Metabolic Syndrome in Childhood: Association With Birth Weight, Maternal Obesity, and Gestational Diabetes Mellitus

Brown University, Providence, Rhode Island, United States
PEDIATRICS (Impact Factor: 5.47). 04/2005; 115(3):e290-6. DOI: 10.1542/peds.2004-1808
Source: PubMed


Childhood obesity has contributed to an increased incidence of type 2 diabetes mellitus and metabolic syndrome (MS) among children. Intrauterine exposure to diabetes and size at birth are risk factors for type 2 diabetes mellitus, but their association with MS in childhood has not been demonstrated. We examined the development of MS among large-for-gestational-age (LGA) and appropriate-for-gestational age (AGA) children.
The major components of MS (obesity, hypertension, dyslipidemia, and glucose intolerance) were evaluated in a longitudinal cohort study of children at age 6, 7, 9, and 11 years who were LGA (n = 84) or AGA (n = 95) offspring of mothers with or without gestational diabetes mellitus (GDM). The cohort consisted of 4 groups, ie, LGA offspring of control mothers, LGA offspring of mothers with GDM, AGA offspring of control mothers, and AGA offspring of mothers with GDM. Biometric and anthropometric measurements were obtained at 6, 7, 9, and 11 years. Biochemical testing included measurements of postprandial glucose and insulin levels and high-density lipoprotein (HDL) cholesterol levels at 6 and 7 years and of fasting glucose, insulin, triglyceride, and HDL cholesterol levels at 9 and 11 years. We defined the components of MS as (1) obesity (BMI >85th percentile for age), (2) diastolic or systolic blood pressure >95th percentile for age, (3) postprandial glucose level >140 mg/dL or fasting glucose level >110 mg/dL, (4) triglyceride level >95th percentile for age, and (5) HDL level <5th percentile for age.
There were no differences in baseline characteristics (gender, race, socioeconomic status, and maternal weight gain during pregnancy) for the 4 groups except for birth weight, but there was a trend toward a higher prevalence of maternal obesity before pregnancy in the LGA/GDM group. Obesity (BMI >85th percentile) at 11 years was present in 25% to 35% of the children, but rates were not different between LGA and AGA offspring. There was a trend toward a higher incidence of insulin resistance, defined as a fasting glucose/insulin ratio of <7, in the LGA/GDM group at 11 years. Analysis of insulin resistance at 11 years in a multivariate logistic regression revealed that childhood obesity and the combination of LGA status and maternal GDM were associated with insulin resistance, with odds ratios of 4.3 (95% confidence interval [CI]: 1.5-11.9) and 10.4 (95% CI: 1.5-74.4), respectively. The prevalence at any time of > or =2 components of MS was 50% for the LGA/GDM group, which was significantly higher than values for the LGA/control group (29%), AGA/GDM group (21%), and AGA/control group (18%). The prevalence of > or =3 components of MS at age 11 was 15% for the LGA/GDM group, compared with 3.0% to 5.3% for the other groups. Cox regression analysis was performed to determine the independent hazard (risk) of developing MS attributable to birth weight, gender, maternal prepregnancy obesity, and GDM. For Cox analyses, we defined MS as > or =2 of the following 4 components: obesity, hypertension (systolic or diastolic), glucose intolerance, and dyslipidemia (elevated triglyceride levels or low HDL levels). LGA status and maternal obesity increased the risk of MS approximately twofold, with hazard ratios of 2.19 (95% CI: 1.25-3.82) and 1.81 (95% CI: 1.03-3.19), respectively. GDM and gender were not independently significant. To determine the cumulative hazard of developing MS with time, we plotted the risk according to LGA or AGA category for the control and GDM groups from 6 years to 11 years, with Cox regression analyses. The risk of developing MS with time was not significantly different between LGA and AGA offspring in the control group but was significantly different between LGA and AGA offspring in the GDM group, with a 3.6-fold greater risk among LGA children by 11 years.
We showed that LGA offspring of diabetic mothers were at significant risk of developing MS in childhood. The prevalence of MS in the other groups was similar to the prevalence (4.8%) among white adolescents in the 1988-1994 National Health and Nutrition Examination Survey. This effect of LGA with maternal GDM on childhood MS was previously demonstrated for Pima Indian children but not the general population. We also found that children exposed to maternal obesity were at increased risk of developing MS, which suggests that obese mothers who do not fulfill the clinical criteria for GDM may still have metabolic factors that affect fetal growth and postnatal outcomes. Children who are LGA at birth and exposed to an intrauterine environment of either diabetes or maternal obesity are at increased risk of developing MS. Given the increased obesity prevalence, these findings have implications for perpetuating the cycle of obesity, insulin resistance, and their consequences in subsequent generations.

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    • "A. Fetal programming prevention: preventing the first hit Compared with children born to normal weight mothers, those born to mothers who are obese have greater risk of obesity and cardiometabolic disease (Boney et al., 2005; Dabelea et al., 2008; Lau et al., 2014; Yu et al., 2013). Infants born to obese, nondiabetic mothers have elevated adiposity and insulin resistance emerging as early as birth (Catalano et al., 2009). "
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    ABSTRACT: Prenatal development is recognized as a critical period in the etiology of obesity and cardiometabolic disease. Potential strategies to reduce maternal obesity-induced risk later in life have been largely overlooked. In this paper, we first propose a conceptual framework for the role of public health and preventive medicine in mitigating the effects of fetal programming. Second, we review a small but growing body of research (through August 2015) that examines interactive effects of maternal obesity and two public health foci - diet and physical activity - in the offspring. Results of the review support the hypothesis that diet and physical activity after early life can attenuate disease susceptibility induced by maternal obesity, but human evidence is scant. Based on the review, we identify major gaps relevant for prevention research, such as characterizing the type and dose response of dietary and physical activity exposures that modify the adverse effects of maternal obesity in the offspring. Third, we discuss potential implications of interactions between maternal obesity and postnatal dietary and physical activity exposures for interventions to mitigate maternal obesity-induced risk among children. Our conceptual framework, evidence review, and future research directions offer a platform to develop, test, and implement fetal programming mitigation strategies for the current and future generations of children.
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    • "Evidence shows that the status of maternal nutrition (both undernutrition and overnutrition) can influence the epigenetic state of the fetal genome and alter fetal nutrition and endocrine status, and result in developmental adaptations, termed " fetal programming " [9] [10] [18] [20] [21]. Although this adaptive mechanism promotes the survival of embryos and fetuses, it results in a wide array of considerable health problems in affected offspring (Fig. 1). "
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    The Journal of nutritional biochemistry 08/2015; DOI:10.1016/j.jnutbio.2015.08.003 · 3.79 Impact Factor
    • "Subsequent studies of maternal under-nutrition and, more recently, maternal over-nutrition have demonstrated that the maternal nutritional environment and foetal and neonatal growth, collectively known as the first 1000 days of life, are key determinants of health in the next generation (de Rooij et al., 2006; Lumey and Stein, 1997; Ravelli et al., 1976, 1999). In humans, maternal obesity is associated with low and high birth weight (Cedergren, 2004; Gaudet et al., 2014) and increased risk of obesity and metabolic dysfunction in the offspring both in childhood (Boney et al., 2005; Whitaker, 2004) as well as in adulthood (Brisbois et al., 2012; Cooper et al., 2010). Maternal obesity is also associated with increased risk of offspring cardiovascular disease (Drake and Reynolds, 2010), type 2 diabetes (Berends and Ozanne, 2012), and neurodevelopmental and psychiatric disorders, including ADHD, autism, schizophrenia, and mood disorders (Mehta et al., 2014; Rodriguez, 2010). "
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