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Pharmacokinetics of a netilmicin loading dose on the first postnatal day in preterm neonates with very low gestational age.

OBJECTIVE: Pharmacokinetic parameters are important for dose adjustment of aminoglycosides, but they are highly variable in neonates. In this study the pharmacokinetics of a netilmicin loading dose was investigated on the first postnatal day in preterm neonates with very low gestational age (GA). METHODS: In an open prospective study, 20 neonates with GA between 22.9 and 32.0 weeks and suspected postnatal bacterial infection received an intravenous loading dose of 5 mg/kg netilmicin over 1 h during the first postnatal day. Netilmicin serum concentrations were determined by an enzyme multiplied immunoassay. RESULTS: The systemic clearance of netilmicin normalized to body weight (BW) was not significantly different in three GA subgroups (0.59+/- 0.02 ml/min/kg for GA <24 weeks, 0.72+/-0.14 ml/min/kg for GA 24-27 weeks, and 0.62+/-0.19 ml/min/kg for GA 27-32 weeks, P=0.123). Similar results were also obtained for serum elimination half-time and for the distribution volume normalized to BW. Multiple regression analysis showed that systemic clearance and volume of distribution (both not normalized to BW) significantly correlated with BW (P<0.0001) but not with GA. In the entire group, 20% of peak concentrations were below the target of 6 mg/l, and 63% of trough concentrations were above the target of 2 mg/l. CONCLUSION: In neonates with very low GA, the pharmacokinetic parameters of netilmicin determined after an intravenous loading dose were not dependent on GA when normalized to BW. A number of neonates did not reach targeted peak and trough netilmicin serum concentrations, suggesting that a higher loading dose and a prolonged dosing interval might enhance the effectiveness and safety of netilmicin in preterm neonates immediately after birth.

Anti-Bacterial Agents↗

The postnatal maturation of the immunoglobulin heavy chain IgG repertoire in human preterm neonates is slower than in term neonates.

During the perinatal period the development of the IgH chain CDR3 (CDR-H3) repertoire of IgM transcripts is maturity-dependent and not influenced by premature exposure to Ag. To study whether maturity-dependent restrictions also predominate in the perinatal IgG repertoire we compared 1000 IgG transcripts from cord blood and venous blood of extremely preterm neonates (24-28 wk of gestation) and of term neonates from birth until early infancy with those of adults. We found the following. First, premature contact with the extrauterine environment induced the premature development of an IgG repertoire. However after preterm birth the diversification of the IgG repertoire was slower than that after term birth. Second, the IgG repertoire of preterm neonates retained immature characteristics such as short CDR-H3 regions and overrepresentation of D(H)7-27. Third, despite premature exposure to the extrauterine environment, somatic mutation frequency in IgG transcripts of preterm infants remained low until they reached a postconceptional age corresponding to the end of term gestation. Thereafter, somatic mutations accumulated with age at similar rates in preterm and term neonates and reached 30% of the adult level after 6 mo. In conclusion, class switch was inducible already at the beginning of the third trimester of gestation, but the developing IgG repertoire was characterized by similar restrictions as those of the developing IgM repertoire. Those B cells expressing more "mature" H chain sequences were not preferentially selected into the IgG repertoire. Therefore, the postnatal IgG repertoire of preterm infants until the expected date of delivery differs from the postnatal repertoire of term neonates.

Antibody Diversity↗

A randomized, double-blind, placebo-controlled investigation of the safety of intravenous immune globulin administration to preterm neonates.

Intravenous immune globulin (750 mg/kg), or an equivalent volume of a placebo, was administered during the first week of life, in a randomized trial, to 20 preterm neonates weighing 710 to 1800 g. A variety of laboratory and clinical values were measured serially and analyzed for possible untoward effects. Serum IgG levels were also determined serially. No differences in heart rate, respiratory rate, urine output, blood glucose, serum osmolality, BUN, SGPT, pH, blood gasses, serum electrolytes, total or direct bilirubin, blood leukocyte concentration, absolute neutrophil count, or blood platelet concentration were observed between the intravenous immune globulin (IVIG) and placebo recipients before or following IVIG administration. The red blood cell concentration of IVIG recipients diminished transiently and only slightly (P less than .05). Serum IgG levels increased from 503 +/- 162 mg/dL (X +/- SD) to 1492 +/- 201 mg/dL 15 minutes after the IVIG administration (P less than .001). After 8 days, serum IgG levels were still elevated, at 675 +/- 297 mg/dL. All patients randomized to receive the placebo experienced a diminution in serum IgG over this 8-day period (P less than .01). All 20 patients survived and none in either group had a documented nosocomial infection. This study suggests that IVIG can safely be administered to preterm neonates, resulting in serum IgG levels comparable to those of term infants.

Blood Chemical Analysis↗

Randomised trial of effect of delayed intravenous lipid administration on chronic lung disease in preterm neonates.

A recent sevenfold increase in the annual incidence of chronic neonatal lung disease (CNLD) on an intensive care unit was attributed to the early administration of intravenous lipid (IVL) in ventilated preterm neonates. When logistic regression was used to eliminate other confounding variables, early delivery of IVL was independently associated with an eight-fold increase in the likelihood of CNLD. Consequently, we designed a prospective study to detect a halving of the incidence of CNLD by delaying IVL administration from 5 days (as is routine practice) to 14 days. Sixty-four parenterally fed preterm neonates weighing < 1,500 g at birth were randomised to receive IVL either on day 5 or day 14. Analysis was by intention to treat, since several infants in the latter group required no parenteral nutrition by day 14. Our results showed that the relative risk (95% confidence interval) of CNLD at 28 postnatal days was 1.15 (0.81-1.62); at 36 weeks postconception, it was 1.08 (0.59-1.99). A study population of > 2,000 would be required to determine whether these relative risks were significantly different from 1.

Chronic Disease↗

Cardiovascular response to dopamine in hypotensive preterm neonates with severe hyaline membrane disease.

The effect of low dose (2, 4, and 8 micrograms/kg per min) dopamine infusion on blood pressure, heart rate and renal function was studied in 18 hypotensive, preterm infants with severe hyaline membrane disease (HMD). Significant dose-related effects found during dopamine infusion were systolic and diastolic blood pressure elevation and diuretic effect, while heart rate increase occurred only with 8 micrograms/kg per min of the drug. This indicates, that in the preterm neonate, dopamine at low doses has a pronounced effect on the alpha- and dopamine-receptors, while its beta-receptor stimulating activity is minimal. We demonstrated a significantly decreased metabolic clearance rate of dopamine in preterm infants. Thus, beside the differences in the vascular receptors' maturation, the decreased metabolic clearance rate should also be taken into account when explaining the cardiovascular and renal effects of low dose dopamine infusion in these babies. Dopamine was found to be useful in normalizing low arterial blood pressure, in improving impaired peripheral circulation, and in producing a marked diuresis in hypotensive preterm neonates with severe hyaline membrane disease.

Blood Pressure↗

Prenatal MgSO4 treatment modifies the erythrocyte band 3 in preterm neonates.

Magnesium sulphate that is widely used to prevent preterm labour or treatment for imminent eclampsia is also suggested to decrease a cerebral palsy in preterm newborns. However, the molecular mechanism of MgSO4 protection in fetus remains unknown. Since Mg2+ very rapidly crosses the placenta, we assayed whether it may exert an effect on newborn erythrocytes, particularly on anion exchange band 3. The study groups consisted of preterm neonates born from mothers who received prenatally magnesium sulphate and a control group, without prenatal Mg2+ administration. We compared the selected erythrocyte parameters including ATP concentration, membrane lipids peroxidation, the band 3 amount and its phosphotyrosine level, assayed after delivery and 24h later. At birth, ATP concentration was higher in control newborns and decreased after 24h, reaching the level found in the MgSO4-treated group. Band 3 and P-Tyr amounts were unchanged in MgSO4-treated newborns during examined period. In the control group, the lower Mg concentration after delivery correlated with the lowered band 3 phosphorylation. We have also observed enlarged TBARS content in control membranes. Our results demonstrate that prenatal administration of magnesium sulphate significantly altered some erythrocyte parameters. These data suggest that MgSO4 may modify the erythrocytes metabolism in preterm newborns. Since band 3 exhibits the same structural and functional activities as in the brain, the elucidation of MgSO4 influence is of special importance.

Adenosine Triphosphate↗

Role of plasma B-type natriuretic peptide in screening for hemodynamically significant patent ductus arteriosus in preterm neonates.

BACKGROUND: B-type natriuretic peptide (BNP) is a hormone secreted by the ventricles under hemodynamic stress and congestive failure. OBJECTIVE: The objective of the present study was to evaluate whether BNP can be used as a valid screening test for the presence of a hemodynamically significant patent ductus arteriosus (hsPDA) in the preterm neonate. MATERIALS AND METHODS: This was a prospective blinded study involving preterm neonates with birth weights <or=1500 g and gestational age <or=34 weeks. Each enrolled neonate underwent the initial echocardiogram for a clinical suspicion of patent ductus arteriosus (PDA) and BNP assay within 3 hours of each other. Those neonates who did not have a PDA or who were not treated underwent a repeat echo and BNP measurement 48 to 72 hours after the first echo. In patients who received treatment for a PDA, an echo and BNP were repeated 48 to 72 hours after completion of treatment. RESULTS: A total of 29 newborns with a median birth weight of 870 g (560 to 1325 g) and a median gestation of 26 weeks (24 to 31 weeks) were enrolled at a median age of 7 days (2 to 28 days). BNP levels were significantly higher in neonates with hsPDA (n=14) compared to those without (n=15) (508.5+/-618.2 vs 59.5+/-69.9 pg/ml, p<0.005). At a cutoff value of 70 pg/ml, BNP had a sensitivity of 92.9%, specificity of 73.3%, positive likelihood ratio of 3.5 and negative likelihood ratio of 0.09 for detection of hsPDA. BNP levels dropped significantly after medical or surgical closure of hsPDA (n=12), (404.9+/-159.2 to 25.1+/-4.1 pg/ml, p=0.03). CONCLUSIONS: Elevation of plasma BNP accurately detects the presence of hsPDA in premature infants. Successful closure is reflected by a corresponding decrease in BNP. At a cutoff of 70 pg/ml, BNP is a useful screening tool for diagnosis and for monitoring efficacy of treatment of hsPDA.

Ductus Arteriosus, Patent↗

Patent ductus arteriosus in preterm neonates.

Failure of the ductus arteriosus to close within 48-96 hours of postnatal age results in a left to right shunt across the ductus and overloading of the pulmonary circulation. This is more likely to happen in premature neonates with respiratory distress syndrome. Deterioration in the respiratory status on day 3-4 in a ventilated neonate and unexplained metabolic acidosis may be the earliest indicators of a patent ductus arteriosus (PDA). Indomethacin is the main stay of medical management of PDA in preterm neonates. Guidelines for administration of indomethacin have been described in the protocol. Restricted fluid therapy may be beneficial in the prevention of PDA in preterm neonates. Presence of PDA in a term neonate should be investigated to rule out an underlying congenital heart disease.

Cyclooxygenase Inhibitors↗

The voiding pattern of healthy preterm neonates.

PURPOSE: To elucidate further the maturation of voiding habits from gestation to infancy we investigated the free voiding pattern of healthy preterm neonates. MATERIALS AND METHODS: We evaluated 11 male and 8 female healthy preterm newborns at a mean of 32 weeks after cessation of menstrual flow (postmenstrual age). Assessment was done in the neonatal ward using 4-hour voiding observation, a method described previously in studies of free voiding pattern of full-term newborns. RESULTS: The voiding pattern of male and female preterm neonates was characterized by 1 void per hour and a mean voided volume of 53% of bladder capacity with 58% frequency of interrupted voiding. Residual urine was increased but varied during observation (mean 11% bladder capacity) and was 0 after at least 1 void during 4 hours in 14 of the 19 subjects. Two-thirds of all voiding occurred during sleep, whereas a third of the newborns showed signs of arousal with a mean awake time of only 17 minutes. CONCLUSIONS: The voiding pattern of preterm versus full-term subjects is characterized by an increased number of interrupted voidings, further indicating that these voidings represent immature behavior of detrusor-sphincter coordination. Also, the high number of voidings during sleep suggest a more immature pattern for preterm newborns.

Female↗

A randomized, controlled evaluation of two commercially available human breast milk fortifiers in healthy preterm neonates.

OBJECTIVE: To evaluate the added nutritional value of the two commercially available human breast milk fortifiers: Similac Natural Care (NC) and Enfamil Powder (EP). DESIGN: A randomized controlled evaluation in healthy preterm neonates. SETTING: Neonatal Intensive Care Unit, Royal University Hospital, Saskatoon, Saskatchewan, and Neonatal Intensive Care Unit, Jewish General Hospital, Montreal, Quebec, Canada. SUBJECTS: Healthy preterm infants admitted to and cared for in the aforementioned neonatal intensive care units. INTERVENTIONS: Healthy preterm neonates who were receiving expressed breast milk from their own mothers were supplemented with human milk fortifiers (NC and EP) per manufacturer's recommendations. MAIN OUTCOME MEASURES: Gestational age and birth weight, gender, and race. At entry to and exit from the study, serum concentrations of albumin, protein, calcium, phosphorus, and alkaline phosphatase. The age at which the supplements were added and the number of days the infant remained in the hospital. Daily weight gain, head circumference, length, and height were also measured. STATISTICAL ANALYSES PERFORMED: Student's t test was used to test the differences between the groups and within the groups at entry to and exit from the study. Fisher's exact test was used to determine differences in race, size, and gestational age in each group. When necessary, a chi 2 test was used to analyze the preponderance of either sex in each group. A Wilcoxon rank test was applied to the true exit date to determine whether the bias was comparable in each group. RESULTS: The mean (+/- standard error) gestational age and birth weight were similar in both groups: 30 +/- 0.3 weeks and 1,314 +/- 40 g, respectively, for NC vs 29.6 +/- 0.35 weeks and 1,262 +/- 45 g, respectively, for EP. At entry to the study, values for the NC group (N = 29) were albumin 31 +/- 1.2 g/L, serum protein 48 +/- 1.4 g/L, calcium 2.4 +/- 0.03 mmol/L, phosphorus 1.85 +/- 0.08 mmol/L, alkaline phosphatase 347 +/- 27 IU/L. The values for the EP group (N = 30) were albumin 32 +/- 0.9 g/L, serum protein 49 +/- 1.4 g/L, calcium 2.4 +/- 0.4 mmol/L, phosphorus 1.9 +/- 0.1 mmol/L, alkaline phosphatase 420 +/- 34 IU/L. At the study exit, the values for the NC group were albumin 30 +/- 0.7 g/L, serum protein 45 +/- 0.9 g/L, calcium 2.4 +/- 0.3 mmol/L, phosphorus 1.96 +/- 0.07 mmol/L, and alkaline phosphatase 371 +/- 23 IU/L. The values for the EP group were albumin 32 +/- 1.0 g/L, serum protein 46.0 +/- 1.4 g/L, calcium 2.5 +/- 0.03 mmol/L, serum phosphorus 2.2 +/- 0.1, and alkaline phosphatase 367 +/- 27 IU/L. No significant differences were observed between groups at entry to and exit from the study. However, in the EP group the alkaline phosphatase decreased significantly (P = .02) from entry to exit and calcium increased significantly during the same period compared with the NC group (P = .003). The mean daily weight gain was 33 +/- 0.7 g for the NC group and 31 +/- 1 g for the EP group. The weekly gain in head circumference and body length were also similar in both groups: approximately 1 cm/week. Both groups tolerated the fortifiers well. APPLICATIONS/CONCLUSIONS: These findings suggest that both products provide the additional nutritional support necessary for optimal overall postnatal growth in healthy preterm infants. The differences in calcium and alkaline phosphatase may be due to the differences in vitamin D content in fortifiers 88 IU/100 mL in mixed NC vs 270 IU/100 mL in mixed EP. This observation calls for careful monitoring of calcium and alkaline phosphatase values and possible adjustments of vitamin D intake when fortifiers are used for extended periods.

Alkaline Phosphatase↗

Arterial oxygen saturation in preterm neonates without respiratory failure.

To obtain normal data on arterial oxygen saturation as measured by pulse oximetry (SpO2; Nellcor N200), we obtained 12-hour tape recordings of SpO2, photoplethysmographic waveforms, instantaneous pulse rate, and observations of breathing movements on 55 preterm neonates (25 girls) who had been admitted to one of four special care baby units but had no signs of respiratory distress and were breathing room air at 24 hours of age. Their median gestational age at birth was 35 weeks (range, 30 to 36), and their median age at the time of study 1 day (range, 1 to 7). Median baseline SpO2, measured only during regular breathing, was 99.4% (range, 90.7 to 100; 5th percentile, 95.5). Ten recordings (18%) contained a total of 83 episodes of desaturation (defined as a fall in SpO2 to < or = 80% for > or = 4 seconds). The 95th percentile for desaturation frequency was eight per recording. One infant had 55 episodes of desaturation and thus accounted for two thirds of all episodes observed. Only one of the episodes of desaturation in this infant, and none of those in the other nine infants, had been noted clinically, nor had the abnormally low baseline SpO2 (90.7%) in one infant. Baseline SpO2 in these nondistressed preterm neonates was higher than might be expected, given the SpO2 levels currently recommended for preterm infants with respiratory failure. A minority of infants, however, had a low baseline SpO2 or a high frequency of episodes of desaturation, the potential effects of which remain to be determined.

Arteries↗

Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study.

BACKGROUND: Colonization by Candida species is the most important predictor of the development of invasive fungal disease in preterm neonates, and the enteric reservoir is a major site of colonization. We evaluated the effectiveness of an orally supplemented probiotic (Lactobacillus casei subspecies rhamnosus; Dicoflor [Dicofarm spa]; 6 x 10(9) cfu/day) in the prevention of gastrointestinal colonization by Candida species in preterm, very low birth weight (i.e., < 1500-g) neonates during their stay in a neonatal intensive care unit. METHODS: Over a 12-month period, a prospective, randomized, blind, clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit. During the first 3 days of life, the neonates were randomly assigned to receive either an oral probiotic added to human (maternal or pooled donors') milk (group A) or human milk alone (group B) for 6 weeks or until discharge from the NICU, if the neonate was discharged before 6 weeks. On a weekly basis, specimens obtained from various sites (i.e., oropharyngeal, stool, gastric aspirate, and rectal specimens) were collected from all patients for surveillance culture, to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract. RESULTS: The incidence of fungal enteric colonization (with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site) was significantly lower in group A than in group B (23.1% vs. 48.8%; relative risk, 0.315 [95% confidence interval, 0.120-0.826]; P = .01). The numbers of fungal isolates obtained from each neonate (P = .005) and from each colonized patient (P = .005) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001-1500 g. There were no changes in the relative proportions of the different Candida strains. No adverse effects potentially associated with the probiotic were recorded. CONCLUSIONS: Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by Candida species among very low birth weight neonates.

Administration, Oral↗

Measurement of right ventricular volume in healthy term and preterm neonates.

BACKGROUND: Pulmonary hypertension is associated with worse perinatal outcomes in infants with respiratory disorders. In such infants right ventricular dysfunction may result in poor pulmonary blood flow. OBJECTIVE: To evaluate the practicability and repeatability of echocardiographic measurements of right ventricular volume in healthy term and preterm neonates, and to follow changes in right ventricular volume over the first 2 days of life. METHODS: Serial echocardiographic examinations were performed on day 0, 1, and 2 on healthy term and preterm neonates. Two methods of estimating right ventricular volume were assessed: the ellipsoid approximation and Simpson's stacked discs methods. Systolic and diastolic volumes on days 1 and 2 were compared with baseline values on day 0. Term and preterm volumes were compared at the same time points. RESULTS: Thirty five infants were recruited, 18 term and 17 preterm. Right ventricular volumes were significantly lower on day 1 and day 2 than baseline in both term and preterm infants. Median (interquartile range) end systolic and diastolic volumes for term infants on days 0, 1, and 2 were 1.04 (0.88-1.44), 0.82 (0.70-1.03), 0.92 (0.72-0.97) ml/kg and 2.21 (2.10-2.75), 2.05 (1.81-2.38), 1.91 (1.81-2.13) ml/kg respectively. In preterm infants the values were 1.09 (0.91-1.16), 0.72 (0.54-0.91), 0.61 (0.54-0.76) ml/kg and 2.09 (1.71-2.25), 1.47 (1.23-1.98), 1.43 (1.22-1.78) ml/kg respectively. CONCLUSION: Right ventricular volume decreases over the first 2 days of life in healthy term and preterm infants.

Cardiac Output↗

Mechanisms of blood pressure increase induced by dopamine in hypotensive preterm neonates.

AIMS: To compare changes in global haemodynamics as well as anterior cerebral and superior mesenteric artery perfusion after dopamine treatment. METHODS: Anterior cerebal and superior mesenteric artery perfusion was measured using Doppler ultrasonography in hypotensive preterm neonates in whom cardiac output increased (group 1, n=10) or decreased (group 2, n=40) after dopamine treatment. RESULTS: Despite a lower dopamine infusion rate, the blood pressure increase (mm Hg) in group 2 [Delta=13(1); mean(SE)] exceeded that in group 1 [Delta=8(1)], while systemic vascular resistance (mm Hg/l/min/kg) rose in group 2 [Delta=106 (37)], but was unchanged in group 1 [Delta=9 (6)]. Anterior cerebral artery blood velocity and resistance were unaffected by dopamine. However, compared with unchanged values in group 1, superior mesenteric artery blood velocity fell by 14.7(4.8) cm/s and resistance increased by 4.1(0.7) mm Hg/cm in group 2. CONCLUSIONS: These results suggest that, in a portion of hypotensive preterm neonates, the increase in blood pressure induced by dopamine is related to a predominant vasoconstrictor action and is associated with a fall in bowel perfusion.

Blood Pressure↗

Computer classification of state in healthy preterm neonates.

Nineteen electroencephalographic (EEG) sleep measures describing four physiologic aspects of sleep behavior (i.e. sleep continuity, EEG spectra, body and eye movements, and autonomic measures) were derived from visual and computer analyses of 71 24-channel, 3-hour EEG sleep recordings on 52 healthy preterm neonates from 28-36.5 weeks postconceptional age (PCA). Forty-eight subjects were neurodevelopmentally normal up to 2 years of age. Four electrographic states that comprise tracé discontinu of the preterm neonate were defined in terms of increasing seconds of EEG quiescence per minute. A regression analysis was performed after transformations of nonlinear data sets representing the 19 EEG sleep measures, with the four sleep states as outcome variables. Postconceptional age was also included in these analyses as the 20th explanatory variable. Four measures best defined the EEG sleep states, explaining 75% of the variance: decreasing rapid eye movements per minute, decreasing numbers of spontaneous arousals per minute, increasing spectral theta energies, and decreasing facial movements per minute. Other cerebral and noncerebral measures, including total spectral EEG energies, spectral EEG energies in three bandwidths (i.e. delta, alpha, beta), cardiac and respiratory measures, and body movements, did not contribute as significantly to the prediction. Inclusion of PCA into the regression equation with the four EEG measures, selected by the analysis procedure, indicated that its contribution to state prediction was also small; the effect of PCA on state was found to be explained by the four EEG sleep measures.

Electroencephalography↗

Genetic polymorphisms and risk for acute renal failure in preterm neonates.

Acute renal failure (ARF) affects about 10% of severely ill neonates. Recent studies have shown that genetic polymorphisms of proteins that play a role in neonatal physiology may contribute to individual susceptibility to both ARF and its risk factors. Our review summarizes the data collected to date. Studies have shown that the risk of preterm neonates for ARF is directly associated with a combination of high tumor necrosis factor-alpha producer and low interleukin-6 producer genotypes, as well as with low heat shock protein 72 producer genotype. Premature birth is itself the most important risk factor for a number of complications, including ARF, and recent studies have also shown an association between several maternal and fetal cytokine genetic polymorphisms and increased inflammatory response in preterm neonates. These polymorphisms could also be associated with increased risk for disorders such as sepsis and necrotizing enterocolitis, which lead to renal hypoperfusion and ARF. Genetic polymorphisms of the renin-angiotensin-aldosterone system have not been shown to directly influence risk for ARF. They may, however, be associated with patent ductus arteriosus, poor postnatal adaptation, and heart failure, which are all prevalent risk factors for ARF.

Acute Kidney Injury↗

Ventilator-associated sinus arrhythmia in a preterm neonate--an indicator for a mature autonomic nervous system?

According to control theory, the interactions between respiration and heart rate (i.e. respiratory sinus arrhythmia, RSA, and breath amplitude sinus arrhythmia, BASA) reflect the inner workings of the physiological control systems of respiration and circulation. This paper reports on a preterm neonate (28.5 weeks old, 940 g) who showed the presence of ventilation-associated sinus arrhythmia (VASA) under moderate artificial ventilation. His heart rate variability was entrained to the ventilatory stimulus. VASA and entrainment suggest that the parasympathetic part of the autonomic nervous system might be more mature than expected in some preterm neonates.

Arrhythmia, Sinus↗

Effects of hypoxia on megakaryocyte progenitors obtained from the umbilical cord blood of term and preterm neonates.

BACKGROUND: Placental insufficiency is associated with early-onset thrombocytopenia in preterm neonates. Prior studies demonstrated a reduction in circulating megakaryocyte (Mk) progenitors, suggesting decreased platelet production. We hypothesized that decreased Mk production is the result of a direct inhibitory effect of hypoxia on the proliferation of Mk progenitors, or a hypoxia-induced change in the fetal hematopoietic environment. OBJECTIVE: To test the effects of hypoxia on the clonogenic maturation of Mk progenitors obtained from term and preterm cord blood CD34(pos) cells, either cultured alone or in conjunction with CD34(neg) light density mononuclear cells (LDMCs). METHODS: CD34(pos) cells and CD34(neg) LDMCs were isolated from the cord blood of term and preterm deliveries, and mobilized peripheral blood CD34(pos) cells were obtained from healthy adults. CD34(pos) cells were then cultured alone or co-cultured with CD34(neg) LDMCs in a semisolid, serum-free media containing rTpo, IL-3, and IL-6. Cultures were exposed to 20%, 5%, or 1% oxygen for 10-12 days. Mk colonies were then quantified following immunohistochemical staining. RESULTS: Pure CD34(pos) cells from preterm (n = 5) and term (n = 5) neonates and from adults (n = 4) generated similar numbers of Mk colonies in all three oxygen concentrations. However, the number of Mk colonies in preterm co-cultures was progressively lower with decreasing O(2) concentrations. CONCLUSIONS: Hypoxia did not appear to directly inhibit colony formation of Mk progenitors from preterm and term cord blood CD34(pos) cells. However, co-culture studies showed a decrease in Mk colony formation with hypoxia, suggesting an indirect inhibitory effect of hypoxia on Mk clonogenic maturation mediated by non-progenitor cells in the hematopoietic microenvironment.

Antigens, CD34↗