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Alterations of lymphocyte subsets in children of diabetic mothers
1Diabetes Research Institute, City Hospital Schwabing, Munich, Germany.
Insights
Children born to diabetic mothers show altered immune cell development, with decreased lymphocytes in neonates and changes in T cells in early childhood. These immune shifts may reflect adaptation to the maternal diabetic environment.
Area of Science:
- Immunology
- Pediatrics
- Endocrinology
Background:
- Maternal diabetes can impact fetal development, including the immune system.
- Understanding immune system maturation in offspring of diabetic mothers is crucial for long-term health.
- Previous research has not fully elucidated the specific immunophenotypic changes in children exposed to maternal diabetes in utero.
Purpose of the Study:
- To investigate the impact of maternal diabetes on lymphocyte subpopulations in healthy children.
- To compare immune markers in offspring of mothers with insulin-dependent diabetes mellitus (IDDM) and gestational diabetes.
- To assess immune system development across various pediatric age groups.
Main Methods:
- Two-colour flow cytometry was used to analyze immunophenotypic markers of lymphocyte subpopulations.
- 160 children of diabetic mothers and control groups (neonates of healthy mothers, reference population) were studied.
- Participants ranged from neonates to adolescents (7-17 years).
Main Results:
- Neonates of diabetic mothers exhibited significantly decreased percentages of total lymphocytes, T cells, and B cells compared to controls.
- Offspring of mothers with IDDM showed more pronounced differences in lymphocyte counts than those with gestational diabetes.
- Children aged 1-6 years born to diabetic mothers had higher total lymphocyte percentages and lower activated T cells compared to a reference population.
Conclusions:
- Maternal diabetes influences the maturation of the immune system in offspring, with distinct changes observed in neonates and young children.
- The observed immune alterations may represent an adaptive response to the maternal metabolic and autoimmune environment.
- No significant differences were found between offspring of IDDM and gestational diabetes mothers, nor in high-risk children for IDDM development.
Abstract:
To investigate the impact of diabetic mothers on the maturation of the immune system in their offspring, immunophenotypic markers of major lymphocyte subpopulations were evaluated by two-colour flow cytometric analysis in 160 healthy children of diabetic mothers (100 with insulin-dependent diabetes mellitus (IDDM): 48 with gestational diabetes), including 22 neonates, 45 infants aged 8-12 months, 46 children aged 1-2 years, 29 children aged 3-6 years and 18 children aged 7-17 years. Results were compared with 21 neonates of healthy mothers from our hospital and with 110 paediatric subjects of a reference population. In neonates of diabetic mothers, percentages of total lymphocytes (p = 0.044), T and B lymphocytes (p = 0.004, respectively) were significantly decreased compared to our neonates of healthy mothers. By subdividing the group of neonates in offspring of mothers with IDDM (n = 15) or gestational diabetes (n = 7), differences compared to normal neonates were mainly observed in neonates of mothers with IDDM (T lymphocytes: p = 0.006; B lymphocytes: p = 0.008). In cord blood, 45.5% of neonates had antibodies to islet cells, insulin or glutamic acid decarboxylase, most likely transmitted through the placenta of the diabetic mother. No association was found between alterations of lymphocyte subsets and antibody-positivity in cord blood, nor was there any correlation of lymphocyte counts and mean HbA1 during pregnancy, maternal age at delivery, diabetes duration, or neonatal birth weight, respectively. Comparisons among age groups from newborn infants through adolescents revealed higher percentages of total lymphocytes and lower percentages of activated T cells in children of diabetic mothers compared to children of the reference population between the age of 1 to 6 years (67-73% of the cases above and 62-77% below the interquartiles of the reference range, respectively). No significant differences in lymphocyte subpopulations between children of mothers with IDDM diabetes and gestational diabetes have been detected. In addition, there were no abnormalities of lymphocyte subsets in children who are at high risk for the development of IDDM. In summary, we suggest that the observed changes in children of diabetic mothers may reflect a cellular immune reaction to the particular maternal environment, characterized by both an abnormal metabolic state and persisting autoimmunity in the affected mother.