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Neonates with extra-renal pelvis: the first 2 years.

Extra-renal pelvis (ERpel) is a common ultrasonographic finding among neonates who have undergone recurrent ultrasound examinations for a better definition of prenatal renal pelvic dilatation. This study tries to determine whether or not ERpel has important prognostic implications. Seventy-nine neonates (17 female) were examined. All had a diagnosis of prenatal renal pelvis dilatation, which was shown by postnatal ultrasound to be ERpel. Sixty ERpel neonates were examined 1.5 months to 2.5 months after the ultrasound (US) diagnosis by both Tc-99m diethylene triamine penta-acetic acid (DPTA) dynamic renal scanning and (99m)Tc-pertechnetate direct cystography. Clinical assessment, urine cultures and renal ultrasound follow-up were maintained for 2 years. The proportion of urinary tract infections (UTIs) in patients with ERpel was compared with that of the total neonatal and infantile population with normal US scans in the region of our hospital. Associated minor congenital malformations were found in 12 of 79 neonates (15.2%). Four had a family history of ERpel. Among 60 neonates who underwent renal scanning, 36 (60%) were found to have urinary retention in the collecting system. Another nine (15%) had vesico-ureteral (VU) reflux, of which seven had urinary retention. Fifteen (25%) showed normal isotope imaging. Urinary tract infection was diagnosed in 16 ERpel neonates in whom only one exhibited VU reflux (grade 2). The incidence of neonatal UTI in the ERpel group was more than that of either neonatal or infantile UTI in those with normal US scans in the local population (20.2% vs 1.2% and 4.3%, respectively). Fifty-three infants completed a 2-year follow-up. Repeat renal ultrasonography indicated that one infant (1.8%) had developed bilateral hydronephrosis, 12 (22.6%) had unchanged findings, 18 (40%) showed an improvement (decrease of ERpel width or resolution in one side) and, in 22 (41.5%) infants, the condition had resolved. No clinical or kidney function deterioration was observed. Seven patients (13.2%) each had one episode of UTI during the 2-year follow-up period; none of them had VU reflux. Neonatal ERpel is more frequent in male infants. It is associated with greater rates of minor congenital malformations, VU reflux and UTI than in the general population of the same ages. The increased UTI incidence is not attributed to VU reflux.

Abnormalities, Multiple↗

First urinary tract infection in neonates, infants and young children: a comparative study.

In an attempt to evaluate first urinary tract infection (UTI) in neonates and infants, we estimated retrospectively in 296 patients (62 neonates and 234 infants) clinical and laboratory findings, occurrence of vesicoureteral reflux (VUR), urinary tract abnormalities and pyelonephritis. First UTI occurred more often in male than female neonates, whereas male and female infants/young children were affected at an equal rate. The pathogens isolated in urine cultures of neonates and infants did not statistically significantly differ (P>0.05); Escherichia coli predominated. Gram-negative bacteria other than E. coli affected boys more often than girls (P=0.0022). Fever was the most frequent symptom. Neonates had lower-grade fever of shorter duration than infants (P<0.05). The incidence of reflux and urinary tract abnormalities did not differ between neonates and infants, male and female neonates and infants (P>0.05). Pyelonephritis affected neonates and infants at an equal rate; it was more prevalent among female patients (P=0.038) and patients with VUR or urinary tract abnormalities other than VUR (P<0.0001). Neonates with reflux were more often affected by Gram-negative bacteria other than E. coli than were neonates without reflux (P=0.0008).

Child, Preschool↗

Antigen presentation by neonatal murine spleen cells.

The ability of murine neonatal spleen cells to present soluble antigen to T-helper cells and to produce growth factors in response to subsequent cellular interactions was studied. The T-helper-cell line (D10-G4.1) (D10), which is specific for the soluble antigen conalbumin presented on H-2-matched (H-2k) antigen-presenting cells, was used as cooperating and indicator cells in these cellular interactions. The D10 cells are TH2 T-helper cells which secrete the autocrine growth factor IL-4 and can also respond to exogenous IL-2 (T. R. Mosmann and R. L. Coffmann, Immunol. Today 8, 223, 1987). D10 cells require exogenous IL-1 for their proliferation and secrete, in addition to IL-4, IL-1 inducer factor and GM-CSF. The ability of neonatal spleen cells to present antigen and to stimulate D10 cells to produce IL-4 and proliferate is low. During antigen presentation there is an augmentation of IL-1 and IL-2 production by the antigen-presenting spleen cell population. However, neonatal spleen cells do not respond to the same levels as do adult spleen cells. The addition of exogenous IL-1 cannot repair the antigen presentation by neonatal cells. Experiments in which the antigen processing and presentation steps were separated from those requiring growth factor induction and secretion demonstrate that neonatal spleen cells are impaired in their ability to perform adequate antigen processing and presentation. The neonatal spleen cells are as competent as adult cells to cooperate with T-helper cells and secrete growth factors, provided antigen processing and presentation is performed by fully competent adult spleen cells. Experiments in which neonatal and adult antigen-presenting spleen cell populations were mixed, and others in which plastic adherent and nonadherent cells were separated, could not detect any suppressor mechanisms responsible for the low antigen presentation of neonatal cells. Thus, neonatal spleen cells are impaired in the initial stages of antigen processing and presentation. This impairment which leads to low levels of growth factor production is the major determinant in the ineffectual stimulation of T-helper cells by neonatal spleen cells.

Animals↗

Receptor binding activity of high-density lipoproteins containing apoprotein E from abetalipoproteinemic and normal neonate plasma.

The receptor binding properties of lipoproteins derived from neonates and abetalipoproteinemic patients were examined. Compared to normal adults, the neonate plasma contained reduced cholesterol levels, with only 40% of the total cholesterol transported in the low-density lipoproteins (LDL). When compared at equal cholesterol concentrations, however, the total neonate lipoproteins (d less than 1.21) were as effective as adult d less than 1.21 lipoproteins in stimulating cholesteryl ester formation in cultured human fibroblasts. Analysis of the neonate lipoproteins explained their enhanced ability to deliver cholesterol to the cells via LDL (apoprotein B,E) receptors: the neonate d = 1.02-1.063 fraction contained, in addition to LDL, alpha 2-migrating, apoprotein E-rich high-density lipoproteins (HDL1), which were isolated by Geon-Pevikon electrophoresis. In binding studies performed with human fibroblasts at 4 degrees C, the neonate HDL1 were 14-fold more effective than either neonate or adult human LDL in displacing 125I-LDL from apo-B,E receptors. The neonate HDL (d = 1.063-1.21) contained a subfraction rich in apo-E and apo(E-A-II), which was isolated by heparin-Sepharose chromatography. This fraction was also active in displacing 125I-LDL from the receptors on cultured fibroblasts. Apoprotein E-containing HDL subclasses, similar to those described in the blood of neonates, were present in the d less than 1.063 and d = 1.063-1.21 lipoprotein fractions of patients with abetalipoproteinemia. These HDL with apo-E were enriched in cholesterol and were as effective as normal LDL in competing with 125I-LDL for apo-B,E receptor-mediated binding, internalization, and degradation. When incubated with cultured human fibroblasts, the HDL with apo-E from the abetalipoproteinemic subjects increased the cholesteryl ester mass three- to fourfold. These studies suggest that neonates and abetalipoproteinemic subjects may depend (at least in part) upon lipoproteins containing apo-E to deliver cholesterol to various tissues via the LDL (apo-B,E) receptor.

Abetalipoproteinemia↗

Analysis of carbohydrate-intolerant profiles of mothers with normal glucose tolerance tests and their large for gestational age neonates.

OBJECTIVE: To examine endocrine states of mothers with normal 75-g oral glucose tolerance tests (GTTs) who gave birth to large for gestational age (LGA) neonates (group I) and to examine those neonates. METHODS: We examined plasma glucose levels and serum immunoreactive insulin responses after the 75-g oral GTT was given to group I mothers (N = 34), mothers with an abnormal oral GTT who gave birth to LGA neonates (group II, N = 21), and those with normal oral GTTs having appropriate for gestational age neonates (group III, N = 173). We also examined the infants, checking neonatal birth weight, levels of immunoreactive insulin and C-peptide immunoreactivity in cord sera at birth and the lowest blood sugar level after birth to see if a correlation existed between them. RESULTS: Group I and II mothers showed higher titers in plasma glucose levels and remarkably enhanced ratios of 60- to 30-minute immunoreactive insulin values (immunoreactive insulin up-ratio) after load compared with those of group III mothers. Cord serum immunoreactive insulin and C-peptide immunoreactivity were significantly higher and the lowest blood sugar level was significantly reduced in group I and II neonates compared with those in group III. We observed a positive correlation between cord serum immunoreactive insulin, C-peptide immunoreactivity, and birth weight, but a negative correlation between cord serum immunoreactive insulin, birth weight, and the lowest blood sugar level in group I and II neonates (strongest tendency in group II), but not in group III neonates. CONCLUSION: All of the abnormal carbohydrate metabolic responses in group I mothers and neonates may result in the promotion of growth in LGA fetuses similar to group II, but to a lesser extent. Identification of group I mothers by the immunoreactive insulin up-ratio after oral GTT will help predict the occurrence of LGA neonates and their possible hypoglycemia.

Birth Weight↗

The effect of cigarette smoking on neonatal anthropometric measurements.

OBJECTIVE: To estimate the effect of maternal cigarette smoking on birth weight, crown-heel length, and ten other neonatal anthropometric measurements. METHODS: Data are from a cohort study on risk factors for fetal growth retardation (FGR) in multiparous women conducted from December 1985 through October 1988. Information on smoking status was collected four times during pregnancy. Data analysis included 1205 singleton infants of women delivering at term. Neonatal anthropometric measurements were obtained within 48 hours of birth, including birth weight, crown-heel length, ponderal index, head and abdominal circumferences, arm length and circumference, femur length and thigh circumference, and triceps, thigh, and subscapular skinfold measurements. Analysis of covariance models were used to assess the independent effect of smoking on each neonatal measurement. RESULTS: Neonates born to women who reported smoking during the first trimester had a 0.6-1.9% reduction in most neonatal anthropometric measurements, resulting in an overall reduction of birth weight of 130 g (4%). Neonates born to women who continued to smoke throughout pregnancy had an average adjusted reduction in birth weight of 189 g (5.9%), compared with a 55 g (1.7%) reduction for neonates born to women who stopped smoking after the first trimester. For women who continued to smoke throughout pregnancy, an increased number of cigarettes smoked was associated with increased reductions in birth weight and neonatal chest and abdominal circumferences. For women who stopped smoking after the first trimester, stopping was a better predictor of neonatal anthropometric measurements than the number of cigarettes smoked early in pregnancy. CONCLUSIONS: Except for the ponderal index, all neonatal anthropometric measurements studied showed some negative effect of maternal cigarette smoking. Head circumference is the measurement least reduced. Smoking cessation is a better predictor of infant size than the number of cigarettes smoked in the first trimester.

Adult↗

Endoscopic examination of the neonatal larynx at extubation: a prospective study of variables associated with laryngeal damage.

Despite postmortem and clinical studies, the etiological factors that determine why only a proportion of intubated neonates develop subglottic stenosis remain unclear. This prospective study was initiated to identify factors that were associated with laryngeal abnormalities secondary to intubation. Thirty neonates were examined at extubation by two independent observers blinded to the neonate's ventilatory history. Thirty-six possible prognostic indicators were recorded for each neonate. After screening by univariate (chi 2) analysis, 10 indicators were selected for further analysis. Of these 10 selected only two indicators showed an association with the laryngeal appearance. Active neonates had significantly more abnormalities in the supraglottis (P = 0.004) than those who were quiescent. Younger neonates had more abnormalities in the glottis though the significance level was marginal (P = 0.056). Other prognostic indicators, including birthweight, gestational age, duration of intubation and frequency of intubation, were not significantly related to laryngeal appearance. This study supports the hypothesis that the etiology of laryngotracheal stenosis is multifactorial, and has identified two possible etiological factors: age and neonatal activity. Neonatal activity has not been identified previously as an etiological factor. The contribution of individual factors may vary from one neonatal unit to another, as a result of variation in intubation, ventilation and extubation policy. This could explain the inconsistency in etiological factors identified by previous studies. It is therefore not yet possible to recommend a standard technique for the ventilation of premature neonates that would further reduce the incidence of laryngotracheal stenosis.

Erythema↗

Causes of death in neonates born with a heart malformation.

All deceased infants were autopsied in a territory with a population of 1 220 000 inhabitants and a mean of 17 410 live births a year. During a period of 25 years (which preceded the introduction of advanced neonatal cardiac surgery), 393 neonates (6% of all deceased neonates) had died in whom a congenital heart malformation was found at autopsy. 118 (30%) of deaths were due to noncardiac causes. Lethal congenital noncardiac malformations caused death in 38 (10%) neonates. A perinatal disease (including birth trauma) was the cause in 65 (16%) neonates. An association of a noncardiac congenital malformation with a perinatal disease was involved in 6 (2%) neonates and a birth weight lower than 1000 g (together with a lethal perinatal disease or alone) was considered responsible in 9 (2%) neonates. Noncardiac but not unambiguously lethal malformations (mostly multiple) could at least have contributed to the fatal outcome in a further 86 (22%) neonates. A low birth weight could have contributed to death in 102 (26%) neonates, particularly in 42 (11%) neonates with a low birth weight associated with multiple noncardiac nonlethal malformations. A most probable or possible noncardiac cause of death was found in all cases of atrial septal defect, in 93% of tetralogies of Fallot, in 84% of ventricular septal defects, in 72% of hearts with double outlet right ventricle and in 57% of those with aortic coarctation. A congenital heart malformation was considered responsible for a fatal outcome in 82% of cases with discordant ventriculoarterial connexions ("transposition of the great arteries"), 79% of hypoplastic left hearts, 68% of pulmonary atresias and 53% of tricuspid atresias. The high proportion of noncardiac death noted to occur in the first postnatal day was found rapidly to decrease in the following days.

Age Factors↗

Comparison of hind limb muscle mass in neonate and adult prosimian primates.

Little ontogenetic data exist to indicate whether muscular organization of neonates reflects adult locomotion (e.g., leaping) or infant activities like clinging or the initial quadrupedal phase of locomotion that typifies most infant primates. In the present study, five species of primates with contrasting modes of locomotion were examined. Twenty-eight preserved neonatal and adult cadavers were studied by careful dissection of the hip, thigh, and leg muscles. Wet weights were taken of limb muscles after removal, and the muscles were combined into major functional groups (e.g., flexors, extensors) of each limb segment. Results demonstrate that the distribution of muscle mass within the thigh and within the leg are similar between neonates and adults for all species, with major groups varying by 5% or less in all but two age comparisons. Crural indices of the neonates are nearly identical to those of the adults, but leg/thigh muscle mass ratios were higher in the neonates. Species vary greatly in the percentage of adult limb segment muscle mass present in neonates, with Tarsius syrichta having the greatest percentage for all segments and two lemurids showing the least. These results primarily track differences in relative body mass at birth rather than developmental differences. The adaptive distribution of muscle, as discussed previously for adult prosimians, appears to be established at birth. Neonates of leaping species already have much larger quadriceps muscles than quadrupeds. Differences between large- and small-bodied leapers (e.g., pronounced superficial plantarflexor masses in tarsiers and pronounced deep plantarflexor masses in sifakas) also are present in neonates. Ratios of muscle mass over body mass are smaller in all neonates than in their adult counterparts, suggesting that the neonates are relatively poorly muscled, and that muscle mass must increase with positive allometry during growth.

Aging↗

Minimal access surgery in neonates and infants.

BACKGROUND: Minimal access surgery (MAS) in small infants carries an important consideration. The tolerance of these small babies and the assumed physiological effect of MAS, in addition to the required anesthetic and surgical skills, have made it difficult to perform these types of procedures in many international centers. The present article reviews our experience with MAS in neonates and infants in the first year of life. METHODS: The medical records of all neonates and infants (<1 year) who underwent MAS over a period of 3 years were retrospectively reviewed for demographic information, procedures, operative time, complications, outcomes, and follow-up. Most of the operations were performed with 3-mm instruments and scopes and mean insufflation pressure of 10 mm Hg (range, 4-15 mm Hg). RESULT: Seventy neonates and infants were included in this study: 19 females and 51 males. The weight ranged from 1.3 to 8.2 kg (mean, 4.3 kg). The mean age was 93 days (range, 1 day to 12 months). Twenty-four (34%) were neonates (first 30 days of life). Procedures performed included repair of tracheoesophageal fistula, lobectomy, repair of diaphragmatic or hiatus hernias, pull-through for imperforated anus and Hirschsprung's disease, plication of the diaphragm, Kasai procedure, excision of choledochal cyst, pyloromyotomy, Ladd's procedure, and reduction of intussusceptions. There were 2 conversions, both in neonates with tracheoesophageal fistula. All patients tolerated the procedure very well, with lesser degrees in neonates undergoing thoracoscopic procedures. Two neonates had postoperative hypothermia (<35 degrees C) and 1 neonate had high PCO2 postoperatively. There was 1 mortality and no morbidities. The follow-up ranged from 1 month to 3 years (mean, 19 months). CONCLUSION: Minimal access surgery in neonates and infants is safe and well tolerated. Intraoperative monitoring of end-tidal CO2 and core temperature is essential in avoiding unwanted effects of performing these procedures, especially in neonates.

Feasibility Studies↗

The size 1 LMA-ProSeal: Comparison with the LMA-Classic during pressure controlled ventilation in a neonatal intubation manikin.

BACKGROUND: The classic laryngeal mask airway (cLMA) has been demonstrated to be effective for airway management during neonatal resuscitation. However, high airway pressures, when required, cannot be achieved with this device. A neonatal prototype of the LMA-ProSeal (PLMA), which might improve the oropharyngeal leak pressure, has recently been produced. The airway sealing pressures of the cLMA and the PLMA were compared in a neonatal manikin. METHODS: A neonatal PLMA and a neonatal cLMA were positioned at random in a neonatal intubation manikin (Neonate Airway Trainer; Laerdal, Norway). A Dräeger pressure controlled ventilator (Dräeger 8000; Dräegerwerk AG, Germany) was connected to the airway tubes and increasing inspiratory pressures (from 10 to 40 cm H2O) of positive pressure ventilation applied. The peak and the mean airway pressures obtained with each device were recorded. RESULTS: The airway pressures obtained with PLMA were significantly higher than those obtained with cLMA (p < 0.01) at levels of positive pressure ventilation of 25, 30, 35 and 40 cm H2O. CONCLUSIONS: The neonatal PLMA allows higher airway pressure ventilation than the cLMA, in a neonatal intubation manikin. If confirmed clinically, this may have important implications during neonatal resuscitation when high airway pressures are required.

Cardiopulmonary Resuscitation↗

Perinatal transport to a regional perinatal center in a metropolitan area: Maternal versus neonatal transport.

A prospective study was undertaken to evaluate antenatal maternal referral, acute maternal transport, and neonatal transport to a regional perinatal center in a metropolitan area. During an 18-month period, there were 143 antenatal maternal referrals, 254 antenatal maternal transports, and 506 neonatal transports. Indications for the antenatal referrals were maternal diseases of a chronic nature. This group had a 28.7% incidence of delivery by primary cesarean section, a 15.8% incidence of low-birth weight infants, and a 30.8% incidence of neonatal admissions to the Neonatal Intensive Care Unit (NICU). The perinatal mortality rate was 13.7 per thousand which compares favorably with that of low-risk obstetric patients. Indications for the antenatal maternal transports were mainly premature labor and/or premature rupture of the membranes and third-trimester bleeding. There was a 37% incidence of delivery by primary cesarean section and a 71.5% incidence of low-birth weight infants, and 77.4% of the newborn infants were admitted to the NICU. The perinatal mortality rate was 137.4 per thousand live births. Compared to postnatal neonatal transports, the neonates transported antenatally had a slightly higher mortality rate which was not statistically significant. One hundred thirty-one neonates transported antenatally could be matched in sequential order of admission with 131 neonates transported postnatally of comparable birth weights and gestational ages. Although there was a significant increase in the incidence of delivery by cesarean section among the mothers transported antenatally, the neonates in this group had a significantly lower incidence of respiratory distress syndrome and other morbidity and a shorter hospitalization. This study suggests that antenatal referral and transport of high-risk parturient patients to a regional perinatal center may significantly decrease neonatal morbidity and length of hospitalization.

California↗

Outcome of very-low-birth-weight infants: does antepartum versus neonatal referral have a better impact on mortality, morbidity, or long-term outcome?

To evaluate the effect of aggressive intrapartum and early neonatal resuscitation on perinatal mortality, neonatal morbidity, and long-term outcome, we evaluated two groups of low-birth-weight infants who received different intrapartum and early neonatal care. One group of infants was delivered at a university-based regional perinatal center offering both high-risk obstetric and tertiary neonatal care. The second population consisted of infants from five community hospitals with level I nurseries. These two groups were selected because they differed in the ability to provide intrapartum and early neonatal care and because a total base population could be evaluated. During the 4-year study period, 174 infants with birth weights of 500 to 1499 gm were delivered at the university center and 297 infants were delivered at the community hospitals. At the university center, there was a significant reduction in fetal deaths, a delay in the time of neonatal deaths, and a reduction in hyaline membrane disease. Neonatal mortality rates at the university center were not reduced, and the incidence of sequelae was not affected. These data suggest that for the smallest infant, intrapartum and immediate neonatal care at a tertiary center may decrease fetal mortality and neonatal morbidity rates. Neonatal mortality and long-term outcome, however, may be less affected.

Child Development↗

Risk factors for neonatal death in twin gestations in the state of South Carolina.

OBJECTIVE: The aim of the study was to describe risk factors for neonatal death among twins born in South Carolina. STUDY DESIGN: South Carolina publicly accessible live birth and infant death cohort files for live-born twins >500 g were reviewed for the years 1988 through 1993. Infants with lethal anomalies were deleted from the cohort before analysis. Risk factors for neonatal death were determined for the entire cohort and for the birth weight categories of 500 to 999 g, 1000 to 1499 g, 1500 to 2499 g, and >/=2500 g. Statistical comparisons were performed with the Mantel-Haenszel chi2 test and multivariate logistic regression. RESULTS: Of 7833 live-born twins, 263 (3.4%) died during the neonatal period. The mean birth weight was 2357 +/- 650 g (range 500-5358 g) at a mean gestational age of 35.7 +/- 3.5 weeks. Overall neonatal mortality rates were significantly increased (P <.001) for twins whose mothers were nonwhite (4.2 vs 2.8%), were <20 years old (6.0 vs 3.2%), or received no prenatal care (14.7 vs 3.1%). After we controlled for population characteristics with multivariate techniques, analysis revealed birth weight <2500 g and residence in the most populous urban areas to be associated with increased neonatal mortality rates. After stratification into birth weight categories, race was no longer a significant variable; in fact, nonwhite twins had a survival advantage at birth weights <1500 g, but this was not significant. Maternal age <20 years was associated with a higher neonatal mortality rate for infants with birth weights between 1500 and 2499 g. Absence of prenatal care significantly increased the neonatal mortality rate for twins >/=1500 g but not for those who were smaller. For infants weighing 500 to 999 g neonatal mortality rates were significantly lower at hospitals with >/=2000 deliveries/y than at hospitals with lower delivery volumes (P =.005). CONCLUSIONS: Although the overall neonatal mortality rate for twins continues to improve, increased rates are still seen among blacks, teenagers, and women who receive no prenatal care. Twins between 500 and 999 g have significantly reduced neonatal mortality rates when delivered at hospitals with a high obstetric volume.

Adult↗

C-reactive protein as biochemical indicator of bacterial infection in neonates.

Serial quantitative measurements of C-reactive protein (CRP) were performed, using an automated enzyme immunoassay method, in 127 neonates (114 premature and 13 full-term) classified in three groups: neonates with a normal postnatal course (group 1, n = 69), neonates with clinical suspicion of bacterial infection but with negative cultures (group 2, n = 49), and neonates with proven bacterial infection (group 3, n = 9). A total of 545 serial serum CRP concentrations were determined. In group 1, CRP concentrations were below the detection limit of the method (10 mg/L) except in one neonate who suffered from neonatal anoxia but whose clinical course was uncomplicated (CRP: 31 mg/L within 24 h of life). Thirty-three neonates of group 2 had CRP values consistently below 10 mg/L while 16 had elevated CRP concentrations at least on one occasion ranging from 10 to 70 mg/L. Diagnoses other than bacterial infection could explain the raised CRP concentrations in neonates of group 2. CRP concentrations were found to be elevated (greater than 80 mg/L) during the course of infectious diseases in all neonates with proven bacterial infection (septicemia (4), pneumonia (1), multiple micro-abscesses (1), urinary tract infection (3]. Serial measurement of CRP concentrations are shown to be valuable in detecting bacterial infection in neonates as well as in following the efficacy of antimicrobial therapy.

Bacterial Infections↗

A comparison of neonatal and adult multiorgan failure in a rat model.

BACKGROUND/PURPOSE: To establish a neonatal animal model of multiorgan failure (MOF) for the histological study of the sequence and severity of neonatal MOF in comparison to a model of adult MOF. METHODS: Neonatal and adult Sprague-Dawley rats received a single intraperitoneal injection of the inflammatory agent Zymosan. Rats were weighed; randomly killed on days 1 through 6; and heart, lung, liver, kidney, spleen, and ileocecum harvested for histological examination. RESULTS: Neonatal animals receiving Zymosan showed a significant increase in total body weight not seen in adults. The sequence and severity of MOF-induced organ damage were strikingly different in adult and neonatal animals. Mild lung damage was seen as early as day 1 in adult rats receiving Zymosan. This progressed to moderate damage by day 2 and severe damage by day 6. Lungs of neonatal rats receiving Zymosan showed only mild damage by day 4, which had progressed no further by day 6. Mortality rate was not significantly different between adult and neonatal animals receiving Zymosan. CONCLUSIONS: Zymosan can be used in a neonatal animal model to incite MOF. In the neonatal animal model of MOF there is (1) substantial early capillary leak as shown by increased body weight; (2) a unique progression of organ involvement-liver, kidney, lung compared with adult animals with MOF-lung, liver, kidney; and (3) relative sparing of the lung from injury. These findings are consistent with previous clinical observations of a difference in neonatal and adult MOF.

Age Factors↗

Adenoviral-mediated gene transfer to murine small intestine is more efficient in neonates than adults.

PURPOSE: The authors sought to assess the feasibility of in vivo gene transfer to the small intestine using recombinant adenovirus in neonatal and adult mice. METHODS: H5.010CMVlacZ is a replication-defective, E1-deleted human type 5 adenovirus, which contains the lacZ gene under the control of a cytomegalovirus promoter and enhancer. The lacZ gene was used as a marker because its gene product, beta-galactosidase, is readily detected by X-gal histochemistry. Sixty neonatal (3 to 5 days old) and 45 adult (6 to 8 weeks old) C57BL/6 mice were investigated. Intestinal gene transfer was attempted with H5.010CMVlacZ by intraperitoneal (i.p.), intraluminal (IL), and intramural (i.m.) injection. Based on prior studies, the optimal dose of H5.010CMVlacZ was 1 x 10(8) plaque forming units (pfu/mL). Control animals received saline injections. Gene transfer on repeat administration of adenovirus has been shown to be prevented by neutralizing antibody. To determine if neonatal inoculation induced a humoral immune response, neonates (n = 5) that received i.p. injections were rechallenged with intravenous H5.010CMV alkphos, a similar adenoviral construct containing the alkaline phosphatase marker gene. Serum samples were analyzed by Western blot to detect the presence of adenoviral-specific antibody. RESULTS: Gene transfer to neonatal small intestine was successful by IL gastric (n = 8/10), IL jejunal (n = 9/10) and i.p. (n = 10/10) routes 2 days after injection. Macroscopic staining was present in 90% of standardized 2-cm small bowel segments. Transgene expression was identified in intestinal smooth muscle, serosa, and epithelium. Gene transfer to the adult small intestine was successful by IL jejunal (n = 4/5), i.m. (n = 5/5), and i.p. (n = 1/5) injection of adenoviruslacZ with focal staining (< 5% of 2-cm segments) in epithelium including crypts, muscle, and serosa. Three weeks after i.p. H5.010CMVlacZ in neonates, intravenous injection with H5.010CMValkphos resulted in hepatic transgene expression (n = 4/5) that was indistinguishable from a primary intravenous inoculation; persistent, lacZ expression was not detectable in the liver or intestine (n = 0/5). Western blot analysis detected adenoviral-specific antibodies after adult IM but not after neonatal i.p. injection. Furthermore, 3 weeks after neonatal i.p. injection repeat administration by the i.m. route was successful (n = 4/ 4). CONCLUSION: Gene transfer to neonatal and adult small intestine is feasible using recombinant adenovirus and is more efficient in neonates as indicated by increased surface area of marker gene expression, effectiveness of intraperitoneal delivery, and the ability to readminister recombinant adenovirus.

Adenoviruses, Human↗

Does extracorporeal membrane oxygenation benefit neonates with congenital diaphragmatic hernia? Application of a predictive equation.

The overall survival of neonates with congenital diaphragmatic hernia (CDH) remains poor despite the advent of extracorporeal membrane oxygenation (ECMO). Attempts at accurately predicting survival have been largely unsuccessful. The purpose of this study was twofold: (1) to identify independent predictors of survival from a cohort of CDH neonates treated at the authors' institution when ECMO was not available and combine them to form a predictive equation, and (2) to apply the equation prospectively in a cohort of CDH neonates, treated at the same institution when ECMO was available, to determine whether ECMO improves outcome. From the clinical data of 62 CDH neonates treated at the authors' center by the same team of university neonatologists and pediatric surgeons between 1983 and 1993 (before ECMO availability), 15 preoperative and seven operative variables were selected as potential independent predictors. When subjected to multivariate, stepwise logistic regression analysis, four variables were identified as statistically significant (P < .05), independent predictors of survival: (1) ventilatory index (VI), (2) best preoperative PaCO2, (3) birth weight (BW), and (4) Apgar score at 5 minutes. When combined via logistic regression analysis, the following predictive equation was formulated: P (probability of survival to discharge) = [1 + e(x)]-1 where x = 4.9 - 0.68 (Apgar) - 0.0032 (BW) + 0.0063 (VI) + 0.063 (PaCO2). Applying a standard cut-off rate of survival at less than 20%, the equation yielded a sensitivity of 94% and a specificity of 82% in identifying the correct outcome of patients treated with conventional ventilatory management. The overall survival rate was 66%. Since the availability of ECMO at the center, 32 CDH neonates were treated using the same conventional ventilatory treatment and surgical repair by the same university staff. The overall survival rate was 69%. The predictive equation was applied prospectively to all neonates to determine predicted outcome, but was not used to decide the treatment method. Eighteen neonates received conventional therapy alone; 16 of 18 survived (89%). Fifteen of the 16 patients who survived had their outcomes predicted correctly (94%). Fourteen neonates did not respond to conventional therapy and required ECMO; 6 of 14 survived (43%). Six of the eight patients predicted to survive, lived (75%). All six patients predicted to die, died despite the addition of ECMO therapy (100%). The mean hospital cost, per ECMO patient who died, was $277,264.75 +/- $59,500.71 (SE). An odds ratio analysis, using the four independent predictors to standardize for degree of illness, was performed to assess the risk associated with adding ECMO therapy. The result was 1.25 (P = 0.75). Although the cohort was not large enough to eliminate significant beta error, the data strongly suggested no advantage of ECMO. At this center, absolute survival rates for neonates with CDH have not been significantly altered since ECMO has become available (66% v 69%). The authors conclude that the predictive equation remains an accurate measurement of survival at their center even when ECMO is used as a salvage therapy. The method of creating a predictive equation may be applied at any institution to determine the potential outcome of CDH neonates and assess the effect of ECMO, or other salvage therapies, on survival rates.

Decision Support Techniques↗