A nationwide follow-up study of children of women with type 1 diabetes mellitus

Abstract

Previous studies have shown that children of women with type 1 diabetes are at risk for cardiometabolic diseases later in life, such as obesity, hypertension and type 2 diabetes. However, most of these studies have been performed in children of mixed cohorts of women with type 1, type 2 and/or gestational diabetes, or in children who were born >20 years ago when glycemic control was not as good as in current times. It has been concluded from a previous nationwide study on pregnancy outcome in women with type 1 diabetes in The Netherlands that the risk of perinatal complications was still increased as compared to the non-diabetic population, despite the fact that prepregnancy care and glycemic control during pregnancy were near-optimal. In this follow-up study we investigated whether the good glycemic control during pregnancy would have beneficial effects regarding the long term adverse effects on the development in the offspring. Therefore, we investigated several aspects of the development at 6-8 years of age in a nationwide cohort of 213 children of women with type 1 diabetes and compared them to those in a control group of 79 children of non-diabetic women. Overall intelligence, fasting glucose regulation, lipid metabolism, cardiac function and prevalence of childhood overweight and other components of the metabolic syndrome were comparable in both groups. Based on these findings, we suggest that near-optimal glycemic control during pregnancy in women with type 1 diabetes may therefore prevent, or at least lower, the incidence of adverse effects on later development in the offspring. However, we did find a slightly higher mean systolic blood pressure and a higher in vitro pro-inflammatory cytokine response in children of women with type 1 diabetes. Future follow-up studies should show whether these subtle cardiovascular and immunological differences may nonetheless be indicative of later cardiometabolic morbidity in these children. We suggest that in the mean time the goal of pregnant diabetic women and their attending physicians should be to achieve the lowest HbA1c level possible, without increasing the incidence of severe maternal hypoglycemia (as this may be harmful to the mother). Children of women with type 1 diabetes who were macrosomic at birth (with a birth weight >90th percentile for gestational age, sex and parity) had developed twice as much overweight compared with children who had a birth weight appropriate for gestational age. Possible targets for prevention of childhood overweight in children of diabetic women are fetal macrosomia, maternal overweight, and an increase in body mass index standard deviation score during the first years of life. Furthermore, severe maternal hypoglycemia during pregnancy had no proven adverse effects on later neurocognitive functioning in the offspring. However, we found that severe neonatal hypoglycemia (which has a high incidence in the direct neonatal period) influenced later neurocognition, and should therefore be avoided. Maternal HbA1c during pregnancy did poorly relate to developmental outcome measures in the offspring, possibly because it is not a reliable indicator of glycemic control during pregnancy.