Prenatal exposure to environmental toxins and comprehensive dental findings in a population cohort of children.

Environmental toxins are known to have many impacts on growth and development in humans, starting in utero. Alterations in amelogenesis, caused by chemical and physical trauma that occur during the antenatal, perinatal and postnatal time periods, may result in developmental defects in deciduous and permanent tooth enamel, as demonstrated in animal studies. These defects can be clinically visible and result in a variety of morphological and functional problems in the dentition. Since enamel does not remodel after formation, it may serve as a permanent record of insults during organ development.Our primary purpose was to investigate any possible relationship between intrauterine exposure to endocrine disrupting chemicals (phenols and phthalates) and developmental defects in enamel in children, while also accounting for fluoride exposure. Our secondary purpose was to report descriptively on findings from comprehensive dental examinations performed on 356 children that were drawn from the general paediatric population. A cohort of children from the Utah Children's Project (N = 356) that had full medical exams, comprehensive medical and family histories and available biospecimens were given extraoral and intraoral examinations. They also completed an oral health questionnaire. Standardized intraoral photographs were taken of the teeth and viewed by standardised examiners and the dental observations were recorded for a full inventory of findings, including: tooth morphology, caries, restorations, colorations, attrition, erosion, fractures and hypomineralization. Perinatal maternal urine samples were assessed for the concentration of fluoride, phenols and phthalates, including bisphenol A (BPA).Pairwise statistical analyses were done to correlate the dental findings with one another and with the presence of environment chemicals found in the urine samples. Hypomineralization was the most common finding (96% of children; 37% of deciduous teeth, 42% of permanent teeth), consistent with molar incisor hypomineralization (MIH) described in other human populations. No consistent correlations were seen between dental findings and the presence of phenols and phthalates in prenatal urine, but the number of samples available for the assessment was limited (n = 35).In conclusion, we found a high proportion of dental hypomineralization in a population based paediatric cohort, but did not find an association with prenatal exposure to phenols and phthalates.

Associations of early childhood medication exposure and molar incisor hypomineralization (MIH): A routine data analysis.

OBJECTIVES: Molar incisor hypomineralization (MIH) has become a major oral health problem of widely unknown origin. Besides genetic predisposition, exposure to certain drugs in early childhood are suspected to be associated with MIH. Aim of this routine data analysis was to examine associations of MIH and exposure to medication as well as perinatal factors. METHODS: Individuals with MIH were identified in claims data using a validated predefined specific treatment pattern. The database was a comprehensive routine data set of a major national health insurance company (BARMER, Germany). Based on this treatment pattern a MIH group and an unaffected control group were formed for analysis. Various medical data including medical diagnoses and prescriptions were available. Associations were examined comparing results for a set of variables in both groups. Differences between the groups were tested for significance using T-tests (P<0.01). RESULTS: Between 2010 to 2019, a total of 298,502 children between 6 and 9 years of age were included in this analysis. 22,947 were assigned to the MIH group. For individuals in this group, significantly larger prescription quantities in the main ATC (Anatomical, Therapeutic, Chemical) groups J (antiinfectives for systemic use), R (respiratory system) and S (sensory organs) were found in the first 4 years of life compared to MIH unaffected individuals. With antibiotics, there were both significantly larger prescription quantities and significantly higher numbers of respective prescriptions in the first 4 years of life. The differences amounted up to about 10.62% in frequently used antibiotics to be found in ATC J01D (other beta-lactam antibacterials) for the number of prescriptions in the 4th year of life. No association was found for premature birth, mode of delivery or the use of antipyretic or anti-inflammatory medication. CONCLUSIONS: While perinatal factors do not seem to be associated with MIH development, early life exposure to antibiotics might play a role. CLINICAL SIGNIFICANCE STATEMENT: Although causal relations can still not be proven, a responsible use of the unquestionably beneficial antibiotics is encouraged from a clinical point of view.

Relationship between molar incisor hypomineralization, intrapartium medication and illnesses in the first year of life.

Molar incisor hypomineralization (MIH) affects the first permanent molars and permanent incisors whose formative embryological process develops around birth and the first year of life. This study's main objective is to assess the relationship between MIH, on the one hand, with the administration during childbirth of epidural bupivacaine, intramuscular meperidine with haloperidol, synthetic intravenous oxytocin, and prostaglandins such as dinoprostone vaginally, and on the other hand, with suffered pathologies during the first year of life. Cross-sectional retrospective study was carried out on 111 children who attended dental check-ups. Oral examination was carried out to determine MIH involvement. Data on the administration of medications during delivery and the illnesses suffered by the children in the first year of life were taken from the hospital records. Significant relationship with Pearson's chi-square was found between the presence of MIH and the administration of meperidine with haloperidol intramuscularly and the vaginal administration of dinoprostone during labour. Also in children who have suffered serious infections and those who have received antibiotics in early childhood. In recent years there has been a growing trend in many countries to medicalize childbirth even above what the World Health Organization recommends. Some of the drugs used in these protocols could be involved in the appearance of dental mineralization alterations of the MIH type and this would help to explain the increase in its prevalence.

Effects of antibiotics on the developing enamel in neonatal mice.

PURPOSE: Identifying factors causing Molar-Incisor Hypomineralization (MIH) is an ongoing challenge. Preterm infants, routinely treated with antibiotics in cases of suspected sepsis, are more commonly affected by dental developmental defects. This study aimed to investigate the effects of gentamycin and ampicillin on the developing enamel in neonatal CD-1 mice in vivo. METHODS: Neonatal mice were randomized into a study (n = 36) and a control (n = 35) group. Antibiotics were injected intravenously for 4 days. All mice were sacrificed after 15-18 days. Micro-CT was used to analyse the mineral density (MD) of the enamel and the proportion of the enamel object volume (vol%) in first molars and incisors. RESULTS: We demonstrated a significantly lower vol% enamel in the maxillary (30.9% vs. 32.7%; p = 0.004) and mandibular (32.5% vs. 34.6%; p = 0.015) molars in the study group than in the controls. The incisors were divided into segments upon analysis. We demonstrated both lower vol% and lower MD of the enamel in most segments in treated individuals compared to controls (p < 0.05). CONCLUSION: The reduced MD and vol% in the molars and incisors are likely to have been caused by the antibiotics given during tooth development. The presented analysis of teeth in neonatal mice with micro-CT could be a valid model for further research on dental developmental defects.

Molar-incisor hypomineralization (MIH), dental fluorosis, and caries in rural areas with different fluoride levels in the drinking water.

AIM: This study determined the prevalence of molar-incisor hypomineralization (MIH) and its association with dental fluorosis and caries in children living in rural areas in north-eastern Brazil who are exposed to residual fluoride (F) levels in the drinking water. DESIGN: A census was carried out with 610 schoolchildren aged 6 to 12 years. The European Academy of Paediatric Dentistry criteria, Thysltrup and Fejerskov index, and World Health Organization index were used for diagnosis of MIH, dental fluorosis, and caries detection, respectively. The association between the outcome and exposure variables was determined by robust Poisson regression (P < .05). RESULTS: Water F-levels varied from 0.06 to 1.98 ppm. MIH was not related to fluoride levels in the drinking water, but it showed an inverse and direct correlation with dental caries and fluorosis, respectively. Children with MIH had a higher DMFT, and severe MIH cases were most frequent in children with dental fluorosis. CONCLUSION: Drinking water F-levels were not directly related to the occurrence of MIH in schoolchildren. The severity of MIH, however, was likely to be associated with dental fluorosis in areas with moderate to high fluoride levels in the drinking water.

Use of Antibiotics in early Childhood and Dental Enamel Defects in 6- to 12-year-old Children in Primary Health Care.

Dental enamel defects (DED) are lesions that occur due several factors. Proper care is needed to promote their treatment and prevention. The aim of this study was to evaluate the occurrence of DED in permanent teeth of children who used antimicrobial drugs in the first four years of life. This is a crosssectional study carried out in a Primary Health Care (PHC) service, which included children from six to 12 years of age. DED were evaluated by oral examination, and data on the use of antimicrobials in early childhood were collected based on medical records. Data were analyzed with the chi-square test and Fisher's exact test. The sample included 144 children. In relation to DED, 50% (72) and 20.1% (29) presented opacity and hypoplasia, respectively. Amoxicillin was the most frequently prescribed drug, followed by sulfamethoxazole + trimethoprim. Among the children, 78.5% (113) were prescribed antimicrobial drugs at least once during the first 4 years of life, and 55% (79) of them presented some type of DED. There was no statistically significant association between the variables analyzed. In conclusion, there was high prevalence of children with DED, and amoxicillin was the most commonly prescribed antibiotic.

Os defeitos do esmalte dentário (DED) são lesões que ocorrem devido a vários fatores e é necessária atenção para promover seu tratamento e prevenção. O objetivo foi avaliar a ocorrência de DED em dentes permanentes de crianças que usaram antimicrobianos nos primeiros quatro anos de vida. Tratase de um estudo transversal realizado em um serviço de Atenção Primária à Saúde (APS), que incluiu crianças de seis a 12 aos de idade. A DED foi avaliada por dados de exames bucais, e os dados sobre o uso de antimicrobiano na primeira infância foram coletados com base em prontuários médicos. A análise foi realizada com o teste do qui-quadrado e o teste exato de Fisher. A amostra foi composta por 144 crianças. Em relação ao DED, 50%(72) e 20,1%(29) apresentaram opacidade e hipoplasia, respectivamente. A amoxicilina foi o medicamento prescrito com mais freqüência, seguido pelo sulfametoxazol+trimetoprim. Entre as crianças, 78,5%(113) receberam medicamentos antimicrobianos pelo menos uma vez nos primeiros 4 anos de vida e 55%(79) deles apresentaram algum tipo de DED. Não houve associação estatisticamente significante entre as variáveis analisadas. Em conclusão, houve uma alta prevalência de crianças com DED e a amoxicilina foi o antibiótico mais comumente prescrito.

Use of Antibiotics in early Childhood and Dental Enamel Defects in 6- to 12-year-old Children in Primary Health Care / Uso de antibióticos na primeira infância e defeitos de esmalte dentário em crianças de 6 a 12 anos na Atenção Primária à Saúde

ABSTRACT Dental enamel defects (DED) are lesions that occur due several factors. Proper care is needed to promote their treatment and prevention. The aim of this study was to evaluate the occurrence of DED in permanent teeth of children who used antimicrobial drugs in the first four years of life. This is a crosssectional study carried out in a Primary Health Care (PHC) service, which included children from six to 12 years of age. DED were evaluated by oral examination, and data on the use of antimicrobials in early childhood were collected based on medical records. Data were analyzed with the chisquare test and Fisher's exact test. The sample included 144 children. In relation to DED, 50% (72) and 20.1% (29) presented opacity and hypoplasia, respectively. Amoxicillin was the most frequently prescribed drug, followed by sulfamethoxazole + trimethoprim. Among the children, 78.5% (113) were prescribed antimicrobial drugs at least once during the first 4 years of life, and 55% (79) of them presented some type of DED. There was no statistically significant association between the variables analyzed. In conclusion, there was high prevalence of children with DED, and amoxicillin was the most commonly prescribed antibiotic.

RESUMO Os defeitos do esmalte dentário (DED) são lesões que ocorrem devido a vários fatores e é necessária atenção para promover seu tratamento e prevenção. O objetivo foi avaliar a ocorrência de DED em dentes permanentes de crianças que usaram antimicrobianos nos primeiros quatro anos de vida. Tratase de um estudo transversal realizado em um serviço de Atenção Primária à Saúde (APS), que incluiu crianças de seis a 12 anos de idade. A DED foi avaliada por dados de exames bucais, e os dados sobre o uso de antimicrobiano na primeira infância foram coletados com base em prontuários médicos. A análise foi realizada com o teste do quiquadrado e o teste exato de Fisher. A amostra foi composta por 144 crianças. Em relação ao DED, 50%(72) e 20,1%(29) apresentaram opacidade e hipoplasia, respectivamente. A amoxicilina foi o medicamento prescrito com mais freqüência, seguido pelo sulfametoxazol+ trimetoprim. Entre as crianças, 78,5%(113) receberam medica mentos antimicrobianos pelo menos uma vez nos primeiros 4 anos de vida e 55%(79) deles apresentaram algum tipo de DED. Não houve associação estatisticamente significante entre as variáveis analisadas. Em conclusão, houve uma alta prevalência de crianças com DED e a amoxicilina foi o antibiótico mais comumente prescrito.

[Oral cavity as a target and a marker of environmental exposures: developmental dental defects]. / La sphère orale, cible et marqueur de l'exposition environnementale - I. Défauts du développement dentaire.

The oral cavity is one of the main route for environmental contaminations associated to many chronic diseases (cancers, fertility and behavior disorders for example) via alimentation, medications and respiration. These environmental factors including, among others, endocrine disruptors and excessive fluoride can disrupt dental development and thus generate irreversible enamel defects. These defects are then treated with materials that may release molecules capable of generating these defects, leading to a vicious circle, particularly in pregnant women and young children. The present paper aims to review the state of knowledge, questions and controversies on common environmental factors in contact with the oral cavity. It also reviews their mechanisms of action and the mediators involved in enamel pathologies associated with environmental conditions. Dental tissues can not only be targeted by environmental factors but can also serve as early and easily accessible markers of exposure to these agents. Understanding and characterizing the environmental impact in the oral cavity will help to prevent multiple diseases, oral and distant, whose link with oral homeostasis is just being explored.

TITLE: La sphère orale, cible et marqueur de l'exposition environnementale - I. Défauts du développement dentaire. ABSTRACT: La cavité buccale est l'une des voies majeures des contaminations environnementales connues pour être impliquées dans de nombreuses pathologies chroniques (cancers, troubles de la fertilité et du comportement) via l'alimentation, les médications ou même la respiration. Ces facteurs environnementaux incluant, entre autres, des perturbateurs endocriniens et le fluor en excès, peuvent perturber le développement dentaire et ainsi générer des défauts irréversibles de l'émail. Ces défauts sont alors traités avec des matériaux dont certains libèrent des molécules capables à leur tour de générer ces défauts, conduisant à un cercle vicieux, notamment chez la femme enceinte et le jeune enfant. Cette synthèse fait le point sur l'état des connaissances, les questions et controverses sur les facteurs environnementaux courants susceptibles d'entrer en contact avec la sphère orale, leurs mécanismes d'actions et les médiateurs impliqués dans les pathologies de l'émail associées aux conditions environnementales.

Congenital syphilis or mercury treatment: dental alterations in a twelfth- or thirteenth-century child from Medinaceli, Soria, Spain.

Syphilis, together with its variant congenital syphilis, is a disease caused by Treponema pallidum subsp. pallidum. This paper documents possible new skeletal evidence for congenital syphilis from the Medieval Era (twelfth and thirteenth centuries CE) burial site of Medinaceli in the Province of Soria in North-Central Spain. What is involved is dental alteration due to congenital syphilis, mercury treatment, or a combination of both. This study focuses on the hypoplastic dental changes observed in a child approximately eight years of age. Only a fragmented skull with left maxilla and the left side of the mandible were preserved. Macroscopic analysis, X-rays, computerized tomography (CT) and mercury detection analysis by inductively coupled plasma mass spectrometry (ICP-MS) techniques were used to observe dental abnormalities. In addition to extensive caries in the upper second deciduous molar, pulpo-alveolar lesions and facial alterations were observed. The absence of the rest of the skeleton tends to make a diagnosis of congenital syphilis difficult. However, the dental stigmata observed do permit a reasonable diagnosis.

The higher prevalence of developmental defects of enamel in the dioxin-affected region than non-dioxin-affected region: result from a cross-sectional study in Vietnam.

Developmental defects of enamel (DDE) are induced and regulated by several factors including genetics and the environment. There is evidence showing that dioxin in polluted areas has a strong effect on the health and development of teeth. However, there has been no study on DDE in the dioxin-affected regions in Vietnam. To identify the effect of dioxin on the prevalence of DDE in studied areas in Vietnam, a cross-sectional study was conducted in 2200 adults in the A Luoi district in the Thua Thien Hue province (the dioxin-affected region) and in the Kim Bang district in the Ha Nam province (dioxin-unaffected region) in 2015. All subjects were interviewed using a structured questionnaire and their teeth were examined and scored for enamel defects based on the 1992 FDI criteria. The defected teeth were then photographed. Our results showed that the DDE rate in A Luoi was 20.5% when measured as mouth prevalence and 5.8% when measured as tooth prevalence, while the rates in Kim Bang were 10.4 and 2.32% for mouth and tooth prevalence, respectively. Demarcated opacities were predominated in both districts (45.5% in A Luoi and 52.2% in Kim Bang). The DDE rate of the anterior teeth group was higher than that of the posterior teeth group. Most lesions presented on the buccal surface of the tooth. Overall, the DDE prevalence in the dioxin-affected region was 2.2 times higher than that in non-dioxin-affected region in the studied regions in Vietnam.

[Doxycycline can be given to children without risk of staining of teeth]. / Doxycyklin kan ges till barn i alla åldrar - Ingen risk för missfärgning av tänder eller emaljhypoplasi.

Doxycycline can be given to children without risk of staining of teeth In Sweden, several hundred children are treated for Lyme neuroborreliosis annually, the majority of which are treated with intravenous ceftriaxone. Older tetracycline class antibiotics can cause permanent staining of the teeth. For doxycycline this has never been shown. Three publications on children exposed to doxycycline from three months of age show no risk of staining of the teeth. Changing the recommended treatment for children with Lyme neuroborreliosis to oral doxycycline would markedly simplify treatment for children and parents and reduce healthcare costs.

The end of a dogma: the safety of doxycycline use in young children for malaria treatment.

Anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has spread from Southeast Asia to Africa. Furthermore, the recent emergence of resistance to artemisinin-based combination therapy (ACT) in Southeast Asia highlights the need to identify new anti-malarial drugs. Doxycycline is recommended for malaria chemoprophylaxis for travel in endemic areas, or in combination with the use of quinine for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails. However, doxycycline is not used in young children under 8 years of age due to its contraindication due to the risk of yellow tooth discolouration and dental enamel hypoplasia. Doxycycline was developed after tetracycline and was labelled with the same side-effects as the earlier tetracyclines. However, recent studies report little or no effects of doxycycline on tooth staining or dental enamel hypoplasia in children under 8 years of age. In the United States, the Centers for Disease Control and Prevention have recommended the use of doxycycline for the treatment of acute and chronic Q fever and tick-borne rickettsial diseases in young children. It is time to rehabilitate doxycycline and to recommend it for malaria treatment in children under 8 years of age.

Developmental defects of enamel in first permanent molars associated with use of asthma drugs in preschool aged children: A retrospective case-control study.

AIM: To investigate the association between the occurrences of developmental defects of enamel (DDE), in first permanent molars, and bronchodilators and/or corticosteroid intake for asthma-like episodic treatment at preschool age, in 6-12 year old children. METHODS: Children of the case group (n = 70) were followed in the Paediatric Pulmonary Unit and the Unit of Allergology, Asthma and Inflammation at 'Aghia Sofia' Children's Hospital, Athens, Greece and had used asthma drugs during their first 4 years of life. The control group (n = 70) consisted of healthy children who visited the Postgraduate Paediatric Dental Clinic, University of Athens. Information regarding demographic data, medical history, pregnancy, birth weight, duration of breastfeeding, mother's smoking habits and antibiotic use at preschool age was obtained through a structured questionnaire. Details concerning asthma drugs used were extracted from medical records. The children in both groups underwent an oral examination under standard clinical conditions and all surfaces of first permanent molars were assessed for enamel defects using the modified DDE Index. Chi square statistics, Mann-Whitney U test, Spearman correlation coefficient and logistic regression analysis were used for statistical analysis of the data (p ≤ 0.05). RESULTS: DDE were present in 24 children (34.3%) in the case group and only in 6 (8.6%) in the control, with the difference between the two groups being statistically significant (p < 0.001), while the estimated odds ratio was 5.56. Among the children with DDE in the case group, 41.6% had at least one hypoplastic molar with loss of enamel. The type of asthma drug, age at treatment onset and duration of drug use were not significantly associated with the severity or extent of DDE. Among the possible influential factors, gender was the only statistical significant factor. CONCLUSIONS: Children treated with asthma drugs for asthma-like episodes at a preschool age showed an overall increased risk for developing enamel defects in their first permanent molars. Severe hypoplastic lesions with loss of enamel was a frequent finding among affected molars.

Drugs related to the etiology of molar incisor hypomineralization: A systematic review.

BACKGROUND: Molar incisor hypomineralization (MIH) is an idiopathic syndrome that has been associated with several etiologic factors. The authors' objective was to systematically review studies in which the investigators had studied how the etiology of MIH was related to medication intake. TYPES OF STUDIES REVIEWED: The search covered a period from January 1, 1965, to September 29, 2014. The search revealed 1,042 articles, to which the authors applied eligibility criteria and selected 20 studies for review. The authors considered 9 of the 20 studies to be high quality. The drugs used in these studies were chemotherapeutic drugs, antibiotics, asthma drugs, antiepileptic drugs, antiviral drugs, antifungal drugs, and antiparasitic drugs. RESULTS: Two reviewers independently performed risk-of-bias assessment and data extraction. The investigators of all of the studies had reported enamel defects, but only 2 sets of investigators had used the term "molar incisor hypomineralization." Owing to the different methodologies used by the investigators of the selected studies, the authors could not perform a meta-analysis of the study results. CONCLUSIONS: More well-designed prospective studies are needed to clarify the relationship between MIH and medication. PRACTICAL IMPLICATIONS: It would be convenient to establish a preventive protocol in patients with a potential risk of developing MIH to avoid the complications that are characteristic of this disease.

Diagnosing congenital syphilis using Hutchinson's method: Differentiating between syphilitic, mercurial, and syphilitic-mercurial dental defects.

OBJECTIVES: This study focuses on the dental abnormalities observed by Sir Jonathan Hutchinson, Henry Moon and Alfred Fournier in patients with congenital syphilis and in those treated with mercury, in order to define alterations in dental morphology attributable to each of these causes. These definitions are applied to reported paleopathological cases, exploring various etiologies behind the defects, in order to aid in the diagnosis of congenital syphilis. METHODS: Original works were examined for descriptions of dental abnormalities in congenital syphilis and in mercurial treatments. These descriptions were compared with dentitions of paleopathological cases (n = 4) demonstrating abnormalities attributed to congenital syphilis. RESULTS: Distinct morphological differences were recognized between congenital syphilitic teeth and teeth affected by mercury. Mercury produces a pronounced deficiency in enamel of incisors, canines and first permanent molars that become rugged and pitted, and of dirty grey honeycombed appearance. Mercury-induced dental changes are evident in three out of four cases studied here. In one case, only syphilitic changes were present. DISCUSSION: Dental changes in congenital syphilis range from no visible signs to those beyond the classical models of Hutchinson, Moon and Fournier. Treatment of neonates and infants with mercury produces additional changes. Signs of disease and treatment with mercury on teeth may occur together; permanent incisors, first molars and canines, are typically affected, premolars and second/third molars are usually spared. Signs of treatment with mercury might be the only evidence of the occurrence of the disease as mercury was rarely used to treat other diseases.

Association of amoxicillin use and molar incisor hypomineralization in piglets: visual and mineral density evaluation.

AIM: The aim of the present study was to determine the prevalence of MIH both visually and quantitatively, and describes the range of mineral densities of enamel specimens from three groups of piglets where two groups were given different doses of amoxicillin in infancy. METHODS: In this blind randomized clinical study, 20 piglets were randomly divided into three groups. Group A received a standard dose (50mg/kg/day) and Group B received a high dose (90mg/kg/day) of amoxicillin in selected days of the month (20 working days) they were born. Group K did not receive any medication and served as control. Thirteen right mandibular permanent first molars (PFMs) were randomly collected from 3 groups of piglets at age 10 months for evaluation under X-ray micro-tomography. Tomographic data were obtained using a Skyscan 1174 compact micro-CT in the Department of Anatomy. RESULTS: Prevalence of MIH was 0% in all groups. MD values were quantified after enamel grey level (0-255) measurements on horizontal cross-sectional slices. After MD measurements, the effects of amoxicillin use on MIH are presented. CONCLUSIONS: While MIH is a multifactorial disturbance, the present study attempted to highlight the clinical findings of a possible relationship between amoxicillin use and MIH with the aid of X-ray micro-tomography.

Is maternal use of medicines during pregnancy associated with deciduous molar hypomineralisation in the offspring? A prospective, population-based study.

BACKGROUND: The effects of maternal use of medicines during pregnancy on tooth development has scarcely been studied; only negative effects of tetracycline on tooth germs are known (irreversible tooth discoloration and enamel hypoplasia). OBJECTIVE: The aim of this study was to investigate whether antibacterials and anti-allergic and anti-asthma medicines, being the most frequently used medicines during pregnancy, are associated with deciduous molar hypomineralisation (DMH) and, if so, which specific medicines. MATERIALS AND METHODS: To clarify this possible association, the participants of the Generation R Study, a population-based prospective cohort study from fetal life until young adulthood, were studied. Data on medicine use during pregnancy were retrieved from pharmacies. Clinical photographs of the second primary molars, which were scored for DMH, were taken with an intra-oral camera in 6,690 children (mean age 6.2 years, standard deviation [SD] ± 0.53; 49.9 % girls). RESULTS: During pregnancy, 20.3 % of the mothers used antibacterials, 12.3 % anti-asthma medicines and 5.4 % anti-allergic medicines. The prevalence of DMH was 9.0 % in the study group. There was no association between the use of anti-asthma medicines, anti-allergic medicines (odds ratio [OR]: 0.97 [95 % CI 0.61-1.54]; OR: 1.04 [0.54-2.03]) or antibacterials (OR: 0.73 [0.49-1.09]) during pregnancy and DMH (all p-values >0.05). The study had sufficient power (80 %) to detect significant associations. CONCLUSION: Maternal use of antibacterials, anti-allergic medicines or anti-asthma medicines during pregnancy is not associated with the development of DMH in the offspring.

Enamel defects reflect perinatal exposure to bisphenol A.

Endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), are environmental ubiquitous pollutants and associated with a growing health concern. Anecdotally, molar incisor hypomineralization (MIH) is increasing concurrently with EDC-related conditions, which has led us to investigate the effect of BPA on amelogenesis. Rats were exposed daily to BPA from conception until day 30 or 100. At day 30, BPA-affected enamel exhibited hypomineralization similar to human MIH. Scanning electron microscopy and elemental analysis revealed an abnormal accumulation of organic material in erupted enamel. BPA-affected enamel had an abnormal accumulation of exogenous albumin in the maturation stage. Quantitative real-time PCR, Western blotting, and luciferase reporter assays revealed increased expression of enamelin but decreased expression of kallikrein 4 (protease essential for removing enamel proteins) via transcriptional regulation. Data suggest that BPA exerts its effects on amelogenesis by disrupting normal protein removal from the enamel matrix. Interestingly, in 100-day-old rats, erupting incisor enamel was normal, suggesting amelogenesis is only sensitive to MIH-causing agents during a specific time window during development (as reported for human MIH). The present work documents the first experimental model that replicates MIH and presents BPA as a potential causative agent of MIH. Because human enamel defects are irreversible, MIH may provide an easily accessible marker for reporting early EDC exposure in humans.

Developmental enamel defects in children prenatally exposed to anti-epileptic drugs.

OBJECTIVE: Some anti-epileptic drugs (AED) have well-known teratogenic effects. The aim of the present study was to elucidate the effect of prenatal exposure to AED and the risk of enamel defects in the primary and permanent dentition. METHODS: A total of 38 exposed and 129 non-exposed children, 6-10 years of age, were recruited from the Aarhus Birth Cohort and the Department of Neurology, Viborg Regional Hospital, Denmark. Medication during pregnancy was confirmed by the Danish Prescription Database. All children had their teeth examined and outcomes in terms of enamel opacities and enamel hypoplasia were recorded. RESULTS: Children prenatally exposed to AED have an increased prevalence of enamel hypoplasia (11% vs. 4%, odds ratio (OR) = 3.6 [95% confidence interval (CI): 0.9 to 15.4]), diffuse opacities (18% vs. 7%, OR = 3.0; [95% CI: 1.0 to 8.7, p<0.05]), and numerous (>3) white opacities (18% vs. 10%, OR = 2.2; [95% CI: 0.8 to 6.1]) in the primary dentition. In the permanent dentition, an increased risk of numerous (>3) white opacities (34% vs. 12%, OR = 3.3; [95% CI: 1.3 to 8.4]) was found. CONCLUSIONS: The present study shows that children prenatally exposed to AED have an increased risk of developing numerous teeth with white opacities in their primary and permanent dentition. In addition, they also have an increased risk of developing diffuse opacities and enamel hypoplasia in their primary teeth.