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Early arterial lactate and prediction of outcome in preterm neonates admitted to a neonatal intensive care unit.

AIM: In the present study early arterial lactate samples were examined to predict adverse outcome in preterm neonates. SUBJECTS AND METHODS: 88 preterm neonates (mean gestational age 29.8 weeks, mean birth weight 1,225 g) had arterial lactate levels measured from indwelling arterial catheters within the first 3 h of life. An adverse outcome was defined as death or abnormal neurodevelopment. The positive (PPV) and negative predictive value (NPV) of early arterial lactate levels for an adverse outcome (death or neurodevelopmental abnormalities) were calculated using receiver operating characteristic analysis. RESULTS: PPV and NPV of arterial lactate within 3 h after birth were 0.47 and 0.92, respectively, with a cutoff value of 5.7 mmol/l. Umbilical blood gas values and 1 and 5 min Apgar scores had much lower PPVs. CONCLUSION: Arterial lactate levels within 3 h of life can be used to select preterm neonates who are at risk of an adverse outcome.

Apgar Score↗

Intestinal permeability and carrier-mediated monosaccharide absorption in preterm neonates during the early postnatal period.

Immaturity of intestinal epithelial barrier function and absorptive capacity may play a role in the pathophysiology of intestinal complications in preterm neonates during the early postnatal period. We determined the intestinal permeability and carrier-mediated absorption of monosaccharides in preterm neonates during the first 2 wk after birth. Fifty-nine preterm neonates born between 25 and 32 wk gestation were included within 24 h of birth. Neonates received exclusively parenteral nutrition during the first 7 d after birth; enteral feeding was initiated at d 8. An intestinal permeability-absorption test was performed at 1, 4, 7, and 14 d after birth. The lactulose-to-rhamnose ratio was determined as a marker of intestinal permeability. Urinary excretion percentages of D-xylose and 3-O-methyl-D-glucose were determined as markers of passive and active carrier-mediated monosaccharide absorption, respectively. Intestinal permeability transiently increased between d 1 and 7 in all neonates (p < 0.05). Carrier-mediated monosaccharide absorption increased between d 1 and 14 in neonates of 28-30 wk (p < 0.05) to the level observed in the neonates of 30-32 wk gestation. In neonates <28 wk, intestinal permeability at d 7 was higher (p < 0.05) and carrier-mediated monosaccharide absorption at d 14 was lower (p < 0.01) as compared with neonates >or=28 wk. The barrier function of the intestinal epithelium transiently decreases during the first week after birth in preterm neonates who are not enterally fed. Diminished barrier function and low monosaccharide absorptive capacity, particularly in neonates <28 wk, may predispose these patients to the development of intestinal complications during the early postnatal period.

Female↗

Stress responses in preterm neonates after normal and at-risk pregnancies.

OBJECTIVE: To evaluate the autonomic response in preterm neonates born after an at-risk pregnancy. METHODOLOGY: Twenty-one preterm neonates (gestational age; GA) 29-37 weeks; bodyweight (BW): 720-2113 g; postnatal age: 2-126 days), born after at-risk pregnancies (stressed (STR) group), were compared to 30 preterm neonates (GA: 26-36 weeks; BW: 813-2380 g: postnatal age: 2-86 days) without any intrauterine risk factor (C group). A 10 s pain stimulus was given on the forefoot and heart rate, respiratory rate and blood pressure were measured at 15 and 30 s, at 1, 2, 3, 4 and 5 min. After 10 s ocular compression six cardiac variables were recorded. RESULTS: After the pain stimulus the STR-group had a significant increase of heart rate at 15 s and an increase of diastolic blood pressure at 30 s. In the C group a significant increase of heart rate at 15 s was recorded. For the respiratory rate both groups showed an initial depression (significant at 15 s in the C group) followed by an increase. The time to react to the ocular compression was significantly shorter in the STR-group than in the C-group and thus more parasympathetic. CONCLUSIONS: We hypothesize that the different sympathetic and parasympathetic reaction patterns of the vital parameters to triggers in the STR-group are due to chronic stress, pointing to an altered maturation of the two components of the autonomic nervous system after chronic intrauterine stress (CIUSTR).

Analysis of Variance↗

Work of breathing during constant- and variable-flow nasal continuous positive airway pressure in preterm neonates.

BACKGROUND: Constant-flow nasal continuous positive airway pressure (NCPAP) often is used in preterm neonates to recruit and maintain lung volume. Physical model studies indicate that a variable-flow NCPAP device provides more stable volume recruitment with less imposed work of breathing (WOB). Although superior lung recruitment with variable-flow NCPAP has been demonstrated in preterm neonates, corroborating WOB data are lacking. OBJECTIVE: To measure and compare WOB associated with the use of variable-flow versus constant-flow NCPAP in preterm neonates. METHODS: Twenty-four preterm infants who were receiving constant-flow NCPAP (means, SD) and had birth weight of 1024 +/- 253 g, gestational age of 28 +/- 1.7 weeks, age of 14 +/- 13 days, and FIO(2) of 0.3 +/- 0.1 were studied. Variable-flow and constant-flow NCPAP were applied in random order. We measured changes in lung volume and tidal ventilation (V(T)) by DC-coupled/calibrated respiratory inductance plethysmography as well as esophageal pressures at NCPAP of 8, 6, 4, and 0 cm H(2)O. Inspiratory WOB (WOB(I)) and lung compliance were calculated from the esophageal pressure and V(T) data using standard methods. WOB was divided by V(T) to standardize the results. RESULTS: WOB(I) decreased at all CPAP levels with variable-flow NCPAP, with a maximal decrease at 4 cm H(2)O. WOB(I) increased at all CPAP levels with constant-flow CPAP. Lung compliance increased at all NCPAP levels with variable-flow, with a relative decrease at 8 cm H(2)O, whereas it increased only at 8 cm H(2)O with constant-flow NCPAP. Compared with constant-flow NCPAP, WOB(I) was 13% to 29% lower with variable-flow NCPAP. CONCLUSION: WOB(I) is decreased with variable-flow NCPAP compared with constant-flow NCPAP. The increase in WOB(I) with constant-flow NCPAP indicates the presence of appreciable imposed WOB with this device. Our study, performed in neonates with little lung disease, indicates the possibility of lung overdistention at CPAP of 6 to 8 cm H(2)O with the variable-flow device. Further study is necessary to determine the efficacy of variable-flow NCPAP in neonates with significant lung disease and its use over extended periods of time.continuous-flow and variable-flow NCPAP, work of breathing, premature neonates, lung compliance.

Equipment Design↗

Intraventricular hemorrhage in preterm neonates--a two year experience.

A prospective brain sonograph study was performed on 134 preterm neonates with birth weight of less than 2500 gm. Ten (7.5%) infants had intraventricular hemorrhage (IVH). The incidence of IVH in preterm neonates weighing less than 1500 gm was 13% and in neonates of less than 32 weeks gestation was 11.27%. Ninety percent of the IVH occurred within the first 72 hours of life. Prematurity, and hypoxia were considered as significant contributing factors for neonatal IVH. Six of the 7 infants with IVH grade I have a favorable neurological outcome. One of the 3 infants with IVH grade III has psychomotor delay. Routine brain sonograph study is considered practical and invaluable for diagnosis of IVH in preterm neonates.

Cerebral Hemorrhage↗

Aerosolized furosemide in the treatment of acute respiratory distress and possible bronchopulmonary dysplasia in preterm neonates.

OBJECTIVE: To review the efficacy and safety of inhaled furosemide in the treatment of acute respiratory distress and possible bronchopulmonary dysplasia (BPD) in preterm neonates receiving ventilator and oxygen support. DATA SOURCES: A MEDLINE search was performed from January 1966 to December 1998 using the key words inhaled or aerosolized furosemide, BPD, preterm, neonate, and infant newborn. STUDY SELECTION AND DATA EXTRACTION: All clinical trials involving the use of inhaled furosemide in ventilator- and oxygen-dependent preterm neonates with acute respiratory distress and possible BPD were evaluated. DATA SYNTHESIS: Inhaled furosemide 1 and 2 mg/kg has improved pulmonary function in preterm neonates without significant adverse effects. However, only a single dose of inhaled furosemide was used in these trials, and pulmonary functions were monitored for only two or four hours after administration. CONCLUSIONS: Inhaled furosemide may be effective, but studies are needed to determine the optimal dosage regimen and long-term risks and benefits of its use in these patients.

Administration, Inhalation↗

Inflation time in mechanical ventilation of preterm neonates.

The importance of the preterm infant's inspiratory time in determining the optimum inflation time during mechanical ventilation was investigated. The optimum inflation time was defined as that which was most commonly associated with synchronous respiration and maximum minute volume. Twelve preterm infants were studied on 14 occasions. They were ventilated at rates of 60, 75, 90, 105 and 120 breaths/min, with an inspiratory: expiratory ratio of 1:1.2. These rates were chosen as they resulted in inflation times approximating to the spontaneous inspiratory time measured during a brief period of disconnection, on continuous positive airways pressure (CPAP), and greater than that measured on CPAP. Inspiratory time during disconnection was always shorter than that measured on CPAP (P less than 0.01). Synchrony was most commonly provoked and minute volume greatest at the shortest inflation time (P less than 0.01). We conclude fast ventilator rates are most efficacious for preterm neonates. As previously shown, this rate can be estimated by examining the standard reference range of rates in relation to gestational age.

Gestational Age↗

Intravenous immunoglobulin in the treatment of Salmonella typhimurium infections in preterm neonates.

The purpose of this study was to determine the role of intravenous immunoglobulin (IVIG) administration in preterm neonates with S. typhimurium infection. A randomized trial of 47 preterm neonates with intestinal or extraintestinal S. typhimurium infection was performed. Neonates were randomly divided into two groups: 22 neonates were only given cefoperazone (group 1); 25 neonates were given cefoperazone plus IVIG (group 2). IVIG was given at a dose of 500 mg/kg on days 1, 2, 3, and 8 after entry into the study. Following treatment, bacteremia, complications, mortality rate, recovery time, and duration of antimicrobial therapy were evaluated in two groups. Bacteremia was found in 31.4% in group 1 and 8% in group 2 (P < .05); complications developed in 81.8% in group 1 and 16% in group 2 (P < 0.01); mortality was 40.9% in group 1 and 12% in group 2 (P < .05). Recovery took 15 days in group 1 and 8 days in group 2 (P < .01). The duration of antimicrobial therapy was 20 days in group 1 and 14 days in group 2 (P < .01). We conclude that IVIG treatment in combination with antibiotics in preterm neonates with S. typhimurium infection reduces the complications, mortality rate, and duration of therapy.

Cefoperazone↗

Hyperglycaemia as a possible marker of invasive fungal infection in preterm neonates.

AIM: The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognition and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. METHODS: We performed a case-control study on neonates with birthweight less than 1250 g admitted to our tertiary-level unit during the years 1998-2004 (n = 383), comparing those with invasive fungal infection (n = 45, group A) to matched controls with late-onset sepsis caused by bacterial agents (n = 46, group B). We investigated in both groups the occurrence of hyperglycaemia (serum glycaemia > 215 mg/dl, i.e. 12 mmol/l) in the first month of life, and its temporal relationship with the episodes of sepsis. RESULTS: Hyperglycaemia occurred significantly more often in group A (21/45, 46.6%) than in group B neonates (11/46, 23.9%) (OR 1.95, 95% CI 1.235-4.432, p = 0.008). Moreover, in 19 of 21 (90.4%) neonates with hyperglycaemia in group A, the carbohydrate intolerance episode typically occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis (p = 0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia (p = 0.15). CONCLUSIONS: Hyperglycaemia is significantly more frequent in neonates who subsequently develop fungal rather than bacterial late-onset sepsis, with a typical 3-d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be carefully evaluated for systemic fungal infection whenever signs of carbohydrate intolerance occur.

Biomarkers↗

The evolution of a simplified method for interpretation of EEG in the preterm neonate.

We describe the evolution of a simplified method for the interpretation of serial EEG in preterm neonates which was tested in a first sample and revised and improved in a second sample of preterm neonates. There were 185 EEGs in the first sample and 206 EEGs in the second sample. The interpretation of the EEGs was related to mental, motor and neurological outcome in late infancy. Serial EEG is an excellent indicator of brain function in the preterm neonate.

Brain↗

Platelet function in term and preterm neonates.

Platelet dysfunction likely contributes to the pathophysiology of catastrophic hemorrhages in preterm neonates. In vitro studies have demonstrated that platelets of both term and preterm neonates are hyporesponsive to a variety of agonists. In contrast,template bleeding times of term neonates are shorter than those from adults. Very little is known about this and other tests of primary hemostasis in premature and sick neonates in the neonatal intensive care unit (NICU). This article covers the current knowledge of platelet function in preterm and term neonates and review show new agents (such as recombinant thrombopoietin and recombinant factor VIIa) may enhance neonatal platelet function.

Blood Platelets↗

Acute effects of gentamicin on glomerular and tubular functions in preterm neonates.

It has been reported that gentamicin causes natriuresis, magnesuria and calciuria in neonates. The aim of this study was to determine the acute effects of trough and peak levels of gentamicin on the values of serum creatinine (SCr), urine albumin/urine creatinine (UA/UCr), fractional excretion of sodium and potassium (FENa, FEK) and urine calcium/urine creatinine (UCa/UCr) in preterm neonates treated with gentamicin for suspected infection. Baseline levels of serum and urine Cr, Na and K and urine albumin and Ca levels together with trough and peak gentamicin levels were measured in 61 preterm neonates at the start of the therapy, on the day of the third gentamicin dose and 48-72 h after the cessation of the gentamicin therapy. Therapeutic trough and peak levels were recorded in 56 (91.8%) and 39 (63.9%) of the preterm neonates, respectively, whereas high trough (>2 mg/dl) and peak (>9.99 mg/dl) levels were recorded in five (8.1%) and 11 (18%) of the 61 preterm neonates, respectively. Trough and peak levels of gentamicin were positively correlated with SCr, UA/UCr, FENa, FEK and UCa/UCr values. The UA/UCr, FENa and UCa/UCr values recorded during treatment were statistically significantly different from sub-therapeutic, therapeutic and high peak gentamicin levels. Gentamicin was found to have a serum peak level-dependent microalbuminuric, natriuric and calciuric effect in preterm neonates. Based on these results, we suggest that when the monitoring of serum gentamicin levels is not possible, the monitoring of UA/UCr, FENa and UCa/UCr can be useful as a noninvasive alternative.

Albuminuria↗

Critical closing pressure in preterm neonates: towards a comprehensive model of cerebral autoregulation.

In preterm neonates, intraventricular haemorrhage is linked to the dysfunction of cerebral autoregulation (AR). We aimed at tracing the critical closing pressure (CCP) in order to quantify AR and to reveal its inner workings. In an observational study, 10 preterm neonates (median, range: ga 28 weeks, 25 to 32 weeks; bw 1070, 685 to 1730 g; age 2d, 1 to 7 d) were continuously Doppler traced (a. carotis interna) for > 10 min. Systemic blood pressure (BP, a. umbilicalis, a. radialis, a. temporalis) was recorded simultaneously (> 1200 cardiac cycles each). Systolic BP was on average 11 mmHg above CCP. There was a striking parallel between both variables, even in cases of sudden spontaneous BP fluctuations > 30% (r = 0.72, 0.41 to 0.99), while systolic cerebral blood flow velocity remained largely unaffected (r = -0.15, -0.75 to 0.53), indicating a properly functioning AR. CCP was 28 mmHg, 14 to 38 mmHg. Based on our data, a physiological model of AR is developed, integrating anatomy, metabolic and neuronal pathways with former physiologic findings--including low frequency cycling of cerebral blood flow velocity. Tracing of CCP is thought to have the potential to identify infants with impaired AR. Since this method is noninvasive and independent of angle of insonation (thus rendering it uncritical in probe fixation), it is a promising tool for sustained monitoring of cerebral haemadynamics in the clinical setting.

Blood Flow Velocity↗

Furosemide nephrolithiasis causing ureteral obstruction and urinoma in a preterm neonate.

Nephrolithiasis and nephrocalcinosis in low-birth-weight, preterm neonates are well-documented complications of furosemide administration. Perinephric urinomas and urinary ascites have been previously reported as complications of obstruction due to posterior urethral valves or ureteropelvic junction obstruction. We present an unusual case of furosemide-induced nephrolithiasis causing ureteral obstruction, urinoma, and acute renal failure in a preterm neonate.

Acute Kidney Injury↗

Serum free thyroxine and free triiodothyronine concentrations in healthy fullterm, preterm and sick preterm neonates.

There are few data available on free thyroid hormone concentrations in the early neonatal period. With the widespread application of screening procedures for detecting congenital hypothyroidism there is a need for reference ranges in neonates. In this study we have evaluated thyroid function in healthy fullterm and preterm neonates, and sick neonates all within one to 10 days postnatal age. Our data indicates that free thyroxine but not free triiodothyronine is higher in fullterm neonates than the adult reference range and that both free thyroid hormone concentrations are reduced in healthy and sick preterm neonates as compared to fullterm neonates. Assessment of thyroid function in the early neonatal period needs to take into account these changes particularly in preterm and sick preterm neonates.

Female↗

Ultrasound grading of cerebral ventricular dilatation in preterm neonates.

OBJECTIVE: To compare three grading systems previously described for the measurement of cerebral ventricular dilatation in preterm neonates using ultrasound scans and then to compare these with expert clinical judgement. METHODS: Eighty-one preterm neonates <1500 g birthweight or < 32 weeks' gestation, with normal, mild, moderate or severely dilated ventricles recorded predominantly during the first 2 weeks of life were selected to ensure a broad representation of ventricular size. Their cranial ultrasound scans obtained nearest to 6 weeks of age were studied. The ventricular index, the diagonal width in the coronal plane and the ventricular height in the parasagittal plane were measured adjacent to the foramen of Monro and were used to grade the degree of dilatation. In 20 of these neonates, this grading was compared with grading based on expert clinical judgement. RESULTS: Grading according to the ventricular index defined 79% of the scans as normal. However, only 44% and 39% were considered to be normal according to vertical height and diagonal width, respectively. There was a high level of correlation between expert clinical judgement and grading based on ventricular height measurement (r = 0.812; area under receiver operating characteristic (ROC) curve = 0.922) and the diagonal width (r = 0.806; area under ROC curve = 0.935). Ventricular index correlated poorly with clinical judgement (r = 0.298; area under ROC curve = 0.604). CONCLUSIONS: The measurement of ventricular height and the measurement of diagonal width correlated well with expert clinical judgement. The ventricular index correlated poorly and was less sensitive to mild dilatation. There was no correlation between the ventricular index and the other two measures. The ventricular height and the diagonal width are more appropriate for assessing ventricular dilatation in preterm neonates.

Australia↗

Kangaroo care is effective in diminishing pain response in preterm neonates.

OBJECTIVE: To test the efficacy of maternal skin-to-skin contact, or kangaroo care (KC), on diminishing the pain response of preterm neonates to heel lancing. DESIGN: A crossover design was used, in which the neonates served as their own controls. Subjects Preterm neonates (n = 74), between 32 and 36 weeks' postmenstrual age and within 10 days of birth, who were breathing without assistance and who were not receiving sedatives or analgesics in 3 level II to III neonatal intensive care units in Canada. INTERVENTIONS: In the experimental condition, the neonate was held in KC for 30 minutes before the heel-lancing procedure and remained in KC for the duration of the procedure. In the control condition, the neonate was in the prone position in the isolette. The ordering of conditions was random. MAIN OUTCOME MEASURES: The primary outcome was the Premature Infant Pain Profile, which is composed of 3 facial actions, maximum heart rate, and minimum oxygen saturation changes from baseline in 30-second blocks. Videotapes, taken with the camera positioned on the neonate's face so that an observer could not tell whether the neonate was being held or was in the isolette, were coded by research assistants who were naïve to the purpose of the study. Heart rate and oxygen levels were continuously monitored into a computer for later analysis. A repeated-measures analysis of covariance was used, with order of condition and site as factors and severity of illness as a covariate. RESULTS: Premature Infant Pain Profile scores across the first 90 seconds from the heel-lancing procedure were significantly (.002<P<.04) lower by 2 points in the KC condition. CONCLUSIONS: For preterm neonates who are 32 weeks' postmenstrual age or older, KC seems to effectively decrease pain from heel lancing. Further study is needed to determine if younger neonates or those requiring assistance in breathing, or older infants or toddlers, would benefit from KC, or if it would remain effective over several procedures. Given its effectiveness, and that parents of neonates in critical care units want to participate more in comforting their children, KC is a potentially beneficial strategy for promoting family health.

Blood Specimen Collection↗

[Renal tubular function in preterm neonates].

Renal tubular function and functional changes in the preterm neonate are discussed. The proximal tubule has a limited capacity in preserving sodium, leading to a daily sodium need from 3 to 5 mEq/kg/day. The reabsorption of glucose, phosphate and amino acids is also low compared to older children but increases quickly for glucose and phosphate. At the level of the distal tubule, a temporary insensibility for aldosterone leads to a lowered sodium-potassium exchange. A limitation in acid excretion is present. Concentration capacity is restricted with a maximal urine osmolality of 360 mosm/liter. Despite this immature tubular function a glomerulotubular balance exists even in the preterm neonate. The kidneys are thus capable to preserve their homeostatic function.

Acid-Base Equilibrium↗