Hematologic Parameters and Vaso-occlusive Phenotype Are Associated With Molar-incisor Hypomineralization in Children With Sickle Cell Disease
Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction Sickle cell disease (SCD) is characterized by chronic hemolysis, systemic inflammation, and recurrent vaso-occlusive episodes, leading to tissue hypoxia and damage from early childhood. Molar-incisor hypomineralization (MIH) is a clinically relevant developmental enamel defect that compromises oral health, increases restorative treatment needs, and negatively affects children's oral health-related quality of life. During this period, amelogenesis of the first permanent molars takes place and depends on adequate blood supply and proper ameloblast function. Although developmental enamel defects have been reported in children with SCD, few studies have investigated their relationship with hematologic parameters and clinical disease phenotypes. Objective To investigate the association between hematologic parameters, clinical phenotypes of sickle cell disease, and the occurrence of molar-incisor hypomineralization (MIH), as well as to compare its prevalence with that of healthy children. Materials and Methods A retrospective cohort study was conducted including 60 children with SCD, aged 6–14 years, followed at a tertiary hematology referral center, and 605 age-matched healthy controls. MIH was diagnosed according to the European Academy of Paediatric Dentistry criteria. Demographic, clinical, and laboratory data were obtained from medical records. Hematologic parameters assessed from birth to three years of age, corresponding to the developmental period of the first permanent molars, included complete blood count, erythroblast count, and lactate dehydrogenase (LDH) levels. Patients were classified into hemolytic and vaso-occlusive clinical phenotypes. Associations were assessed using the chi-square, Fisher's exact, and Mann-Whitney tests (p<0.05). Results The prevalence of MIH was significantly higher in children with SCD than in healthy controls (63.3% vs. 18.2%; prevalence ratio = 3.48; 95% CI, 2.66–4.54; p<0.001). Among children with SCD, MIH was significantly more frequent in those with the vaso-occlusive phenotype than in those with the hemolytic phenotype (86.8% vs. 22.7%; p<0.001). In addition, children with MIH had lower erythroblast counts during the developmental period of the first permanent molars (0.2 vs. 1.0; p=0.014). No significant associations were found between MIH and LDH levels or other clinical variables evaluated. Discussion The findings suggest that hematologic alterations associated with SCD severity may influence enamel formation. The association between MIH and the vaso-occlusive phenotype supports the hypothesis that recurrent ischemic and hypoxic events during amelogenesis may impair ameloblast function and enamel mineralization. Moreover, the lower erythroblast counts observed in children with MIH suggest that early hematologic alterations may also contribute to this process. Collectively, these findings support the hypothesis that the severity of systemic alterations during early childhood may influence enamel development in children with SCD. Conclusion Children with sickle cell disease presented a higher prevalence of MIH than healthy controls, and this condition was associated with the vaso-occlusive phenotype and lower erythroblast counts. These findings suggest that greater disease severity during early childhood may contribute to impaired enamel development, highlighting MIH as a potential oral marker of systemic disease burden in children with SCD.
Authors: Kelly Fernanda MOLENA, Mariana Andrade COSTA, Alana Cândido PAULO, Francisco Wanderley Garcia DE PAULA-SILVA, Raquel Assed Bezerra DA SILVA, Karina Alessandra Michelão Grecca PIERONI, Cristina Bueno BRANDÃO, Leda Regina Fernandes MUGAYAR, Ana Cristina Silva PINTO, Alexandra Mussolino DE QUEIROZ, Leandro Dorigan DE MACEDO, Fabricio Kitazono DE CARVALHO
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223140548