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.

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.

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.

CBS c.844ins68 Polymorphism Frequencies in Control Populations: Implications on Nonsyndromic Cleft Lip With or Without Cleft Palate.

INTRODUCTION: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with substantial clinical and social impact. Folate deficiency is one of the factors that have been associated with increased risk for NSCLP. Polymorphisms in folate and homocysteine pathway genes may act as susceptibility factors. OBJECTIVE: The objective of this study was to evaluate prevalence estimates of cystathionine beta-synthase (CBS) insertion of 68-bp (c.844ins68) polymorphisms and their correlation with NSCLP. MATERIAL AND METHODS: A total of 236 unrelated individuals from seven Indian populations and an additional 355 cases with NSCLP and 357 controls without NSCLP were included in this study. We investigated the CBS c.844ins68 polymorphism in all samples. Genotyping was performed with polymerase chain reaction and electrophoresis. The data were statistically analyzed using the chi-square test. RESULTS: The CBS c.844ins68 allele is present in six of the seven populations analyzed, and allele frequencies range from 1.5% in Balija to 9.1% in Sugali populations. The CBS c.844ins68 polymorphism showed a significant protective effect on NSCLP at both genotype (WW versus WI: odds ratio [OR] = 0.54, 95% confidence interval [CI] = 0.31 to 0.95, P = .149) and allele levels (W versus I: OR = 0.56, 95% CI = 0.32 to 0.96, P = .033). CONCLUSIONS: The current study observed significant differences in the frequency of the CBS 844ins68 allele across populations. There is a significant association between CBS c.844ins68 polymorphism and cleft lip and palate in the Indian population. Additional studies are warranted to identify the functional variants in the genes controlling homocysteine as etiological contributors to the formation of oral clefts.

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.

Significant association of MTHFD1 1958G>A single nucleotide polymorphism with nonsyndromic cleft lip and palate in Indian population.

OBJECTIVE: Nonsyndromic cleft lip and palate (NSCLP) is genetically distinct from those with syndromic clefts, and accounts for ~70% of cases with Oral clefts. Folate, or vitamin B9, is an essential nutrient in our diet. Allelic variants in genes involved in the folate pathway might be expected to have an impact on risk of oral clefts. Given the key role of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) in folate metabolism, it would be of significant interest to assess its role in NSCLP etiology. STUDY DESIGN: The present study aims at examining the association between MTHFD1 1958G>A polymorphism and NSCLP risk by conducting a case-control study in south Indian population. Our sample comprised of 142 cases with nonsyndromic clefts and 141 controls without clefts or family history of clefting. The MTHFD1 1958G>A polymorphism was genotyped using PCR-RFLP. RESULTS: An increased risk was found for the heterozygous 1958GA (OR=2.44; P=0.020) and homozygous 1958AA (OR=2.45; P=0.012) genotypes in the children. When the dominant model (AG+AA vs GG) was applied the risk remained the same as co-dominant model, but the level of significance increased (OR=2.44; P=0.002). CONCLUSION: The results indicated the MTHFD1 1958G>A polymorphism to be one of the important genetic determinants of NSCLP risk in South Indian subjects.

Speech outcome following late primary palate repair.

OBJECTIVE: Early palate repair is recommended to minimize the development of disordered speech. We studied the speech outcome of late palate repair in 131 patients. The success of late palate repair is questioned because of the persistence of learned, compensatory misarticulations that are difficult to correct in spite of the establishment of correct palatal anatomy and a competent velopharyngeal mechanism. The objective of this study is to highlight the speech results following late primary repair of the palate. SETTINGS AND DESIGN: Retrospective analysis of speech outcomes in 131 patients with cleft lip and palate who underwent primary palate repair after the age of 10 years between November 2000 and December 2004. None of the patients had received supervised institution-based speech therapy. However, all patients were counseled and oriented and demonstrated the correct place and manner of articulation for the phonemes misarticulated by them. Preoperative and 6- to 12-month postoperative speech samples were assessed within the parameters of articulation, hypernasality, nasal air emission, and speech intelligibility. OUTCOME: The analysis indicated improvement in all speech parameters leading to an overall improvement in postoperative intelligibility for most patients. CONCLUSION: Although definite improvement occurs in all parameters of speech following late primary palate repair, residual speech problems persist in most patients, requiring further evaluation and appropriate treatment.

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.

Primary bilateral cleft lip repair with management of premaxilla without preoperative orthopedics.

OBJECTIVE: In developing countries, children with cleft lip and palate present at various age for primary repair. Even if they come at an appropriate age, logistic and financial problems prevent us from providing preoperative orthopedic treatment for children with bilateral complete cleft lip and palate (BCLP). We present our protocol and technique of primary repair for BCLP without preoperative orthopedics at different ages. SETTING AND DESIGN: We operated on 240 children with BCLP from 2001 to 2003. One hundred ten children younger than 1 year were operated on for primary surgeries, 99 children were between 2 and 10 years, and 40 were older than 10 years. Of the 110 patients who had primary repairs for BCLP without preoperative orthopedic before age of 1 year, seventy children were studied for dental occlusion and premaxillary position at age of 5 to 7 years. Children operated on after the age of 1 year had palate repair before lip repair. Children operated on after 10 years, the protocol was modified to tackle protruding premaxilla at the time of palate repair. OUTCOME: Of 70 patients operated on before 1 year of age, 83% had an occlusion with anterior and deep bites of the premaxilla of variable degree at age of 5 to 7 years. Thirteen percent had buccal bite, and these patients had small premaxilla before lip repair. CONCLUSIONS: Modification of protocol was necessary for children with BCLP who approached later than 1 year of age for primary treatment. Bilateral cleft lip repair without any preoperative orthopedic in young babies will mould the premaxilla. The size of premaxilla can predict the growth potential of maxilla.

Radial, renal and craniofacial anomalies: Baller-Gerold syndrome.

The Baller-Gerold syndrome is a rare syndrome with very few cases published in literature. Craniosynostosis and radial aplasia are striking features, easy to diagnose. However, there are many differential diagnoses. Often, the question raised is whether the Baller-Gerald syndrome is a distinct entity. We report a patient with findings of craniosynostosis and radial aplasia consistent with the diagnosis of the Baller-Gerold syndrome. Genotypic heterogeneity could possibly underlie the phenotypic variability exhibited by these cases.

Roberts-SC syndrome, a rare syndrome and cleft palate repair.

Roberts SC syndrome is a rare syndrome with only 17 previously recognized patients reported in medical literature. The syndrome is characterized by multiple malformations, particularly, symmetrical limb reduction, craniofacial anomalies such as bilateral cleft lip and palate, micrognathia, and severe growth and mental retardation. Our patient, a young child of five years having Roberts-SC, was successfully operated for cleft palate under general anesthesia. The main features of the syndrome and the technical problems of anesthesia and surgery are discussed in this report.

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.