Consequences of being born small for gestational age on body composition: an 8-year follow-up study.

CONTEXT: Increased fat mass has been reported in children and adults born small for gestational age (SGA). However, the progression of anthropometric parameters have been poorly documented in SGA adults. OBJECTIVE: We hypothesized that SGA individuals would remain susceptible to gain more fat when adults beyond the period of postnatal catch-up growth. STUDY POPULATION AND DESIGN: From a community-based cohort, 389 subjects born full-term SGA (body weight < 10th percentile) were compared with 462 subjects born appropriate for gestational age (25th < body weight < 75th percentile). Anthropometric parameters were measured at 22 and 30 yr as well as body composition (by multifrequency bioelectrical impedancometry and skinfold thickness) at 30 yr. RESULTS: Both groups gained weight, body mass index (BMI), and waist circumference. Progression of BMI was significantly greater in SGA (1.8 +/- 2.6 vs. 1.4 +/- 2.6 kg/m(2); P = 0.03). At 30 yr, the proportion of obese individuals was significantly increased in SGA (12.1 vs. 6.5%; P = 0.02), and percent body fat was significantly higher (23.5 +/- 8.7 vs. 21.9 +/- 8.0%; P = 0.01), the observation of which was confirmed by skinfold measures. Similarly, waist circumference gain was significantly greater in SGA (6.4 +/- 7.6 vs. 5.5 +/- 7.9, P = 0.04 when adjusted for gender and age). CONCLUSION: Over 8-yr follow-up, adults born SGA gained more BMI than appropriate for gestational age, resulting in greater fat mass with more abdominal fat. These data suggest that the consequences of fetal growth restriction on body composition are evolving beyond the period of early postnatal catch-up.

TCF7L2 rs7903146 variant does not associate with smallness for gestational age in the French population.

BACKGROUND: In adults, the TCF7L2 rs7903146 T allele, commonly associated with type 2 diabetes (T2D), has been also associated with a lower body mass index (BMI) in T2D individuals and with a smaller waist circumference in subjects with impaired glucose tolerance. METHODS: The present association study aimed at analyzing the contribution of the rs7903146 SNP to smallness for gestational age (SGA) and metabolic profiles in subjects with SGA or appropriate for gestational age birth weight (AGA). Two groups of French Caucasian subjects were selected on birth data: SGA (birth weight < 10th percentile; n = 764), and AGA (25th < birth weight < 75th percentile; n = 627). Family-based association tests were also performed in 3,012 subjects from 628 SGA and AGA pedigrees. RESULTS: The rs7903146 genotypic distributions between AGA (30.7%) and SGA (29.0%) were not statistically different (allelic OR = 0.92 [0.78-1.09], p = 0.34). Family association-based studies did not show a distortion of T allele transmission in SGA subjects (p = 0.52). No significant effect of the T allele was detected on any of the metabolic parameters in the SGA group. However, in the AGA group, trends towards a lower insulin secretion (p = 0.03) and a higher fasting glycaemia (p = 0.002) were detected in carriers of the T allele. CONCLUSION: The TCF7L2 rs7903146 variant neither increases the risk for SGA nor modulates birth weight and young adulthood glucose homeostasis in French Caucasian subjects born with SGA.

The INS VNTR locus does not associate with smallness for gestational age (SGA) but interacts with SGA to increase insulin resistance in young adults.

CONTEXT: Both adverse intrauterine events and genetic background have been suggested to promote insulin resistance in subjects born small for gestational age (SGA). Among candidate genes that potentially influence both fetal growth and glucose metabolism is insulin. The potential effect of the insulin gene VNTR (INS) on birth weight has been controversial so far. OBJECTIVE: The present association study aimed at testing for the contribution of the INS VNTR locus on birth weight and on the metabolic profile of young adults born SGA (mean age, 22 yr). Two groups of subjects were selected on birth data: SGA (birth weight < 10th percentile; n = 735), and appropriate for gestational age (AGA; birth weight between 25th and 75th percentiles; n = 886). All subjects were genotyped for rs689 A/T single nucleotide polymorphism, in complete linkage disequilibrium with the INS VNTR classes I and III, respectively. RESULTS: Class I INS frequencies were similar in the two groups (70% in AGA; 72% in SGA; P = 0.42). There was significant effect on mean birth weight in neither SGA (P = 0.99) nor AGA (P = 0.18). Although the INS VNTR locus did not associate with anomalies of insulin resistance indices in the AGA group, in the SGA group, INS VNTR class III allele was associated with higher insulin resistance (quantitative insulin sensitivity check index = 0.38 vs. 0.39; P = 0.05). Furthermore, there was evidence of an interaction between the SGA/AGA status and INS VNTR locus on insulin resistance indices (P = 0.01) in a multivariate analysis. CONCLUSION: The INS VNTR locus does not associate in a major way with SGA in the French population. However, our data support an interaction between severe fetal growth restriction and INS VNTR locus, which were associated with insulin resistance in young adults born SGA.

SGA children with moderate catch-up growth are showing the impaired insulin secretion at the age of 4.

BACKGROUND: Being born small for gestational age (SGA) is a risk factor for later development of type 2 diabetes. The development of glucose tolerance disorders in adults involves insulin resistance and impaired insulin secretion. OBJECTIVE: To evaluate insulin secretion and insulin sensitivity in a 4-yr old cohort of SGA. METHODS: 85 children were prospectively followed from mid-gestation to 4 years of age. Fetal growth velocity (FGV) was measured using ultrasound measurements. Body composition and hormonal profile were measured at birth, 1 and 4 years. RESULTS: 23 SGA babies had lower birth weight compared to 62 AGA (-1.9±0.3 vs. -0.6±0.8 z-score; p<0.0001) and they were thinner at birth (ponderal index 24.8±1.8 vs. 26.3±3.1 kg/m3; p = 0.01 and fat mass 11±2.6 vs. 12.9±3.1%; p = 0.01). No significant differences in other measured metabolic and hormonal parameters were observed between two groups at birth. SGA infants experienced an early catch-up growth in weight (mean gain of 1.1±0.6 SD) during the first year of life. At 4 years, SGA children remain lighter than AGA, but with weight z-score in the normal range (-0.1±1.3 vs. 0.5±1.3 z-score; p = 0.05). No excess of fat mass was observed (19±4.8 vs. 19.7±4.1%; p = 0.45). 120-min plasma glucose was significantly higher (6.2±1.1 vs. 5.6±0.9 mmol/l; p = 0.006) and insulinogenic index was significantly lower (0.28±0.15 vs. 0.40±2.4; p = 0.02) in the SGA group at 4-yrs of life contrasting with a preserved insulin sensitivity (QUICKI 0.47±0.09 vs. 0.43±0.05; p = 0.06). CONCLUSION: SGA children with compensatory catch-up growth in first year of life show mild disturbances of glucose tolerance associated to a lower insulinogenic index at 4-yrs of age suggesting impairment of ß-cell function.

Innate small babies are metabolically healthy children.

BACKGROUND: Being born small for gestational age (SGA) is regarded as a risk factor for later metabolic complications. The SGA is defined as a birth weight below -2 SD of the distribution for sex and gestational age. However, the definition of SGA does not distinguish between those born after fetal growth restriction and innate SGA (iSGA). OBJECTIVE: Our objective was to test whether innate SGA infants show any metabolic complications at the age of 2 yr in comparison with infants born appropriate for gestational age (AGA). METHODS: Fifty-eight infants with family SGA risk factors (SGA in a previous pregnancy or among parents, maternal height less than -2 sd for adult height in French women, and small fetal size at second-trimester ultrasound examination) were prospectively followed from midgestation to 2 yr of age. Fetal growth velocity was measured from ultrasound measurements. Body composition and hormonal profile were measured at birth and 1 and 2 yr. RESULTS: Fetal growth velocity was not significantly different between iSGA and AGA (-0.17 ± 0.2 vs. -0.17 ± 0.3 percentiles/d of gestation; P = 0.96). iSGA infants were significantly lighter at birth (-1.7 ± 0.45 vs. 0.46 ± 0.77 SD; P < 0.0001) and at 4 months of age (-0.85 ± 0.88 vs. 0.29 ± 1 SD; P < 0.0001), and they remain so over follow-up (-0.73 ± 1.08 vs. 0.2 ± 1.02 SD; P = 0.0014 at 2 yr). Height z-scores and percent fat time courses followed a similar pattern. No differences in any of the metabolic and hormonal parameters were observed between iSGA and AGA up to 2 yr (insulin at birth, 5.1 ± 6.8 vs. 5.2 ± 4.6 mIU/liter, P = 0.2; at 2 yr, 2 ± 1.6 vs. 2 ± 1.5 mIU/liter, P = 0.66). CONCLUSION: Infants born iSGA do not experience severe fetal growth restriction and do not show any evidence of metabolic risk either at birth or in the first 2 yr of life.

Evaluation of an ELISA assay for total proinsulin and establishment of reference values during an oral glucose tolerance test in a healthy population.

OBJECTIVES: Assessment of the analytical performance of the Total Proinsulin ELISA Kit (Millipore) and determination of reference values. DESIGN AND METHODS: Imprecision, specificity, antibodies interference and reference values in normoglycaemic non-obese adults were determined. RESULTS: The inter-assay CV is <6.9%, the limits of detection and quantification are 0.2 and 0.6 pmol/L. Molar cross-reactivity of split proinsulins varies from 103 to 92.5%. The interference of anti-(pro)insulin antibodies can be eliminated with the use of polyethylene glycol. The reference values are 2.7-14.2 pmol/L at fasting, 8.5-56.5 pmol/L at T30 min and 11.9-70.5 pmol/L at T120 min during an OGTT. CONCLUSION: The reference values established for this kit, which showed good analytical performances, allow for a better assessment of pathologies associated with increased proinsulinaemia.

Bone mineral content at birth is determined both by birth weight and fetal growth pattern.

Adult peak bone mass is related to birth weight, suggesting it could be affected by fetal growth pattern. Small-for-gestational-age (SGA) newborns have lower bone mineral content (BMC), but what about adapted-for-gestational-age (AGA) newborns with fetal growth restriction? The purpose of the study was to determine the respective role of birth weight and fetal growth pattern on BMC. Full-term newborns from SGA high-risk pregnancies were included (n = 185). Estimated fetal weight percentiles were measured monthly from mid-gestation to birth, and restricted fetal growth (FGR) was defined as a loss by more than 20 percentiles. BMC was measured at birth, using dual x-ray absorptiometry. Newborns were SGA (n = 56) or AGA (n = 129). Newborns with FGR (n = 111) were AGA (n = 71) or SGA (n = 41). BMC was significantly lower in SGA than AGA (1.48 +/- 0.02 vs. 1.87 +/- 0.04 g/cm) and lower when FGR irrespective of birth weight (1.66 g/cm +/- 0.03 vs. 1.89 g +/- 0.05). In multivariate analysis, FGR and SGA were significant and independent predictors of low BMC. In conclusion, fetal growth pattern affects BMC not only in SGA infants but also when birth weight is maintained in the normal range.

Serum adiponectin and leptin concentrations in HIV-infected children with fat redistribution syndrome.

Human immunodeficiency virus (HIV)-related lipodystrophy is characterized by adipose tissue redistribution, dyslipidemia, and insulin resistance. We hypothesized that fat redistribution and metabolic abnormalities in HIV-infected children are related to alterations in endocrine function of adipose tissue. A multicenter study was conducted in 130 HIV-infected children. Lipodystrophy definition was based on the central to peripheral skinfold ratio. Fasting adiponectin, leptin, insulin concentrations, glycemia, and lipid profile were measured in all children. Fat redistribution syndrome was apparent in 32 children: 14 with atrophic (LPDA) and 18 with hypertrophic lipodystrophy (LPDH). Mean serum adiponectin levels were significantly decreased in LPDA and LPDH groups compared with the group with no lipodystrophy (LPD-). Fasting insulin concentration was significantly higher in LPDA and LPDH groups versus LPD-. Mean serum leptin concentration was significantly increased only in LPDH compared with LPDA and LPD- groups. Triglyceride levels were significantly increased and high-density lipoprotein (HDL)-cholesterol concentration decreased in the LPDA versus LPD- group. Controlling for puberty stage, gender, percentage of total fat mass, serum lipids, HIV treatment, and disease severity, adiponectin was significantly and inversely associated with central obesity and insulin/glucose ratio. Fat redistribution had no significant effect on leptin concentration, which was directly related to the percentage of body fat, female gender, and insulin/glucose ratio. In conclusion, HIV-infected children with symptoms of fat redistribution have decreased levels of adiponectin, associated with insulin resistance and dyslipidemia.

Time course of catch-up in adiposity influences adult anthropometry in individuals who were born small for gestational age.

Although necessary for a normal final height in individuals who were born small for gestational age (SGA), catch-up growth is associated with drastic changes in body composition that have been suspected to favor the later development of the long-term metabolic complications by promoting central adiposity; however, the specific contribution of catch-up itself on these later complications remains unclear. Therefore, the aim of the study was to characterize the dynamic changes in adiposity during childhood in individuals who were born SGA and to investigate their consequences on adulthood. The magnitude and the time course of postnatal changes in body mass index (BMI) relative to birth and their consequences on adult adiposity were investigated in 127 adults who were born SGA and had available serial anthropometric data in childhood (0-6 y) and adulthood. Catch-up in BMI, observed in 91% of individuals who were born SGA, was mostly completed within the first or second year of age. Overall, adult BMI was correlated with the magnitude of gain in BMI during childhood. However, this effect was significant only when this gain persisted after the first year of life. Similarly, the influence of the magnitude in gain in BMI on the risk for adult BMI >25 kg/m(2) was significantly influenced by the age at which the gain in BMI occurred. In summary, although the extent of catch-up in BMI affects adiposity in adulthood, this effect is mostly deleterious when occurring after 1 y of age, suggesting that a rapid catch-up process should be more suitable than a delayed one. Whether this observation holds through regarding the metabolic syndrome remains to be elucidated.

Longitudinal evaluation and risk factors of lipodystrophy and associated metabolic changes in HIV-infected children.

OBJECTIVE: To assess the rate of progression of lipodystrophy and the associated metabolic disturbances over a 2-year period in children and to assess risk factors associated with lipodystrophy and metabolic disturbances. DESIGN: Multicenter 2-year prospective study with a standardized evaluation. METHODS: One hundred thirty children (median age = 10 years, 64 boys and 66 girls) receiving antiretroviral therapy were recruited in 3 pediatric clinics. Lipodystrophy was defined based on 4 skinfold thickness measurements. Fasting lipids and glucose profile were measured in all children. RESULTS: The proportion of children presenting with lipodystrophy was 24.6%. Nineteen percent of children had high-density lipoprotein values less than 1 mmol/L. Twenty-two percent and 15% of children had values greater than 2 standard deviations for age and gender for cholesterol and triglycerides, respectively. A total of 13.2% showed insulin resistance. A total of 42.7% showed at least 1 of these biologic disturbances. Prospective follow-up showed no progression at all over 2 years, except for a doubling of the number of children with insulin resistance. In multivariate analyses, ethnicity, previous severe clinical condition, duration of HIV infection, and nucleoside reverse transcriptase inhibitor treatment were significantly associated with lipodystrophy. Tanner stage V of puberty, severe clinical symptoms and protease inhibitor treatment were independently associated with the risk of metabolic disturbances. CONCLUSIONS: Puberty seems to be the time when HIV-infected children taking potent antiretroviral therapy are more likely to develop lipodystrophy and metabolic complications, especially in children with a severe underlying HIV infection. Once developed, lipodystrophy and metabolic changes seem to be extremely stable with time.