EFFECT OF ORAL LIPID ADMINISTRATION ON GLUCOSE HOMEOSTASIS IN SMALL-FOR-GESTATIONAL-AGE INFANTS

ABSTRACT. The metabolic effect of feeding with 1.3 g/kg bw lipids (67% medium chain triglycerides) was studied in 15 small-for-gestational age (SGA) term infants. It was compared to a control group of 7 SGA term infants, to 7 term infants with an appropriate birth weight (AGA) and to 7 AGA preterm infants. Plasma glucose concentration rose from ( M ±SE) 3.6±0.2 to 4.4±0.3 mmol/1 at 30 min in SGA term infants ( p <0.01). A similar increase was observed in AGA term and preterm infants. The lipid load produced no change in plasma glucagon concentration but a significant increase in insulin/glucagon molar ratio was observed in AGA term infants only. In term SGA infants, the disappearance rate of glucose in plasma after the lipid load was similar to the control: 1.24% per min. The evolution of blood pyruvate and lactate concentration was not modified by the lipid load. Despite lower concentrations of free fatty acids and ketone bodies (KB) in SGA infants than in AGA term infants, the lipid load induced a 120% increase of ketone bodies in SGA infants and a 40% increase only in AGA infants. These data show that these lipids produce a hyperglycemic response in SGA infants as in AGA infants without any change of the disappearance rate of glucose. They suggest that these lipids can stimulate gluconeogenesis and ketogenesis in SGA infants.     

Fatty Acid Composition of Subcutaneous Adipose Tissue in Mother-Infant Pairs

ABSTRACT. The fatty acid composition of microsamples from 10 AGA term, 8 SGA term, 7 AGA preterm and 4 SGA preterm, 2–4 day old infants and their mothers were analyzed. In AGA preterm newborns the mean percent of palmitic and stearic acid was lower and the mean percent of linoleic acid was higher than in AGA term infants indicating that there is an increase in fatty acids derived by synthesis from glucose throughout gestation. SGA infants had relative amounts of palmitic and stearic acid similar to what was found in AGA term infants. This indicates that the enzymes involved in synthesis of fatty acids from glucose are intact in intrauterine growth retardation (IUGR). The absolute amount of adipose tissue and fatty acids, however, is smaller in SGA infants due to a reduced availability of glucose in IUGR gestation. No differences were found in the fatty acid composition of subcutaneous adipose tissue from the mothers in the 4 groups. All mothers had a lower mean percent of palmitic and stearic acid and a higher mean percent of oleic and linoleic acid than their infants, ensuring a transplacental gradient to the fetus of this latter essential fatty acid. The fatty acid composition of plasma free fatty acids generally reflected the composition of the subcutaneous adipose tissue in the infants.     

Fatty acid composition of subcutaneous adipose tissue in mother-infant pairs

The fatty acid composition of microsamples from 10 AGA term, 8 SGA term, 7 AGA preterm and 4 SGA preterm, 2-4 day old infants and their mothers were analyzed. In AGA preterm newborns the mean percent of palmitic and stearic acid was lower and the mean percent of linoleic acid was higher than in AGA term infants indicating that there is an increase in fatty acids derived by synthesis from glucose throughout gestation. SGA infants had relative amounts of palmitic and stearic acid similar to what was found in AGA term infants. This indicates that the enzymes involved in synthesis of fatty acids from glucose are intact in intrauterine growth retardation (IUGR). The absolute amount of adipose tissue and fatty acids, however, is smaller in SGA infants due to a reduced availability of glucose in IUGR gestation. No differences were found in the fatty acid composition of subcutaneous adipose tissue from the mothers in the 4 groups. All mothers had a lower mean percent of palmitic and stearic acid and a higher mean percent of oleic and linoleic acid than their infants, ensuring a transplacental gradient to the fetus of this latter essential fatty acid. The fatty acid composition of plasma free fatty acids generally reflected the composition of the subcutaneous adipose tissue in the infants.     

Glucose production and oxidation in preterm infants during total parenteral nutrition

During total parenteral nutrition in preterm infants, glucose may be infused at high rates, but it is not known if the endogenous glucose production is fully suppressed under these circumstances. Eight preterm appropriate for gestational age (AGA) (birth wt: 1613 +/- 151 g, gestational age: 31.1 +/- 1.5 wk) and eight preterm small for gestational age (SGA) newborn infants (1185 +/- 241 g, 32.9 +/- 2.6 wk) receiving a glucose infusion rate of 7.55 +/- 0.56 and 8.16 +/- 0.65 mg/kg.min, respectively, were studied during continuous total parenteral nutrition at postnatal d 8. Glucose oxidation rate was determined with a primed constant infusion of [U-13C] glucose, measuring the 13CO2 production in breath gas by isotope ratio mass spectrometry and the glucose production rate in plasma by gas chromatography mass spectrometry. In breath gas of AGA and SGA infants, 60 and 65%, respectively, of the infused tracer appeared as 13CO2. The glucose production rates were 7.97 +/- 1.61 and 8.12 +/- 1.84 mg/kg.min in AGA and SGA infants, respectively, indicating that no significant endogenous glucose production occurred. The glucose oxidation calculated from the glucose production and 13CO2 production was 4.74 +/- 0.99 mg/kg.min in AGA infants and was significantly different from the carbohydrate oxidation rate of 6.62 +/- 1.23 mg/kg.min measured by simultaneous indirect calorimetry. In SGA infants, however, the glucose and carbohydrate oxidation rates were not significantly different at 5.33 +/- 1.56 and 6.16 +/- 2.45 mg/kg.min. It is concluded that 1-wk-old AGA or SGA preterm infants receiving total parenteral nutrition of 80 kcal/kg.d produce no endogenous glucose and their glucose oxidation rates are similar at 63-65% of the glucose infused. It is suggested that the significant difference between glucose and carbohydrate oxidation rates observed in AGA but not in SGA infants is due either to a higher rate of lipogenesis from carbohydrates, or, less likely, to a higher rate of glycogen oxidation.     

Glycerol metabolism and triglyceride-fatty acid cycling in the human newborn: effect of maternal diabetes and intrauterine growth retardation.

Kinetics of glycerol metabolism and triglyceride/fatty acid cycling were quantified in 12 healthy, normal, appropriate-for-gestational-age (AGA) infants, eight small-for-gestational-age (SGA) infants, and five infants of insulin-dependent diabetic mothers (IDM) at less than 48 h of age. Stable isotope-labeled [2-13C]glycerol and [6,6-2H2]glucose in combination with indirect respiratory calorimetry were used. The tracers were used as constant rate infusion and steady state isotopic enrichment of glucose, glycerol, and bicarbonate was measured by mass spectrometric methods. After a 7- to 9-h fast, the plasma glucose, glycerol, and FFA concentrations were similar in the AGA and IDM groups. In the SGA group, the plasma glucose concentration was significantly lower than that in the AGA group throughout the study, but plasma FFA and glycerol concentrations were not different from those in the AGA infants. Plasma betahydroxybutyrate concentration was significantly elevated in the AGA group compared with IDM and SGA infants (AGA 0.59 +/- 0.39, SGA 0.35 +/- 0.09, IDM 0.33 +/- 0.21 mmol/L; mean +/- SD). The rate of appearance of glycerol was significantly elevated (p less than 0.05) in SGA infants (AGA 9.47 +/- 2.11, IDM 9.55 +/- 2.14, SGA 12.15 +/- 3.87 mumol/kg.min). Between 80 and 90% of glycerol turnover was converted to glucose, accounting for 20% of glucose turnover with no significant difference in the three groups. Approximately 35% of glycerol carbon was recovered in the bicarbonate (CO2) pool. Less than 5% of CO2 carbon was derived from glycerol. Estimation of triglyceride-fatty acid cycle revealed that the triglyceride energy mobilized was increased in SGA infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Whole blood fatty acid composition differs in term versus mildly preterm infants: small versus matched appropriate for gestational age

To investigate the associations between whole blood fatty acid (FA) profile and restricted intrauterine growth, any small for gestational age (SGA) infant born in our maternity ward through 1 y was matched with two appropriate for gestational age (AGA), of the same GA +/- 0.5 wk, infants, further subdivided into term and preterm. Whole blood was collected at d 4 on a strip and FA % composition assessed by means of gas chromatography. The whole sample consisted of 28 SGA versus 56 AGA born at term and 20 SGA versus 40 AGA born preterm at around 35 wks. Parent FA of the n-6 and n-3 FA families were higher in preterm groups, whereas docosahexaenoic acid was higher in term AGA (median % values, 3.9 versus 3.7 in term SGA, 2.8 in preterm AGA, and 2.5 in preterm SGA, p < 0.001). Term AGA had markedly higher values for the docosahexaenoic acid/alpha-linolenic acid ratio (median value: 91, versus 18 in term SGA, 12 in preterm AGA, and 10 in preterm SGA, p < 0.001). Term SGA had significantly lower levels of total monounsaturated FA and higher levels of eicosapentaenoic acid. Therefore, the 4-d whole blood FA pattern is associated with both GA and birth weight.     

Decreased bone mineral content in small-for-gestational-age infants compared with appropriate-for-gestational-age infants: normal serum 25-hydroxyvitamin D and decreasing parathyroid hormone

Bone mineral content was determined by photon absorptiometry, adapted for use in neonates, in 23 small-for-gestational-age (SGA) infants of 31 to 42 weeks of gestational age, for 12 weeks. At birth, term SGA infants had lower bone mineral content than term appropriate-for-gestational-age (AGA) infants; postnatal increase in bone mineral content was slow and lagged significantly behind that of term AGA infants. Preterm SGA infants had bone mineral content that was similar to that of preterm AGA infants at birth; postnatal bone mineral content was similar to that of preterm AGA infants, but was decreased compared with the expected intrauterine bone mineral content. Serum 25-hydroxyvitamin D concentrations and parathyroid hormone levels were the same for SGA and AGA infants. Serum 25-hydroxyvitamin D concentrations decreased slightly with postnatal age and remained within normal limits. Serum parathyroid hormone concentrations decreased in both SGA and AGA infants and reached undetectable levels at 10 to 12 weeks of age.     

Glucose kinetics in glucose-infused small for gestational age infants

To evaluate the maturation of glucose homeostasis in the small for gestational age (SGA) neonate, glucose kinetics were measured with 78% enriched D-[U-13C]glucose by the prime plus constant infusion technique in nine SGA infants and compared with the rate obtained in seven term appropriate for gestational age infants and 13 preterm appropriate for gestational age infants. All of the infants had received glucose intravenously from birth and continued to receive the glucose infusion throughout the study. Fasting plasma glucose and plasma insulin concentrations and plasma [13/12C]ratios were measured during the steady state turnover period. From this data, the glucose production rate was derived. During the turnover period, the SGA and both groups of appropriate for gestational age infants had similar average plasma glucose, plasma insulin, plasma glucagon concentrations, and similar persistent rates of glucose production during glucose infusion. We conclude that under stimulation of glucose infusion, the SGA infant and his AGA counterpart have similar hormonal regulatory responses as well as functional integrity in handling glucose during the second day after birth.     

Macromolecular absorption in small-for-gestational-age infants

Using human alpha-lactalbumin as a marker protein, macromolecular absorption was studied in 40 preterm infants, appropriate for gestational age (AGA), in 12 AGA term infants and in 18 preterm infants, small for gestational age (SGA). The absorption of alpha-lactalbumin was measured as concentration in serum after a human milk feed and expressed as micrograms alpha-lactalbumin/l serum/l human milk/kg body weight on day 7, 14, 21 and 42 after delivery. The serum concentration of alpha-lactalbumin was correlated negatively with maturity and postnatal age. In the SGA infants, the concentration of alpha-lactalbumin was significantly higher than in the AGA infants of similar gestational age. The data show that intrauterine growth retardation causes a delayed postnatal decrease in macromolecular absorption. This may indicate delayed intestinal maturation.     

Identification of lymphocyte subsets in the newborn using a variety of monoclonal antibodies.

Using a small sample of peripheral venous blood, the normal range for lymphocyte subpopulations (T-cell, B-cell, T-suppressor cell, and T-helper cell) was defined in non-infected preterm and term infants. Lymphocyte subsets were identified using a variety of monoclonal antisera, and analysis was performed using a fluorescent activated cell sorter. Such methods allow an objective assessment of absolute numbers of cells per unit volume of whole blood. There was no significant difference in absolute numbers of lymphocyte subsets between term and preterm appropriate for gestational age (AGA) infants. Infants who were small for gestational age (SGA) had a significant deficiency in absolute numbers of total T-cells, helper and inducer T-lymphocytes, and B-cells compared with both term and preterm AGA infants. All newborn infants (term and preterm; AGA and SGA) had a highly significant increase in absolute numbers of both helper and suppressor T-lymphocytes compared with normal adults.     

Growth of 519 Small for Gestational Age Infants during the First Two Years of Life

ABSTRACT. The physical growth of 519 small for gestational age infants (SGA), with a birth weight below the 10th percentile on our own growth curve, born in the region of University Central Hospital of Turku during the period June 1,1981-May 31, 1982, was studied. The study population consists of 4 517 term, appropriate for gestational age (AGA) infants, 488 term SGA infants, 320 preterm AGA infants and 31 preterm SGA infants. The degree of intrauterine growth retardation (IUGR) seemed to have an effect on physical growth in term SGA infants. Those term SGA infants with a low Ponderal Index (PI) (type II) were taller and had a larger head circumference at the age of 24 months than term SGA infants with adequate PI (type I). Among the preterm SGA infants the degree of IUGR seemed to have no effect on later growth. Smoking is still one of the main risk factors associated with poor intrauterine growth. In this study we also found that smoking has an effect on later growth; the children of smoking mothers were smaller than those of non-smoking mothers in the AGA group. Among the SGA infants the infants of non-smoking mothers were bigger than those of smoking mothers. This difference could be explained by other factors associated with SGA. We found that in spite of the catch-up growth during the first months, 26% of the severely SGA infants (birth weight below the 2.5th percentile) still had a weight below the 2.5th percentile at the age of 24 months.     

Lipid metabolism in the neonate. III. The ketogenic effect of Intralipid infusion in the neonate.

The ketogenic potential of Intralipid was studied in two groups of infants: 12 were SGA and 15 AGA; all were clinically stable and less than 48 hours of age. During four-hour Intralipid tolerance tests, the SGA infants achieved significantly higher plasma TG and FFA levels. Both groups of infants significantly increased the concentration of ketone bodies; however, there was no difference in the levels achieved. In view of the slower clearance rate of TG and the higher levels of FFA in SGA infants, it is speculated that in addition to a possible defective lipoprotein lipase system and a decrease in number and size of the adipose cells, beta-oxidation of FFA to ketones may be occurring at a slower rate. The generation of high levels of ketones during Intralipid infusion period in both groups of infants indicates that SGA infants can handle ketone bodies as readily as AGA infants.     

Intrauterine growth restriction and postnatal steroid treatment effects on insulin sensitivity in preterm neonates

OBJECTIVES: To study whether intrauterine growth restriction (IUGR) is associated with decreased sensitivity to the main fetal growth factor, insulin, and the effect of glucocorticoid therapy on insulin sensitivity in preterm infants. STUDY DESIGN: Newborn infants with a birth weight (BW) of< 1500 g were classified as appropriate for gestational age ([AGA], BW within +/- 1 SD, n = 10), or small for gestational age ([SGA], BW <-2 SD, n = 13); 5 AGA infants and 8 SGA infants received systemic steroids. An abbreviated modified minimal model test was performed, consisting of sequential blood samples for glucose and insulin assays, and intravenous infusions of 0.3 g/kg glucose and 0.02 U/kg regular human insulin. The insulin sensitivity index (S(I)) was calculated using a computer program. RESULTS: The basal insulin/glucose ratio (I/G) and S(I) did not differ between the AGA and SGA groups. Steroids did not influence the I/G nor the S(I) of AGA infants (10.2 +/- 6.7 vs 8.2 +/- 2.3), but decreased the S(I) in the SGA group (12.2 +/- 5.1 vs 5.3 +/- 2.7, P <.05). CONCLUSIONS: Insulin sensitivity of neonates can be measured by the modified minimal model. IUGR is not associated with impaired fetal glucose tolerance. Early neonatal steroid treatment decreases insulin sensitivity in SGA infants, which may contribute to their risk of having hyperglycemia.     

Catch-up growth in appropriate- or small-for-gestational age preterm infants

The aim was to evaluate postnatal growth of preterm infants in childhood and to determine factors that have an effect on catch-up growth (CUG). Ninety-six (42F, 54M) preterm born children with a gestational age of 32.6+/-2.9 weeks and birth weight of 1815+/-668 g were evaluated at age 4.7+/-1.1 years. Preterm children with birth weight and/or length below 10th percentile were accepted as small-for-gestational age (SGA) and those above as appropriate-for-gestational age (AGA). Height SDS was similar (-0.5+/-1.0) in preterm AGA and SGA children. Both groups had low body mass index (BMI) SDS (-0.6+/-1.4 and -1.0+/-1.5, respectively). Of the preterm SGA children, 65.8% showed a CUG in height and 3.8% catch- down growth. These rates were 24.6% and 33.5% in preterm AGA children. CUG in height was best explained by birth length and mother's height and CUG in weight by birth weight and mother's weight. In conclusion, although most of the preterm SGA children show CUG, they reach a compromised height in childhood. A number of preterm AGA children show a catch-down growth.     

Assessment of proportional growth of very low birth weight infants fed banked human milk

Twenty appropriate (mean +/- S.D., gestational age (AGA): 29.9 +/- 1.5 weeks) and 15 small (GA: 34.6 +/- 2.4 weeks) for gestational age (SGA) very low birth weight infants fed banked mature human milk were studied until term for anthropometric parameters: midarm (MAC), chest (CC), head (HC) circumferences, triceps (TSKF) and subscapular (SSKF) skinfold thickness recorded at 15 and 60 s, dynamic skinfold (delta % SKF), muscle (AMA) and fat (AFA) areas, weight and length. In AGA infants, all the parameters at term were significantly lower in extrauterine (EUL) that in intrauterine life (IUL). At term the relative proportion of AFA to total arm area was increased in EUL compared to IUL both in AGA (25.87 +/- 3.8 vs. 23.26 +/- 1.27% respectively, P less than 0.01) and in SGA infants (21.89 +/- 4.63 vs. 18.81 +/- 3.9 respectively, P less than 0.05). SGA infants showed a similar growth in EUL compared to IUL, and a significantly lower AMA and AFA than in AGA infants in EUL. Although HC was in both infants below the 10th centile at term, the ratio weight/HC2 suggests a relative preservation of head growth in EUL compared to IUL (AGA: 20.72 less than 0.87 vs. 22.65 +/- 1.46 respectively, P less than 0.001; SGA; 20.82 +/- 1.16 vs. 21.62 +/- 1.86 respectively, NS). Delta %SKF were negatively correlated with post-conceptional age suggesting a loss of extracellular water in AGA (delta %TSKF: r = -0.287, P less than 0.02) and in SGA infants (delta %TSKF: r = -0.301, P less than 0.02; delta %SSKF: r = -0.316, P less than 0.02). An intrauterine model of discrimination between AGA and SGA infants does not apply to EUL. An equation was established in SGA infants with the best discriminant parameters giving a predictive post-conceptional age: post-conceptual age (PCA) (weeks) = 0.276 HC (cm) + 0.723 CC (cm) - 0.122 MAC (cm) + 0.5 TSKF (mm) + 10.173, (r = 0.867, P less than 0.001) allowing a clear discrimination between AGA and SGA infants. These results suggest that infants show quite different growth patterns between IUL and EUL both for AGA and SGA infants.     

Plasma lipids, phospholipid fatty acids and indices of glycaemia in 10-year-old children born as small-for-gestational-age or preterm infants

Low birthweight has been epidemiologically associated with unfavourable plasma lipid profiles and enhanced risk of cardiovascular morbidity in adulthood. Plasma lipids, lipoprotein cholesterols, apolipoproteins, fatty acid composition of plasma phospholipids and basic indices of glycaemia were investigated in 10-y-old children born with similarly low birthweights as small-for-gestational-age (SGA; n = 16) or preterm infants (n = 16). Plasma total cholesterol (4.32 +/- 0.57 vs 4.60 +/- 0.52, mmol l(-1), mean +/- SD, SGA vs preterm subjects), low-density lipoprotein cholesterol (2.54 +/- 0.51 vs 2.65 +/- 0.51) and high-density lipoprotein cholesterol (1.61 +/- 0.25 vs 1.76 +/- 0.18) concentrations did not differ between the 2 groups. There was no difference in plasma triacylglycerol, apolipoprotein A-I and B, insulin and glucose concentrations or phospholipid fatty acid values. There was no correlation between indices of lipid and carbohydrate metabolism. In conclusion, plasma lipid profiles and basic indices of glycaemia are not different in 10-y-old children born with similarly low birthweights as SGA or preterm infants.     

Factors associated with weaning in full term and preterm infants

BACKGROUND: The optimal age for the introduction of solid foods (weaning) in infants is poorly researched yet may have implications for both short and longer term health. Many parents do not comply with current guidelines. OBJECTIVE: To determine and compare the age at weaning in term appropriate size for gestational age (AGA), small for gestational age (SGA), and preterm infants, and factors associated with weaning age in these groups. DESIGN: Data from > 2000 infants from seven prospective randomised trails conducted between 1990 and 1997 were used to address the objectives. RESULTS: Most infants, term AGA, SGA, or preterm, received solids before 4 months of age. Only 2% of term infants were exclusively breast fed to 6 months of age. Formula fed infants received solids on average two weeks earlier than breast fed infants. Preterm infants were significantly more likely, and term SGA infants less likely, to receive solids at both 6 and 12 weeks after term than term AGA infants. Weight at 6 weeks of age was a stronger predictor of earlier weaning than either birth weight or weight gain from birth to 6 weeks in term infants. In preterm infants, formula feeding and maternal smoking were associated with earlier weaning. CONCLUSIONS: Infants born in the mid 1990s were weaned on average earlier than the 4 months recommended by the Department of Health. Earlier weaning was associated with less positive health behaviours. Further research is required to provide evidence based weaning guidelines, including specific advice for SGA and preterm infants, and to investigate longer term consequences of weaning practices.     

High risk appropriate for gestational age (AGA) and small for gestational age (SGA) preterm infants. Neurological handicap and developmental abnormalities at five years of age

Outcome at five years of age of 110 high risk AGA, 71 high risk SGA preterm infants with similar birth weight and 102 term control infants was studied. Mean IQ in the 3 groups was not statistically different. Major handicaps were found in 16.3% of the AGA and in 8.5% of the SGA preterms. There was no major handicap among the controls. Minor neurodevelopmental abnormalities were present in 25.6% of AGA, 28.2% of SGA and 19.6% of controls. The types of neurodevelopmental handicaps were different in the 3 groups and generally more severe in the AGA group. All the major handicaps among AGA preterms were found in children with severe neonatal complications. In the SGA preterm group, only 1/3 of the major handicaps can be related to perinatal complications. Affective and behavior disorders were probably related in some way to neurodevelopmental achievement. This study showed that preterm infants with GA less than or equal to 32 weeks are more at risk than more mature SGA preterms with similar birth weight.     

Metabolic and endocrine events at the time of the first feed of human milk in preterm and term infants.

The first feed of breast milk given to a group of 12 term infants was previously shown to increase the levels of blood glucose and plasma insulin, growth hormone (GH), gastrin, and enteroglucagon. We have now studied the effects of the first feed of breast milk in two similar groups of preterm infants, to compare the results with those obtained for the term infant. One group of 8 preterm infants received a bolus (2.5 ml/kg) of breast milk via a nasogastric tube; the other group of 5 infants received a continuous intragastric infusion (2.5 ml/kg per hour) of breast milk. No change occurred in the concentrations of blood glucose, lactate, pyruvate, or ketone bodies, or in plasma insulin, GH, pancreatic glucagon, or enteroglucagon in either the ''bolus fed'' or the ''infusion fed'' group of preterm infants. Thus the marked metabolic and endocrine changes in term infants after the first feed do not occur in preterm infants with standard methods of feeding.     

Cardiac hypertrophy and altered hemodynamic adaptation in growth-restricted preterm infants

The objective was to elucidate hemodynamic adaptation in very low birth weight (<1500 g) infants after intrauterine growth retardation. 31 growth-retarded (SGA, birth weight <-2 SD) and 32 appropriate for gestational age (AGA, birth weight within +/- 1 SD range) infants were enrolled. In SGA infants, the diastolic diameters of the interventricular septum and the left ventricle were increased, and serum brain natriuretic peptide (BNP) was elevated. Left ventricular output (LVO) of the AGA infants increased from 150 +/- 28 to 283 +/- 82 mL/kg/min during the study (p < 0.01). The SGA infants had a higher initial LVO than the AGA infants (243 +/- 47 versus 150 +/- 28 mL/kg/min, p < 0.05), but did not show further LVO increase during the study period. Red cell (RCV) and blood (BV) volume were assessed by Hb subtype analysis, when packed donor red cells were transfused. RCV and BV did not differ between the groups initially, but RCV increased by 18% and BV by 29% in the AGA group during the first 3 d. On day 3, AGA infants had larger BV than the SGA infants (88 +/- 5 versus 73 +/- 12 mL/kg, p < 0.05). In conclusion, cardiac hypertrophy, elevated initial LVO and BNP of the SGA infants suggest increased cardiac workload after intrauterine growth retardation. Based on the BV and RCV data, blood volume regulation may also be impaired. The data suggest that SGA preterm infants may be exposed to an increased risk of circulatory failure during early adaptation.