Medially Positioned Single Mucoperiosteal Flap With and Without Allograft Membrane for Repair of Congenital Cleft Palate in 4 Dogs.

Congenital cleft of the secondary palate occurs when there is failure of one or both maxillary processes to fuse with the nasal septum during embryonic development. Palatal cleft severity can range from a simple focal fissure of the caudal soft palate to full-thickness defects of varied widths involving the entire soft and hard palate. A novel staged medially positioned single mucoperiosteal flap technique in 4 canine patients is reported. This flap technique is based on the major palatine and infraorbital arteries with strategic extractions of maxillary teeth and placement of allograft membrane in 3 of 4 cases for treatment of clefts wider than may be repaired effectively by traditional methods.

Maternal Metabolic Status and Orofacial Cleft Risk: A Case-Control Study in Thailand.

OBJECTIVES: Metabolic syndrome (MetS) has been suggested to play a role in congenital defects. This study investigated the association of MetS and its components with orofacial clefts (OFCs). METHODS: We conducted a case-control study in Northeast Thailand. Ninety-four cases with cleft lip, with or without cleft palate, were frequency matched with 94 controls on the infant's age and mother's education. We administered a mother's health questionnaire and collected anthropometric measurements and blood samples. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were performed among infants without a family history of OFCs, mothers who were not currently breastfeeding, and mothers who were >6 months postpartum. RESULTS: When compared to mothers of normal weight, the OR associated with OFCs were 2.44 (95% CI, 1.04-5.76, P = .04) in overweight mothers, and 3.30 (95% CI, 1.14-9.57, P = .03) in obese mothers. Low HDL-C raised the risk of OFCs 2.95 times (95% CI, 1.41-6.14, P = .004) compared to normal HDL-C levels. Mothers with 4 or 5 features of MetS were 2.77 times as likely to have the affected child than those who did not (95% CI, 0.43-17.76), but this difference was not statistically significant (P = .28). Subgroup analyses showed similar results, uncovering an additional significant association between underweight mothers and OFCs. CONCLUSIONS: The results indicate a robust association between underweight and overweight/obese maternal body mass index and increased OFC risk. Additionally, low HDL-C in mothers is linked to an elevated risk of OFCs. Further research is needed to evaluate if promoting strategies to maintain optimal body weight and enhance HDL-C levels in reproductive-age and pregnant women icould contribute to a reduction of the risk of OFCs in their progeny.

White matter tract integrity in isolated oral clefts: relationship to cognition and reading skills.

Children with isolated cleft of the lip and/or palate (iCL/P) have been shown to be at risk for impaired reading ability. Structural and functional neuroimaging studies have revealed subtle morphological and functional abnormalities correlated to cognition and reading ability. However, the integrity of white matter tracts and their potential relationship to reading performance in iCL/P is under-studied. The purpose of the present study was to evaluate white matter integrity related to cognition and reading skills among participants with and without iCL/P. Data from two cross-sectional, case/control studies with similar neuropsychological batteries and diffusion tensor imaging (DTI) protocols were combined. The final sample included 210 participants (ages 7 to 27 years). Group and sex differences in fractional anisotropy (FA) values were examined between participants with (n = 105) and without (n = 105) iCL/P. Potential associations between FA values and age, cognition, and reading skills were also evaluated separately by group and sex. Sex effects were prominent in association and projection fibers, and effects of cleft status were found in association fibers and cerebellar regions, with isolated associations to reading skills. Findings provide preliminary understanding of microstructural associations to cognitive and reading performance among children, adolescents, and young adults with iCL/P.

The Hard Palate Sweep: a multiplanar 2-dimensional sonographic method for the prenatal detection of cleft palate.

BACKGROUND: Prenatal diagnosis of cleft palate is challenging. Numerous 2-dimensional and 3-dimensional methods have been proposed to assess the integrity of the fetal palate, yet detection rates remain relatively low. We propose the "Hard Palate Sweep," a novel 2-dimensional method that enables clear demonstration of the entire fetal palate throughout pregnancy, in a single sweep, avoiding acoustic shadows cast by surrounding bones. OBJECTIVE: This study aimed to assess the feasibility and performance of the Hard Palate Sweep, performed throughout pregnancy. STUDY DESIGN: This was a prospective cross-sectional study performed between 2018 and 2022 in pregnant patients referred for a routine or targeted anomaly scan between 13 and 40 weeks of gestation. The presence or absence of a cleft palate was determined using the "Hard Palate Sweep." This was compared with the postnatal palate integrity assessment. Test feasibility and performance indices, including sensitivity, specificity, and positive and negative predictive values were calculated. Offline clips were reviewed by 2 investigators for the assessment of inter- and intraoperator agreement, using Cohen's kappa formula. The study protocol was approved by the institutional ethics committee. All participating patients were informed and provided consent. RESULTS: A total of 676 fetuses were included in the study. The Hard Palate Sweep was successfully performed in all cases, and 19 cases were determined to have a cleft palate. Of these, 13 cases were excluded because postmortem confirmation was not performed, leaving 663 cases available for analysis. Six cases determined to have a cleft palate were confirmed postnatally. In 655 of 657 cases prenatally determined to have an intact palate, this was confirmed postnatally. In the 2 remaining cases, rare forms of cleft palate were diagnosed postnatally, rendering 75% sensitivity, 100% specificity, 100% positive predictive value, and 99.7% negative predictive value for the Hard Palate Sweep (P<.001). There was complete intra- and interoperator agreement (kappa=1; P<.0001). CONCLUSION: The Hard Palate Sweep is a feasible and accurate method for prenatally detecting a cleft palate. It was successfully performed in all attempted cases between 13 and 40 weeks of gestation. This method is reproducible, offering high sensitivity and specificity. Implemented routinely, the Hard Palate Sweep is expected to increase the prenatal detection of cleft palate.

Isolated nonsyndromic cleft palate: multicenter epidemiological study in the Brazil.

BACKGROUND: Nonsyndromic orofacial clefts (NSOC) are the craniofacial most common congenital malformations. There are evidences that the nonsyndromic cleft palate (NSCP) development differs from other NSOC. However, most of the publications treat NSCP without considering that information. Furthermore, few studies focus on NSCP. The aim of this study was to describe epidemiological findings of patients with isolated NSCP in Brazil. METHODS: In this cross-sectional multicenter study, four reference Centers for treatment in three different Brazilian states was investigated. Data were obtained from clinical records of patients, between November 2021 and June 2022. Researched variables were sociodemographic, clinical characteristics and pregnancy and family history. Pearson's chi-square and ANOVA One-way tests were used for associations. RESULTS: Majority were female (58.1%), white (60.7%) with incomplete NSCP (61.2%). There was an association between complete NSCP and a positive history of medical problems during pregnancy (p = 0.016; 27.9%; OR: 1.94; 1.12-3.35). Systemic alterations were perceived in 40.6% of the sample with odds ratio for development of the complete type (OR: 1.21; 0.74-1.97). Higher OR was visualized in medication use during pregnancy (OR: 1.35; 0.76-2.37) and positive family history of oral cleft (OR: 1.44; 0.80-2.55). Dental and surgical care was associated with higher age groups (p < 0.050). CONCLUSIONS: NSCP was most prevalent in white skin color female. Complete NSCP is associated with medical problems during pregnancy. Medication use during pregnancy and positive family history of oral cleft increase the chance of developing complete NSCP.

Evaluation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human cases with orofacial clefts: A systematic review.

INTRODUCTION: The interaction between several cell populations or many genes and the coordination of multiple signal transmission pathways can lead to defects such as orofacial clefts (OFCs). Herein, a systematic review was designed to evaluate a group of important biomarkers (matrix metalloproteinases [MMPs] and tissue inhibitors of metalloproteinases [TIMPs]) in human cases with OFCs. MATERIAL AND METHODS: Four databases including PubMed, Scopus, Web of Science, and Cochrane Library databases were searched until March 10, 2023, without any restriction. STRING, the protein-protein interaction (PPI) network software, was applied to investigate the functional interactions among the examined genes. The effect sizes including odds ratio (OR) dealing with a 95% confidence interval (CI), were extracted by the Comprehensive Meta-Analysis version 2.0 (CMA 2.0) software. RESULTS: Thirty-one articles were entered into the systematic review that four articles were analyzed in the meta-analysis. Single studies reported that several polymorphisms of MMPs (rs243865, rs9923304, rs17576, rs6094237, rs7119194, and rs7188573); and TIMPs (rs8179096, rs7502916, rs4789936, rs6501266, rs7211674, rs7212662, and rs242082) had an association with OFC risk. There was no significant difference for MMP-3 rs3025058 polymorphism in allelic (OR: 0.832; P=0.490), dominant (OR: 1.177; P=0.873), and recessive (OR: 0.363; P=0.433) models and MMP-9 rs17576 polymorphism in an allelic model (OR: 0.885; P=0.107) between the OFC cases and the controls. Based on immunohistochemistry reports, three MMPs (MMP-2, MMP-8, and MMP-9) and TIMP-2 had significant correlations with several other biomarkers in OFC cases. CONCLUSIONS: MMPs and TIMPs can impact the tissue and cells affected by OFCs and the process of apoptosis. The interaction between some biomarkers with MMPs and TIMPs (e.g., TGFb1) in OFCs can be interesting for future research.

Prevalence and Patterns of Orofacial Clefts among Children from Different Regions of Saudi Arabia: A Systematic Review.

Aim and objective: To report on the prevalence and patterns of orofacial clefts (OFC) among Saudi Arabian children by analyzing the results of the studies that have been reported in the literature. Materials and methods: A data search was carried out for the articles that had reported on the prevalence of OFC among the Saudi Arabian population in databases like Web of Science, PubMed, Google Scholar, Scopus, and Saudi Digital Library. Articles that were published over the last 15 years were included in this study, following which 13 studies were assessed for qualitative data. Newcastle-Ottawa Quality Assessment Scales for cross-sectional studies were used for analyzing the methodological quality of these studies. Results: The prevalence of OFC was within the range of 0.65-1.9/1,000 live births. The highest was witnessed in the Medina region. Parent's consanguinity was the most common risk factor in OFC cases in the included studies. OFC was found to be higher among the male population in comparison with the female. Conclusion: The prevalence of OFC in Saudi Arabian children follows the global patterns of OFC. Isolated cleft lip (CL) and cleft palate (CP) are the most common forms of OFC. The prevalence of orofacial anomalies was reported more among children born to parents who had consanguineous marriages. Considering the higher rate of consanguinity among this population, there is an urgent need of developing educational and counseling programs to address the genetic consequences. How to cite this article: Albalawi F Alsaeed S, Alalola B, et al. Prevalence and Patterns of Orofacial Clefts among Children from Different Regions of Saudi Arabia: A Systematic Review. Int J Clin Pediatr Dent 2023;16(1):124-130.

Genetic Analysis of the Single-Nucleotide Polymorphisms rs880810, rs545793, rs80094639, and rs13251901 in Nonsyndromic Oral Clefts: A Case-Parent Trio Study.

Oral clefts, including cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), are the most common types of congenital anomalies of the human face. Various genetic and environmental factors play a role in developing oral clefts. Several studies have shown the association of the PAX7 gene and the 8q24 region with these oral clefts in different populations worldwide. However, there are no reported studies on the possible connection between the PAX7 gene and the 8q24 region nucleotide variants and the risk of developing nonsyndromic oral clefts (NSOC) in the Indian population. Hence, this study aimed to test the possible association between PAX7 gene single-nucleotide polymorphisms (SNPs) rs880810, rs545793,rs80094639, and rs13251901 of the 8q24 region using a case-parent trio design. Forty case-parent trios were selected from the CLP center. Genomic DNA was isolated from the cases and their parents. The rs880810, rs545793, rs80094639, and rs13251901 were genotyped by the MassARRAY technique. PLINK software was used for statistical analysis. All the SNPs were tested for Hardy-Weinberg equilibrium. No statistical significance was found with any SNPs, as none of the genotyped SNPs showed a p -value of less than 0.05. Hence, the rs880810, rs545793, and rs80094639 of the PAX7 gene, and rs13251901 of the 8q24 region are not associated with NSOC in the Indian population.

Assessing medical product safety during pregnancy using parameterizable tools in the sentinel distributed database.

PURPOSE: The US Food and Drug Administration established the Sentinel System to monitor the safety of medical products. A component of this system includes parameterizable analytic tools to identify mother-infant pairs and evaluate infant outcomes to enable the routine monitoring of the utilization and safety of drugs used in pregnancy. We assessed the feasibility of using the data and tools in the Sentinel System by assessing a known association between topiramate use during pregnancy and oral clefts in the infant. METHODS: We identified mother-infant pairs using the mother-infant linkage table from six data partners contributing to the Sentinel Distributed Database from January 1, 2000, to September 30, 2015. We compared mother-infant pairs with first-trimester exposure to topiramate to mother-infant pairs that were topiramate-unexposed or lamotrigine-exposed and used a validated algorithm to identify oral clefts in the infant. We estimated adjusted risk ratios through propensity score stratification. RESULTS: There were 2007 topiramate-exposed and 1 066 086 unexposed mother-infant pairs in the main comparison. In the active-comparator analysis, there were 1996 topiramate-exposed and 2859 lamotrigine-exposed mother-infant pairs. After propensity score stratification, the odds ratio for oral clefts was 2.92 (95% CI: 1.43, 5.93) comparing the topiramate-exposed to unexposed groups and 2.72 (95% CI: 0.75, 9.93) comparing the topiramate-exposed to lamotrigine-exposed groups. CONCLUSIONS: We found an increased risk of oral clefts after topiramate exposure in the first trimester in the Sentinel database. These results are similar to prior published observational study results and demonstrate the ability of Sentinel's data and analytic tools to assess medical product safety in cohorts of mother-infant pairs in a timely manner.

[Association study between haplotypes of WNT signaling pathway genes and nonsyndromic oral clefts among Chinese Han populations].

OBJECTIVE: To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios. METHODS: The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07). RESULTS: After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10-4). CONCLUSION: This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.

Evaluation of genome-wide association signals for nonsyndromic cleft lip with or without cleft palate in a multiethnic Brazilian population.

OBJECTIVE: To evaluate previous nonsyndromic cleft lip with or without cleft palate (NSCL±P) associated signals in 4p16.2, 8p11.23, 12q13.13, 12q13.2 and 17q21.32 in a multiethnic Brazilian cohort. DESIGN: The single nucleotide polymorphisms (SNPs) rs34246903 in 4p16.2, rs13317 in 8p11.23 (FGFR1, fibroblast growth factor receptor 1), rs3741442 in 12q13.13, rs705704 in 12q13.2 and rs4968247 in 17q21.32 were genotyped with TaqMan allelic discrimination assays in a case-control sample including 801 NSCL±P patients [233 nonsyndromic cleft lip (NSCLO) and 568 nonsyndromic cleft lip and palate (NSCLP)] and 881 healthy controls. Multiple logistic regression analyses, considering sex and genomic ancestry as covariates, were conducted, and the p value was adjusted with Bonferroni multiple correction testing (p ≤ 0.01). RESULTS: Although several associations were identified, those that resisted the multiple correction testing involved the alleles and genotypes of rs34246903 and rs13317. The NSCLO group had a lower frequency of the minor C allele of rs34246903 compared to controls, giving an odds ratio (OR) of 0.74 [95% confidence interval (CI): 0.59-0.93, p = 0.01]. The rs34246903 CC genotype (homozygous) and the recessive model revealed significant protective associations with NSCLO, yielding ORs of 0.50 (95% CI: 0.29-0.85, p = 0.005) and 0.55 (95% CI: 0.33-0.93, p = 0.01) respectively. The presence of C variant allele of rs13317 (OR: 0.81, 95% CI: 0.69-0.96, p = 0.01) as well the TC genotype (OR: 0.77, 95% CI: 0.62-0.94, p = 0.01) and the dominant model (OR: 0.77, 95% CI: 0.63-0.94, p = 0.009) showed significant associations with reduced risk of NSCL±P. CONCLUSION: Our study is the first to support the association of rs34246903 (4p16.2) with NSCLO and rs13317 within FGFR1 with NSCL±P in the highly admixed Brazilian population. Further studies are needed to determine the functionality of those SNPs or to identify the causal markers in linkage disequilibrium with those susceptibility markers.

Co-occurring anomalies in congenital oral clefts.

Oral clefts (OCs) are frequently co-occurring with other non-OC congenital anomalies. The types and the prevalence of anomalies co-occurring with OCs vary in the reported studies. The aims of this report were to study the types and the prevalence of the anomalies co-occurring with OCs in a well-defined population. The types and the prevalence of anomalies co-occurring in cases with OCs were ascertained in all terminations of pregnancy, stillbirths, and live births in 387,067 births occurring consecutively during the period 1979-2007 in the area covered by our registry of congenital anomalies which is population based, 789 cases of OCs were registered during the study period with a prevalence of 20.4 per 10,000 births, 39.5% of the cases had associated non-OC anomalies. Associated anomalies were more common in cases with cleft palate (52.4%) than in cases with cleft lip and palate (37.3%) and in cases with cleft lip only (16.8%). Chromosomal abnormalities were present in 94 (11.9%) cases including 27 trisomies 13, 15 trisomies 18, 12 22 q11.2 deletion, and 40 other chromosomal abnormalities. Nonchromosomal recognizable conditions were diagnosed in 38 cases (4.8%) including syndromes, associations, spectrums and sequences. Multiple congenital anomalies (MCAs) were present in 180 cases (22.8%). The most frequent MCA were in the musculoskeletal system (16.7%), the central nervous system (15.0%), the urogenital system (13.7%), the cardiovascular system (8.6%), and the digestive system (6.6%). The high prevalence of associated anomalies justifies a thorough screening for other congenital anomalies in cases with OCs.

Association study between haplotypes of WNT signaling pathway genes and nonsyndromic oral clefts among Chinese Han populations / 北京大学学报(医学版)

OBJECTIVE@#To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios.@*METHODS@#The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07).@*RESULTS@#After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10-4).@*CONCLUSION@#This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.

The effects of state facial surgery mandates on timeliness of primary cleft repair surgery in the United States.

OBJECTIVE: This study examines the effects of state facial surgery mandates on the timeliness of primary cleft repair surgery for privately insured children with oral clefts in the United States. MATERIALS AND METHODS: Using IBM Health MarketScan® Database from 2001 to 2017, we estimate regression models separately for age at cleft lip repair and cleft palate repair by having a mandate while considering child-level factors and other state differences. The sample includes 1,451 children who had primary cleft lip repair by age 12 months, and 1,402 children who had primary cleft palate repair by age 18 months. RESULTS: A mandate was associated with earlier cleft lip repair by 13 days (95% CI, -21.5 to -4.7 days) when controlling for state differences, regardless if the child had other birth defects. For children needing cleft palate repair, a mandate was associated with earlier surgery by 87 days (95% CI, -136.1 to -38.4 days) only when no other birth defects were present. CONCLUSIONS: State facial surgery mandates were associated with earlier cleft lip repair for children with or without other birth defects, and earlier cleft palate repair for children without other birth defects (besides oral clefts). Findings suggest benefits to privately insured children with oral clefts from state mandates to cover needed services.

Advantages of using toothpaste containing propolis and plant oils for gingivitis prevention and oral cavity hygiene in cleft lip/palate patients.

BACKGROUND: The anti-inflammatory and antibacterial action of preparations used during oral hygiene procedures is particularly important in patients with oral cleft. Few reports have been published assessing the influence of natural products on the state of the oral cavity in patients with oral cleft. The aim of this study was to assess the effect of toothpaste containing Polish propolis and plant oils on oral cavity health in patients with oral cleft treated orthodontically. MATERIALS AND METHODS: A total of 50 patients aged 9-16 years old (20 females, 23 males) were selected and randomly assigned into two groups. Group (A) received toothpaste with Polish propolis, tea tree oil, menthol, and rosemary oil. Group (B) received toothpaste without active ingredients (placebo). A baseline assessment was followed by an oral hygiene index (OHI, debris OHI-D, and calculus OHI-C component) and gingival bleeding index (GBI) after 35 days. The methodology of the oral condition assessment included the presence of cleft malformation as a dysmorphic of the anterior maxilla segment. RESULTS: In group A, improvement in oral cavity hygiene assessed for incisors and molars was found (OHI-T p = 0.011). For the gingival condition, a decrease in the gingival bleeding index - total (GBI-T p = 0.002), as well as for the incisors (GBI-I p = 0.007) and molars (GBI-M p = 0.017) was found. CONCLUSIONS: This research confirms the biological effectiveness of toothpaste with Polish propolis and plant oils. These results may be clinically useful for improving preventative oral care and for control of oral infectious diseases during orthodontic treatment in patients with oral cleft.

Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial Cleft.

Two large studies of case-parent trios ascertained through a proband with a non-syndromic orofacial cleft (OFC, which includes cleft lip and palate, cleft lip alone, or cleft palate alone) were used to test for possible gene-environment (G × E) interaction between genome-wide markers (both observed and imputed) and self-reported maternal exposure to smoking, alcohol consumption, and multivitamin supplementation during pregnancy. The parent studies were as follows: GENEVA, which included 1,939 case-parent trios recruited largely through treatment centers in Europe, the United States, and Asia, and 1,443 case-parent trios from the Pittsburgh Orofacial Cleft Study (POFC) also ascertained through a proband with an OFC including three major racial/ethnic groups (European, Asian, and Latin American). Exposure rates to these environmental risk factors (maternal smoking, alcohol consumption, and multivitamin supplementation) varied across studies and among racial/ethnic groups, creating substantial differences in power to detect G × E interaction, but the trio design should minimize spurious results due to population stratification. The GENEVA and POFC studies were analyzed separately, and a meta-analysis was conducted across both studies to test for G × E interaction using the 2 df test of gene and G × E interaction and the 1 df test for G × E interaction alone. The 2 df test confirmed effects for several recognized risk genes, suggesting modest G × E effects. This analysis did reveal suggestive evidence for G × Vitamin interaction for CASP9 on 1p36 located about 3 Mb from PAX7, a recognized risk gene. Several regions gave suggestive evidence of G × E interaction in the 1 df test. For example, for G × Smoking interaction, the 1 df test suggested markers in MUSK on 9q31.3 from meta-analysis. Markers near SLCO3A1 also showed suggestive evidence in the 1 df test for G × Alcohol interaction, and rs41117 near RETREG1 (a.k.a. FAM134B) also gave suggestive significance in the meta-analysis of the 1 df test for G × Vitamin interaction. While it remains quite difficult to obtain definitive evidence for G × E interaction in genome-wide studies, perhaps due to small effect sizes of individual genes combined with low exposure rates, this analysis of two large case-parent trio studies argues for considering possible G × E interaction in any comprehensive study of complex and heterogeneous disorders such as OFC.

The Prevalence of Nonsyndromic Oral Clefts in Twins Compared to Singletons: The Association With Birth Weight.

PURPOSE: To examine the prevalence of nonsyndromic oral clefts in twins compared to singletons in the United States and to evaluate the association between birth weight and nonsyndromic oral clefts. DESIGN: A large population-based cross-sectional study was performed using the data from the US National Center for Health Statistics database in 2017. PARTICIPANTS: Our sample consisted of 128 310 twins and 3 723 273 singletons. METHODS: The variables collected were sociodemographic variables, environmental predictors, and clinical measures. Descriptive analysis, bivariate, and multivariate logistic regression were performed. MAIN OUTCOME MEASURE: The main outcome variable in our study is nonsyndromic oral clefts. RESULTS: The prevalence of nonsyndromic oral clefts was 5.22 per 10 000 in twins and 5.12 per 10 000 in singletons. Results show no significant risk of nonsyndromic oral clefts in twins compared to singletons (P = .92). There was a significant relationship between birth weight and infant diagnosed with nonsyndromic oral clefts (P = .01). Unadjusted odds ratio for birth weight was 2.52 (95% CI: 2.25-2.82). Adjusted odds for potential confounders such as mother's age, race, mother's education, gender of the infant, APGAR 5-minute score, gestational age, prenatal smoking, number of prenatal care visits, and mother's body mass index were resulted in similar but with a slightly lower odds of 2.11 (95% CI: 1.78-2.50). CONCLUSION: Compared to singletons, twins did not have higher risk of nonsyndromic oral clefts. Infants with low birth weight were more prone to have nonsyndromic oral clefts.

Association between ABO, Rh blood groups, lip and dermatoglyphic patterns, and nonsyndromic oral clefts: A case-control study.

OBJECTIVE: The objective of the study is to determine the association between nonsyndromic oral clefts (OC) in children and ABO, Rh blood groups, lip, and dermatoglyphic patterns of their unaffected parents. METHODS: This case-control study was conducted at a tertiary cleft center in Chennai, India, among 240 individuals comprising 80 units (40 cases and controls, respectively). Each unit (triad) was constituted by a child (0-12 years of age) either born with nonsyndromic OC (cases) or with no diagnosed congenital anomaly (control) and their unaffected parents (mother and father). ABO and Rh blood groups, specific lip print, fingerprint pattern, and palmar asymmetry were recorded for each individual. Strength of association of related factors was assessed by multivariable logistic regression reported as adjusted odds ratios and 95% confidence interval. RESULTS: A1-positive blood group was found to be considerably higher among case mothers (14.39 [1.57-32.27]). A higher odds of OCs were observed among case mothers with whorl lip pattern (1.51 [1.16-3.17]) and radial loop pattern in fingers (1.44 [1.09-2.31]) relative to controls. In addition, palmar asymmetry was distinctively higher among case parents compared to controls (P < 0.01). CONCLUSION: Findings indicate that A1-positive blood group, higher frequency of whorl lip, and radial loop finger patterns in mothers and higher ulnar loop pattern in fathers and palmar asymmetry in both parents increases odds of occurrence of OC among their offspring. These identifiable traits offer potential scope for better service planning among resource-constrained disadvantaged communities in India.

Maternal exposure to sulfur dioxide and the risk of oral clefts in Liaoning Province, China: a population-based case-control study.

There is limited and equivocal epidemiological evidence relating to the association between maternal sulfur dioxide (SO2) exposure and the risk of oral clefts (OCs) in offspring. We performed a population-based case-control study in Liaoning province to evaluate aforementioned relationship during 3 months before conception, the first trimester of pregnancy, and their single months. The study involved 3086 patients with OCs and 7950 controls. Data relating to SO2 concentration was acquired from air monitoring stations throughout the study period. We used a multivariable logistic regression model to evaluate the association between exposure to SO2 and the risk of OCs during the exposure windows. Maternal SO2 exposure was positively related to OCs during the 3 months before conception (odds ratio = 1.38, 95% confidence interval: 1.15-1.65; P for trend < 0.01). Positive relationships were obtained from the first and second months before conception and the first month of pregnancy. Thus, our research reflects a relationship between SO2 exposure and the risk of OCs. Future studies are now required to verify the association between SO2 exposure and OCs during pregnancy and indicate the most relevant vulnerable exposure time windows.