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Aim: To determine serum C-reactive protein (CRP) concentrations in healthy term-born infants shortly after birth., Methods: We sampled blood from 182 infants along with the routine neonatal screening programme at 48-72 hours of age from consecutively recruited healthy infants without signs of infection and a gestational age (GA) of at least 37 weeks. The blood was stored at minus 20°C until analysis in one assay after the end of the study., Results: The CRP levels were positively skewed. The median concentration was 5.0 mg/L, 48.9% of the neonates had values <5.0 mg/L, 19.8% ≥10.0 mg/L, 7.1% ≥20.0 mg/L and 1.1% (2 neonates) >30 mg/L. The CRP level was positively related to GA and duration of labour, slightly higher in boys than girls and after vaginal compared to Caesarean delivery., Conclusion: In healthy neonates born at term, the CRP concentrations did not vary substantially with various common perinatal clinical conditions, and levels above 30 mg/L were uncommon at two to three days of age., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: Piglets models have often been used to study the effects of dopamine infusion on hypotension in neonates. However, piglets need higher doses of dopamine than neonates to increase blood pressure. We investigated whether this difference was due to interspecific difference in dopamine pharmacokinetics., Methods: Arterial blood samples were drawn from six neonates admitted to the neonatal intensive care unit of Copenhagen University Hospital and 20 newborn piglets during continuous dopamine infusion. Furthermore, to estimate the piglet plasma dopamine half-life, blood samples were drawn at 2.5-minute intervals after the dopamine infusion was discontinued. The plasma dopamine content was analysed by high-performance liquid chromatography with electrochemical detection., Results: The dopamine displayed first-order kinetics in piglets and had a half-life of 2.5 minutes, while the median plasma clearance was 627.9 mL/kg/minute (interquartile range 452.6-1914.4). Both piglets and neonates showed large interindividual variations in plasma clearance, but the median tended to be lower in neonates (384.9, interquartile range 114.2-480.2 mL/kg/minute)., Conclusion: Our results suggest that pharmacokinetic differences may explain the interspecific difference in required doses of dopamine infusion to increase blood pressure. This is important when translating the results obtained in piglet models to treating neonatal hypotension with dopamine., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: It is unclear whether maternal intrapartum antibiotic treatment (IAT) continues to exert a bactericidal effect on common pathogens in neonates. We studied the in vitro bactericidal effect of IAT on the cord and peripheral venous blood of newborn infants., Methods: Umbilical cord and peripheral venous blood from newborn infants born at Kaplan Medical Center, Israel, from April to October 2014 were studied for serum bactericidal titres against Group B Streptococcus (GBS) and Escherichia coli (E. coli) strains. We studied 60 samples of umbilical cord blood and 18 samples of peripheral venous blood from 60 newborn infants whose mothers received IAT. The controls were 10 samples of cord blood from mothers without IAT., Results: Cord blood exerted a bactericidal effect against 98% of GBS isolates but only 8% of E.coli isolates. Peripheral blood exerted a bactericidal effect against GBS in 94% of cases, but not against E. coli. No bactericidal effect was seen in the blood from the controls., Conclusion: We found a continued bactericidal effect of umbilical cord blood and neonatal peripheral blood from newborn infants of IAT-treated mothers, mainly against GBS, but rarely against E. Coli. These findings may assist clinicians treating at-risk infants exposed to IAT., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: This Swedish study determined which species of coagulase-negative staphylococci (CoNS) were found in neonatal blood cultures and whether they included Staphylococcus capitis clones with decreased susceptibility to vancomycin., Methods: CoNS isolates (n = 332) from neonatal blood cultures collected at Örebro University Hospital during 1987-2014 were identified to species level with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). The antibiotic susceptibility pattern of S. capitis isolates was determined by the disc diffusion test and Etest, and the presence of heterogeneous glycopeptide-intermediate S. capitis (hGISC) was evaluated., Results: Staphylococcus epidermidis (67.4%), Staphylococcus haemolyticus (10.5%) and S. capitis (9.6%) were the most common CoNS species. Of the S. capitis isolates, 75% were methicillin-resistant and 44% were multidrug-resistant. No isolate showed decreased susceptibility to vancomycin, but at least 59% displayed the hGISC phenotype. Staphylococcus capitis isolates related to the strain CR01 displaying pulsotype NRCS-A were found., Conclusion: Staphylococcus epidermidis, S. haemolyticus and S. capitis were the predominant species detected in neonatal blood cultures by MALDI-TOF MS. The number of episodes caused by S. capitis increased during the study period, but no isolates with decreased susceptibility to vancomycin were identified. However, S. capitis isolates related to the strain CR01 displaying pulsotype NRCS-A were found., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: This study compared obstetric units practicing routine or selective umbilical cord blood gas analysis, with respect to the risk of missing samples in high-risk deliveries and in infants with birth asphyxia., Methods: This was a Swedish population-based cohort study that used register data for 155 235 deliveries of live singleton infants between 2008 and 2014. Risk ratios and 95% confidence intervals were calculated to estimate the association between routine and selective umbilical cord blood gas sampling strategies and the risk of missing samples., Results: Selective sampling increased the risk ratios when routine sampling was used as the reference, with a value of 1.0, and these were significant in high-risk deliveries and birth asphyxia. The risk ratios for selective sampling were large-for-gestational age (9.07), preterm delivery at up to 36 weeks of gestation (8.24), small-for-gestational age (7.94), two or more foetal scalp blood samples (5.96), an Apgar score of less than seven at one minute (2.36), emergency Caesarean section (1.67) and instrumental vaginal delivery (1.24)., Conclusion: Compared with routine sampling, selective umbilical cord blood gas sampling significantly increased the risks of missing samples in high-risk deliveries and in infants with birth asphyxia., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Unlabelled: Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most extensively examined biological markers for early prediction of acute kidney injury, but there is a lack of data on normal NGAL values in healthy term-born infants. This encouraged us to established serum and urine levels using samples collected from 38 girls and 50 boys, born at a median age of 39 weeks, during the first 48 hours after birth., Conclusion: Our findings showed that urine NGAL, but not serum levels, were significantly higher in girls than in boys., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: Automated haematology analysers are increasingly being used. Normal ranges for automated immature granulocyte counts (IG%) are described in adults and children as <1%, but are not reported for newborns, who often have complete blood count with differential in evaluation for early-onset sepsis. Therefore, this study aimed to describe IG% during the first 48 hours of life (HOL) in newborns and determine the clinical factors affecting IG%., Methods: We carried out retrospective chart reviews for newborns ≥35 weeks gestational age with one or more complete blood count with differential in the first 48 HOL. Clinical history and automated haematology results were reviewed., Results: Forty-seven of 215 subjects had two or more complete blood counts within 48 h. In the first 48 HOL, IG% ranged from 0 to 8.4% (95th percentile 5.2%). At <12 h, 70% of samples had IG% >1%. IG% appears to decrease over time. Earlier hour of life and higher birth weight were independently associated with higher IG%., Conclusion: Immature granulocyte counts in newborns appeared to be higher than reported for other age groups. Use of adult and child norms for IG% would not be appropriate for newborns being evaluated for early-onset sepsis., (©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: Lactate dehydrogenase (LDH) increases in several critical conditions that cause cell damage and could potentially be used for early detection of serious illness in the newborn. Our aim was to investigate the relationship between the early clinical course of NICU infants and LDH in plasma at admission., Methods: LDH was measured in a cohort of patients consecutively admitted to a major NICU in Hanoi. The infants were classified as 'obviously needing intensive care during the first week' (n = 83) or 'not receiving intensive care measures during the first week' (n = 260) by a senior neonatologist blinded to the LDH and lactate activity., Results: LDH differed significantly between the groups in infants born after 32 gestational weeks. LDH differed with the vitality of the patient (F = 26.25, p < 0.0001) at admittance and correlated with lactate (R = 0.496, p < 0.0001). Also, the predictive value for obvious need of intensive care was higher for LDH than for lactate assessed by area under the curve calculated with ROC-curves [0.82 (0.77-0.88) vs. 0.67 (0.60-0.75)]., Conclusion: There is a strong relationship between bad clinical condition of infants during first week of life and elevated plasma LDH. The results suggest that LDH might be a valuable support in decision making in the neonatal period., (© 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.)

Aims:   The aims of the study were to determine human breast milk adiponectin concentration and to investigate its relationship with serum adiponectin concentration in lactating mothers and their infants and also to evaluate the relationship between serum adiponectin concentration and anthropometric parameters in nurses and infants., Methods:   We enrolled 60 healthy term breastfed (BF) infants and their lactating mothers. Adiponectin was determined by radioimmunoassay test in serum and by enzyme-linked immunosorbent assay test in human milk (HM). Infants' and mothers' anthropometric parameters were measured., Results:   Median (25‰, 75‰) adiponectin concentration in HM was 9.99 (3.59, 20.52) ng/mL. Serum adiponectin concentration in infants was 60.49 (45.76, 74.24) μg/mL and in lactating mothers 21.14 (12.61, 29.66) μg/mL. Adiponectin concentration in HM correlated positively with adiponectin in mothers' serum; r = 0.60 (p < 0.001) and in infants' serum r = 0.37 (p = 0.015). Adiponectin in HM correlated negatively with infants' age r = -0.3 (p = 0.04). Infants' serum adiponectin correlated negatively with their weight r = -0.35 (p = 0.005), length r = -0.35 (p = 0.006) and age r = -0.46 (p < 0.001) and mothers' serum adiponectin with their weight r = -0.37 (p = 0.02) and body mass index r = -0.45 (p = 0.004)., Conclusions:   The observed correlations between adiponectin in mothers, HM and BF infants may be suggestive for a metabolic link between nurses and infants through milk., (© 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.)

Aim: To evaluate the accuracy in transcutaneous (Tc) blood gas monitoring in newborn infants, including extremely low birth weight infants, during neonatal intensive care., Methods: Tc PO(2) /PCO(2) was monitored in the neonatal intensive care unit (NICU) during stable infant conditions. In comparison, simultaneous arterial PO(2) and PCO(2) was measured. Sixty measurements were taken in 46 infants with median (range) birth weight of 0.93 (0.53-4.7) kg and at median (range) age of 8.5 (1-44) days. Comparison of measurements was performed using Bland-Altman plots, and the mean (95% CI) of the difference was calculated. Comparison was also performed in relation to body weight, postnatal age and oxygen requirement., Results: The mean (95% CI) difference in PO(2) (TcPO(2)-aPO(2)) was 0.3 (-0.2-0.9) kPa, and the corresponding difference in PCO(2) (TcPCO(2)-aPCO(2)) was 0.4 (0.03-0.8, p < 0.05) kPa. Some differences were related to body weight, age and oxygen requirement, but these differences were small., Conclusion: There was good agreement between TcPO(2)/TcPCO(2) and corresponding arterial measurements. The mean difference between the methods was small and clinically acceptable in a current NICU. Tc blood gas monitoring could be recommended as a valuable complement for blood gas monitoring also in extremely low birth weight infants., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Aim: To determine cathelicidin antimicrobial peptide LL37subcellular distribution in cord neutrophils and normal plasma LL37 levels in mothers and neonates, relate them to delivery mode and relevant biochemical markers, including 25-OHvitamin D [25(OH)D] as this molecules increases cathelicidin gene expression., Methods: A total of 115 infants were included, n = 68 with normal delivery and n = 47 with elective Caesarean section (C-section), a subset of these being 50 mother-infant pairs. Biomarkers were determined in maternal and cord blood. Subcellular peptide LL37 distribution was analysed with immunoelectron microscopy., Results: Cord plasma LL37 levels were three-times higher after normal delivery compared with C-section. A highly significant correlation was observed between maternal and cord plasma LL37 levels, regardless of delivery mode. No relationship was found between LL37 and 25(OH)D levels. Neutrophils from cord blood after normal delivery contained 10-times more cytoplasmatic cathelicidin peptide compared with corresponding cells after C-section where a strict granular localization was found., Conclusion: These data are consistent with a placental transfer of LL37 and identifies maternal stores as the critical factor determining neonatal plasma LL37 level. An additional enhancement of neonatal cathelicidin mobilization and release is connected to normal delivery stress.

Aim: Delivery by C-section (CS) has been associated with increased risk for allergy, diabetes and leukaemia. Whereas the underlying cause is unknown, epigenetic change of the genome has been suggested as a candidate molecular mechanism for perinatal contributions to later disease risk. We hypothesized that mode of delivery affects epigenetic activity in newborn infants., Methods: A total of 37 newborn infants were included. Spontaneous vaginal delivery (VD) occurred in 21, and 16 infants were delivered by elective CS. Blood was sampled from the umbilical cord and 3-5 days after birth. DNA-methylation was analyzed in leucocytes., Results: Infants born by CS exhibited higher DNA-methylation in leucocytes compared with that of those born by VD (p < 0.001). After VD, newborn infants exhibited stable levels of DNA-methylation, as evidenced by comparing cord blood values with those 3-5 days after birth (p = 0.55). On postnatal days 3-5, DNA-methylation had decreased in the CS group (p = 0.01) and was no longer significantly different from that of VD (p = 0.10)., Conclusion: DNA-methylation is higher in infants delivered by CS than in infants vaginally born. Although currently unknown how gene expression is affected, or whether epigenetic differences related to mode of delivery are long-lasting, our findings open a new area of clinical research with potentially important public health implications.

Aim: To prospectively investigate circulating concentrations of the adipokine and angiogenic factor apelin in mother/infant pairs and correlate them with respective insulin concentrations., Methods: Plasma apelin concentrations were determined in 40 mothers and their singleton full-term foetuses and neonates on day 1 (N1) and 4 (N4) of life., Results: Maternal apelin concentrations were lower compared to foetal, N1 and N4 ones (p<0.001 in all cases). N1 apelin concentrations were lower compared to foetal and N4 ones (p=0.002 and p=0.005, respectively). Maternal apelin concentrations positively correlated with foetal, N1 and N4 concentrations (r=0.663, p<0.001, r=0.486, p=0.003, r=0.484, p=0.003, respectively). Foetal apelin concentrations positively correlated with N1 and N4 ones (r=0.337, p=0.044 and r=0.574, p<0.001, respectively). N1 apelin concentrations positively correlated with N4 ones (r=0.513, p=0.001). No association was found between apelin concentrations and birthweight, gender, parity or mode of delivery. No significant correlations were observed between apelin and insulin concentrations., Conclusions: Concentrations of apelin are high in the foetus, possibly suggesting its potential role in intrauterine development. Apelin expression in placental tissue could account for its higher foetal concentrations and for its down-regulation soon after birth. The postnatal increase of apelin concentrations could presumably point to a gradual initiation of ex utero angiogenesis.

Aim: To further evaluate the underlying mechanism of a formerly demonstrated immature anti-inflammatory response in neonates (1)., Methods: Interleukin (IL)-10 production was measured by enzyme-linked immunosorbent-assay (ELISA) after anti-CD3/anti-CD28 costimulation of neonatal and adult T cells. IL-10 receptor expression on T lymphocytes, B lymphocytes and monocytes were analysed by flow cytometry in neonates and adult controls., Results: After anti-CD3/anti-CD28 costimulation, IL-10 production of neonatal T lymphocytes was profoundly reduced (median 247 pg/mL vs. 1062 pg/mL, p < 0.0001). IL-10 receptor expression was diminished on neonatal T lymphocytes compared to adults (3% vs. 39.5% IL-10 receptor positive lymphocytes; p < 0.0001). On neonatal B lymphocytes and monocytes the IL-10 receptor expression was comparable to adult controls., Conclusion: The strongly reduced IL-10 receptor expression on the main immune regulative T lymphocytes in conjunction with a significantly impaired synthesis of IL-10 may play a crucial role in the formerly demonstrated deficient anti-inflammatory immune response in neonates.

Aim: To prospectively investigate blood visfatin concentrations during the perinatal period in normal pregnancies., Methods: Visfatin concentrations were determined in maternal, umbilical cord (representing the foetal state) and neonatal blood on day 1 (N1) and 4 (N4)., Results: Maternal and foetal visfatin concentrations were similar (18.83+/-4.27 and 19.35+/-4.90 ng/mL, respectively). There were significant correlations between maternal and foetal (r=0.742, p<0.001), as well as between N1 and N4 (r=0.487, p=0.029) visfatin concentrations. Foetal concentrations were significantly elevated compared to N1 (p=0.032). There was no difference between N1 and N4 concentrations. However, there was a correlation between birth weight and neonatal visfatin concentrations: there was a mean increase in N1 and N4 visfatin concentrations by 0.221 ng/mL and 0.292 ng/mL, respectively, for every unit increase in customized centile (adjusted birth weight) (p=0.021 and p=0.005, respectively). No association was found between serum visfatin concentrations and gender, parity or mode of delivery., Conclusions: Expression in foetal membranes and placental transfer could be responsible for higher blood visfatin concentrations during intrauterine life. Customized centiles seem to be independent predictor variables for postnatal visfatin concentrations. This finding could be attributed to the production of visfatin in adipose tissue, a main contributor to birth weight and consequently to customized centiles.

Aim: To investigate energy substrate production and its hormonal regulation in infants born small for gestational age., Methods: Eleven infants, aged 24.4 +/- 5.3 hour, were studied following a fast of 4.0 +/- 0.6 hour. Gestational age was 35.4 +/- 2.8 weeks and birth weight 1804 +/- 472 g (<-2 SD). Rates of glucose production and lipolysis were analyzed using [6,6-(2)H(2)]-glucose and [2-(13)C]-glycerol., Results: Plasma levels of glucose and glycerol were 4.1 +/- 1.1 mmol x L(-1) and 224 +/- 79 micromol x L(-1), respectively. Glucose appearance averaged 30.3 +/- 8.2 and glucose production rate 21.1 +/- 6.1 micromol x kg(-1) x minutes(-1). Glycerol production rate was 5.6 +/- 1.6 micromol x kg(-1) x minutes(-1), correlating strongly to birth weight (r = 0.904, p < 0.001). Of the glycerol produced, 55 +/- 22% was converted to glucose, corresponding to 8 +/- 3% of the glucose production., Conclusions: Even though the infants could produce energy substrates, lipolysis was reduced and the glucose production was in the low end of the normal range compared with infants born appropriate for gestational age. The correlation between glycerol production and birth weight indicates that lipolysis depends on the amount of stored fat. Data on insulin and insulin-like growth factor binding protein 1 support the view that insulin sensitivity in these infants is reduced in the liver but increased peripherally.

Aim: To evaluate the relationship between serum leptin concentration in infants and infant and maternal BMI., Methods: 75 healthy term infants aged 0-12 mo, 51 exclusively breastfed (BF) for at least 4 mo and 24 formula fed (FF), were included in a cross-sectional study. Weight, length and cranial circumference of infants and their mothers were measured, body mass index (BMI) was calculated using the formula weight (kg)/height (m2) and infant serum leptin concentration was determined., Results: A significant positive correlation between infant serum leptin concentration and maternal BMI was observed in BF infants (r = 0.389, p = 0.005), confirmed in a multiple regression model adjusted for infant age and infant BMI (beta = 0.065, p = 0.006), but not in FF infants. As regards the first 4 mo of life, we have already observed a positive correlation between infant serum leptin concentration and maternal BMI in BF infants (beta = 0.113, p = 0.005), but not in FF infants., Conclusion: In BF infants, serum leptin concentration correlates positively with maternal BMI. Higher maternal BMI values might increase leptin levels in breast milk, and maternal adiposity could be involved in infant energy balance.

Aims: To measure and compare cardiac troponin I, cardiac troponin T and creatine kinase MB concentrations in the umbilical cord blood of healthy term infants and to investigate the relationship between maternal and neonatal troponin values at birth., Methods: Troponin I, troponin T and creatine kinase MB concentrations were measured from the umbilical cord samples of 85 healthy term neonates and in the blood samples of their respective mothers at birth., Results: Median (interquartile range) umbilical cord concentrations were 0 microg/L (0-0) for troponin I, 0 microg/L (0-0.019) for troponin T and 4.90 microg/L (3.90-6.61) for creatine kinase MB. Troponin I and T concentrations were higher than the detection limit for the assay in 2 (2.3%) and 41 (48.2%) neonates, respectively. Two mothers (2.3%) had cTnT levels above the detection limit; none of them had increased levels of cTnI., Conclusion: Probably owing to differences in expression and assay detection limits, cord blood troponin T concentrations are frequently over the detection limit at birth, while troponin I is mostly undetectable and comparable with that in healthy pregnant women. These cardiac regulatory proteins are of neonatal origin and are not influenced by maternal levels.

Unlabelled: In neonates, despite poor platelet function in various in vitro tests, closure times (CTs) in PFA-100 measurements are shorter than in adults. Neonates have a higher polymeric von Willebrand factor (vWF). They also have a higher haematocrit and higher white blood cell count than adults. which may interfere with the evaluation of platelet and vWF function by means of the PFA-100 in neonates. To assess the role of different blood constituents on neonatal CTs, red blood cell, platelet and white blood cell counts in cord blood were modified. These modifications did not provide any evidence that the difference in number between adult and neonatal blood cells was responsible for shorter neonatal CTs. In further experiments, platelets and/or vWF were inhibited by means of abciximab and anti-vWF antibody, and mixing experiments with neonatal platelet-rich and platelet-poor plasma were performed. The results showed that short cord blood PFA-100 CTs were caused by a constituent of neonatal platelet-poor plasma, probably the neonatal high multimeric vWF., Conclusion: This study demonstrates that CTs in neonates are dependent on the same components, platelets and vWF, as in adults, making it likely that the PFA-100 can be used in neonates in the same way as in adults to investigate platelet and vWF function.

Unlabelled: Total magnesium, ionized calcium, potassium and sodium concentrations in mixed umbilical cord blood and venous blood serum at a median (min.-max.) age of 33 h (24-48 h) were assessed colorimetrically in 46 asphyxiated and 35 healthy term infants. Asphyxiated infants without any signs or with signs of mild hypoxic-ischaemic encephalopathy (HIE) had significantly higher, and infants with severe HIE lower umbilical cord blood serum total magnesium (mean (95%CI) 0.81 (0.75-0.87) mmol/l and 0.64 (0.47-0.87) mmol/l, respectively, p < 0.05) compared with the control group (0.72 (0.69-0.76)mmol/l). An increase in serum total magnesium in spite of normalized acid-base status in asphyxiated infants suffering from severe HIE compared with the control group infants was found by the second day of life (0.97 (0.87-1.07) mmol/l and 0.86 (0.81-0.9) mmol/l, respectively, p < 0.05). At the age of 24-48 h hypermagnesaemia (>2 SD) was discovered in 36%, hyponatremia (<2 SD) in 38%, and hypocalcaemia (<2 SD) in 23% of asphyxiated infants. Derangements (>2 SD) in at least two electrolytes by the second day of life were significantly associated with poor outcome., Conclusions: Magnesium, calcium and sodium derangements are a frequent finding in asphyxiated infants, and these abnormalities are significantly associated with poor outcome. For a better outcome prediction, the routine determination of magnesium in addition to other electrolytes in asphyxiated infants is recommended.

Unlabelled: Serum transferrin receptor (sTfR) concentration reflects functional iron status and erythropoietic activity. The aims of this study were to examine gender differences of erythropoiesis in newborns and to evaluate the influences of maternal anaemia or iron deficiency on foetal cord blood parameters for iron status and sTfR. In total, 527 newborns and their mothers were examined. Reticulocytes were analysed by flow cytometry and sTfR was measured by an immunoenzymometric method. There were no sex differences in haematological or iron parameters. However, the reticulocyte maturity index (RMI) of male neonates was 37.45%, significantly higher than the 26.81% in female neonates (p <0.01). The high fluorescence reticulocytes (HFR) and middle fluorescence reticulocytes (MFR) of male neonates were 4.91% and 22.36%, respectively, while those of female neonates were 3.31% and 17.83%, respectively (p < 0.01 for each gender). The sTfR concentrations of male and female neonates were 6.27 mg/l and 5.09 mg/l, respectively (p < 0.01). Values for serum iron, ferritin and reticulocyte subpopulations were significantly lower in the newborns of anaemic mothers. However, newborns of iron-deficient mothers showed no differences in iron parameters from those of non-iron-deficient mothers., Conclusions: The higher values of RMI and sTfR observed in male neonates indicate that erythropoietic activity is higher in this group. Iron transport to the foetus appears to be independent of maternal iron deficiency. However, iron transport and erythropoiesis in newborns seems to decline from the time that the mothers acquire frank iron deficiency anaemia.

Adrenomedullin is a peptide that induces pulmonary vasodilation in experimental animals. Adrenomedullin was measured in blood samples from cord artery and vein from 41 term newborns. In 23 of the newborns delivered vaginally, levels of adrenomedullin in the cord artery, 71.8+/-45.8 pg ml(-1) (mean +/- SD), and vein, 75.6+/-45.2 pg ml(-1), were significantly higher than in 18 newborns delivered by elective Caesarean section (40.7+/-14.6 pg ml(-1) and 32.4+/-10.3 pg ml(-1), respectively; both p < 0.01). A significant correlation existed between the concentration of adrenomedullin and pH in the cord artery (r = -0.545, p = 0.002). The fetus responds to birth stress by secreting high concentrations of adrenomedullin. As a potent vasodilator, the peptide may play a role in postnatal cardiovascular adaptation.

The purpose of this study was to compare the performance and accuracy of the HemoCue B-Glucose photometer system and reagent strip tests used in conjunction with reflectance photometry against a reference plasma glucose method. One hundred consecutive babies admitted to the neonatal unit over a 6-month period were enrolled in the study. Each baby had a heelprick capillary glucose measured by HemoCue and reagent strip tests. At the same time venous plasma glucose and haematocrit were measured. The mean difference between the reagent strip test and plasma glucose was significantly less than the corresponding value for the HemoCue (0.015 +/- 1.41 vs 0.837 +/- 1.565 mmol l-1, mean +/- SD); however, the agreement limits between both methods and plasma glucose were wide. No significant effect of haematocrit was detected on either method. The HemoCue photometer does not offer any advantage over the widely used reagent strip tests in the neonatal period. However, the limits of agreement of both methods compared with plasma glucose are too wide to be clinically acceptable in the neonatal period.

The insulin-like growth factors (IGF-I and IGF-II) and their binding proteins (IGFBPs) have been implicated in regulating fetal growth and development. The aim of this study was to determine whether fetal IGFs correlate with auxologic data at birth and/or gestational age. Venous cord blood was obtained from 138 healthy newborns immediately after birth and clinical data were recorded using a standardized data sheet. For the determination of IGF-I and IGF-II, IGFBP-blocked radioimmunoassays were used. A coated-tube immunoradiometric assay was applied for the measurement of free IGF-I. IGFBP-1, -2, and -3 were measured using specific radioimmunoassays. IGF-I levels were 61 +/- 21 ng ml(-1), median 61 ng ml(-1), range 19-114 ng ml(-1); IGF-II levels were 466 +/- 80 ng ml(-1), median 457 ng ml(-1), range 311-701 ng ml(-1); free IGF-I levels were 2.4 +/- 1.8 ng ml(-1), median 1.8 ng ml(-1), range 0.4-7.8 ng ml(-1). The concentration of IGFBP-1 was 144 +/- 110 ng ml(-1), median 113 ng ml(-1), range 20-626 ng ml(-1); that of IGFBP-2 was 1165 +/- 455 ng ml(-1), median 1119 ng ml(-1), range 440-3466 ng ml(-1). IGFBP-3 levels were 1272 +/- 280 ng ml(-1), median 1272 ng ml(-1), range 600-1966 ng ml(-1). IGF-I levels correlated significantly with IGFBP-3 levels (r = 0.71), birthweight (r = 0.48) and birth length (r = 0.37). There were significant inverse correlations between IGF-I and both IGFBP-1 (r = -0.45) and IGFBP-2 (r = -0.62). Although free IGF-I levels correlated (r = 0.71) with total IGF-I, only marginally significant correlations were found between free IGF-I and birthweight (r = 0.25). According to multiple regression analysis free IGF-I levels were only dependent upon total IGF-I, IGFBP-2 and IGFBP-1, whereas IGFBP-3 levels did not contribute to the variance of free IGF-I concentrations in venous cord blood. There was no significant correlation between IGF-II and auxologic data at birth. When IGF-I and IGFBP-3 levels were analysed with respect to gestational age a biphasic pattern with maxima at 270 d was observed. IGFBP-2 exhibited a reversed pattern with a minimum at 265 d of gestation. In conclusion, these data suggest that IGF-I and the IGFBPs, but not IGF-II, play a role in the regulation of late fetal growth and development.

The aim of this study was to determine serum lecithin: cholesterol acyltransferase (LCAT) activity in parallel with HDL2 and HDL3 composition in cord sera of small for gestational age (SGA) newborns, and to compare them with those obtained from appropriate for gestational age (AGA) newborns. LCAT activity was assayed by conversion of [3H]cholesterol to labelled cholesteryl ester. HDL2 and HDL3 were separated by ultracentrifugation. Serum cholesteryl ester, apolipoprotein (apo) A-I concentrations and LCAT activity were significantly lower (-47%, -18% and -56%, respectively), whereas serum triglyceride amounts were twofold higher in SGA newborns than in AGA newborns. In SGA newborns, HDL2 and HDL3 levels were low, and HDL3 and HDL2 phospholipid and HDL2-cholesteryl ester contents were diminished. HDL3-apo A-I, A-II, C-III and E values were lower in SGA newborns. In HDL2, apo A-I, A-II and E concentrations were decreased. Therefore, in SGA newborns, the reduced LCAT activity was associated with quantitative and qualitative changes in HDL2 and HDL3 particles.

Objective: To assess the levels and development of the various complement components in preterm infants, particularly among those born before 34 weeks' gestation., Subjects and Methods: We measured the complement system's activities (CH50 and AP50) as well as its various components (C1q,r,s, C2-C9, Factor B, and properdin) in 25 preterm infants [gestational age (GA) 28-33 weeks], 35 preterm infants (GA 34-36 weeks), 50 full-term newborn infants (GA 37-42 weeks), and 49 healthy adults as control subjects., Results and Conclusions: The results of these studies are: (i) complement levels and activity were significantly reduced in preterm and full-term neonates when compared with adult levels, with the exception of C7 which was within the normal range in most infants. C8 and C9 were the most markedly reduced at all gestational ages. (ii) Complement levels correlated significantly with gestational age, but not with birth-weight, type of delivery, or gender. (iii) Between 28 and 33 weeks' gestation, there appeared to be almost no development of the complement system.

Differences in cord serum low density lipoprotein (LDL) composition between male and female neonates with normal or high (> or = 100 mg/dl or > or = 2.59 mmol/l) serum cholesterol levels were studied in 548 full-term newborn infants of the Toledo Study (Spain), where the absence of known perinatal factors that would alter lipid levels in cord blood was confirmed. The percentage of females with a high serum total cholesterol (TC) level was higher (p < 0.02) than that of males. ANOVA two-way analysis shows significant interaction of gender and cholesterol level upon LDL-cholesterol, triglycerides and LDL-cholesterol/Apoprotein (Apo) B ratio. However, Apo B was higher in those neonates, both male and female, with high cholesterol levels. The LDL fraction carried about 55% of TC in females with high TC levels (HF), whereas it transported just 40% in males with high TC levels (HM). LDL appeared more enriched in cholesterol than in Apo B in HF than in HM (p < 0.01). An increased level of small LDL particles should be associated with the higher triglyceride level found amongst HM. Results in LDL composition suggest that metabolic gender-related differences in infants with normal or high TC are presented at birth.

Objective: To compare the plasminogen activators (tPA, uPA) and their inhibitors (PAI-1, PAI-2) at different gestational ages, related to levels in women at term and non-pregnant women., Methods: Blood samples were obtained by puncture of the umbilical cord vein, in gestational weeks 39-40 (n = 21), 30-32 (n = 15), and 27-29 (n = 9). Analyses of PA and PAI antigen concentrations and of PAI-1 activity were performed., Results: The mean tPA antigen level in term newborn infants was 14.5 micrograms/l compared to the premature newborns (7.0 micrograms/l), women at term (7.5 micrograms/l) and non-pregnant women (2.3 micrograms/l). PAI-1 activity and PAI-2 antigen concentrations were also higher in term newborn than in premature infants., Conclusions: The plasma levels of the plasminogen activators and inhibitors are higher in term newborn compared with premature newborn infants, reflecting maturation of protein synthesis.

The aim of this study was to investigate serum digoxin-like immunoreactive substance (DLIS) levels in 60 healthy term infants when they reached 1-6 months of age with regard to feeding regimen. Group I consisted of 30 infants fed exclusively on breast milk. Groups II and III each consisted of 15 infants fed on formula and cow's milk, and on formula and cow's milk supplemented by breast milk, respectively. Mean serum DLIS concentrations were 0.03 +/- 0.05, 0.18 +/- 0.09 and 0.15 +/- 0.09 ng/ml in groups I-III, respectively. The difference between the DLIS levels in groups II and III was not significant. Serum DLIS levels of infants in groups II and III, on the other hand, were significantly higher than in group I (p < 0.05). These findings were interpreted to suggest that artificial nutrients may cause volume expansion and an increase in endogenous DLIS levels. The latter response is possibly a protective mechanism to decrease volume expansion in groups II and III.

Cord serum apolipoproteins (Apo) A-I and B from 548 healthy, full-term singletons were studied. Females displayed slightly, but significantly, higher Apo A-I levels (p < 0.001) than males, particularly at weeks 38 and 39 (p < 0.05), whereas Apo B was not gender affected but likewise increased (p < 0.05) between weeks 37 and 41. Apo A-I values increased (p < 0.05) with gestational age in males, but with birthweight in females. Results suggest that small gender and age-related metabolic differences exist at birth in term infants.

Full-term infants fed formula without dietary long-chain polyunsaturated fatty acids (LCF) exhibit significantly lower plasma LCP values than breast-fed infants. We studied prospectively two groups of healthy full-term infants fed conventional infant formula without LCP (F, n = 10) or the same formula enriched with both omega-6 and omega-3 LCP (LCP-F, n = 12). Anthropometric data were obtained and fatty acid (FA) compositions of plasma phospholipids, triglycerides and sterol esters as well as plasma retinol and alpha-tocopherol concentrations were determined at 5 days and 1, 2, 3 and 4 months of age. Gains in weight, length and head circumference did not differ between the two groups throughout the study period. Plasma FA values did not differ at 5 days of age. Between 1 and 4 months of age, plasma phospholipids of infants fed LCP-F consistently had significantly (p < 0.05) higher percentages of arachidonic acid (1 month: 9.7 (0.8) versus 7.0 (1.3) %wt/wt, 4 months: 8.7 (0.5) versus 6.6 (1.0) %wt/wt, median (interquartile range), LCP-F versus F) and docosahexaenoic acid (1 month: 2.9 (0.5) versus 1.6 (0.3) %wt/wt; 4 months: 2.9 (0.4) versus 0.9 (0.3) %wt/wt). Plasma retinol and alpha-tocopherol concentrations did not differ between the two groups throughout the study. We conclude that this form of LCP enrichment of formula for full-term infants effectively enhances plasma LCP contents without detectable adverse effects. The potential effects on functional outcome need to be studied carefully in prospective clinical trials.

The relationship between serum concentrations of glucose, insulin and glucagon during the first two days of life was studied in healthy newborns. The first capillary blood sample was obtained at 3-15 h of age (median 6 h; day 0) and a second sample approximately 24 h later (day 1). Serum glucose concentrations in the first sample averaged 2.1 +/- 0.07 mmol/l (mean +/- SEM; n = 60) and were positively correlated with postnatal age (p < 0.01). Serum glucagon concentrations in the first sample averaged 570 +/- 32 pg/ml and were inversely correlated with glucose concentrations (p < 0.0001). At the second sampling, serum glucose concentrations had increased to 2.9 +/- 0.07 mmol/l (p < 0.001; n = 57) and serum glucagon concentrations had decreased to 403 +/- 22 pg/ml (p < 0.001). Serum insulin concentrations were 11.7 +/- 0.3 microU/ml and 10.2 +/- 0.3 microU/ml at the two samplings and did not correlate with serum glucose concentrations. The relationship of serum glucose and hormone concentrations to maternal and infant characteristics was studied by stepwise regression analysis. Serum glucose concentration on day 0 was positively correlated with postnatal age (p < 0.01) and birth weight (p < 0.05) but inversely correlated with duration of labour (p < 0.05). Serum glucose concentration on day 1 was positively correlated with birth weight (p < 0.0001) and inversely correlated with maternal prep-pregnancy weight (p < 0.05). Similar analyses of serum hormone concentrations did not demonstrate any relationships with maternal or infant characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Using high pressure liquid chromatography on strong cation exchange column, we analyzed capillary blood from 141 healthy full-term newborns for lactate and pyruvate concentrations. Total range of lactate was 367-3245 mumol/l and reference interval (mean +/- 2 SD) was 260-2212 mumol/l. Total range of pyruvate was 10-141 mumol/l and reference interval (10th/90th percentile) was 12-71 mumol/l.

Lipid emulsion (Intralipid) causes free radical-mediated damage to human cells in vitro. Incubation with 0.44% Intralipid for 17 h caused 40.3 +/- 3.8% haemolysis in adult human erythrocytes and 26.5 +/- 8.1% in erythrocytes from term newborns (p = 0.0001). In adult erythrocytes mean corpuscular volume increased 68.7 +/- 8.2% and in newborn erythrocytes 54.8 +/- 10.4% (p = 0.0012). Initial concentrations of reduced glutathione in adult and newborn erythrocytes were 65.1 +/- 2.5 and 62.1 +/- 4.0 mg/dl, respectively (ns); after incubation, glutathione concentrations were 21.0 +/- 4.0 and in 25.7 +/- 5.2 mg/dl in adult and newborn erythrocytes, respectively (p = 0.0004). After incubation the concentrations of thiobarbituric acid reactive material and conjugated dienes in newborn erythrocytes (2.8 +/- 0.2 microM and 0.223 +/- 0.019 OD 233, respectively) were higher than those of adult erythrocytes (2.1 +/- 0.4 microM and 0.138 +/- 0.012 OD 233) (p = 0.0001). In both adult and newborn erythrocytes, the effects of Intralipid were significantly inhibited by 0.6 mM deferroxamine or 8 mM sodium etidronate. Despite higher susceptibility to lipid peroxidation of the cell membrane, newborn erythrocytes are more resistant than adult erythrocytes to free radical-mediated effects such as depletion of intracellular glutathione, cell swelling and haemolysis.

This study was done to compare postnatal alterations in blood viscosity (capillary viscometer) and its determinants: hematocrit, plasma viscosity (capillary viscometer), red cell aggregation (Myrenne aggregometer) and red cell deformability (rheoscope) in the first five days of postnatal life in full-term neonates with early (< 10 s) and late (3 min) cord-clamping. The fetal blood volume of the placenta ("residual placental blood volume") decreased from 52 +/- 8 ml/kg of neonatal body weight after early cord-clamping to 15 +/- 4 ml/kg after later cord-clamping. Neonatal blood volume, calculated as the difference between an assumed total feto-placental blood volume of 115 ml/kg and the measured fetal blood volume of the placenta, was 50% higher in the late cord-clamped infants than in the early cord-clamped infants. Both groups showed similar viscosity, hematocrit and other rheological parameters in cord blood. In the infants with early cord-clamping, the hematocrit decreased from 0.48 +/- 0.04 l/l at birth to 0.43 +/- 0.6 l/l after 24 h (p < 0.05). Whole blood viscosity did not change significantly with age. After late cord-clamping, the hematocrit rose from 0.50 +/- 0.04% at birth to 0.63 +/- 0.05 l/l at 2 h of age (p < 0.005) and dropped to 0.59 +/- 0.5 l/l (p < 0.05) at 24 h. Blood viscosity increased by 40% (p < 0.001) within the first 2 h, but did not change significantly during the following five days. In both groups, plasma viscosity and red cell aggregation increased significantly (p < 0.05) on day 5 due to significant increases in total plasma protein and fibrinogen concentrations (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The kinetics of virus-specific IgG subclasses (IgG 1-4) among newborns and their mothers has not yet been determined. In this report, we examined anti-herpes simplex virus IgG activities (HSV-IgG) and its subclasses in CSF and serum of premature or term newborns without HSV infection and in the serum of their mothers using ELISA. We found that CSF/serum ratios of HSV-IgG and IgG subclasses (IgG 1-4) in newborns with a gestational age less than 38 weeks were higher than those of term newborns. These findings indicate that the blood-brain barrier against HSV-IgG and IgG subclasses is insufficient in newborns. Furthermore, we found that HSV-IgG subclasses, which were transferred across the placenta and later transferred across the blood-brain barrier had a tendency to be proportional to each of the maternal HSV-IgG subclasses.

We determined plasma endothelin-1-like immunoreactivity and atrial natriuretic factor concentrations in preterm and full-term newborn infants during the first month of life. Plasma endothelin-1-like immunoreactivity levels were far greater than those of maternal blood in the newborn infants. The highest plasma endothelin-1-like immunoreactivity levels were observed on the first day of life (8.7 +/- 3.7 pmol/l) and gradually decreased with age. There was no significant difference in plasma endothelin-1-like immunoreactivity levels between preterm and full-term infants. A good correlation was observed between plasma endothelin-1-like immunoreactivity levels and atrial natriuretic factor concentrations (p < 0.01). These results suggest that circulating endothelin may regulate the cardiovascular system in the newborn period.

Breast milk provides an excellent supply of most nutrients for newborn infants. Infant formulae should be nutritionally comparable to breast milk especially with regard to critical nutrients like iron and other trace elements. Infant formulae supplemented with various amounts of bovine lactoferrin were given to two groups of infants. These infants were compared with infants receiving unsupplemented formula and breast-fed infants. The effects of these diets on levels of haemoglobin, haematocrit, serum iron, ferritin and zinc were examined for a study period of 150 days. At birth, concentrations of iron, haemoglobin, haematocrit and zinc were comparable in all four feeding groups. The fact that the serum zinc level was not altered by lactoferrin supplementation appears to rule out an in-vivo effect of lactoferrin on zinc nutrition of infants. Ferritin levels of breast-fed infants were significantly higher than in non-supplemented formula-fed infants at day 30 and day 90. This difference was seen only at day 30, when comparing breast-fed infants to lactoferrin-supplemented formula-fed infants. Comparing the infants receiving formulae, the formula supplemented with the higher amount of bovine lactoferrin induced significantly higher serum ferritin levels compared to the unsupplemented formula at day 90 and day 150. These observations favour the idea that lactoferrin may be involved in iron absorption. Since this effect was pronounced only after 90 days, it has to be discussed as to whether this effect is a convincing argument for supplementing infant formulae with bovine lactoferrin.

The yellow colour of the skin was measured just after birth in 100 mature newborns using a jaundice meter. The skin colour was significantly correlated to the cord bilirubin concentration (rho = 0.26, p = 0.009), but unrelated to cord reserve albumin concentration, cord albumin concentration, cord haemoglobin concentration, birth weight and gestational age. In 123 other mature newborns, the basal yellow colour of the skin was estimated on the basis of meter readings taken just after birth. Correction of meter readings taken on the third postnatal day for the basal yellow skin colour improved neither the correlation between the meter readings and the bilirubin concentration nor the ability of the meter readings to predict hyperbilirubinaemia.

The plasma concentrations of antithrombin III, protein C and protein S in capillary and venous blood samples obtained simultaneously from 30 neonates were compared in order to determine the suitability of using capillary blood for estimation of these proteins with anticoagulant action. Our findings showed that while capillary and venous blood did not differ significantly in antithrombin III functional activity and protein C antigen levels, the capillary samples had significantly lower protein C functional activity and higher antithrombin III antigen level. Protein S antigen level was also significantly higher in the capillary samples although the difference was relatively small. The capillary and venous concentrations of the binding protein of protein S, C4b binding protein, were almost identical.

The levels of atherogenic lipid fractions are higher in children with a family history of ischemic cardiovascular disease (CD). This study was designed to examine this relationship in neonates. A total of 1276 newborns were investigated; 400 cord blood samples were collected for measurement of triglycerides (TG), total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C); on day 4, 1200 capillary samples were taken for TC and TG measurements. Male newborns with a positive history of CD had higher concentrations of cord blood TC (P less than 0.04) and LDL-C (P less than 0.02). On day 4 this difference in TC was no longer detectable (LDL-C not determined). A coronary heart disease (CHD) risk factor family history is sensitive (0.87) in predicting high cord blood concentrations of LDL-C, the specificity being 0.46 and the positive predicting value 0.08.