Long-term metabolic effects of high birth weight: a critical review of the literature.

Recent studies in USA, Europe, and across the world have revealed a continuous increase of mean birth weight in the last 2 decades. Strong evidence exists from several studies indicating that individuals born with a low birth weight are more likely to present cardiometabolic complications in later life. So far, the long-term consequences of high birth weight have not been clearly defined. This review examines the role of high birth weight on the development of cardiometabolic consequences (obesity, body composition, type 2 diabetes mellitus, and cardiovascular disease) in childhood and adulthood. The majority of the studies show that high BW is associated with an increased risk for obesity. To a certain extent high birth weight affects diseases of the heart and circulatory, but does not constitutes a risk for the development of type 2 diabetes mellitus in the general population. Maternal glycemia and the subsequent fetus hyperinsulinemia appear to be the key component for increased fetal growth. With the increase in incidence of diabetes mellitus and obesity over the years, the number of high birth weight infants is likely to increase. The elucidation of the relationship between high birth weight and the cardiometabolic disorders will be particularly important.

Vitamin D levels and insulin resistance in children born with severe growth restriction.

This study was designed to examine differences in serum 25(OH)D levels between small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) prepubertal children in correlation with birth weight and indices of insulin resistance and ß-cell function. Sixty-five nonobese children were examined at age 5-7.5 years; 27 born SGA and 38 matched AGA. Body weight, height, BMI, and waist circumference were recorded and fasting serum levels of glucose, insulin, 25(OH)D, and parathyroid hormone (PTH) were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) and the ß-cell function index (HOMA-ß%) were estimated. The mean level of 25(OH)D was higher in the SGA group (26.2±10 vs. 17.2±7 ng/ml, p<0.01) but that of PTH was no different. The insulin resistance and ß-cell function indices were higher in the SGA group: HOMA-IR 1.34±0.67 vs. 0.99±0.53, and HOMA-ß% 135±56 vs. 97±60 in the SGA and AGA groups, respectively. In the SGA group, 25(OH)D was correlated with HOMA-ß% but not with HOMA-IR or insulin. In multiple regression, in the total cohort 25(OH)D and HOMA-IR were independently negatively correlated with birth weight (ß= - 0.31, ß= - 0.36, p<0.05) respectively. In conclusion, at prepuberty severely in utero growth restricted children have increased birth weight dependent levels of 25(OH)D, which might exert a regulatory role on ß-cell function.

Serum insulin-like growth factor I (IGF-I), IGF-binding proteins-1 and -3, and postnatal growth of late preterm infants.

Late preterm infants may have impaired early growth. The role of circulating insulin-like growth factors (IGFs) in the regulation of postnatal growth of these infants is unclear. The aim of the study was to investigate prospectively the serum levels of IGFs during the first year of life in late preterm infants and their association with birth weight and early postnatal growth. The study was conducted on 112 infants, born appropriate for gestational age (GA) at GA 32-36 weeks. Serum levels of IGF-I and IGF-binding proteins (IGFBP) -1 and -3, and anthropometric measurements were recorded at the chronological age of 2 and 6 weeks, and 3, 6, 9, and 12 months. The mean levels of both IGF-I and IGFBP-3 were found to be lower at 2 and 6 weeks, 82±44, 100±31 ng/ml, and 1.7±0.8, 2.1±1 µg/ml, respectively, but then rose and remained stable between 3 and 12 months. The levels of IGFBP-1 were lower at the 3 first study points and increased gradually thereafter. Birth weight correlated positively with the level IGF-I at 2 and 6 weeks (R=0.35, 0.37; p<0.01), but negatively at 12 months (R= - 0.34; p<0.01), independent of other factors. At all study points up to 6 months, the level of IGF-I was higher in infants who showed more rapid growth in either body weight or crown heel length. In late preterm infants, the serum IGF-I level is closely related to early accelerated growth. Its diverse associations with birth weight may imply a regulatory effect on regression of growth towards the mean.

Visfatin levels in prepubertal children born small or large for gestational age.

Children born small (SGA) or large (LGA) for gestational age are prone to develop insulin resistance (IR) during childhood. Visfatin, a hormone with insulin-mimetic actions, has been associated with IR. This study was designed to examine whether serum level of visfatin is correlated with metabolic indices of IR, in prepuberty in association with the intrauterine growth pattern. The following parameters were evaluated at a mean age of 6.5±1.2 years in 155 prepubertal children born appropriate for the gestational age (AGA) (n=63), or SGA (n=42), or LGA (n=50): serum levels of visfatin, adiponectin, leptin, fasting glucose (G(F)) and insulin (I(F)), the homeostasis model assessment IR index (HOMA-IR), plasma lipids, anthropometric indices at birth and the time of evaluation, and obesity indices [waist circumference (WC), body mass index (BMI) and skinfold thickness]. The mean serum level of visfatin was lower in the SGA than in the AGA and the LGA children (9±5.2 vs. 11.8±5.1 and 12.7±5.6 ng/ml, respectively, p<0.01). Girls had lower visfatin levels than boys (10.4±4.3 ng/ml vs. 12.5±6.7 ng/ml, p<0.05). Visfatin was not correlated with IR indices. In multiple regression analysis visfatin level was positively correlated with birth weight z-score (t=2.56, beta=0.24, p<0.01) and crown to heel z-score (t=2.46, beta=0.22, p=0.014), independent of age, gender, maternal weight before pregnancy, maternal weight gain during pregnancy, BMI z-score, WC z-score, serum leptin and adiponectin, and HOMA-IR. In conclusion serum visfatin level was lower in prepubertal SGA children but not correlated with IR indices. Low birth weight was an independent predictor of visfatin level.

Vitamin D and parathormone levels of late-preterm formula fed infants during the first year of life.

BACKGROUND/OBJECTIVES: Preterm infants are at risk for low vitamin D but documentation on late-preterm infants is sparse. This prospective study monitored longitudinally vitamin D and parathormone (PTH) levels in late-preterm formula fed infants during the first year of life, taking into consideration in utero and postnatal growth, and season and diet. SUBJECTS/METHODS: The study population comprised 128 infants of gestational age (GA) 32-36 weeks, of which 102 were appropriate (AGA) and the remaining 26 were small for GA (SGA). Serum levels of vitamin D (25(OH)D), PTH calcium, phosphate (P) and alkaline phosphate were estimated at 2 and 6 weeks, and at 3, 6, 9 and 12 months of age. RESULTS: The 25(OH)D levels were relatively low at 2 and 6 weeks in both AGA and SGA infants (21±11, 20±7 ng/ml and 25±16, 23±8 ng/ml, respectively), but increased at 6 months (45±14, 47±10 ng/ml) and remained stable thereafter. SGA infants had lower 25(OH)D levels at 9 and 12 months (AGA 45±14, 47±18 ng/ml vs SGA 38±13, 37±13 ng/ml, P<0.05). Deficiency of 25(OH)D (<20 ng/ml) was found in 18.5% of measurements in 92 (72%) infants, and its insufficiency (20-32 ng/ml) was found in 29.2% of measurements in 99 (77.3%) infants. Most measurements with vitamin D <32 ng/ml were observed at the first three study points, where PTH showed an inverse association with 25(OH)D, reaching a plateau thereafter. CONCLUSIONS: Late-preterm, formula fed infants may have suboptimal vitamin D levels and elevated PTH, especially, during the first 3 months. Those born SGA may have lower vitamin D levels up to the end of the first year of life.

Growth factors, adiponectin, leptin and body mass index in pre-pubertal children born large for gestational age.

OBJECTIVE: To examine whether the IGF axis in pre-pubertal children born large for gestational age (LGA) differs from that of those born appropriate for gestational age (AGA). RESEARCH DESIGN AND METHODS: The study population consisted of 98 non-obese children aged 5.5-8 yr, of whom 37 were LGA, with birth weight (BW) > 90th percentile, and 61 AGA. The LGA children were subdivided into two subgroups, with BW 90th-97th percentile (no.=24) and BW > 97th percentile (no.=13), respectively. Total and free IGF-I, their binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), leptin, adiponectin, fasting glucose (GF) and insulin (IF) were measured, and the homeostasis model assessment for insulin resistance (HOMA-IR index) was determined. RESULTS: IGF-I, free IGF-I and IGFBP-1 were similar in both groups. Both LGA subgroups had lower IGFBP-3 levels than the AGA group (2.34 ± 0.61 and 2.70 ± 0.90, respectively, vs 3.92 ± 1.1 µg/ml, p < 0.01). Adiponectin was higher in the 90th-97th percentile LGA subgroup than the AGA group (p<0.01). GF and IF were higher in the LGA group (86.5 ± 5.6 mg/dl, p < 0.01, and 5.84 ± 2.13 µU/ml, respectively, p < 0.05) than in the AGA group (82.6 ± 7.7 mg/dl and 4.62 ± 1.9 µU/ml, respectively), as was the HOMA-IR index (1.27 ± 0.60 vs 0.94 ± 0.43, p < 0.01). These three parameters were also found higher in the >97th percentile LGA subgroup. CONCLUSION: The IGF axis was not different in pre-pubertal children born LGA or AGA, with the exception of IGFBP-3, which was lower in the LGA children. In LGA pre-pubertal children the severity of intrauterine overgrowth was associated with the insulin resistance indices.

Retinopathy of prematurity and other ocular problems in premature infants weighing less than 1500 g at birth.

PURPOSE: To estimate the incidence of retinopathy of prematurity and other ocular problems in a population of preterm infants. METHODS: This retrospective study included all infants with gestational age (GA) <32 weeks and birth weight (BW) <1500 g cared for in the neonatal intensive care unit (NICU) over a period of nine years (1992-2000). Ophthalmological examination was started the 4th week of life and included refractive examination, examination of the cornea and funduscopy under mydriasis. An ocular motility test was done after the 2nd month. RESULTS: The study included 194 infants. Stage I and II retinopathy occurred in 51 infants but regressed spontaneously. Five of the 194 (2.5%) had to undergo cryopexy. Optic disc atrophy was observed in association with peri-intraventricular hemorrhage (PIIVH) (grade IV) in seven infants. Fifteen infants (7.7%) had retinal hemorrhages which were absorbed by three months of age. Almost 20% of the study infants developed high refractive errors and 13.4% strabismus. CONCLUSIONS: Not only retinopathy of prematurity, but other serious ocular problems were observed in this population of preterm infants. The role of PIIVH III-IV in the pathogenesis of certain ocular problems needs further elucidation.