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Changes in anterior fontanel pressure in preterm neonates during tracheal intubation.

Anterior fontanel pressure (AFP), a noninvasive indicator of intracranial pressure (ICP), was monitored during tracheal intubation in two groups of preterm neonates without neurologic disease. Anterior fontanel pressure was monitored and recorded continuously with a Ladd AFP monitor. Systolic and mean blood pressures were recorded at 1-min intervals. In group 1 (n = 6) patients, 0.02 mg/kg intravenous atropine was administered and awake intubation was performed. Group 2 (n = 6) patients received 0.02 mg/kg intravenous atropine and 0.1 mg/kg pancuronium and one of four anesthetics--0.75% isoflurane, 0.5% halothane, 20 micrograms/kg fentanyl, or 2 mg/kg ketamine--with intubation after 10 min of mask ventilation. In group 1, AFP increased from 7.7 cm H2O to 23.8 cm H2O (P less than 0.05); the mean increase in AFP was 197%. Anterior fontanel pressure did not change significantly in group 2. Significant increases in AFP may increase the risk of intraventricular hemorrhage in preterm neonates. The present data indicate that indirectly measured ICP increases significantly during awake tracheal intubation in preterm neonates and that this increase can be prevented by prior administration of pancuronium and a general anesthetic.

Anesthesia, General↗

Renal impairment associated with indomethacin treatment for patent ductus arteriosus in extremely preterm neonates--is postnatal age at start of treatment important?

OBJECTIVE: To study serum creatinine (SCr) levels following indomethacin for patent ductus arteriosus (PDA) closure in extremely preterm neonates in relation to postnatal age at the start of treatment. METHODS: This was a retrospective (January 2000-December 2002) analysis of data on preterm neonates (gestation <29 weeks) who received indomethacin for PDA. Pre-existing renal malformation and/or impairment and high serum levels of nephrotoxic drugs were criteria for exclusion. RESULTS: Indomethacin was commenced at postnatal age <7 days and >or=7 days in 60 (group 1) and 30 (group 2) neonates, respectively. The median (Q1, Q3) gestational age and birth weight for group 1 and group 2 neonates were 25 (23, 27) vs. 25 (24, 26) weeks and 740 (620, 909) vs. 780 (663, 966) grams, respectively. Postnatal age <7 days at start of indomethacin was associated with higher baseline (0.083 (0.074, 0.090) vs. 0.073 (0.054, 0.083) mmol/L, p=0.001) and peak SCr levels (0.099 (0.089,0.109) vs. 0.090 (0.064, 0.104) mmol/L, p=0.015). Logistic regression analysis controlling for gestational age and baseline SCr level indicated that postnatal age >or=7 days was a risk factor for elevated SCr after indomethacin (OR=13.4, 95% CI: 3.8-46.6, p < 0.001). CONCLUSION: Postnatal age >or=7 days at the start of indomethacin is a predictor of a significant rise in SCr in extremely preterm neonates.

Age Factors↗

Nonnutritive sucking during tube feedings: effects on preterm neonates in an intensive care unit.

Preterm neonates (mean 32 weeks' gestation, 1,300 gm birth weight) were provided a pacifier for nonnutritive sucking during tube feedings in the intensive care nursery. Their clinical course, subsequent bottle feeding behavior, and performance on the Brazelton Neonatal Behavior Assessment scale were compared with those of control group infants. The infants provided with pacifiers averaged 27 fewer tube feedings, started bottle feeding three days earlier, averaged a greater weight gain per day, and were discharged eight days earlier for an average hospital cost savings of approximately $3,500. Formula intake was similar for the two groups, although nurses appeared to provide more feeding stimulation for the control infants. On the Brazelton scale, the infants provided with pacifiers showed weak reflexes more frequently. Increased restfulness and diminished activity level in these infants may have contributed to the appearance of weak reflexes. The consistency between these findings and those of previous investigators suggests that the provision of a pacifier for nonnutritive sucking during tube feedings may be a cost-effective form of intervention.

Body Weight↗

Serial sonography of posthemorrhagic ventricular dilatation and porencephaly after intracranial hemorrhage in the preterm neonate.

Changes in ventricular size and brain parenchyma were documented in 40 preterm neonates with intracranial hemorrhage (ICH), who were serially examined for 3 weeks or more. Sonography disclosed a close relation between the severity of the intracranial hemorrhage and the development of progressive ventricular dilatation. Eighty percent of preterm neonates with minor degrees of intracranial hemorrhage (localized subependymal hemorrhage or subependymal hemorrhage with small intraventricular hemorrhage [subependymal/intraventricular hemorrhage]) did not develop significant ventricular dilatation, whereas all of the neonates with intraventricular and/or intraparenchymal hemorrhage developed moderate or severe ventricular dilatation. Spontaneous resolution of moderate and/or severe ventricular dilatation occurred by the end of the third week in about one-third of neonates with intracranial hemorrhage. Progressive ventricular dilatation was documented in 10 of 15 neonates with major intraventricular and/or intraparenchymal hemorrhage. The therapeutic implications of the findings are discussed.

Cerebral Hemorrhage↗

Ventilator-associated pneumonia in extremely preterm neonates in a neonatal intensive care unit: characteristics, risk factors, and outcomes.

OBJECTIVE: To determine the rates, characteristics, risk factors, and outcomes of ventilator-associated pneumonia (VAP) in extremely preterm neonates in a neonatal intensive care unit (NICU). METHODS: A prospective cohort study was conducted at the St Louis Children's Hospital on all patients who had birth weight or=48 hours from October 2000 to July 2001. Extremely preterm neonates were defined as neonates with estimated gestational age (EGA) <28 weeks. The primary outcome was the development of VAP. Secondary outcomes were death and NICU length of stay (LOS). Multiple logistic regression was performed to determine independent predictors for VAP and mortality. RESULTS: A total of 229 patients were enrolled. Sixty-seven (29%) had EGA <28 weeks. Nineteen episodes of VAP occurred in 19 (28.3%) of 67 mechanically ventilated patients. VAP rates were 6.5 per 1000 ventilator days for patients with EGA <28 weeks and 4 per 1000 ventilator days for EGA >or=28 weeks. By multivariate analysis, bloodstream infection before VAP (adjusted odds ratio: 3.5; 95% confidence interval [CI]: 1.2-10.8) was an independent risk factor for VAP after adjustment for the duration of endotracheal intubation. Ventilator-associated pneumonia (adjusted odds ratio: 3.4; 95% CI: 1.2-12.3) was an independent predictor of mortality. A strong association between VAP and mortality was observed in neonates who stayed in the NICU >30 days (relative risk: 8.0; 95% CI: 1.9-35.0). Patients with VAP also had prolonged NICU LOS (median: 138 vs 82 days). CONCLUSIONS: VAP occurred at high rates in extremely preterm neonates and was associated with increased mortality. Additional studies are needed to develop interventions to prevent VAP in NICU patients.

Cohort Studies↗

Comparison of a neonatal versus general-purpose amino acid formulation in preterm neonates.

Twenty preterm infants were randomly assigned to receive either a general-purpose intravenous amino acid solution or a neonatal formula at 1.5 gm/kg/day with 50 nonprotein energy calories for 1 week. Both groups demonstrated similar rates of weight gain and similar liver function test results, but comparison of changes from baseline amino acid values disclosed significant intergroup differences for levels of plasma glycine, taurine, valine, and methionine after 7 days of infusion. Comparison of plasma aminograms of study patients with those of normally growing, enterally fed preterm infants showed that infants who received the neonatal solution had similar amino acid profiles, with the exception of low plasma concentrations of tyrosine and elevated concentrations of threonine. The general-purpose solution, as compared with findings in historic enteral controls, produced low plasma valine, tyrosine, and taurine levels, and elevated levels of glycine and methionine. Advantages with the neonatal amino acid solution include reductions in plasma glycine and methionine levels, plus the provision of taurine. Providing tyrosine remains a problem.

Amino Acids↗

Consistent management of repeated procedural pain with sucrose in preterm neonates: Is it effective and safe for repeated use over time?

OBJECTIVE: Preterm neonates undergo numerous painful procedures in the neonatal intensive care unit (NICU). Sucrose, with and without pacifiers, is effective and safe for relieving pain from single painful events. However, repeated use of sucrose for multiple painful procedures has not been adequately evaluated. The study objectives were to: 1) determine the efficacy and safety of consistent management of repeated procedural pain with sucrose; and 2) explore the impact of consistent pain management on clinical outcomes and neurobiological risk status. METHODS: Sixty-six preterm infants were randomized to receive standard care (positioning and swaddling; n = 21), sterile water plus pacifier (n = 23), or 24% sucrose plus pacifier (n = 22) prior to all painful procedures in the NICU during the first 28 days of life. Also, at a routine heel lance at 7, 14, 21, and 28 days of life, data were collected to determine efficacy and immediate and long-term adverse events. Data on clinical outcomes and neurobiological risk status were collected at 28 days or NICU discharge. RESULTS: There was no intervention by time interaction (P = 0.60). There was a significant main effect of intervention (P = 0.03) between the sucrose plus pacifier group, and the standard care group (P = 0.01), but there was no main effect of time (P = 0.72). No group differences existed for adverse events, clinical outcomes, or neurobiological risk status. DISCUSSION: Consistent management of painful procedures with sucrose plus pacifier was effective and safe for preterm neonates during their stay in the NICU. Further exploration of consistent pain management with sucrose on clinical, developmental, and neurobiological outcomes is required.

Analysis of Variance↗

Postnatal development of disaccharidase activities in jejunal fluid of preterm neonates.

Because human fetuses of 26-30 weeks gestation are known to have low levels of intestinal mucosal lactase activity, it has been assumed that live born preterm neonates of comparable gestational age are also lactase deficient. We have previously shown that disaccharidase activities in jejunal fluid in infants are highly significantly correlated with enzyme activities in the adjacent mucosa. We have now measured disaccharidase activities cross-sectionally and longitudinally in the jejunal fluid of a group of very preterm neonates of 26-29 weeks gestation who were fed with pasteurised human milk. Lactase activity was within the normal range for older infants and children within the first week of life. Sucrase: lactase ratios fell significantly in the second and third weeks of life, strongly suggesting a further increase in lactase activity. This increase was independent of postconceptional age. Preterm neonates are not as lactase deficient as previously believed, and this has implications in the search for optimal feeding regimes.

Age Factors↗

Relationship between extracellular matrix both in choroid plexus and the wall of lateral ventricles and intraventricular hemorrhage in preterm neonates.

Pathogenesis of intraventricular hemorrhage (IVH) may relate to immature vessels. However extracellular matrix--such as Type IV collagen, laminin, and fibronectin has a direct bearing on the development of the endothelium and the immature microvessel. Twenty specimens taken from lateral ventricular walls and choroid plexus in 10 preterm neonates who died of intraventricular hemorrhage and another 10 preterm neonates who died of non-intraventricular hemorrhage, were marked with antibodies against Type IV collagen, laminin, and fibronectin. Average areas of positive staining around the microvessels in the IVH group showed less staining than that in the non-IVH group (P < 0.05), and the microvessel count of discontinuous positive staining in IVH group was more than that in non-IVH group, P < 0.05. We conclude that lacking Type IV collagen, laminin, and fibronectin may result not only in an incomplete basement membrane in choroid plexus and subependymal immature microvessels but also may be a factor contributing to IVH in preterm neonates.

Cerebral Hemorrhage↗

Do cry features reflect pain intensity in preterm neonates? A preliminary study.

The purpose of this study was to investigate if cries from preterm neonates would reflect changes in pain intensity following interventions. The cries from 25 preterm neonates from an original sample of 122 were audiorecorded while the infant was undergoing heelstick during a randomized crossover design testing the efficacy of: pacifier with sucrose or water, or prone position as compared to standard care. Both pacifier conditions reduced procedural pain according to a validated composite pain measure (the Premature Infant Pain Profile). There were proportionately fewer cries in the two pacifier groups compared to the prone positioning and standard care groups, and cry duration was positively correlated with PIPP scores. However, neither cry duration nor fundamental frequency reflected group differences. Further research is needed to determine if cry is a sensitive and valid indicator of pain in preterm infants.

Blood Specimen Collection↗

Ultrasonography of the infant hip. Part IV: Normal development in the newborn and preterm neonate.

Based on preterm and term infants studied by ultrasonography, and on anatomical sections of various gestational ages the physiological maturation of the hip joint is analysed. Current concepts of a linear growth pattern with an arrest immediately after delivery are confirmed. A more rapid growth and ossification of the acetabular edge than of the femoral head postpartum is suggested. To avoid overtreatment, knowledge of the normal range of development as seen in ultrasonography is mandatory.

Acetabulum↗

Intraparenchymal hemorrhage in preterm neonates: a broadening spectrum.

Among 800 neonates screened for cerebral bleeding, perinatal sonography identified 35 preterm neonates with intraparenchymal hemorrhage (IPH). The observed IPHs were categorized in five general groups: classical grade-IV hemorrhage (16 patients), grade-IV hemorrhage with coexisting but anatomically separate hemorrhages (four patients), grade-IV hemorrhage with later development of secondary parenchymal hemorrhages at distant sites (five patients), hemorrhagic periventricular leukomalacia (four patients), and parenchymal hemorrhage unrelated to grade-IV hemorrhages (six patients). Thirty IPHs had concurrent germinal matrix hemorrhages, but in only 16 patients did the IPH represent an extension of the subependymal hematoma and therefore qualify as pure grade-IV hemorrhage according to the most popular classification. The high concurrence of periventricular leukomalacia (80-100% in most groups) and germinal-matrix-remote IPHs supports the concept that most IPHs in preterm neonates represent secondary hemorrhages into ischemic brain tissue.

Brain↗

Cocaine-exposed preterm neonates show behavioral and hormonal differences.

OBJECTIVE: Prematurity has been associated with prenatal cocaine exposure, but most studies on the behavioral effects of prenatal cocaine exposure have been restricted to full-term infant samples. The current study focused on behavioral and hormonal responses in preterm cocaine-exposed infants compared with a cohort of non-cocaine-exposed infants of similar gestational age. METHODOLOGY: A comparison between 30 cocaine-exposed and 30 non-cocaine-exposed preterm neonates suggested that the cocaine-exposed neonates were born to mothers who had higher parity and more obstetric complications. In addition, mothers of cocaine-exposed preterm neonates visited, touched, held, and fed their infants less frequently than mothers of nonexposed infants. RESULTS: The cocaine-exposed infants had smaller head circumferences at birth, spent more time in the neonatal intensive care unit, and had a greater incidence of periventricular-intraventricular hemorrhages. They also had inferior Brazelton cluster scores, including lower state regulation and range-of-state scores, and greater depression. During sleep-wake behavior observations, they showed difficulty maintaining alert states and self-regulating their behavior, and they spent more time in indeterminate sleep and had decreased periods of quiet sleep and increased levels of agitated behavior, including tremulousness, mouthing, multiple limb movements, and clenched fists. Finally, higher urinary norepinephrine, dopamine, and cortisol levels and lower plasma insulin levels were noted in the cocaine-exposed preterm neonates. CONCLUSIONS: These findings highlight the need for follow-up assessments and early intervention.

Case-Control Studies↗

Population pharmacokinetics of gentamicin in preterm neonates: evaluation of a once-daily dosage regimen.

Population pharmacokinetic parameters of gentamicin in preterm neonates on a once-daily dosage regimen of 3.0 mg/kg given intravenously every 24 hours were established prospectively. In 34 preterm neonates with a mean gestational age of 32 +/- 4 (SD), 182 serum gentamicin levels (91 peak/trough pairs) were determined. Individual adjustments of dose or dosage interval were calculated by computer-aided Bayesian forecasting. The parameters Vd, ke, and CL for each patient were obtained by the nonparametric estimation of maximization method. The predictive power of the model was calculated and the pharmacokinetic estimates were statistically analyzed with SPSS/PC. Cluster analysis showed a division into 2 subpopulations (designated 1 and 2) on the basis of postnatal age. The mean +/- SD postnatal age of subpopulation 1 (n = 29) was 6 +/- 2 days (range 1-7) and of subpopulation 2 (n = 5) 15 +/- 4 days (range 12-24). The mean +/- SD gentamicin relative clearances of subpopulation 1 and subpopulation 2 were 0.0515 +/- 0.0128 and 0.1026 +/- 0.0102 L kg(-1) hr(-1), respectively (p < 0.05). The mean +/- SD values for Vd (Lkg(-1)) in both populations 1 and 2 were 0.6916 +/- 0.1670 and 0.7509 +/- 0.1961, respectively (not significantly different). For ke these data were 0.0744 +/- 0.0200 and 0.1366 +/- 0.0522 (p < 0.05). Statistics showed that the data for Vd and ke of subpopulation 1 were normally distributed (Vd and ke skewness 1.61 and 1.46; kurtosis 3.09 and 3.10 respectively). The model yielded a bias of -0.11 mg/L and a precision of 0.36 mg/L. It is recommended that gentamicin be started in a dosage of 3.5 mg/kg intravenously once-daily under close monitoring.

Age Factors↗

Changes in serum insulin-like growth factors, not leptin, are associated with postnatal weight gain in preterm neonates.

BACKGROUND: Serum concentrations of conventional nutrition-related proteins, such as albumin, prealbumin, transferrin, and retinol-binding protein, are usually inconsistent with changes in anthropometric measurements in the postnatal period. The aim of this study was to evaluate how reliable growth hormone (GH), insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and leptin, the proteins known to be involved in the regulation of growth, are in reflecting postnatal growth and nutritional status in preterm neonates. METHODS: Blood samples and anthropometric measurements were collected from 55 preterm neonates (chronological age 30.4 +/- 2.8 weeks) for 4 continuous weeks (weeks 0 to 3). RESULTS: After adjusting for chronological age, body weights and serum IGF-II concentrations were significantly greater and serum transferrin concentrations were significantly lower in weeks 2 and 3 than in week 0 (repeated-measures analysis of variance (ANOVA) and Bonferroni test, p < .05). Forward stepwise multivariate regression analysis showed that change in total IGF-I (week 0 to week 3) was a positive predictor, and changes in insulin and prealbumin were negative predictors of postnatal weight gain. In addition, daily fat intake was a positive predictor of postnatal length increases, and changes in prealbumin, insulin, and GH were negative predictors of postnatal changes in the ponderal index (weight x length(-3)). Changes in GH and IGFBP-2 were negative predictors of changes in head circumference and triceps skinfold thickness, respectively. CONCLUSIONS: Serial measurements of serum IGF-I and IGF-II may be useful adjuncts to anthropometric measurements for monitoring postnatal growth and nutritional status in preterm neonates.

Analysis of Variance↗

Spontaneous and evoked otoacoustic emissions in preterm neonates.

Spontaneous (SOEs) and evoked otoacoustic emissions (EOEs) were recorded in a group of preterm neonates (N = 134 ears) in order to study the basic properties of SOEs and EOEs as a function of gestational age. In the study, it was found that: 1. EOEs were recorded in 93% of the tested ears; 2. SOEs were recorded in 61% of the tested ears; 3. there were no statistically significant variations of EOE amplitude with gestational age; 4. EOE spectrum did not vary with age; and 5. the two main factors influencing EOE amplitude were the SOE presence and the fast Fourier transform spectrum, especially the lower limit of the spectrum. Thus, the maturation of outer hair cell properties appears to be complete at 32 weeks of gestational age. Because a number of infants at risk for hearing loss are preterm babies, screening for EOEs, an objective, rapid, and nontraumatic technique, may prove useful in evaluating peripheral auditory dysfunction in preterm neonates.

Cochlea↗

Increased cerebral blood flow and plasma epinephrine in hypoglycemic, preterm neonates.

Cerebral blood flow, plasma epinephrine, and plasma norepinephrine were measured in 25 spontaneously breathing, preterm neonates (mean gestational age 30.4 weeks) 2 hours after birth, during a routine screening for low blood glucose levels. Increased cerebral blood flow and plasma epinephrine values were observed when blood glucose levels were low, whereas plasma norepinephrine was constant throughout the blood glucose range. Hypoglycemia (defined as blood glucose concentration less than 30 mg/dL) was found in 13 neonates who were treated with intravenous glucose and milk enterally. Blood glucose levels were normal in the remaining 12 control neonates who received milk by a gastric line. Approximately 30 minutes after treatment with intravenous glucose and/or milk, cerebral blood flow had decreased by a mean of 11.3% in the 13 hypoglycemic neonates but was still 37.5% higher than cerebral blood flow in the control neonates despite normalization of plasma epinephrine concentration. Mean arterial blood pressure and blood gas values were identical between groups throughout the investigation. It is suggested that a normal coupling between cerebral metabolic demands and flow is present in very preterm neonates and that epinephrine may play a role in the cerebral hyperperfusion. Although none of the neonates had clinical signs of hypoglycemia, the data suggest that counterregulatory mechanisms are invoked when blood glucose values are less than 30 to 45 mg/dL.

Blood Glucose↗

Birth-related fatigue in 34-36-week preterm neonates: rapid recovery with very early kangaroo (skin-to-skin) care.

OBJECTIVE: To test preterm neonates' physiologic and behavioral responses when placed skin-to-skin on their mother's chests, called kangaroo care (KC), for the first 6 hours after birth, instead of having the neonates go to an intensive care unit. DESIGN: Convenience sampling was used in this descriptive study to enroll neonates who were given continuous KC beginning soon after birth in the delivery room and continuing for 6 hours. Heart rate, respiratory rate, oxygen saturation, abdominal temperature, and behavioral state were recorded each minute. SETTING: Data were collected in the delivery room and in a private labor room in tropical Cali, Colombia. PARTICIPANTS: Six 34-36-week preterm neonates with 5-minute APGAR scores of 6 or more were enrolled. Two neonates had grunting respirations before KC was begun. RESULTS: Temperature rose rapidly to thermoneutral range. With few exceptions, heart rate, respiratory rate, and oxygen saturation remained within normal limits; grunting respirations in two neonates disappeared with warmed humidified oxygen and continuous KC. Sleep predominated, and neonates were discharged home by 48 hours being fully breastfed, suggesting that KC was an environment conducive to recovery from fatigue. CONCLUSIONS: These data suggest that KC beginning in the delivery room can be given safely and perhaps with benefit to 34-36-week gestation neonates who appear healthy at birth. Kangaroo care was conducive to recovery from birth-related fatigue.

Body Temperature↗