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Medium-chain triglycerides in formula for preterm neonates: implications for hepatic and extrahepatic metabolism.

Medium-chain fatty acids are an important energy source for preterm neonates. Based on assumptions from earlier investigations, 40% to 60% of fatty acids in formula designed for preterm neonates are C6:0 to C12:0. This review will reevaluate these assumptions about C6:0 to C12:0 fatty acids. More recent investigations have indicated that when C6:0 to C12:0 fatty acids are administered in high concentrations, they are metabolized in several tissues by carnitine-dependent mechanisms. Incomplete oxidation of C6:0 to C12:0 fatty acids may result in elevated dicarboxylic acid levels. Feeding formulas high in C6:0 to C12:0 fatty acids has not improved nitrogen retention or growth of preterm neonates. Current data indicate that the fatty acid profiles of formula for preterm neonates are not optimal. Optimization of the fatty acid profile in the diet awaits an improved understanding of the metabolism of fatty acids of all chain lengths in the preterm neonate.

Animals↗

Polymorphonuclear leukocyte function in the preterm neonate: effect of chronologic age.

In this study, effect of chronologic age on polymorphonuclear leukocyte (PMN) chemiluminescence and random and chemotactic motility was evaluated in 38 stable preterm neonates of less than 32 weeks' gestation during the first month of life. Chemiluminescence and random and chemotactic motility of PMNs from preterm neonates were first evaluated at mean postnatal age of 9.8 days and then weekly for an ensuing 21-day period. For comparison, one blood sample was obtained for PMN functions from 14 healthy term neonates younger than 72 hours of age and seven normal adults. On day 1 PMN chemiluminescence and random and chemotactic motility values in preterm neonates were significantly lower (P less than .001) compared with those in term neonates and PMN function values of term neonates were significantly lower (P less than .001) than those of adults. Although initial PMN chemiluminescence and random and chemotactic motility values in preterm neonates were depressed, subsequent values on days 7, 14, and 21 increased significantly (P less than .002). On day 21 (mean postnatal age of 30.8 days) no differences existed in chemiluminescent activity and random motility between preterm and term neonates; chemotactic motility in preterm neonates, however, remained impaired. Mean cumulative age (gestational age at birth plus postnatal age) of preterm neonates on day 21 of study was 32.5 weeks, suggesting that chronologic age has more effect on maturational changes in PMN functions than gestational age.

Aging↗

Transtubular potassium concentration gradient in preterm neonates.

To determine the postnatal changes in mineralocorticoid action on the cortical distal nephron in preterm neonates, we evaluated the transtubular potassium gradient (TTKG) and its relationship to other renal and non-renal parameters in 16 preterm neonates during the first 5 weeks of life. Preterm neonates were divided into two groups according to their gestational age: the first group (group A, n=9) had a gestational age less than 30 weeks and the second group (group B, n=7) had a gestational age over 30 weeks. TTKG in both groups increased significantly with postnatal age, and TTKG in group A was significantly lower than that in group B (P=0.0003; two-way repeated analysis of variance). TTKG in group A was significantly lower during the 2 weeks of postnatal life than that in full-term neonates [TTKG during 1st week (mean+/-SD) 3.73+/-1.32, P<0.00001; during 2nd week 7.77+/-3.60, P=0.0096 versus full-term neonates (n=19); 11.56+/-3.23]. TTKG in group B was significantly lower only during the 1st week of life (6.55+/-2.71, P=0.0013) compared with full-term neonates. Plasma aldosterone concentration did not correlate with TTKG value. Stepwise regression analysis showed that postnatal age, cortical lumen sodium concentration (CLNa), and clinical condition requiring the use of mechanical ventilation were independent variables that correlated significantly with TTKG. We postulate that the low TTKG level in preterm neonates might reflect the prematurity of renal function (early postnatal age, CLNa) and the condition(s), relating to immaturity, such as the use of mechanical ventilation.

Age Factors↗

Morphine does not provide adequate analgesia for acute procedural pain among preterm neonates.

BACKGROUND: Morphine alleviates prolonged pain, reduces behavioral and hormonal stress responses induced by surgery among term neonates, and improves ventilator synchrony and sedation among ventilated preterm neonates, but its analgesic effects on the acute pain caused by invasive procedures remain unclear. OBJECTIVE: To investigate the analgesic efficacy of intravenously administered morphine on heel stick-induced acute pain among preterm neonates. DESIGN: This study was nested within a prospective, randomized, double-blind, multicenter, placebo-controlled trial (the NEOPAIN Trial). SETTING: A tertiary-care NICU in a teaching hospital. PARTICIPANTS: Forty-two preterm neonates undergoing ventilation. INTERVENTIONS: Neonates were randomized to either the morphine (loading dose of 100 microg/kg, followed by infusions of 10-30 microg/kg per hour according to gestation, N = 21) or placebo (5% dextrose infusions, N = 21) group. Pain responses to 3 heel sticks were evaluated, ie, before the loading dose (T1), 2 to 3 hours after the loading dose (T2), and 20 to 28 hours after the loading dose (T3). MAIN OUTCOMES MEASURES: Pain was assessed with the Douleur Aiguë Nouveau-né (DAN) scale (behavioral pain scale) and the Premature Infant Pain Profile (PIPP) (multidimensional pain scale); plasma morphine levels were measured at T3. RESULTS: Infants in the placebo and morphine groups had similar gestational ages (mean +/- SD: 27.2 +/- 1.7 vs 27.3 +/- 1.8 weeks) and birth weights (972 +/- 270 vs 947 +/- 269 g). Mean +/- SD DAN pain scores at T1, T2, and T3 were 4.8 +/- 4.0, 4.6 +/- 2.9, and 4.7 +/- 3.6, respectively, for the placebo group and 4.5 +/- 3.8, 4.4 +/- 3.7, and 3.1 +/- 3.4 for the morphine group. The within-group factor (pain at T1, T2, and T3) was not statistically different over time. The between-group analysis (infants receiving placebo versus those receiving morphine) showed no significant differences. Mean +/- SD PIPP pain scores at T1, T2, and T3 were 11.5 +/- 4.8, 11.1 +/- 3.7, and 9.1 +/- 4.0, respectively, for the placebo group and 10.0 +/- 3.6, 8.8 +/- 4.9, and 7.8 +/- 3.6 for the morphine group. The within-group factor was statistically different over time. The between-group analysis showed no significant differences. Mean +/- SD plasma morphine levels at T3 were 0.44 +/- 1.79 ng/mL and 63.36 +/- 33.35 ng/mL for the placebo and morphine groups, respectively. There was no correlation between plasma morphine levels and pain scores at T3 (DAN, R = -0.05; PIPP, R = -0.02). CONCLUSIONS: Despite its routine use in the NICU, morphine given as a loading dose followed by continuous intravenous infusions does not appear to provide adequate analgesia for the acute pain caused by invasive procedures among ventilated preterm neonates.

Acute Disease↗

A double-blind placebo-controlled study on prophylactic use of cisapride on feed intolerance and gastric emptying in preterm neonates.

OBJECTIVE: To evaluate whether prophylactic use of cisapride will reduce the incidence of feed intolerance and gastro-esophageal reflux, and improve gastric emptying in early neonatal period in preterm babies. DESIGN: Double blind randomized controlled trial. SETTING: Hospital based. SUBJECTS: Forty nine preterm babies between 29-34 weeks of gestation were administered either cisapride or placebo. METHODS: Babies were enrolled in the study once they reached 30 ml/kg/day of enteral feeding or when 25% of total fluid intake was received through the enteral route. Those with sepsis, congenital malformations and on aminophylline were excluded. The subjects were randomized to receive either cisapride or placebo in a dose of 0.2 mg/kg/dose every 8 hourly for 14 days or till discharge. During the study period babies were observed for clinical signs of feed intolerance as judged by increase in abdominal girth, increased prefeed gastric residuals or vomiting. Gastro-esophageal reflux and gastric emptying time was assessed by Technetium phytate scan on day 7 +/- 1. RESULTS: Feed intolerance was noticed in 59% of study and 41% of control population. No significant difference was noticed in the two groups in the total number of episodes of feed intolerance (1.54 +/- 2.4 vs 1.18 +/- 1.6). Nearly 50% of babies in each group had gastro-esophageal reflux. Gastric emptying time (mean (SD) and median) was found to be comparable (p = 0.70) in those on drug and placebo (58.1 (32.2 min) 48.8 min) vs (53.8 (34.6 min) 43.4 min). CONCLUSION: Cisapride does not reduce the incidence of feed intolerance, gastro-esophageal reflux and does not improve gastric emptying in normal preterm neonates.

Cisapride↗

Axillary and tympanic membrane temperature recording in the preterm neonate: a comparative study.

STUDY AIMS: The aim of this study is to compare axillary temperature recordings with those of the tympanic membrane, in healthy preterm neonates, to ascertain whether there is any significant difference between the two recordings, in particular in relation to postnatal age, and if so to evaluate the clinical implications. RATIONALE: Immature thermoregulatory mechanisms, and small body size, mean preterm neonates are prone to temperature maintenance problems, and thermal stress is associated with increased morbidity and mortality. In order to ensure minimal handling, the ideal method of temperature recording would be rapid, painless and reproducible, and accurately reflect core temperature, whilst considering safety, comfort, ease of procedure and cost effectiveness. Recording of the tympanic membrane temperature is rapid and noninvasive, however, the accuracy of this method in preterm neonates has not been established. STUDY DESIGN: A comparative descriptive design was used, to describe differences in the recorded temperature in healthy preterm neonates, of gestational age of 27-37 weeks, related to temperature recording. METHOD: A second comparison was undertaken to establish difference in mean temperature recordings dependant on postnatal age of the baby in days. The sample included all babies fitting the selection criteria, admitted to the Neonatal Unit during the study period. Following approval by the local research ethics committee tympanic membrane and axillary temperatures were recorded consecutively for 7 days (n=154), using the Genius Model 3000A tympanic thermometer and a glass and mercury thermometer. RESULTS: A t-test demonstrated a statistically significant difference between the recordings (P < 0.05), tympanic membrane recordings being higher. However, analysis of variance indicated that this difference was not associated with postnatal age, and thus the presence of vernix in the auditory canal (P > 0.05). The findings were not, however, deemed clinically significant in that no change in care or treatment resulted from differences in temperature recordings. CONCLUSIONS: Whilst the findings cannot be applied to sick preterm neonate, it was concluded that tympanic membrane temperature recordings in healthy preterm neonates are safe, accurate, easy, and comfortable for the baby, and appropriate with this client group provided staff are trained in the technique.

Age Factors↗

Effects of neurobehavioral assessment on feeding and weight gain in preterm neonates.

Neonatal intensive care unit personnel and parents often are concerned that developmental assessment will tire preterm neonates and impair their feeding ability and subsequent weight gain. Therefore, the amount of fluid consumed by 108 preterm neonates (<or=36.5 wk gestational age) was compared before and after administration of the Neurobehavioral Assessment of the Preterm Infant (NAPI). In addition, the weight gain of 35 preterm neonates who were administered the NAPI was compared with that of a matched control group of 35 preterm neonates who were not administered the NAPI. There were no differences in the amount of fluid consumed before and after NAPI administration, and there were no differences in weight gain between neonates who were and were not administered the NAPI. The effects of NAPI administration did not differ as a function of gestational age group. Therefore, the NAPI can be administered safely to preterm neonates without affecting feeding performance or weight gain.

Drinking↗

Abnormal FcRIII expression by neutrophils from very preterm neonates.

To further investigate the neutrophil dysfunction of newborn infants, we have measured expression of the neutrophil Fc gamma receptors FcRIII and FcRII in extremely immature preterm neonates born at 24 to 32 weeks of gestation. Fc receptor expression was measured by FACS analysis of cells stained with monoclonal antibody Leu11b for FcRIII and IV-3 for FcRII. "Well" preterm neonates displayed reduced FcRIII, 51.05 +/- 2.0 (mean fluorescence channel +/- SE) when compared with term neonates, 69.24 +/- 5.5 and adult controls, 71.83 +/- 3.0. "Stressed" preterm neonates with severe respiratory distress syndrome or septicemia had a further downregulation of FcRIII, 32.67 +/- 3.0 and 35.75 +/- 1.8, respectively, associated with grossly abnormal cellular fluorescence distribution. In well preterm neonates, expression of FcRIII improved to adult levels during the first two postnatal weeks, suggesting a postnatal maturation of function. Stressed neonates had signs of partial neutrophil activation (increased Mac-1 expression and chemotactic ability), leading us to propose that the further downregulation of FcRIII may be due to receptor shedding in vivo by partially activated cells. FcRII expression was found to be equivalent to adult levels in both well preterm and stressed neonates. Reduced neutrophil FcRIII expression may provide some explanation for the reported abnormalities of phagocytosis and bacterial killing in preterm neonates.

Antigens, Differentiation↗

Reticulated platelet percentages in term and preterm neonates.

OBJECTIVES: The authors aimed to determine whether their reticulated platelet percentage (RP%) analysis technique was suitable for use in term and preterm neonates and to characterize RP% values among nonthrombocytopenic neonates. METHODS: The authors modified a whole blood method that uses dual-color CD41 staining for platelet gating and thiazole orange for RNA content, combined with RNase treatment of half the sample to subtract non-RNA fluorescence. The RP% was measured in samples from 10 healthy adults and then a longitudinal study was performed in 15 nonthrombocytopenic preterm neonates on days of life 0 to 1, 2 to 5, 6 to 10, and then weekly until day 28. The authors also performed a cross-sectional study of RP% in 22 nonthrombocytopenic neonates of different gestational age (GA) and postconceptional age (PCA). RESULTS: Overall, neonates had a higher RP% (2.7 +/- 1.6%) than adults (1.1 +/- 0.5%; P < 0.01). In preterm neonates, an increase in the RP% occurred between days 0 and 1 (3.3 +/- 1.3%) and days 2 and 5 (5.1 +/- 1.8%; P = 0.003). By days 6 to 10, the RP% decreased to 3.2 +/- 1.1% and remained unchanged throughout the rest of the study period. In neonates less than 7 days old, an inverse relationship was observed between RP% and GA (n = 20, r = -0.70; P = 0.0005). A correlation between RP% and PCA was not seen in neonates 7 days of age or older. CONCLUSIONS: This method for determining RP% is suitable for use in term and preterm neonates. In preterm infants, the RP% significantly increases over the first 2 to 5 days of life and then decreases to a stable level over the first 28 days. RP% is generally higher in neonates than in adults. Among preterm infants in the first week of life, the RP% is inversely related to GA.

Adult↗

Thymic size in preterm neonates: a sonographic study.

AIM: To assess the variation in size of the thymus in vivo in preterm neonates and to identify relations between thymic size and gestational age (GA), birthweight, occurrence of postnatal infections and maternal alcohol and tobacco intake during pregnancy. METHODS: Eighty preterm neonates with a GA between 24 and 36 wk, and a birthweight between 490 and 4110 g were examined between days 0 and 19 after birth. The thymic size was assessed by sonography as a volume estimate, the so-called thymic index (Ti). The median Ti was 5.2 (1.2-17.9). Ti was positively correlated with birthweight and GA and negatively correlated with occurrence of postnatal infection (p < 0.01, p = 0.03, p = 0.05, R2 = 0.68). A correlation between thymic size and maternal alcohol and tobacco intake was not demonstrated. CONCLUSION: It is possible to assess the size of the thymus by sonography in very low-birthweight and preterm neonates. A normal range for Ti in preterm neonates has been established. The sonographic method is a safe and effective technique for measuring the size of the thymus in preterm infants.

Alcohol Drinking↗

Tactile/kinesthetic stimulation effects on preterm neonates.

Tactile/kinesthetic stimulation was given to 20 preterm neonates (mean gestational age, 31 weeks; mean birth weight, 1,280 g; mean time in neonatal intensive care unit, 20 days) during transitional ("grower") nursery care, and their growth, sleep-wake behavior, and Brazelton scale performance was compared with a group of 20 control neonates. The tactile/kinesthetic stimulation consisted of body stroking and passive movements of the limbs for three, 15-minute periods per day for a 10 days. The stimulated neonates averaged a 47% greater weight gain per day (mean 25 g v 17 g), were more active and alert during sleep/wake behavior observations, and showed more mature habituation, orientation, motor, and range of state behavior on the Brazelton scale than control infants. Finally, their hospital stay was 6 days shorter, yielding a cost savings of approximately $3,000 per infant. These data suggest that tactile/kinesthetic stimulation may be a cost effective way of facilitating growth and behavioral organization even in very small preterm neonates.

Body Weight↗

Diminished transcription of interleukin-8 by monocytes from preterm neonates.

Developmental delays, which impair antibacterial host defense, are present in the neutrophil system of human preterm neonates. We hypothesized that diminished production of interleukin-8 (IL-8), a neutrophil chemotactic peptide, might in part be responsible for these defects. To test this, monocytes from the blood of preterm neonates, term neonates, and adults were isolated immunologically by "negative panning" and subsequently stimulated with interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), or lipopolysaccharide (LPS), after which IL-8 levels in the supernatants were measured by ELISA. Total cellular RNA was extracted and IL-8 mRNA was assessed by Northern blotting and by competitive polymerase chain reaction (PCR) analyses. After stimulation with IL-1 alpha, IL-8 accumulation was lowest in supernatants of monocytes from preterm neonates, intermediate in supernatants of monocytes from term neonates and greatest from monocytes of adults. Similarly, when stimulated with TNF-alpha or LPS, monocytes from preterm neonates produced less IL-8 than cells from term neonates and adults. These differences in IL-8 concentrations paralleled differences in IL-8 mRNA expression.

Adult↗

Regional hemodynamic effects of dopamine in the sick preterm neonate.

OBJECTIVE: To study the effects of dopamine on renal, mesenteric, and cerebral blood flow in sick preterm neonates. STUDY DESIGN: The pulsatility index was used to assess the dopamine-induced changes in renal, mesenteric, and cerebral blood flow by means of color Doppler ultrasonography in 23 nonhypotensive preterm neonates (birth weight: 981 +/- 314 g; postnatal age: <2 days). Dopamine was given at a dose of 6.1 +/- 3.0 microgram/kg per minute to combat oliguria, impaired peripheral perfusion, or both. Blood flow velocity measurements were made before and during dopamine administration, with each patient serving as his or her own control subject. RESULTS: Dopamine significantly increased blood pressure and urine output. Dopamine decreased the pulsatility index in the renal artery (2.98 +/- 1.18 vs 1.68 +/- 0.45; P <.05) while the pulsatility index in the superior mesenteric and medial cerebral artery was not affected. Thus renal blood flow increased while mesenteric and cerebral blood flow remained unchanged during dopamine treatment. The increase in renal blood flow was independent of the blood pressure changes. CONCLUSIONS: These findings suggest a functionally mature renal, but not mesenteric, vasodilatory dopaminergic response in the preterm neonate. The observations also indicate the lack of an effect of low- to medium-dose dopamine on cerebral hemodynamics in the nonhypotensive preterm neonate.

Blood Flow Velocity↗

Reliability of two behavioral tools to assess pain in preterm neonates.

CONTEXT: One of the main difficulties in adequately treating the pain of neonatal patients is the scarcity of validated pain evaluation methods for this population. OBJECTIVE: To analyze the reliability of two behavioral pain scales in neonates. TYPE OF STUDY: Cross-sectional. SETTING: University hospital neonatal intensive care unit. PARTICIPANTS: 22 preterm neonates were studied, with gestational age of 34 +/- 2 weeks, birth weight of 1804 +/- 584 g, 68% female, 30 +/- 12 hours of life, and 30% intubated. PROCEDURES: Two neonatologists (A and B) observed the patients at the bedside and on video films for 10 minutes. The Neonatal Facial Coding System and the Clinical Scoring System were scored at 1, 5, and 10 minutes. The final score was the median of the three values for each observer and scale. A and B were blinded to each other. Video assessments were made three months after bedside evaluations. MAIN MEASUREMENTS: End scores were compared between the observers using the intraclass correlation coefficient and bias analysis (paired t test and signal test). RESULTS: For the Neonatal Facial Coding System, at the bedside and on video, A and B showed a significant correlation of scores (intraclass correlation score: 0.62), without bias between them (t test and signal test: p > 0.05). For the Clinical Scoring System bedside assessment, A and B showed correlation of scores (intraclass correlation score: 0.55), but bias was also detected between them: A scored on average two points higher than B (paired t test and signal test: p < 0.05). For the Clinical Scoring System video assessment, A and B did not show correlation of scores (intraclass correlation score: 0.25), and bias was also detected between them (paired t-test and signal test: p < 0.05). CONCLUSION: The results strengthen the reliability of the Neonatal Facial Coding System for bedside pain assessment in preterm neonates.

Beds↗

Serial sonographic monitoring of intracranial hemorrhage (ICH) and its sequelae in the preterm neonate.

This study documents changes in ventricular size and brain parenchyma that occurred in 41 preterm neonates that had intracranial hemorrhage, out of 136 preterm neonates that were serially examined. Serial real-time sonographic examinations disclosed a close relationship between the severity of ICH and the development of progressive ventricular dilatation. Eighty percent of preterm neonates with minor degrees of ICH [localized subependymal hemorrhage (SEH) or SEH with small intraventricular hemorrhage (SEH/IVH)] did not develop significant ventricular dilatation, whereas all of the neonates with IVH and/or intraparenchymal hemorrhage (IPH) developed moderate or severe ventricular dilatation. Spontaneous resolution of moderate and/or severe ventricular dilatation did occur by the end of the third week of life in approximately one third of neonates with ICH. The therapeutic implications of the findings are discussed.

Birth Weight↗

Early maturation of evoked otoacoustic emissions and medial olivocochlear reflex in preterm neonates.

The present study was designed to investigate the early maturation of the brainstem regulation of the cochlear function in preterm neonates. Evoked otoacoustic emissions (EOAE) and their regulation via the medial olivocochlear efferent (MOC) reflex were investigated in a large population of preterm neonates and compared with full-term neonates and young babies from birth to 4 y and school-aged children. In 28-wk preterm neonates, EOAE were seen in the mid-frequency range. These responses extended both to the low (down to 1025 Hz) and high (up to 6152 Hz) frequency ranges at 38 wk of gestational age and remained stable up to 4 mo. At this stage, the amplitude of EOAE overlapped adult values. EOAE amplitudes then decreased to reach adult values at 3 y of age. Maturation of MOC efferents innervating the outer hair cells was investigated by studying the suppressive effect of contralateral sound on the EOAE amplitudes (MOC reflex). The first MOC responses were recorded in preterm neonates of 32-33 wk of gestational age, reaching adult-like values at 37 wk of gestational age. The maximum effect of MOC efferent activation occurred between 2000 and 4000 Hz. These results suggest that, in humans, MOC efferents mature in utero. Thus, testing the MOC reflex may have a clinical relevance to detect an abnormal development of the auditory pathways, particularly of a brainstem circuitry not explored through conventional testing.

Child, Preschool↗

Crossover trial of analgesic efficacy of glucose and pacifier in very preterm neonates during subcutaneous injections.

OBJECTIVE: Very preterm newborns undergo multiple invasive procedures. Nonpharmacological interventions are valuable alternatives for pain relief during minor procedures in neonates. Oral sucrose analgesia has been widely studied in term and preterm neonates during painful procedures. The analgesic effect of oral glucose in very preterm infants has not yet been reported. The objectives of this study were to assess the analgesic effect of orally administered glucose and to determine the synergetic analgesic effect of glucose and pacifiers during subcutaneous injections in very preterm neonates using a validated behavioral acute pain rating scale. DESIGN: Two crossover trials. SETTING: One neonatal intensive care unit in a community-based general hospital. METHODS: A prospective study was conducted in 40 very preterm neonates. Each infant received 2 treatments in a crossover manner during 2 consecutive subcutaneous injections of erythropoietin. The first trial (25 infants) was intended to compare oral 30% glucose (0.3 mL) versus placebo (0.3 mL of sterile water); the second trial (15 infants) compared oral 30% glucose (0.3 mL) versus oral 30% glucose (0.3 mL) followed by sucking a pacifier. The primary outcome measure was the evaluation of pain induced by a subcutaneous injection of erythropoietin, using Douleur Aiguë Nouveau-né scale (0 no pain, 10 maximum pain). RESULTS: Twenty-four infants completed the study in the first trial and 15 in the second one. Mean (95% confidence interval [CI]) gestational age, birth weight, postnatal age, and weight at inclusion for neonates in the first and second trial were, respectively, 28.1 (95% CI: 27.3-29.0) and 29.1 (95% CI: 27.8-30.4) weeks, 1036 (95% CI: 944-1128) and 995 (95% CI: 848-1141) g, 26.4 (95% CI: 22.4-30.3) and 26 (95% CI: 22.0-29.9) days, and 1234 (95% CI: 1120-1348) and 1209 (95% CI: 1059-1359) g. In the first trial, median (interquartile) pain scores for placebo and 30% glucose, respectively, were 7 (2.5-9.75) and 4.5 (1-6). In the second trial, median (interquartile) pain scores for 30% glucose and for 30% glucose plus pacifier, respectively, were 4 (2-7) and 4 (1-6). CONCLUSIONS: A small dose of 0.3 mL of 30% oral glucose has an analgesic effect in very preterm neonates during subcutaneous injections. This effect is clinically evident because it can be detected by a behavioral pain rating scale. The synergetic analgesic effect of glucose plus sucking a pacifier is less obvious in very preterm neonates as opposed to what other studies have showed in full-term infants.

Administration, Oral↗

Etiology of nephrocalcinosis in preterm neonates: association of nutritional intake and urinary parameters.

BACKGROUND: Nephrocalcinosis (NC) in preterm neonates has been described frequently, and small-scale studies suggest an unfavorable effect on renal function. The etiologic factors have not yet been fully clarified. We performed a prospective observational study to identify factors that influence the development of NC. METHODS: The study population consisted of 215 preterm neonates with a gestational age <32 weeks. Clinical characteristics and intake in the first four weeks of calcium, phosphorus, vitamin D, protein, and ascorbic acid were noted. Serum calcium, phosphate, vitamin D, magnesium, uric acid, creatinine, urea and urinary calcium, phosphate, oxalate, citrate, magnesium, uric acid, and creatinine were assessed at four weeks of age and at term. Renal ultrasonography (US) was performed at four weeks and at term. At term was defined as a postconceptional age of 38 to 42 weeks. RESULTS: NC was diagnosed by means of US in 33% at four weeks and in 41% at term. Patients with NC at four weeks had a significantly higher mean intake of calcium (P < 0.05), phosphorus (P < 0.05), and ascorbic acid (P < 0.01) than patients without NC. They had a higher mean serum calcium (2.55 vs. 2.46 mmol/L, P < 0.01) and a higher mean urinary calcium/creatinine ratio (2.6 vs. 2.1 mmol/mmol, P < 0.05). Patients with NC at term had a lower birth weight (1142 vs. 1260 g, P < 0.05) and a lower gestational age (28.8 vs. 29.4 weeks, P < 0.05), were treated significantly longer with furosemide, dexamethasone, theophylline, and thiazides, developed chronic lung disease more frequently (40 vs. 16%, P < 0.001), and had a higher mean urinary calcium/creatinine ratio (2.7 vs. 2.3 mmol/mmol, P < 0.05) and a lower mean urinary citrate/calcium ratio (1.1 vs. 1.7 mmol/mmol, P = 0.005). CONCLUSIONS: NC develops as a result of an imbalance between stone-inhibiting and stone-promoting factors. A high intake of calcium, phosphorus, and ascorbic acid, a low urinary citrate/calcium ratio, a high urinary calcium/creatinine ratio, immaturity, and medication to prevent or treat chronic lung disease with hypercalciuric side effects appear to contribute to the high incidence of NC in preterm neonates.

Ascorbic Acid↗