Neurodevelopmental Follow-Up of Children Born to Mothers with Graves' Disease and Neonatal Hyperthyroidism.

INTRODUCTION: Neonatal hyperthyroidism, often caused by maternal Graves' disease (GD), carries potential neurodevelopmental risks for children. Excessive thyroid hormones during fetal development are linked to neurological issues like ADHD and epilepsy. However, the impact of transient neonatal hyperthyroidism is not well understood. METHODS: In a retrospective study at the Royal Children's Hospital in Melbourne, 21 neonates with hyperthyroidism from mothers with GD were examined. Of these, the parents of 10 children consented to participate; thus, questionnaires assessing executive functions, behavior, and social communication were completed. The outcomes were compared to those of control subjects recruited from the community using standardized tools (BRIEF, SDQ, SCQ). The results were analyzed against socio-demographic factors, maternal, and neonatal health. RESULTS: No significant demographic or clinical differences were found between study participants (n = 10) and non-participants (n = 11). Participants, compared to controls, showed similar family demographics but a higher proportion of control parents had university-level education (p = 0.003). Patients displayed more social (SCQ scores: 12.1 ± 2.5 vs. 6 ± 1.07, p = 0.008) and behavioral difficulties (SDQ scores: 10.2 ± 2.17 vs. 6.14 ± 1.03, p = 0.03), with increased executive function challenges (BRIEF scores indicating problem-solving and self-regulation difficulties). Significant effects of family living situation and partner education level on neurodevelopmental measures were noted, underscoring the influence of socio-demographic factors. CONCLUSIONS: These findings suggest neonatal hyperthyroidism might lead to subtle neurodevelopmental variations, with socio-economic elements and family dynamics possibly intensifying these effects. While most children did not show severe impairments, early detection and intervention are recommended. The research emphasizes the necessity for inclusive care approaches that consider socio-economic factors for children affected by neonatal hyperthyroidism.

Hijos de madres con enfermedad de Basedow Graves / Newborn of mothers with Graves' disease

Resumen: Introducción: La causa más frecuente de hipertiroidismo congénito es la enfermedad de Basedow Graves (EG) materna, en la que anticuerpos anti receptor de hormona tiroestimulante (TSH) (TRAb) atraviesan la placenta estimulando al receptor de TSH fetal y/o neonatal para producir hormonas ti roideas. La disfunción tiroidea en estos pacientes se confirma con el aumento de las concentraciones de tiroxina (T4) y triyodotironina (T3) acompañado de niveles de TSH suprimida. Objetivos: Carac terizar la evolución clínica y bioquímica de los recién nacidos (RN) hijos de madres con EG, y sugerir recomendaciones respecto al tratamiento y seguimiento. Material y Método: Se realizó una revisión de la literatura usando la base de datos MEDLINE, identificando artículos que incluyeran más de 30 RN de madres con EG y describieran su evolución. Se agregaron además revisiones del tema enfati zando la evaluación y manejo de los hijos de madres con EG. Resultados: Se incluyeron 9 estudios de cohorte que incorporaron 790 embarazadas. Hubo heterogeneidad entre los trabajos; un porcentaje variable de los hijos desarrolló tirotoxicosis neonatal, la que fue más frecuente cuando las madres presentaron concentraciones elevadas de TRAb. El tratamiento de los RN se inició según diferentes criterios. La literatura recomienda tratar los casos de hipertiroidismo clínico y considerarlo en casos de hipertiroidismo bioquímico. Conclusión: Los hijos de madres con EG y TRAb elevados deben ser evaluados por la probabilidad de desarrollar tirotoxicosis neonatal. Se sugiere controlar función tiroidea periódicamente durante el primer mes de vida y tratar los pacientes con hipertiroidismo clínico y bioquímico.

Abstract: Introduction: The most frequent cause of congenital hyperthyroidism is maternal Graves' disease (GD), in which thyroid stimulating hormone (TSH) receptor antibodies (TRAb) cross the placenta and stimulate the fetal and/or neonatal TSH receptor to produce thyroid hormones. Thyroid dys function in these patients is confirmed by increased thyroxine (T4) and triiodothyronine (T3) levels accompanied by suppressed TSH levels. Objective: To characterize the clinical and biochemical evo lution of newborns of mothers with GD and to suggest recommendations regarding treatment and follow-up. Material and Method: A literature review using the MEDLINE database was made, iden tifying scientific articles that included more than 30 neonates of mothers with GD and described their evolution. In addition, a review of the topic with an emphasis on the evaluation and management of these patients was included. Results: Nine cohort studies were included, with a total of 790 pregnant women. There was high heterogeneity among the studies. A variable percentage of newborns deve loped neonatal thyrotoxicosis, which was more frequent in those patients whose mothers had high levels of TRAb. The treatment of newborns was initiated according to different criteria. The literature recommends treating cases of clinical hyperthyroidism and considers it in cases of biochemical hy perthyroidism. Conclusion: Children of mothers with GD and high TRAb should be evaluated due to the likelihood of developing neonatal thyrotoxicosis. It is suggested to monitor thyroid function periodically during the first month of life and treat patients with clinical and biochemical hyper thyroidism.

Prediction of Neonatal Hyperthyroidism.

OBJECTIVES: To assess whether it is possible to identify the neonatal predictors of neonatal hyperthyroidism at the presymptomatic stage of the disease. STUDY DESIGN: This retrospective multicenter study in 10 maternity units was based on the medical records of all patients monitored for a pregnancy between January 1, 2007, and January 1, 2014. Among 280 000 births, 2288 medical records of women with thyroid dysfunction were selected and screened. Of these, 415 women had Graves disease and were positive for thyrotropin receptor antibody during pregnancy, and were included. RESULTS: A thyroid-stimulating hormone (TSH) level of less than 0.90 mIU/L between days 3 and 7 of life predicted neonatal hyperthyroidism with a sensitivity 78% (95% CI, 74%-82%) and a and specificity of 99% (95% CI, 98%-100%), a positive predictive value of 90% (95% CI, 87%-93%), a negative predictive value of 98% (95% CI, 97%-99%), and an area under the receiver operating characteristic curve of 0.99 (95% CI, 0.97-1.0). A thyrotropin receptor antibody (TRAb) elimination time was calculated using the equation: 7.28 + 2.88 × log() + 11.62 log(TRAb2). CONCLUSIONS: All newborns with a TSH level of less than 0.90 mIU/L should be examined by a pediatrician. Using TSH, it is possible to screen for neonatal hypothyroidism and for neonatal hyperthyroidism with a TSH cutoff of 0.90 mIU/L, and this shows the relevance of our study in terms of public health.

Resistencia a la hormona tiroidea y embarazo: caso clínico / Thyroid hormone resistance syndrome and pregnancy: case report

Thyroid hormone resistance syndrome is a genetic disease determined by a mutation that modifies the configuration of the beta thyroid hormone receptor, affecting its T3 binding capacity. Increased T3 and T4, determined by a compensatory TSH elevation secondary to pituitary resistance, allows an euthyroid functional state in most of the cases. The coexistence of pregnancy and thyroid hormone resistance is uncommon. Therefore, the optimal diagnosis and treatment strategy has not been determined. We report a 32 years old woman with thyroid hormone resistance, that became pregnant. During her pregnancy, she wassupplemented with levothyroxine in doses of 50 to 60 ug/day and remained euthyroid. Fetal development and growth were normal.