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Vagal activity, gastric motility, and weight gain in massaged preterm neonates.

OBJECTIVE: Multiple studies have documented an increase in weight gain after 5 to 10 days of massage therapy for preterm neonates. The massaged preterm neonates did not consume more calories than the control neonates. One potential mechanism for these effects might involve massage-induced increases in vagal activity, which in turn may lead to increased gastric motility and thereby weight gain. STUDY DESIGN: The present randomized study explored this potential underlying mechanism by assessing gastric motility and sympathetic and parasympathetic nervous system activity in response to massage therapy (moderate pressure) versus sham massage (light pressure) and control conditions in a group of preterm neonates. RESULTS: Compared with preterm neonates receiving sham massage, preterm neonates receiving massage therapy exhibited greater weight gain and increased vagal tone and gastric motility during and immediately after treatment. Gastric motility and vagal tone during massage therapy were significantly related to weight gain. CONCLUSION: The weight gain experienced by preterm neonates receiving moderate-pressure massage therapy may be mediated by increased vagal activity and gastric motility.

Analysis of Variance↗

Decreased adherence, chemotaxis and phagocytic activities of neutrophils from preterm neonates.

Using microanalytic assays various phagocytic functions of separated neutrophils from preterm neonates (mean birthweight 1,506 g, n = 13) were simultaneously studied. Adherence of neutrophils to nylon fibre was decreased in cells from preterm infants (77.1 +/- 3.1%) when compared with adult controls (86.9 +/- 2.1%, mean +/- 1 SD, p less than 0.05). In addition neutrophil chemotaxis in response to zymosan activated serum was reduced in preterm neonates (131.9 +/- 19.7, adults 166.6 +/- 11.1, p less than 0.001); directed migration towards Formyl-Methionyl-Leucyl-Phenylalanine was also decreased (preterm neonates 93.4 +/- 15, adults 111.1 +/- 16.8, p less than 0.05). Preterm infants had a higher percentage of slow moving neutrophils when compared with adults (p less than 0.001). Phagocytosis of Candida albicans was reduced in neutrophils from preterm neonates (phagocytic index: preterm neonates 41.4 +/- 12.7, adults 83 +/- 7.2). Adult neutrophils ingested more Candida per cell (p less than 0.001). Chemiluminescence, exocytosis of elastase and lactoferrin during uptake of opsonized zymosan was also reduced in neutrophils from preterm neonates. However, random migration, phagocytosis of Staphylococcus aureus and production of O2- in response to Phorbol myristate acetate or opsonized zymosan were identical in cells from either source. We conclude, that these abnormalities of neutrophils could predispose the preterm infant to serious and often overwhelming bacterial and fungal infections.

Adult↗

Overestimation of serum vancomycin concentrations using a fluorescence polarization immunoassay (Tdx) in preterm neonates.

Serum vancomycin concentrations determined by fluorescence polarization immunoassay (FPIA) with a specific high-performance liquid chromatography (HPLC) method in preterm neonates were compared. Preterm neonates (< 38 weeks gestational age) requiring vancomycin therapy and serum vancomycin concentration monitoring were enrolled. Peak serum vancomycin concentration samples were collected and independently analyzed by FPIA and HPLC. Multivariate and stratified data analysis was done with mean absolute error and mean percent error as dependent variables and independent variables as postconceptional age, postnatal age, gestational age, weight, and duration of therapy to characterize the findings. A total of 15 paired vancomycin concentrations were analyzed from neonates with a mean gestational age of 30 +/- 4 weeks. The mean percentage error of FPIA versus HPLC vancomycin concentrations was 18.1 +/- 11.1% and the mean absolute error was 3.7 +/- 2.0 mg/l. Postconceptional age, weight, and time from initiation of therapy to sample collection were independent variables which best characterized the overestimation of FPIA vancomycin concentrations. The FPIA vancomycin assay method overestimated actual vancomycin concentrations in preterm neonates. Preterm neonates less than 30 weeks postconceptional age, less than 1,200 g body weight, and duration of therapy greater than 48 h prior to concentration determination had the greatest difference in FPIA and HPLC results. Significant error in pharmacokinetic parameter estimations and dosage adjustments is possible when vancomycin concentrations are determined by FPIA.

Chromatography, High Pressure Liquid↗

Elevated urine pregnanetriolone definitively establishes the diagnosis of classical 21-hydroxylase deficiency in term and preterm neonates.

Elevated blood 17alpha-hydroxyprogesterone (17OHP) level, although widely used for the screening of classical 21-hydroxylase deficiency (21OHD) in neonates, has frequently been found in some neonates without classical 21OHD, particularly preterm neonates. We studied the diagnostic value of the metabolite of 21-deoxycortisol (pregnanetriolone, Ptl) and the metabolite of 17OHP (pregnanetriol, PT) in identifying 21OHD in term and preterm neonates with elevated blood 17OHP on the newborn screening. Spot urine samples from 59 classical 21OHD neonates (50 term, 9 preterm), 83 neonates without 21OHD having transiently elevated blood 17OHP (non-21OHD) (49 term, 34 preterm), and 62 control term neonates were studied using gas chromatography/mass spectrometry in selected ion monitoring analysis for Ptl, PT, 5beta-tetrahydrocortisone (betaTHE), and 5alpha-tetrahydrocortisone (alphaTHE). Ptl and Ptl/(betaTHE+alphaTHE) showed no overlap between 21OHD and non-21OHD, and 21OHD and controls, respectively (Ptl was 0.46-124 mg/g creatinine in 21OHD term, 0.80-26.9 mg/g creatinine in 21OHD preterm, < or = 0.08 mg/g creatinine in non-21OHD term, < or =0.06 mg/g creatinine in non-21OHD preterm, and < or = 0.07 mg/g creatinine in controls). PT and PT/(betaTHE+alphaTHE) showed significant overlap between 21OHD and non-21OHD. The above data indicate that spot urine Ptl is a highly specific marker of 21OHD with a cutoff value of 0.1 mg/g creatinine, yielding an unambiguous separation between 21OHD and non-21OHD in term and preterm neonates.

17-alpha-Hydroxyprogesterone↗

Yeast colonisation & fungaemia in preterm neonates in a tertiary care centre.

Seventy consecutive preterm neonates who stayed in the hospital for more than seven days between March and October 1996, were studied for colonisation at oral, umbilical, groin, and rectal areas and for fungaemia. Overall, 71.4 per cent of the neonates were colonised and colonisation occurred within 24 h in 38 per cent preterm neonates. Neonates weighing less than 1500 g were colonised more frequently at more than one site and had higher load of yeast. Candida albicans (19%), Pichia (Hansenula) anomala (17.5%), C. tropicalis (13.2%), C. parapsilosis (12.3%) and Trichosporon cutaneum (10.0%) were the predominant colonising yeasts. Fungaemia was detected in 22.8 per cent of preterm neonates with predominance of P. anomala fungaemia (62.5%). Prematurity, male sex, broad spectrum antibiotic therapy, intubation and higher colonising rate were identified as significant risk factors for development of fungaemia. Except one strain of C. tropicalis, all yeast strains were sensitive to commonly used systemic antifungal agents. Study highlights the importance of routine surveillance of yeast colonisation of preterm neonates with identifying possible risk factors.

Anti-Bacterial Agents↗

[Cerebral hemorrhage and periventricular leucomalacia in preterm neonates after intravenous tocolysis with fenoterol: results of postnatal ultrasound examination].

BACKGROUND: This study tested whether tocolysis with beta-adrenergic agonists (Fenoterol) had an effect on the frequency of cerebral lesions in preterm neonates. PATIENTS AND METHODS: Head ultrasound scans of preterm neonates who were born after long-term (> 24 h) tocolysis were compared with scans of preterm neonates without preceding tocolysis. The gestational and neonatal data were analyzed retrospectively. RESULTS: Preterm neonates after (n = 102) and without (n = 101) tocolysis were subdivided into three groups according to their gestational age (23 - 28 wk: n = 41; 29 - 33 wk: n = 66; 34 - 36 wk: n = 96). Within these groups, no significant differences were found with respect to birth weight, rate of cesarean section, or pulmonary morbidity. Preterm babies < 28 weeks of gestation from the control group had lower Apgar scores (after 1 and 5 minutes, respectively) and arterial umbilical cord pH values. Intravenous tocolysis did not lead to an increase in pseudocystic periventricular leucomalacia (PVL) or intracerebral hemorrhage (ICH) in any of the subgroups studies. However, cerebral lesions were found in preterm neonates after tocolysis who exhibited signs of infection (29 - 33 wk: PVL n = 2; 23 - 28 wk: ICH n = 1) and in preterm neonates without tocolysis who had undergone fetal hypoxia or abruptio placentae (29 - 33 wk: PVL n = 4; antenatal terminal vein bleeding n = 1; 23 - 28 wk: PVL n = 2; terminal vein bleeding n = 5; posterior cerebral artery bleeding n = 1). When compared to preterm neonates of 34 - 36 weeks of gestation, the risk of infection was increased 4-fold in neonates of 29 - 33 weeks of gestation (odds ratio 5.43, 1.10 - 26.83) and 10-fold in neonates of 23 - 28 weeks of gestation (odds ratio 20.50, 3.65 - 115.03). Chorioamnionitis also was a more common finding in preterm neonates < 28 weeks of gestation. CONCLUSION: Preterm neonates who were born after intravenous long-term (> 24 h) tocolysis with Fenoterol do not exhibit an increase in periventricular leucomalacia or intracranial hemorrhage. The occurrence of cerebral lesions in these patients merely depends on their degree of immaturity and on the presence or absence of perinatal infection. In preterm neonates without tocolysis, brain lesions are mainly associated with hypoxic events.

Cerebral Hemorrhage↗

[Otoacoustic emissions of full-term and preterm neonates].

Transiently evoked otoacoustic emission (TEOAE), distortion product otoacoustic emission (DPOAE), and spontaneous otoacoustic emission (SOAE) were measured in 45 full-term neonates (68 ears) and 12 preterm neonates (20 ears) with ILO88 & 92. Measurements were performed in the nursery of the obstetrics ward or NICU (not sound proof room) under natural sleeping condition after nursing. No sedating agent was used. TEOAEs were rated "good response" in 61 (89.7%) of 68 full-term neonate ears. DPOAEs were rated "good response" in 40 (71.4%) of 56 full-term neonate ears. SOAEs were detectable in 25 (62.5%) of 40 full-term neonate ears. Considering the high positive rate of TEOAE in full-term neonates and the easy and noninvasive method of measurement, we concluded that TEOAE is useful for auditory screening in neonates. There was failure to detect TEOAEs in 7 ears and the measurements were all performed within 6 days after birth. Some reports claim that residual amnion in the external auditory canal or the middle ear in the first few days after birth causes slight hearing loss. Thus, we expected that making the measurements more than 7 days after birth might yield higher "good response" rates. We sometimes found that the Total Echo Powers of TEOAEs were reduced by the poor condition of the ear probe. Thus, we must be very careful in regard to this technical problem in order to perform accurate examinations. Because of its lower "good response" rate, DPOAE was not as useful for screening as TEOAE. Because of the movements or respiratory noises of the newborn infants, it was hard to detect reliable DPOAEs, particularly in the low frequency range. On the other hand, because of its frequency specificity, particurally at high frequencies, DPOAE will be useful for detecting the partial hearing impairment such as congenital high-tone hearing impairment. It would be difficult to use SOAE as a clinical test. Because it is not an evoked response, its mechanism of generation is not well understood. We expect that following longitudinal changes in SOAE in neonates may yield some information about it. We measured mainly TEOAE in preterm neonates because we had to complete the measurements as soon as possible. High Total Echo Powers of TEOAEs were recorded in most infants over 38 weeks of PCA (post conceptional age). The earliest case showed reliable TEOAE at 35 weeks PCA. In most cases that could be measured twice on different days, the Total Echo Powers of TEOAE, were higher in the second time. We therefore concluded that TEOAE might serve as an examination for monitoring the maturation of preterm neonate hearing.

Female↗

Comparison between tryptophan methoxyindole and kynurenine metabolic pathways in normal and preterm neonates and in neonates with acute fetal distress.

OBJECTIVE: To analyze the kynurenine and methoxyindole metabolic pathways of tryptophan in order to identify changes in premature neonates and in neonates suffering from fetal distress. METHODS: One hundred and twelve neonates were assigned to three groups: normal neonates (control group), preterm neonates (neonates born before the 37th gestational week) and neonates suffering from fetal distress. Each of these groups was then divided in two subgroups according to the time of birth corresponding with the time of blood sampling: a diurnal subgroup, comprising neonates whose blood was sampled between 0900 and 2100 h, and a nocturnal subgroup, comprising neonates whose blood was sampled between 2100 and 0900 h. Blood samples from the umbilical artery and vein were taken in the delivery room at birth from each neonate for measurement of melatonin, the main methoxyindole pathway metabolite. Urine samples were collected from 0900 to 2100 h (diurnal groups) and from 2100 to 0900 h (nocturnal groups), and the presence of kynurenic acid, xanturenic acid, 3-hydroxyantranilic acid, L-kynurenine and 3-hydroxykynurenine determined. RESULTS: The results show the existence of diurnal/nocturnal differences in the concentration of melatonin in cord blood and in the urinary excretion of kynurenines. In normal neonates, the production of methoxyindoles (determined as melatonin) is decreased during the day and increases at night, whereas production of kynurenines is high during the day, decreasing at night. In the fetal distress group, a significant increase in the umbilical artery concentration of melatonin was found. This group also showed a reduction in L-kynurenine concentrations in the diurnal and nocturnal groups, and an increase in xanturenic acid and 3-hydroxyantranilic acid during the day. Correlation and regression studies confirmed that the differences in the day/night pattern of the tryptophan metabolic pathways were greater in normal neonates than in the preterm and fetal distress groups. CONCLUSIONS: The results indicate the existence of an imbalance in tryptophan metabolites in preterm infants and those with fetal distress, blunting the normal diurnal/nocturnal rhythm of both melatonin and kynurenines.

Acute Disease↗

Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial.

BACKGROUND: Opioid analgesia is commonly used during neonatal intensive care. We undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial to investigate whether pre-emptive morphine analgesia decreases the rate of a composite primary outcome of neonatal death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL) in preterm neonates. METHODS: Ventilated preterm neonates (n=898) from 16 centres were randomly assigned masked placebo (n=449) or morphine (n=449) infusions. After a loading dose (100 microg/kg), morphine infusions (23-26 weeks of gestation 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); 30-32 weeks 30 microg kg(-1) h(-1)) were continued as long as clinically justified (maximum 14 days). Open-label morphine could be given on clinical judgment (placebo group 242/443 [54.6%], morphine group 202/446 [45.3%]). Analyses were by intention to treat. FINDINGS: Baseline variables were similar in the randomised groups. The placebo and morphine groups had similar rates of the composite outcome (105/408 [26%] vs 115/419 [27%]), neonatal death (47/449 [11%] vs 58/449 [13%]), severe IVH (46/429 [11%] vs 55/411 [13%]), and PVL (34/367 [9%] vs 27/367 [7%]). For neonates who were not given open-label morphine, rates of the composite outcome (53/225 [24%] vs 27/179 [15%], p=0.0338) and severe IVH (19/219 [9%] vs 6/189 [3%], p=0.0209) were higher in the morphine group than the placebo group. Placebo-group neonates receiving open-label morphine had worse rates of the composite outcome than those not receiving open-label morphine (78/228 [34%] vs 27/179 [15%], p<0.0001). Morphine-group neonates receiving open-label morphine were more likely to develop severe IVH (36/190 [19%] vs 19/219 [9%], p=0.0024). INTERPRETATION: Pre-emptive morphine infusions did not reduce the frequency of severe IVH, PVL, or death in ventilated preterm neonates, but intermittent boluses of open-label morphine were associated with an increased rate of the composite outcome. The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates.

Analgesics, Opioid↗

Urinary excretion of darbepoetin after intravenous vs subcutaneous administration to preterm neonates.

OBJECTIVE: Previous studies suggest that darbepoetin might stimulate erythropoiesis in preterm neonates more effectively if injected subcutaneously (s.c.) than if infused intravenously (i.v.). It has been postulated that this is because very high plasma concentrations after i.v. dosing result in urinary loss of the drug. However, this theory has not been tested systematically, and no direct comparisons have been made between s.c. and i.v. dosing of darbepoetin in preterm neonates. STUDY DESIGN: Preterm neonates were eligible for this pilot study if they were born at < or =32 weeks gestation with a weight of < or =1500 g, and had a hemoglobin < or =10.5 g/dl. The darbepoetin was given (4 microg/kg) i.v., over 4 h, if an i.v. was already in place and s.c. if no i.v. was in place. Urine was collected for drug quantification before dosing and for 48 h after. Blood was obtained for immature reticulocyte fraction (IRF), absolute reticulocyte count (ARC) and reticulocyte % before and 96 h after dosing. RESULTS: Ten preterm neonates were studied: five received i.v. and five received s.c. darbepoetin. No adverse effects of the administrations were detected. IRF, ARC and reticulocyte % increased in the i.v. and s.c. recipients, and no difference in magnitude of increase was apparent between the groups. Before the darbepoetin was administered, none of the patients had any erythropoietin (Epo) detected in their urine. After i.v. dosing, no darbepoetin was detected in any of the samples, on any of the subjects, over the subsequent 48 h. After s.c. dosing, three of the patients had minimal urinary Epo detected. The patient with the largest urinary loss of drug had only 0.13% of the administered dose detected in the urine. Thus, essentially no urinary loss of drug was observed following either i.v. or s.c. darbepoetin dosing. CONCLUSION: Darbepoetin loss into the urine was below detectable limits among seven patients, while three had minimally detectable urinary losses. i.v. and s.c. dosing resulted in approximately equivalent increases in reticulocyte response when measured 96 h after dosing. On this basis, we speculate that if a patient who is to receive darbepoetin has an i.v. in place, the drug can be given i.v., thus avoiding any discomfort associated with an s.c. injection.

Darbepoetin alfa↗

The minimum alveolar concentration (MAC) of isoflurane in preterm neonates.

Studies in fetal lambs suggested that the minimum alveolar concentration (MAC) in preterm neonates may be less than that in full-term neonates and older infants. To determine the MAC of isoflurane in preterm neonates, 20 patients less than 32 weeks gestation at birth and 16 patients 32-37 weeks gestation at birth, all less than 1 month post-natal age, were studied. Following tracheal intubation, the neonates were anesthetized with a predetermined end-tidal concentration of isoflurane in oxygen and air. The move-no move responses to skin incision were recorded, and MAC was determined using the "up-and-down" technique. Heart rate and systolic arterial pressure were recorded awake, before skin incision, and after skin incision. MAC (mean +/- SD) of isoflurane in preterm neonates less than 32 weeks gestation was 1.28 +/- 0.17%, and MAC in neonates 32-37 weeks gestation was 1.41 +/- 0.18% (P less than 0.05). Although heart rate did not decrease significantly in either group during the study, systolic arterial pressure decreased between 20 and 30% below awake values both before and after skin incision in both age groups (P less than 0.01). We conclude that the MAC of isoflurane in preterm neonates less than 32 weeks gestation is significantly less than that in preterm neonates 32-37 weeks gestation, and that systolic arterial pressure decreases to a similar extent at approximately 1 MAC isoflurane in both age groups.

Anesthesia, Endotracheal↗

Longitudinal evaluation of salivary cortisol levels in full-term and preterm neonates.

The aim of the present study was to test the practicability of sequential cortisol determinations in saliva of low birth weight neonates and to evaluate the impact of systemic and inhaled glucocorticoid therapy on saliva concentrations of cortisol in preterm neonates with bronchopulmonary dysplasia (BPD). Salivary cortisol levels were measured by RIA in saliva samples from 10 full-term and 10 preterm healthy neonates and from 20 preterm neonates with BPD during systemic [dexamethasone (DEX); n = 10] or topical steroid therapy [budesonide (BUD); n = 10]. Saliva samples of each individual were collected on 3 consecutive days at 06.00, 12. 00, 18.00 and 24.00 h. Cortisol levels in saliva ranged from 0.8 to 60.6 nmol/l (median 6.5 nmol/l) in full-term neonates, from 0.6 to 52.1 nmol/l (median 5.5 nmol/l) in preterm neonates, from 0.4 to 14. 0 nmol/l (median 1.0 nmol/l) in preterm neonates treated with DEX and from 0.4 to 15.2 nmol/l (median 2.5 nmol/l) in preterm neonates treated with BUD. Autocorrelation analysis revealed a distinct endogenous cortisol rhythm in 2 of the 10 healthy full-term neonates and in 3 of the 10 healthy preterm neonates with a wavelength of 12-30 h. Salivary cortisol levels in preterm neonates treated with DEX or BUD were significantly lower than those measured in healthy preterm neonates. These results demonstrate that the measurement of salivary cortisol levels is a reliable and practicable way of assessing adrenal function in full-term and preterm neonates. This study also shows for the first time that some neonates display an endogenous cortisol rhythm which is not coupled to the exogenous day/night cycle. Furthermore, systemic and nebulized glucocorticoids suppress adrenal function in low-birth-weight neonates. After treatment these children should be closely monitored for potential adrenal insufficiency.

Administration, Topical↗

Impaired neutrophil phagocytosis in preterm neonates: lack of correlation with expression of immunoglobulin or complement receptors.

Preterm neonates are vulnerable to infection as a result of a compromised immune system. The function of neutrophils from 'well', 'stressed', and 'maturing' preterm neonates was compared with term neonate and adult neutrophils using a whole-blood phagocytosis assay. Cell surface expression of complement receptors and immunoglobulin G receptors was measured on neutrophils in whole blood from the same samples. Fewer actively phagocytosing neutrophils were found in all preterm neonate samples, especially in maturing neonates. Phagocytic rates were slower, and the number of Escherichia coli ingested was smaller in preterm neonate than in term neonate neutrophils. Expression of immunoglobulin G receptors and complement receptor 3 on neutrophils was not directly related to phagocytic activity.

Adult↗

Combined microsurgical and thrombolytic salvage of an ischaemic lower limb in a 1079 gram preterm neonate.

A 1079 gram preterm neonate suffered complete avulsion of the common and external iliac arteries during aortic balloon valvotomy resulting in complete ischaemia of the lower limb. Salvage by microsurgical extra-anatomic vascular bypass was unsuccessful but additional thrombolytic therapy allowed restoration of blood supply. The limb was then seen to be dependent upon the microvascular bypass. In this case salvage depended upon combined medical and surgical treatment, and the case points to benefits from such a combined approach to therapy.

Aortic Valve Stenosis↗

[Long-term outcome of preterm neonates: the message behind the statistics].

In view of the current progress in neonatal intensive care, the present outcome of former preterm neonates does not necessarily reflect the future outcome of today's preterm neonates. In spite of this statistical uncertainty, long-term follow-up studies performed in the past few years point to the fact that the sequelae of prematurity may appear well beyond infancy and may be revealed in varying manners with increasing age. Therefore, a chronological account of the consequences of prematurity is given in this paper, ranging from perinatal mortality/morbidity to the problems to be observed during early childhood, preschool age, and adolescence right up to the long-term sequelae arising in later adulthood. Within this context, a two-fold paradigm shift in neonatology becomes apparent in that, first, the outcome of preterm neonates is not a result of immaturity per se, yet is significantly influenced by the factors leading to preterm birth (inflammation, intrauterine growth restriction), and, second, the sequelae of prematurity do not end with the end of neonatal intensive care, but are greatly modulated by familial conditions in their further course. Even though the statistical data are still subject to changes, these insights form the basis of a structured long-term follow-up of preterm neonates which, after the progressive establishment of acute treatment strategies, will become an increasingly important challenge to neonatology within the framework of paediatrics.

Adolescent↗

Gestational age assessment in preterm neonates weighing less than 1500 grams.

Postnatal assessment of gestational age in preterm neonates traditionally has been performed using the methods of Dubowitz and Ballard. This study was designed to determine the accuracy of these methods in a sample of very low birth weight preterm neonates. Dubowitz and Ballard examinations were done on 110 preterm neonates within the first 72 hours of life by a neonatologist masked to the gestational age assessed antenatally. Mean birth weight was 1066 +/- 256 g (SD). These data were compared with gestational age assessments using last menstrual period and best obstetric estimate calculated by an obstetrician unaware of the neonatal examination. Mean gestational age using last menstrual period was 28.3 +/- 2.9 weeks. Mean differences between last menstrual period and Dubowitz/Ballard were -2.8 +/- 2.1 weeks and -2.6 +/- 2.2 weeks, respectively. Results using best obstetric estimate were similar. An ophthalmologist examined lens vessels of 89 neonates. A similar pattern toward overestimation of gestational age interval by Dubowitz/Ballard was seen at each lens vessel grade. The Dubowitz and Ballard examinations are inaccurate methods of assessing gestational age in preterm neonates with birth weights less than 1500 g.

Birth Weight↗

Association of pulmonary inflammation and increased microvascular permeability during the development of bronchopulmonary dysplasia: a sequential analysis of inflammatory mediators in respiratory fluids of high-risk preterm neonates.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) of preterm neonates is associated with an increased recruitment of inflammatory cells into the airways. To evaluate further the role of inflammation in the pathogenesis of BPD, tracheobronchial aspirate fluid of neonates with birth weight < 1200 g (n = 59) was sequentially analyzed in a prospective study. METHODS: Tracheobronchial aspirate fluid was assessed for chemotactic activity, neutrophil cell count, concentrations of elastase-alpha 1-proteinase inhibitor and activity of free elastase, concentrations of chemoattractants (complement component C5-derived anaphylatoxin, leukotriene B4, interleukin-8), and albumin concentrations as well as alpha 1-proteinase inhibitor activity. The secretory component for immunoglobulin A was used as reference protein. Only specimens without evidence of microbiological colonization were studied. RESULTS: In neonates with prolonged respiratory disease (BPD-risk neonates, n = 24, fraction of inspired oxygen > or = 0.3 and/or peak inspiratory pressure > or = 16 cm H2O at day 10 postnatal age, birth weight 892 +/- 36 g, gestational age 27.2 +/- 0.3 weeks) chemotactic activity, cell count, concentrations of the chemoattractants complement component C5-derived anaphylatoxin, leukotriene B4, interleukin-8, as well as levels of elastase-alpha 1-proteinase inhibitor were significantly higher at day 10 and/or day 15 of postnatal age compared with neonates without chronic pulmonary disease (total n = 35; day 10, n = 11; day 15, n = 8). There was no difference in free elastolytic activity. Concentrations of albumin as well as alpha 1-proteinase inhibitor activity were higher in BPD-risk patients on day 15, indicating an increased pulmonary leak. CONCLUSION: We conclude that preterm neonates at risk for the development of BPD show an enhanced inflammatory reaction in the lungs and an associated increase in pulmonary microvascular permeability. We speculate that inflammation may play an important role in the pathogenesis of BPD.

Albumins↗

Maturation of phasic and continuity measures during sleep in preterm neonates.

Different physiologic measures during EEG sleep periods in preterm neonates are postulated to change with maturation and reflect functional brain development. Forty-three healthy preterm neonates received 3-h EEG sleep studies in an environmentally controlled setting. Postconceptional ages of neonates at each recording session ranged from 28 to 35 wk. Minute-by-minute analyses of EEG discontinuity, motility, arousals, and REM were performed. Eight phasic events and continuity measures of sleep were tabulated. Data were analyzed using Spearman rank order correlation coefficients. Increases in arousal numbers (p < 0.001) and durations (p < 0.001) were noted with age only during continuous periods of EEG activity (i.e. active sleep). REM also increased with corrected age during indeterminate or transitional sleep (p < 0.002) and decreased during quiet sleep (p < 0.01). Decreases in small body movements per minute (p = 0.02) and large body movements per minute (p < 0.001) occurred only during discontinuous periods of EEG activity (i.e. quiet sleep). Sleep efficiency (p < 0.001), maintenance (p < 0.001), and latency (p = 0.01) also decreased with increasing postconceptional age. Cycle length between two segments of continuous EEG with an intervening period of EEG discontinuity also lengthened with maturation (p < 0.001). These findings are discussed in the context of previously reported differences in phasic and continuity measures noted between preterm and full-term infants at matched full-term postconceptional ages. Changes in phasic and continuity measures with increasing postconceptional ages reflect maturation of specific neuronal processes of the CNS within a rudimentary sleep cycle of the preterm neonate.

Electroencephalography↗