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Mechanism of hypothyroidism action on insulin-like growth factor-I and -II from neonatal to adult rats: insulin mediates thyroid hormone effects in the neonatal period.

The effects of thyroid hormone deficiency on serum levels and liver messenger RNA (mRNA) expression of insulin-like growth factors (IGFs) were studied in neonatal (until 20 days of life), weaned (22-37 days), and adult (72-87 days) rats, short periods (5, 10, and 15 days) after thyroidectomy (T). Serum levels and liver mRNA expression of IGF-I, plasma and pituitary GH, plasma insulin, and glycemia were measured in all populations; and serum levels and liver mRNA expression of IGF-II were measured only in the neonatal populations. Surprisingly, plasma insulin and GH and serum and liver mRNA expression of IGF-I were found elevated in T neonatal rats, and they decreased in weaned and adult rats and in neonatal rats rendered hypothyroid by mercapto-1-methylimidazole (MMI) treatment (MMI-hypothyroid). T and MMI-treatment of neonatal rats disturbed the normal pattern of progressive decrease of IGF-II with age. A positive correlation between insulin and IGF-I and a poor correlation between GH and IGF-I were found in both hypothyroid neonates (T and MMI-hypothyroid). On the contrary, a positive correlation between GH and IGF-I and a poor correlation between insulin and IGF-I were found for control and T adult rats. Because plasma insulin and GH changed in the same direction in all groups, insulin secretion in T neonatal was suppressed by streptozotocin, and insulin was given to T adult rats. The combined results of these experiments support the idea that the effects of thyroid hormones on IGF-I secretion are age-dependent, and they are mediated mainly by insulin during the neonatal period and by GH during adulthood.

Aging↗

Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death.

BACKGROUND: We reported previously that the use of cephalosporin among premature neonates increased the risk of subsequent fungal sepsis. As a result, we recommended that ampicillin and gentamicin be used as empiric coverage for early-onset neonatal sepsis while culture results are awaited. OBJECTIVES: To describe antibiotic use during the first 3 days after birth for neonates admitted to the NICU and to evaluate the outcomes for neonates treated with 2 different antibiotic regimens. METHODS: We assembled a cohort of inborn neonates, from our deidentified administrative database, who had documented exposure to ampicillin during the first 3 days after birth. Infants treated concurrently with cefotaxime or gentamicin were evaluated, to identify the factors that were associated independently with death before discharge, with both univariate and multivariate analyses. RESULTS: There were 128,914 neonates selected as the study cohort; 24,111 were treated concurrently with ampicillin and cefotaxime and 104,803 were treated concurrently with ampicillin and gentamicin. Logistic modeling showed that neonates treated with ampicillin/cefotaxime were more likely to die (adjusted odds ratio: 1.5; 95% confidence interval: 1.4-1.7) and were less likely to be discharged to home or foster care than were neonates treated with ampicillin/gentamicin. This observation was true across all estimated gestational ages. Other factors that were associated independently with death included immature gestational age, need for assisted ventilation on the day of admission to the NICU, indications of perinatal asphyxia or major congenital anomaly, and reported use of ampicillin/cefotaxime. CONCLUSIONS: For patients receiving ampicillin, the concurrent use of cefotaxime during the first 3 days after birth either is a surrogate for an unrecognized factor or is itself associated with an increased risk of death, compared with the concurrent use of gentamicin.

Ampicillin↗

[Risk factors for neonatal asphyxia in neonates weighing more than 1000 grams]

OBJECTIVE: To evaluate some of the risk factors for neonatal asphyxia in neonates weighing more than 1000 grams. METHODS: In a population of 13.385 consecutive deliveries, from January 1991 to December 1994, 135 newborns with neonatal asphyxia were compared with 135 without the disease, in a casecontrol study, matched by birth weight, at the Neonatology Unit of the Pediatric Department of the Universidade Estadual de Campinas (UNICAMP). The statistical analysis employed was bivariate and multiple by logistic regression, and expressed as odds ratio (OR) with 95% confidence intervals. RESULTS: In the bivariate analysis, the factors significantly associated with asphyxia were: abruptio placentae [OR = 8.00 (1.07-353.4)], cesarean section [OR = 2.94 (1.64 -5.55)], breech presentation [OR = 3.33 (1.54 - 7.98)], abnormal fetal heart rates [OR = 4.88 (2.25-12.08)], prolonged rupture of membranes [OR = 4.33 (1.19-23.71)], a meconial hemorrhagic or infected amniotic fluid [OR = 9.00 (3.58 - 29.03)], oligohydramnios or polyhydramnios [OR =5.00 (1.88 - 16.76), use of anesthesia [OR = 2.56 (1.41 - 4.89)] and general anesthesia [OR = 14.00 (2.13 - 598.8)], male sex [OR = 2.06 (1.12 - 3.92)] and a gestational age of less than 37 weeks [OR = 3.29 (1.37 - 9.07). After multiple analysis, abnormal amniotic fluid, oligohydramnios or polyhydramnios, and anesthesia were the only factors associated with neonatal asphyxia, and more than six prenatal visits was a protector factor. CONCLUSIONS: Obstetrical, perinatal and neonatal clinical events are associated with neonatal asphyxia, that concerted efforts to provide adequate prenatal care, optimal assistance during delivery and birth, and appropriate neonatal intensive care should significantly reduce neonatal morbidity and mortality.

Journal Article↗

[Differential patterns of neonatal and post-neonatal mortality rates in Goiânia, Brazil, 1992-1996: use of spatial analysis to identify high-risk areas].

The aim of this study was to investigate the spatial pattern of neonatal and post-neonatal mortality in the city of Goiânia, Central Brazil. Analyses were based on linked birth and death certificates relating to 101,000 in-hospital live births from mothers residing in the city of Goiânia over the 1992-1996 period. Overall neonatal and post-neonatal mortality probabilities were calculated using the linked database. The empirical Bayes method was applied to smooth the estimated rates and minimize random fluctuation. Spatial units of analysis were 65 urban districts, corresponding to the urban planning sectors. The following exploratory spatial analyses were applied: "global" Moran's I statistic, local Moran LISA map, and Gi* local statistics. For both neonatal and post-neonatal mortality there was statistically significant spatial autocorrelation. Results of post-neonatal mortality showed a high-risk cluster located on the outskirts of the city. For the neonatal period, a heterogeneous mortality pattern was found with high-risk districts in all regions, including central areas.

Brazil↗

[Chorioamnionitis and early-onset neonatal sepsis do not significantly affect levels of interleukin-6 in very low birth weight neonates].

OBJECTIVE: To determine the influence of maternal chorioamnionitis and neonatal sepsis on interleukin-6 (IL-6) levels in cord blood and in blood obtained from very low birth weight (VLBW) infants within the first two hours of life. DESIGN: Prospective clinical study. SETTING: Institute for the Care of Mother and Child, Prague. METHODS: We measured the serum levels of IL-6 in 30 consecutive VLBW infants born in our institute. IL-6 levels were evaluated in cord blood and in neonatal blood within 2 hours after delivery. Maternal chorioamnionitis and neonatal sepsis within the first 72 hours of life were monitored. RESULTS: Maternal chorioamnionitis was detected in 7 of 30 patients (23.3%). There was no significant increase in IL-6 level in cord blood of newborns with maternal chorioamnionitis (p = 0.42). Serum level of IL-6 in this group did not differ from the level in newborns of mothers without signs of intraamniotic infection (p = 0.39). Neonatal early-onset sepsis was diagnosed in 7 of 30 patients (23.3%). There was no influence of neonatal sepsis on IL-6 level in cord blood (p = 0.98) and IL-6 level in neonatal blood (p = 0.19). We did not find any correlation between the group "chorioamnionitis positive" and "sepsis positive" (p = 0.31). CONCLUSION: IL-6 in cord blood or in neonatal blood within 2 hours of life was not enough sensitive and specific marker of maternal chorioamnionitis as well as for early-onset neonatal sepsis in the group of very low birth weight infants.

Biomarkers↗

[Influence of selected neonatal diseases on the incidence of gastroesophageal reflux in preterm neonates].

AIM: To assess the correlation between the incidence of gastroesophageal reflux and chosen neonatal diseases. MATERIAL AND METHODS: Analysis of 106 neonates born before 38 weeks of pregnancy was undertaken. All patients had 24-hour pH-metry and according to the result of this examination we diagnosed or excluded acid gastroesophageal reflux. The correlation between acid gastroesophageal reflux and chosen neonatal diseases, such as congenital infection, intrauterine growth retardation, pneumonia, respiratory distress syndrome, intraventricular hemorrhage, was analyzed. RESULTS: Gastroesophageal reflux was diagnosed in 25 neonates (23.6%). Congenital infection, respiratory distress syndrome, pneumonia and intraventricular hemorrhage showed no influence on the incidence of acid gastroesophageal reflux. Up to 50% of neonates with intrauterine growth retardation had gastroesophageal reflux, whereas in eutrophic neonates it was diagnosed in 16.7% cases. The risk of incidence of gastroesophageal reflux in neonates with intrauterine growth retardation was almost 5 times higher than in eutrophic neonates. CONCLUSIONS: No correlation between gastroesophageal reflux and congenital infection, respiratory distress syndrome, pneumonia, intraventricular hemorrhage has been found. The incidence of gastroesophageal reflux was higher in infants with intrauterine growth retardation.

Cerebral Hemorrhage↗

Reduction of neonatal mortality after multiple doses of bovine surfactant in low birth weight neonates with respiratory distress syndrome.

To determine if outcomes of low birth weight neonates with respiratory distress syndrome can be improved by the administration of multiple doses of bovine surfactant, we conducted two identical multicenter, controlled trials, and the results were combined for analysis. Seven hundred and ninety-eight neonates weighing 600 to 1750 g at birth who had developed respiratory distress syndrome within 6 hours of birth were assigned randomly to receive either 100 mg of phospholipid/kg of Survanta, a modified bovine surfactant (n = 402), or a sham dosing procedure (n = 396). Neonates whose respiratory distress persisted could be given up to three more doses, with all doses to be given in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Fewer Survanta-treated neonates died of any cause (18.4% vs 27.3%, P = .002), died of respiratory distress syndrome (9.0% vs 20.3%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (51.2% vs 64.6%, P less than .001). Neonates who received Survanta also had greater improvement in their oxygenation and ventilatory status from baseline to 72 hours than did control neonates. Survanta-treated neonates were at lowered risk for developing pulmonary interstitial emphysema (18.6% vs 39.3%, P less than .001) and other pulmonary air leaks (11.5% vs 25.9%, P less than .001). We conclude that multiple doses of Survanta given after diagnosis of respiratory distress syndrome reduce mortality and morbidity.

Administration, Inhalation↗

Decreasing mortality associated with the introduction of surfactant therapy: an observational study of neonates weighing 601 to 1300 grams at birth. The Members of the National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: To determine whether the introduction of surfactant therapy was associated with decreased mortality for high-risk preterm neonates weighing 601 to 1300 g at birth. DESIGN: Before-after observational study. SETTING: Eight tertiary care neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network. PATIENTS: The outcomes for neonates with birth weight 601 to 1300 g admitted in the 2 years before surfactants became available (n = 2780) were compared with those of neonates admitted in the year beginning 2 months after surfactants became available (n = 1413). MAIN OUTCOME MEASURES: The primary outcome measure was in-hospital mortality; secondary outcome measures included durations of assisted ventilation, length of hospitalization, and neonatal morbidity. RESULTS: Forty percent of neonates in the postsurfactant group received surfactant (range 28% to 69% at the centers). Mortality decreased from 27.8% before to 19.9% after surfactant therapy was introduced (Mantel-Haenszel chi 2 = 31.4, P = .001). The adjusted odds ratio for mortality after surfactants became available was 0.73 (95% confidence interval 0.55 to 0.95). The duration of assisted ventilation and length of hospitalization increased after surfactants were introduced (P = .0001 for both outcomes). CONCLUSION: Mortality for neonates weighing 601 to 1300 g decreased after surfactant therapy was introduced, suggesting that the efficacy of surfactants demonstrated in randomized controlled trials will translate into effectiveness in routine clinical care.

Female↗

A multicenter, randomized trial comparing synthetic surfactant with modified bovine surfactant extract in the treatment of neonatal respiratory distress syndrome. Vermont-Oxford Neonatal Network.

OBJECTIVE: To compare the efficacy of a synthetic surfactant (Exosurf Neonatal, Burroughs-Wellcome Co) and a modified bovine surfactant extract (Survanta, Ross Laboratories) in the treatment of neonatal respiratory distress syndrome (RDS). DESIGN: Multicenter, randomized trial. SETTING: Thirty-eight neonatal intensive care units participating in the Vermont-Oxford Neonatal Network. PATIENTS: Premature infants (n = 1296) weighing 501 to 1500 g with RDS requiring assisted ventilation with 30% oxygen or more were enrolled within 6 hours of birth. INTERVENTIONS: Infants were randomly assigned to receive up to four intratracheal doses of the synthetic surfactant (Exosurf Neonatal, n = 644) or the modified bovine surfactant extract (Survanta, n = 652). MAIN OUTCOME MEASURE: The primary outcome measure was the occurrence of death or chronic lung disease 28 days after birth. RESULTS: Death or chronic lung disease occurred in 57% of the infants treated with Exosurf Neonatal and in 54% of those infants treated with Survanta (relative risk [RR], 0.95; 95% confidence interval [CI], 0.86 to 1.04). Infants with birth weights of 1001 to 1500 g who received Survanta had a significantly lower risk of chronic lung disease or death at 28 days (Survanta, 27% vs Exosurf, 34%; RR, 0.78; 95% CI, 0.60 to 0.99). Treatment with Survanta led to significant improvement in several secondary outcome measures. Survanta-treated infants received less supplemental oxygen and had lower mean airway pressure 6 and 72 hours after treatment. Survanta-treated infants had significantly fewer pneumothoraces (Survanta, 9% vs Exosurf, 15%; RR, 0.60; 95% CI, 0.44 to 0.81). There were no differences between the groups in the incidence of other neonatal complications. CONCLUSION: Although no differences were noted between Survanta- and Exosurf-treated infants regarding the primary outcome of death or chronic lung disease at 28 days of age, the significant improvement in secondary clinical outcomes suggests that Survanta is more effective than Exosurf Neonatal in the treatment of established RDS.

Biological Products↗

Perinatal-neonatal and weight specific neonatal mortality in Thailand in 1996 and comparison with 1976 and 1986: a hospital based study.

The study on perinatal mortality, neonatal mortality and weight specific death rate of neonatal infants born at Rajavithi Hospital in 1996 was carried out and compared with the rates of 1976 and 1986. It was found that in 1996 the total number of births was 15613 with 106 stillbirths. The perinatal mortality rate was 9.09 per 1000 births and neonatal mortality rate was 2.90 per 1000 live births. Reduction in perinatal and neonatal mortality rates from 1976 and 1986 to 1996 was observed. The neonatal mortality rate was close to the rate of developed countries but not the perinatal mortality rate. The weight specific neonatal mortality in 1996 was reduced from 1986 and 1976 in all weight groups. It is concluded that the neonatal mortality rate in 1996 was improved because of effective neonatal care. To reduce the low birth weight infant rate by means of an effective family planning program and antenatal care may improve the perinatal mortality rate at Rajavithi Hospital.

Age Distribution↗

Pattern of daily weights among low birth weight neonates in the neonatal intensive care unit: data from a multihospital health-care system.

OBJECTIVES: We sought to generate a contemporary postnatal weight grid for low birth weight (LBW, <2500 g) neonates using actual data, not mathematically derived idealized weight curves. To do this, we collected electronic data from all neonatal intensive care units (NICU) patients weighing 400-2600 g at birth, during 30 consecutive months (January 2003-June 2005) in all four NICU's within a single health system, Intermountain Health Care (IHC). METHODS: A deidentified limited data set was collected from electronic IHC records. Data were limited to the birth weights and all subsequent daily weights, until discharge, death, or transfer to a non-IHC facility. Lines were drawn connecting the exact daily means of body weight for patients in 200 g birth weight groupings, ranging from 400 to 2600 g. We assessed differences in growth patterns predicted by this grid vs three previously published NICU longitudinal weight grids. RESULTS: All recorded weights were electronically extracted for 1813 consecutive patients with dates of birth from January 1, 2003 through June 30, 2005. The daily weights of each patient totaled over 48,000 individual data points. The new grid differed from previously published grids, in that the new grid showed; (1) no predicted postnatal weight loss among neonates in categories<900 g birth weight, (2) less initial weight loss among neonates 900-2500 g, (3) fewer days to regain birth weight among neonates<or=2000 g, and (4) fewer days to gain 100 and 300 g above birth weight in neonates<or=1500 g. SPECULATION: For charting serial weights of LBW neonates in the NICU the new grid may be a useful standard.

Body Weight↗

Candida tropicalis in a neonatal intensive care unit: epidemiologic and molecular analysis of an outbreak of infection with an uncommon neonatal pathogen.

From June to July 1998, two episodes of Candida tropicalis fungemia occurred in the Aristotle University neonatal intensive care unit (ICU). To investigate this uncommon event, a prospective study of fungal colonization and infection was conducted. From December 1998 to December 1999, surveillance cultures of the oral cavities and perinea of the 593 of the 781 neonates admitted to the neonatal ICU who were expected to stay for >7 days were performed. Potential environmental reservoirs and possible risk factors for acquisition of C. tropicalis were searched for. Molecular epidemiologic studies by two methods of restriction fragment length polymorphism analysis and two methods of random amplified polymorphic DNA analysis were performed. Seventy-two neonates were colonized by yeasts (12.1%), of which 30 were colonized by Candida albicans, 17 were colonized by C. tropicalis, and 5 were colonized by Candida parapsilosis. From December 1998 to December 1999, 10 cases of fungemia occurred; 6 were due to C. parapsilosis, 2 were due to C. tropicalis, 1 was due to Candida glabrata, and 1 was due to Trichosporon asahii (12.8/1,000 admissions). Fungemia occurred more frequently in colonized than in noncolonized neonates (P < 0.0001). Genetic analysis of 11 colonization isolates and the two late blood isolates of C. tropicalis demonstrated two genotypes. One blood isolate and nine colonization isolates belonged to a single type. The fungemia/colonization ratio of C. parapsilosis (3/5) was greater than that of C. tropicalis (2/17, P = 0.05), other non-C. albicans Candida spp. (1/11, P = 0.02), or C. albicans (0/27, P = 0.05). Extensive environmental cultures revealed no common source of C. tropicalis or C. parapsilosis. There was neither prophylactic use of azoles nor other risk factors found for acquisition of C. tropicalis except for total parenteral nutrition. A substantial risk of colonization by non-C. albicans Candida spp. in the neonatal ICU may lead to a preponderance of C. tropicalis as a significant cause of neonatal fungemia.

Antifungal Agents↗

Glucose-6-phosphate dehydrogenase deficiency neonatal screening: preliminary evidence that a high percentage of partially deficient female neonates are missed during routine screening.

OBJECTIVES: To provide preliminary evidence that the currently employed semiquantitative method of screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency can only detect infants who are totally deficient for G6PD and misses all cases of partial G6PD deficiency. SETTING: General population: 2150 randomly selected blood samples from the Blood Donation Department, Speliopouleion General Hospital, Athens, Greece. Neonate population: 2000 samples from neonates (50% male; 50% female) in maternity hospitals in the greater Athens area. High risk population: a total of 545 individuals from 133 families in the Athens area, the minimum acceptance criteria being the parents and any brother or sister. METHOD: Blood specimens from neonates or adults were collected and either spotted and dried on special filter paper (Schleicher and Schull 2992, Darmstadt, Germany) or used in tubes after being heparinised. For the quantitative evaluation of G6PD enzyme activity, the Quantase G6PD screening kit (Quantase Limited, Perth, UK) was used. Quantase G6PD controls (Quantase Limited) were used at three levels of G6PD. These controls are rated at 24, 30, and 37 degrees C. Alternatively, we used the Sigma G6PDH controls (Sigma Chemical Company, St Louis, USA) which are rated at 30 and 37 degrees C. The assay was performed according to the instructions included in the kit with the modification for haemoglobin normalisation. RESULTS: General population: 36 females who were classified as having normal enzymatic activity with the semiquantitative test, were classified as partially deficient with the quantitative test. Neonate population: using the quantitative test, the percentage of G6PD deficient neonates in this population was 5.5%, compared with 3.17% reported in routine screening using the semiquantitative method. High risk population: the quantitative method detected 28 cases of total or partial G6PD deficiency in sisters of males with known total deficiency. The semiquantitative CONCLUSIONS: A considerable amount of partially G6PD deficient female neonates (heterozygotes) are undetected and classified as having normal enzymatic activity using the semiquantitative method, which uses a cut off of 2.1 U/g haemoglobin (Hb). The use of a fully quantitative G6PD screening kit is proposed, employing the automated haemoglobin normalisation and a cut off of 6.4 U/g Hb. Any neonate with an activity below this mark should be regarded as G6PD deficient, and all preventive measures should be taken.

Clinical Enzyme Tests↗

Effect of a statewide neonatal resuscitation training program on Apgar scores among high-risk neonates in Illinois.

OBJECTIVE: The national Neonatal Resuscitation Program (NRP), started in 1987, provided training to hospital delivery room personnel to standardize knowledge and skills to reduce neonatal morbidity and mortality and increase successful resuscitation during the first few critical minutes after birth. The Apgar score continues to be used as the best established index of immediate postnatal health. The purpose of this study was to evaluate the impact of the NRP instruction in Illinois hospitals by examining Apgar scores among high-risk infants who are likely to benefit from the NRP. METHODS: A retrospective 3-time period cohort design was used (before the introduction of the NRP, 1985-1988; transition when NRP training occurred, 1989-1990; and after NRP training was completed at least once for some delivery room personnel in each Illinois hospital, 1991-1995). Illinois computerized birth certificate files on a selected group of 636 429 high-risk neonates provided information on Apgar scores and maternal characteristics. The American Academy of Pediatrics provided instructor lists to determine when NRP training started and when it was fully implemented in Illinois. Illinois Department of Public Health provided data to categorize hospitals into levels based on type and intensity of neonatal services (Level I, II, II+, III). High-risk neonates were defined as meeting 1 of the following criteria: maternal age <20 years old or >35 years old, birth weight <2500 g or >4000 g, presence of a maternal medical risk factor, and no prenatal care or prenatal care started after the first trimester. Several exclusion criteria were applied including the following: birth records with missing data, multiple birth or congenital anomaly, and hospital information that indicate no birth deliveries in 1 of the 11 study years or delivery outside of a hospital. One-minute and 5-minute Apgar scores were divided into categories for analysis (0-3, 4-6, 7-10). No change or a decrease in a low (0-6) 1-minute Apgar when compared with the 5-minute Apgar was a primary measure to evaluate effect of NRP resuscitation. Variables examined included the following: race/ethnicity, maternal age, level of education, presence of maternal medical risk factor, trimester started prenatal care, complications of labor and delivery, and a low birth weight. Analysis consisted of chi(2) tests, relative risk calculations, and logistic regression to reveal independent associations with no change in low 1-minute Apgar score or continued low (0-6) 5-minute Apgar. RESULTS: A total of 636 429 high-risk birth records was selected for detailed analyses out of 2 077 533 births in Illinois between 1985 and 1995 for 193 hospitals. The number of active NRP instructors in Illinois changed dramatically during the study period; for example, 1 to 6 between 1987 and 1988 to 1096 to 1242 between 1991 and 1995. The percentage of neonates reported to have low (<7) 1-minute Apgar score decreased in 1991 to 1995 overall and for each of 4 hospital levels. Overall and by hospital level, there was a statistically significant lower proportion of high-risk newborns who showed a decrease or no change in their 5-minute Apgar scores after the NRP instruction. After adjusting for several maternal characteristics, logistic regression analysis revealed that high-risk newborns with a low 1-minute Apgar were more likely to increase their 5-minute Apgar after the NRP instruction in 1991 to 1995. Additional analyses indicated that very low birth weight and low birth weight newborns benefited the most from NRP instruction. CONCLUSION: Although previous research has shown that the NRP instruction improves knowledge and skill among health care personnel in the delivery room, both short-term and long-term, there has been little evidence to demonstrate NRP impact on infant morbidity. Several strategies were used in this study to control for bias and to adjust for secular trends in decreased infant morbidity during the study period. This study demonstrated sufficient support for the hypothesis that a significant improvement occurred among neonates in their Apgar score after the NRP instruction in Illinois. Empirical support is provided for the clinical effectiveness of NRP instruction.

Apgar Score↗

Efficacy of oral phenobarbitone in term "at risk" neonates in decreasing neonatal hyperbilirubinemia: a randomized double-blinded, placebo controlled trial.

OBJECTIVE: To evaluate the efficacy of oral phenobarbitone in "at risk " term neonates (with high cord bilirubin) in decreasing hyperbilirubinemia. DESIGN: Double blind, placebo-control, randomized trial. SETTING: Tertiary level neonatal unit. OUTCOME: Primary-hyperbilirubinemia defined as total serum bilirubin (TSB) greater than 13 mg/dL. Secondary-TSB at 72 +/- 12 hr, need for phototherapy or exchange transfusion and side effects of phenobarbitone therapy. METHODS: All consecutively born term healthy neonates with cord bilirubin > or = 2.5 mg/dL were randomly assigned to receive either phenobarbitone (n = 37) or placebo (n = 38) after obtaining informed consent. Phenobarbitone was administered orally (5 mg/kg/day) for 3 days starting within 12 hours of birth. The neonates were followed up till seven days of life. TSB was estimated in neonates who developed jaundice with clinically assessed level of 8-10 mg/dL and at 72 +/-12 hours of age in 55 neonates. RESULTS: The baseline characteristics were similar in two groups. There was no significant reduction in incidence of hyperbilirubinemia in phenobarbitone group compared to in placebo group (6/37 (16.2%) versus 13/38 (34.3%); RR 0.47, 95% confidence interval: 0.20-1.11; risk difference: -18.1%, 95% confidence interval: -39.5 to 3.3%). However TSB at 72 +/-12 hours in phenobarbitone group (mean +/- S.D: 10.0 +/- 3.7 mg/dL) was significantly lesser than in placebo group (mean +/- S.D: 12.3 +/- 3.3 mg/dL) (difference of means: -2.3 mg/dL, 95% confidence interval: -3.9 to -0.7 mg/dl, P = 0.018). No significant difference with respect to need for treatment was observed in two groups. No significant adverse effects of phenobarbitone were noted. CONCLUSIONS: Prophylactic phenobarbitone is not helpful in reducing the incidence of hyper-bilirubinemia in "at risk" term neonates.

Double-Blind Method↗

Umbilical cord and neonatal cortisol levels. Effect of gestational and neonatal factors.

To evaluate the effect of the type of delivery, gestational age, maternal dexamethasone treatment, and neonatal complications on the serum cortisol levels in early infancy, a total of 92 neonates were investigated with 611 cortisol determinations (specific radioimmunoassay after Lipidex chromatography). Umbilical cord blood samples were taken immediately after delivery and capillary blood samples from the infant's heel 30--60 minutes after delivery and at 8:00 AM and PM on the second, fourth, and sixth days of life. Umbilical cord cortisol concentration after elective cesarean section was lower than after emergency cesarean section or after normal vaginal delivery, while neonatal cortisol values did not show any correlation with the type of delivery. Prematurity did not affect neonatal cortisol levels. In postterm infants the activation of cortisol production was retarded to some degree. After maternal dexamethasone therapy, neonatal cortisol concentration decreased 30--60 minutes after delivery, but from the second day on it was at the same level as in infants without maternal therapy. Respiratory distress syndrome, especially in fatal cases, caused an elevation in neonatal cortisol levels, while hyperbilirubinemia did not have an effect on plasma cortisol concentrations of the neonates.

Adult↗

Neonatal mortality and morbidity in a neonatal unit: impact of improved perinatal care in recent 10 years.

Analysis of the neonatal mortality record at the neonatal unit of Changhua Christian Hospital for the five-year period from 1989 to 1993 (period 2) is presented and compared with that of the period 1979-1983 (period 1). This retrospective study is to evaluate whether the mortality rate and causes of neonatal death are affected by the changing perinatal care environment in Changhua area. This study shows that the mortality rate of the all admitted babies was dramatically decreased in period 2 (18% vs 12.35%, P < 0.01) and the mortality rate of delivered babies in our hospital was significantly decreased in period 2, too. (32.74% vs 11.61%, P < 0.001). However, the mortality rate of the babies referred from other hospitals was not different between the two periods (12.30% vs 12.72%, P > 0.05). These results can be explained by the higher quality of prenatal and delivery care, higher standard of neonatal intensive care for the sick neonates in period 2 and a comprehensive transport system which was established in 1987. RDS, prematurity, sepsis, asphyxia (particularly MAS with PPHN) and congenital malformations were still the main causes of neonatal death in period 2. We suggested that prevention, early diagnosis and intervention of these disorders and regionalization of perinatal care with a more comprehensive transport system are mandatory in Changhua area.

Cause of Death↗

CD45 isoform expression on human neonatal T cells: expression and turnover of CD45 isoforms on neonatal versus adult T cells after activation.

Neonatal T cells are phenotypically similar to "naive" T cells from adult donors in the CD45 isoform expression. Despite the phenotypic similarity, large differences were found between neonatal and adult T cells when T cells were activated. After activation with PHA, adult CD45RA+ T cells began to express CD45RO and no loss of CD45RA expression had yet occurred at Day 3 post-stimulation. Three days after activation, CD45RA+ neonatal T cells also coexpressed CD45RO; however, in contrast to adult T cells, a marked loss of CD45RA was observed. We analyzed the rapid loss of CD45RA found in neonatal T cells. The de novo synthesis of CD45 isoforms in neonatal T cells was essentially the same as that in the adult T cells. Turnover of the CD45RA was very rapid in both resting adult and neonatal T cells. After activation with PHA, the turnover of CD45RA on adult T cells was decreased significantly, while the turnover of CD45RA on neonatal T cells was not changed after activation. Therefore, the regulation of CD45 isoform expression not only involves switches in alternative splicing, but also involves different regulation of turnover of these isoforms from the cell membrane.

Adult↗