Changes in leptin concentration during the early postnatal period: adjustment to extrauterine life?

There are substantial alterations in fuel homeostasis immediately after birth. Leptin is a putative regulator of energy metabolism. Consequently, the aim of this study was to examine whether there are changes in circulating leptin concentrations during the early postnatal period. Umbilical cord mixed blood samples were taken at delivery, and a venous blood sample was obtained at 3 d of age from 38 healthy newborn infants (20 male, 18 female; gestational age 36.3 to 41.9 wk) for analysis of leptin concentration with radioimmunoassay. Cord plasma leptin concentration was 9.7+/-5.2 microg/L (mean+/-SD), with no gender difference between male (8.6+/-4.6 microg/L) and female (10.9+/-5.6 microg/L) infants. In male newborns, cord plasma leptin concentration correlated with arm circumference (r = 0.48, p < 0.05), and in female newborns with body mass index (r = 0.62, p < 0.01), thickness of the s.c. fat (r = 0.54, p < 0.05), and arm circumference (r = 0.72, p < 0.01). By the third postnatal day, plasma leptin decreased similarly in male (to 1.8+/-0.4 microg/L, p < 0.001) and female (to 2.3+/-0.8 microg/L, p < 0.001) infants, when there was a significant gender difference in leptin levels (p = 0.01). At 3 d of age, plasma leptin correlated with weight (r = 0.49, p < 0.05) and arm circumference (r = 0.49, p < 0.05) in female but not in male newborns. In conclusion, 1) circulating leptin already correlates with adiposity at birth in female but not in male newborn infants and 2) leptin decreases markedly in both genders by the third postnatal day, and the gender difference with higher leptin levels in females develops by that time. Thus, the postnatal decrease in plasma leptin concentration may be a physiologically feasible adaptation to profound alterations in fuel homeostasis during the first days of extrauterine life.     

Iron status at 9 months of infants with low iron stores at birth

OBJECTIVE: To determine the 9-month follow-up iron status of infants born with abnormally low serum ferritin concentrations.Study design: Ten infants of >34 weeks' gestation with cord serum ferritin concentrations <5th percentile at birth (<70 microg/L) and 12 control infants with cord serum ferritin concentrations >80 microg/L had follow-up serum ferritin concentrations measured at 9 +/- 1 month of age. The mean follow-up ferritins, incidences of iron deficiency and iron-deficiency anemia, and growth rates from 0 to 12 months were compared between the two groups. RESULTS: At follow-up, the low birth ferritin group had a lower mean ferritin than the control group (30 +/- 17 vs 57 +/- 33 microg/L; P =.03), but no infant in either group had iron deficiency (serum ferritin <10 microg/L) or iron-deficiency anemia. Both groups grew equally well, but more rapid growth rates were associated with lower follow-up ferritin concentrations only in the low birth ferritin group (r = -0.52; P =.05). Both groups were predominantly breast-fed without iron supplementation before 6 months. CONCLUSIONS: Infants born with serum ferritin concentrations <5th percentile continue to have significantly lower ferritin concentrations at 9 months of age compared with infants born with normal iron status, potentially conferring a greater risk of later onset iron deficiency in the second postnatal year.     

Testosterone and estradiol concentrations in paired maternal and cord sera and their correlation with the concentration of chorionic gonadotropin.

Testosterone (T) and estradiol (E2) concentrations were determined and correlated with beta human chorionic gonadotropin (beta-HCG) concentrations in 43 paired maternal and cord sera (22 female and 21 male infants). Mean (+/- SD) maternal E2 concentrations were significantly (P less than .005) higher when the sex of the fetus was male than when the sex of the fetus was female (20.6 +/- 3.9 vs 13.5 +/- 3.2 ng/ml). Maternal T concentrations were not significantly different when related to the sex of the fetus (males, 114.8 +/- 60.7 vs females, 113.8 +/- 54.5 ng/100 ml, P greater than .1). Regression analysis did not show a significant correlation between maternal T or E2 concentrations and maternal beta-HCG concentrations. Mean cord serum T and E2 concentrations of male infants were significantly greater than that of female infants (T, 38.8 +/- 8.5 vs 25.8 +/- 7.1 ng/100 ml, P less than .005; E2, 9.1 +/- 3.3 vs 6.6 +/- 2.0 ng/ml, P less than .005). Regression analysis showed a significant (P less than .005) correlation between cord beta-HCG concentrations and E2 concentrations for male infants (r = .7) and female infants (r = .6). A significant correlation between cord beta-HCG concentrations and T concentrations was found for male infants (r = .5; P less than .01) but not for female infants (r = .3; P greater than .05). There was no correlation between maternal and infant E2 concentrations (males, r = .3, P greater than .05; females, r = .3, P greater than .2) or T concentrations (males, r = .02, P greater than 0.4; females, r = .06, P greater than .3). These data (1) confirm the sex difference in cord serum T and E2 concentrations, (2) indicate that the lower beta-HCG concentrations in mothers of male infants are associated with E2 concentrations which are greater than those in mothers of female infants, and (3) are consistent with an influence of beta-HCG on fetal T and E2 secretion.     

The Relationship between Decreased Iron Stores, Serum Iron and Neonatal Hypoglycemia in Large-for-Date Newborn Infants

ABSTRACT. We assessed the relationship between neonatal hypoglycemia and newborn iron status in 15 hypoglycemic, large-for-date newborn infants, 12 of whom were infants of diabetic mothers. These infants had significantly lower mean serum iron concentrations, ferritin concentrations, percent iron-binding saturation and calculated iron stores, and significantly higher mean transferrin concentrations, total iron-binding capacity concentrations and mid-arm circumference: head circumference ratios when compared with either 15 euglycemic large-for-date or 15 euglycemic appropriate-for-date control infants ( p < 0.001 for all comparisons). All hypoglycemic infants had ferritin concentrations below the 5th percentile as compared to 3 % of controls ( p < 0.001), and 67 % had transferrin concentrations above the 95th percentile (controls: 0 %; p < 0.001). Only the hypoglycemic infants demonstrated a significant negative linear correlation between ferritin and transferrin concentrations ( r =−0.83; p < 0.001). Decreased serum iron concentrations were associated with size at birth ( r =−0.60; p = 0.01) and with increased red cell iron ( r =−0.60; p = 0.01), implying a redistribution of iron dependent on the degree of fetal hyperglycemia and hyperinsulinemia. Infants with increased red cell iron had more profound neonatal hypoglycemia. These results show a significant association between decreased iron stores and neonatal hypoglycemia in macrosomic newborn infants associated with a significant shift of iron into red blood cells.     

Serum adiponectin concentrations in newborn infants in early postnatal life

Serum adiponectin levels were investigated in 28 small-for-gestational-age (SGA) and 34 appropriate-for-gestational-age (AGA) term neonates to examine how fetal growth correlates with adiponectin levels. A blood sample for determination of adiponectin was obtained during the first 24 h of life. The levels of serum adiponectin were significantly higher in all newborn infants than in healthy children (28.7 +/- 17.0 versus 9.3 +/- 6.1 microg/mL; p < 0.01). There was a significant difference in adiponectin levels between SGA and AGA infants (23.2 +/- 14.8 versus 33.2 +/- 17.5 microg/mL; p=0.02). For all of the newborn groups, serum adiponectin levels correlated positively with birth weight (r=0.27, p <0.05) and head circumference (r=0.30, p <0.05). There was no relationship between serum adiponectin levels and gestational age, birth length, blood glucose levels, or blood sampling time after birth. There was no gender difference in adiponectin levels in the entire newborn group (30.0 +/- 19.7 versus 28.0 +/- 15.5 microg/mL, in male and female infants). Our results suggest that hyperadiponectinemia and a positive relationship between the serum levels of adiponectin and birth weight in newborns cannot be explained by the low percentage of body fat alone. Lower adiponectin levels in SGA infants than in AGA infants are unlikely to suggest insulin resistance in intrauterine growth-retarded infants in early postnatal life but may be a predisposing factor in the future development of insulin resistance or type 2 diabetes.     

The relationship between decreased iron stores, serum iron and neonatal hypoglycemia in large-for-date newborn infants

We assessed the relationship between neonatal hypoglycemia and newborn iron status in 15 hypoglycemic, large-for-date newborn infants, 12 of whom were infants of diabetic mothers. These infants had significantly lower mean serum iron concentrations, ferritin concentrations, percent iron-binding saturation and calculated iron stores, and significantly higher mean transferrin concentrations, total iron-binding capacity concentrations and mid-arm circumference:head circumference ratios when compared with either 15 euglycemic large-for-date or 15 euglycemic appropriate-for-date control infants (p less than 0.001 for all comparisons). All hypoglycemic infants had ferritin concentrations below the 5th percentile as compared to 3% of controls (p less than 0.001), and 67% had transferrin concentrations above the 95th percentile (controls: 0%; p less than 0.001). Only the hypoglycemic infants demonstrated a significant negative linear correlation between ferritin and transferrin concentrations (r = -0.83; p less than 0.001). Decreased serum iron concentrations were associated with size at birth (r = -0.60; p = 0.01) and with increased red cell iron (r = -0.60; p = 0.01), implying a redistribution of iron dependent on the degree of fetal hyperglycemia and hyperinsulinemia. Infants with increased red cell iron had more profound neonatal hypoglycemia. These results show a significant association between decreased iron stores and neonatal hypoglycemia in macrosomic newborn infants associated with a significant shift of iron into red blood cells.     

Smoking during pregnancy--hematological observations in the newborn

Hematological values were measured in 28 newborn infants of mothers smoking 10-20 cigarettes daily during pregnancy, and in 25 infants of non-smokers. Higher hematocrit levels were found on the 1st day of life in infants of smoking mothers (60.8 +/- 5.0%, mean +/- S.D.) compared to controls (57.5 +/- 4.8%) (p less than 0.05). The hematocrit levels correlated positively with the maternal smoking level (r = 0.318, p less than 0.05) and the maternal serum thiocyanate concentrations at delivery (r = 0.389, p less than 0.01). Cord serum values for erythropoietin, serum-iron, transferrin and ferritin showed no statistically significant difference between the two groups. A significant inverse correlation was found between the hematocrit value on the 1st day of life and the cord serum ferritin concentration (r = -0.495, p less than 0.005). The present results suggest that maternal smoking stimulates fetal erythropoiesis, probably through a hypoxic effect on the fetus, dose related to the maternal smoking level. Increased erythropoiesis may cause increased iron incorporation into erythrocytes at expense of iron storage in the bone marrow and reticuloendothelial system.     

Hepatic iron storage in very low birthweight infants after multiple blood transfusions

OBJECTIVE: To investigate the effect of multiple blood transfusions on hepatic iron storage in preterm, very low birthweight (VLBW) infants. METHODS: Seventeen VLBW infants who died within the first six months of life and underwent postmortem examination were studied. Serum ferritin, iron, and total iron binding capacity were measured within the week before the infants' death. Liver iron concentration was quantitatively determined by atomic absorption spectrophotometry and semiquantitatively assessed by histochemical liver iron grading. The clinical characteristics and the iron results were compared between infants receiving < 100 ml of blood (group A) and those receiving >/= 100 ml (group B). Spearman's correlation coefficient was used to evaluate the relation between the volume of blood transfused and serum/liver iron concentrations. Statistically significant variables associated with liver iron concentration were further subjected to multivariate stepwise regression analysis. RESULTS: Infants in group B had significantly higher serum iron (p < 0.01), serum ferritin (p < 0.01), and liver iron concentration (p < 0.01) than those in group A. The total and net volume of blood transfused were significantly associated with liver iron concentration (p < 0.001, r = 0.86; p < 0.001, r = 0.71 respectively), semiquantitative histochemical liver iron grading (p < 0.001, r = 0.80; p < 0.005, r = 0.71 respectively), and serum ferritin (p < 0.001, r = 0.84; p < 0.01, r = 0.69 respectively). In addition, both liver iron concentration and liver iron grading were found to be significantly associated with serum ferritin (p < 0.001, r = 0.76; p < 0.005, r = 0.68 respectively). Multivariate stepwise regression analysis indicated that the (log) liver iron concentration was significantly associated with the (log) volume of blood transfusion (p < 0.001; regression coefficient 0.39, SE 0.09), after adjustment for gestational age (R(2) = 0.84). CONCLUSIONS: This study showed a significant positive relation between the volume of blood transfused and the liver iron concentration in preterm VLBW infants. Although the transfusional blood volume correlated closely with the amount of iron deposited in hepatic tissues, clinical manifestations of iron overload were not observed. Carers should be aware of this potential harmful effect before prescribing blood or routine iron supplement to vulnerable preterm infants.     

Effect of gestational age upon prealbumin and retinol binding protein in preterm and term infants

The relationships between maternal and umbilical cord levels of prealbumin and retinol binding protein (RBP) were studied in 68 mothers and in their appropriate-for-gestational-age neonates delivered between 25 and 42 weeks gestation. Arterial and venous concentrations of prealbumin and RBP in cord sera were also studied in a subsample of eight infants. In cord sera, prealbumin and RBP levels increased with gestational age (prealbumin, r = 0.47; RBP, r = 0.40, p less than 0.01), and were significantly different in neonates born at term compared to those born prematurely (mean +/- SD, prealbumin 12.0 +/- 3.9 mg/dl vs. 8.8 +/- 2.3 mg/dl, p less than 0.001; RBP, 2.3 +/- 0.8 vs. 1.8 +/- 0.5 mg/dl, p less than 0.005). No significant differences between arterial and venous concentrations of prealbumin and RBP were observed in cord blood. In maternal blood, serum prealbumin and RBP concentrations did not increase with length of gestation (25-42 weeks). Maternal prealbumin was not correlated significantly with infants' cord serum levels; the correlation coefficient for RBP was 0.29, p less than 0.05. Maternal prealbumin and RBP serum levels were approximately twice the values seen in neonates born both at term and prematurely. Although the difference between premature and full-term cord levels of prealbumin and RBP may reflect an increase in hepatic protein synthesis that occurs with maturation of the fetus and/or a change in placental function after 37 weeks gestation, neither of these factors sufficiently explains the variance in neonatal prealbumin and RBP levels.     

Increased leptin concentration in preterm infants of pre-eclamptic mothers

AIM: To study the effect of maternal pre-eclampsia on cord plasma leptin concentrations in preterm infants. METHODS: Leptin concentration was analysed in cord plasma of 74 preterm infants, gestational age 24 to 32 weeks. Of these, 14 were born to pre-eclamptic mothers, in 10 intrauterine growth retardation (IUGR) was present, and 59 had been exposed antenatally to corticosteroids. RESULTS: The mean (SD) concentration of cord plasma leptin was 1.31 (0.88) microg/l. A significant correlation was found between leptin concentration and gestational age (r = 0.336; p = 0.0037). Leptin levels were higher in infants of pre-eclamptic mothers (p = 0.0007), in those with IUGR (p = 0.0005), and in infants exposed antenatally to corticosteroids (p = 0.02). In multiple regression analysis, leptin was associated with gestational age and maternal pre-eclampsia (both p < 0.05), but not with antenatal corticosteroids. CONCLUSIONS: Increased fetal leptin in maternal pre-eclampsia may reflect a physiological adaptation to fetal stress such as hypoxia.     

The role of cord blood IGF-I levels in preterm osteopenia

OBJECTIVE: Osteopenia is a frequent condition in preterm infants. This prospective study was designed to assess the relationship between cord blood insulin-like growth factor-I (IGF-I) levels and bone mineralization in healthy premature infants. METHODS: Twenty preterm infants (ten males and ten females) were studied. We determined the bone mineral density (BMD) and bone mineral content (BMC) of healthy premature infants by dual-energy X-ray absorptiometry and also studied the correlation between IGF-I and other parameters and the influence of cord blood IGF-I concentrations on bone mineralization in these infants. RESULTS: The mean concentration of IGF-I was 13.6 +/- 16.9 ng/ml and BMD and BMC were 0.249 +/- 0.06 g/cm2 and 3.09 +/- 1.18 g, respectively. Cord serum levels of IGF-I had significantly positive correlations with BMD (r = 0.605, p = 0.008), but not BMC (r = 0.242, p = 0.367). In stepwise regression analysis, IGF-I emerged as a significant predictor of BMD (beta = 0.595, p = 0.015) contributing to 35.4% of its variability. CONCLUSION: We found a relationship between cord blood IGF-I and BMD in preterm neonates, suggesting that even within an unremarkable population, IGF-I might be important to ensuring bone health.     

Cardiac troponin T in neonates after acute and long-term tocolysis

The present study was designed to determine the levels of cardiac troponin T (cTnT) in cord blood of neonates exposed in utero to tocolytic therapy by beta-sympathomimetics. cTnT in 40 neonates after acute tocolysis (0.24 +/- 0.05 microg/l) was significantly higher (p < 0.05) in comparison with the control group (0.05 +/- 0.01 microg/l). The maximal values were reached in about the 3rd day of therapy (0.39 +/- 0.11 microg/l). cTnT in 30 neonates after long-term tocolysis was 0.12 +/- 0.03 microg/l. No correlation was found between cTnT and CK and its isoenzyme CK-MB or ECG. CK, unlike cTnT, significantly correlated with gestational age (r = 0.57, p < 0.05) and birth weight (r = 0.55, p < 0.05). It is possible to conclude that acute tocolytic therapy by beta-sympathomimetics increases the cTnT levels in cord blood and cardiac troponin T is more useful for the laboratory diagnosis of neonatal myocardial injury than CK-MB.     

Umbilical cord levels of interleukin-1 receptor antagonist and neonatal outcome

BACKGROUND: Previous studies indicate that there may be infant gender differences in cytokine expression associated with differences in neonatal morbidity. OBJECTIVE: We tested the hypothesis that umbilical cord interleukin-1 receptor antagonist (IL-1ra) correlates with infant gender and neonatal outcome in preterm infants. STUDY DESIGN: IL-1ra was measured in cord blood taken from 58 preterm infants (33 males, 25 females) with gestational age less than 32 weeks. Receiver operating characteristics (ROC) curve were used for identifying IL-1ra values with high sensitivity and specificity for neonatal morbidity and adverse outcome, i.e., death or survival with severe intraventricular hemorrhage or periventricular leukomalacia. RESULTS: In the female infants, but not the male infants, cord IL-1ra values correlated with postnatal depression, expressed as Apgar scores at 1 min (correlation coefficient, r(s); p value: -0.542; 0.005), 5 min (-0.571; 0.018), and 10 min (-0.442; 0.035); and postnatal age at intubation (-0.799; 0.001). The ROC area under the curve (AUC) was 0.735 for adverse outcome (p=0.013), and 0.683 for bronchopulmonary dysplasia (p=0.021) when all infants were included. However, there was a significant gender difference in the ROC curve for adverse outcome (p=0.026), with AUC 0.640 (p=0.240) in males and AUC 0.929 (p=0.008) in females. Above a chosen cutoff at 13,500 ng/l for IL-1ra cord the sensitivity and specificity for predicting adverse outcome was 100 and 81%, respectively in females versus 50 and 84% in males. CONCLUSION: Increased levels of cord IL-1ra levels are associated with neonatal morbidity and adverse outcome in preterm infants. Comparable levels of IL-1ra have different predictive value depending on infant gender.     

The ontogeny of serum immunoreactive pancreatic lipase and cationic trypsinogen in the premature human infant

We evaluated the development of the exocrine pancreas in 16 healthy preterm infants (29.3 +/- 1.6 weeks). The infants were fed breast milk with formula supplements (n = 8) or formula alone (n = 8). Growth was monitored weekly for 12 weeks then at 3, 6, 9, 12 months. At the same intervals sera were determined for pancreatic lipase and cationic trypsinogen. In addition, cord blood samples were analysed from another 33 preterm (27.6 +/- 5.2 weeks) and 75 healthy full-term infants. Serum pancreatic lipase in the cord blood of term (3.7 +/- 0.4 micrograms/l) and preterm infants (1.8 +/- 0.2 micrograms/l) was significantly below values reported for older children (10.5 +/- 0.9 micrograms/l; p less than 0.001). In the preterm infant, serum lipase was also significantly lower than values obtained at term (p less than 0.001). At birth, serum trypsinogen for preterm (16.8 +/- 1.3 micrograms/l) and term infants (23.3 +/- 1.9 micrograms/l) were below those for older children (31.4 +/- 3.7 micrograms/l; p less than 0.05). Over the first 3 weeks of life, serum lipase and trypsinogen increased significantly. From 3 weeks to 12 months of age, serum trypsinogen values remained unchanged, but serum lipase increased dramatically after 10 weeks of age. Thus, at 6 and 12 months of age, the preterm infants had significantly higher serum lipase values than infants of the same age born at term. These two pancreatic enzymes appear to show independent age-related maturation in infants born before term. The rate of maturation of lipase appears to be accelerated by exposure to the extrauterine environment.     

Study of maternal influences on fetal iron status at term using cord blood transferrin receptors

AIMS: To determine effects of maternal iron depletion and smoking on iron status of term babies using serum transferrin receptors (STfR) and their ratio to ferritin (TfR-F index) in cord blood. METHODS: Iron, ferritin, STfR, and haemoglobin (Hb) concentration were measured and TfR-F index calculated in 67 cord /maternal blood pairs. Twenty six mothers were iron depleted (ferritin <10 microg/l) and 28 were smokers. RESULTS: Maternal iron depletion was associated with decreased cord ferritin (113 v 171 microg/l) and Hb (156 v 168 g/l) but no change in STfR or TfR-F index. Smoking was associated with increased cord Hb (168 v 157 g/l) and TfR-F index (4.1 v 3.4), and decreased ferritin (123 v 190 microg/l). Cord TfR-F index and Hb were positively correlated (r = 0.48). CONCLUSIONS: Maternal iron depletion is associated with reduced fetal iron stores but no change in free iron availability. Smoking is associated with increased fetal iron requirements for erythropoiesis.     

Does gender affect neonatal hyperbilirubinemia in low-birth-weight infants?

BACKGROUND: Neonatal mortality and morbidity are gender-biased in low-birth-weight (LBW) infants. The male disadvantage theory has been suggested to be responsible for these maturational differences. OBJECTIVE: To examine the impact of gender on neonatal hyperbilirubinemia. DESIGN/METHODS: A retrospective observational study. Data on all LBW infants admitted to George Washington University neonatal intensive care unit and surviving for >48 hrs from January 1992 to March 2003 were analyzed. Males and females were compared for gestational age, birth weight, race, Apgar scores at 1 and 5 mins, peak bilirubin levels, sepsis, and intraventricular hemorrhage (IVH). Significant differences were entered in a regression model to detect the influence of gender on bilirubin (Bili). Analysis was repeated after stratification of infants into: group A, <1000 g; group B, 1000-1499 g; and group C, 1500-2499 g. RESULTS: A total of 840 infants were included in this study. When comparing males (n = 407) with females (n = 433), significant differences were detected in birth weight (1,539 +/- 541 vs. 1,428 +/- 549 g; p = .003), IVH (14.2% vs. 9%; p = .025), and Bili (10.1 +/- 3.0 vs. 9.2 +/- 2.8 mg%; p < .001). No differences were detected in gestational age, sepsis, or Apgar 1 and 5. Difference in Bili for the entire group remained significant in the regression model (regression coefficient [RC] = 0.79 +/- 0.22; p < .001). In subgroup analyses: group A Bili (8.4 +/- 2.3 vs. 8.0 +/- 2.0; p = .14) and group B Bili (9.0 +/- 2.1 vs. 9.2 +/- 2.2; p = .51) did not differ in bivariate or multivariate analyses. In group C, Bili was (11.3 +/- 3.1 vs. 10.1 +/- 3.3; p < .001) and remained the only significant difference in the regression model (RC = 1.19 +/- 0.37; p = .001). CONCLUSIONS: Bili in LBW infants is significantly higher in males when compared with females. After stratification to birth weight subgroups, significance is retained in the 1500- to 2499-g group after logistic regression analysis. Bili levels in infants <1500 g are influenced more significantly by factors other than gender, such as sepsis and IVH.     

Relationship between cord blood levels of IGF-I and ferritin in healthy term neonates

OBJECTIVE: We hypothesize that the balance of maternal and fetal insulin-like growth factor-I (IGF-I) concentrations contributes to the regulation of substrate distribution between mother and fetus, and may thus mediate the maintenance of blood ferritin concentration in the fetus. Therefore, the relationship between cord blood IGF-I to ferritin concentration was investigated. INFANTS AND METHODS: Twenty-six term neonates were recruited. Anthropometric measures were recorded and umbilical cord blood samples were collected at birth. We studied serum concentrations of IGF-I in relation to blood ferritin and anthropometric data in term neonates. To assess the importance of the correlation of ferritin with both IGF-I and all other parameters, multiple linear regression analysis was carried out, with ferritin as the dependent variable and IGF-I and anthropometric parameters as independent variables. RESULTS: The mean concentrations of cord blood IGF-I and ferritin levels were 45.2 +/- 36.8 ng/ml and 225.5 +/- 124.2 ng/ml, respectively, at birth. A positive correlation was observed between IGF-I and ferritin concentrations of term neonates (r = 0.53, p = 0.005). IGF-I emerged as a significant predictor of ferritin concentration (beta = 1.79, p = 0.005) contributing to 28% of its variability. CONCLUSIONS: We showed a relationship between cord blood IGF-I and ferritin levels in term neonates, suggesting that even within an unremarkable population, fetal ferritin level may be influenced by IGF-I. Moreover, we speculated that IGF-I might also be important in the regulation of placental transport of ferritin.     

Influence of gestational age and intrauterine growth on leptin concentrations in venous cord blood of human newborns

BACKGROUND: The ob gene product leptin is involved in the regulation of body weight and energy expenditure, suggesting a potential role of leptin in embryonal and fetal development and progression of pregnancy. In term infants, leptin concentrations showed a positive correlation with birth weight. We aimed at comparing leptin cord blood levels in AGA (appropriate for gestational age) to SGA (small for gestational age) preterm and term newborns. PATIENTS AND METHODS: Ninety-seven human newborns, 47 females and 50 males, 33 born at term and 64 born before 36 weeks of gestation, were studied prospectively. Leptin concentrations in venous cord blood were determined using a specific RIA (radioimmunoassay). RESULTS: In term newborns, mean gestational age (GA) was 39 weeks (wk) (+/- 0.7 wk) and mean birth weight (BW) was 3316 g (+/- 473 g); in preterm newborns (n = 64), mean GA was 30 wk (+/- 5.0 wk) and mean BW was 1398 g (+/- 505 g). Mean standard deviation score of birth weight (BW SDS) was calculated as - 0.47. Mean leptin concentrations in term newborns differed significantly from those in preterm newborns (9.21 +/- 2.63 ng/ml vs. 1.58 +/- 0.88 ng/ml; p < 0.0001). In preterm and term infants, leptin concentrations showed a linear correlation with BW (r = 0.46; p < 0.0001) and GA (r = 0.48; p < 0.0001), respectively. Leptin levels were best predicted by an exponential regression model with GA (Leptin = exp(- 4.41 + 0.14 x GA); r = 0.61; p < 0.0001). Using multivariate regression analysis (r = 0.57; p < 0.0001), we found significant influences of GA (p < 0.00001) and BW SDS (p < 0.05) on leptin levels. No difference was observed between leptin values in AGA versus SGA preterm infants. CONCLUSION: These data suggest fetal leptin levels to be primarily determined by GA and additionally modulated by growth restriction in term newborns. We found a dramatic increase at weeks 33 to 35 of gestation and no modulation by BW SDS in very preterm infants.     

Lack of prognostic significance of early elevated serum uric acid levels in low birthweight infants

This study examined the utility of serum uric acid concentrations in the first day of life to identify infants with severe brain injury (grade III or IV intraventricular hemorrhage and/or periventricular leukomalacia). The serum uric acid concentrations in infants with severe brain injury were compared to those without. Severe brain injury was assessed in 151 infants with birthweight < or = 1,251 g admitted before 24 h of life. The risk of severe brain injury was related to 5-min Apgar scores (odds ratio 0.79, CI 0.63-0.98, p < 0.05) and seizures in the first day of life (odds ratio 4.44, CI 1.004-19.66, p < 0.05), but the mean uric acid levels did not differ between those with and without severe brain injury [5.11 +/- 1.88 mg/dl (303.9 +/- 111.8 micromol/l) vs. 5.77 +/- 2.13 mg/dl (343.2 +/- 126.7 micromol/l), p = 0.200]. Uric acid levels were related to serum creatinine (p < 0.001), time of uric acid sample (p < 0.001), maternal hypertension (p < 0.001), and base deficit (p = 0.032). Of the 80 infants seen in neurodevelopmental follow-up at a median 11 months postconceptional age, uric acid concentrations did not differ between the abnormal (n = 20) and normal subjects [5.38 +/- 1.72 mg/dl (320.0 +/- 102.3 micromol/l) vs. 6.02 +/- 2.55 mg/dl (358.1 +/- 151.8 micromol/l), p = 0.197]. Uric acid may not be a useful early marker for premature infants with severe brain injury.     

Umbilical vein plasma concentrations of asymmetrical dimethylarginine are increased in male but not female neonates delivered preterm: a pilot study

BACKGROUND: Infants born term have substantially elevated plasma concentrations of the endogenous nitric oxide synthase antagonist asymmetrical dimethylarginine (ADMA) that normalize with growth. The plasma levels of ADMA in preterm newborns are unknown. SUBJECTS AND METHODS: Plasma concentrations of ADMA, symmetrical dimethylarginine (SDMA) and L-arginine were analyzed from venous umbilical cord blood samples of 19 preterm and 21 term infants by high performance liquid chromatography. RESULTS: Male preterm newborns (n=11) had higher ADMA (median [95% confidence interval (CI)]: 1.90 [1.73-2.10] micromol/l) than females born preterm (n=8; 1.57 [1.24-1.69] micromol/l; p<0.005). In term born males (n=10) and females (n=11) ADMA was significantly lower than in preterm male infants (all p<0.005), and without sex differences. SDMA and L-arginine concentrations were comparable between all groups. ADMA correlated inversely with body weight in male preterm newborns (r=-0.67; p<0.03). CONCLUSION: Male neonates delivered preterm have significantly higher umbilical cord venous plasma concentrations of ADMA compared to female neonates and infants born term. The sex difference and the time course of elevated ADMA may play a role in development and warrant further investigation.