Neonatal Macrosomia Is an Independent Risk Factor for Adult Metabolic Syndrome

Abstract

Background: Weight in infancy correlates with risk of type 2 diabetes, hypertension, and obesity in adulthood. Clinical observations have been confounded by obesity-prone genotypes and obesity-linked lifestyles. Objectives: To define the effects of isolated neonatal macrosomia in isogenic animals, we compared macrosomic and control C57Bl6 mice co-fostered by healthy dams receiving standard laboratory feed. Methods: Naturally occurring neonatal macrosomia was identified by a gender-specific weanling weight above the 90th percentile for the colony. Macrosomic and control mice were phenotyped in adulthood by exercise wheel, tail cuff and intraperitoneal insulin or glucose challenge. Results: Compared to control males, adult males with a history of neonatal macrosomia had significantly increased body weight, reduced voluntary activity, insulin resistance, fasting hyperinsulinemia, and impaired glucose tolerance. In contrast, adult females with neonatal macrosomia had no significant alteration in body weight or endocrine phenotypes, but did have higher blood pressures and lower heart rates than control females. After these baseline studies, all mice were switched to a hypercaloric, high fat diet (5 kcal/g, 45% of energy as fat). Twenty weeks later, male mice had impaired glucose tolerance and insulin resistance, independent of their weanling weight classification. While on high fat feeds, macrosomic males maintained a significantly higher body weight than control males. Conclusions: We conclude that (1) in our murine model, neonatal macrosomia is an independent risk factor of adult metabolic syndrome, and (2) neonatal macrosomia accentuates the sexually dimorphic predisposition of C57Bl6 male mice towards glucose intolerance and C57Bl6 female mice towards hypertension.

Three dimensional image analysis of minor salivary glands in 180-day rats born with macrosomia

“…(1) Physical development Acceleration Group consists of the oversized (m ≥6.3×10 -3 kg) descendants of young (3 -5 months) animals with average weight-height parameters and standard nutrition ration before zoogamy and during pregnancy [21].…”

“…Numerous data given in a number of works witness that the development of dental violations have strong connection with the state of person's health and with the presence of various diseases including those caused by metabolic mechanisms [3,4,5,6,7,8]. However, relatively few studies have been performed to examine the effect of fetal macrosomia on dental pathology formation.…”

Adipokines in umbilical cord blood from children born large for gestational age

“…Accordingly, there is increasing evidence supporting the developmental origins of a health and disease hypothesis that suggests a prenatal programming towards later childhood obesity and metabolic dysregulation through the intrauterine environment (2,3). Consequently, infants that are born large for gestational age (LGA) are more likely to be obese in childhood and adolescence (4)(5)(6) and are at risk of cardiovascular and metabolic obesity-related complications later in life (7).…”

HbA1c and birthweight in women with pre-conception type 1 and type 2 diabetes: a population-based cohort study

“…Small for gestational age (SGA) is less often associated with maternal diabetes per se, but has been reported in association with severe vascular complications [9,10] and can result in higher neonatal morbidity and mortality. Both birthweight extremes in offspring of mothers with diabetes are associated with a higher risk of complications during the pregnancy, labour and neonatal period [2,11] as well as with a potential increase in diseases in childhood and adulthood, including obesity, cardiovascular disease, diabetes and metabolic syndrome [12][13][14][15].…”