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[Pharmacokinetic and clinical studies on amikacin in neonates].

Pharmacokinetic and clinical studies on amikacin (AMK) were performed in neonates and the results obtained are summarized as follows. 1. After intramuscular injection of single doses of AMK at 3 mg/kg, peak serum levels were 6.8 micrograms/ml in a 2-day-old neonate and 7.0 micrograms/ml in a 20-day-old neonate. Serum levels of AMK in the above 2 neonates at 8 hours after injection were 1.5 micrograms/ml and 1.4 micrograms/ml, respectively, and the half-life of AMK was 3.3 hours. After intramuscular injection of single doses of 4 mg/kg of AMK, the mean peak serum level was 8.1 +/- 1.1 micrograms/ml, and half-lives of AMK were 6.1 hours in a 1-day-old neonate and 4.0 hours in a 3-day-old neonate. The mean peak serum level of AMK reached at 1 hour after intramuscular administrations at single dose of 6 mg/kg was 10.5 +/- 0.5 micrograms/ml in a 3-day and a 4-day-old neonates. Serum levels at 8 hours after administrations were 3.1 micrograms/ml and 2.8 micrograms/ml, in the 3-day and the 4-day-old neonates, respectively. Half-lives of AMK in sera were 3.9 hours in the 3-day-old neonate and 3.5 hours in the 4-day-old neonate. 2. In three 2-day-old neonates, the mean peak serum level of AMK after an intravenous drip infusion for 30 minutes at single dose of 3 mg/kg was 10.0 +/- 1.1 micrograms/ml at the end of infusion and serum levels decreased to 2.3 +/- 0.6 micrograms/ml at 6.5 hours after infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

F-actin content of neonate and adult neutrophils.

We utilized flow cytometric analysis of NBDphallacidin-stained cells to measure F-actin content, expressed as fluorescent channel numbers, and we compared the microfilamentous cytoskeletal organization in neutrophils from healthy neonates (36 to 38 weeks gestational age) and adults. Basal F-actin content in neonate cord blood neutrophils is higher than that of adults. The elevation is intrinsic to the cell and not related to parturition because basal F-actin content of neonatal cells obtained by venipuncture (days 1 to 8 of age) is also elevated (38 +/- 10, N = 15) when compared to adults (21 +/- 7.0, N = 27). The rate of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced actin polymerization is similar in adult and neonatal neutrophils and is maximal by 30 to 45 seconds at 25 degrees C. Adult, neonatal cord, and neonatal venipuncture neutrophils increase F-actin content to a similar extent following 0.5 mumol/L fMLP activation (52 +/- 18, N = 27; 58.7 +/- 18, N = 18; 51.5 +/- 7.0, N = 15, respectively). However, the relative increase in F-actin content following fMLP activation is much greater in adult (2.37-fold) than neonatal neutrophils (1.28-fold). This difference is due to the elevated basal F-actin content of neonatal cells. Comparison of distribution of F-actin content among basal, neonatal neutrophils reveals two subpopulations of neutrophils with respect to F-actin content--approximately 25% with F-actin content similar to that of adult neutrophils and 75% with F-actin content greater than that of adult cells. Following fMLP activation, the subpopulations disappear. The results suggest that abnormalities in microfilamentous cytoskeletal organization of neonatal cells may, in part, be responsible for decreased chemotactic response of neonatal neutrophils.

Actins↗

[Resistance index of anterior cerebral artery in the diagnosis of hypoxic ischemic encephalopathy in neonates].

OBJECTIVE: To study the relationship between the resistance index (RI) of the anterior cerebral artery and hypoxic ischemic encephapathy (HIE) in neonates for the purpose of finding out a method of diagnosing and predicting HIE and its prognosis. METHOD: The anterior cerebral artery blood flow velocity waveform (aCAFV) of neonates was recorded by a continuous Doppler technique and RI value was measured. 230 observations on 67 cases of high risk neonates and 534 on 182 normal neonates were performed. The mean value of RI and its standard deviation in normal neonates chosen served as control. The relationship between the standardized incidence of abnormal RI of the anterior cerebral artery and HIE was studied in high risk neonates. RESULT: In normal neonates (control group), RI was 0.62 +/- 0.09, and was in positive correlation (r = 0.72, P < 0.05) with the days after birth. The normal aCAFV was a regular waveform. In high risk neonates, the standardized incidence of abnormal RI in the neonates most likely to be attacked by HIE (A group) was significantly higher than that in control group (P < 0.001), but there was no significant difference between the other babies (B group) and control group (P > 0.05). However, the standardized incidence of abnormal RI in the A group was also significantly higher than that in the B group (P < 0.001). In the cases who were severely attacked by HIE, the standardized incidence of irregular waveform was the highest. Furthermore, when irregular aCAFV waveform appears, the incidence of pernicious complication of HIE and mortality of neonates were significantly increased in all cases. CONCLUSION: The abnormal RI value of anterior cerebral artery implies the existence of HIE in neonates. The prognosis is poor when irregular blood flow waveform appears.

Blood Flow Velocity↗

Supplemental complement component C9 enhances the capacity of neonatal serum to kill multiple isolates of pathogenic Escherichia coli.

Previous studies demonstrated that, compared with adult serum, neonatal serum contained a diminished concentration of complement component C9 and that supplemental C9 enhanced the capacity of neonatal serum to kill an isolate of Escherichia coli. Therefore, experiments were designed to determine the mechanisms by which supplemental C9 enhances the bactericidal capacity of neonatal serum and to determine whether supplemental C9 enhances the capacity of neonatal serum to kill several different pathogenic strains of E. coli. A radiobinding assay and immunogold electron microscopy using a monoclonal anti-C9 antibody revealed that, compared with 40% adult serum, neonatal serum deposited a diminished quantity of C9 onto E. coli O7w:K1:NM. Supplemental C9 (75 mg/L) significantly enhanced the quantity of C9 deposited by the neonatal serum. Treatment with 10 mM MgEGTA (a mixture of 100 mM MgCl2 and 100 mM EGTA that blocks activation of the classic complement pathway but leaves the alternative pathway intact) abolished the capacity of neonatal serum to deposit C9 and to kill the bacteria. Supplemental C9 enhanced the capacity of neonatal serum to kill eight different blood isolates of E. coli. Therefore, supplemental C9 enhanced the capacity of neonatal serum to kill E. coli by increasing the total quantity of C9 deposited via activation of the classic complement pathway. Neonatal serum contained sufficient quantities of classic pathway components, other than C9, to deposit the supplemental C9 onto E. coli and to enhance bacterial killing. The bactericidal activity of neonatal serum against multiple isolates of pathogenic E. coli was increased after C9 supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Thyroid function in healthy and sick neonates.

BACKGROUND: Low serum thyroid hormone concentrations are frequently observed in critically ill patients. Low-birth-weight preterm infants have also been reported to contain lower serum thyroxine (T4) levels when compared with normal term infants. Investigating the differences of the thyroid function between sick and healthy term and preterm infants becomes a worthwhile task. METHODS: Thyroid functions were measured in 80 newborn infants (including 31 critically ill neonates admitted to neonatal intensive care unit and 49 healthy controlled neonates). The neonates were divided into three groups in terms of gestational age. Group 1 consisted of 10 sick and 12 healthy term neonates with a gestational age > or = 38 weeks. Group 2 consisted of 9 sick and 26 healthy preterm infants with gestational ages ranging between 32 and 36 weeks. Group 3 consisted of 12 sick and 11 healthy very low birth weight (VLBW) infants with a gestational age < or = 31 weeks. Serum thyroxine (T4), thyroid stimulating hormone (TSH), free T4, and triiodothyronine (T3) concentrations were measured at 1 and 5 days after birth. RESULTS: Observed data indicated that sick neonates in three groups had significantly lower T4 values (p = 0.05) than healthy term and preterm neonates. TSH levels of sick neonates in three groups were not significantly different (p > 0.05) from those of healthy neonates on day 1 and day 5. Serum free T4 levels were significantly lower (p < 0.05) in sick than in healthy premature infants. Sick VLBW premature infants had significantly lower T3 values (p < 0.05) than healthy VLBW premature infants on day 1 and day 5. CONCLUSIONS: Low serum T4, free T4, T3 concentrations are commonly found in sick neonates, whereas serum TSH values are not significantly different between sick and healthy neonates.

Asphyxia Neonatorum↗

Oxidation of proteins in neonatal lungs.

OBJECTIVE: To develop a method capable of quantifying the oxidative modification of proteins in pulmonary fluid obtained during routine suctioning of neonates receiving ventilation, thus providing an integrated assessment of antioxidant defenses. DESIGN: Consecutive sample of neonates receiving ventilation. SETTING: Neonatal intensive care unit. PATIENTS: Twenty-six neonates receiving ventilation with a gestational age of 24 to 42 weeks, from whom 246 samples were collected and analyzed. MEASUREMENTS AND RESULTS: The carbonyl content in the lavage samples was measured by reaction with 2,4-dinitrophenylhydrazine followed by high-pressure liquid chromatography. Oxidation of proteins caused introduction of carbonyl groups into the side chains of the protein, providing a convenient and relatively specific marker of oxidative damage. On the first day of life, the initial protein-bound carbonyl for each neonate was usually low and consequently was not significantly related to birth weight, gestational age, or initial ventilatory requirements. Examination of the changes in pulmonary protein carbonyl in the first days of life revealed correlations of interest. In the first day of life, four neonates whose average inspired oxygen were < 40% showed no increase in carbonyl content, whereas four neonates whose inspired oxygen was > 40% showed an average increase in carbonyl of 51% (P < .001). Also, the need for ventilation > 3 days was correlated with elevated carbonyl in those first 3 days. The carbonyl content averaged over the first 3 days was 0.13 +/- 0.02 mol carbonyl/mol protein for the eight neonates receiving ventilation < 72 hours, whereas the nine needing longer ventilation had a carbonyl content of 0.28 +/- 0.03 mol carbonyl/mol protein (P < .05). Seven neonates were treated with dexamethasone because of ventilator dependence at 14 days of age. In these neonates, treatment was associated with a 50% reduction in carbonyl content within 48 hours (P < .02). CONCLUSIONS: Oxidative damage to pulmonary proteins can be quantitated in samples obtained during routine suctioning of neonates receiving ventilation. The amount of oxidatively modified protein may provide a quantitative assessment of oxygen toxicity and of pulmonary antioxidant defenses.

Bronchoalveolar Lavage Fluid↗

Comparison of prophylaxis and rescue treatment with Curosurf in neonates less than 30 weeks' gestation: a randomized trial.

OBJECTIVE: The aim of this randomized clinical trial was to evaluate the immediate effects of prophylactic administration of Curosurf and to compare outcomes after prophylactic or expectant management. STUDY DESIGN: Porcine surfactant (Curosurf, 200 mg/kg body weight) was administered intratracheally within 10 minutes of birth to preterm neonates with a gestational age of 26 to 29 weeks (n = 75); rescue-eligible neonates (n = 72) were initially subjected to a sham maneuver. The primary end points of the trial, evaluated at the age of 6 hours, were to obtain (1) a 40% decrease in the ratio between transcutaneous oxygen tension (tcPO2) (kPa) and fraction of inspired oxygen (FIO2), and (2) a 50% decrease in the incidence of radiologically verified respiratory distress syndrome (RDS). After 6 to 24 hours, a similar dose of surfactant was given to the neonates of both the prophylaxis and the rescue-eligible group, if they needed mechanical ventilation with an FIO2 > or = 0.6. RESULTS: At 6 hours the prophylaxis group had, in comparison with the rescue-eligible group, significantly higher tcPO2/FIO2 ratios (mean +/- SD: 39.7 +/- 15.3 vs 28.1 +/- 18.1; P < .001) and less severe RDS by radiological scoring (chi 2 = 14.9; P = .005). Severe RDS was present in 19% of the prophylactically treated neonates versus 32% in the rescue-eligible group (P < .05). The prophylaxis group needed shorter periods of FIO2 > 0.40 than the rescue-eligible neonates (P < .01), and eight neonates of the prophylaxis group (11%) versus 23 of the rescue-eligible group (32%) qualified for rescue treatment with surfactant in the interval 6 to 24 hours (P < .01). There were no differences in the incidence or severity of pneumothorax, pulmonary interstitial emphysema, cerebral hemorrhage, periventricular leukomalacia, patent ductus arteriosus, in the duration of mechanical ventilation or time in supplemental oxygen, or in mortality. CONCLUSIONS: Subgroup analysis revealed (1) that administration of corticosteroids reduced the risk of developing neonatal RDS as effectively as did surfactant prophylaxis at birth, and (2) that prophylaxis was effective especially in neonates with gestational age < 28 weeks or birth weight < 1000 g, in male neonates, and in neonates who had received no antenatal treatment with corticosteroids. Our data indicate that prophylactic treatment with surfactant should be considered in high-risk neonates fulfilling these latter criteria.

Biological Products↗

Cuta neous basophil responses in neonatal guinea pigs: active immunization, hapten specific transfer with small amounts of serum, and preferential elicitation with phytohemagglutinin skin testing.

Previous studies have demonstrated a failure to elicit delayed hypersensitivity skin responses in neonatal guinea pigs despite apparent immunologic competence of their lymphocytes and monocytes. The ability of neonatal guinea pigs to manifest cutaneous basophil hypersensitivity (CBH) responses was examined. Neonates were competent to express macroscopic and microscopic aspects of these delayed reactions. Strong cutaneous basophil responses were elicited in newborns (0 to 2 days old) in a hapten-specific manner after intravenous transfer of small amounts of immune serum (0.5 ml) obtained from adult donors. Also, neonatal guinea pigs actively immunized at birth with hapten-carrier conjugates emulsified with incomplete Freund's adjuvant (IFA) and skin tested when 1 week old had 24-hr hapten-specific cutaneous basophil reactions and CBH reactions to the carrier protein as well. Compared with adult CBH reactions, neonatal responses had equal concentrations of basophils, fewer monocuclear cells, less macroscopic erythema, and almost no induration. Hapten-specific CBH reactions also contained significant infiltrates of eosinophils which were more prominent in the ear skin vs flank skin and in neonates vs adults. Immunization with complete Freund's adjuvant (CFA) resulted in a marked difference between adults and neonates; adult PPD reactions were quite indurated and contained many more monoculear cells and few basophils, whereas neonatal PPD reactions were flat, erythematous, nonindurated, and contained relatively few mononuclear cells and more basophils. Thus, neonatal tuberculin reactions elicited by PPD in animals immunized with CFA were examples of CBH. Skin testing nonimmune guinea pigs with phytohemagglutinin (PHA) also revealed marked differences in 24-hr cutaneous reactions between adults and newborns. Adults had indurated and erythematous reactions which contained approximately 20% basophils and 80% mononuclear cells, whereas similar PHA skin tests in newborns elicited small macroscopic reactions, which microscopically showed large infiltrates containing approximately 80% basophils and 20% mononuclear cells. It was concluded that neonatal guinea pigs were not only competent to manifest basophil-containig delayed-type reactions, but that cutaneous basophil responses were preferentially elicited in these animals under a variety of circumstances. These results underline the fact that basophil accumulations are one aspect of delayed skin test responses and that the regulation of the arrival of these cells in neonates is different from that in adult guinea pigs.

Animals↗

CD40 ligand is expressed and functional on activated neonatal T cells.

Deficient CD40 ligand (CD40L) expression by neonatal T cells has been proposed to explain the diminished Ig production by newborns. Therefore, we examined the expression and function of CD40L on activated neonatal CD4+ T cells isolated from cord blood. Anti-CD3 activation of neonatal T cells resulted in the expression of CD40L demonstrated with specific mAb or a soluble CD40.G1 construct. The level of expression was comparable to that of adult memory CD4+ T cells. In contrast, PMA and ionomycin induced only minimal CD40L expression by neonatal T cells, whereas adult memory T cells expressed CD40L comparably after stimulation with PMA and ionomycin or anti-CD3. The expression of CD40L was blocked by cyclosporine and prostaglandin E2 (PGE2). IL-2 IL-4 partially reversed the inhibition of CD40L expression by cyclosporine, and IL-2 reversed the inhibition by PGE2. CD40L expressed by neonatal T cells was functionally active, since neonatal T cell-dependent production of IgG4 and IgE was inhibited by a soluble CD40.G1 construct. Moreover, neonatal T cells supported the secretion of significantly more IgG, IgA, and IgE than CD40L-deficient hyper-IgM T cell clones. In addition, neonatal CD4+ T cells induced CD86 B7-2) expression by neonatal B cells that was blocked by anti-CD40L but not by control mAb. The results indicate that neonatal T cells activated through the TCR/CD3 complex express CD40L and use it to promote CD86 expression, Ig secretion and heavy chain isotype switching by neonatal B cells.

Adult↗

[No solution for neonatal mortality in sub-saharan Africa? Evaluation and perspectives in the urban environment of Niamey, Niger].

Niger has one of the highest mortality rates of infants (222/1000) and children under five years old (318/1000), with 15% of them suffering from malnutrition. Yet, neonatal mortality was not considered as the top priority of public health in Niger, where 85 to 90% of the deliveries succeed without any medical care and 70% of the population live more than 10 kilometers from the nearest medical center. Also, in the African countries which have adopted expensive neonatal care centers following the occidental model, the lethality rate is high and maintenance is difficult. Thus, alternative strategies should be considered to reduce the neonatal mortality, according to the local possibilities. This was carried out in Niamey, the capital of Niger. A retrospective study of the activities in the pediatric and obstetric wards was carried out from 1985 to 1992. This was associated with a descriptive prospective survey of a sample of 149 pregnant women followed from the first prenatal consultation to the end of the neonatal period. Results showed that possibilities exist in Niamey to reduce neonatal mortality. The concentration of medical personnel was high compared to the rest of the country, and the health infrastructure was diversified. However, the knowledge of neonatal care was lacking. Use of prenatal care was high and deliveries at home without medical assistance concerned only 14.3% of the total births. Mortality observed in the obstetrical ward (6.7/1000) corresponded to less than a quarter of the estimated neonatal mortality (28.6/1000). Neonatal mortality in the pediatric ward was high (43.8%), predominantly on the first day of admittance (45% of the deaths), especially for the low birth weights (under 2,500 g) (62.4%). These figures underline the necessity to improve the care of the newborns and to link prenatal prevention, obstetrical care and pediatrics. The prospective survey showed that although the ratio of prenatal visits per woman was high (3.8), the quality of the care was inadequate. Correct newborn care was rare and no examination could detect or prevent complications during the short stay of less than 24 hours in the obstetrical ward. To lower the neonatal mortality, service could be improved concerning the material conditions of prenatal consultations, reorientation of prenatal consultations towards detection, correct treatment of the risk factors of neonatal mortality, obstetrical screening and care, and training of the midwives. The adoption of inexpensive measures was suggested, including the training of pediatric nurses in each maternity ward, screening and treatment of newborns at risk in small units integrated within the obstetrical ward, and the requirement of a consultation before the traditional feast of giving names, which occurs on the seventh day of life in Niger. These measures were considered as priorities before considering construction of expensive neonatal centers and assume the participation of the public health personnel and policy makers. Some of these suggestions are now being implemented.

Health Priorities↗

[Neonatal sepsis: epidemiologic indicators and relation to birth weight and length of hospitalization time].

OBJECTIVE: All cases of neonatal septicemia among neonates admitted to the neonatal unit in the pediatric department (CHUS) in Santiago de Compostela between 1992 and 1995 were studied. Our aims were: 1) To assess the incidence and microbial epidemiology. 2) To study the incidence of coagulase-negative staphylococci (CONS) sepsis stratified according to birth weight and gestational age. 3) To assess the incidence density of sepsis (IDS) and 4) To analyze the associated mortality. PATIENTS AND METHODS: One hundred eighteen episodes of sepsis in 103 neonates which fulfilled clinical and laboratory criteria with positive blood cultures were included in this study. Between the years of 1992 and 1995 there were 318 neonates suspect of having sepsis among the 2,083 who were admitted to the unit during this period and which came from our own maternity department, as well as other centers. RESULTS: In this period there were 10,457 live births in our maternity department. The annual incidence of sepsis was 6/1000 live births. Early onset sepsis was observed in 2.5/1000 live births (26 cases) and the occurrence of late onset increased to 3.5/1000 live births (36 cases). Neonatal sepsis was confirmed in 103 neonates (4.9%) corresponding to 118 episodes of sepsis. S. epidermidis was the most frequent agent isolated in blood cultures (38.1%). The highest incidence of sepsis caused by S. epidermidis was observed in neonates below 1500 g (12.1%) and less than 32 weeks gestational age (13.4%). The incidence was lower in those whose birth weights were more than 2500 g (1.9%) and > 37 weeks of gestational age (1.6%), p < 0.001. Overall mortality due to sepsis was 0.7% and increased to 5.0% among hospitalized newborns with birth weights below 1500 g. The average IDS stratified in three groups of birth weight and gestational age was 18 sepsis work-ups per 1000 patient-days of hospitalization, the lowest IDS 12.9/1000 was found in neonates whose birth weights were between 1501 g and 2500 g in comparison with neonates who weighted more than 2500 g (21.5/1000), p < 0.05, and very similar to the IDS found in the intermediate group of gestational age (13.1/1000). CONCLUSIONS: S. epidermidis and other CONS are the main agents causing sepsis in hospitalized neonates, although there is a decreasing trend of incidence (-71.1%) between the years 1992 and 1995 (5.0% vs 1.5%). Gram-negative organisms and S. agalactiae played a minor role as agents causing sepsis even though S. agalactiae is the most important agent in early onset sepsis. Overall mortality associated with sepsis (7/1000 live births) is in or under the average range of international statistics. Indexes of IDS are more valuable as epidemiological tools in assessing septicemia than the simple attack rate because they have taken into consideration the length of stay, number of hospitalized newborns, as well as the number of positive sepsis work-ups in the calculating process.

Birth Weight↗

Neonatal murine B lymphocytes respond to polysaccharide antigens in the presence of IL-1 and IL-6.

Unlike adults, neonates are unable to respond to polysaccharide Ags, making them especially vulnerable to pathogenic encapsulated bacteria. Since the Ab response to polysaccharides in adult mice requires certain cytokines, it was hypothesized that neonatal murine B cells may be competent to respond to such Ags, but may fail to do so due to a deficiency of cytokines. Neonatal splenocyte cultures, which were otherwise unresponsive to trinitrophenyl (TNP)-Ficoll, a haptenated polysaccharide Ag, mounted an adult-like Ab response when supplemented with IL-1. However, IL-1 failed to induce such a response to TNP-Ficoll when purified B cells were used instead. Although IL-6 alone did not induce a response in whole spleen cells or purified B cells from neonates, it synergized with IL-1 in inducing purified neonatal B cells to respond to TNP-Ficoll. The avidity of the cytokine-induced neonatal anti-TNP Abs was comparable to that of Abs made by adult splenocyte cultures. One effect of IL-1 may be at the level of clonal expansion, since it induced neonatal B cells to proliferate in response to anti-IgM, which was further enhanced by IL-6. The spontaneous secretion of IL-1 by neonatal splenocytes was below the detection limit, while adult splenocytes secreted 30.8 +/- 5.2 U/ml, which is of the same order of magnitude as what was required to stimulate neonatal B cells to respond to TNP-Ficoll. Thus, the neonatal unresponsiveness to polysaccharide Ags could be due to the inability of a non-B cell population resident in the neonatal spleen to secrete sufficient quantities of IL-1.

Age Factors↗

Rationale and potential use of cytokines in the prevention and treatment of neonatal sepsis.

Despite advances in the use of newer antimicrobials and aggressive supportive care, sepsis and its sequalae remain a major source of morbidity and mortality in the neonate. The VLBW neonate is especially at high risk. We and others have demonstrated that neonatal MNC are deficient in their production of G-CSF and GM-CSF, which, in part, may explain the neonates propensity to develop neutropenia during times of sepsis. G-CSF and GM-CSF have been shown to both enhance neonatal neutrophil superoxide production in vitro and to increase circulating neutrophil numbers through expansion of the NSP in the BM in neonatal rats and humans. G-CSF is protective (if given with or before antibiotics) during experimental GBS in the neonatal rat and appears to be well tolerated (both short term and 2 years after its use) in the human neonate. In a phase II randomized pilot multicenter study, GM-CSF prophylaxis in the VLBW neonate was well tolerated during 4 weeks of administration and was noted to have significantly reduced the incidence of nosocomial infections. Future efficacy and safety studies in more neonates need to be completed and assessed before the routine pharmacologic use of G-CSF or GM-CSF is recommended to prevent and treat neonatal sepsis.

Animals↗

Dedicated neonatal retrieval teams improve delivery room resuscitation of outborn premature infants.

BACKGROUND: Morbidity related to ineffective resuscitation and stabilization of premature infants is increased when delivery occurs outside tertiary perinatal centers. The regional neonatal transport team received extensive training to expand their scope of practice to include delivery room resuscitation allowing them to attend high-risk deliveries in community hospitals when maternal transfer was not possible. OBJECTIVE: Compare the resuscitation and stabilization of premature infants when a specialized neonatal retrieval team (SNRT) is in attendance at delivery with immediate resuscitation and stabilization performed by the referral hospital team (RHT). STUDY DESIGN: We assessed the impact of a specially trained neonatal transport team by comparing the initial resuscitation process, airway and vascular access skills, illness severity and patient stabilization in both groups. RESULTS: Neonates resuscitated by the RHT were more likely to receive oxygen, mask CPAP, bag and mask ventilation and cardiac compressions for a significantly longer time period. Neonates resuscitated by the SNRT were intubated more promptly (8.5 minutes {1 to 22} vs 16 minutes {1 to 90}, p=0.035) following a fewer number of attempts. The endotracheal tube was correctly positioned on radiological assessment in 72% of cases in the SNRT group vs 38.1% in the RHT group (p<0.001). Many neonates had no vascular access (31%) and were profoundly hypothermic (38.5%) on arrival of the SNRT. Although there was no significant difference in maximum FiO(2) or oxygenation index, babies with respiratory distress syndrome resuscitated by the RHT were less likely to receive surfactant therapy (76.6 vs 34.4%, p=0.001). There was no difference in transport-related mortality between the groups CONCLUSIONS: The presence of a highly skilled transport team at a high-risk preterm delivery improves the quality of neonatal resuscitation by increasing intubation success rates and achieving earlier vascular access. Neonates resuscitated by dedicated neonatal retrieval teams were less likely to become significantly hypothermic. Although the severity of RDS was similar neonates in the RHT were less likely to receive surfactant.

Analysis of Variance↗

A 2-year study of neonatal mortality in a large Malaysian hospital.

A 2-year study was carried out in the Maternity Hospital, Kuala Lumpur to determine the neonatal mortality rates. This Hospital functions both as the local service centre as well as the national referral centre in Malaysia. Its neonatal services, however, were equipped and manned at those below Level III perinatal centre. During the study period 52, 877 livebirths took place in the Hospital. In 1987 and 1988 respectively, the low birthweight (less than 2500 gm) rates were: 112.8 and 101.9 per 1000 livebirths, very low birthweight (less than 1500 gm) rates: 11.1 and 8.8 per 1000 livebirths, neonatal mortality rates: 12.5 and 10.7 per 1000 livebirths and neonatal mortality risk ratio: 1.15 and 1.27. There was significant difference in mortality rates among the Malay, Chinese and Indian babies born in this hospital: the Indians had the highest and the Chinese the lowest rates. Babies delivered by breech or lower segment Caesarean section (LSCS) also had significantly higher mortality than those delivered by other modes of delivery. Low birthweight neonates constituted less than 45% of the total special care nursery admission but contributed to more than 70% of the total neonatal deaths. The common causes of neonatal deaths were problems of prematurity, infection, asphyxia and congenital malformations. Preterm and low birthweight neonates died primarily from problems of prematurity or infection. Term and larger neonates died mainly from asphyxia. More than 75% of the neonatal deaths occurred before 7 days of life. Improvement of antenatal care in the community and upgrading of perinatal services in this Hospital could help to lower the morbidity and mortality due to preventable causes.

Birth Weight↗

Neonatal jaundice and molecular mutations in glucose-6-phosphate dehydrogenase deficient newborn infants.

Molecular mutations of the glucose-6-phosphate dehydrogenase (G6PD) gene and clinical manifestations of neonatal jaundice in 112 male and 50 female Chinese neonates with G6PD deficiency were studied. In the 112 males, the nucleotide (nt) 1376 (G-->T) mutation was the dominant type (50.0%), followed by nt 1388 (G-->A) (16.1%), nt 493 (A-->G) (8.0%), nt 1024 (C-->T) (6.2%), nt 95 (A-->G) (5.4%), nt 392 (G-->T) (1.8%), nt 487 (G-->A) (1.8%), nt 871 (G-->A) (0.9%), and nt 1360 (C-->T) (0.9%). The nt 871 variant has not been reported in Taiwan before. The occurrence rates for nt 1376, nt 1388, nt 493, nt 95, and nt 1024 mutations in the 50 females were 44.0%, 18.0%, 12.0%, 6.0%, and 6.0%, respectively. The type of G6PD mutation in 10 male and 7 female neonates has not been identified yet. Although G6PD deficient neonates had higher frequency of phototherapy than G6PD normal neonates in both sexes, a significant difference in the prevalence of hyperbilirubinemia (peak bilirubin > or = 15.0 mg/dl) between G6PD deficient and normal neonates was found only in males. Further analysis showed that duration of phototherapy was longer in G6PD deficient male neonates than in the control group, while the outcome of phototherapy was better in subjects with non-nt 1376 mutations than subjects with the nt 1376 mutation. Most (78.3%) of the 23 G6PD deficient neonates who subsequently suffered from neonatal hyperbilirubinemia carried the nt 1376 mutation. The results of this study indicate that the nucleotide substitution at 1376 is the most common and important mutation for G6PD deficiency in Chinese neonates in Taiwan.

Base Sequence↗

Neonatal seizures: early-onset seizure syndromes and their consequences for development.

The determination of the developmental consequences of seizure syndromes in the neonate is based upon a number of factors which include: understanding of the clinical and electroencephalographic (EEG) features of neonatal seizures; current theories of the mechanisms by which neonatal seizures are generated; a current classification of neonatal seizures; potential etiologic and risk factors for seizures; and therapies. In addition, different seizure types, mechanisms of generation and etiologies of cerebral dysfunction may vary with conceptional age of the infant. There are a few distinct neonatal epileptic syndromes, which are rare, have been well described: benign neonatal convulsions; benign neonatal familial convulsions; early myoclonic encephalopathy and early infantile epileptic encephalopathy. The prognosis for the first two is relatively good while the outcome for the other two with encephalopathy is catastrophic. However, the majority of neonatal seizures occur as acute, reactive events in association with a wide range of etiologic factors. These etiologic factors, as well as those of the more traditionally defined syndromes, are the main determinants of eventual developmental outcome of neonates who experience seizures. Although experimental data suggests that some epileptic seizures eventually may have physiological, histological, metabolic, or behavioral consequences, there is yet direct evidence in humans to suggest that the occurrence of seizures themselves in the neonate is the main determinant of long-term outcome.

Acute Disease↗

Do we need new indications for ECMO in neonates pretreated with high-frequency ventilation and/or inhaled nitric oxide?

OBJECTIVE: High-frequency ventilation (HFV) and/or inhaled nitric oxide (iNO) has reduced ECMO in neonates. But, frequently, improvement with HFV/iNO is temporary and only prolongs lung injury without preventing ECMO. We tried to identify a threshold oxygenation index (OI) that predicts temporary or persistent improvement with HFV/iNO in neonatal ECMO candidates as early as possible. DESIGN: Cohort study of all neonates with OI > 40 during intermittent positive pressure ventilation between 1992 and 1997. The first treatment was HFV; at an OI > 40 during HFV, iNO was added; at an OI > 40 during HFV+iNO, ECMO was initiated. Temporary improvement was defined as secondary need for ECMO or fatal chronic lung disease without ECMO. SETTING: University hospital level III neonatal intensive care unit. MAIN RESULTS: Ten of the 34 neonates studied rapidly required ECMO despite HFV/iNO. Eleven neonates temporarily improved for 1-10 days before the OI was again > 40. Nine received ECMO, two were denied ECMO after mechanical ventilation > 14 days and died of chronic lung disease. Thirteen neonates persistently improved with HFV/iNO without ECMO. The OI before, at 24 h or 48 h of HFV/iNO did not predict temporary or persistent improvement. However, after 72 h of HFV/iNO, neonates with persistent improvement had lower OIs than those with temporary improvement [median OI 16 (4-24) vs 31 (20-40); P = 0.0004]. In all neonates with an OI > or = 25 after 72 h, HFV/iNO eventually failed (positive predictive value 100%, sensitivity 91 %, specificity 100%, positive likelihood ratio 91). CONCLUSION: For neonates pretreated with HFV/iNO, an OI > 40 is an inadequate ECMO indication. Based on our data we hypothesize that an OI > or = 25 after 72 h of HFV/ iNO is a better ECMO indication that avoids prolonged barotrauma.

Administration, Inhalation↗