The association between birth size and cardiometabolic disease risk may be U-shaped. Being born small for gestational age (SGA) has a definitive association with later cardiovascular risk, but the impact of being born large for gestational age (LGA) on cardiometabolic health is more controversial. In addition to birth size, early postnatal growth pattern and later weight gain affect cardiometabolic risk in adulthood. Most SGA-born children have catch-up and LGA-born children have catch-down growth during the first years of life. The extent of this early compensatory growth may contribute to the adverse health outcomes. Both SGA-and LGAborn children are at an increased risk for overweight and obesity. This may have a long-term impact on cardiometabolic health as overweight tends to track to adulthood. Other cardiometabolic risk factors, including alterations in glucose metabolism, dyslipidemia, hypertension, and lowgrade inflammation are associated with birth weight. Many of these risk factors are related to overweight or adverse fat distribution. Since later cardiometabolic risk is often mediated by early growth pattern and later overweight in SGA and LGA children, it is important to focus on staying normal weight throughout life. Hence, effective interventions to reduce cardiometabolic risk in LGA and SGA children should be developed.

BackgroundChildren born small for gestational age (SGA) have higher serum dehydroepiandrosterone sulfate (DHEAS) concentrations than children born appropriate for gestational age (AGA). The overall metabolic risk associated with birth weight is U-shaped, but it is not known whether children born large for gestational age (LGA) have elevated serum DHEAS levels.MethodsA cohort of 49 children born LGA, 56 children born AGA, and 23 children born SGA were studied at 5-8 years of age. Anthropometric data at birth, at the age of 2 years, and at examination were recorded. Fasting blood samples were collected for serum analyses of DHEAS, insulin-like growth factor 1 (IGF-1), and insulin concentrations.ResultsThe children born LGA had lower serum DHEAS levels adjusted for body mass index (BMI) standard deviation score (SDS) and age than the rest of the children. Lower birth weight SDS and higher weight gain during the first 2 years of life predicted higher serum DHEAS levels. Higher serum IGF-1 levels were also associated with higher prevalence of adrenarchal DHEAS levels.ConclusionBeing born LGA was associated with lower DHEAS levels, whereas small birth size and early catch-up growth predicted higher levels. This suggests that genetic or early epigenetic factors have an impact on adrenarche. IGF-1 may be a mediator in this process.

BackgroundBirth weight has an impact on adult bone mass. Higher birth weight is associated with greater bone mineral content (BMC) and children born small for gestational age (SGA) are at an increased risk for impaired accrual of bone mass. Our aim was to study whether the impact of birth size or early childhood growth on bone mass is visible already in mid-childhood.MethodsWe studied 49 children born large for gestational age (LGA), 56 children born appropriate for gestational age (AGA), and 23 children born SGA at 5.0-8.7 years of age. Body composition was assessed by whole-body dual-energy X-ray absorptiometry. Fasting blood samples and anthropometric data were collected.ResultsThe children born SGA had lower bone mineral density (BMD) Z-score (P<0.001) and age- and sex-adjusted BMD (P<0.005) than the LGA and AGA children. Adjusted BMC, muscle mass, and body fat percentage (%BF) did not differ between the study groups. Muscle mass, BMI SD score (SDS), %BF, and serum dehydroepiandrosterone sulfate (DHEAS) concentration were the strongest predictors of high BMD in mid-childhood.ConclusionSGA-born children had lower BMD in mid-childhood compared with AGA- and LGA-born ones. Muscle mass or BMI SDS, %BF, and DHEAS were significant predictors of childhood BMD.

Background: Maternal gestational diabetes mellitus (GDM) and overweight are associated with an increased risk of obesity and the metabolic syndrome in the adult offspring. We studied the influence of maternal GDM on prepubertal children’s height, weight, body mass index (BMI), lipid and glucose metabolism, and low-grade inflammation. Methods: A cohort of 135 prepubertal Caucasian children (age range 4.4–9.7 years) was studied in a controlled cross-sectional study. Seventy-seven children had been exposed to maternal GDM, and 58 children born after a normal pregnancy served as controls. The outcomes were height, weight, BMI, blood pressure, and biochemical markers of glucose and lipid metabolism and inflammation. Results: There were no differences in height, weight, BMI, fasting serum insulin, plasma glucose, lipids, or blood pressure between the study groups. However, high-sensitivity C-reactive protein (hs-CRP) was significantly higher in the GDM group than in the controls (p = 0.001). Conclusions: Higher hs-CRP as a marker of low-grade inflammation was detected in prepubertal children exposed to maternal GDM, but no differences were seen in height, weight, BMI, or markers of glucose and lipid metabolism compared to control children. This finding may reflect an ongoing process of metabolic changes in children born after a GDM pregnancy.

Background: Both large and small birth sizes are associated with an increased risk of developing cardiovascular and metabolic problems later in life. We studied whether such associations can be observed at prepubertal age. Methods: A cohort of 49 large (LGA), 56 appropriate (AGA), and 23 small for gestational age (SGA)-born children (age range 5-8 years) were studied. Being born SGA, AGA, or LGA was the exposure, and being overweight at prepubertal age was the main outcome. Blood pressure measurements, laboratory parameters, and whole-body dual-energy X-ray absorptiometry were secondary outcomes. Results: The LGA-born children were significantly taller than the AGA controls (p = 0.03), and the SGA children were lighter and shorter compared to the AGA (p = 0.002 and 0.001) and LGA children (p < 0.001). The mean plasma glucose was higher in the LGA than in the SGA group (p = 0.006). Being born LGA (OR 3.82) and the ponderal index Z-score at birth (OR 4.24) were strong predictors for being overweight or obese in childhood. Conclusion: The children born LGA remained taller and heavier than those born AGA or SGA in mid-childhood, and they had a higher body mass index and body fat percentage than the SGA-born children. The differences in other cardiometabolic risk factors were minimal between the birth size groups.

Context:Birth size has an impact on later cardiometabolic risk that is strongly related to low-grade inflammation.Objective:To evaluate plasma interleukin-1 receptor antagonist (IL-1ra) concentrations in relation to birth size and cardiometabolic and inflammatory markers in prepubertal children.Design:A cohort study. Anthropometric data were recorded. Fasting blood samples were collected for plasma analyses of IL-1ra, alanine transaminase, total cholesterol, high- and low-density lipoprotein cholesterols, triglyceride, glucose, and serum analyses of 25-hydroxyvitamin D [25(OH)D] and high-sensitivity C-reactive protein (hs-CRP) concentrations.Participants:Forty-nine large for gestational age (LGA), 56 appropriate for gestational age, and 23 small for gestational age (SGA) children at 5 to 8 years of age were examined.Main Outcome Measures:Differences in IL-1ra concentrations among the birth-size groups and associations between IL-1ra and other metabolic markers were assessed.Results:Body mass index (BMI) standard deviation score (SDS)-adjusted plasma IL-1ra concentrations were highest in the SGA- and lowest in the LGA-born children (P = 0.015). Age- and sex-adjusted IL-1ra concentrations had strongest associations with BMI SDS (P < 0.001) and hs-CRP (P < 0.001, also when further adjusted for BMI SDS).Conclusions:Prepubertal children born SGA had the highest and those born LGA the lowest IL-1ra concentrations in this study cohort. Most associations found between IL-1ra and the studied metabolic parameters were weight related, but the association with hs-CRP remained strong after adjustment for BMI. It seems that at prepuberty, SGA children have a stronger inflammatory state than LGA children and may thus be at a greater risk for later metabolic disturbances.

<b><i>Background:</i></b> Maternal gestational diabetes mellitus (GDM) and overweight are associated with an increased risk of obesity and the metabolic syndrome in the adult offspring. We studied the influence of maternal GDM on prepubertal children’s body composition and bone mineral biochemistry. <b><i>Methods:</i></b> A total of 134 prepubertal Caucasian children (age range 4.4–9.7 years) were studied in a controlled cross-sectional study. Seventy-six children had been exposed to maternal GDM and 58 children born after a normal pregnancy served as controls. The outcome variables were body fat %, android fat %, gynoid fat %, android/gynoid fat ratio, bone mineral density (BMD), bone mineral content (BMC), muscle mass, lean mass (LM) and serum 25-hydroxyvitamin D, ionized calcium, phosphate, and alkaline phosphatase concentrations. <b><i>Results:</i></b> There were no differences in body fat %, android fat %, BMD, BMC, muscle mass, or LM between the study groups. Gynoid fat % was higher in the GDM than control children (<i>p</i> = 0.03). Android fat %, gynoid fat %, and android/gynoid fat ratio were higher in the GDM boys than control boys (<i>p</i> = 0.046, 0.037, and 0.038) respectively, but no differences were found between the GDM and control girls. <b><i>Conclusions:</i></b> Boys exposed to maternal GDM presented with more unfavorable fat distribution than their controls, whereas no difference was found between the girls. Otherwise, the differences in body composition were minimal between prepubertal GDM and control children.

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