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Comparison of methods of bag and mask ventilation for neonatal resuscitation.

BACKGROUND: There are a variety of manual bagging devices used for neonatal resuscitation. To our knowledge, there has been no comparison of the ability of different operators to utilize such devices for the delivery of predetermined inspiratory and end-expiratory pressures. In addition, the use of prolonged inflation may be of benefit for infants who require bag and mask ventilation, and there has been no evaluation of the ability of a variety of operators to reliably deliver such breaths using currently available equipment. METHODS: We utilized a neonatal manikin (Laerdal Armonk, NY) with a functional larynx and lungs, and a clear cushioned mask (Owens-BriGam, Morganton, NC). We studied a latex-free disposable anesthesia type bag (Model 5126 Vital Signs, Totawa, NJ), a Jackson-Rees (JR) type anesthesia bag (Model E191 Anesthesia Associates, San Marcos, CA) fitted with a Norman elbow and a flow-control tail-piece (Dupaco, Oceanside, CA), and the Neopuff (Fisher and Paykel, Auckland, New Zealand), an FDA approved mechanical device that is flow-controlled and pressure-limited, specifically designed to facilitate neonatal resuscitation. The ventilating pressures were continuously recorded throughout the process. We evaluated neonatal nurses, neonatal nurse practitioners, neonatal staff and fellows, pediatric residents and neonatal respiratory therapists. RESULTS: The peak inspiratory pressure (PIP) was significantly different between operators using either anesthesia bag, P<0.001. Similar results were found for positive end-expiratory pressure (PEEP) with a significant difference among the operator groups, P<0.001. All the differences in post hoc analysis were between the therapists and the other groups, P<0.05. Therapists produced significantly higher pressures than the other groups for both PIP and PEEP (P<0.001). The PIP was similar for all groups using the Neopuff device. The PIP and PEEP delivered by the Neopuff differed from the other two devices independent of the operators (P<0.05). On post hoc analysis, there was a significant difference between the disposable anesthesia bag and Neopuff for both PIP and PEEP for the therapists, whereas among the non-therapists, there was a difference in PIP with the JR device producing a greater PIP (26.6+/-3.8 cmH(2)O) compared with the Neopuff and disposable anesthesia bag (24.8+/-1.1 cmH(2)O, 24.8+/-4.3 cmH(2)O). The level of PEEP was significantly different among all three devices for the non-therapists (1.3+/-1.6 cmH(2)O, Disposable; 2.9+/-1.2 cmH(2)O, JR; 4.7+/-0.5 cmH(2)O, Neopuff; P<0.05). Only the therapists were able to consistently deliver PEEP with the anesthesia bags, whereas all operators could generate the target PEEP with the Neopuff (P<0.05). We compared the pressure delivered during the first second to the pressure delivered during the fifth second during prolonged 5-s inflations. The absolute differences between the first and fifth second for the Neopuff versus the anesthesia bags were significantly different with a median of 7.1 cmH(2)O for the anesthesia bags compared with 0.2 cmH(2)O for the Neopuff, P<0.001, reflecting the difficulty in obtaining and maintaining the target inflation pressures. CONCLUSIONS: Our experience suggests that the Neopuff, a purpose-built neonatal resuscitator ventilator, facilitates the delivery of the desired airway pressures while maximizing the operators ability to obtain and maintain a patent airway, and facilitates the delivery of prolonged inflations. Further research is required to determine the clinical benefit of end-expiratory pressure and prolonged inflations in neonatal resuscitation.

Analysis of Variance↗

Thrombopoietin in the fetus and neonate.

C-mpl ligand or thrombopoietin (Tpo) is increasingly recognised as the major regulator of platelet homeostasis in humans. Relatively little is known about Tpo in the fetus and neonate but no evidence has yet been found to suggest any fundamental difference in Tpo structure, function and regulation in the fetus and neonate compared to older age groups. Tpo mRNA transcripts have been detected in the fetus as early as 6 weeks post conception and the liver appears to be the main site of Tpo production in both the fetus and neonate. The vast majority of healthy newborns have detectable levels of circulating Tpo and raised Tpo levels are commonly, but not consistently, found in thrombocytopenic neonates. In adults receptor binding and subsequent metabolism of Tpo is proposed as the main method of regulation of the circulating Tpo level. Preliminary studies in neonates showing increased Tpo levels most often during thrombocytopenia accompanied by reduced megakaryocytopoiesis supports this concept. In addition to this demonstrable fetal and neonatal endogenous Tpo production megakaryocyte progenitor and precursor cells from the fetus and from preterm and term newborns proliferate and differentiate extensively in-vitro in response to exogenous Tpo. Furthermore a recent study has shown a marked rise in platelet count in newborn rhesus monkeys administered one form of recombinant Tpo. Although these studies remain at an early stage together these findings strongly suggest that, as in adults, Tpo is the major regulator of platelet homeostasis in the fetus and neonate. Thrombocytopenia is common in sick neonates and progress in understanding this important clinical problem is likely to be greatly enhanced by the current and future research into Tpo production, function and regulation in the healthy and thrombocytopenic fetus and neonate.

Adult↗

Electroencephalogram confirmatory rate in neonatal seizures.

The electroencephalogram (EEG) is confirmatory in 70% of children and adults with seizures, although gestation- and etiology-specific EEG confirmatory rates in neonates have not been well defined. All neonates treated for seizures and who underwent EEG were identified from 4,575 neonates admitted between 1985 and 1996 to a neonatal intensive care unit. The relationship between EEG findings (epileptiform discharges and background abnormalities) and gestation, mortality rate, and seizure etiology was examined using the Student t test. One hundred eighty-three neonates treated for seizures underwent a total of 352 EEGs: 144 of these neonates (79%) had an abnormal EEG (epileptiform discharges in 113 (60%) and nonepileptiform background abnormalities in 31). The EEG confirmatory rate increased with gestation (63% at 28 weeks vs 77% at term, P < 0.02). Etiology for seizures also influenced the EEG confirmatory rate: central nervous system (CNS) infection 95% (P < 0.05), hypoxic-ischemic encephalopathy 80% (P < 0.05), germinal matrix-intraventricular hemorrhage 65%, and CNS malformations 65%. The EEG confirmatory rate was predictive of neonatal mortality (19% vs 6%, P < 0.03). The EEG was directly confirmatory (epileptiform discharges) in 60% and supportive (nonepileptiform background abnormalities) in a further 17% of neonates with seizures. Gestation and etiology influence the EEG confirmatory rate in neonatal seizures.

Brain Diseases↗

Early diagnostic markers for neonatal sepsis: comparing C-reactive protein, interleukin-6, soluble tumour necrosis factor receptors and soluble adhesion molecules.

We compared six inflammatory mediators (C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumour necrosis factor receptors (p55 and p75) and soluble adhesion molecules (ICAM-1, E-selectin)) as early diagnostic tests for neonatal sepsis, and studied the possible benefit of combining parameters. Blood samples were obtained from 166 consecutively admitted neonates, who were suspected to suffer from infection within the first week of life. Neonates were retrospectively classified as infected (sepsis, clinical sepsis or pneumonia), possibly infected, or non-infected. Twenty-four infected neonates had higher serum levels of all six mediators (all P < 0.05), and 18 possibly infected neonates had higher levels of CRP, IL-6, ICAM-1 and E-selectin (all P < 0.05), than neonates without infection (n = 124). Receiver operator characteristic plots showed that CRP was the single best diagnostic test. Multiple logistic regression modelling, including various combinations of two to six mediators, consistently showed that IL-6, in addition to CRP, predicted sepsis. With infected and possibly infected neonates as the reference standard, a combined test of CRP > or = 10 mg/l and/or IL-6 > or = 20 pg/ml had a sensitivity of 85%, specificity of 62%, and negative likelihood ratio of 0.24. Using infected neonates as reference standard alone, and including possibly infected as controls, sensitivity increased to 96%, whereas specificity decreased to 58%; a negative test result (CRP < 10 mg/l and IL-6 < 20 pg/ml) ruled out sepsis with high certainty (likelihood ratio = 0.07). CRP performed best as a diagnostic test for neonatal sepsis. Diagnostic accuracy was further improved by combining CRP and IL-6, whereas the other parameters (p55, p75, ICAM-1 and E-selectin) added no further diagnostic information.

Biomarkers↗

Cause-specific trends in neonatal mortality among black and white infants, United States, 1980-1995.

OBJECTIVE: Although neonatal mortality has been declining more rapidly than postneonatal mortality in recent decades, neonatal mortality continues to account for close to two-thirds of all infant deaths. This report uses U.S. vital statistics data to describe national trends in the major causes of neonatal mortality among black and white infants from 1980 to 1995. METHODS: Mortality rates were estimated as the number of deaths due to each cause (based on International Classification of Diseases, 9th Revision, codes) divided by the number of live births during the same time period. Linear regression models and smoothed rates were used to describe trends. RESULTS: During the study period, neonatal mortality declined 4.0% per year for white infants and 2.2% per year for black infants, and the black-white gap increased from 2.0 to 2.4. By 1995, disorders relating to short gestation and low birth weight were the number one cause of neonatal death for black infants and the number two cause for white infants, had the highest black-white disparity (4.6, up from 3.3 in 1980), and accounted for almost 40% of excess deaths to black infants (up from 24% in 1980). Congenital anomalies were the number two cause of neonatal death for black infants and the highest ranked cause for white infants in 1995, and it is the only cause for which there was not a substantial excess risk to black infants. CONCLUSIONS: Large declines in neonatal mortality have been achieved in recent years, but not in the black-white gap, which has increased. Declines were slower for black than white infants overall and for almost all causes. Prevention of preterm delivery and low birth weight continue to be a priority for reducing neonatal mortality, particularly among black infants. Although congenital anomalies do not contribute substantially to the black-white gap, their diagnosis, treatment, and prevention is critical to reducing overall neonatal mortality.

Black People↗

Consequences of prenatal ultrasound diagnosis: a preliminary report on neonates with congenital malformations.

OBJECTIVE: The aim of the present study was to examine the sensitivity of prenatal ultrasound diagnosis in neonates referred for surgery, and to test whether a prenatal versus postnatal diagnosis influenced mode of delivery and neonatal outcome of these infants. PATIENTS: Thirty-six consecutive neonates with congenital diaphragmatic hernia, abdominal wall defects, bladder exstrophy and meningomyelocele were included. RESULTS: The sensitivity of prenatal ultrasound for diagnosis of the congenital malformations was 7/36 (19%) at 17-18th week of gestation, and overall 13/36 (36%). Overall sensitivity was 2/8 in neonates with congenital diaphragmatic hernia, 6/12 in neonates with abdominal wall defects, 5/13 in neonates with meningomyelocele, whereas none of three cases with bladder exstrophy were detected prenatally. No significant improvement in neonatal morbidity was found comparing the prenatally and postnatally diagnosed groups. The neonatal survival rate was 10/13 (77%) in the prenatally diagnosed group and 22/23 (96%) in the postnatally diagnosed group (p=0.12). CONCLUSIONS: The sensitivity of prenatal ultrasound in diagnosing the congenital malformations under study in a low risk population was 19% at 17-18th week of gestation and 36% throughout the pregnancy. Prenatal diagnosis altered management of labor, but caused no improvement in neonatal outcome.

Congenital Abnormalities↗

Neonatal outcome of gastroschisis and exomphalos: a 10-year review.

OBJECTIVE: To study neonatal outcomes associated with gastroschisis and exomphalos in a regional neonatal unit. METHODS: A retrospective (1988-97) data analysis to study the effect of the type of defect/surgery, mode/place of delivery and associated anomalies on time to start and reach full feeds, duration of total parental nutrition (TPN) support and total hospital stay. Exact bivariate test procedures were used for data analysis. RESULTS: Twenty-one cases of gastroschisis (17 inborn) and five cases (four inborn) of exomphalos were identified. Of these, 23.8% cases of gastroschisis and 60% of cases of exomphalos had associated gut anomalies. The survival rates for gastroschisis and exomphalos were 91 and 100%, respectively. The median time to start and reach full enteral feeds in outborn neonates was longer than in inborn neonates (9 vs 25 days, respectively, P = 0.01; and 16 vs 49 days, respectively, P = 0.01), as was the duration of TPN support (14 vs 42 days, respectively; P = 0.02). Neonates with gastroschisis had significant delays in starting and reaching full feeds compared with neonates with exomphalos (median 13 vs 4.5 days, respectively, P = 0.03; and 24 vs 8, respectively, P = 0.02) and they required prolonged support with TPN (median 23 vs 6 days, respectively; P= 0.01). Antenatal detection was significantly more frequent in inborn compared with outborn neonates (100 vs 67%, respectively; P = 0.03). The severity of associated gut anomalies and the delivery to surgery interval did not differ significantly to explain the increased morbidity in outborn neonates. Outcome was not significantly different after analysis by type of surgery and mode of delivery. CONCLUSIONS: Increased morbidity in outborn neonates may be related to factors such as temperature, care, hydration status, care of the defect and vascular compromise of prolapsed gut during prolonged transportation.

Australia↗

"Avian-type" renal medullary tubule organization causes immaturity of urine-concentrating ability in neonates.

BACKGROUND: While neonatal kidneys are not powerful in concentrating urine, they already dilute urine as efficiently as adult kidneys. To elucidate the basis for this paradoxical immaturity in urine-concentrating ability, we investigated the function of Henle's loop and collecting ducts (IMCDs) in the inner medulla of neonatal rat kidneys. METHODS: Analyses of individual renal tubules in the inner medulla of neonatal and adult rat kidneys were performed by measuring mRNA expression of membrane transporters, transepithelial voltages, and isotopic water and ion fluxes. Immunofluorescent identification of the rCCC2 and rCLC-K1 using polyclonal antibodies was also performed in neonatal and adult kidney slices. RESULTS: On day 1, the transepithelial voltages (V(Ts)) in the thin ascending limbs (tALs) and IMCDs were 14.6 +/- 1.1 mV (N = 27) and -42.7 +/- 6.1 mV (N = 14), respectively. The V(Ts) in the thin descending limbs (tDLs) were zero on day 1. The V(Ts) in the tALs were strongly inhibited by luminal bumetanide or basolateral ouabain, suggesting the presence of a NaCl reabsorption mechanism similar to that in the thick ascending limb (TAL). The diffusional voltage (V(D)) of the tAL due to transepithelial NaCl gradient was almost insensitive to a chloride channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). The V(Ts) in the IMCDs were strongly inhibited by luminal amiloride. On day 1, both the tDL and tAL were impermeable to water, indicating the water impermeability of the entire loop. Diffusional water permeability (P(dw)) and urea permeabilities (P(urea)) in the IMCDs indicated virtual impermeability to water and urea on day 1. Stimulation by vasopressin (1 nmol/L) revealed that only P(dw) was sensitive to vasopressin by day 14. A partial isoosmolar replacement of luminal urea by NaCl evoked negligible water flux across the neonatal IMCDs, indicating the absence of urea-dependent volume flux in the neonatal IMCD. These transport characteristics in each neonatal tubule are similar to those in quail kidneys. Identification of mRNAs and immunofluorescent studies for specific transporters, including rAQP-1, rCCC2, rCLC-K1, rENaC beta subunit, rAQP-2, and rUT-A1, supported these findings. CONCLUSION: We hypothesize that the renal medullary tubule organization of neonatal rats shares a tremendous similarity with avian renal medulla. The qualitative changes in the organization of medullary tubules may be primarily responsible for the immature urine-concentrating ability in mammalian neonates.

Age Factors↗

Modulation of calcium oxalate monohydrate crystallization kinetics by urine of preterm neonates.

Preterm neonates frequently develop nephrocalcinosis (NC). However, the cause has not yet been elucidated. This study focuses on the effects of urine from preterm neonates on crystallization kinetics. Urine samples were collected and renal ultrasound examinations of preterm neonates (gestational age < 32 weeks) were performed during the first weeks of life, at term, and ages 6, 12, and 24 months. The effect of urine on crystallization was determined using a seeded crystal growth system, which measures the square root of solubility product ( radicalLc), percentage of growth inhibition (GI), and agglomeration inhibition ([tm]) of calcium oxalate crystals. Data for preterm neonates in the first weeks of life (n = 19) were compared with those for full-term neonates (n = 17) and healthy adults. Moreover, the correlation between [tm] and urinary (U)citrate level was studied. Mean radicalLc (0.27 +/- 0.1 versus 0.36 +/- 0.08 mmol/L) and mean [tm] (81 +/- 32 versus 143 +/- 97 minutes) were lower and mean Ucalcium-creatinine (2.20 +/- 1.74 versus 0.46 +/- 0.73 mol/mol) and Uoxalate-creatinine ratios (0.39 +/- 0.21 versus 0.16 +/- 0.09 mol/mol) were greater in preterm neonates in the first weeks of life compared with full-term neonates (p < 0.05). Furthermore, [tm] was less than the lower limit for healthy adults for all but one preterm neonate; [tm] increased and Ucalcium-creatinine and Uoxalate-creatinine ratios decreased with age (p < 0.005). There was a correlation between [tm] and citrate excretion (coefficient of 38; P < 0.001). Patients with and without NC at term did not differ statistically in mean radicalLc, percentage of GI, or [tm]. In conclusion, urine from preterm neonates in the first weeks of life is highly supersaturated and has a defective ability to inhibit calcium oxalate crystal agglomeration. This ability improves with age and is citrate mediated. We suggest that both the high level of supersaturation and defective ability to inhibit calcium oxalate crystal agglomeration contribute to the high incidence of NC.

Adult↗

[Inhibition of meconium induced activation of granulocytes from neonates and adults by pentoxyphylline].

BACKGROUND: Neutrophil activation plays a crucial role in the pathogenesis of the meconium aspiration syndrome. Therefore antiinflammatory strategies may offer therapeutic options. The methylxanthinderivative pentoxyphylline (PTX) is known to inhibit the tumor necrosis factor alpha-synthesis and neutrophil degranulation and thus may have beneficial effects on meconium-induced pulmonary inflammation. Effects of PTX on PMN-degranulation in neonatal whole blood have not yet been studied. PATIENTS AND METHODS: Heparin-anticoagulated (3 IE/ml) whole blood of healthy neonates (n = 6) and adult volunteers (n = 6) was incubated for 45 min. Spontaneous PMN-degranulation was compared with meconium-induced (3 mg/ml) and PTX-inhibited (0,025 - 0,4 mg/ml) degranulation by means of elastase (EL) and lactoferrin (LF) release from azurophilic and specific granules. EL- and LF plasma concentration was measured by immunoluminometric methods. RESULTS: Spontaneous degranulation of neonatal PMN was found to be significantly increased after 15 minutes compared with cells from adults (EL and LF concentration: 674 and 660 ng/10 6 PMN vs. 284 and 261 ng/10 6 PMN). At 45 minutes adult PMN showed an acceleration of degranulation in contrast to neonatal cells (EL and LF: 1827 and 1232 ng/10 6 PMN vs. 1400 and 860 ng/10 6 PMN). In presence of PTX (0,4 mg/ml) spontaneous release of EL and LF from neonatal PMN was inhibited by nearly 70 % at 45 min. while degranulation from adult PMN was found to be completely inhibited at 15 min. and reduced by 82 % and 78 % at 45 min. In presence of meconium (3 mg/ml) an increased degranulation of EL from PMN of both neonates and adults (317 % and 170 %) could be observed while LF release was found to be increased from neonatal cells only (267 % and 113 % respectively). PTX inhibited meconium-induced EL release in blood of bath neonates and adults by 63 % and 66 %, while LF release was inhibited by 72 % and 57 % respectively. CONCLUSION: Neonatal PMN exhibit an increased degranulation from azurophilic and specific granules compared with cells from adults. PTX was found to be an effective inhibitor of spontaneous and meconium induced PMN degranulation and may offer new therapeutic options.

Adult↗

Maternal smoking and partial exchange transfusion for neonatal polycythemia.

The aim of this study was to determine if maternal smoking was associated with an increased need for partial exchange transfusion for symptomatic polycythemia in term neonates. The study population consisted of 8,961 term neonates, of whom 28.7% were categorized as babies born to mothers who smoked. The incidence of partial exchange transfusion was determined in neonates whose mothers smoked and in neonates of nonsmokers. Partial exchange transfusion was performed in 41 neonates of mothers who smoked (1.59%; n = 2,572) versus 41 neonates of nonsmokers (0.64%; n = 6,389) ( p = 0.000). In babies requiring a partial exchange transfusion birth weights were 2,908 +/- 659 g (smokers) versus 3,474 +/- 770 g, (nonsmokers) ( p <0.001) and the babies born to mothers who smoked were 9 times more likely to be small-for-gestational age (SGA) and 5 times less likely to be large-for-gestational age (LGA). Term neonates of mothers who smoke during pregnancy require a partial exchange transfusion for neonatal polycythemia approximately two and a half times as often as neonates of mothers who do not smoke.

Case-Control Studies↗

Long-term course of neonatal diabetes.

BACKGROUND: Neonatal diabetes mellitus--defined here as hyperglycemia occurring within the first month of life that lasts for at least two weeks and requires insulin therapy--is a very rare form of the disease. Little is known about it, particularly with respect to its long-term course. METHODS: We studied two brothers who had neonatal diabetes and obtained follow-up information on 34 patients described in the literature as well as information on 21 additional patients. Forty-seven of the patients had neonatal diabetes, as defined above, and in 10 others the onset was between the first and third month of life. RESULTS: Twenty-six of the 57 infants had permanent diabetes, 18 had transient diabetes, and 13 had transient diabetes that recurred when they were 7 to 20 years old. Neonatal diabetes was associated with the Wolcott-Rallison syndrome in six infants, hyperuricemia due to phosphoribosyl-ATP pyrophosphatase hyperactivity in two, and celiac disease in two. Forty-one of 45 neonates in whom the duration of gestation and birth weight were known were small for their gestational ages. There were two pairs of affected twins and four other families with two or more infants with neonatal diabetes, but only three parents had diabetes. The incidence of neonatal diabetes mellitus in Germany has been estimated to be 1 in 500,000 neonates. CONCLUSIONS: Neonatal diabetes differs from insulin-dependent diabetes in that its course is highly variable. Some patients have permanent diabetes, but others have transient or lasting remissions.

Diabetes Mellitus↗

Neonatal sepsis and death after multiple courses of antenatal betamethasone therapy.

OBJECTIVE: This study was undertaken to compare the effects of single versus multiple courses of betamethasone therapy on the frequencies of neonatal outcomes and perinatal infectious morbidity among singleton pregnancies complicated by preterm delivery. STUDY DESIGN: We performed a nonconcurrent prospective analysis of singleton pregnancies delivered between 24 and 34 weeks' gestation after antenatal betamethasone exposure. Patients were categorized into two groups according to betamethasone exposure: (1) two 12-mg doses in a 24-hour interval on admission (single-course group) and (2) repeated dosing after the initial single course (multiple-course group). All patients received prophylactic antibiotics for group B streptococci. Any patients with ruptured membranes for >24 hours before delivery were excluded. Data were analyzed with the Student t test, the chi(2) test, and the Fisher exact test. Multiple logistic regression analyses were performed to examine the effect of each steroid dosing regimen on early-onset neonatal sepsis and neonatal death. P <.05 was considered significant for all 2-tailed tests. RESULTS: A total of 453 patients were included, with 267 in the single-course group and 186 in the multiple-course group. The two groups were similar with respect to maternal demographic characteristics, gestational age at delivery, mode of delivery, birth weight, and maternal group B streptococcal colonization. Multiple courses were significantly associated with early-onset neonatal sepsis (odds ratio, 5.00; 95% confidence interval, 1.3-23. 2), chorioamnionitis (odds ratio, 9.96; 95% confidence interval, 2. 1-64.6), endometritis (odds ratio, 3.61; 95% confidence interval, 1. 7-8.1), and neonatal death (odds ratio, 2.92; 95% confidence interval, 1.3-6.9). The frequencies of the other neonatal outcomes analyzed, including respiratory distress syndrome and grade III or IV intraventricular hemorrhage, were similar between the 2 groups. Multiple logistic regression analyses confirmed that multiple courses of antenatal betamethasone were independently associated with early-onset neonatal sepsis (odds ratio, 1.25; 95% confidence interval, 1.1-1.9) and neonatal death (odds ratio, 1.70; 95% confidence interval, 1.1-1.9). CONCLUSIONS: Multiple courses of antenatal betamethasone are associated with increased risks of perinatal infectious morbidity and neonatal death.

Adult↗

Adverse maternal and neonatal outcome of prolonged course of magnesium sulfate tocolysis.

BACKGROUND: Magnesium sulfate continues to be widely used as a tocolytic agent despite a paucity of evidence supporting its use. Many practitioners use prolonged courses of magnesium sulfate, sometimes for months. This study was conducted to determine maternal and neonatal outcome of patients exposed to prolonged tocolytic magnesium sulfate. METHODS: A retrospective review of maternal and neonatal charts (1995-2003) of pregnancies that received tocolytic magnesium sulfate. Cases who received magnesium sulfate >48 h (n=78) were compared to controls who received it < or =48 h (n=77) for maternal side effects and neonatal outcome. RESULTS: Cases were more likely to be nulliparous (55.1% versus 37.7%, p=0.044), multiple gestations (33.3% versus 10.4%, p=0.001), and of lower gestational age (29.0+/-3.9 versus 30.5+/-3.8 weeks, p=0.017) compared to controls. The median magnesium sulfate infused was 154 (78-5,500) versus 54 (8-86) g (p<0.001) and the highest maternal magnesium level was 6.5+/-1.7 versus 5.6+/-1.9 mg/dl (p=0.002) in cases and controls, respectively. Cases were more likely to have > or =1 adverse side effect (30.8% versus 15.6%, p=0.045). The median neonatal magnesium level was significantly higher in cases (3.3 (1.4-7.2) versus 2.6 (1.1-5.2) mg/dl, p=0.016); however, neonatal mortality and other neonatal morbidity rates were similar in both groups. Abnormal bone mineralization was encountered in 3 neonates (cases). CONCLUSIONS: Maternal morbidity rate is higher with prolonged intake of tocolytic magnesium sulfate compared to < or =48-h regimen. Despite similar neonatal morbidity and mortality rates, bone demineralization in the neonates may be encountered.

Adult↗

Six day antimicrobial therapy for early-onset group B streptococcal infection in near-term and term neonates.

Antibiotics for the treatment of group B streptococcal (GBS) infection are usually given for 7-10 d. The aim of this prospective investigation was to study whether antibiotic treatment for 6 d is sufficient to treat early-onset GBS infection in term and near-term neonates. During a 2 y period 67 neonates of GBS-positive mothers developed GBS infection and were admitted to the neonatal intensive care unit. All neonates showed clinical signs of infection, C-reactive protein levels > 20 mg/l and/or elevated immature to total neutrophil ratio > 0.25. Two groups were differentiated: 10 neonates with proven sepsis with GBS-positive blood cultures (15%) and 57 neonates with presumed GBS infection with negative blood cultures but with GBS-positive surface swab cultures of ear (68%), nasopharyngeal (21%) or gastric aspirate (16%). All patients were GBS positive in 1 or more cultures. Antimicrobial therapy with ampicillin and cefotaxime was discontinued after 6 d. At that time all neonates were asymptomatic and laboratory results were normal. No relapse or death within 4 weeks after therapy was detected. In conclusion, antibiotic therapy for 6 d was sufficient to treat 10 neonates with proven and 57 neonates with presumed early-onset GBS infection. Owing to the small sample size, further studies are needed to show significant differences to longer therapy regimens.

Anti-Bacterial Agents↗

Levels of soluble ICAM-1 in premature and full-term neonates with infection.

BACKGROUND: Infection in the neonatal period is an extremely serious condition and diagnosis is difficult. C-reactive protein (CRP) is widely used as a marker of infection; however, its usefulness is limited in the early phase. The role of soluble intracellular adhesion molecule-1 (sICAM-1), an adhesion molecule, has been examined in recent studies as an early marker of neonatal infection with controversial results. AIM: Assessment of sICAM-1 concentrations and correlation with CRP, which is the currently used marker of infection, in order to use sICAM as an early diagnostic tool in neonates suspected for infection METHODS: Blood samples and blood cultures were obtained from two groups of pre-term and full-term neonates with clinical suspicion of infection prior to the initiation of antibiotics. The sICAM-1 and CRP values were compared with the corresponding noninfected ones (n = 10 each). RESULTS: The sICAM-1 levels were found increased in the group of both premature and term neonates with infection compared with the corresponding healthy ones (P < 0.0001). Prematurity combined with infection resulted in excessive increase of the levels of sICAM-1 in comparison with full-term infected newborns (p < 0.001). CRP values were normal in all samples except one in both full-term and premature infected neonates on day 1 of clinically suspected infection. Serial detection of CRP values on days 2 and 4 of infection revealed a pattern according to which CRP values in premature neonates continued rising, while in the group of full terms these values, after rising on the second day, lowered on day 4. CONCLUSIONS: Increased sICAM-1 levels can be detected early in both full-term and premature neonates with sepsis while CRP levels are within normal range at the same time. Assessment of sICAM-1 concentrations may be used as a diagnostic tool in neonates suspected for infection, resulting in earlier initiation of antibiotic therapy and therefore improving their outcome.

Bacterial Infections↗

Neonatal exposure to the glutamate receptor antagonist MK-801: effects on locomotor activity and pre-pulse inhibition before and after sexual maturity in rats.

Neonatal lesions of the ventral hippocampus in rats lead to post- but not pre-pubertal behavioral changes suggesting adolescent onset of dopaminergic hypersensitivity and providing an animal model of schizophrenia. Neonatal exposure to glutamate receptor antagonists produces accelerated apoptosis leading to neuronal loss in central nervous system structures including the hippocampus. This suggested that neonatal MK-801 might lead to behavioural changes like those reported following ventral hippocampal lesions. Thus, rats received MK-801 (0, 0.5, 1.0 mg/kg ip) on postnatal day 3 (P3) and were tested pre- (P35) and post-pubertally (P56). MK-801 produced an increase in TUNEL staining in the hippocampus and other forebrain structures, confirming the induction of apoptosis. Results showed little difference in locomotor activity between neonatal saline- and MK-801-treated groups during habituation or following saline injection but increased activity was seen in the 0.5 mg/kg MK-801 group following amphetamine (1.5 mg/kg i.p.) at P35 but not P56. In tests of pre-pulse inhibition (PPI), neonatal saline and MK-801 groups showed stable startle amplitudes, minimal responding to the pre-pulse stimuli alone, an increase in PPI with increases in pre-pulse intensity, and reduced PPI with apomorphine (0.1 mg/kg s.c.). At P56, neonatal MK-801 groups tested following vehicle showed less sensitivity to changes in pre-pulse intensity. It was concluded that neonatal MK-801 increases apoptotic cell loss in the hippocampus but does not produce behavioural effects like those seen after neonatal ventral hippocampal lesions. However, neonatal MK-801 did lead to increases in locomotor activity in juveniles but not adults and reduced sensitivity to pre-pulse intensity in PPI tests in adulthood.

Journal Article↗

Alterations in Thl/Th2 cytokine concentrations in early neonatal life.

OBJECTIVE: To determine postnatal changes in neonatal serum concentrations of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and its soluble receptor (sIL-4R). METHODS: Forty-five healthy term neonates, 25 of the neonates' mothers and 27 healthy adults (controls) participated in the study. Cytokine concentrations were measured in blood samples from the umbilical cord, from the neonates on the 1st and 5th day after birth, from mothers and from controls. RESULTS: IFN-gamma concentrations were significantly lower in the umbilical cord, compared to concentrations in the controls (p < 0.04), and increased significantly from the umbilical cord to levels in neonates on day 5 (p < 0.03). In mothers and the umbilical cord, IFN-gamma concentrations were dependent on the mode of delivery, being higher after vaginal delivery than after elective Cesarean section (p < 0.005; p < 0.006, respectively). IL-4 concentrations in the umbilical cord for 1-day and 5-day neonates were significantly elevated compared to those in mothers (p < 0.001; p < 0.0007; p < 0.0001, respectively) and controls (p < 0.05; p < 0.01; p < 0.006, respectively). sIL-4R concentrations in all neonatal samples were significantly elevated compared to those in controls (p < 0.0001), the highest being found in 1-day-old neonates. A strong negative correlation was found between IL-4 and sIL-4R concentrations in 1- and 5-day-old neonates (r = -0.48, p < 0.002; r = -0.45, p < 0.0065, respectively). Moreover, IFN-gamma/IL-4 ratio increased significantly from the umbilical cord to 5 days of life (p < 0.03). CONCLUSIONS: Our findings indicate an earlier development of IL-4 than IFN-gamma, which could be viewed as a developmental characteristic in the ontogeny of the immune system.

Adult↗