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Phenobarbital compared with phenytoin for the treatment of neonatal seizures.

BACKGROUND: Seizures occur in 1 to 2 percent of neonates admitted to an intensive care unit. The treatment is usually with either phenobarbital or phenytoin, but the efficacy of the two drugs has not been compared directly. METHODS: From 1990 to 1995, we studied 59 neonates with seizures that were confirmed by electroencephalography. The neonates were randomly assigned to receive either phenobarbital or phenytoin intravenously, at doses sufficient to achieve free plasma concentrations of 25 microg per milliliter for phenobarbital and 3 microg per milliliter for phenytoin. Neonates whose seizures were not controlled by the assigned drug were then treated with both drugs. Seizure control was assessed by electroencephalographic criteria. RESULTS: Seizures were controlled in 13 of the 30 neonates assigned to receive phenobarbital (43 percent) and 13 of the 29 neonates assigned to receive phenytoin (45 percent; P=1.00). When combined treatment is considered, seizure control was achieved in 17 (57 percent) of the neonates assigned to receive phenobarbital first and 18 (62 percent) of those assigned to receive phenytoin first (P=0.67). The severity of the seizures was a stronger predictor of the success of treatment than was the assigned agent. Neonates with mild seizures or with seizures that were decreasing in severity before treatment were more likely to have their seizures end, regardless of the treatment assignment. CONCLUSIONS: Phenobarbital and phenytoin are equally but incompletely effective as anticonvulsants in neonates. With either drug given alone, the seizures were controlled in fewer than half of the neonates.

Anticonvulsants↗

The relationship between nucleated red blood cell counts and early-onset neonatal seizures.

OBJECTIVE: This study was undertaken to better define the timing of neurologic insult in neonates with early-onset seizures through evaluation of neonatal nucleated red blood cell levels. STUDY DESIGN: Medical records and the International Classification of Diseases, Ninth Revision codes were used to identify all term neonates with neonatal convulsions who were delivered at our institution (January 1, 1990-December 31, 1995). Each neonate with early-onset seizures was matched to the next 3 neonates who met the following criteria: gestational age > or =37 weeks, no early-onset seizures, birth weight > or =800 g, umbilical artery pH > or =7.25, and a 5-minute Apgar score >7. Demographic characteristics, clinical factors, and mean initial nucleated red blood cell counts were compared between groups. RESULTS: During the 6-year study period, there were a total of 36, 490 singleton term deliveries of infants who were alive at birth. Forty-five (0.1%) of these neonates had early-onset seizures. Thirty neonates with early-onset seizures met the inclusion criteria. Mean nucleated red blood cell counts (number of nucleated red blood cells per 100 white blood cells) for neonates with early-onset seizures were significantly increased compared with those of control neonates (18.4 +/- 22.0 vs 4.6 +/- 4.5; P <.0008). CONCLUSIONS: Our findings are suggestive of the hypothesis that neurologic injury leading to early-onset seizures often occurs before the intrapartum period.

Amniotic Fluid↗

Circulating thrombopoietin levels in neonates with infection.

Thrombocytopenia is a commonly encountered hematologic complication in neonates with sepsis. Thrombopoietin (TPO) is the principal physiologic regulator of megakariocytopoiesis and platelet production. This study was carried out to determine whether variations in circulating TPO levels would occur in infected neonates and/or if they would correlate with platelet counts. In a prospective study of 36 sick neonates (gestational age 24-42 wk) admitted to a regional Neonatal Intensive Care Unit (NICU), blood was collected for TPO measurements and platelet counts on admission to the NICU, if infection was inferred, and at recovery before discharge. An additional group of 15 apparently healthy neonates was also studied (median postnatal age at the time of blood sampling for TPO assessment: 4 d, range 1-10) as control. TPO was measured on plasma samples using a commercially available enzyme-immunosorbent assay (ELISA). On admission, the majority (21/36) of the sick neonates had non-infectious diseases, 2 had early onset sepsis, and 13 had infection (defined as the presence of clinical signs of sepsis, abnormal leukocyte counts or C-reactive protein values, and positive results on local cultures, but negative blood culture results). During the hospital stay, 5 neonates developed sepsis (positive blood culture) and 6 had infection (as previously defined) or necrotizing enterocolitis (NEC). The median TPO level (1704 pg/ml, range 51-3912) was higher during sepsis (either early or late) than during infection (included NEC) (198 pg/ml, range 21-2504), or non-infectious disease (659 pg/ml, range 0-2533), while platelet counts (median value 37,000 cells/microl, range 15,000-486,000) were lower than during either infection (included NEC) (median value 238,000 cells/microl, range 49,000-655,000) or non-infectious disease (median value 110,000 cells/microl, range 45,000-549,000). When infants had recovered from these illnesses, TPO concentrations markedly dropped (median value 59 pg/ml, range 0-825). These values were similar to those found in the control neonates (median TPO level 85 pg/ml, range 43-620). In infected neonates (sepsis plus infection), TPO levels inversely correlated with platelet counts (r = -0.634, p = 0.001) as did those of infants with non-infectious disease (r = -0.574, p = 0.006), while there was no significant correlation between TPO levels and platelet counts in the samples obtained after recovery or in the control infants. We conclude that infected neonates have high circulating TPO levels in the face of low platelet counts. Whether larger TPO concentrations following exogenous administration of recombinant TPO would restore the number of circulating platelets warrants further investigation.

C-Reactive Protein↗

The impact of route of delivery and presentation on twin neonatal and infant mortality: a population-based study in the USA, 1995-97.

OBJECTIVE: We examined whether the route of delivery for near-term (> or = 34 weeks' gestation) twins, as candidates for vaginal delivery, affected neonatal and infant mortality rates. We further evaluated whether these mortality rates were modified by fetal presentation. METHODS: A population-based retrospective cohort study based on the matched multiple births data in the USA (1995-97) was performed. Analyses were restricted to non-malformed liveborn twins delivered at (> or = 34 weeks' gestation. Twins with breech-breech and breech-vertex presentations were excluded, since they are not candidates for vaginal delivery. Neonatal mortality rates (death within the first 27 days) and post-neonatal mortality rates (death between 28 and 365 days) per 1000 twin live births, by route of delivery and fetal presentation, were derived. The associations between neonatal mortality, post-neonatal mortality and the route of delivery for vertex-breech versus vertex-vertex presentations were expressed based on relative risks (RR) and 95% confidence intervals (CI) derived from logistic regression models based on the method of generalized estimating equations. RESULTS: Of the 177,622 twins analyzed, 87% (n = 154,531) presented as vertex-vertex. Fifty-five per cent (n = 97,692) of twins were both delivered vaginally, 41% (n = 72,825) were both delivered by Cesarean section and, of the remaining 4% (n = 7,105), the first twin was delivered vaginally and the second by Cesarean section. Twins with vertex-breech presentations delivered by Cesarean-cesarean sections, as well as those with vertex-vertex presentations delivered vaginally, had the lowest neonatal mortality rate (1.6 per 1000 live births). The highest neonatal mortality rate in the vertex-breech pairs occurred with vaginal-Cesarean deliveries (2.7 per 1000 live births). Among twins with vertex-vertex presentations, twins delivered via the vaginal-Cesarean route experienced the highest neonatal mortality (3.8 per 1000 live births). The RR for neonatal mortality in this group was 2.24 (95% CI 1.35, 3.72) compared with twins both delivered vaginally. CONCLUSION: Route of delivery and fetal presentation both confer an impact on twin infant mortality rates. Strategies to reduce discordant routes in complicated vaginal deliveries may lead to improved neonatal survival.

Cohort Studies↗

Outcome of preterm and term neonates of mothers with malignant diseases diagnosed during pregnancy.

OBJECTIVE: To investigate the outcome of preterm and term neonates born to mothers with malignant diseases diagnosed during pregnancy. METHODS: A retrospective analysis with a matched-paired control group in a third level obstetric department and third level neonatal department of the University Hospital Frankfurt. Patients were preterm and term neonates from mothers with oncologic diseases diagnosed during pregnancy and matched-paired preterm and term neonates from healthy mothers. MEASUREMENTS AND RESULTS: Nineteen preterm and three term (1 x twins) neonates from 21 mothers with oncologic diseases and matched-paired neonates from 21 healthy mothers were included. With the exception of one case, pregnancy was terminated because of the necessity for maternal oncological treatment. Children from mothers with malignant diseases had a significantly lower birth weight and a tendency towards a higher incidence of high-grade respiratory distress syndrome. No significant differences concerning Apgar scores, red blood cell (RBC), white blood cell (WBC), and platelet (PLT) counts postpartum, and duration of hospital days between the two groups of neonates were observed. CONCLUSION: Direct perinatal outcome of preterm or term neonates from mothers with malignant diseases diagnosed during ongoing intact pregnancy does not differ from the outcome of a comparable group of neonates from healthy mothers. This might be in contrast to the long-term outcome of this special patient group. In our study we could find no elevated mortality in neonates where pregnancy was terminated because of the need for maternal chemotherapeutic therapy.

Adult↗

Preterm premature rupture of membranes is not an independent risk factor for neonatal morbidity.

OBJECTIVE: To evaluate the risk factors for development of neonatal morbidity in cases of preterm premature rupture of membranes (PPROM). METHODS: The study population consisted of 2326 singleton preterm births occurring between 1994 and 1997 at Soroka University Medical Center. The neonatal morbidity included respiratory distress syndrome, intraventricular hemorrhage (grade III-IV), necrotizing enterocolitis, periventricular leukomalacia, bronchopulmonary dysplasia, neonatal pneumonia and sepsis. A cross-sectional study was designed to compare neonatal morbidity between two groups: the study group consisted of patients with PPROM (n = 376) and the comparison group of patients without PPROM (n = 1950). RESULTS: The prevalence of the neonatal morbidity associated with PPROM was 13.0% (49/376). There was no statistically significant difference in neonatal morbidity rates between the PPROM group and the group with intact membranes in any of the birth-weight groups (Mantel-Haenszel weighted odds ratio 1.20; 95% CI 0.80-1.20), or gestational-age groups (Mantel-Haenszel weighted odds ratio 1.03; 95% CI 0.79-1.55). There was no statistically significant difference in neonatal morbidity between patients with PPROM and those with intact membranes according to clinical chorioamnionitis. Congenital anomalies did not influence the neonatal morbidity when comparing patients with and without PPROM (44.4% vs. 32.8%, respectively; p = 0.23). CONCLUSIONS: PPROM was not an independent risk factor for neonatal morbidity in preterm births. Neonatal morbidity was affected mainly by prematurity itself, rather than by the occurrence of PPROM.

Adult↗

Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study.

BACKGROUND: Colonization by Candida species is the most important predictor of the development of invasive fungal disease in preterm neonates, and the enteric reservoir is a major site of colonization. We evaluated the effectiveness of an orally supplemented probiotic (Lactobacillus casei subspecies rhamnosus; Dicoflor [Dicofarm spa]; 6 x 10(9) cfu/day) in the prevention of gastrointestinal colonization by Candida species in preterm, very low birth weight (i.e., < 1500-g) neonates during their stay in a neonatal intensive care unit. METHODS: Over a 12-month period, a prospective, randomized, blind, clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit. During the first 3 days of life, the neonates were randomly assigned to receive either an oral probiotic added to human (maternal or pooled donors') milk (group A) or human milk alone (group B) for 6 weeks or until discharge from the NICU, if the neonate was discharged before 6 weeks. On a weekly basis, specimens obtained from various sites (i.e., oropharyngeal, stool, gastric aspirate, and rectal specimens) were collected from all patients for surveillance culture, to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract. RESULTS: The incidence of fungal enteric colonization (with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site) was significantly lower in group A than in group B (23.1% vs. 48.8%; relative risk, 0.315 [95% confidence interval, 0.120-0.826]; P = .01). The numbers of fungal isolates obtained from each neonate (P = .005) and from each colonized patient (P = .005) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001-1500 g. There were no changes in the relative proportions of the different Candida strains. No adverse effects potentially associated with the probiotic were recorded. CONCLUSIONS: Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by Candida species among very low birth weight neonates.

Administration, Oral↗

Neonatal thyrotropin profile as an index for severity of iodine deficiency and surveillance of iodine prophylactic program.

Neonatal serum thyrotropin (TSH) level has been proposed as an index for the monitoring and surveillance of an iodine prophylactic program. We have determined an effective way to put this idea into practice. During the first phase of our study, neonatal serum TSH levels were obtained from umbilical cord blood of neonates born in Chiangmai and Nan provinces, where several districts were areas of severe iodine deficiency, and were compared with those of neonates born in Bangkok, which was a control area. The median and (95% CI [confidence interval]) of serum TSH level of neonates born in Chiangmai 5.8 (5.7-5.9) microU/mL was significantly higher than in Nan 5.1 (5.0-5.2) microU/mL, and in Bangkok 3.7 (3.7-3.8) microU/mL. Neonatal serum free thyroxine (FT4) concentration in Bangkok was higher than in Nan; while the reciprocal was true for neonatal TSH concentration in randomly selected samples (FT4 1.6 [1.6-1.7] ng/dL vs. 1.5 [1.5-1.6] ng/dL and TSH 3.5 [3.3-3.9] microU/mL vs. 5.5 [5.2-5.9] microU/mL, respectively.) When odds ratio of the likelihood of having neonatal TSH level higher than in Bangkok was calculated using 95th percentile value of neonatal TSH level in Bangkok as a cut-off point, the odds ratio of TSH profile in all districts in Chiangmai and Nan were greater than unity. In the second phase of our study, data were collected from 32 district and 10 provincial hospitals. The optimum number of samples in each hospital derived from the first phase of our study was at least 178. Discrepancy between goiter rate and odds ratio of TSH profile was observed, but there was a significant correlation between the two indices (r = 0.67, p < .001). Our study confirmed the practical utility of neonatal TSH profile as a biological index for assessment and monitoring and surveillance of an iodine prophylactic program at a district hospital in a developing country.

Fetal Blood↗

Subclinical vitamin D deficiency in neonates: definition and response to vitamin D supplements.

To determine the biological criteria for neonatal vitamin D deficiency, serum 25-hydroxyvitamin D (calcidiol), parathyroid hormone (PTH), calcium, phosphates, and alkaline phosphatase (ALP) activity were measured during the winter-spring period in 80 healthy neonates and their mothers 3-6 d after delivery. A longitudinal 3-mo survey of the serum biology of 52 of these neonates consuming formula was also performed to test the influence of their neonatal vitamin D status on the effects of two oral ergocalciferol supplements (500 and 1000 IU or 12.5 and 25 micrograms/d). At birth, 63.7% of the infants had calcidiol concentrations < or = 30 nmol/L. Most of them had no other biological sign evocative of vitamin D deficiency, but 14 neonates had low calcidiol concentrations and serum PTH concentrations > 60 ng/L, the upper limit of the adult normal range. They also had a significantly lower mean serum calcium concentration than did neonates with calcidiol concentrations > 30 nmol/L. On the basis of the association of low calcidiol concentrations (< or = 30 nmol/L) and high PTH concentrations (> 60 ng/L) as criteria for vitamin D deficiency, 24% of the neonates born to unsupplemented mothers were found to be vitamin D-deficient. Neonatal vitamin D status influenced the response of the infants to vitamin D supplements. Neonates with no sign of vitamin D deficiency showed similar changes in their serum calcidiol, calcium, phosphate, and PTH concentrations and ALP activity and no toxic effect (hypercalcemia or highly elevated calcidiol concentration) was observed whatever their vitamin D intake. In contrast, neonates with subclinical vitamin D deficiency had normalized serum PTH within 1 mo only when they were given 1000 IU ergocalciferol (25 micrograms)/d in addition to their formula.

Adult↗

Inefficient bacteriolysis of Escherichia coli by serum from human neonates.

To assess bacteriolysis in human neonates, Escherichia coli O7w:K1:NM were incubated with sera from eight healthy neonates, serum pooled from the eight neonates, and serum pooled from healthy adults. The adult serum killed E. coli. In contrast, the bacteria were not killed during incubation with sera from the eight neonates, the pooled neonatal serum, or with heat-inactivated adult serum. However, the combination of pooled neonatal serum and heat-inactivated adult serum killed the bacteria. Supplemental IgG-containing antibodies that bound to E. coli did not enhance the bactericidal activity of the neonatal serum. Ten of 12 blood isolates of E. coli from septic neonates but only 8 of 15 isolates from septic adults were serum-sensitive (killed during incubation with adult serum) (P less than .05). Therefore, neonatal serum killed E. coli inefficiently and was deficient in non-IgG heat-stabile component(s) required for bacterial killing. Compared with adults, neonates were more frequently septic with serum-sensitive strains of E. coli.

Adult↗

Neonates' vitamin A status in relation to birth weight, gestational age, and sex.

Vitamin A status was assessed in a randomly selected group of neonates at delivery. A total of 105 neonates were included in the study. Cord vitamin A concentration was determined by high performance liquid chromatography (HPLC). Of 105 neonates, 53 (50.5 per cent) were males and 49 49.5 per cent) were females. The mean body weight of male neonates was slightly greater that that of female neonates (3271 +/- 575 vs. 3139 +/- 552 g). Mean cord plasma vitamin A level of the males was significantly lower (p < 0.05) than that of the female neonates (12.2 +/- 4.6 and 14.7 +/- 5.2 micrograms/100 ml respectively). The mean body weight of premature neonates (2186 +/- 530 g) was significantly lower (p < 0.05) compared with the mean body weight of full term neonates (3279 +/- 495 g). Cord plasma of preterm neonates had mean value of vitamin A significantly lower (p < 0.05) than full term neonates (8.3 +/- 3.2 vs 13.8 +/- 4.5 micrograms/100 ml). A trend of increasing birth weight with increasing cord plasma vitamin A level was evident.

Birth Weight↗

Nonspecific human IgG reduces survival in neonatal rats infected with Escherichia coli.

BACKGROUND: Human intravenous IgG (IVIG) containing specific antibodies protects neonatal rats from septic death. However, IVIG has immunosuppressive properties and clinical trials of IVIG in neonates at risk for sepsis have yielded conflicting results. HYPOTHESIS: This study was designed to test the hypothesis that nonspecific antibodies in IVIG reduce survival in neonatal rats infected with Escherichia coli. METHODS: Specific antibodies were adsorbed from IVIG with E. coli to produce IVIG/anti-E. coli-. After transthoracic administration of E. coli, survival was determined in neonatal rats injected intraperitoneally with phosphate-buffered saline, IVIG/anti-E. coli- (500 mg/kg) or IVIG containing anti-E. coli antibodies (IVIG/anti-E. coli+). Complement-mediated hemolytic activity of neonatal rat serum was quantified using sensitized sheep erythrocytes. RESULTS: Compared with placebo, intraperitoneal IVIG/anti-E. coli- reduced neonatal survival after E. coli infection. In contrast, IVIG/anti-E. coli+ protected infected animals. Both IVIG/anti-E. coli- and IVIG/anti-E. coli+ impaired the complement-mediated hemolytic activity of neonatal rat serum. CONCLUSIONS: IVIG contained (1) nonspecific antibodies that reduced survival in neonatal rats infected with E. coli and (2) protective anti-E. coli antibodies that enhanced survival in neonatal rats infected with E. coli. We speculate that in clinical trials of IVIG to treat or prevent neonatal sepsis, inconsistent results may be caused, in part, by lot-to-lot variations in the ratio of immunosuppressive, nonspecific antibodies to protective, specific antibodies.

Animals↗

Prediction of mortality in neonates with congenital diaphragmatic hernia treated with extracorporeal membrane oxygenation.

OBJECTIVE: To determine if data collected by the Extracorporeal Life Support Organization Registry could be used to identify neonates with congenital diaphragmatic hernia who had a > 90% mortality rate, despite the use of extracorporeal membrane oxygenation (ECMO) support. DESIGN: We retrospectively reviewed data reported to the Extracorporeal Life Support Organization Registry on neonates with congenital diaphragmatic hernia. PATIENTS: Data regarding 1,089 neonates with congenital diaphragmatic hernia reported to the Extracorporeal Life Support Organization Registry between 1980 and 1992 formed the basis of this study. All of the neonates studied had been treated with ECMO. This patient population includes neonates with right- and left-sided diaphragmatic hernia. This registry does not include neonates with congenital diaphragmatic hernia who were not treated with ECMO. MEASUREMENTS AND MAIN RESULTS: Of 1,089 neonates with congenital diaphragmatic hernia, 679 (62%) survived. There were no differences between the two groups in gender or in the year they were treated. Survival rate did not significantly increase over the years between 1980 and 1992. When compared with survivors, nonsurvivors were more immature (38 +/- 2 vs. 39 +/- 2 wks; p = .01), had lower birth weights (3.0 +/- 0.5 vs. 3.21 +/- 0.53 kg; p = .001), were more often prenatally diagnosed (42% vs. 32%; p = .03), were cannulated at a younger age (31 +/- 54 vs. 40 +/- 50 hrs; p = .01), and had more severe respiratory compromise (higher peak pressures and PaCO2, lower PaO2 values). Multivariate analysis showed that arterial pH and PaO2 just before ECMO, and birth weight, had the highest discriminant coefficients. By using these variables in a discriminant function (D[fx] = 0.68 x pH + 0.62 x birth weight + 0.29 x PaO2; using standardized coefficients and variables), we could identify neonates who died with a sensitivity of 62%, a specificity of 63%, a positive-predictive value of 50%, and a negative-predictive value of 74%. No single variable or combination of variables yielded better results. CONCLUSIONS: Although a number of factors identify neonates with diaphragmatic hernia as being at higher risk of dying despite ECMO support, data currently collected by the neonatal Extracorporeal Life Support Organization Registry do not allow clinicians to effectively discriminate nonsurvivors from survivors.

Analysis of Variance↗

Induction of allograft tolerance with neonatal skin.

B6AF1 recipients treated with various combinations of ALS, CsA, and BMC were grafted with C3H skin from adult or neonatal donors. A survival advantage of neonatal skin compared with adult skin was clearly demonstrated in groups treated with ALS and CsA (median survival time [MST] = 89 days, neonatal skin; 50 days, adult skin), ALS and BMC, (MST = 92 days, neonatal; 64 days, adult skin), or with ALS only (MST = 55 days and 35 days, respectively). In these groups only neonatal grafts were observed to survive greater than 100 days. Also, once it was underway, rejection of the neonatal skin proceeded more slowly than that of adult skin. ALS/BMC/CsA treatment of adult skin recipients improved graft survival modestly (MST = 77 days, 20% of grafts surviving greater than 100 days). But neonatal graft survival was prolonged remarkably by the ALS/BMC/CsA treatment, with 95% of grafts surviving greater than 100 days and 84% surviving greater than 240 days. After bearing neonatal grafts for greater than 150 days, these mice were challenged with C3H adult skin grafts. The second grafts were uniformly accepted for greater than 135 additional days, but third-party grafts were rejected promptly. This specific tolerance could not be abrogated by injection of normal B6AF1 spleen cells, and rejection of the grafts by adoptively transferred sensitized cells was delayed (MST = 35 days). That the tolerance developed in response to grafting neonatal skin to ALS/BMC/CsA-treated recipients extends to adult tissue suggests that understanding of the immunoregulatory signal provided by the neonatal tissue might lead to a tolerogenic protocol for use with adult allografts.

Animals↗

Premedication for tracheal intubation: a prospective survey in 75 neonatal and pediatric intensive care units.

OBJECTIVE: In children, like in adults, tracheal intubation is a painful procedure that may induce hypertension, tachycardia, and other undesirable hemodynamic disorders. Although premature neonates are very sensitive to pain and vulnerable to its long-term effects, the need for sedation before tracheal intubation is still discussed in neonatal units. Our objective was to investigate the practice of premedication before tracheal intubation in neonatal and pediatric units and determine the influence of premedication on intubating conditions. DESIGN: We performed a 10-day prospective survey in 75 neonatal and pediatric intensive care units among the 98 licensed in France. A questionnaire was completed for each intubation performed in each surveyed unit. SUBJECTS: A total of 204 patients were studied: 140 neonates, 52 infants, and 12 children. MAIN RESULTS: Data on 204 tracheal intubations were collected from 223 that were performed during the study period (participation rate, 91.4%). Premedication was used before intubation for 37.1%, 67.3%, and 91.7% of neonates, infants, and children, respectively (p <.0001). In the subgroup of neonates, premedication was particularly rare for the youngest and the smallest infants. Midazolam was the principle hypnotic used in neonates, whereas propofol was mainly used in children. Opioids or muscle relaxants were used in 16.2% and 4.4% of the patients, respectively. A low success rate and a high incidence of hypoxemia and bradycardia were correlated with the inexperience of the operator. Premedication did not significantly influence either the success rate or the undesirable events associated with tracheal intubation. CONCLUSION: Use of premedication before tracheal intubation is limited in neonates and increases according to the age of the patient. Midazolam does not seem to be an accurate choice to improve intubating conditions in neonates and infants. Because tracheal intubation is a technique that requires a skill only developed by regular practice, operators who have limited experience with intubating children should be supported by senior operators.

Anesthesia↗

A novel and effective approach of developing aggressive experimental autoimmune gastritis in neonatal thymectomized BALB/c mouse by polyinosinic:polycytidylic acid.

Neonatal thymectomy induces autoimmune gastritis (AIG) in 40-70% of BALB/c mice. We presumed that induction of autoimmunity by polyinosinic:polycytidylic acid (poly I:C) might allow development of a more aggressive model of AIG. A group of BALB/c mice were thymectomized on day 3 after birth. Neonatal thymectomized mice were either injected with poly I:C or phosphate-buffered saline (PBS). Non thymectomized neonatal BALB/c mice were injected with only poly I:C. All neonatal thymectomized mice injected with poly I:C developed 3 cardinal features of AIG: (1) moderate to severe degree gastritis (2) presence of autoantibody to H(+)/K(+) ATPase and (3) loss of parietal cells. However, only 70% of the PBS-treated neonatal thymectomized BALB/c mice developed some, but not, all features of AIG. A mild degree of AIG was seen in 12 of 31 nonthymectomized BALB/c mice administered with only poly I:C. Administration of poly I:C in neonatal thymectomized BALB/c mice in the first and second week appeared to be the most effective for induction of aggressive AIG. The levels of interleukin (IL)-6, IL-12p70, interferon-gamma and tumour necrosis factor-alpha were significantly higher in poly I:C-injected thymectomized mice compared to PBS-injected neonatal thymectomized mice (P < 0.05). The frequencies of CD4(+)CD25(+) regulatory T cells in the spleen were significantly decreased in neonatal thymectomized mice administered with poly I:C compared to PBS-treated neonatal thymectomized mice (P < 0.01). Taken together, these results suggest that induction of inflammatory cytokines and reduction of regulatory T cells by poly I:C might contribute to the development of an aggressive model of AIG in neonatal thymectomized BALB/c mice.

Animals↗

Age at neonatal death in Ontario, 1979-1987: implications for the interpretation of mortality markers.

Recent evidence concerning time trends in infant mortality rates suggests faster falls in early compared with late deaths. This may be due to rapid advances in neonatal care. This study was undertaken to examine the timing of neonatal death in Ontario between 1979 and 1987. Trends with time, gestational age and type of birth hospital were examined. Evidence suggests that, controlling for level of birth hospital and gestational age, there was a time trend of an increasing proportion of late neonatal deaths. This suggests that early neonatal mortality was decreasing more rapidly than late neonatal mortality. Controlling for year of birth and gestational age, it was observed that the proportion of late neonatal deaths was higher for those born in a tertiary rather than community hospital. In combination, these findings suggest that, due to advances in neonatal care, a disproportionately high number of early neonatal deaths are increasingly being prevented. The findings have implications for the interpretation of routinely available mortality markers. The authors conclude that early neonatal death rate may be becoming a less useful marker and that a measure of perinatal mortality which includes late neonatal deaths would be a useful addition to the currently collected mortality markers.

Data Interpretation, Statistical↗

Necrotising enterocolitis hospitalisations among neonates in the United States.

The objective of this study was to estimate the rate and describe the epidemiology of necrotising enterocolitis (NEC) among neonates (infants <1 month of age) hospitalised in the United States. Hospital discharge records for neonates with an NEC diagnosis and an in-hospital death or routine discharge were selected for analysis from the 2000 Kids' Inpatient Database. An estimated 4463 (SE = 219) hospitalisations associated with NEC occurred among neonates in the United States during the year 2000, resulting in a hospitalisation rate of 109.9 [95% CI 97.2, 122.6] per 100 000 livebirths. The rate of NEC hospitalisations was highest among non-Hispanic Black neonates. The median hospital length of stay was 49 days. The in-hospital fatality rate was 15.2% (SE = 1.0%). Neonates who underwent a surgical procedure during hospitalisation were more likely to have a longer length of stay and to die than were those who did not have surgical intervention. Low-birthweight (LBW) neonates with NEC were more likely than LBW neonates hospitalised with other diagnoses to be very LBW (VLBW), non-Hispanic Black and male. In addition, compared with LBW neonates hospitalised with other diagnoses, LBW neonates with NEC had higher hospital charges and longer lengths of stay, and were more likely to die during hospitalisation. This study provides the first national estimate of the rate of hospitalisation for NEC among neonates in the United States. During 2000, there was one NEC hospitalisation per 1000 livebirths, with approximately 1 in 7 NEC hospitalisations ending in death. NEC accounts for substantial morbidity; thus, the development of prevention strategies and effective therapies continues to be an important issue.

Enterocolitis, Necrotizing↗