To investigate the impact of diabetic mothers on the maturation of the
immune system in their offspring, immunophenotypic markers of major l
ymphocyte 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), in
cluding 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. Re
sults were compared with 21 neonates of healthy mothers from our hospi
tal and with 110 paediatric subjects of a reference population. In neo
nates of diabetic mothers, percentages of total lymphocytes (p = 0.044
), T and B lymphocytes (p = 0.004, respectively) were significantly de
creased compared to our neonates of healthy mothers. By subdividing th
e group of neonates in offspring of mothers with IDDM (n = 15) or gest
ational 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 ha
d antibodies to islet cells, insulin or glutamic acid decarboxylase, m
ost likely transmitted through the placenta of the diabetic mother. No
association was found between alterations of lymphocyte subsets and a
ntibody-positivity in cord blood, nor was there any correlation of lym
phocyte counts and mean HbA(1) during pregnancy, maternal age at deliv
ery, diabetes duration, or neonatal birth weight, respectively. Compar
isons among age groups from newborn infants through adolescents reveal
ed higher percentages of total lymphocytes and lower percentages of ac
tivated T cells in children of diabetic mothers compared to children o
f 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 subpop
ulations between children of mothers with IDDM diabetes and gestationa
l diabetes have been detected. In addition, there were no abnormalitie
s of lymphocyte subsets in children who are at high risk for the devel
opment of IDDM. In summary, we suggest that the observed changes in ch
ildren of diabetic mothers may reflect a cellular immune reaction to t
he particular maternal environment, characterized by both an abnormal
metabolic state and persisting autoimmunity in the affected mother.