniform definitions and comparable assessments. Prospective studies and the standard application of validated assessments are needed to build an evidence base guiding standards of care for infants and children with RS.

Pre-maxillary complex morphology in bilateral cleft and hypothesis on laterality of deviated pre-maxilla.

INTRODUCTION: Pre-maxillary complex (pre-maxilla [PMX] + vomer) morphology in bilateral complete cleft of primary and secondary palate (BCLCP) is very complex and less reviewed in literature. MATERIALS AND METHODS: In this retrospective cross-sectional study, 200 consecutive BCLCP patients were selected. Their pre-operative clinical photographs and dental casts were evaluated by a single investigator at two different points of time, to study the morphology of PMX and vomer with special emphasis on deviation of vomer and rotation of PMX. RESULTS: It is found that in above 70% of patients, PMX and vomer both displaced or deviated towards left side in horizontal plane and PMX rotated anticlockwise at PMX vomerine suture (PVS). In 10% of cases, both PMX and vomer are displaced towards the right side, PMX rotated clockwise at PVS. In 11% of cases, vomer is displaced towards the left side, but PMX rotated clockwise at PVS. In 5% of cases, vomer is displaced towards the right side, but PMX rotated anticlockwise at PVS. Both PMX and vomer are in midline in 4% of cases. CONCLUSION: Specific morphological deviation of vomer and PMX has been studied. We put forward the probable hypothesis to explain the deviation and rotation of PMX.

SATB2 gene variants in non-syndromic cleft lip with or without cleft palate in Indian population.

OBJECTIVES: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common craniofacial birth defects and little is known about its aetiology. Initial studies of cytogenetic analysis provided the clues for possible genes involved in the pathogenesis of NSCL/P. This approach led to the identification of SATB2 gene on 2q32-q33. The aim of this study was to determine the association between SATB2 mutations and NSCL/P. MATERIALS AND METHODS: The rs137853127, rs200074373 and rs1992950 mutations of the SATB2 gene were investigated in 173 patients with NSCL/P and 176 normal controls using Kbioscience KASPar chemistry, which is a competitive allele-specific PCR SNP genotyping system. RESULTS: The mutations in exon 6 (rs137853127 and rs200074373) were monomorphic, the intronic variant (rs1992950) was polymorphic and genotype distribution was in agreement with Hardy-Weinberg equilibrium. The rs1992950 genotype distribution is not statistically significant between NSCL/P and controls. CONCLUSION: Our findings suggest that the SATB2 gene variations do not contribute to the development of NSCL/P in the south Indian population.

Polymorphic variants near 1p22 and 20q11.2 loci and the risk of non-syndromic cleft lip and palate in South Indian population.

BACKGROUND: Recent genome-wide association studies (GWAS) have reported multiple genetic risk loci for non-syndromic orofacial clefts (NSOFCs) in many populations. However, the contribution of these loci to NSOFC in India, which comprises one-fifth of the global population, is completely lacking. Our aim was to replicate the association of the SNPs located on 1p22 chromosomal loci (rs540026, rs481931) and 20q11.2 (rs13041247, rs11696257) in the aetiology of NSOFCs, in South Indian populations. METHODS: The SNPs were genotyped by using KBiosciences KASPar SNP genotyping chemistry in 173 cases and 176 controls for NSOFCs in South India. To estimate the association between these SNPs and NSOFCs, chi-square test was adopted. Odds ratios (OR) with 95% confidence intervals (CI) were also calculated in order to assess the risk. RESULTS: Single nucleotide polymorphisms located at chromosomal region 1p22 are not found to be associated with cleft lip with or without non-syndromic cleft palate (NSCL/P) and non-syndromic cleft palate only (NSCPO) at either the genotype or allele levels. Further, there is no LD observed between these variants. The polymorphic variants near 20q11.2 (rs13041247, rs11696257) are in complete linkage disequilibrium (LD) and are significantly associated with only NSCL/P in genotypic (p=0.013) and allelic models (p=0.029). In the genotypic model significance persisted even after Bonferroni correction (p<0.016). CONCLUSION: These results suggest that 20q11.2 SNPs could play a contributory role in the pathophysiology and risk of NSCL/P, while the variations in 1p22 do not underlie the pathophysiology of NSOFCs in South Indian populations.

Evidence of the involvement of the polymorphisms near MSX1 gene in non-syndromic cleft lip with or without cleft palate.

OBJECTIVE: Non-syndromic cleft lip, with or without cleft palate (NSCL/P) is a common craniofacial birth defect, characterised by an incomplete separation between nasal and oral cavities without any other congenital anomaly in humans. Several genes which play a role in cell differentiation, migration, growth and apoptosis, have been associated with clefting. The purpose of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) near MSX1 gene and NSCL/P among South Indian population. METHODS: A case-control analysis of five single nucleotide polymorphisms near MSX1 gene (rs11726039, rs868257, rs6446693, rs1907998 and rs6832405) was carried out in 173 patients with NSCL/P and 176 unaffected controls to determine their association with NSCL/P. RESULTS: All SNPs were polymorphic in the study population. Comparisons of allele and genotype frequencies revealed that the C variant allele and the TC/CC genotypes of rs11726039 was significantly higher in controls than in the NSCL/P group (OR: 0.63; 95% CI: 0.41-0.097; p=0.037). However, neither of these findings remained significant after Bonferroni correction for multiple comparisons. The frequencies of rs868257, rs6446693, rs1907998 and rs6832405 minor alleles and genotypes were similar between the control and NSCL/P groups. No significant linkage disequilibrium (LD) was observed. Genotype-genotype interaction and the haplotype analysis did not reveal any significant association with NSCL/P. CONCLUSIONS: The study results were suggestive of a positive association between MSX1 rs11726039 and NSCL/P in the South Indian population.

Management of post midface distraction occlusal discrepancy using temporary anchorage devices in a cleft patient.

Open bite deformity following a successful midface advancement by distraction osteogenesis is a common complication. Temporary anchorage devices can be deployed during the distraction and post-distraction settling phases for restoring the occlusion even in severe cases. The following report describes the management of severe anterior open bite following maxillary distraction.

A randomized controlled trial comparing two techniques for unilateral cleft lip and palate: Growth and speech outcomes during mixed dentition.

OBJECTIVE: To study the growth and speech outcomes in children who were operated on for unilateral cleft lip and palate (UCLP) by a single surgeon using two different treatment protocols. MATERIAL AND METHODS: A total of 200 consecutive patients with nonsyndromic UCLP were randomly allocated to two different treatment protocols. Of the 200 patients, 179 completed the protocol. However, only 85 patients presented for follow-up during the mixed dentition period (7-10 years of age). The following treatment protocol was followed. Protocol 1 consisted of the vomer flap (VF), whereby patients underwent primary lip nose repair and vomer flap for hard palate single-layer closure, followed by soft palate repair 6 months later; Protocol 2 consisted of the two-flap technique (TF), whereby the cleft palate (CP) was repaired by two-flap technique after primary lip and nose repair. GOSLON Yardstick scores for dental arch relation, and speech outcomes based on universal reporting parameters, were noted. RESULTS: A total of 40 patients in the VF group and 45 in the TF group completed the treatment protocols. The GOSLON scores showed marginally better outcomes in the VF group compared to the TF group. Statistically significant differences were found only in two speech parameters, with better outcomes in the TF group. CONCLUSIONS: Our results showed marginally better growth outcome in the VF group compared to the TF group. However, the speech outcomes were better in the TF group.