Oral and dental alterations and growth disruption following chemotherapy in long-term survivors of childhood malignancies.

PURPOSE: More attention has been focused on the long-term side effects of treatment protocols since impressive advances in childhood cancer treatment have resulted in a growing population of patients. The purpose of this study was to investigate the disturbances of dento-facial development in children who were long-term survivors of childhood malignancies. METHODS: Fifty-three children (mean age, 10 years + 4 months) in long-term remission underwent oral/dental and radiographic examinations after completion of therapy. Crown and root malformations, gingival/periodontal status, enamel defects, discolorations, decayed and unerupted teeth, premature apexifications, agenesis, maximal interincisal opening and lateral movement of jaws, and soft tissue abnormalities were noted. Caries were evaluated by the decayed-missing-filled teeth (DMFT) index. Forty healthy children (mean age, 12 years + 4 months) belonging to the same age group and socioeconomic community were served as controls. All participants in the study were evaluated in terms of craniofacial development. RESULTS: The data of the study showed that higher prevalence of root malformation, unerupted teeth, and enamel hypoplasia were detected as a consequence of childhood cancer and/or antineoplastic therapy. Although no differences of craniofacial growth and development were observed between groups (P > 0.05), plaque and gingival index scores were statistically higher in the study group (P < 0.05). CONCLUSION: A range of variations in dental structures is recognized as a side effect of childhood cancer therapy in long-term survivors of pediatric malignancies that may affect their quality of life.

Dry mouth: Xerostomia and salivary gland hypofunction.

BACKGROUND: Mouth dryness may present as salivary gland hypofunction (SGH), xerostomia or both. It is considered one of the most underappreciated, underdiagnosed and undermanaged oral health conditions. Despite its common presentation and adverse impact on life quality, it is also generally poorly understood. Increased awareness of the condition is important in addressing these problems. OBJECTIVE: This article discusses SGH and xerostomia, and the associated intra-oral and extra-oral implications. It also summarises currently available management approaches and the evidence behind them. DISCUSSION: SGH and xerostomia are complex problems. None of the currently available management approaches are entirely satisfactory. Addressing the causative or contributing factors is therefore paramount. While oral health complaints are generally left up to the dental professional to manage, the nature of mouth dryness necessitates increased dialogue between the dental and medical professions to ensure optimal patient care.

Knowledge of Nairobi East District Community Health Workers concerning HIV-related orofacial lesions and other common oral lesions.

BACKGROUND: Human immunodeficiency virus (HIV) related orofacial lesions (HROLs) impact negatively on the health of patients and could be managed at primary healthcare (PHC) level. Community health workers (CHWs) are crucial in optimal patient management through patient identification, education and early referral for professional care. The study objective was to assess knowledge of Nairobi East district CHWs regarding HROLs and other common oral diseases. METHODS: Of the total population of CHWs, 815 [94.5%] completed a 56-item questionnaire covering 5 topics: general dental knowledge, knowledge about HROLs, past encounters with HROLs, current care at community level, opinions regarding oral health problems; and items concerning background characteristics and past training activities. Confirmatory factor analysis revealed Cronbach's alpha coefficient values of 0.45, 0.59, 0.79, 0.50 and 0.09 respectively. The first four topics were confirmed as domains. Mean minimum score was 0 and mean maximum score was 1 for each variable. However, for 'past encounters with HROLs, the minimum score was 0 and maximum score was 5. RESULTS: CHWs had moderate knowledge about general oral health (mean = 0.47) and HROLs (mean = 0.43). None had been formally trained in oral health aspects. Although they had high opinions regarding their role in identifying, educating and referring patients with HROLs (mean = 0.80) to the health facilities, they actually rarely referred such patients. CONCLUSIONS: CHWs need training for building competence in promoting oral health among general and HIV patients in their communities and in early identification and management of non-HIV oral lesions.

The association of ambient air pollution and traffic exposures with selected congenital anomalies in the San Joaquin Valley of California.

Congenital anomalies are a leading cause of infant mortality and are important contributors to subsequent morbidity. Studies suggest associations between environmental contaminants and some anomalies, although evidence is limited. We aimed to investigate whether ambient air pollutant and traffic exposures in early gestation contribute to the risk of selected congenital anomalies in the San Joaquin Valley of California, 1997-2006. Seven exposures and 5 outcomes were included for a total of 35 investigated associations. We observed increased odds of neural tube defects when comparing the highest with the lowest quartile of exposure for several pollutants after adjusting for maternal race/ethnicity, education, and multivitamin use. The adjusted odds ratio for neural tube defects among those with the highest carbon monoxide exposure was 1.9 (95% confidence interval: 1.1, 3.2) compared with those with the lowest exposure, and there was a monotonic exposure-response across quartiles. The highest quartile of nitrogen oxide exposure was associated with neural tube defects (adjusted odds ratio = 1.8, 95% confidence interval: 1.1, 2.8). The adjusted odds ratio for the highest quartile of nitrogen dioxide exposure was 1.7 (95% confidence interval: 1.1, 2.7). Ozone was associated with decreased odds of neural tube defects. Our results extend the limited body of evidence regarding air pollution exposure and adverse birth outcomes.

Maternal bereavement in the antenatal period and oral cleft in the offspring.

STUDY QUESTION: Is maternal bereavement (emotional stress) due to loss of a close relative in the antenatal period associated with the risk of oral cleft in the offspring? SUMMARY ANSWER: Our study suggests prenatal maternal bereavement is associated with an increased risk of oral cleft in the offspring, especially when the bereavement was due to a sudden death or death of a child. WHAT IS KNOWN ALREADY: The aetiology of oral cleft is unknown but includes both genetic and environmental causes. STUDY DESIGN, SIZE AND DURATION: We performed a population-based cohort study based on several national registers in Denmark from 1978 to 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our final study population consisted of 1 771 663 children. Of these 35 118 (2%) were born to mothers who experienced bereavement in the exposure window from 1 year before pregnancy to the end of the first trimester. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 3043 children were diagnosed with a cleft; 968 with cleft lip, 1206 with cleft lip and palate and 869 with a cleft palate. For overall bereavement the prevalence was 1.7 per 1 000 live born in the unexposed children and 2.2 per 1 000 live born in the exposed children. Overall, maternal bereavement due to the death of a close relative from 1 year before conception to the end of the first trimester was associated with a significantly increased risk of oral cleft [odds ratio (OR): 1.28, 95% confidence interval (CI): 1.01; 1.61). When mothers lost a relative due to a sudden death, the risk of oral cleft in the offspring was higher (OR: 1.76, 95% CI: 1.06; 2.94). Losing a relative in the time period before pregnancy and during the first trimester showed a tendency to an increased risk. The risk increase was 77% when the mother was bereaved due to sudden death and the estimation was robust in different analytical strategies. LIMITATIONS, REASONS FOR CAUTION: It is a limitation that we only studied live born children, but most children with isolated oral cleft would survive their pregnancy and birth. Since oral cleft are rare and despite the large study population, we still had a relatively small number of cases, which results in limited power to detect small differences. We did not have actual measurements of the maternal cortisol concentration, but we believe that bereavement due to death of a close relative produces a strong stress reaction in most people. Also we did not have the opportunity to adjust for intake of folic acid and use of anti-depressant; however, analysis in a subset of the data showed no difference in these intakes between exposed and unexposed mothers. WIDER IMPLICATIONS OF THE FINDINGS: With this study we add a large-scale human cohort study to the body of literature on stress and birth defects. Our study is in agreement with previously published results and can be generalized to similar populations like the native Danish population. Severe stress may be added to the list of potential causes for oral cleft.

Dental and oral anomalies in incontinentia pigmenti: a systematic review.

OBJECTIVES: Incontinentia pigmenti (IP) is an X-linked genodermatosis caused by a mutation of the IKBKG gene. The objective of this study was to present a systematic review of the dental and oral types of anomalies, to determine the total number and sex distribution of the anomalies, and to analyze possible therapies. MATERIALS AND METHODS: We analyzed the literature data from 1,286 IP cases from the period 1993-2010. RESULTS: Dental and/or oral anomalies were diagnosed for 54.38% of the investigated IP patients. Most of the anomaly types were dental, and the most frequent of these were dental shape anomalies, hypodontia, and delayed dentition. The most frequent oral anomaly types were cleft palate and high arched palate. IKBKG exon 4-10 deletion was present in 86.36% of genetically confirmed IP patients. CONCLUSIONS: According to the frequency, dental and/or oral anomalies represent the most frequent and important IP minor criteria. The most frequent mutation was IKBKG exon 4-10 deletion. The majority of dental anomalies and some of the oral anomalies could be corrected. CLINICAL RELEVANCE: Because of the presence of cleft palate and high arched palate in IP patients, these two anomalies may be considered as diagnostic IP minor criteria as well.

Prosthodontic rehabilitation in patient with ectodermal dysplasia combining preprosthetic techniques: a case report.

Oral manifestations in ectodermal dysplasia include oligodontia, alveolar ridges hypoplasia, and others. Due to the special conditions in terms of unhealthy teeth and lack of bone, implant-supported rehabilitation seems to offer the most satisfactory outcome. A 27-year-old male diagnosed with ectodermal dysplasia was referred to our department for oral rehabilitation. Oral manifestations included oligodontia, maxillary and mandibular atrophy, mandibular alveolar ridge with knife-edge morphology, and conical teeth. Treatment planning consisted of a Le Fort I osteotomy with interpositional grafts, bilateral sinus lift, and placement of maxillary and mandibular inlay and onlay corticocancellous grafts, using autologous iliac crest bone. In the second surgery, all remaining teeth were removed and 11 endosteal implants were placed. Six months after implant placement, a bimaxillary fixed implant-supported prosthesis was delivered, maintaining a satisfactory esthetic and functional result after a 2-year follow-up. The use of combined preprosthetic techniques allows the placement of endosteal implants and a fixed implant-supported prosthesis in patients with oligodontia and ectodermal dysplasia, providing an esthetic and functional oral rehabilitation.

Maternal occupational exposure to organic solvents during early pregnancy and risks of neural tube defects and orofacial clefts.

OBJECTIVES: Though toxicological experiments demonstrate the teratogenicity of organic solvents in animal models, epidemiologic studies have reported inconsistent results. Using data from the population-based National Birth Defects Prevention Study, the authors examined the relation between maternal occupational exposure to aromatic solvents, chlorinated solvents and Stoddard solvent during early pregnancy and neural tube defects (NTDs) and orofacial clefts (OFCs). METHODS: Cases of NTDs (anencephaly, spina bifida and encephalocoele) and OFCs (cleft lip ± cleft palate and cleft palate alone) delivered between 1997 and 2002 were identified by birth defect surveillance registries in eight states; non-malformed control infants were selected using birth certificates or hospital records. Maternal solvent exposure was estimated by industrial hygienist review of self-reported occupational histories in combination with a literature-derived exposure database. ORs and 95% CIs for the association between solvent class and each birth defect group and component phenotype were estimated using multivariable logistic regression, adjusting for maternal age, race/ethnicity, education, pre-pregnancy body mass index, folic acid supplement use and smoking. RESULTS: The prevalence of exposure to any solvent among mothers of NTD cases (n = 511), OFC cases (n = 1163) and controls (n = 2977) was 13.1%, 9.6% and 8.2%, respectively. Exposure to chlorinated solvents was associated with increased odds of NTDs (OR = 1.96, CI 1.34 to 2.87), especially spina bifida (OR = 2.26, CI 1.44 to 3.53). No solvent class was strongly associated with OFCs in these data. CONCLUSIONS: The findings suggest that maternal occupational exposure to chlorinated solvents during early pregnancy is positively associated with the prevalence of NTDs in offspring.

Oral-facial-digital syndrome type 1: oral features in 12 patients submitted to clinical and radiographic examination.

OBJECTIVE: To evaluate the oral features in individuals with oral-facial-digital syndrome type 1 (OFD 1), previously diagnosed by the Genetic Sector of the Hospital of Rehabilitation of Craniofacial Anomalies of the University of São Paulo (HRAC-USP). DESIGN: Twelve patients with OFD 1 were examined clinically and radiographically; their medical files were also evaluated. RESULTS: Associated oral malformations were observed in all patients (100%). The most frequent findings were tongue hamartomas, multiple buccal frena, asymmetric lips, asymmetric tongue, and bilateral maxillary gingival swelling. Interestingly, atrophy of the maxillary midline frenum was also observed in all the individuals examined. CONCLUSIONS: Several extra and intraoral alterations were observed in patients with OFD 1. The authors suggest the inclusion of atrophy of the maxillary midline frenum as a commonly found characteristic of OFD 1.

Are the oral-facial-digital syndromes ciliopathies?

The first oral-facial-digital syndrome was described in 1941 by Mohr, followed by a report by Papillon-Léage and Psaume [Papillon-Léage and Psaume (1954); Rev Stomatol (Paris) 55:209-227]. Ironically, these became known as oral-facial-digital syndrome (OFDS) II and I, respectively. Since then, numerous other examples of OFDS have been published, and current classification systems include up to 13 different types of OFDS. Other than for OFDS I, the causative gene defects for these conditions are unknown. Recently however the finding that primary ciliary defects can cause multiple anomaly syndromes that phenotypically overlap with the OFDS suggests that many, if not all of the OFDS could be caused by mutations in ciliary proteins. This review presents the evidence for suggesting that the search for causative genes should focus on those that are related to ciliary structure and function.

Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies.

BACKGROUND: This study examined the association between maternal smoking and alcohol use (including binge drinking) during the periconceptional period (i.e., 2 months before through 2 months after conception) and the risk of orofacial clefts, NTDs, and conotruncal heart defects in offspring. METHODS: Data were drawn from a population-based case-control study of fetuses and live-born infants among a cohort of California births between July 1999 and June 2003. The 1,355 cases comprised of 701 orofacial clefts, 337 NTDs, and 323 conotruncal heart defects. Information on smoking and alcohol consumption was obtained via telephone interviews with mothers of 1,355 (80% of eligibles) cases and 700 (77% of eligibles) nonmalformed, live-born controls. RESULTS: Maternal smoking of five cigarettes or less per day was associated with reduced risks of NTDs (OR 0.7; 95% CI: 0.3, 1.4), whereas the risk associated with higher cigarette consumption was lower for conotruncal heart defects (OR 0.5; 95% CI: 0.2, 1.2). Maternal intake of alcohol less than 1 day per week was associated with a 1.6- to 2.1-fold higher risk of NTDs (95% CI: 0.9, 2.6), d-transposition of the great arteries (95% CI: 1.1, 3.2), and multiple cleft lip with or without cleft palate (CLP) (95% CI: 0.8, 4.5). Risks associated with more frequent alcohol intake were 2.1 for NTDs (95% CI: 1.1, 4.0) and 2.6 for multiple CLP (95% CI: 1.1, 6.1). CONCLUSIONS: This study observed that maternal alcohol intake increased the risk for d-transposition of the great arteries, NTDs, and multiple CLP in infants. By contrast, smoking was associated with a lower risk of NTDs and conotruncal heart defects.

Masticatory dysfunction in persons with Down's syndrome. Part 1: aetiology and incidence.

The functional and anatomical characteristics of Down's syndrome have direct repercussions on oral health. Orofacial dysfunction is on account of poor neuromotor control, muscle weakness, dental anomalies, dysmorphology and intercurrent illness. In particular, feeding and swallowing are impaired. The aim of this first article was to summarize the orofacial difficulties encountered by persons with Down's syndrome at all stages of life and to explain their aetiology. Indicators are proposed for the identification of masticatory problems within this population and reduced masticatory efficiency is discussed in relation to repercussions on oral and general health and on the social integration of persons with Down's syndrome. A second article will describe techniques for preventing, treating and compensating for masticatory dysfunction in this population.

Oral and craniofacial manifestations in a Hunter syndrome patient with hematopoietic stem cell transplantation: A case report.

We described herein the oral and craniofacial features of a 7-year-old boy, diagnosed in utero with mucopolysaccharidosis II (MPS II), who was treated with hematopoietic stem cell transplantation (HSCT) at 70 days of age. The main oral clinical findings were the following: macroglossia, posterior cross-bite, crowding, pointed cuspid teeth, delayed tooth eruption, retained primary teeth, and enamel hypoplasia. The image examination showed: retention eruption, posterior primary teeth with short roots, absence of some permanent teeth, and stretching of the stylohyoid processes bilaterally. This patient showed the importance of early diagnosis and HSCT therapy in attenuating the clinical and radiographic oral and craniofacial manifestations of the MPS II patient.

Ellis-Van Creveld Syndrome in a Neonate.

Ellis-van Creveld syndrome is a rare form of skeletal and chondroectodermal dysplasia which affects all the three ectodermal, mesodermal, and endodermal derivatives. It has an autosomal recessive inheritance. This is caused by mutations in 1 of 2 genes, EVC 1 or EVC 2. This syndrome has a constellation of characteristic features that include bilateral post-axial polydactyly, mainly involving the upper limbs, hypoplastic nails and teeth, congenital heart defects, and chondroectodermal dysplasia. It is mainly a disorder of Amish population where incidence of this disease is 1/5000 and its incidence in non-Amish population is 7/1000000. Our patient had all the major characteristic features consistent with Ellis-van Creveld syndrome including post-axial polydactyly, teeth and nail abnormalities, congenital heart defect and skeletal dysplasia. Until now, only five cases have been reported from this region of the world, none of them diagnosed in neonatal life and having characteristic common atrium.

Chondroectodermal dysplasia (Ellis van Creveld syndrome): a report of three cases with review of literature.

Chondroectodermal dysplasia is a rare mesenchymal - ectodermal dysplasia first described in 1940 by Richard W.B. Ellis and Simon van Creveld now known as Ellis van Creveld syndrome. It is also known as Mesvectodermal dysplasia. Majority of cases were characteristically seen in one particular inbred population from the Amish community of Lancaster County, Pennsylvania, U.S.A. The syndrome manifests with several skeletal anomalies, oral mucosal and dental anomalies, congenital cardiac defects and nail dysplasia. Ellis van Creveld syndrome may be differentiated from other chondrodystrophies like achondroplasia, chondroplasia punctata, asphyxiating thorasic dystrophy and Morquio's syndrome. The presence of oral mucosal and dental alterations like notching of the lower alveolar process, fusion of the upper lip with gingival mucosal margin, occasional presence of neonatal teeth, oligodontia and conical shape of anterior teeth will confirm the diagnosis of Ellis van Creveld syndrome and hence its importance to dentists.

Is it safe to use lamotrigine during pregnancy? A prospective comparative observational study.

BACKGROUND: Lamotrigine is a second-generation antiepileptic drug, also used as a mood stabilizer. Published data on its use in human pregnancy are largely derived from pregnancy registries. Pregnancy experience in most studies has been reassuring. However, data from the North American Antiepileptic Drug Pregnancy Registry suggested an increased risk for oral clefts. The primary objective of the study was to evaluate the rate of major anomalies after lamotrigine exposure during pregnancy compared with pregnancies of women counseled for nonteratogenic exposure (NTE). METHODS: Callers who contacted the Israeli Teratology Information Service regarding lamotrigine treatment or NTE during pregnancy between 1997 and 2008 were prospectively followed-up. RESULTS: The rate of major congenital anomalies was similar between 218 lamotrigine exposed pregnancies (208 in the first trimester) and 865 NTE-pregnancies. There was no case of oral cleft in the lamotrigine-exposed group. The median lamotrigine dose in the beginning of pregnancy was 200 mg/d. The dose was increased during pregnancy in 29%. The majority of women in the cohort (82%) were treated for neurologic indications, while 18% for psychiatric disorders. Monotherapy was taken by 72%. CONCLUSION: The data available, thus far, on lamotrigine monotherpy-exposed pregnancies are encouraging. However, further studies are needed to determine with greater certainty the overall risk for major anomalies, as well as the specific risk for oral clefts. Based on the current and previously published data, lamotrigine, seems a reasonable alternative for pregnant women when clinically indicated. Birth Defects Research 109:1196-1203, 2017. © 2017 Wiley Periodicals, Inc.

Prevalence of Orofacial Clefts among Live Births in China: A Systematic Review and Meta-Analysis.

BACKGROUND: Orofacial clefts (OFCs) are common human birth defects in China. However, studies on the prevalence of OFCs present inconsistent results. The overall prevalence and geographic distribution of OFCs are poorly described in China. Thus, we conducted a systematic review and meta-analysis to estimate the prevalence of OFCs. METHODS: The systematic review and meta-analysis were conducted on the basis of an established protocol (PROSPERO 2015: CRD42015030198). We systematically searched for articles in four electronic databases, including Embase, PubMed, Wanfang Database, and China National Knowledge Infrastructure (CNKI) to identify relevant studies about prevalence of OFCs in China. Meta-analysis, including subgroup analysis, was conducted to estimate the pooled prevalence. RESULTS: A total of 41 studies published between 1986 and 2015 were included in our analysis. The sample size ranged from 2,586 to 4,611,808 live births. The random-effects model of meta-analysis showed that the overall prevalence of OFCs in China was 1.4 per 1000 live births (95% confidence interval [CI], 1.1-1.7). In subgroup analysis based on geographic regions, we found that OFC prevalence in Southwest (2.3 per 1000 live births, 95% CI, 1.1-4.7) was higher than that in other regions of China. There were no significant time trends of OFCs during the study period (p-value = 0.47). CONCLUSION: The overall prevalence of OFCs in China was 1.4 per 1000 live births. No significant secular trend of prevalence has been found in this analysis. Further studies need to be conducted to explore the etiology of OFC to better control the risk of this common birth defect. Birth Defects Research 109:1011-1019, 2017. © 2017 Wiley Periodicals, Inc.