Glucose and Lipid Metabolism in Small For Gestational Age Infants at
48 Hours of Age
Rodrigo A. Bazaes, MD*; Teresa E. Salazar, MSc*; Enrica Pittaluga, MD‡; Vero´nica Pen˜a, MD§; Ange´lica Alegrı´a, MD‡; Germa´n I´n˜iguez, MSc*; Ken K. Ong, MD储; David B. Dunger, MD储; and
M. Vero´nica Mericq, MD*
ABSTRACT. Objective. To study the consequences of low birth weight on glucose and lipid metabolism 48 hours after delivery.
Methods. We studied 136 small for gestational age (SGA) and 34 appropriate for gestational age (AGA) term neonates who were born in Santiago, Chile. Prefeeding venous blood was obtained 48 hours after birth for de-termination of glucose, free fatty acids, -hydroxy bu-tyrate, insulin, C-peptide, leptin, sex hormone-binding globulin, insulin-like growth factor-binding protein-1 (IGFBP-1), and cortisol.
Results. SGA newborns had lower glucose (SGA ver-sus AGA, median [interquartile range]: 3.6 mmol/L [2.9 – 4.1 mmol/L] vs 3.9 mmol/L [3.6 – 4.6 mmol/L]) and insulin levels (31.3 pmol/L [20.8 – 47.9 pmol/L] vs 62.5 pmol/L [53.5–154.9]) than AGA infants, and they had higher glu-cose/insulin ratios (13.9 mg/dL/uIU/mL [8.6 –19.1 mg/dL/ uIU/mL] vs 8.2 mg/dL/uIU/mL [4.6 –14.1 mg/dL/uIU/mL]). SGA infants also had higher levels of IGFBP-1 (5.1 nmol/L [4.4 – 6.7 nmol/L] vs 2.9 nmol/l [1.4 – 4.2 nmol/L]), free fatty acids (0.72 mEq/L [0.43–1.00 mEq/L] vs 0.33 mEq/L [0.26 – 0.54 mEq/L]) and-hydroxy butyrate (0.41 mEq/L [0.15– 0.91 mEq/L] vs 0.09 mEq/L [0.05– 0.13 mEq/ L]). Sex-hormone binding globulin levels were not sig-nificantly different between the 2 groups.
Conclusions. In early postnatal life, SGA infants dis-play an increased insulin sensitivity with respect to glu-cose disposal but not with respect to suppression of lipolysis, ketogenesis, and hepatic production of IG-FBP-1. It will be important to determine how these dif-ferential sensitivities to insulin vary with increasing age. Pediatrics2003;111:804 – 809;Barker hypothesis, low birth weight, insulin sensitivity.
ABBREVIATIONS. LBW, low birth weight; SGA, small for gesta-tional age; AGA, appropriate for gestagesta-tional age; SHBG, sex hor-mone-binding globulin; IGFBP-1, insulin-like growth factor-bind-ing protein-1; FFA, free fatty acid; RIA, radioimmunoassay; CV, coefficient of variation; bOH-B, -hydroxy-butyrate; G/I, glu-cose/insulin; HOMA, homeostasis model assessment; GH, growth hormone.
L
ow birth weight (LBW) has been associated with a broad range of adult conditions, includ-ing hypertension, glucose intolerance and type 2 diabetes, dyslipidemia, polycystic ovary syndrome, exaggerated adrenarche with precocious pubarche, and male infertility.1,2 Altered sensitivity to insulin in these conditions is usually present, a central ele-ment that has also been related to LBW.1Although these correlations were initially identified in adult-hood, they also have been found during adolescence and in prepubertal children.2,3The pathophysiological determinants for these strong epidemiologic associations have proved hard to identify.4It remains questionable whether a spe-cific genetic background explains both LBW and adult disease.5Alternatively, an “in utero program-ming” model has been proposed by Barker et al.1 According to these authors, an adverse intrauterine environment during a critical period of development induces a metabolic response for survival that per-sists into adulthood. The nature of this programming is not yet clear, but long-term, tissue-specific modi-fications of insulin sensitivity may be critical.1,6 Mechanisms involved in this process have also been elusive, but a role for elevated in utero plasma levels of glucocorticoids in growth-restricted fetuses has been proposed.7
A central prediction of Barker’s model is that the results of metabolic and endocrine programming should be present during early postnatal life and infancy. More precise, it can be expected that small for gestational age (SGA) newborns, when compared with their appropriate for gestational age (AGA) counterparts, should display differences in their sen-sitivity to insulin. However, assessment of insulin sensitivity in newborns is complicated by risks im-posed by classical methodologies, which need mul-tiple blood samples and the infusion of exogenous glucose and/or insulin.8 In addition, most of these methods have not been validated in children. There-fore, we are reliant on measures of fasting blood glucose, insulin, and C-peptide levels, comple-mented by other indirect measures of insulin sensi-tivity, such as plasma sex hormone-binding globulin (SHBG) and insulin-like growth factor-binding pro-tein-1 (IGFBP-1) levels.9 –11In addition, lipid metab-olism, as evidenced by plasma levels of triglycerides, cholesterol, free fatty acids (FFAs), and ketone
bod-From the *Institute for Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile; ‡Neonatology Unit, So´tero del Rı´o Hospital, Santiago, Chile; §Neonatology Unit, San Borja-Arriara´n Hospital, Santiago, Chile; and储Department of Paediatrics, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom.
Received for publication May 28, 2002; accepted Sep 19, 2002.
Reprint requests to (M.V.M.) Institute for Maternal and Child Research, School of Medicine, University of Chile, Casilla 226-3, Santiago, Chile. E-mail: vmericq@machi.med.uchile.cl
ies, has been found to reflect insulin action in differ-ent conditions, including the newborn.12
Previous reports show significant differences re-garding hormonal levels in SGA versus AGA new-borns. Low cord blood levels of insulin, IGF-I, and leptin, as well as high IGFBP-1 values, have been consistently found in SGA neonates.11,13,14However, a simultaneous and integral profile of the effects of LBW on insulin sensitivity and -cell function shortly after birth, in otherwise healthy infants, is still lacking.
To determine the metabolic and endocrine conse-quences of LBW during early postnatal life, we are prospectively studying a cohort of full-term SGA and AGA newborns from Santiago, Chile. In this report, we describe preliminary results from this cohort in the early neonatal period regarding whole-body in-termediate metabolism.
METHODS Patients
Infants in this study were born between July 1999 and October 2000 at 2 public hospitals (San Borja-Arriara´n and So´tero del Rı´o) in Santiago, Chile. Protocols and consent forms were approved by respective institutional review boards. All mothers signed written consent after being appropriately informed.
A total of 136 SGA newborns (46 boys and 90 girls) were recruited. The inclusion criteria for infants were born at term (gestational age⬎37 weeks), a birth weight below the fifth per-centile for the Chilean population adjusted for gender and gesta-tional age,15 and an uneventful delivery. Infants who showed
malformations or evidence for genetic disorders were excluded. Thirty-four healthy, full-term AGA newborns (birth weight be-tween percentiles 10 and 90; 19 boys and 15 girls) were also recruited as controls. All infants in both groups were breastfed, with similar frequencies ranging from 3 to 4 hours.
At recruitment, anthropometric data from parents, as well as pregnancy and delivery events were retrieved from clinical records. Data from newborns (gender, gestational age, birth weight, crown-heel length, and head circumference) were also recorded, andzscores for anthropometric parameters were calcu-lated using local normative data.15
Forty-eight hours after birth (range: 40 – 48 hours), a 3-mL blood sample was obtained from newborns. Samples were withdrawn immediately before feeding, ie, in fasting conditions (range: 3- to 4-hour fasting). Blood was immediately centrifuged, and the se-rum was stored at⫺20°C until processing. Concomitantly, blood glucose concentration was determined using a commercial glu-cometer (Accutrend Sensor Comfort, Roche Diagnostics Inc, Basel, Switzerland), which yields values 8⫾5% higher than standard enzymatic methods for glycemias between 2.2 and 5 mmol/l.
Laboratory Procedures
Serum insulin was measured using a commercial radioimmu-noassay (RIA) from Immunotech (Marseille, France). Serum cor-tisol and C-peptide were also determined by RIA, using kits supplied by DPC (Los Angeles, CA). Serum leptin, IGFBP-1, and SHBG were measured by immunoradiometric assays from DSL (Webster, TX). Intra-assay coefficients of variation (CVs) were 3.8% for insulin, 4.1% for C-peptide, 4.5% for cortisol, 4.6% for leptin, 3.5% for IGFBP-1, and 3.1% for SHBG. Interassay CVs were 4.7% for insulin, 5.6% for C-peptide, 5.9% for cortisol, 6.2% for leptin, 4.2% for IGFBP-1, and 5.4% for SHBG. Cross-reactivities for our insulin RIA were declared by the manufacturer as follows: 68% against des-64 – 65-proinsulin, 55% against proinsulin, and 50% against des-31–32-proinsulin.
FFAs were determined using a kit from Wako Chemicals (Neus, Germany). This assay is based on the esterification of FFA into acyl-co-enzyme A, followed by its enzymatic oxidation. This latter reaction yields hydrogen peroxide, which is then colori-metrically quantified. -Hydroxy-butyrate (bOH-B) was mea-sured using a kit from Sigma (St Louis, MO). This measurement
relies on the enzymatic oxidation of-HBA into acetoacetate in presence of nicotinamide-adenine dinucleotide. The resulting product is then spectrophotometrically detected at 340 nm wave-length. Intra-assay CVs were 1.7% for FFA and 3.7% for bOH-B. Interassay CVs were 7.2% for FFA and 10.3% for bOH-B.
Assessment of Insulin Sensitivity
None of the parameters used to assess insulin sensitivity in adults has been validated in neonates. Despite this, it seems rea-sonable that plasma glucose and insulin levels start regulating each other in a closed loop shortly after birth (see Results). There-fore, we calculated the plasma glucose/insulin (G/I) ratio, as well as the homeostasis model assessment (HOMA) of insulin sensitiv-ity and -cell function16 using the HOMA-CIGMA Calculator
program v2.00 (Diabetes Research Laboratory, Oxford, United Kingdom). This model, originally developed in prediabetic adults, relies on the inverse relationship between plasma levels of glucose and insulin in fasting conditions. In addition, SHBG and IGFBP-1 were used as indicators of hepatic sensitivity to insulin.
Statistical Analysis
Results are expressed as median [interquartile range]. Differ-ences between groups were assessed by nonparametric tests (Mann-WhitneyU), as a result of different sample sizes and non-normal distribution of some variables. Correlation between vari-ables was evaluated using parametric statistics (Pearson), except for variables displaying nonnormal distributions even after log transformation (Spearmantest). Analyses were performed with SPSS v 10.0 (SPSS, Inc, Chicago, IL), in a x86-based computer. Differences and correlations were considered significant atP ⬍
.05.
RESULTS
All newborns were delivered at full-term, with a mean gestational age of 39 weeks (Table 1). Predict-ably, SGA infants were shorter (47.0 cm [45.7– 48.0 cm] vs 50.0 cm [50.0 –51.8 cm];P⬍.001) and lighter (2540 g [2410 –2695 g] vs 3640 g [3315–3895 g]; P⬍ .001) than AGA neonates, and their lower ponderal indices (2.46 g/cm3[2.29 –2.62 g/cm3] vs 2.77 g/cm3 [2.57–2.90 g/cm3];P⬍.001) indicate that they were also slightly thinner (Table 1). Reported parental age and height were not different between groups (Table 1); however, weight gain during pregnancy was lower in SGA mothers compared with AGA mothers (11 kg [8 –15 kg] vs 14 kg [10 –18 kg];P⬍ .05).
Forty-eight hours after birth (Table 2), SGA infants had lower blood glucose levels than AGA infants (3.6 mmol/L [2.9 – 4.1 mmol/L] vs 3.9 mmol/L [3.6 – 4.6 mmol/L]; P ⬍ .001). SGA infants also had lower plasma insulin (31.3 pmol/L [20.8 – 47.9 pmol/L] vs 62.5 pmol/L [53.5–154.9 pmol/L]; P ⬍ .001) and C-peptide levels (47.9 pmol/L [16.5–94.1 pmol/L] vs 199.7 pmol/L [72.6 –290.4 pmol/L]; P ⬍ .001) than AGA infants.
AGA infants (84% [52–158%] vs 136% [90 –238%]; P ⬍ .05; Fig 1).
Plasma FFA levels in SGA neonates were almost double the levels in AGA newborns (0.72 mEq/L [0.43–1.00 mEq/L] vs 0.33 mEq/L [0.26 – 0.54 mEq/ L];P⬍.001), and bOH-B levels were 5 times higher in SGA than in AGA infants (0.41 mEq/L [0.15– 0.91 mEq/L] vs 0.09 mEq/L [0.05– 0.13 mEq/L]; P ⬍ .001). In addition, SGA newborns displayed higher FFA/insulin ratio than AGA infants (2.4 [0.9 – 4.4] vs 0.4 [0.3–1.3];P ⬍ .001), and the same was observed for the bOH-B/insulin ratio (12.7 [3.0 –37.4] vs 1.5 [0.5–3.2]; P ⬍ .001). Both plasma FFA and bOH-B levels were inversely correlated with insulin levels (FFA:r⫽ ⫺0.292;P⬍.001; bOH-B:r⫽ ⫺0.337;P⬍ .001).
Plasma IGFBP-1 levels were significantly higher in SGA infants compared with AGA newborns (5.1 nmol/L [4.4 – 6.7 nmol/L] vs 2.9 nmol/L [1.4 – 4.2 nmol/L];P ⬍ .001). The IGFBP-1/insulin ratio was also higher in SGA infants (0.16 [0.09 – 0.29] vs 0.04 [0.01– 0.07];P⬍.001). No difference in plasma corti-sol was found (SGA: 231.8 nmol/L [162.8 –378.1 nmol/L]; AGA: 191.8 nmol/L [129.7– 436.1 nmol/ L]).
Plasma concentrations of SHBG and leptin were analyzed separately by gender because of previously reported differences in these parameters (Table 2). For SHBG, there were no differences between SGA and AGA in both boys (40.8 nmol/L [30.5–54.8 nmol/L] vs 42.1 nmol/L [24.6 – 64.3 nmol/L]) and girls (37.7 nmol/L [29.8 –50.7 nmol/L] vs 42.8 nmol/L [34.7– 60.1 nmol/L]). In addition, no corre-lation was observed between plasma insulin and SHBG levels. Plasma leptin concentrations were much lower in SGA than in AGA infants (13.1 pmol/L [3.1–26.6 pmol/L] vs 153.4 pmol/L [60.0 – 287.5 pmol/L];P⬍ .001). Leptin levels were higher in girls both in SGA (18.8 pmol/L [6.3–31.3 pmol/L] vs 6.3 pmol/L [3.1–18.8 pmol/L]; P ⬍ .001) and in AGA newborns (200.0 pmol/L [119.4 – 423.1 pmol/L] vs 106.9 pmol/L [31.3–231.3 pmol/L]; P ⬍ .001). None of the remaining metabolic measures showed any difference between genders.
When used as a continuous variable, ponderal in-dex was positively correlated with C-peptide (Spear-man⫽0.191,P⫽.014) and leptin levels (Spearman
⫽0.381,P⬍.001). A negative correlation between ponderal index and IGFBP-1 (Spearman⫽ ⫺0.230, P⬍ .01) and FFA levels (Spearman⫽ ⫺0.212,P⬍ .01) was also observed.
TABLE 1. Clinical Data from Parents, Pregnancies, and Newborns
SGA AGA
n Median
[Interquartile Range]
n Median
[Interquartile Range]
Maternal age (y) 135 24 [19–31] 33 27 [21–33]
Paternal age (y) 129 27 [22–34] 31 31 [25–37]
Maternal height (cm) 136 155 [152–159] 33 156 [153–161]
Paternal height (cm) 84 170 [163–174] 29 170 [164–173]
Weight gain during pregnancy (kg)
122 11.0 [8.0–15.0]* 32 14.0 [10.0–18.0]
Gestational age 135 39 [38–39] 33 39 [38–40]
Birth weight (g) 135 2540 [2410–2695]* 33 3640 [3315–3895]
Length (cm) 134 47.0 [45.7–48.0]* 33 50.0 [50.0–51.8]
Ponderal index (g/m3) 134 2.46 [2.29–2.62]* 33 2.77 [2.57–2.90]
Head circumference (cm) 130 32.5 [32.0–33.5]* 33 35.0 [34.0–36.0]
*P⬍.05. †P⬍.001.
TABLE 2. Laboratory From SGA and AGA Newborns 48 Hours After Birth
SGA AGA
n Median
[Interquartile Range]
n Median
[Interquartile Range]
Blood glucose (mmol/L) 121 3.6 [2.9–4.1]* 31 3.9 [3.6–4.6]
Insulin (pmol/L) 133 31.3 [20.8–47.9]* 33 62.5 [53.5–154.9]
G/I ratio (mg/dL/uIU/mL) 119 13.9 [8.6–19.1]* 29 8.2 [4.6–14.1]
C-peptide (pmol/L) 132 47.9 [16.5–94.1]* 34 199.7 [72.6–290.4]
Cortisol (nmol/L) 133 231.8 [162.8–378.1] 34 191.8 [129.7–436.1]
IGFBP-1 (nmol/L) 133 5.1 [4.4–6.7]* 34 2.9 [1.4–4.2]
FFA (mEq/L) 129 0.72 [0.43–1.00]* 32 0.33 [0.26–0.54]
bOH-B (mEq/L) 124 0.41 [0.15–0.91]* 32 0.09 [0.05–0.13]
Leptin (pmol/L) 133 13.1 [3.1–26.6]* 34 153.4 [60.0–287.5]
Boys 42 6.3 [3.1–18.8]* 19 106.9 [31.3–231.3]
Girls 90 18.8 [6.3–31.3]* 15 200.0 [119.4–423.1]
SHBG (nmol/L) 133 38.3 [30.1–50.9] 34 42.5 [28.0–62.9]
Boys 42 40.8 [30.5–54.8] 19 42.1 [24.6–64.3]
Girls 90 37.7 [29.8–50.7] 15 42.8 [34.7–60.1]
DISCUSSION
Early consequences of LBW have been recognized for a long time, with a strong emphasis on acute metabolic complications.17 However, an integral as-sessment of the effects of LBW on intermediate me-tabolism shortly after birth was still lacking. Our findings indicate that glucose metabolism is modi-fied in SGA newborns 48 hours after birth, with significantly lower plasma glucose and insulin levels than AGA infants. Remarkably, this occurs in the absence of perinatal complications, ie, in otherwise healthy infants born at full term.
Our observations are in accordance with a number of animal studies indicating that glucose metabolism and insulin action are profoundly modified in situa-tions in which a low birth weight is present. Assess-ment of glucose metabolism in the growth-retarded lamb shows a long-term tendency to hypoglycemia and hypoinsulinemia, with an increased G/I ratio.18 The same has been observed in the growth-restricted rat, which in addition displays a significant -cell hypoplasia.19,20 Nevertheless, analysis of glucose
metabolism in the newborn should be taken cau-tiously: first-phase insulin release appears only 12 hours after birth in the neonatal lamb, and full closed-loop glucose homeostasis is thought to be achieved in this model after 5 days of postnatal life.18
Studies in humans have resulted in similar conclu-sions. Economides et al21 measured plasma glucose and insulin in third-trimester SGA and AGA fetuses by chordocentesis. They found lower glucose and insulin, as well as a higher G/I ratio in growth-retarded fetuses. Hawdon et al12,22–24also examined some aspects of neonatal glucose metabolism in the SGA infant. They found lower plasma glucose levels in SGA newborns only at birth (as measured in cord blood) but not during the following days. They also found higher plasma lactate, pyruvate, glycerol, and FFA levels in SGA newborns within the first 6 hours of life. However, starting from the second day after birth, these gluconeogenic substrates were lower in SGA than in AGA infants, which was attributed to a higher caloric intake as a result of hospital care
tices.22,23 Importantly, these authors did not find a significant correlation between blood glucose and plasma insulin/C-peptide levels. This precluded any conclusion regarding insulin sensitivity and/or se-cretion in the neonatal period.22–24
In contrast to Hawdon et al, we did find such a correlation, which may be attributable to our larger sample size, as well as stricter inclusion criteria and tighter time frame. This correlation may be inter-preted as a result of full closed-loop control of insulin secretion and suggests that G/I ratio and HOMA might be useful parameters for evaluating insulin sensitivity in neonates. We found that SGA infants, as compared with AGA newborns, during the third day of life seem to be more insulin sensitive.
Unfortunately, we could not establish whether this pattern is maintained during the first week of post-natal life, because of local hospital practices encour-aging early discharge after delivery. Nonetheless, results from Hawdon et al12,22–24 indicate that after 48 hours of life, the acute metabolic modifications induced by parturition (possibly mediated by corti-sol and catecholamines) have already subsided. Therefore, it is possible that our findings reflect met-abolic modifications that may persist after a normal glucose supply is restored.
Besides controlling glucose concentrations, insulin has other metabolic actions that were also modified in SGA newborns. Plasma FFA and bOH-B levels, which are negatively regulated by insulin, were higher in SGA infants than in AGA newborns. This finding is somewhat difficult to interpret considering insulin secretion only: both FFA/insulin and bOH-B/insulin ratios were also higher in SGA infants. Therefore, lipolysis and ketogenesis in SGA new-borns seem to be less inhibited by insulin than in AGA infants. This might result from the action of insulin-antagonizing hormones, particularly in the presence of lower glucose and insulin levels. In fact, it has been shown that SGA newborns have higher plasma growth hormone (GH) and lower IGF-I levels than AGA infants during the first week of life.11,14 GH is a potent lipolytic and ketogenic hormone, and it has been proposed to protect the fetal and neonatal brain from hypoglycemia.25
IGFBP-1 is a sensitive marker of insulin action on the hepatocyte, and its expression is both potently and rapidly downregulated by insulin.10Our results show that SGA infants have higher IGFBP-1 levels than AGA newborns, which could not be explained by lower plasma insulin because the IGFBP-1/insu-lin ratio was also higher in SGA neonates. Higher plasma GH levels in this group may be again con-tributing to increased hepatic expression of IGFBP-1.11,14
Regarding SHBG, another hepatic protein regu-lated by insulin, Simmons26reported in newborns a negative correlation between cord blood insulin and serum SHBG levels, in both boys and girls. In our group, we did not find any difference in plasma SHBG between SGA and AGA infants (either boys or girls). It is possible that in presence of lower insulin levels, as those observed in SGA newborns, other factors (eg, sex steroids) might be more potent
reg-ulators of SHBG than insulin. Taken together, our observations on IGFBP-1 and SHBG levels suggest that hepatic insulin sensitivity, in contrast to periph-eral, may not be increased in SGA infants shortly after birth.
Plasma leptin has been repeatedly found to corre-late with adipose mass,13 and that is confirmed by our results. It is interesting that the previously re-ported sex differences in leptin concentrations are clearly present 48 hours after birth.
Our findings highlight the complexity of the met-abolic adaptation in SGA neonates, as evident shortly after birth. Regarding glucose metabolism, the combination of increased peripheral insulin sen-sitivity and reduced insulin secretion in SGA new-borns seems to be adequate in conditions of limited nutrient availability and reduced energy stores. This may be particularly relevant during the first hours of extrauterine life, characterized by an intense catabo-lism. However, because these modifications are still present after 48 hours of free access to nutrients, it might be possible that some of them persist in the long term.
Our data indicate that insulin actions on lipolysis, ketogenesis, and IGFBP-1 secretion were not in-creased. As mentioned, lower IGF-I and higher GH levels, consistently reported in SGA infants, may explain these latter findings. However, they might also be expected to result in reduced sensitivity to insulin with respect to glucose uptake, which we did not observe.
To our knowledge, this is the first large study specifically designed to assess changes in intermedi-ate metabolism in SGA newborns. In particular, we studied breastfed infants during a very short time frame (48 hours after delivery), whereas previous reports include infants within the first 211or 712,22–24 days of life. Nonetheless, it should be noted that all newborns in our cohort were delivered at full term. Therefore, our observations may not reflect meta-bolic adaptation in infants exposed to more adverse conditions in utero, who are usually delivered ear-lier.
Moreover, it has been proposed that the results of prenatal growth retardation, as evident in SGA new-borns, are modified by events during early postnatal life, as a result of an accelerated growth in these children (the “catch-up growth” hypothesis).27 This idea has received support from a number of studies showing that the metabolic consequences of LBW are more evident in individuals who become obese dur-ing childhood.3In addition, it has been shown that SGA children are at a higher risk of obesity.28In the long term, this “adiposity rebound” could overcome the effects of LBW observed at birth and lead to the development of insulin resistance. At present, there is only 1 prospective study (the ALSPAC cohort in the United Kingdom)14,28 analyzing the combined effects of LBW and weight gain on sensitivity to insulin. Critically, in this cohort, children were not metabolically studied during early infancy, thus lim-iting the chance to detect such interaction.
for the present study will also participate in a yearly follow-up, assessing both changes in glucose metab-olism and anthropometric variables.
ACKNOWLEDGMENTS
This work was supported by grant 1000939 from FONDECYT, Chile. Dr Bazaes is supported by a doctoral fellowship from Fundacio´n Andes, Chile.
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SAME OLD, SAME OLD
“It’s pretty astounding to go from a year ago thinking this is one of the most benign drugs to a 180 degree turn in the opposite direction.”
Dr Susan Hendrix, a gynecologist, on the government decision to require warn-ing labels on drugs containwarn-ing estrogen.
New York Times.January 9, 2003
DOI: 10.1542/peds.111.4.804
2003;111;804
Pediatrics
Alegría, Germán Íñiguez, Ken K. Ong, David B. Dunger and M. Verónica Mericq
Rodrigo A. Bazaes, Teresa E. Salazar, Enrica Pittaluga, Verónica Peña, Angélica
of Age
Glucose and Lipid Metabolism in Small For Gestational Age Infants at 48 Hours
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DOI: 10.1542/peds.111.4.804
2003;111;804
Pediatrics
Alegría, Germán Íñiguez, Ken K. Ong, David B. Dunger and M. Verónica Mericq
Rodrigo A. Bazaes, Teresa E. Salazar, Enrica Pittaluga, Verónica Peña, Angélica
of Age
Glucose and Lipid Metabolism in Small For Gestational Age Infants at 48 Hours
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