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Flow cytometric measurement of HLA-DR expression on circulating monocytes in healthy and sick neonates using monocyte negative selection.

UNLABELLED: The aim of this study was to investigate the effect of prematurity, neonatal sepsis, respiratory distress syndrome (RDS) and perinatal asphyxia on monocyte HLA-DR expression of neonates using a flow cytometric method based on monocyte negative selection. The subjects were one hundred and thirty-one neonates (59 healthy, 44 septicaemic, 20 with RDS and eight with perinatal asphyxia) and 20 healthy adults. Monocyte HLA-DR expression was measured using one-colour HLA-DR labelling in a gate for monocytes obtained using the combination of CD3-CD19--PE/CD15--FITC MoAbs. In addition, the common dual staining method using MoAbs against two CD14 epitopes (TUK4, MO2) was evaluated. With the one-colour HLA-DR labelling higher purity and recovery values of monocytes were achieved than with the dual labelling METHOD: Healthy neonates had significantly lower percentages of HLA-DR(+) monocytes than adults (69 +/- 13% versus 91.5 +/- 2.5%) and comparable mean fluorescence intensity (MFI) (119 +/- 25 versus 131 +/- 26). Values did not differ significantly between healthy term and preterm neonates. Preterm neonates with RDS had a significantly lower percentage of HLA-DR(+) monocytes than the healthy preterm neonates. In neonates with asphyxia both parameters were comparable to those of the healthy ones. Septicaemic neonates presented significantly lower values of both parameters than the healthy, RDS and asphyxiated neonates. Monocyte negative selection provides a reliable estimation of HLA-DR expression on monocytes. Expression of monocyte HLA-DR is lower in healthy neonates in comparison with adults and is further decreased in neonates with sepsis and RDS, but it is not influenced by prematurity and perinatal asphyxia.

Adult↗

Metabolism and nutritional support in the surgical neonate.

Various factors can influence the metabolism of surgical neonates. These include prematurity, operative stress, critical illness, and sepsis. The nutritional management of surgical infants with congenital or acquired intestinal abnormalities has improved after the introduction of parenteral nutrition. This article is focused on the energy and protein metabolism of surgical neonates with particular reference to the metabolic response to operative trauma and sepsis. The metabolic utilization of intravenous nutrients also is discussed. The metabolic response to operative trauma is different between neonates and adults. Infants have high rates of protein turnover and are avid retainers of nitrogen. Energy expenditure increases only transiently (4 to 6 hours) after major surgery in neonates. Protein turnover and catabolism seems not to be affected by major operative procedures in neonates. In neonates on parenteral nutrition, carbohydrate and fat have an equivalent effect on protein metabolism. The main determinants of fat utilization are carbohydrate intake and resting energy expenditure. Parenteral nutrition in surgical neonates is associated with increased production of oxygen-free radicals. This seems to be related to intravenous fat administration. Promoting fat utilization by reducing the carbohydrate to fat ratio in the intravenous diet reduces free radical activity to a similar extent as fat exclusion. Glutamine appears to be safe for use in neonates and infants and is "conditionally essential" in very-low birth weight infants and in septic neonates. Enteral glutamine supplementation in very-low birth weight infants reduces the risk of sepsis. The metabolism of surgical neonates is affected by operative trauma, critical illness, and sepsis. Nutritional support in surgical neonates has a profound impact on outcome. Exogenous glutamine can modulate immune, metabolic, and inflammatory responses. Further investigations are needed to clarify the clinical benefit of parenteral or enteral glutamine administration in surgical neonates.

Anesthesia, General↗

Impact of ECMO on neonatal mortality in Michigan (1980-1999).

PURPOSE: Although extracorporeal membrane oxygenation (ECMO) is a potentially lifesaving intervention, the effect of ECMO on neonatal mortality has never been evaluated. In this study, we examined the relationship between increased ECMO utilization and its effect on the neonatal mortality rate in the state of Michigan. METHODS: Neonatal mortality data were obtained from the Michigan State Department of Community Health. Data included total annual live births, total neonatal deaths, and deaths from respiratory causes in neonates > or =35 weeks' gestational age (ie, potential ECMO candidates). Pooled ECMO patient data from Michigan's 3 ECMO centers were obtained from the Extracorporeal Life Support Organization (ELSO) Registry. Associations between ECMO volume and neonatal mortality rates were assessed using simple linear regression. A scatterplot of ECMO volume and mortality rates was created, and the resulting fitted regression lines were superimposed on the plots. Statistical significance of the associations (ie, difference in slope of the regression line from zero) were based on a standard 2-sided Wald test for the regression slope parameter. RESULTS: From 1980 through 1999, 1,061 neonates were treated with ECMO in Michigan, and 875 (82.5%) survived. When annual neonatal mortality rate (from all causes) and the rate from respiratory causes versus ECMO volume (cases per year) are superimposed with fitted regression lines, both are significantly different from zero (P =.041 and P =.002, respectively). The model predicts that for every 100 neonates treated with ECMO in Michigan, 38 lives are saved. The model also can be used to predict the annual neonatal mortality rate in Michigan if ECMO had not been utilized. CONCLUSIONS: A strong association exists between ECMO volume and observed reductions in neonatal mortality seen in Michigan over the last 2 decades. This is the first study to show an association between ECMO and neonatal mortality rate at the population level.

Extracorporeal Membrane Oxygenation↗

Association of ABO incompatibility with elevation of nucleated red blood cell counts in term neonates.

OBJECTIVE: Nucleated red blood cells in the circulation in term neonates have been associated with a wide range of pathologic conditions. We sought to examine the relationship between nucleated red blood cells in the circulation of term neonates and maternal-neonatal blood type compatibility. STUDY DESIGN: We prospectively collected umbilical blood from all live-born neonates delivered at our institution. Venous blood was analyzed for nucleated red blood cells and is reported as the number of nucleated red blood cells per 100 white blood cells. We reviewed maternal and neonatal records for neonates born at > or =37 weeks' gestation for correlative clinical data. Statistical analysis was performed with the SAS statistical software package (version 6.12; SAS Institute, Inc, Cary, NC). Kruskal-Wallis analysis was used as a nonparametric test. RESULTS: We evaluated 1661 neonates delivered during the study period and found a mean (+/-SD) of 9.29 +/- 18.56 nucleated red blood cells per 100 white blood cells (range, 0-327 nucleated red blood cells per 100 white blood cells). Nucleated red blood cell counts were lower in ABO-compatible maternal-fetal dyads (mean +/- SD, 8.29 +/- 12.84 nucleated red blood cells per 100 white blood cells; range, 0-216 nucleated red blood cells per 100 white blood cells) than in ABO-incompatible dyads (mean +/- SD, 13.16 +/- 13.16 nucleated red blood cells per 100 white blood cells; range, 0-327 nucleated red blood cells/100 white blood cells; P =.006). Neonates of mothers with blood groups A and B had significantly lower nucleated red blood cell counts (P <.05). Dyads with maternal type O and neonate type B had significantly higher nucleated red blood cell counts (P <.002). Nonparametric testing determined that type O mother and type B neonate combinations had significantly higher umbilical cord nucleated red blood cell counts (P <.001). CONCLUSION: Maternal-fetal ABO incompatibility is associated with elevation of nucleated red blood cell count in term neonates. Nucleated red blood cell elevation does not always connote a serious pathologic process, however, because ABO incompatibility usually does not adversely affect neonatal outcome. The clinical significance of an elevated nucleated red blood cell count thus is limited.

ABO Blood-Group System↗

Identification of febrile neonates unlikely to have bacterial infections.

OBJECTIVE: A prospective study was undertaken to evaluate the usefulness of low risk criteria for identifying febrile neonates unlikely to have bacterial infections, particularly bacteremia and meningitis. Using these criteria we wished to check whether these low risk neonates can be safely managed as inpatients under close observation but without receiving empiric antibiotic therapy. STUDY DESIGN: We conducted a prospective study of 250 consecutive infants 28 days of age or less (range, 4 to 28 days) who had rectal temperatures of at least 38 degrees C. After a complete history, physical examination and sepsis workup, the 131 febrile neonates with clinical and laboratory findings indicating low risk for bacterial infections were hospitalized, closely observed and not given antibiotics. The low risk criteria used to identify these neonates included well appearance; absence of physical signs of an ear, eye or soft tissue infection; a white blood cell count of 5000 to 15,000/mm3, a neutrophil band form count of < 1500/mm3, a spun urine specimen that had < 10 white blood cells per high power field on microscopy and a C-reactive protein value of < 20 mg/l. The remaining 119 febrile neonates who did not meet the low risk criteria were hospitalized and given empiric antibiotics pending culture results. RESULTS: The overall incidence of bacterial infections in the 250 febrile neonates was 16.4% (41 neonates) with bacteremia and/or meningitis occurring in 4.4% (11 neonates). Of the 131 low risk neonates only one (0.8%) had a bacterial infection (urinary tract infection) compared with 40 (33.6%) among the 119 who did not meet the criteria (P < 0.05). The negative predictive value of these criteria for excluding bacterial infections was 99.2% (95% confidence interval, 97.7% to 100%). For bacteremia and meningitis this figure became 100%. However, the positive predictive value and specificity of the criteria were too low to identify all febrile neonates with bacterial infections. Among the low risk group 58 (44.3%) were reclassified on the second or third hospital day, because of continued fever (35), poor activity (14) and white blood cell count > 15000/mm3 on a repeat blood test (9). They were given antibiotics, but only 1 had a urinary tract infection. This patient was then treated with a 7-day course of antibiotics. All low risk neonates recovered uneventfully with no relapses observed during their hospital stay or at the time of minimum 1-week outpatient follow-up visits. CONCLUSION: By the low risk criteria a substantial number of febrile neonates at low risk for bacterial infections can be identified and managed safely as inpatients without antibiotic therapy.

Anti-Bacterial Agents↗

Early neonatal presentations to the pediatric emergency department.

UNLABELLED: As a result of shorter postpartum hospital stays, many medical concerns, which traditionally have been managed in newborn nurseries, are presenting to the pediatric emergency department (PED). We undertook a study to determine the profile of early neonatal visits to the PED. In addition, we examined the influence of maternal factors and length of postpartum hospital stay on PED visits. METHODS: We conducted a retrospective chart review of all neonates < or = 8 days of age who presented to the PED between June 1990 and May 1995. Data gathered from neonatal and corresponding maternal charts included neonatal and maternal demographics, prenatal instruction, length of postpartum stay, source of referral, age at presentation, presenting complaint, diagnosis, disposition, and course in hospital, if admitted. RESULTS: A total of 559 neonatal visits were identified. Neonatal use of the PED increased 245% compared to an overall increase in PED use of 8.7% during the study period. Jaundice, difficulty breathing, feeding problems, and irritability were the most common presenting complaints while the most frequent diagnoses were normal physiology, jaundice, feeding problems, and query sepsis. Our overall admission rate was 33%. Self-referred patients were at a significantly lower risk of serious illness (16% admitted vs 49 % of consult patients). The self-referral rate increased with maternal age less than 21, single marital status, no prenatal classes, and primiparity. The length of postpartum hospital stay was identified in 389 neonates (55 early discharge (ED) and 334 non-early discharge (NED). The ED group had a significant increase in annual PED utilization compared to the NED group changing from 2% of the total population in study year 1 to over 31% in the final year. The ED and NED groups did not differ significantly with respect to the majority of chief complaints, frequency of PED diagnoses, admission rates, or maternal characteristics. CONCLUSIONS: Use of the PED by neonates < or = 8 days of age increased significantly over the study period. The majority of neonates presented by self-referral and were discharged with advice only. Mothers who were young, single, primiparous, or who had not attended prenatal classes presented with neonates who were less seriously ill. Although ED neonates represent an enlarging subset of PED visitors, they do not appear to differ significantly from NED neonates with respect to PED complaints, diagnoses, and disposition.

Adult↗

Role of endothelin in neonatal morphine tolerance.

Management of neonatal opioid tolerance and withdrawal symptoms remains a major challenge in neonatal intensive care units. We provide evidence that central endothelin (ET) mechanisms are involved in the development of morphine tolerance in neonatal rats. Pregnant rats were rendered tolerant to morphine and rat pups were delivered by cesarean section. The effect of morphine tolerance on characteristics of ET receptors in neonatal rats was determined. The affinity (Kd) and density (Bmax) of [I]ET-1 binding in the brain was found to be similar in placebo and morphine-tolerant neonatal rats. Morphine and ET-1-induced G-protein stimulation was determined in placebo and morphine-tolerant neonatal rats by [S]GTPgammaS binding assay. Morphine produced significantly lower (P < 0.05) maximal stimulation in morphine-tolerant neonatal rats (33.10%) when compared with placebo-treated neonatal rats (90.90%). Maximal stimulation produced by ET-1 in morphine-tolerant neonatal rats (41.26%) was also significantly lower (P < 0.05) as compared with placebo-treated neonatal rats (92.23%). This is the first report indicating the involvement of ET in neonatal morphine tolerance as evidenced by attenuation of ET-1-induced stimulation of GTP binding in neonatal rats tolerant to morphine.

Analgesics, Opioid↗

Anthropometric measurements for neonates, 23 to 29 weeks gestation, in the 1990s.

Reference data describing weight, length, and head circumference (anthropometric measurements) at birth were published by Lubchenco and Usher before 1970. Few attempts have been made to investigate whether these data are appropriate for today's cohort of preterm neonates. We analysed anthropometric data for neonates born between 23 and 29 weeks' gestation. Reference charts were developed from the measurements obtained from neonatal records, and gestational age, obtained from maternal charts, on 975 neonates delivered at four neonatal centres in Michigan during 1992 and 1997. The analysis was confined to children with gestational age that was consistent or within 7 days by last menstrual period, obstetric examination, ultrasound and neonatal determinations. At 23 to 29 weeks' gestation, ethnicity and multiple births did not have any significant impact on birthweight but girls were lighter. We compared our anthropometric charts with those presently being used at many neonatal centres. In our study, physical measurements at birth of preterm neonates born between 1992 and 1997 were significantly different from those currently used to assess growth status. Furthermore data derived from published studies that utilised birth certificates with gestational age based on last menstrual period seem to overestimate birthweight. For preterm infants, our findings are concordant with recently published values from 18 states of the US. Because of improved survival, gestational age assessment and perinatal care of preterm neonates, development of new reference anthropometric measurements for neonates is overdue. Our Michigan data of 23-29 weeks preterm provides new national reference values, which we recommend for use in US neonatal centres for extremely preterm neonates.

Anthropometry↗

Thrombin generation in factor VIII-depleted neonatal plasma: nearly normal because of physiologically low antithrombin and tissue factor pathway inhibitor.

BACKGROUND: Bleeding in hemophilic neonates has a low incidence. A possible explanation for this could be the peculiarities of the neonatal hemostatic system, especially low levels of the inhibitors tissue factor pathway inhibitor (TFPI) and antithrombin (AT). OBJECTIVE: We investigated the influence of an elevation of these inhibitors to adult levels on the thrombin generation (TG) in normal neonatal plasma and factor (F) VIII-depleted neonatal plasma by means of incubation with anti-FVIII-antibodies. PATIENTS/METHODS: TG was measured after activation with low amounts of tissue factor (TF) by using Calibrated Automated Thrombography. RESULTS: TG in FVIII-depleted neonatal plasma was nearly as high as in normal neonatal plasma. TG decreased after elevation of AT in both neonatal plasmas. After elevation of TFPI TG decreased much more in FVIII-depleted neonatal plasma than in normal neonatal plasma. After elevation of both inhibitors their synergistic effect led to a stronger decrease of TG in FVIII-depleted neonatal plasma. TG measured in plasma of one hemophilic newborn showed the same pattern as in FVIII-depleted neonatal plasma. CONCLUSION: Our observation provides a biochemical basis for the rare bleeding in hemophilic neonates and shows the important role of the natural inhibitors in the hemostatic system of hemophilic patients.

Adult↗

L-type Ca2+ currents in ventricular myocytes from neonatal and adult rats.

Postnatal changes in the slow Ca2+ current (I(Ca)(L)) were investigated in freshly isolated ventricular myocytes from neonatal (1-7 days old) and adult (2-4 months old) rats, using whole-cell voltage clamp and single-channel recordings. The membrane capacitance (mean+/-SEM) averaged 23.2+/-0.5 pF in neonates (n = 163) and 140+/-4.1 pF in adults (n = 143). I(Ca)(L) was measured as the peak inward current at a test potential of +10 mV (or +20 mV) by applying a 300-ms pulse from a holding potential of -40 mV; 1.8 mM Ca2+ was used as charge carrier. The basal ICa(L) density was 6.7+/-0.2 pA/pF in neonatal and 7.8+/-0.2 pA/pF in adult cells (p < 0.05). The time course of inactivation of the fast component (at +10 ms) was significantly longer in the neonatal (10.7+/-1.4 ms) than in the adult (6.6+/-0.4 ms) cells (p < 0.05). Ryanodine (10+/-M) significantly increased this value to 18.0+/-1.9 in neonate (n = 8) and to 17.7+/-2.0 in adult (n = 9). For steady-state inactivation, the half-inactivation potential (Vh) was not changed in either group. For steady-state activation, Vh was 5.1 mV in the neonatal (n = 6) and -7.9 mV in the adult cells (n = 7). Single-channel recordings revealed that long openings (mode-2 behavior) were occasionally observed in the neonatal cells (11 events from 1080 traces/11 cells), but not in the adult cells (400 traces/4 cells). Slope conductance was 24 pS in both the neonatal and adult cells. Results in rat ventricular myocytes suggest the following: (i) the peak Ca2+ current density is already well developed in the neonatal period (being about 85% of the adult value); (ii) the fast component of inactivation is slower in neonates than in adults; and (iii) naturally occurring long openings are occasionally observed in the neonatal stage but not in the adult. Thus, the L-type Ca2+ channels of the neonate were slightly lower in density, were inactivated more slowly, and occasionally exhibited mode-2 behavior as compared with those of the adult.

Age Factors↗

Oxygen tolerance in neonatal rats: role of subcellular superoxide generation.

We compared the superoxide anion generating capacity of subcellular fractions from the lungs of neonatal and adult rats. Microsomal and mitochondrial fractions from adult rats produced approximately three times more superoxide (nanomoles per minute per milligram protein) than fractions from neonatal rats in the presence of 100% O2. Subcellular superoxide anion generating capacity was also examined in adult and neonatal rats exposed to greater than 95% fractional concentration of O2 in inspired gas. The O2- produced by mitochondrial and microsomal fractions of adult and neonatal rats increased above control levels for the first 24 h and declined below control values after 48 h of exposure in adults, whereas the elevated O2- production was sustained in microsomal fractions of neonates through 60 h. During the course of hyperoxic exposure, the largest difference in the superoxide generating capacity between adult and neonate was observed after 8-24 h of hyperoxia. The microsomal and mitochondrial fractions from adult rats produced three to seven times more O2- compared with neonatal rats. Cu,Zn superoxide dismutase (SOD) increased during the course of hyperoxia only in neonates at 8, 24, and 48 h of exposure. No change was observed in the activity of Mn SOD. The ratio of SOD activity (units per lung) to subcellular superoxide generating capacity (nanomoles per minute per lung) was calculated for the normal adults and neonates. The ratio for adult rats averaged 23 and 17 for mitochondrial and microsomal fractions, respectively, and 51 for neonatal rats for both subcellular fractions under normoxic conditions. These results suggest that O2- tolerance of neonates may be explained by the favorable balance between antioxidant defenses and subcellular superoxide generating capacity. The role of increased activity of Cu,Zn SOD as an accompanying or a causative phenomenon in O2 tolerance of neonates could not be determined from these experiments.

Aging↗

Islet cell response in the neonatal rat after exposure to a high-fat diet during pregnancy.

Although pancreatic beta-cells are capable of adapting their mass in response to insulin requirements, evidence has shown that a dietary insult could compromise this ability. Fetal malnutrition has been linked to low birth weight and the development of type 2 diabetes later in life, while reduced beta-cell mass has been reported in adult rats fed a high-fat diet (HFD). Reported here are the effects of exposure to a HFD, during different periods of gestation, on neonatal rat weight and beta- and alpha-cell development. The experimental groups were composed of neonatal offspring obtained from Wistar rats fed a high-fat (40% as energy) diet for either the first (HF1), second (HF2), or third (HF3) week, or all three (HF1-3) weeks of gestation. Neonatal weights and circulating glucose and insulin concentrations were measured on postnatal day 1, after which the pancreata were excised and processed for histological immunocytochemical examination and image analysis. HF1 and HF2 neonates were hypoglycemic, whereas HF1-3 neonates were hyperglycemic. Low birth weights were observed only in HF1 neonates. No significant differences were detected in the circulating insulin concentrations in the neonates, although beta-cell volume and numbers were reduced in HF1-3 neonates. beta-cell numbers also declined in HF1 and HF3 neonates. alpha-cell volume, number and size were, however, increased in HF1-3 neonates. alpha-cell size was also increased in HF1 and HF3 neonates. In neonates, exposure to a maternal HFD throughout gestation was found to have the most adverse effect on beta-cell development and resulted in hyperglycemia.

Animals↗

Amniotic fluid tumor necrosis factor-alpha is a marker for the prediction of early-onset neonatal sepsis in preterm labor.

BACKGROUND: Our purpose was to determine whether amniotic fluid concentrations of tumor necrosis factor-alpha are of value in the prediction of early-onset neonatal sepsis (proven or suspected) in patients with preterm labor and intact membranes. METHODS: The relationship between amniotic fluid tumor necrosis factor-alpha concentrations and early-onset neonatal sepsis was examined in 59 consecutive patients with preterm labor and intact membranes who delivered preterm neonates within 72 h after transabdominal amniocentesis. Early-onset neonatal sepsis was defined either as the presence of a positive blood culture or as suspected sepsis within 72 h of delivery. Tumor necrosis factor-alpha was determined by enzyme-linked immunosorbent assays. RESULTS: Patients delivering neonates with early-onset neonatal sepsis had significantly higher median amniotic fluid TNF-alpha concentrations than patients delivering neonates without early-onset neonatal sepsis (p < 0.0005). An amniotic fluid tumor necrosis factor-alpha concentration > or =41 pg/ml had a sensitivity of 82% (23/29) and specificity of 79% (38/48) in the prediction of early-onset neonatal sepsis. Multiple logistic regression indicated that elevated amniotic fluid tumor necrosis factor-alpha (> or =41 pg/ml) was the only independent predictor of early-onset neonatal sepsis (odds ratio 12.9, 95% confidence interval 1.3-125.3, p=0.01) after correction for known confounding variables. CONCLUSIONS: (1) Amniotic fluid tumor necrosis factor-alpha is a marker for the prediction of early-onset neonatal sepsis in patients with preterm labor and intact membranes. (2) Amniotic fluid tumor necrosis factor-alpha is a better independent predictor of early-onset neonatal sepsis than placental histologic finding or amniotic fluid culture.

Adult↗

Preliminary report: rhG-CSF may reduce the incidence of neonatal sepsis in prolonged preeclampsia-associated neutropenia.

OBJECTIVES: To determine whether adjunctive therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) could reverse the neutropenia and reduce the incidence of sepsis (</=28 days postnatal age) in neonates with prolonged preeclampsia-associated neutropenia compared with conventional therapy. STUDY DESIGN: An intravenous infusion of rhG-CSF (10 microgram/kg/day x 3 days for 10 neonates or 5 microgram/kg/day x 3 days for 5 neonates) was administered to ventilated patients with prolonged (>/=3 consecutive days in the first postnatal week) preeclampsia-associated neutropenia (absolute neutrophil count [ANC] <1500/mm3). Neutrophilic responses and the incidence of neonatal sepsis in the next 28 postnatal days were compared with 13 case-matched control neonates who also had prolonged preeclampsia-associated neutropenia. Sepsis was defined as at least one positive blood culture in a newly symptomatic neonate treated with antibiotics for >/=7 days. RESULTS: No significant differences existed among the three groups in the birth weight, gestational age, sex, growth retardation, method of delivery, magnitude of respiratory support, use of surfactant, usage of intravascular catheters, or in the initial (pretreatment) ANC. The average baseline ANC (pretreatment) in the 10 microgram rhG-CSF group was 815 +/- 169/mm3 (mean +/- SEM), in the 5 microgram group it was 786 +/- 165/mm3, and in the conventional group it was 965 +/- 283. Eighteen of 28 (64%) neonates with preeclampsia-associated neutropenia were neutropenic at birth, the other 10 (36%) had normal neutrophil counts at birth but subsequently developed >/=3 days of neutropenia between 24 and 120 hours after birth. The ANC increased by 2-fold at 24 hours, by 4-fold at 72 hours, and 14-fold by the 7th day in the 10-microgram group. In the 5-microgram group, a 2-fold and 5-fold increase occurred at 72 hours and 7 days, respectively. In the conventionally-treated group, only a 4-fold increase was seen as late as 7 days after achieving entry criteria. Sepsis was observed in 13% (2/15) of the rhG-CSF-treated neonates compared with an incidence of 54% (7/13) in the conventionally-treated neonates. Conclusions. rhG-CSF increases the ANC significantly (at 10 microgram/kg/day x 3 days) and reduces the incidence of neonatal sepsis in critically ill ventilated neonates with prolonged preeclampsia-associated neutropenia when compared with conventional therapy. A future prospective, randomized, and blinded trial is needed to validate the beneficial effects of prophylactic rhG-CSF therapy in neonates with prolonged preeclampsia-associated neutropenia.

Cross Infection↗

Association between serum macrophage colony-stimulating factor levels and monocyte and thrombocyte counts in healthy, hypoxic, and septic term neonates.

OBJECTIVE: Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that mainly stimulates the growth, differentiation, and proliferation of cells of the monocyte-macrophage lineage. There are only limited numbers of studies about M-CSF levels in neonates, but high levels of serum M-CSF have been reported in septic and some thrombocytopenic adult patients. In this study, we investigated the serum M-CSF levels in healthy, septic, and hypoxic term neonates on the first day of life and examined the relationship of serum M-CSF levels and circulating monocyte and thrombocyte counts in these newborn infants. STUDY DESIGN: Three groups were defined in this prospective study: group 1, healthy neonates with no risk factors (n = 40); group 2, neonates who had severe hypoxia (n = 20); and group 3, neonates who fulfilled the criteria for early-onset sepsis (n = 18). Blood samples were collected for complete blood cell count and serum M-CSF levels by peripheral venipuncture from each infant in the first 24 hours after birth before any medical therapy. RESULTS: The gestational ages and birth weights did not differ significantly between the groups. Serum M-CSF levels of the septic neonates were significantly higher than of both healthy and hypoxic neonates, but did not differ significantly between the healthy and hypoxic neonates. There was no significant correlation between serum M-CSF levels and circulating monocyte counts, but there was a significant inverse correlation between serum M-CSF levels and thrombocyte counts. When this correlation was analyzed according to groups, we determined that this inverse correlation between M-CSF levels and thrombocyte counts was especially significant in the septic neonate group, but not significant in the healthy and hypoxic neonate groups. CONCLUSIONS: Serum M-CSF levels are significantly higher in neonates with sepsis. High serum M-CSF levels may have a possible role in the pathogenesis of thrombocytopenia in neonates with sepsis.

Asphyxia Neonatorum↗

Reduced risk of neonatal respiratory infections among breastfed girls but not boys.

OBJECTIVE: The effect of breastfeeding on community-acquired neonatal infections has not been well studied, although the neonatal period is one of special vulnerability to infectious pathogens. Respiratory tract infections are the neonatal infection most commonly diagnosed after nursery discharge. We therefore chose respiratory tract infections diagnosed after nursery discharge as representative of neonatal community-acquired infection and studied the impact of breastfeeding on this neonatal infection syndrome. METHODS: An unmatched nested case-control study was performed within a previously defined study cohort of 13 224 mother-infant pairs delivering between October 1, 1990, and March 31, 1998. Infants who were delivered at < 37 weeks' gestation were excluded. Neonatal respiratory tract infections were defined using modified National Nosocomial Infections Surveillance System criteria and were included in the case series when diagnosed after nursery discharge and at age < or =30 days. Infant feeding status during the first month of life was ascertained using automated text search of electronic medical records and was categorized as exclusive breastfeeding, mixed feeding, or exclusive formula feeding. RESULTS: A total of 241 neonatal respiratory tract infections were found, and 1205 control subjects were selected. Compared with control subjects, case infants were more often born during the winter respiratory syncytial virus season (48% vs 33%), more likely to have a sibling present (70% vs 54%), and more likely to be a member of a socioeconomically at-risk family (24% vs 18%). Case patients were less likely to be exclusively breastfed (38% vs 44%) and equally likely to be exposed to mixed feeding (35% vs 34%) relative to control subjects. When compared with formula feeding only, the odds ratio (OR) of exclusive breastfeeding was 0.70 (95% confidence interval [CI]: 0.49-0.99) and that of mixed feeding was 0.83 (95% CI: 0.58-1.2). However, when stratified by infant sex, the inverse association between breastfeeding and risk of neonatal respiratory tract infection was confined to neonatal girls, for whom the unadjusted ORs associated with breastfeeding only and mixed feeding were 0.5 (95% CI: 0.29-0.78) and 0.6 (95% CI: 0.35-0.93), respectively. There was no meaningful association between breastfeeding and risk of neonatal respiratory tract infection among neonatal boys, for whom the unadjusted ORs associated with breastfeeding only and mixed feeding were 1.1 (95% CI: 0.63-1.8) and 1.3 (95% CI: 0.74-2.1), respectively. After adjustment for year of birth, season of birth, siblings, and socioeconomic status, both exclusive breastfeeding and mixed feeding remained protective among girls, with ORs of 0.5 (0.29-0.78) and 0.6 (0.34-0.93), respectively. The corresponding ORs for boys were 1.1 (0.64-2.0) and 1.4 (0.78-2.4). CONCLUSIONS: Breastfeeding was inversely associated with reduced risk of neonatal respiratory tract infections in girls but not in boys. Breastfeeding may confer protection against some community-acquired infections as early as the first month of life.

Boston↗

Renal outcome of neonatal renal venous thrombosis: review of 28 patients and effectiveness of fibrinolytics and heparin in 10 patients.

OBJECTIVES: Neonatal renal venous thrombosis is a rare disorder that can result in severe renal damage. To evaluate the experience over 10 years and review the effectiveness of fibrinolytic and/or heparin therapy, chart reviews were performed for newborns with renal venous thrombosis. PATIENTS, INTERVENTIONS, AND OUTCOME MEASURES: Twenty-eight newborns with renal venous thrombosis were treated at Children's Hospitals and Clinics of Minnesota and Fairview University Medical Center from 1991 to 2001. RESULTS: Unilateral involvement was noted in 25 neonates (89%) and bilateral involvement in 3 (11%). Unilateral renal venous thrombosis affected mostly term infants, whereas 2 of 3 infants with bilateral renal venous thrombosis were <32 weeks' gestational age (birth weight: 745-1505 g). One mother had antiphospholipid syndrome. Of 11 neonates evaluated for congenital thrombophilia, 1 had the factor V Leiden mutation. Ten neonates received either unfractionated or low molecular weight heparin for 3 days to 7 months. Three infants with unilateral renal venous thrombosis treated with heparin alone did not seem to benefit from such therapy. Seven neonates were treated with fibrinolytics and unfractionated heparin (4 neonates with unilateral renal venous thrombosis and 3 with bilateral renal venous thrombosis). Treatment with fibrinolytics did not result in restoration of renal function in the 4 neonates with unilateral renal venous thrombosis but was associated with return of almost normal function in the 2 neonates with bilateral renal venous thrombosis who received fibrinolytics immediately after renal venous thrombosis diagnosis. Two neonates treated with fibrinolytics suffered bleeding complications at the area of adrenal hemorrhage. Two neonates (not treated for renal venous thrombosis) died as a result of underlying disease. CONCLUSIONS: Most neonatal renal venous thrombosis is unilateral and does not respond to fibrinolytic therapy and heparin. The use of fibrinolytics may prevent chronic renal failure in neonates with bilateral renal venous thrombosis if begun within 24 hours of diagnosis. Fibrinolytic therapy, however, is associated with a risk of bleeding, specifically if there is an associated adrenal hemorrhage.

Female↗

Upsurge in neonatal tetanus in Benin City, Nigeria.

BACKGROUND: Neonatal tetanus was on the decline from mid 1970's to mid 1990's due to the various efforts by many governments of the developing countries and such agencies as World Health Organisation (WHO) and United Nation's Children's Fund (UNICEF). However recently there appear to be an increase in neonatal tetanus despite these interventions leading to increasing neonatal morbidity and mortality. OBJECTIVE: To study the upsurge in neonatal tetanus despite the various interventions, examine possible causes responsible for it and proffer suggestions for eliminating neonatal tetanus by new target date of 2005 set by World Health Organisation. DESIGN: A prospective study. SETTING: The study was done at the University of Benin Teaching Hospital, Benin city and Modic Medical Centre, a private paediatric hospital in Benin City, Nigeria between January 1997 to December 2001. SUBJECTS: In 1996, it was noticed that cases of neonatal tetanus had increased suddenly among the total admissions. Morbidity and mortality among the under six months children had also increased and about ten percent of it was due to neonatal tetanus. It became imperative therefore to determine the magnitude of this problem. Consequently, cases of neonatal tetanus admitted to Special Care Baby Unit (SCBU) of the University of Benin Teaching Hospital and the Intensive Care Unit (ICU) of the Modic Medical Centre, a private paediatric hospital in Benin over a five year period January 1997 to December 2001 were examined. One hundred and fifty three tetanus cases were recorded during the period comprising 87 (56.9%) males and 66 (43.1%) females. RESULTS: The annual incidence in UBTH was 6.9% (99/1425) and 5.3% (54/1021) in Modic Centre. Forty three point eight percent (67/153) survived while 56.2% (86/153) died. There was a yearly increase in incidence of neonatal tetanus of total neonatal admissions. Average age on admission was 8.8 days and incubation period was 5-22 days. Only 40 (26.1%) did not have any antenatal care. Eighteen of the 40 (45%) mothers who had antenatal care had two doses of tetanus toxoid only. Many of the mothers were ignorant about immunisation, feared about the consequences of immunisation, some got disenchanted with it because of the out of stock syndromes associated with the vaccines whenever they visited the health centres. Some of them did not even know about antenatal care. CONCLUSION: Problem identified included lack of awareness of antenatal services among the target population, under utilisation of antenatal service, non immunisation with tetanus toxoid vaccines, negative cultural beliefs, primordial cord care, lack of economic and decision making empowerment of the target population and lack of government commitment towards elimination of neonatal tetanus. The following recommendations which may lead to elimination of Neonatal Tetanus were made: Strengthening school health programmes, intensive mobilisation and advocacy, regular availability of tetanus toxoid vaccines, empowerment of the target population, training and retraining personnel including Traditional Birth Attendants and increasing commitment by various tiers of government.

Attitude to Health↗