Long-Term Prospective Evaluation of Offspring of Diabetic Mothers

Abstract

We have suggested that altered maternal metabolism may affect the subsequent anthropometric and neuropsychological development of children who were in utero during disturbances in maternal fuel economy. This study reports the physical growth through 8 yr of age and the neuropsychological development through 4 yr of age in offspring of diabetic mothers (ODM). At birth, 50% of infants had weights greater than 90th percentile for gestational age. By 12 mo, length and weight were similar to the general population. Height remained normal until 7 yr of age, when it became slightly greater than average. After 5 yr of age, relative weight increased dramatically, and by 8 yr of age, half of the ODM had weights greater than 90th percentile. This childhood obesity in ODM is correlated with maternal prepregnant weight and independently with amniotic fluid insulin at 32-38 wk gestation. The Brazelton Neonatal Behavioral Assessment Scale (BNBAS) was administered to 185 newborn ODM. Significant correlations were found between poorer second- and third-trimester glycemic regulation and lower scores in three of four newborn BNBAS dimensions. The Stanford-Binet Intelligence Scale was measured in 102 ODM at 4 yr of age. We found an inverse correlation between childhood IQ and second- and third-trimester maternal lipid metabolism (serum free fatty acids and beta-hydroxybutyrate). This correlation is not explained by adverse perinatal events, socioeconomic status, maternal IQ, ethnicity, or diabetes type. These long-range associations between altered maternal metabolism and childhood growth and development continue to support Freinkel's hypothesis of fuel-mediated teratogenesis.

Overweight and obesity in infants of mothers with long-term insulin-dependent diabetes or gestational diabetes

“…Nevertheless, analysis of our data by means of BMI as a second independent method, using a different reference population, con®rmed an increase of frequencies of overweight with rising age in infants of diabetic mothers. These observations are in good accordance with those reported by Silverman et al 9 and Gerlini et al 8 Indicating a persistence of increased body weight from birth to later life we observed positive correlations between SI and BMI at birth and SI and BMI in childhood, respectively. Verdy et al 31 reported that overweight newborns of diabetic mothers are at increased risk to be overweight in adulthood too.…”

“…A number of investigators used the SI or a variant of this measure to estimate overweight in children. 8,9,15 Weight/height-ratios are known to be good predictors of body fat. 24 In Europe, the use of weight/height-ratio is recommended for estimation of obesity in childhood.…”

Fetal programming of glucose–insulin metabolism

“…In addition diabetic mothers can give birth to large macrosomic offspring and this intrauterine exposure to diabetes is often a prelude to risk factors M a n u s c r i p t 6 for insulin resistance and type 2 diabetes (18,19). This exposure to maternal diabetes also affects the development of the endocrine pancreas (20) and can manifest itself with elevated levels of insulin in the amniotic fluid during pregnancy (21).…”

Fetal growth is increased by maternal type 1 diabetes and HLA DR4-related gene interactions

“…Factors that affect birthweight within demographically similar births include pre-pregnancy weight, weight gain during pregnancy, maternal smoking, parity and disease [9]. Maternal diabetes increases birthweight [10,11]. More recently, genes that influence the risk of type 1 diabetes have also been shown to affect birthweight and/or childhood weight gain [12,13].…”