Búsqueda de marcadores precoces del neurodesarrollo en hijos/as de madres con diabetes gestacional / GD-Brain

Abstract

Introduction: Gestational Diabetes Mellitus (GDM) is the most common pathology during pregnancy, showing a rising trend in recent years parallel to the obesity epidemic. Recent studies suggest that children born to mothers with GDM may have neurodevelopmental alterations, but the underlying mechanisms are unknown. GDM is characterized by abnormal placental function that can disrupt the transfer of essential compounds for children's cognitive development, such as long-chain polyunsaturated fatty acids (LC-PUFAs), especially docosahexaenoic acid (DHA). Children born to mothers with GDM have lower DHA levels at birth, but their long-term levels during childhood and their consequences on child neurodevelopment are still unknown. Objective: To assess potential differences in neurodevelopment in 8-year-old children born to mothers with GDM compared to those born to healthy mothers and to identify early and persistent biomarkers of neurodevelopment in the early stages of life. Method: A prospective longitudinal observational study of a "mother-child" cohort in 8-year-old children born to mothers with gestational diabetes compared to a control group of healthy mothers. A total of 156 mother-child pairs were evaluated at 8 years ± 6 months of age, coming from two cohorts (49 mother-child pairs from the GDM cohort in Murcia and 107 mother-child pairs from the PREOBE cohort at the University of Granada), resulting in 80 children born to mothers with GDM and 76 controls. Measures of intelligence (K-BIT), neurodevelopment (BENCI), temperament (EAS and TMCQ), behavior (CBCL), anthropometric assessment, dietary habits, and physical activity of the children were obtained. Fatty acid levels were analyzed in the oral mucosa of 8-year-old children and in umbilical cord blood at birth. Results: Children born to mothers with GDM have a higher Body Mass Index at 8 years of age, despite maintaining similar diets and lifestyles, which could be explained by metabolic programming induced during pregnancy. Children born to mothers with GDM have lower levels of DHA in venous blood phospholipids at birth. Subsequently, in childhood, there is a tendency to have a higher percentage of saturated fatty acids in the oral mucosa, but no significant differences in DHA content in the oral mucosa at 8.5 years of age. Children born to mothers with GDM had a higher risk of experiencing behavioral and emotional problems, both internalizing and externalizing types, and were at greater risk of attention problems. Additionally, children born to mothers with GDM scored lower in Verbal Intelligence Quotient and Total Intelligence Quotient (IQ) than the controls. In terms of temperament, they exhibited higher levels of fantasy and perceptual sensitivity and tended to score higher on impulsivity and inhibitory control. The concentration of DHA at birth could be used as a predictive biomarker for later childhood behavioral problems, showing even superior predictive capability compared to analyzing DHA in children at 8.5 years of age. Conclusion: The results confirm the importance of maintaining adequate DHA intake from gestation, especially in women with GDM. GDM has a negative impact on the body mass index of the offspring, intellectual neurodevelopment, and attention skills at 8 years of age. These children are at greater risk of experiencing emotional and behavioral problems