Oral Clefts Research Articles

Folic Acid Before and During Pregnancy

Folate is a key nutrient required to maintain optimal health, especially when planning a family or during pregnancy. The functionality of folate centres on the production of healthy red blood cells, important for the transportation of oxygen around the body. It supports development of the foetal nervous system specifically neural tube growth, with evidence showing that taking folic acid supplements before and during pregnancy reduces the chance of the baby developing spina bifida and other conditions affecting the spine and neural tube.1 Folate is essential for DNA replication, and may protect against miscarriage, premature birth and low birth weight, with beneficial effects in the prevention of structural anomalies, congenital heart disease and oral clefts.2

The Safety of Alcohol Pharmacotherapies in Pregnancy: A Scoping Review of Human and Animal Research.

Alcohol pharmacotherapies pose unknown teratogenic risks in pregnancy and are therefore recommended to be avoided. This limits treatment options for pregnant individuals with alcohol use disorders (AUD). The information on the safety of these medications during pregnancy is uncertain, prompting a scoping review. The objective of this review was to investigate available information on the safety of alcohol pharmacotherapies in pregnancy. Studies published between January 1990 and July 2023 were identified through searches in BIOSIS, Embase, PsycINFO and MEDLINE databases, using terms related to pregnancy and alcohol pharmacotherapies. The alcohol pharmacotherapies investigated were naltrexone, acamprosate, disulfiram, nalmefene, baclofen, gabapentin and topiramate. Studies were screened by two independent reviewers. Covidence software facilitated the management, screening and extraction of studies. A total of 105 studies were included in the review (naltrexone: 21, acamprosate: 4, disulfiram: 3, baclofen: 3, nalmefene: 0, topiramate: 55, gabapentin: 32) with some studies investigating multiple medications. Studies investigating naltrexone's safety in pregnancy focussed on opioid use disorders, with limited evidence regarding its safety in the context of AUD. Despite concerns about higher rates of some pregnancy complications, studies generally indicate naltrexone as a safer option compared with opioid agonists or alcohol during pregnancy. Acamprosate was not clearly associated with adverse effects of exposure in pregnancy, with two pre-clinical studies suggesting potential neuroprotective properties. Disulfiram has a high risk of congenital anomalies when used in pregnancy, believed to be due to its mechanism of action. Prenatal topiramate has also been associated with an increased risk of congenital anomalies, particularly oral clefts. There were mixed results concerning the safety of prenatal gabapentin and little to no literature investigating the safety of baclofen or nalmefene during pregnancy. There is insufficient research on the safety of alcohol pharmacotherapies in pregnancy. Despite this, given alcohol's teratogenic effects, naltrexone could be considered to help maintain abstinence in pregnant individuals with AUD, particularly when psychosocial treatments have failed.

Comparison of palatal fistula incidence post palatoplasty with Veau-wardill kilner technique between men and women

Cleft palate is a congenital abnormality that occurs in the mouth and surrounding structures. The most used classification of cleft palate by Veau (1931). To repair the palatal defect, shape and function, surgical correction is necessary. There are various types of palatoplasty techniques that can be used, such as Veau-Wardill-Kilner. Palatoplasty may causes complications such as palatal fistula. Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Airlangga University has been carrying out a social service for cleft lip and palate surgery repair since year 2008 in various regions in Indonesia. However, until now, there is no data available related with the incidence of palatal fistula. Purpose: To observe the comparison between the palatal fistula incidence post palatoplasty using Veau-Wardill-Kilner technique based on gender. Methods: This study based on 113 palatoplasty cases using Veau-Wardill-Kilner technique taken from Oral and Maxillofacial Cleft Palate Surgery Social Service data, Faculty of Dental Medicine, Airlangga University from the period of 2013 until 2022. Data analysis used Kruskal-Wallis on IBM SPSS version 29 Windows. Results: from 113 patients, 20 cases (17,7%) showed that there is developed palatal fistula. Between the incidence of palatal fistula in men and women observed after palatoplasty procedure using Veau-Wardill-Kilner, higher percentages of palatal fistula were found in women (p=0.426). Conclusion: The incidence of palatal fistula post palatoplasty using Veau-Wardill-Kilner technique in women is higher than men.

Three-dimensional Assessment of Longitudinal Surgical Outcome in Patients with Unilateral Cleft Lip and Palate: A Modified Rotation Advancement Technique.

Optimization of a modified rotation advancement technique is hampered by lack of objective measures to quantify the longitudinal surgical outcome. We collected and assessed facial 3D images of 115 consecutive patients who underwent primary repair between 2017 and 2019. Photogrammetry was performed preoperatively, immediately postoperatively and at a first and second follow-up interval, occurring at an average year of 0.6 and 5.3 years, respectively. 10 additional age-matched noncleft control subjects were also included. Growth lag in cleft side lateral lip and gradual elongation of medial lip height on the cleft side caused continuous deviation of philtrum towards the cleft side. The columellar length on the cleft side continued to grow slower, accompanied by a persistent widening of alar base width on the cleft side, leading to in the gradual deviation of columella towards the cleft side. The pre-operative and post-operative nasolabial asymmetry would increase with greater degree of postoperative deficiencies. Right clefts presented with greater degrees of deficiencies in lateral lip height in preoperative measurement, but this discrepancy of the laterality of clefts was not observed in the two follow-up periods. The surgical outcome of this modified rotational advancement technique in unilateral cleft lip primary repair is promising. Growth lag in lateral lip and lateral displacement of alar base cause continuous deviation of philtrum towards the cleft side. Pre-operative severity does predict post-operative outcomes. Laterality of oral clefts does not significantly affect the long-term outcomes of surgery. This surgical technique meets the current trend of cleft lip and palate primary repair and is worth promoting.

Cleft lip/palate patients’ oral health status: an epidemiological study at a Brazilian pediatric hospital

Cleft lip/palate is a congenital maxillofacial malformation which results from genetic and environmental factors. In Brazil, the prevalence is 1 in every 673 live births. Several alterations result from oral clefts and affects function, aesthetics, and social life. Due to morphofunctional changes, these patients are more susceptible to disorders of the oral cavity. This study aimed to conduct an epidemiological study about alterations of the stomatognathic complex in cleft lip/palate patients at Albert Sabin Pediatric Hospital in Fortaleza, Ceará, Brazil. Files containing medical records, imaging exams and dental models of 64 patients from 2005 to 2017 were analyzed. There was a higher prevalence of males, patients from the countryside and the left unilateral transforaminal cleft subtype. 85.9% of the patients had undergone cheiloplasty and palatoplasty. About 74% of patients had dental agenesis, 71.9% developed the precanine tooth, 26.6% presented dental shape anomalies and 65.6% presented maxillary atresia. The mean DMFT index (decayed, missing, and filled teeth) of the patients was 3.51. These results corroborate and add valuable information to the available literature on cleft lip/palate patients. Our results demonstrate that cleft patients present dental and skeletal alteration that need specialized treatment.

Clinical Study of Photobiomodulation Effect at Postoperative Clefted Alveolar Ridge Bone Grafting.

This study aimed to evaluate photobiomodulation (PBM) adjunct effect on pain, swelling, and face temperature in individuals with oral cleft submitted to alveolar ridge bone grafting (ABG). The sample consisted of 46 patients with either incomplete or complete unilateral cleft lip and palate aged from 9 to 18 years, both sexes, who underwent ABG with chin donor area. Subjects were randomly divided into 3 groups: (1) Control (C): ABG (n=17); (2) PBM: ABG with PBM (n=14); (3) Simulated photobiomodulation (SPBM): ABG with SPBM (n=15). Aluminum Gallium Arsenide (GaAlAs) infrared laser was used at 808±10nm and power of 100mW±20%. GaAlAs infrared laser was applied on 14 points in the subject's face at 4J per point, at 2 times: Immediate postoperative period and 24 hours postoperative. The authors evaluated pain, swelling, and face temperature at 24 hours postoperative; at 7-day postoperative, the authors evaluated pain, medication use, and swelling decreasing perception. No statistically significant difference occurred between groups C, PBM, and SPBM. At 24 hours postoperative, pain values showed statistically significant difference (P=0.04) between group C and SPBM. PBM at the tested parameters did not reduce pain and swelling and did not significantly change face temperature of individuals submitted to ARBG.

A Comparative Analysis of Sector Classification and the Impacted Canine Grading System by Kumar and Daigavane in Patients With Unilateral Cleft Lip and Palate Utilizing Orthopantomogram (OPG) as a Diagnostic Tool.

Introduction Non-syndromic oral clefts, affecting one in 700 newborns in India, are the most prevalent craniofacial anomalies, with genetic or environmental causes impacting various life aspects. Studies indicate higher dental disturbances, particularly impacted canines, in cleft lip and palate (CLP) patients compared to non-cleft individuals. Impacted canines, trapped by hard tissues, require early diagnosis to prevent orthodontic issues. The widely used Ericson and Kurol method employs orthopantomograms (OPGs) to classify canine impaction in typical children. However, diagnosing canines in CLP patients is challenging due to palate defects and post-grafting complications. This study aims to compare the utility of the Kumar and Daigavane (KD) grading system and the sector classification to determine the best method for diagnosing impacted canine eruption paths. Method This cross-sectional comparative observational study was conducted at Sharad Pawar Dental College's Department of Orthodontics and Dentofacial Orthopaedics. The sample size, calculated using a significance level of 5% and a prevalence of 1%, required a minimum of 16 participants aged 9-11 years with non-syndromic clefts and impacted canines. Patients with systemic diseases or over 12 years of age were excluded. The sectoral and KD classification systems collected and evaluated OPGs from qualifying cleft patients. Sector classification considered the angle between the occlusal plane or canine tip and the adjacent tooth's long axis, while KD's classification considered the Frankfort horizontal plane, occlusal plane, vertical height from the occlusal plane, canine apex root position, and canine exposure to the cleft defect. Results The study found an 81.25% agreement between the KD grading system and the sector classification, with a Cohen's kappa value of 0.586, indicating a moderate agreement. The KD system showed 81.82% sensitivity and 80.00% specificity, with positive and negative predictive values of 90.00% and 66.67%, respectively. The receiver operating characteristic (ROC) curve analysis revealed the KD system's superior performance in identifying impacted and non-impacted canines compared to the sector classification. Conclusion The KD grading system demonstrated higher efficacy than the sector classification for evaluating the impacted canines in children with unilateral cleft lip and palate (UCLP). The KD system's high sensitivity and specificity make it a valuable tool for predicting canine eruption paths and addressing anatomical challenges in cleft conditions. This study highlights the need for accurate diagnostic tools tailored to cleft patients and contributes to advancing orthodontic treatment outcomes through improved classification systems.

Patient adherence in orthodontics: a protocol for a scoping review

BackgroundPatient adherence is a key factor in achieving orthodontic success. While in recent years there have been changes in orthodontic healthcare, no recent comprehensive reviews regarding adherence in orthodontics are available. Therefore, the aim of this planned scoping review is to systematically map the available literature regarding patient adherence in orthodontics to identify factors associated with patient adherence and to investigate if there are knowledge gaps in the available literature.Methods/designThis protocol was drafted according to guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) statement and the PRISMA extension for Scoping Reviews (PRISMA-ScR). For the methods Arksey and O’Malley’s framework and the Reviewer’s Manual of the Joanna Briggs Institute for conducting scoping reviews were consulted. The inclusion criteria for this scoping review are studies of all designs assessing any form of adherence in orthodontics, published in English from 2006 onwards. The exclusion criteria are studies investigating adherence in the following patients: those with an intellectual or physical disability that could affect their ability to coincide with their therapist’s recommendations and advice, those with oral cleft and craniofacial conditions, and those solely treated for obstructive sleep apnoea. Case reports and studies published in non peer reviewed journals will also be excluded. The following electronic databases will be searched: Embase, PubMed, and Web of Science Core Collection. The following key terms will be used in the search strategies: ‘treatment adherence and compliance’, and ‘orthodontics’. Multiple reviewers will independently screen the results and perform the data charting process. A narrative description will be provided for the analysis of the included studies. The results will be categorized into multiple topics based on recommendations by previous studies into patient adherence. Identified knowledge gaps will be reported and recommendations for future research will be suggested.DiscussionNo systematic review has previously assessed this exact topic. Because of the broad-spectrum research questions and the expected widely scattered literature a scoping review approach was chosen over a systematic review approach. The Academic Centre for Dentistry Amsterdam (ACTA) has been conducting research in patient adherence in orthodontics up to 2006 and therefore only studies published from 2006 onwards will be researched in this review. Identifying knowledge gaps and summarizing and disseminating research findings on this topic is important for every dental professional performing orthodontic treatment. This protocol is registered in the Open Science Framework: https://osf.io/ec6qd

Birth defects among offspring of California firefighters, 2007–2019

PurposeLimited research examines birth defects from maternal or paternal firefighting exposure. This study aims to assess if maternal or paternal occupational exposure to firefighting during periconception is associated with offspring birth defects. MethodsData from California birth certificates (2007–2019) were linked to maternal / offspring hospitalization records. Occupation during the periconceptional period was categorized from vital statistics as the following: paternal non-firefighting (n = 4,135,849), paternal firefighting (n = 22,732), maternal non-firefighting (n = 3,332,255) and maternal firefighting (n = 502). Birth defects were identified using ICD codes, grouped by anatomical regions. Adjusted odds ratios were estimated, and sensitivity analyses explored police officer reference groups and detailed birth defect categories. ResultsOffspring of paternal firefighters had lower odds of circulatory defects (aOR = 0.9, 95% CI 0.8, 1.0), oral clefts (aOR = 0.6, 95% CI 0.4, 0.8) and respiratory defects (0.7, 95% CI 0.6, 0.9) compared to paternal non-firefighters. Associations between maternal firefighting and offspring birth defects were imprecise. Substituting police officers as the reference group attenuated findings. ConclusionsOffspring of paternal firefighters may have similar or slightly lower birth defect odds compared to offspring of non-firefighters. Limited data was available for assessing maternal firefighting outcomes. Future studies should prioritize studies using occupational exposure matrices to limit misclassification of exposure.

Patient adherence in orthodontics: a scoping review

ABSTRACTBackgroundPatient adherence is a key factor in achieving orthodontic treatment success. Despite an evolution in orthodontic healthcare, no recent comprehensive reviews are available on patient adherence in orthodontics. This scoping review provides an evidence-based overview of the literature available on multiple aspects of patient adherence in orthodontics, during both active treatment as well as during the retention phase. Knowledge gaps identified in the literature are listed.MethodsThe protocol for this scoping review was registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/EC6QD). Electronic databases and reference lists of relevant studies were searched up to 9 February 2023. The inclusion criteria were studies investigating any form of patient adherence in orthodontics published in English from 2006 onwards. The exclusion criteria were studies investigating adherence in the following patients: those with an intellectual or physical disability that could affect their ability to coincide with their therapist’s recommendations and advice, those with oral cleft and craniofacial conditions, and those treated solely for obstructive sleep apnoea. Non-peer-reviewed studies and case reports were also excluded.ResultsA total of 3284 articles were identified, 60 of which met the criteria for final inclusion.ConclusionsThere is no conclusive evidence on which factors have a significant impact on patient adherence and how patient adherence can be promoted. The degree of patient adherence is generally not compared to achieved treatment results or stability of treatment results, making it difficult to provide clear statements about the impact of the degree of adherence on desired treatment results or orthodontic stability.

Concomitant use of antidepressants and benzodiazepines during pregnancy and associated risk of congenital malformations: a population-based cohort study in Taiwan

Despite the frequent co-administration of antidepressants and benzodiazepines, the association between such concomitant use during pregnancy and the risk of congenital malformations remains inadequately explored. This study aims to examine the association between concomitant use of antidepressants and benzodiazepines during the first trimester and organ-specific congenital malformations. We conducted a population-based cohort study using Taiwan's National Birth Certificate Application database, the Maternal and Child Health database, and Taiwan's National Health Insurance database. Pregnant people aged 15-50 years with singleton births between Jan 1, 2004, and Dec 31, 2018, were included. Use of antidepressants and benzodiazepines was defined as at least one prescription during the first trimester, and concomitant use was defined as the overlapping prescription of both drugs with an overlapping prescription period. The primary outcomes were overall congenital malformations and eight organ-specific malformations, consisting of the nervous system, heart, respiratory system, oral cleft, digestive system, urinary system, genital system, and limb malformations. Logistic regression models with propensity score fine stratification weighting approach were used to control for measured confounders. Analyses controlling for confounding by indication and sibling comparison analyses were done to address unmeasured confounders. No individuals with lived experience participated in the research or writing process. The cohort included 2 634 021 singleton pregnancies, and 8599 (0·3%) individuals were concomitant users of antidepressants and benzodiazepines during the first trimester (mean age at delivery was 31·8 years [SD 5·2] for pregnancies with exposure to antidepressants and benzodiazepines vs 30·7 years [SD 4·9] for pregnancies without exposure). All study participants were female, and information about ethnicity was not available. Absolute risk of overall malformations was 3·81 per 100 pregnancies with exposure, compared with 2·87 per 100 pregnancies without exposure. The propensity score-weighted odds ratios (weighted ORs) did not suggest an increased risk for overall malformations (weighted OR 1·10, 95% CI 0·94-1·28), heart defects (1·01, 0·83-1·23), or any of the other organ-specific malformations, except for digestive system malformations, for which the weighted OR remained statistically significant after adjustment (1·63, 1·06-2·51). The absence of an increased risk for overall congenital malformations associated with concomitant use of antidepressants and benzodiazepines was supported by the analyses controlling for confounding by indication and sibling-matched comparisons. The findings of this study suggest that the concomitant use of antidepressants and benzodiazepines during the first trimester is not associated with a substantial increase in risk for most malformation subtypes. However, considering other potential adverse effects of using both medications concomitantly, a thorough assessment of the risks and benefits is crucial for clinical decision making. National Science and Technology Council.

Congenital anomalies in Santa Catarina, Southern Brazil: macroregional and temporal birth prevalence for the period 2011-2020.

Congenital anomalies (CAs) are an important cause of infant mortality and efficient surveillance is necessary for their prevention. Therefore, the objective of this study is to establish baselines of prevalence at birth of priority CAs for surveillance in the state of Santa Catarina, using data from the Live Birth Information System considering the period 2011-2019 (baseline) and 2020 (pandemic year). The analyses were carried out based on the mother's residence health macroregion. The CAs were selected following the ICD-10 coding for chapter XVII. Birth prevalence was calculated per 10,000 live births and the confidence interval was established at 95%. 2011-2019 recorded 88.8/10,000 births with CAs (total). For 2011-2019, limb defects (without polydactyly) were the most prevalent (14.1/10,000), followed by congenital heart defects (8.9), oral clefts (8.2), polydactyly (7.9), Down syndrome (5.6), hypospadias (5.4), neural tube defects (4.7), gastroschisis (3.3), undefined sex (1.2), microcephaly (0.8) and omphalocele (0.3). There were no significant differences in temporal and spatial distribution. However, unusual fluctuations were observed in 2020, which may reflect the pandemic in CAs notifications. In the base period, Santa Catarina recorded CAs below the expected level of being identified at birth. With this, we conclude that the training and awareness of teams are essential for the surveillance of CAs in Santa Catarina.

Correlation between FOXN3-SIN3A complex expression in peripheral blood and non-syndromic cleft lip and palate in Xinjiang.

This work aimed to study the correlation between FOXN3-SIN3A complex expression and non-syndromic oral clefts (NSOC) in Xinjiang. In this study, 60 patients with NSOC attending the People's Hospital of Xinjiang Uygur Autonomous Region were recruited into the case group, including 30 cleft lip with or without cleft palate (NSCL/P), 30 cleft palate only (CPO), and 30 healthy children in the control group. The expression levels of FOXN3, SIN3A, and NEAT1 in peripheral blood of each group were detected by high-throughput second-generation sequencing technology and quantitative reverse transcription polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the diagnostic efficiency of NSOC. The comparison of the NSOC and control groups showed that FOXN3, SIN3A, and NEAT1 genes increased compared with the control group. The differences were all statistically significant (P<0.05). The AUCs of FOXN3, SIN3A, and NEAT1 in the NSCL/P group were 0.933 [95%CI=(0.864, 1.000)], 0.822 [(95%CI=(0.713, 0.932)], and 1.000[95%CI= (1.000, 1.000)], respectively. The AUCs of FOX-N3, SIN3A, and NEAT1 in the CPO group were 0.891 [95%CI=(0.806, 0.976)], 0.688 [95%CI=(0.552, 0.824)], and 1.000 [95%CI=(1.000, 1.000)], respectively. The results showed a correlation between the rising gene expression of FOXN3, SIN3A, and NEAT1 in peripheral blood and the occurrence of NSOC in Xinjiang. This work provides a theoretical basis for further study of the FOXN3-SIN3A complex as biomarkers to facilitate the early screening, disease prediction, and early prevention of NSOC.

A retrospective study of congenital anomalies and associated risk factors among children admitted at a tertiary hospital in northwestern Tanzania.

Congenital anomalies in Sub-Sahara Africa (SSA) are understudied despite the significant pediatric health burden. This retrospective longitudinal hospital-based study evaluated the records of 326 inpatient children under the age of two years with congenital anomalies at Bugando Medical Centre, a tertiary referral hospital in northwestern Tanzania. Classical logistic regression was used in the analysis of congenital malformation of muscles, gastrointestinal malformation, oral facial clefts, neural tube defects, and skeletal malformations. A modified poisson regression was used to model risk factors for Central Nervous System (CNS) hydrocephalus and congenital heart disease (CHD). A majority (78.8%) of children included in the study were less than six months of age. Nearly half (48.8%) were diagnosed with CHD followed by CNS hydrocephalus (10.4%) and congenital malformation of muscles (8.9%). Babies whose mothers missed periconceptual folic acid supplementation had 83% higher risk of hydrocephalus (aPR = 1.83, 95% CI = 1.11-1.96) and 78% higher for CHD (aPR = 1.78, 95% CI = 1.31-1.94). Male children had 1.67 higher odds of muscular congenital malformations (aOR = 1.67, 95% CI = 1.23-1.89). Less than 37 gestational age had a 1.86 higher odds of muscular congenital malformations (aOR = 1.86, 95% CI = 1.53-3.66). Our study highlights the critical need for folic acid supplementation and establishes a need for a registry and the potential for mapping.

Association of EPHA3 Gene Variation with Oral Hygiene in an Iranian Population

Background: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most prevalent congenital birth anomaly. The EPHA3 gene is suggested to play a pivotal role in the development of oral clefts. Objectives: This study aimed to evaluate the influence of EPHA3 gene polymorphisms on the risk of NSCL/P within an Iranian cohort. Methods: We performed genotyping of the EPHA3 gene polymorphisms rs7650466, rs1398197, rs17801309, rs1054750, and rs7632427 in 150 NSCL/P patients and 152 healthy controls using PCR-RFLP, T-ARMS-PCR, and ARMS-PCR methods. Results: The results indicated that the rs1398197 variation significantly reduced the risk of NSCL/P in a heterozygous codominant model (OR = 0.58, 95% CI = 0.36 - 0.94, P = 0.027, G/A vs. G/G), a dominant model (OR = 0.56, 95% CI = 0.35 - 0.89, P = 0.014, G/A + A/A vs. G/G), and at the allele level (OR = 0.62, 95% CI = 0.43 - 0.91, P = 0.014, A vs. G). The rs1054750 polymorphism showed a decreased risk of NSCL/P in codominant (OR = 0.62, 95% CI = 0.39 - 0.99, P = 0.047, T/C vs. T/T) and dominant models (OR = 0.62, 95% CI = 0.39 - 0.98, P = 0.042, T/C + C/C vs. T/T). The rs17801309 polymorphism was not associated with any risk or protection from NSCL/P. rs7650466 and rs7632427 were not polymorphic in the study sample. Conclusions: Our findings suggest that variants of the EPHA3 gene may be linked with a reduced risk of NSCL/P.

Contemporary Prevalence of Oral Clefts in the US: Geographic and Socioeconomic Considerations.

Background: Socio-economic status, living environments, and race have been implicated in the development of different congenital abnormalities. As orofacial clefting is the most common anomaly affecting the face, an understanding of its prevalence in the United States and its relationship with different determinants of health is paramount. Therefore, the purpose of this study is to determine the modern prevalence of oral-facial clefting in the United States and its association with different social determinants of health. Methods: Utilizing Epic Cosmos, data from approximately 180 US institutions were queried. Patients born between November 2012 and November 2022 were included. Eight orofacial clefting (OC) cohorts were identified. The Social Vulnerability Index (SVI) was used to assess social determinants of health. Results: Of the 15,697,366 patients identified, 31,216 were diagnosed with OC, resulting in a prevalence of 19.9 (95% CI: 19.7-20.1) per 10,000 live births. OC prevalence was highest among Asian (27.5 CI: 26.2-28.8) and Native American (32.8 CI: 30.4-35.2) patients and lowest among Black patients (12.96 CI: 12.5-13.4). Male and Hispanic patients exhibited higher OC prevalence than female and non-Hispanic patients. No significant differences were found among metropolitan (20.23/10,000), micropolitan (20.18/10,000), and rural populations (20.02/10,000). SVI data demonstrated that OC prevalence was positively associated with the percentage of the population below the poverty line and negatively associated with the proportion of minority language speakers. Conclusions: This study examined the largest US cohort of OC patients to date to define contemporary US prevalence, reporting a marginally higher rate than previous estimates. Multiple social determinants of health were found to be associated with OC prevalence, underscoring the importance of holistic prenatal care. These data may inform clinicians about screening and counseling of expectant families based on socio-economic factors and direct future research as it identifies potential risk factors and provides prevalence data, both of which are useful in addressing common questions related to screening and counseling.

Different fetal effects on fingers from exposure to phenytoin, phenobarbital, and carbamazepine.

Exposure at conception to phenytoin (PHT), phenobarbital (PB), and carbamazepine (CBZ) has been associated with several different effects on the fetus, including hypoplasia of the distal phalanges, dysmorphic facial features, and structural abnormalities such as oral clefts and neural tube defects. One question is whether each of these antiepileptic drugs (AEDs) has the same effects or just similar effects. A systematic examination of the fingers of children exposed at conception to PHT, PB, or CBZ, as monotherapy, has been used to address this question. The findings in the examinations of the fingers of 115 AED-exposed children (40, PHT; 34, PB; 41, CBZ) and their parents were compared to the findings in 111 age- and sex-matched children and their parents. The evaluations used were both subjective assessments and objective measurements. Shortening and narrowing of the fifth fingernail and an increased frequency of arch patterns in the dermal ridges were more common in PHT-exposed children. A significant decrease in the length of the nail, but not width, occurred in the PB-exposed children. Stiffness of the interphalangeal joints was more common in the CBZ-exposed children. The findings in children exposed to PHT, PB, or CBZ, as monotherapy, showed that all three exposures in early pregnancy affected the fingers, but the effects were not the same. The most striking effects were present in PHT-exposed children.

Self-perceived oral health and orofacial aesthetics of cleft patients

PurposeTo evaluate the self-perceived oral health and aesthetics of the dentition and jaw in patients with different types of oral cleft, measured by patient-reported outcome measures (PROMs). Additionally, to compare the results of the PROMs between cleft lip and or/palate (CL/P) patients and non-affected controls.Methods420 CL/P patients treated at the cleft team of the Erasmus Medical Center, Rotterdam, The Netherlands, were included, and 138 non-cleft patients were recruited as control-group. Patient’s perceptions were retrospectively evaluated using the CLEFT-Q Teeth for dental aesthetics at ages 8, 12 and 22, CLEFT-Q Jaw for jaw aesthetics at ages 12 and 22, and the Child Oral Health Impact Profile—Oral Symptoms Subscale (COHIP-OSS) for oral health at ages 8 and 12. One-way ANOVA was used to compare differences in oral health and aesthetic perceptions among age-groups, cleft types, as well as between cases and controls.ResultsCL/P patients were significantly less satisfied than controls with their dental aesthetics (p = 0.001). CL/P patients reported significantly lower satisfaction on CLEFT-Q Teeth scores at ages 8 and 12, than at 22 years (p < 0.001). Patients with the most extensive cleft phenotype, Cleft Lip and Palate (CLAP), reported lowest satisfaction on the CLEFT-Q Teeth. No differences in perceptions of oral health nor in aesthetics of the jaw were found in the different cleft types, ages, nor in study versus control group.ConclusionThis study found differences in self-perceived dental aesthetics: CL/P patients are less satisfied than non-affected controls. CLAP patients are least satisfied, but satisfaction increases with age.

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

ABSTRACT 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.

Association of Commonly Prescribed Antepartum Medications and Incidence of Orofacial Clefting.

Pharmacologic agents are often used in the antepartum period, however, studies on their effect on fetal development are limited. Thus, this study aims to examine the effect of commonly prescribed antepartum medications on the development of orofacial clefting. Utilizing EPIC Cosmos deidentified data from approximately 180 US institutions was queried. Patients born between January 1, 2013, to January 1, 2023, were included. Eight OC cohorts were identified. Gestational medication use was identified by medications prescribed, provider-administered, or reported use by mothers. Medications used in at least 1 in 10,000 pregnancies were included in this analysis. A total of 12 098 newborns with available maternal pharmacologic data were born with any type of orofacial clefting. Prevalence for all oral clefts, any cleft palate, and any cleft lip were 20.56, 18.10, and 10.60 per 10 000 individuals, respectively. Notable significant exposures include most anticonvulsants, such as lamotrigine (OR1.33, CI 1.10-1.62), and topiramate (OR1.35, CI 1.13-1.62), as well as nearly all SSRIs/SNRIs, including fluoxetine (OR1.34, CI 1.19-1.51), sertraline (OR1.25, CI 1.16-1.34), and citalopram (OR1.28, CI 1.11-1.47). Corticosteroids were also correlated including dexamethasone (OR1.19, CI 1.12-1.27), and betamethasone (OR1.64, CI 1.55-1.73), as were antibiotics, including amoxicillin (OR1.22, CI 1.14-1.30), doxycycline (OR1.29, CI 1.10-1.52), and nitrofuran derivatives (OR1.10, CI 1.03-1.17). New associations between commonly prescribed antepartum medications and orofacial clefting were found. These findings should be confirmed as causality is not assessed in this report. Practitioners should be aware of the potential increased risk associated with these medications.