3D evaluation of the maxillary sinus volumes in patients with bilateral cleft lip and palate.

One of the most common congenital anomalies of the head and neck region is a cleft lip and palate. This retrospective case-control research aimed to compare the maxillary sinus volumes in individuals with bilateral cleft lip and palate (BCLP) to a non-cleft control group. The study comprised 72 participants, including 36 patients with BCLP and 36 gender and age-matched control subjects. All topographies were obtained utilizing Cone Beam Computed Tomography (CBCT) for diagnostic purposes, and 3D Dolphin software was utilized for sinus segmentation. Volumetric measurements were taken in cubic millimeters. No significant differences were found between the sex and age distributions of both groups. Additionally, there was no statistically significant difference observed between the BCLP group and the control group on the right and left sides (p > 0.05). However, the mean maxillary sinus volumes of BCLP patients (8014.26 ± 2841.03 mm3) were significantly lower than those of the healthy control group (11,085.21 ± 3146.12 mm3) (p < 0.05). The findings of this study suggest that clinicians should be aware of the lower maxillary sinus volumes in BCLP patients when planning surgical interventions. The utilization of CBCT and sinus segmentation allowed for precise measurement of maxillary sinus volumes, contributing to the existing literature on anatomical variations in BCLP patients.

Divergent growth of the transient brain compartments in fetuses with nonsyndromic isolated clefts involving the primary and secondary palate.

Cleft lip/palate is a common orofacial malformation that often leads to speech/language difficulties as well as developmental delays in affected children, despite surgical repair. Our understanding of brain development in these children is limited. This study aimed to analyze prenatal brain development in fetuses with cleft lip/palate and controls. We examined in utero MRIs of 30 controls and 42 cleft lip/palate fetal cases and measured regional brain volumes. Cleft lip/palate was categorized into groups A (cleft lip or alveolus) and B (any combination of clefts involving the primary and secondary palates). Using a repeated-measures regression model with relative brain hemisphere volumes (%), and after adjusting for multiple comparisons, we did not identify significant differences in regional brain growth between group A and controls. Group B clefts had significantly slower weekly cerebellar growth compared with controls. We also observed divergent brain growth in transient brain structures (cortical plate, subplate, ganglionic eminence) within group B clefts, depending on severity (unilateral or bilateral) and defect location (hemisphere ipsilateral or contralateral to the defect). Further research is needed to explore the association between regional fetal brain growth and cleft lip/palate severity, with the potential to inform early neurodevelopmental biomarkers and personalized diagnostics.

Grainyhead-like 2 interacts with noggin to regulate tissue fusion in mouse.

Defective tissue fusion during mammalian embryogenesis results in congenital anomalies, such as exencephaly, spina bifida and cleft lip and/or palate. The highly conserved transcription factor grainyhead-like 2 (Grhl2) is a crucial regulator of tissue fusion, with mouse models lacking GRHL2 function presenting with a fully penetrant open cranial neural tube, facial and abdominal clefting (abdominoschisis), and an open posterior neuropore. Here, we show that GRHL2 interacts with the soluble morphogen protein and bone morphogenetic protein (BMP) inhibitor noggin (NOG) to impact tissue fusion during development. The maxillary prominence epithelium in embryos lacking Grhl2 shows substantial morphological abnormalities and significant upregulation of NOG expression, together with aberrantly distributed pSMAD5-positive cells within the neural crest cell-derived maxillary prominence mesenchyme, indicative of disrupted BMP signalling. Reducing this elevated NOG expression (by generating Grhl2-/-;Nog+/- embryos) results in delayed embryonic lethality, partial tissue fusion rescue, and restoration of tissue form within the craniofacial epithelia. These data suggest that aberrant epithelial maintenance, partially regulated by noggin-mediated regulation of BMP-SMAD pathways, may underpin tissue fusion defects in Grhl2-/- mice.

Prenatal incidence of cleft lip/palate and cocaine abuse in parents: a systematic review and meta-analysis.

BACKGROUND: The study aimed to investigate the association between maternal cocaine abuse during pregnancy and the prevalence of cleft lip/palate (CL/P) in offspring, synthesizing existing evidence through a systematic review and meta-analysis. CL/P is a congenital craniofacial anomaly with complex etiology, and prior research has suggested potential links between maternal cocaine use and CL/P. However, these associations remain inconclusive. METHODS: A comprehensive literature search was conducted to identify relevant studies published up to the study's cutoff date in September 2021. Several databases were systematically searched using predefined search terms. Inclusion criteria were set to encompass studies reporting on the prevalence of CL/P in infants born to mothers with a history of cocaine use during pregnancy, with a comparison group of non-cocaine-using mothers. Data were extracted, and a meta-analysis was performed using a random-effects model to calculate pooled odds ratios (OR) and relative risks (RR) with their respective 95% confidence intervals (CI). RESULTS: The review included data from 4 studies that met the inclusion criteria. The combined OR from two studies was 0.05 (95% CI: 0.00, 4.41), which does not suggest a statistically significant association between prenatal cocaine exposure and the incidence of CL/P due to the confidence interval crossing the null value. Additionally, the combined RR was 0.17 (95% CI: 0.04, 0.66), indicating a statistically significant decrease in the risk of CL/P associated with prenatal cocaine exposure. These results, with an OR that is not statistically significant and an RR suggesting decreased risk, should be interpreted with caution due to considerable heterogeneity and variability among the included studies' findings. Further research is needed to clarify these associations. CONCLUSION: The findings from this systematic review and meta-analysis suggest that maternal cocaine use during pregnancy is not a statistically significant independent risk factor for the development of CL/P in offspring. These results underscore the multifactorial nature of CL/P etiology and emphasize the importance of considering other genetic, environmental, and nutritional factors in understanding the condition's origins. While the study provides important insights, limitations such as data heterogeneity and potential confounders should be acknowledged. Future research should adopt rigorous study designs and explore a broader range of potential risk factors to comprehensively elucidate CL/P development.

A spectrum of TP63-related disorders with eight affected individuals in five unrelated families.

TP63-related disdorders broadly involve varying combinations of ectodermal dysplasia (sparse hair, hypohydrosis, tooth abnormalities, nail dysplasia), cleft lip/palate, acromelic malformation, split-hand/foot malformation/syndactyly, ankyloblepharon filiforme adnatum, lacrimal duct obstruction, hypopigmentation, and hypoplastic breasts and/or nipples. TP63-related disorders are associated with heterozygous pathogenic variants in TP63 and include seven overlapping phenotypes; Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC), Ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome 3 (EEC3), Limb-mammary syndrome (LMS), Acro-dermo-ungual-lacrimal-tooth syndrome (ADULT), Rapp-Hodgkin syndrome (RHS), Split-hand/foot malformation 4 (SHFM4), and Orofacial cleft 8. We report on five unrelated families with 8 affected individuals in which the probands presented with varying combinations of ectodermal dysplasia, cleft lip/palate, split-hand/foot malformation, lacrimal duct obstruction, and ankyloblepharon filiforme adnatum. The clinical diagnosis involved AEC syndrome (2 patients), EEC3 syndrome (2 patients), and a yet hitherto unclassified TP63-related disorder. Sanger sequence analysis of the TP63 gene was performed revealing five different variants among which four were novel and three were de novo. The identificated TP63 variants co-segregated with the other affected individuals in the families. The abnormalities of ectoderm derived structures including hair, nails, sweat glands, and teeth should alert the physician to the possibility of TP63-related disorders particularly in the presence of orofacial clefting.

A novel TTC26 variant in a patient with hexadactyly, pituitary stalk interruption, hepatopathy, nephropathy, and bilateral lip-palate cleft: A case report and expansion of the phenotype.

Biallelic pathogenic variants in the TTC26 gene are known to cause BRENS (biliary, renal, neurological, skeletal) syndrome, an ultra-rare autosomal recessive condition with only few patients published to date. BRENS syndrome is characterized by hexadactyly, severe neonatal cholestasis, and involvement of the brain, heart, and kidney, however the full phenotypic and genotypic spectrum is unknown. Here, we report on a previously undescribed homozygous intronic TTC26 variant (c.1006-5 T > C) in a patient showing some of the known TTC26-associated features like hexadactyly, hypopituitarism, hepatopathy, nephropathy, and congenital heart defect. Moreover, he presented with a suspected unilateral hearing loss and bilateral cleft lip-palate. The variant is considered to affect correct splicing by the loss of the canonical acceptor splice site and activation of a cryptic acceptor splice site. Hereby, our patient represents one additional patient with BRENS syndrome carrying a previously unreported TTC26 variant. Furthermore, we confirm the involvement of the pituitary gland to be a common clinical feature of the syndrome and broaden the clinical spectrum of TTC26 ciliopathy to include facial clefts and a probable hearing involvement.

Ocular Manifestations in Patients Affected by p63-Associated Disorders: Ectrodactyly-Ectodermal Dysplasia-Clefting (EEC) and Ankyloblepharon-Ectodermal Defects-Cleft Lip Palate (AEC) Syndromes.

BACKGROUND/AIMS: The Ectrodactyly-Ectodermal dysplasia-Clefting (EEC) and Ankyloblepharon-ectodermal defect-cleft lip/palate (AEC) syndromes are rare autosomal dominant diseases caused by heterozygous mutations in the p63 gene. Patients are characterized by abnormalities of the skin, teeth, and hair and have limb defects, orofacial clefting and ectodermal dysplasia. In addition, they often show ocular surface alterations, leading to progressive corneal clouding and eventually blindness. Here, we present 8 cases describing patients affected by EEC (n = 6, with 5 sporadic and 1 familial cases) and AEC (n = 2, both sporadic cases) syndromes. We attempt to provide a description of the ocular disease progression over the years. METHODS: Clinical examinations and monitoring of ocular parameters for the assessment of limbal stem cell deficiency were constantly performed on patients between 2009 and 2023. Quantitative data and comparison with existing cases described in the literature are reported. RESULTS: The therapies supplied to patients were essential for the management of the symptoms, but unfortunately did not halt the progression of the pathology. CONCLUSIONS: A constant monitoring of the patients would help avoid the sudden worsening of symptoms. If the progression of the disease slows down, it would allow for the development of newer therapeutic strategies aimed at correcting the genetic defect.

Schematic Treatment Tree for the Presurgical Nasoalveolar Moulding of Patients with Cleft Lip and Palate.

Background: Cleft lip and palate is the most common and unfortunate congenital defect that is debilitating for both the patients and their parents. Such complex condition demands for a precise and judicious management, as its outcome can drastically influence the quality of life of the child. Aim: To provide a concise treatment algorithm or tree which might guide the clinicians and make it easier for them to opt for a better treatment option when confronting different severities and types of this defect. Material and Methods: The clinical experience at our center alongwith review of current literature is used to propose a decision making treatment tree. Discussion: For the better aesthetics, function and ease of cosmetic surgery, several presurgical procedures have been introduced including the nasoalveolar moulding (NAM) appliance, adhesive tapes with nasal elevators, Figueroa's appliance, Hotz appliance, etc. Conclusion: The schematic decision-making tree may prove beneficial to the healthcare providers specially pedodontists who frequently come across such situations to choose the best treatment option for their patients.

Impact of Orofacial Clefts on Oral Health Quality of Life: A Cross-sectional Survey Study in Saudi Arabia.

AIM: To evaluate the effect of facial clefts on the dental health quality of life of affected individuals, and to determine whether age and gender affect the oral health quality of life differently. MATERIALS AND METHODS: The cross-sectional survey included 50 participants (32 females and 18 males) from the northern region of Saudi Arabia, using a reliable and validated questionnaire, the Child Oral Health Impact Profile (COHIP), which measured self-reported oral health-related quality of life (OHRQoL) in children and adults using a five-point Likert scale. Statistical analysis was performed, and results were considered significant if the p-value was less than 0.05. RESULTS: The highest scores in the oral health domain were related to bad breath and reluctance in speaking or reading aloud in class within the school environment domain, with mean scores of 3.44 ± 1.3 and 3.52 ± 1.2, respectively. Most patients showed apprehension regarding necessary dental treatments (mean = 1.44 ± 0.07). The study found a non-statistically significant difference in tooth discomfort between age groups (p = 0.092), with individuals aged from 20 to 29 experiencing higher levels of discomfort than other age groups surveyed. CONCLUSION: The two topics with the highest mean scores in the oral health domain and the school environment domain were bad breath and not wanting to speak or read aloud in class. Females reported more discomfort, and there was a substantial association between gender and tooth pain/sensitivity. CLINICAL SIGNIFICANCE: Understanding the difficulties cleft patients face is crucial, as doing so will enable dentists to encourage and handle these issues more effectively.

"Challenges and concerns faced by parents of a group of Egyptian children with cleft lip/palate: a qualitative study".

BACKGROUND: Cleft lip and palate are the most common developmental anomalies that affect the mouth and related structures. They can both affect children physiologically, socially, and functionally and lead to psychological distress in their parents. The present study aims to understand the challenges parents of cleft lip and palate patients face in Egypt, elucidate how they cope with these challenges, and assess their concerns for the future. METHODS: For the present phenomenological qualitative exploration, the parents of cleft lip and palate patients attending the cleft care clinic were invited to participate in the study through face-to-face recruitment at the clinic. An interview guide about the research question was developed to include standardized open-ended questions providing a framework for structured discussions. The interviews were audio-recorded after obtaining written informed consent from participants then collected data were transcribed for data analysis. RESULTS: Of the 12 participants, there were nine mothers and three fathers. Their children's ages ranged from 1.5 years to 19 years and had different presentations of cleft lip and palate from unilateral cleft lip to complete bilateral cleft lip and palate. Feeding difficulty was one of the main challenges encountered by the parents. At the same time, fear of being subjected to bullying was the main concern for the future of their children. Six themes were noted that were continually reported: Health & Wellbeing; Parental emotions; Parental attitudes & behaviors; Financial aspects; Relationship aspects; and Career/Education. CONCLUSIONS: There were 4 factors that directly impacted the themes, namely: the type of cleft, gender of the child, gender role of the parent, and the age of the child impacted the parental concerns and the challenges faced under the influence of sociocultural beliefs and existing support systems.

Is caries prevalence site-specific in cleft lip and palate patients? A systematic review and meta-analysis.

Background: Previous systematic reviews indicate that there is an increased prevalence of caries in cleft patients in comparison to their healthy control group. To date, the prevalence of caries between unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) has not been quantitatively evaluated. This review aims to include published studies that examined caries prevalence in patients with UCLP and BCLP to find out whether a quantitative difference exists in caries experience among them. Materials and Methods: Medline/PubMed, Scopus, and EBSCOhost databases were searched from inception to November 2021. The protocol was registered with PROSPERO registration no. CRD2021292425. Prevalence-based studies that evaluated caries experience using the decayed-missing-filled teeth (DMFT) index in the permanent dentition or dmft in case of primary dentition in patients with UCLP or BCLP were included in the analysis with the outcome given in mean and standard deviation. Meta-analysis was performed using a random effect model through a forest plot. An adapted version of the Newcastle-Ottawa Scale for cross-sectional studies was modified to assess the quality of included studies. Results: Three studies were included in the review. The difference in caries prevalence was statistically significant in the permanent and primary dentition which were evaluated using DMFT and dmft scores with P = 0.01 and P = 0.03, respectively. Forest plot values were obtained for permanent dentition (DMFT) and primary dentition (dmft), 0.57 (95% confidence interval [CI]: 1.03-0.11) and 0.36 (95% CI: 0.69-0.03), respectively. The result of the meta-analysis indicates that patients with BCLP have higher caries prevalence. Conclusion: The outcome of the study indicates a higher occurrence of caries in patients with BCLP than UCLP in both permanent and primary dentition.

Association of MMP2 and MMP9 gene polymorphisms with nonsyndromic cleft lip/palate in an Iranian population.

Background: Cleft lip/palate (CL/P) is a prevalent congenital disorder. Matrix metalloproteinases (MMPs) play a role in palatogenesis and have been proposed to be associated with nonsyndromic CL/P development. This study aimed to examine the association of MMP2 (rs243866) and MMP9 (rs3918242) gene polymorphism with nonsyndromic CL/P in an Iranian population. Methods: Blood samples were collected from 120 nonsyndromic CL/P patients and 140 healthy newborns in this case-control study. DNA extraction was performed by the salting-out method, and the samples underwent polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), using Pag and SphI enzymes, for genotyping MMP2 and MMP9 gene polymorphisms. Statistical analysis was performed with SPSS 11.5. Univariate and multivariate logistic regression models were used to calculate the odds ratios and 95% confidence intervals (CIs). The level of statistical significance was set at P<0.05. Results: No significant association was found between MMP2 gene polymorphism and nonsyndromic CL/P. However, the MMP9 gene polymorphism had a significant association with nonsyndromic CL/P, with a higher prevalence of the T allele and TT genotype in the case group than the control group. Conclusion: This study indicated a potential link between MMP9 gene polymorphism and nonsyndromic CL/P in an Iranian population. Future investigations with greater sample diversity and larger sample sizes are required to obtain more comprehensive and robust evidence. In-depth analyses and studies involving different ethnic groups can further enhance our understanding of the genetic underpinnings of CL/P.

A Systematic Review: Early Simultaneous Vomer Flap with Primary Cleft Lip Repair, Does it Bring More Benefits?

INTRODUCTION: Vomer flap is a technique to close cleft lip and palate. This technique is a simple procedure that has many benefits. However, the vomer flap's application together with primary lip closure is still questionable. OBJECTIVE: To find out whether the vomer flap's application in primary cleft lip repair can provide significant benefits. DESIGN: A systematic review was conducted using the PRISMA methodology has been licensed in PROSPERO databases (CRD42023399487). SETTING: A comprehensive search was set out, utilizing eight data sources up to March 2023. PARTICIPANTS: Both cohort studies and randomized control trials regarding the use of vomer flaps performed concurrently with cleft lip repair in children up to six months old. RESULTS: This article involved 8 studies involving 542 patients who met the inclusion criteria, consisting of 6 retrospective cohort studies, 1 RCT study, and 1 prospective cohort study. Vomer flaps provide a reduction in palatal cleft distance of 3-5 mm, a relatively small number of fistulas (0-4%), improvement of velopharyngeal function (nasal tone and nasal emission), maximal development of the maxilla although it is still controversial. CONCLUSION: The vomer flap's application in primary cleft lip repair provides many advantages, such as reduced palatal and alveolar clefts, decreased risk of oronasal fistula, increased velopharyngeal function, and increased maxillary growth. It is reliable for the management of cleft lip and palate.

Airway changes in patients with unilateral cleft lip/palate (UCL/P) after maxillary advancement.

OBJECTIVES: To assess the effect on the retropalatal airway (RPA), retroglossal airway (RGA), and total airway (TA) volumes and cephalometrics (SNA, SNB, ANB, PP-SN, Occl-SN, N-A, A-TVL, B-TVL) after maxillary advancement orthognathic surgery in patients with unilateral cleft lip/palate (UCL/P) using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: The CBCT scans of 30 patients (13 males and 17 females, 17-20 years old) with UCL/P were evaluated at two time points: preoperative (T1) and postoperative (T2). The interval between T1 and T2 ranged from 9-14 weeks, except for two patients in whom the interval was 24 weeks. Intraexaminer reliability was measured with an intraclass correlation coefficient test. A paired t-test was used to compare the airway and cephalometric measurements between T1 and T2, with a P value of .05 being considered significant. RESULTS: From T1 to T2, significant increases were found in the volumes of RPA (from 9574 ± 4573 to 10,472 ± 4767, P = .019), RGA (from 9736 ± 5314 to 11,358 ± 6588, P = .019), and TA (from 19,121 ± 8480 to 21,750 ± 10,078, P = .002). In addition, the RGA (from 385 ± 134 to 427 ± 165, P = .020) and TA (from 730 ± 213 to 772 ± 238, P = .016) sagittal area increased significantly. For minimal cross-sectional area (MCA), only the RPA increased significantly (from 173 ± 115 to 272 ± 129, P = .002). All cephalometric changes were statistically significant between T1 and T2 except for SNB. CONCLUSIONS: Maxillary advancement in patients with UCL/P produces statistically significant increases in the retropalatal (volumetric and MCA), retroglossal (volumetric and sagittal), and total (volumetric and sagittal) airways based on data from CBCT imaging.

Effects of Alt-RAMEC protocol with facemask therapy in cleft lip palate patients in a sample of Pakistani population.

OBJECTIVE: The objective of the study is to evaluate the skeletal, dentoalveolar and soft tissue changes before and after treatment with Alt-RAMEC protocol and protraction headgear in comparison to the controls. MATERIAL AND METHODS: A quasi experimental study was conducted in the orthodontic department on 60 patients of cleft lip and palate. These patients were divided into two groups. Group I was the Alt-RAMEC group that underwent Alt-RAMEC protocol followed by facemask therapy while group II was the control group that underwent RME and facemask therapy. Total treatment time in both the groups was approximately 6 to 7 months. Mean and standard deviation was calculated for all the quantitative variables. Pre and post treatment changes between treatment and control groups were made using paired t-test. Intergroup comparison between treatment and control group was analyzed using independent t-test. Significance for all tests was predetermined at a P-value of ≤ 0.05. RESULTS: The Alt-RAMEC group showed significant forward movement of maxilla and improvement in the maxillary base. A remarkable improvement in SNA was seen. The overall outcome was better maxillo-mandibular relationship as shown by positive ANB values and angle of convexity. More effect on maxilla and least effect on mandible was notified with Alt-RAMEC protocol and facemask therapy. Improvement in transverse relationship was also evident in the Alt-RAMEC group. CONCLUSION: Alt-RAMEC protocol in combination with protraction headgear is a better alternative to treat cleft lip and palate patients in comparison to the conventional protocol.

The impact of passive alveolar molding vs. nasoalveolar molding on cleft width and other parameters of maxillary growth in unilateral cleft lip palate.

OBJECTIVE: Passive alveolar molding (PAM) and nasoalveolar molding (NAM) are established presurgical infant orthodontic (PSIO) therapies for cleft lip palate (CLP) patients. PAM guides maxillary growth with a modified Hotz appliance, while NAM also uses extraoral taping and includes nasal stents. The effects of these techniques on alveolar arch growth have rarely been compared. MATERIAL AND METHODS: We retrospectively compared 3D-scanned maxillary models obtained before and after PSIO from infants with unilateral, non-syndromic CLP treated with PAM (n = 16) versus NAM (n = 13). Nine anatomical points were set digitally by four raters and transversal/sagittal distances and rotations of the maxilla were measured. RESULTS: Both appliances reduced the anterior cleft, but NAM percentage wise more. NAM decreased the anterior and medial transversal width compared to PAM, which led to no change. With both appliances, the posterior width increased. The alveolar arch length of the great and small segments and the sagittal length of the maxilla increased with PAM but only partially with NAM. However, NAM induced a significant greater medial rotation of the larger and smaller segment compared to PAM with respect to the lateral angle. CONCLUSIONS: NAM and PAM presented some significant differences regarding maxillary growth. While NAM reduced the anterior cleft and effectively rotated the segments medially, PAM allowed more transversal and sagittal growth. CLINICAL RELEVANCE: The results of this study should be taken into consideration when to decide whether to use PAM or NAM, since they show a different outcome within the first few months. Further studies are necessary regarding long-term differences.

Functional cleft palate surgery.

Cleft lip and palate (CLP) as a dislocation malformation confronts parents with a malformation of their child that could not be more central and visible: the face. In addition to the stigmatizing appearance, however, in cases of a CLP, food intake, physiological breathing, speech and hearing are also affected. In this paper, the principles of morphofunctional surgical reconstruction of the cleft palate are presented. With the closure of the palate, and restoration of the anatomy, a situation is achieved enabling nasal respiration, normal or near normal speech without nasality, improved ventilation of the middle ear, normal oral functions with coordinated interaction of the tongue with the hard and soft palate important for the oral and pharyngeal phases of feeding. With the establishment of physiological function, in the early phases of the infant and toddler, these activities initiate essential growth stimulation, leading to normalisation of facial and cranial growth. If these functional considerations are disregarded during primary closure, lifelong impairment of one or more of the abovementioned processes often follows. In many cases, despite secondary surgery and revision, it might not be possible to correct and achieve the best possible outcomes, especially if critical stages of development and growth have been missed or there has been significant tissue loss due to resection of existing tissue while primary surgery. This paper describes functional surgical methods and reviews long term, over many decades, results of children with cleft palate.

Oral Microbiome as a Tool of Systemic Disease on Cleft Patients: A New Landscape.

The oral cavity microbiome comprises benign and pathogenic bacteria, with more than 700 species identified. However, the current literature regarding resident bacterial flora in the oropharyngeal cavities in cleft lip/palate (CLP) patients still needs to be completed. This review aims to evaluate the role of the oral microbiome of cleft patients as an indicator in systemic diseases for which cleft patients might be at higher risk in the short or long term. A literature review was performed in July 2020 using Biomedical Reference Collection Comprehensive, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Complete, Dentistry & Oral Sciences Source via Elton B. Stephens Company/Online Database (EBSCO), Turning Research into Practice (TRIP), and PubMed. The keywords used were "oral, bacteria, microbiome, biota, flora, cleft, palate." The resulting 466 articles were deduplicated using Endnote. The total amount of articles' abstracts without duplicates was filtered using a set criterion. The title and abstract filter criteria included 1) cleft lip (CL) and/or cleft palate (CP) patients, 2) changes in the oral microbiome in CL and/or CP patients, 3) male and female patients 0-21 years old, and 4) English language. The full-text filter criteria included 1) CL and/or CP patients vs. non-cleft control patients, 2) oral bacteria, 3) nonprocedural measurements of microorganisms, and 4) case-control studies. A Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) flow chart was created using the EndNote data results. The final five articles of the systematic search indicated that the oral cavity of cleft lip and/or palate patients resulted in 1) contradicting levels of Streptococcus mitis and Streptococcus salivarius; 2) lower levels of Streptococcus gordonii, Bordetella dentium, Fusobacterium nucleatum, Veillonella parvula, Bacillus and Lautropia when compared to the control group; 3) higher levels of Staphylococcus epidermidis and Methicillin-sensitive Staphylococcus aureus compared to the control group; 4) presence of Enterobacter cloacae 36.6%, Klebsiella pneumoni 53.3%, and Klebsiella oxytoca 76.6% vs. absence in the control non-cleft group. Patients with CL and/or CP are at higher risk for caries, periodontal diseases, and upper and lower respiratory infections. The results from this review indicate that relative levels of certain bacteria may be associated with these issues. The lower levels of S. mitis, S. salivarius, S. gordini, and F. nucleatum in the oral cavity of cleft patients could be linked as a possible cause of the higher incidence of tooth decay, gingivitis and periodontal disease as high levels of these bacteria are associated with oral disease. Further, the higher incidence of sinusitis in cleft patients might be linked to low levels of S. salivarius in the oral profile of these patients. Likewise, E. cloacae, K. oxycota, and K. pneumoni have been linked with pneumonia and bronchiolitis, both of which are increased in cleft patients. The oral bacterial dysbiosis of cleft patients observed in this review may play a vital function in the oral microbiome's diversity, which could play a role in disease progression and disease markers. The pattern seen in cleft patients potentially demonstrates how structural abnormalities can lead to the onset of severe infection.

Comparison of post-surgical soft tissue changes between bilateral cleft patients treated with and without a modified nasoalveolar molding appliance: A cohort study.

INTRODUCTION: The advantages of nasoalveolar molding (NAM) treatment for cleft lip and palate (CLP) patients have been well documented. A modified design for bilateral CLP was introduced. AIMS: This paper aimed to: 1- quantify the soft tissue changes after applying modified NAM treatment to these patients; and 2-compare post-surgical changes to a control group where no NAM was used. MATERIAL AND METHODS: At a tertiary care paediatric hospital, a historical cohort group of complete BCLP patients (n=15) was compared to a prospectively collected group of complete BCLP patients who underwent NAM therapy (n=15). In the NAM group (mean age: 1.1mos±0.2), a new modification of the NAM appliance was implemented. In the control group (mean age: 5mos±0.2), no NAM treatment was adopted prior to lip closure surgery. Soft tissue nasolabial segments were measured on initial (T1), post-NAM (T2) and 3 months post-surgery (T3) photographs; measurements were analysed statistically. RESULTS: In the NAM group, cleft size was reduced by 68 to 70% in 4-5months and all measurements improved between T1 and T2. Columellar crest inclination decreased by 74%, columellar length increased by 184%, nostril and bialar widths decreased by 36% and 16%, respectively. The lip philtrum was elongated by 49.5%. At T3, all soft tissue variables statistically improved better in NAM versus non-NAM groups. CONCLUSION: The modified NAM appliance provided improved results of lip approximation and nasal measurements compared to non-NAM treatment.

The Risk of Orofacial Cleft Lip/Palate Due to Maternal Ambient Air Pollution Exposure: A Call for Further Research in South Africa.

Background: Despite being underreported, orofacial cleft lip/palate (CLP) remains in the top five of South Africa's most common congenital disorders. Maternal air pollution exposure has been associated with CLP in neonates. South Africa has high air pollution levels due to domestic burning practices, coal-fired power plants, mining, industry, and traffic pollution, among other sources. We investigated air pollutant levels in geographic locations of CLP cases. Methods: In a retrospective case series study (2006-2020) from a combined dataset by a Gauteng surgeon and South African Operation Smile, the maternal address at pregnancy was obtained for 2,515 CLP cases. Data from the South African Air Quality Information System was used to calculate annual averages of particulate matter (PM) concentrations of particles < 10 µm (PM10) and < 2.5 µm (PM2.5). Correlation analysis determined the relationship between average PM2.5/PM10 concentrations and CLP birth prevalence. Hotspot analysis was done using the Average Nearest Neighbor tool in ArcGIS. Results: Correlation analysis showed an increasing trend of CLP birth prevalence to PM10 (CC = 0.61, 95% CI = 0.38-0.77, p < 0.001) and PM2.5 (CC = 0.63, 95% CI = 0.42-0.77, p < 0.001). Hot spot analysis revealed that areas with higher concentrations of PM10 and PM2.5 had a higher proclivity for maternal residence (z-score = -68.2, p < 0.001). CLP birth prevalence hotspot clusters were identified in district municipalities in the provinces of Gauteng, Limpopo, North-West, Mpumalanga, and Free State. KwaZulu-Natal and Eastern Cape had lower PM10 and PM2.5 concentrations and were cold spot clusters. Conclusions: Maternal exposure to air pollution is known to impact the fetal environment and increase CLP risk. We discovered enough evidence of an effect to warrant further investigation. We advocate for a concerted effort by the government, physicians, researchers, non-government organizations working with CLP patients, and others to collect quality data on all maternal information and pollutant levels in all provinces of South Africa. Collaboration and data sharing for additional research will help us better understand the impact of air pollution on CLP in South Africa.