Longitudinal Speech Outcome at 5 and 10 Years in UCLP: Influence of Speech Therapy and Secondary Velopharyngeal Surgery.

OBJECTIVE: To investigate speech development of children aged 5 and 10 years with repaired unilateral cleft lip and palate (UCLP) and identify speech characteristics when speech proficiency is not at 'peer level' at 10 years. Estimate how the number of speech therapy visits are related to speech proficiency at 10 years, and what factors are predictive of whether a child's speech proficiency at 10 years is at 'peer level' or not. DESIGN: Longitudinal complete datasets from the Scandcleft project. PARTICIPANTS: 320 children from nine cleft palate teams in five countries, operated on with one out of four surgical methods. INTERVENTIONS: Secondary velopharyngeal surgery (VP-surgery) and number of speech therapy visits (ST-visits), a proxy for speech intervention. MAIN OUTCOME MEASURES: 'Peer level' of percentage of consonants correct (PCC, > 91%) and the composite score of velopharyngeal competence (VPC-Sum, 0-1). RESULTS: Speech proficiency improved, with only 23% of the participants at 'peer level' at 5 years, compared to 56% at 10 years. A poorer PCC score was the most sensitive marker for the 44% below 'peer level' at 10-year-of-age. The best predictor of 'peer level' speech proficiency at 10 years was speech proficiency at 5 years. A high number of ST-visits received did not improve the probability of achieving 'peer level' speech, and many children seemed to have received excessive amounts of ST-visits without substantial improvement. CONCLUSIONS: It is important to strive for speech at 'peer level' before age 5. Criteria for speech therapy intervention and for methods used needs to be evidence-based.

Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: Speech proficiency at 10 years of age.

BACKGROUND & AIM: To assess consonant proficiency and velopharyngeal function in 10-year-old children born with unilateral cleft lip and palate (UCLP) within the Scandcleft project. METHODS & PROCEDURES: Three parallel group, randomized, clinical trials were undertaken as an international multicentre study by nine cleft teams in five countries. Three different surgical protocols for primary palate repair (Arm B-Lip and soft palate closure at 3-4 months, hard palate closure at 36 months, Arm C-Lip closure at 3-4 months, hard and soft palate closure at 12 months, and Arm D-Lip closure at 3-4 months combined with a single-layer closure of the hard palate using a vomer flap, soft palate closure at 12 months) were tested against a common procedure (Arm A-Lip and soft palate closure at 3-4 months followed by hard palate closure at 12 months) in the total cohort of 431 children born with a non-syndromic UCLP. Speech audio and video recordings of 399 children were available and perceptually analysed. Percentage of consonants correct (PCC) from a naming test, an overall rating of velopharyngeal competence (VPC) (VPC-Rate), and a composite measure (VPC-Sum) were reported. OUTCOMES & RESULTS: The mean levels of consonant proficiency (PCC score) in the trial arms were 86-92% and between 58% and 83% of the children had VPC (VPC-Sum). Only 50-73% of the participants had a consonant proficiency level with their peers. Girls performed better throughout. Long delay of the hard palate repair (Arm B) indicated lower PCC and simultaneous hard and soft palate closure higher (Arm C). However, the proportion of participants with primary VPC (not including velopharyngeal surgeries) was highest in Arm B (68%) and lowest in Arm C (47%). CONCLUSIONS & IMPLICATIONS: The speech outcome in terms of PCC and VPC was low across the trials. The different protocols had their pros and cons and there is no obvious evidence to recommend any of the protocols as superior. Aspects other than primary surgical method, such as time after velopharyngeal surgery, surgical experience, hearing level, language difficulties and speech therapy, need to be thoroughly reviewed for a better understanding of what has affected speech outcome at 10 years. WHAT THIS PAPER ADDS: What is already known on the subject Speech outcomes at 10 years of age in children treated for UCLP are sparse and contradictory. Previous studies have examined speech outcomes and the relationship with surgical intervention in 5-year-olds. What this study adds to the existing knowledge Speech outcomes based on standardized assessment in a large group of 10-year-old children born with UCLP and surgically treated according to different protocols are presented. While speech therapy had been provided, a large proportion of the children across treatment protocols still needed further speech therapy. What are the potential or actual clinical implications of this work? Aspects other than surgery and speech function might add to the understanding of what affects speech outcome. Effective speech therapy should be available for children in addition to primary surgical repair of the cleft and secondary surgeries if needed.

Dental health of young children prenatally exposed to buprenorphine. A concern of child neglect?

PURPOSE: To study the oral health and dental neglect of prenatally buprenorphine-exposed 3-year-old children. METHODS: The study consisted of 51 children who as newborns tested positive for buprenorphine in a urine screen. The control group comprised 68 children previously unexposed to narcotics. The dentist examined the children and interviewed their guardians. RESULTS: Buprenorphine-exposed children exhibited significantly more early childhood caries than did the control group. Caries indices, the number of decayed, missing and filled teeth or tooth surfaces and decayed teeth were greater in the buprenorphine-exposed children than the control children (p = 0.004, p = 0.004, p = 0.001, respectively). In the buprenorphine group, more children showed visible plaque (p = 0.003) and fewer children were caries-free (p = 0.009) than in the control group. The control children's teeth were also brushed more often than the buprenorphine-exposed children's teeth (p = 0.001) and the parents were more involved in their children's tooth brushing than were those in the buprenorphine-exposed group (p = 0.035). CONCLUSIONS: More caries and dental neglect were found in buprenorphine-exposed children than in controls. These findings highlight the importance of routine dental appointments, caries screening and preventive care for children in substance-abusing families.

Identification and characterization of a collagen-binding protein, Cbm, in Streptococcus mutans.

Streptococcus mutans, a major pathogen of dental caries, is occasionally isolated from the blood of patients with infective endocarditis. Bacterial attachment of exposed collagen tissue in the impaired endothelium is an important step in the onset of infective endocarditis. In our previous studies, some S. mutans strains were shown to possess collagen-binding activities and most of them had an approximately 120-kDa cell-surface collagen-binding protein called Cnm. However, several strains without Cnm proteins show collagen-binding properties. In the present study, another collagen-binding protein, Cbm, was characterized and its coding gene cbm was sequenced in these strains. The amino acid alignment in the putative collagen-binding domain of Cbm was shown to have approximately 80% identity and 90% similarity to the comparable region of Cnm. Cbm-deficient isogenic mutant strains constructed by insertional inactivation of the cbm gene, lacked collagen-binding properties, which were recovered in the complemented mutant. Analyses of a large number of clinical isolates from Japan, Thailand and Finland revealed that cbm-positive strains were present in all of these countries and that cnm-positive and cbm-positive strains were detected in the oral cavity of approximately 10 and 2% of systemically healthy subjects, respectively. In addition, cnm-positive strains were predominantly identified in the serotype f group, whereas cbm-positive strains were frequently detected in serotype k. These results suggest that Cbm as well as Cnm are major cell surface proteins of S. mutans associated with binding to type I collagen and predominantly identified in serotype k strains.

Correlation of biological properties with glucan-binding protein B expression profile in Streptococcus mutans clinical isolates.

OBJECTIVE: Streptococcus mutans is known to be a primary causative agent of dental caries and its surface proteins have been investigated to specify their association with its virulence. Amongst those, 4 glucan-binding proteins (Gbps) are considered to be important factors due to their glucan-binding properties, of which GbpB has been shown to participate in cell-wall construction and cell separation. DESIGN: We examined clinical isolates of S. mutans collected from the oral cavities of Japanese and Finnish subjects, and focused on the association of their GbpB expression profiles and biological properties related to virulence. RESULTS: Western blot analysis of GbpB expression by the isolates revealed a variety of patterns. Strains that showed single and multiple bands were used to designate S and M type strains, respectively, whilst those with no GbpB expression were classified as N type. The distribution of GbpB expression patterns was shown to be quite different between the Japanese and Finnish isolates. Furthermore, the chain length and doubling time of the N type in both populations were significantly longer than those of the other types. CONCLUSION: Our results suggest variations in S. mutans GbpB expression patterns, which may have relationships with the virulence of S. mutans.

Aetiology of Molar-Incisor Hypomineralisation: A systematic review.

AIM: This was to review and assess the studies on aetiology of Molar-Incisor Hypomineralisation (MIH) or, as a proxy, of demarcated opacities in permanent first molars and to consider the potential factors involved with findings obtained in animal experiments. METHODS: A systematic search by Medline online database was performed. Abstracts behind appropriate titles were studied and finally the full articles were evaluated for their strength of evidence in the aetiology of MIH. RESULTS: From a total of 1,142 articles 28 were identified and selected for review. The selected papers covered medical problems in prenatal, perinatal and postnatal period, medication of the child during the first years of life, and exposure to fluoride or environmental toxicants (dioxins and PCBs) in the early childhood. Based on the assessment of the articles it was still not possible to specifically name those factors causing MIH although correlations between several potential factors and MIH were presented. Among the factors suggested and found to cause enamel defects in animal experiments were: high fever, hypoxia, hypocalcaemia, exposure to antibiotics (amoxicillin, a macrolide), and dioxins. CONCLUSION: Despite increased knowledge on the aetiology of MIH insufficient evidence to verify the causative factors exists. Further studies, especially prospective ones, are needed to improve the level and strength of evidence of the role of the present putative factors and to reveal new factors that may be involved. Any combined effect of several factors should be taken into account. Experimental dose/response studies and research on the molecular mechanisms causing the abnormal function of the ameloblasts are also necessary to deepen our knowledge of MIH.

Best Clinical Practice Guidance for clinicians dealing with children presenting with Molar-Incisor-Hypomineralisation (MIH): An EAPD Policy Document.

BACKGROUND: The European Academy of Paediatric Dentistry (EAPD) has long recognised the necessity of promoting further research and knowledge regarding the dental defect described as molar-incisor-hypomineralisation (MIH). Following the establishment by EAPD of the defect diagnostic criteria in 2003, the publication of various papers and a whole issue assigned to the defect in the European Archives of Paediatric Dentistry (2008), an Interim Seminar and Workshop on MIH was organized in Helsinki in 2009. RESULT: The outcome of this event is the present consensus paper on the prevalence, diagnosis, aetiology and treatment for children and adolescents presenting with MIH. A clear diagnostic proposal and a treatment decision-making guide are presented together with suggestions on aetiology and guidance for future research. CONCLUSION: MIH is an important clinical problem that often concerns both the general dental and specialist paediatric dentists; the present 'best clinical practice guidance' aims to further help clinicians dealing with the condition.

Molecular characterization of Streptococcus mutans strains containing the cnm gene encoding a collagen-binding adhesin.

OBJECTIVE: Streptococcus mutans, known to be a major pathogen of dental caries, is also considered to cause infective endocarditis. Its 120-kDa Cnm protein binds to type I collagen, which may be a potential virulence factor. In this study, we characterized S. mutans clinical strains focusing on the cnm gene encoding Cnm. DESIGN: A total of 528 S. mutans strains isolated from Japanese, Finnish, and Thai subjects were investigated. Using molecular techniques, the distribution frequency of cnm-positive strains and location of the inserted cnm were analyzed. Furthermore, isogenic mutant strains were constructed by inactivation of the cnm gene, then their biological properties of collagen-binding and glucan-binding were evaluated. Southern hybridization of the genes encoding glucan-binding proteins was also performed. RESULTS: The distribution frequency of cnm-positive strains from Thai subjects was 12%, similar to that previously reported for Japanese and Finnish subjects. Furthermore, the location of insertion of cnm was the same in all cnm-positive clinical isolates. As for the cnm-inactivated mutant strains constructed from 28 clinical isolates, their collagen-binding activity was negligible. In addition, glucan-binding activity in the cnm-positive clinical isolates was significantly reduced and corresponded to a lack of gbpA encoding glucan-binding protein A. CONCLUSIONS: Our results indicate that strains with cnm genes, the most crucial factor for the collagen-binding property of S. mutans, are detectable at similar frequencies over several different geographic locations. In addition, the common properties of these strains are a high level of collagen-binding activity and tendency for a low level of glucan-binding activity.

Amoxicillin may cause molar incisor hypomineralization.

The etiology of molar incisor hypomineralization (MIH) is unclear. Our hypothesis was that certain antibiotics cause MIH. We examined 141 schoolchildren for MIH and, from their medical files, recorded the use of antibiotics under the age of 4 yrs. MIH was found in 16.3% of children. MIH was more common among those children who had taken, during the first year of life, amoxicillin (OR=2.06; 95% CI, 1.01-4.17) or the rarely prescribed erythromycin (OR=4.14; 95% CI, 1.05-16.4), compared with children who had not received treatment. Mouse E18 teeth were cultured for 10 days with/without amoxicillin at concentrations of 100 microg/mL-4 mg/mL. Amoxicillin increased enamel but not dentin thickness. An altered pattern of amelogenesis may have interfered with mineralization. We conclude that the early use of amoxicillin is among the causative factors of MIH.

Molar-incisor-hypomineralisation and dioxins: new findings.

AIM: According to our earlier study, molar-incisor-hypomineralisation (MIH) was associated with the exposure of a child via mother's milk to polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) in a group of Finnish children born in 1987. Since the levels of PCDD/Fs and PCBs in mother's milk/placenta have remarkably decreased, it was important to find out if an association still exists. METHODS: The study group was composed of 167 mothers and their children. Placental samples from the mothers were collected in maternity hospitals in Helsinki and Oulu in 1995--1999 and concentrations of the 17 most toxic PCDD/PCDF and 36 PCB congeners were measured. After 7-10 years the children were examined for MIH and the mothers were interviewed on the duration of breast-feeding. RESULTS: MIH was found in 24 children (14.4%). The duration of breast-feeding ranged from 0 to 30 months (mean=7.2+/-4.7). WHOPCDD/FTEQ ranged from 2.5 to 39.1 pg/g fat (mean=13.7+/-6.8) and WHOPCBTEQ from 0.7 to 9.8 pg/g fat (mean=2.7+/-1.4). The mean sum of PCDD/Fs was 196+/-105 pg/g fat and that of PCBs was 57.2+/-28.1ng/g fat. The total exposure to PCDD/Fs, which was calculated from the placental concentration (used as a proxy for the milk concentration) and duration of breastfeeding, was not associated with the occurrence or severity of MIH. Neither was the total exposure to PCBs associated with the occurrence or severity of MIH. CONCLUSION: At prevailing levels, exposure of a child via placenta/mother's milk to PCDD/Fs and PCBs is not associated with MIH.

Protein antigen in serotype k Streptococcus mutans clinical isolates.

Streptococcus mutans, a major pathogen of dental caries and infective endocarditis, is classified into serotypes c, e, f, and k, with serotype k strains recently reported to be frequently detected in persons with infective endocarditis. Thus, we hypothesized that common properties associated with infective endocarditis are present in those strains. Fifty-six oral S. mutans strains, including 11 serotype k strains, were analyzed. Western blotting analysis revealed expression of the 3 types of glucosyltransferases in all strains, while expression of the approximately 190-kDa cell-surface protein (PA) was absent in 12 strains, among which the prevalence of serotype k (7/12) was significantly high. Furthermore, cellular hydrophobicity and phagocytosis susceptibility were lower in the group of serotype k strains. These results indicate that the absence of PA expression, low cellular hydrophobicity, and phagocytosis susceptibility are common bacterial properties associated with serotype k strains, which may be associated with virulence for infective endocarditis.

Dioxin alters gene expression in mouse embryonic tooth explants.

Dioxins are ubiquitous environmental poisons that cause disturbances in developing organs, including the teeth. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at the cap stage leads to reduced tooth size and deformation of cuspal morphology. Our hypothesis was that TCDD affects the expression of genes specific for tooth development, which leads to these aberrations. Mouse embryonic E14 tooth germs were cultured for 24 hrs with/without 1 microM TCDD. Analysis of total RNA on Affymetrix arrays showed that TCDD altered the expression of 31 known genes by a fold factor of at least 2. Genes implied in tooth development expressed only slight changes. Genes active at the cap stage were selected for quantitative PCR analysis. Of these, the most highly up-regulated were Follistatin and Runx2, while TGFbeta1 and p21 were the most down-regulated genes. Incomplete tooth morphogenesis caused by TCDD may thus result from modified expression of developmentally regulated genes.

Molar-incisor hypomineralization (MIH) in a group of school-aged children in Benghazi, Libya.

OBJECTIVE: Molar-incisor hypomineralization (MIH) is common in many countries and it has significant impact on treatment need. The aim of the present study was to assess developmental enamel defects with an emphasis to MIH in children from four primary schools in Benghazi, Libya. METHODS: Permanent first molars of a total of 378 (188 females) 7.0-8.9-year-old children were examined for demarcated opacities, diffuse opacities and hypoplasia in their schools using a portable light, a mirror, and a probe. A subgroup of children attending two of the four schools and having all incisors and first molars erupted (N = 154) was examined for enamel defects in these teeth. RESULTS: Eleven children (2.9%) had MIH. The mean value of demarcated opacities in their first molars was 1.5. MIH lesions were found only in 1.1% of the children's first molars (tooth prevalence) and all lesions were mild. Six children (1.6%) had diffuse opacities and 3 (0.8%) had hypoplastic defects in their first molars. Fourteen out of 154 children (9%) who had both incisors and molars examined had some kind of developmental enamel defect: 11 children (7.1%) had demarcated opacities, 3 (1.9%) had diffuse opacities, and none had hypoplasia. CONCLUSION: MIH was rare in Benghazi, Libya. The prevalence was clearly lower than in comparable studies performed in Italy or in Nordic countries, where, according to the earlier reports, MIH is seen in every fifth or sixth child. Our result may be valuable when so far mostly unknown etiology behind MIH is investigated.

The prevalence of Molar Incisor Hypomineralisation (MIH) in a group of Italian school children.

AIM: This epidemiological study in a group of Italian children was undertaken in order to increase our knowledge of the prevalence of Molar Incisor Hypomineralisation (MIH) in different European countries. METHOD: A population of school children aged 7.3 - 8.3 years, living in Lissone, Northern Italy, was examined for the presence and severity of MIH. RESULTS: Of a total of 227 children (113 females), 31 (13.7%) had MIH, the tooth prevalence in the permanent first molars being 5.8%. Fifteen children (6.6%) had demarcated opacities in the incisors with a tooth prevalence of 2.1%. The defects in the molars were mild with the exception of one child who had severe defects. CONCLUSION: MIH was quite common in this Italian town, and the prevalence figures were near those reported in Scandinavian countries but clearly higher than those from Dresden, Germany.

Root-crown ratios of permanent teeth in a healthy Finnish population assessed from panoramic radiographs.

An unfavourable root-crown (R/C) ratio caused by short dental roots may result from a developmental deficiency, root resorption after orthodontic treatment, or dental trauma. In the assessment of root shortening, subjective grading has often been used. For objective tooth measurements, varying materials and methods may make the results impossible to compare. This study used a simple, objective method to assess the R/C ratio (relative root length) of mature permanent teeth from panoramic radiographs (PRGs), tested its reproducibility and calculated the mean values of R/C ratios and their variations in a healthy Caucasian (Finnish) population. Two thousand seven hundred and seventy-nine teeth were measured on 108 PRGs. The intra- and inter-examiner reproducibility of the assessment method was good (Pearson correlation coefficients 0.87 and 0.83, respectively; P < 0.001) and the mean R/C ratios did not differ between the repeated measurements (P > 0.05). The biological variance in all cases exceeded the error variance for each tooth. These facts suggest that the method reported in this study can be used in the assessment of the relative root length of 'normal' teeth and its alterations in teeth with developmental or acquired aberrations of dental roots. Males, overall, tended to have higher R/C ratios than females; P-values varied from non-significant to less than 0.01. With the exception of the permanent lateral incisors in males and the permanent second molars in both genders, the ratios of the antagonist teeth were significantly greater in the mandible than in the maxilla (P < 0.05 for the lateral incisors of females; P < 0.001 for all other teeth). Consequently, in quantifying root shortening in developmentally short-rooted teeth, tooth- and gender-specific reference values should be employed. The Finnish R/C data reported here for all teeth except third molars could be used for comparison with other populations, patient groups or individuals where crown-root aberrations are suspected.

Lactational exposure of Han/Wistar rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin interferes with enamel maturation and retards dentin mineralization.

Exposure to environmental dioxins via mother's milk may be one causative factor of mineralization defects in children's teeth. A prerequisite for the completion of enamel mineralization is the removal of enamel matrix. To test the hypothesis that dioxins interfere with enamel maturation, we administered lactating Han/Wistar rats a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 50 or 1000 micro g/kg) on the day after delivery and analyzed tissue sections of the pup heads at post-natal days (Pn) 9 and 22. By Pn22, the first and second molars of the exposed pups, but not controls, showed retention of enamel matrix. Predentin was thicker than normal. Immunostaining for the aryl hydrocarbon/dioxin receptor (AhR) and cytochrome P4501A1 (CYP1A1) in ameloblasts and odontoblasts was reduced, suggesting that TCDD interferes with tooth mineralization via AhR. Extinction of AhR may lead to abolition of CYP1A1 expression as a sign of impaired dental cell function.

Long-term adverse effects on dentition in children with poor-risk neuroblastoma treated with high-dose chemotherapy and autologous stem cell transplantation with or without total body irradiation.

Chemo- and radiotherapy may have injurious effects on developing teeth. In this long-term follow-up study among poor-risk neuroblastoma (NBL) survivors our aims were: (1) to assess both the type and extent of the side-effects of the anticancer treatment on tooth development; and (2) to develop an index for expressing total damage to the permanent dentition. We studied the dental development from panoramic radiographs (PRG) of 18 long-term survivors treated under the age of 6 years with high-dose (HD) chemotherapy and autologous stem cell transplantation (ASCT) for poor-risk NBL. The myeloablative therapy was either HD chemotherapy and fractionated total body irradiation (TBI) of 10-12 Gy (TBI group, n = 10) or HD chemotherapy only (non-TBI group, n = 8). A defect index (DeI) was developed to describe the damage to the permanent dentition. The DeI was also tested in 18 healthy adolescents. All NBL patients had disturbances in dental development including short roots, arrested root development, microdontia and tooth aplasia. After TBI, 9/10 patients had very severe root defects, in contrast to none in the non-TBI group. All children in the TBI group had 2-12 (mean 6.6) missing permanent teeth, while 2/5 in the non-TBI group (3/8 excluded due to young age) had two and four missing permanent teeth, respectively. Microdontia was found at equal frequency in both groups. The mean value of the DeI was 70.0 (range 28-117) in the TBI group, 15.2 (range 4-34) in the non-TBI group (P<0.001, Mann-Whitney U test) and 1.8 (range 0-15) in healthy adolescents. Disturbances in dental development may compromise occlusal function in poor-risk NBL patients after ASCT, especially when TBI is included in the conditioning regimen. Long-term dental follow-up and rehabilitation is required.

In utero/lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure impairs molar tooth development in rats.

Developmental defects caused by dioxins are causing increasing concern since they occur at low dose levels and are usually permanent. In this study we examined the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at low in utero/lactational exposure levels on rat tooth development in three rat lines, denoted A, B, and C, that differ in their TCDD sensitivity and aryl hydrocarbon receptor structure. These rat lines are derived from TCDD-resistant Han/Wistar (Kuopio) and TCDD-sensitive Long-Evans (Turku/AB) rats by selective breeding. The main target teeth were the third molars, since their development spans from the perinatal period to about 6 weeks after birth. Pregnant dams were exposed to 0.03-1 microg/kg TCDD on gestation day 15. Pups exposed in utero and lactationally were euthanized at the age of 5 or 10 weeks and the jaws were examined. The eruption of the third molar was observed by stereomicroscopy and the jaws were further radiographed. TCDD at 1 microg/kg completely prevented the development of the third lower molars in 60% of males and 50% of females in the most sensitive rat line, C, while only 6% or less of the pups in the more resistant lines A and B were lacking this target tooth. TCDD exposure also dose-dependently diminished the proportion of third molars erupted at the age of 5 weeks. The size of molars was dose-dependently reduced in all rat lines. The third lower molars were most severely affected, and the reduction was significant already at 0.03 microg/kg in line A and at 0.1 microg/kg in lines B and C. The results indicate that impaired tooth development is one of the most sensitive endpoints of TCDD-induced toxicity.