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PubMed2002

Multicenter analysis of platelet transfusion usage among neonates on extracorporeal membrane oxygenation.

OBJECTIVE: Multiple platelet transfusions are invariably given to neonates on extracorporeal membrane oxygenation (ECMO), and no alternative to repeated transfusions exists. Before any alternatives, such as administration of thrombopoietic stimulators, could be contemplated, data regarding the number of platelet transfusions received by neonatal ECMO patients is needed, and the mechanisms that cause the thrombocytopenia of these patients must be better defined. As a step toward determining this, we analyzed the use of platelet transfusions in this group of neonates. We conducted a historic cohort study of neonates who were treated with ECMO to determine the number of platelet units received as a function of 1) days on ECMO, 2) medical diagnosis for which ECMO was instituted, and 3) type of ECMO used (venovenous [VV] vs venoarterial [VA]). METHODS: We reviewed the hospital records of all neonates who were admitted to the neonatal intensive care units at Shands Children's Hospital, Arnold Palmer Hospital for Children and Women, and Tampa General Hospital and treated with ECMO between January 1, 1995, and June 30, 2000. Data were expressed as the number of platelet transfusions versus number of days on ECMO, diagnosis for which ECMO was instituted, and type of ECMO used. RESULTS: Of the 234 ECMO patients, 81 were placed on VV, 138 were placed on VA, and 15 were converted from VV to VA. The average number of platelet transfusions received per day was 1.3 and varied by diagnosis and by type of ECMO. Neonates with meconium aspiration and sepsis required more platelet transfusions per day than neonates with other conditions. Infants who were converted from VV to VA required more transfusions per day (mean: 1.57) than did patients on VA (1.47) or VV (1.06). CONCLUSIONS: Platelet transfusions among neonates on ECMO are dependent of their medical diagnosis; they average 1.3 transfusions per day and are higher on VA than VV ECMO.

Birth Weight↗
PubMed2006

Adverse neonatal outcomes associated with antenatal dexamethasone versus antenatal betamethasone.

OBJECTIVE: Antenatal dexamethasone and betamethasone may not be equally efficacious in the prevention of adverse neonatal outcomes. We compared the risks of periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), and neonatal death among very low birth weight infants who were exposed to dexamethasone, betamethasone, or neither steroid. METHODS: Infants (401-1500 g) in the National Institute of Child Health and Human Development Neonatal Research Network were studied. Multivariate logistic regression analyses compared the 3 groups with regard to PVL, IVH, ROP, and neonatal death, adjusting for network center and selected covariates. RESULTS: A total of 3600 infants met entry criteria. Compared with no antenatal steroids, there were trends for a reduced risk for PVL associated with dexamethasone and betamethasone but no difference in risk between dexamethasone and betamethasone. Dexamethasone reduced the risk for IVH and severe IVH, compared with no antenatal steroid exposure. Betamethasone reduced the risk for IVH, severe IVH, and neonatal death, compared with no antenatal steroids. Compared with betamethasone, dexamethasone had a statistically significant increased risk for neonatal death. There were trends for greater risks associated with dexamethasone compared with betamethasone for IVH and severe ROP. CONCLUSIONS: Betamethasone was associated with a reduced risk for neonatal death, with trends of decreased risk for other adverse neonatal outcomes, compared with dexamethasone. It may be in the best interest of neonates to receive betamethasone rather than dexamethasone when available.

Betamethasone↗
PubMed1992

[Neonatal bacterial meningitis: etiological agents in 109 cases during a 10 year period].

The etiology of purulent meningitis was investigated in 109 newborn infants admitted in a neonatal intensive care unit throughout a ten year period. Bacterial pathogens were isolated from the CSF in 57 (52.2%) neonates. There was a predominance of Gram-negative bacilli isolated in 38 (34.9%) neonates. Gram-positive cocci were isolated from CSF in only 12 (11.0%) neonates. Microorganisms associated with nosocomial septicemia and meningitis in neonates--Klebsiella sp, Salmonella sp. Enterobacter sp, Pseudomonas sp, Flavobacterium meningosepticum and Serratia marcescens--were responsible for presumptive etiology in 38 (49.3%) among 77 patients with positive cultures in "closed sites". They were isolated from 22 (57.0%) neonates with prior hospitalization but only from 12 (34.3%) neonates coming directly from their households (chi 2 = 4.08; p < 0.05). The mortality rate was significantly higher in patients with positive CSF cultures (47.4%) in comparison to patients with negative cultures (18.4%) (X2 = 5.01; p < 0.05). It is possible to conclude that Gram-negative bacilli, many of them of hospital origin, are the major pathogens in this study. An improvement on neonatal health care and a scrupulous control of neonatal nosocomial infections are recommended.

Culture Media↗
PubMed2004

Clinical effectiveness and cost-effectiveness of neonatal screening for inborn errors of metabolism using tandem mass spectrometry: a systematic review.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of tandem mass spectrometry (MS)-based neonatal screening for inborn errors of metabolism (IEM). DATA SOURCES: Fourteen electronic bibliographic databases covering biomedical, science, economic and grey literature, the reference lists of relevant articles and abstracts of conference proceedings and 18 health services research-related resources. REVIEW METHODS: This review is an update of two previous HTA reports of neonatal screening for IEM. These reports have been updated by a systematic review of published research (between 1995 and January 2002) on neonatal screening of inherited metabolic disorders using tandem MS. This was supplemented by a search for economic literature and the application of a modelling exercise to investigate the economics of using tandem MS within a neonatal screening programme in the UK. RESULTS: Evidence from the reviews of IEM found that the UK screening programme for phenylketonuria (PKU) was well established and there was universal agreement that neonatal screening for PKU was justified. Of the many other disorders that can be detected by tandem MS, the best candidate condition for a new screening programme was medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. For many other IEM that can be detected by tandem MS, robust clinical evidence was limited. Cost-effectiveness analysis using economic modelling indicated that substituting the use of tandem MS for existing technologies for the screening of PKU alone could not be justified. However, results from the economic modelling indicate that the addition of screening for MCAD deficiency as part of a neonatal screening programme for PKU using tandem MS would be economically attractive. Using an operational range of 50,000-60,000 specimens per system per year, the mean incremental cost for PKU and MCAD deficiency screening combined using tandem MS from the model was -23,312 British pounds for each cohort of 100,000 neonates screened. This cost saving is associated with a mean incremental gain of 59 life-years. Additional economic modelling using the available evidence does not support including other inherited metabolic diseases within a neonatal screening programme at present. CONCLUSIONS: The evidence appears to support the introduction of tandem MS into a UK neonatal screening programme for PKU and MCAD deficiency combined. Tandem MS has the potential for simultaneous multi-disease screening using a single analytical technique. Although the marginal cost of extending the programme to include other conditions may be relatively small, the application of this new technology to PKU and MCAD deficiency screening does not imply the wholesale inclusion of all disorders detectable by tandem MS. It is suggested that the primary focus of further research should be on the long-term effectiveness of treatment strategies on adverse outcomes (disabilities and impairments) under conventional management and the potential impact of early diagnosis using tandem MS.

Cohort Studies↗
PubMed2002

Neonatal thyroid-stimulating hormone concentrations in northern Sydney: further indications of mild iodine deficiency?

OBJECTIVE: To determine whether thyroid-stimulating hormone (TSH) concentrations in a large sample of neonates meet World Health Organization criteria for an iodine-replete population (< 3% of neonates with whole-blood TSH concentrations > 5 mlU/L), and, in a small subset of neonates, to examine the correlation between maternal urinary iodine and neonatal TSH concentrations. DESIGN: Cross-sectional study of neonatal whole-blood TSH values obtained as part of a routine newborn screening program. SETTING: Royal North Shore Hospital (RNSH) in northern Sydney. PARTICIPANTS: Two anonymous samples of neonates born at RNSH (1316 infants born between August 1998 and April 1999 and 1457 infants born between 1 March and 31 December 2000); and 84 infants whose mothers had attended RNSH between September 1998 and August 1999 and supplied a urine sample for iodine measurement. MAIN OUTCOME MEASURES: Iodine status of neonates (proportion with whole-blood TSH values > 5 mlU/L), and urine iodine concentrations of pregnant women. RESULTS: In the two large population samples of neonates, 8.1% (95% CI, 6.6%-9.5%) and 5.4% (95% Cl, 4.3%-6.6%), respectively, had whole-blood TSH values > 5 mlU/L (prevalence range for mild thyroid deficiency, 3%-19%). Comparing the TSH values of the 1316 anonymous infants and the 84 identified infants showed no difference between the proportions with TSH values > 5 mlU/L (8.1% v 10.7%, respectively; P = 0.39). Urine iodine concentrations in the 84 pregnant women indicated borderline mild iodine deficiency. TSH values in their 84 infants were positively correlated with maternal urine iodine concentrations. CONCLUSIONS: Our results suggest that the population of northern Sydney may have mild iodine deficiency. However, the expected relationship between maternal urine iodine levels and neonatal TSH concentrations was not found.

Congenital Hypothyroidism↗
PubMed2004

[Screening for phenylketonuria and congenital hypothyroidism in 5.8 million neonates in China].

OBJECTIVES: To summarize neonatal screening for phenylketonuria (PKU) and congenital hypothyroidism (CH) in China, to further clarify incidence of the two kinds of diseases in newly-born babies, and to explore issues in neonatal screening and their solutions. METHODS: Neonatal screening for PKU and CH was conducted by 39 neonatal screening centers all over the country, sponsored by the Group of Neonatal Screening, Chinese Society of Child Health Care, Chinese Preventive Medical Association and the Center for Neonatal Screening Quality Control Laboratory, National Center for Clinical Laboratories (NCCL). In each infant a heel prick blood sample was collected at 72 hours postnatal onto standard filter paper. PKU was screened by bacterial inhibition assay and fluorometric method, and CH was screened by TSH measurement by time-resolved fluorescence immunoassay (TRFIA), fluorescence enzyme immunoassay (FEIA) and enzyme immunoassay (EIA). RESULTS: From 1985 to 2001 in China, totally of 5 817 280 newborns were screened for PKU, 522 cases of PKU detected with an incidence of 1:11 144, and 5 524 019 newborns were screened for CH, 1 836 cases of CH detected with an incidence of 1:3 009. Annual average number of newborns screened for congenital genetic diseases was increased by 45.5% in recent six years. CONCLUSIONS: Neonatal screening was developed quickly in China in recent years, especially in some developed cities, such as Shanghai with a coverage of 98.3% in 2001. But, its coverage was about only 10% in China as a whole. In development of neonatal screening, it is necessary to attach more importance to quality of screening and increasing coverage of screening, as well as gradual development of new screening techniques for other neonatal preventable diseases, in addition to PKU and CH, and their application, and improvement of level of child health care in China.

China↗
PubMed1996

Neonatal septic arthritis.

Neonatal septic arthritis has always been considered as separate from its counterpart in older children. The condition is uncommon but serious. Affected neonates usually survive, but with permanent skeletal deformities. Ten cases of neonatal septic arthritis were diagnosed between January 1989 and December 1993 in the neonatal intensive care units of two referral hospitals in the state of Kelantan, Malaysia. All except one neonate was born prematurely. The mean age of presentation was 15.6 days. Joint swelling (10/10), increased warmth (7/10) and erythema of the overlying skin (7/10) were the common presenting signs. Vague constitutional symptoms preceded the definitive signs of septic arthritis in all cases. The total white cell counts were raised with shift to the left. The knee (60%) was not commonly affected, followed by the hip (13%) and ankle (13%). Three neonates had multiple joint involvement. Coexistence of arthritis with osteomyelitis was observed in seven neonates. The commonest organism isolated was methicillin resistant Staphylococcus aureus (9/10). Needle aspiration was performed in nine neonates and one had incision with drainage. Follow up data was available for five neonates and two of these had skeletal morbidity. Early diagnosis by frequent examination of the joints, prompt treatment and control of nosocomial infection are important for management.

Age of Onset↗
PubMed2005

No cry at birth: global estimates of intrapartum stillbirths and intrapartum-related neonatal deaths.

OBJECTIVE: Fewer than 3% of 4 million annual neonatal deaths occur in countries with reliable vital registration (VR) data. Global estimates for asphyxia-related neonatal deaths vary from 0.7 to 1.2 million. Estimates for intrapartum stillbirths are not available. We aimed to estimate the numbers of intrapartum-related neonatal deaths and intrapartum stillbirths in the year 2000. METHODS: Sources of data on neonatal death included: vital registration (VR) data on neonatal death from countries with full (> 90%) VR coverage (48 countries, n = 97,297); studies identified through literature searches (> 4000 abstracts) and meeting inclusion criteria (46 populations, 30 countries, n = 12,355). A regression model was fitted to cause-specific proportionate mortality data from VR and the literature. Predicted cause-specific proportions were applied to the number of neonatal deaths by country, and summed to a global total. Intrapartum stillbirths were estimated using median cause-specific mortality rate by country (73 populations, 52 countries, n = 46,779) or the subregional median in the absence of country data. FINDINGS: Intrapartum-related neonatal deaths were estimated at 0.904 million (uncertainty 0.65-1.17), equivalent to 23% of the global total of 4 million neonatal deaths. Country-level model predictions compared well with population-based data sets not included in the input data. An estimated 1.02 million intrapartum stillbirths (0.66-1.48 million) occur annually, comprising 26% of global stillbirths. CONCLUSION: Intrapartum-related neonatal deaths account for almost 10% of deaths in children aged under 5 years. Intrapartum stillbirths are a huge and invisible problem, but are potentially preventable. Programmatic attention and improved information are required.

Asphyxia Neonatorum↗
PubMed2004

The study of thrombocytopenia in sick neonates.

OBJECTIVE: To determine the number of cases and manifestations of thrombocytopenia in sick neonates. DESIGN: An observational study. PLACE AND DURATION OF STUDY: The study was conducted at Neonatal Intensive Care Unit (NICU) of the Paediatric Department, Jinnah Hospital, Lahore from September 1997 to February 1998. SUBJECTS AND METHODS: A total of 365 neonates from 0-28 days of age admitted with different clinical problems irrespective of birth weight and gestational age were evaluated for thrombocytopenia. These neonates were categorized into five different groups (A-E), which were of neonatal infections, asphyxia neonatorum, preterm and smallness for gestational age, jaundice and miscellaneous respectively. RESULTS: Out of 365 cases, 88 were found to have thrombocytopenia (platelet counts < 150,000 per mm3) which was 24.1% of the total. In group A (neonatal infections), out of 152 neonates, 62 had low platelet counts (40.78%). In group B (neonatal asphyxia), out of 90 only 11 had thrombocytopenia (12.2%). In group C (preterm and small for gestational age), out of 60 cases only 9 had thrombocytopenia. In group D (jaundice), all 33 cases had normal platelet counts. In group E (miscellaneous), out of 30 cases only 6 had thrombocytopenia. The common manifestations in thrombocytopenic babies were petechiae and bruises followed by gastrointestinal hemorrhages. The percentage of manifest thrombocytopenia cases was 56.8% and of occult thrombocytopenia 43.1%. CONCLUSION: The leading causes of thrombocytopenia in sick neonates are infections, asphyxia, complicated pre-maturity and smallness for gestational age. Apart from the platelet counts the bleeding mainfestations also depend upon the underlying ailments.

Asphyxia Neonatorum↗
PubMed1999

Lipid intolerance in neonates receiving dexamethasone for bronchopulmonary dysplasia.

BACKGROUND: We hypothesized that dexamethasone induces hypertriglyceridemia (triglyceride levels >2.82 mmol/L [250 mg/dL]) and increases free fatty acid (FFA) levels and that steroid-induced hypertriglyceridemia is associated with hyperinsulinemia and elevated FFA levels. OBJECTIVE: To study the effect of dexamethasone sodium phosphate on lipid metabolism in neonates receiving intravenous lipids. DESIGN: A prospective cohort study with patients serving as their own controls. SETTING: Neonatal Intensive Care Unit, Children's Hospital at Strong, Rochester, NY. METHODS: All neonates younger than 29 weeks' gestational age at birth receiving 3 g/kg per day of intravenous lipids who were to start dexamethasone therapy for bronchopulmonary dysplasia were eligible. Exclusion criteria included neonates with active infection, prior hypertriglyceridemia, bleeding manifestations, recent surgery, thyroid medication, and human recombinant insulin intravenous infusion therapy. Ten neonates were studied. Blood was drawn for triglyceride, FFA, and insulin assays before initiating and at 1, 2, 3, and 5 days after starting dexamethasone therapy. On day 3, dexamethasone dosage was decreased as per protocol. Intravenous lipid intake was kept constant. Statistical analysis was done using a paired t test. RESULTS: Six of 10 neonates reached a state of hypertriglyceridemia (95% confidence interval, 26.2%-87.8%). The mean average increase in triglycerides, insulin, and FFA levels in neonates receiving 3 g/kg per day of intravenous lipids after initiation of dexamethasone therapy was 0.75 mmol/L (66.6 mg/dL) (P=.007), 127 pmol/L (P = .006), and 47.5 micromol/L (P = .65), respectively. Six neonates who developed hypertriglyceridemia had significantly elevated mean peak FFA levels (918.3 micromol/L) prior to developing hypertriglyceridemia compared with 4 neonates (mean peak FFA levels, 380.2 micromol/L) who had triglyceride levels lower than 2.82 mmol/L (250 mg/dL) (P = .002). CONCLUSION: We conclude that dexamethasone induces hypertriglyceridemia in the presence of hyperinsulinemia and increased FFA levels.

Bronchopulmonary Dysplasia↗
PubMed1996

Immunohistochemical studies on the expression and estrogen dependency of EGF and its receptor and C-fos proto-oncogene in the uterus and vagina of normal and neonatally estrogen-treated mice.

BACKGROUND: The final target cell response to estrogen is dependent not only on the estrogen receptor, but also on autocrine/paracrine interactions with growth factors (e.g., EGF) and proto-oncogenes (e.g., c-fos). Because neonatal estrogen treatment results in permanent changes in the female mouse genital tract (permanent vaginal cornification, cervical adenosis and tumors, changed growth control mechanisms in uterus), it was of interest to study possible acute and permanent effects of such treatment on distribution and levels of EGF, its receptor (EGF-r), and c-fos and to relate such changes to morphological development and appearance of epithelial abnormalities. METHODS: Immunohistochemical techniques using frozen sections from the uterus and vagina of neonatal and adult (ovariectomized, estradiol-treated) females, treated with olive oil or diethylstilbestrol in neonatal life. RESULTS: A difference in stromal-epithelial distribution of EGF was demonstrated with respect to region studied (uterus, vagina) and age (neonatal, adult). EGF was localized mainly in the uterine stroma but in both vaginal epithelium and stroma (with a different pattern compared to uterus). In neonatal females, EGF occurred in both tissue components in both regions, and the distribution pattern was quite different from that in adult females. The EGF level was increased by estrogen in adult but not in neonatal females. EGF-r and c-fos occurred in both uterine epithelium and stroma and in the vaginal epithelium; levels and distribution pattern were affected by estrogen. Neonatal estrogen treatment increased the levels of uterine EGF and c-fos in adult life. CONCLUSIONS: There are distinct developmental changes in the distribution and estrogen sensitivity of EGF. Only further studies can prove or disprove the association between the earlier reported disturbed growth control mechanisms in the uterus of adult but neonatally estrogen-treated females and the increased levels of uterine EGF and c-fos. The present results do not seem to explain mechanisms involved in the origin of neonatally estrogen-induced cervicovaginal epithelial abnormalities, nor do they explain the earlier described difference in estrogen-induced proliferative response between the uterine cervix and uterus proper.

Age Factors↗
PubMed2000

Corticosteroids for the prevention and treatment of post-extubation stridor in neonates, children and adults.

BACKGROUND: Post-extubation stridor may prolong length of stay in the intensive care unit, particularly if airway obstruction is severe and re-intubation proves necessary. Corticosteroids, however, may be associated with adverse effects ranging from hypertension to hyperglycemia, and a more systematic assessment of the efficacy of this therapy is indicated prior to widespread adoption of this practice OBJECTIVES: To determine whether corticosteroids are effective in preventing or treating post-extubation stridor in critically ill infants, children, or adults. SEARCH STRATEGY: Controlled trials were identified through MEDLINE, EMBASE and CINAHL. Bibliographies of all identified trials were examined, and authors of included trials were contacted to confirm the methodology and identify other potentially relevant trials. SELECTION CRITERIA: Any randomized controlled trial that compared administration of corticosteroids by any route with placebo in infants, children, or adults receiving mechanical ventilation via an endotracheal tube in an intensive care unit. DATA COLLECTION AND ANALYSIS: Data from the included studies were extracted independently by two reviewers. The main outcome was the rate of tracheal re-intubation after extubation. The incidence of stridor was examined as a secondary outcome. Subgroup analysis was predetermined to compare preventative use of steroids before extubation and therapeutic use following extubation. Neonates, pediatric patients, and adults were compared separately. A random effects model was used throughout. Methodologic quality of trials was assessed independently by the two reviewers. MAIN RESULTS: Of 251 studies identified, only seven met the criteria for inclusion; three in adults, two in neonates, three in children. All but one examined use of steroids for the prevention of post-extubation stridor; the remaining one concerned treatment of existing post-extubation stridor in children. Patients were drawn from heterogeneous medical/surgical populations. Dexamethasone given intravenously at least once prior to extubation was the most common steroid regimen utilized (uniformly in neonates and children). Prophylactic intervention tended to decrease re-intubation rates among neonates and children, but did not reach statistical significance (neonates RR=0.1, 95% CI 0.01, 1.68; children RR=0.49, 95% CI 0.01, 19.65). Post-extubation stridor was reduced in children (n=216: RR=0.53, 95% CI 0.28, 0.97) but not in neonates. In the neonatal studies, a lower re-intubation rate was seen only in high risk patients treated with multiple doses of steroids around the time of extubation. In three adult studies (total n=1047), no difference in post-extubation stridor (RR=0.86, 95% CI 0.57, 1.30) or re-intubation rates (RR=0.95, 95% CI 0.52, 1.72) was detected. Side effects were reported seldomly and could not be aggregated. REVIEWER'S CONCLUSIONS: In neonates, there is a trend towards a reduced incidence of re-intubation in neonates receiving prophylactic dexamethasone prior to extubation. In children, prophylactic administration of dexamethasone prior to elective extubation reduces the incidence of post-extubation stridor, but the evidence is insufficient to conclude that rates of re-intubation are reduced. In adults, corticosteroids do not appear to reduce the need for re-intubation.

Adrenal Cortex Hormones↗
PubMed2004

Prophylactic versus selective antibiotics for term newborn infants of mothers with risk factors for neonatal infection.

BACKGROUND: Early onset bacterial infection is an important cause of morbidity and mortality in newborn infants. Various factors that increase the risk of neonatal infection have been identified. It is unclear whether asymptomatic newborn infants born to mothers with one or more of these risk factors should receive antibiotics prophylactically rather than selectively if only clinical or microbiological evidence of sepsis emerges. OBJECTIVES: To assess the effect of prophylactic versus selective antibiotic treatment for asymptomatic term neonates born to mothers with risk factors for neonatal infection. SEARCH STRATEGY: We used the standard methods of the Cochrane Neonatal Review Group. We searched MEDLINE (1966 - May 2004), EMBASE (1980 - May 2004), LILACS (1982 - 2003), SciELO (1997 - 2003), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), and Centers for Disease Control and Prevention protocols and guidelines on the subject. SELECTION CRITERIA: Randomized controlled trials, or trials using quasi-random methods of allocation, comparing the use of prophylactic versus selective antibiotics in asymptomatic neonates born to mothers with one or more risk factors for infection. DATA COLLECTION AND ANALYSIS: We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by three reviewers and synthesis of data using relative risk and risk difference. The pre-specified primary outcomes were neonatal mortality, systemic neonatal infection, and need for admission to a neonatal intensive care unit. MAIN RESULTS: We identified two small trials undertaken in the 1970s. Both trials had methodological weaknesses. There was no evidence of an effect on any of the primary outcomes, but because the trials were underpowered, clinically important effect sizes may have been missed. REVIEWERS' CONCLUSIONS: There are insufficient data from randomized controlled trials to guide clinical practice. A large randomized controlled trial is needed in asymptomatic term infants born to mothers with risk factors for infection in their babies, which compares the effect of prophylactic versus selective antibiotics on morbidity, mortality and costs.

Anti-Bacterial Agents↗
PubMed2003

Pentoxifylline for neonatal sepsis.

BACKGROUND: Although the overall incidence of neonatal sepsis has declined over the past decade, mortality remains high in the pre term infant. The high level of mortality and morbidity from sepsis despite the use of potent anti-microbial agents, and the global emergence of antibiotic resistance, have led to the search for new modalities to boost new born host defences. Pentoxifylline, a xanthine derivative and a phosphodiesterase inhibitor, has been shown to possess a broad spectrum of activity modulating inflammation. OBJECTIVES: The primary objective was to assess the effect on mortality and the safety of intravenous pentoxifylline as an adjunct to antibiotic therapy in neonates with suspected or confirmed sepsis. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), MEDLINE, EMBASE and CINAHL were searched in October 2002 and again in March 2003. Science Citation Index for articles referencing Lauterbach 1996 and Lauterbach 1999 was searched as well as proceedings of the Pediatric Academic Societies which were published in Pediatric Research from 1980. Doctoral dissertations and theses were searched from 1980. The reference lists of identified RCTs, and personal files were searched. No language restriction was applied. SELECTION CRITERIA: Studies were included if they were randomised or quasi-randomised trials, assessing the efficacy of pentoxifylline compared to placebo or no intervention as an adjunct to antibiotic therapy of suspected or confirmed sepsis in newborn infants less than 28 days old. Eligible trials were required to report treatment effects on at least one of the following outcomes: all cause mortality during initial hospital stay, neurological development at two years of age or later, length of hospital stay, duration of ventilation via endotracheal intubation, chronic lung disease in survivors, periventricular leukomalacia, necrotising enterocolitis, or adverse events. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted information for the outcomes of interest. Any differences were resolved by mutual discussion. Typical Relative Risk (RR) and Risk Difference (RD) with 95% confidence intervals (CI) using fixed effects model are reported for dichotomous outcomes. NNT was calculated for outcomes for which there was a statistically significant reduction in RD. MAIN RESULTS: Two RCTs enrolled a total of 140 preterm (< 36 weeks) neonates with suspected late onset (> 7 days) sepsis to evaluate the effect of pentoxifylline on neonatal outcomes. However, the two studies reported outcomes of only the 107 randomised patients with confirmed sepsis. The results showed a reduction in 'all cause mortality during hospital stay' following pentoxifylline treatment [typical RR 0.14 (95% CI 0.03, 0.76), RD -0.16 (95% CI -0.27, - 0.04), NNT 6 (95% CI 4, 25)]. No adverse effects due to pentoxifylline were observed in the two included trials. No other outcomes of interest were reported. REVIEWER'S CONCLUSIONS: Current evidence suggests that the use of pentoxifylline as an adjunct to antibiotics in neonatal sepsis reduces mortality without any adverse effects. But the number of neonates studied is small and considerable methodological weaknesses exist in the included trials. Hence these results should be interpreted with caution. Researchers are encouraged to undertake large well-designed trials to confirm or refute the effectiveness of pentoxifylline to reduce mortality and adverse outcomes in neonates with suspected or confirmed neonatal sepsis. Researchers might also compare pentoxifylline with other adjuncts to antibiotics which modulate inflammation (e.g. intravenous immunoglobulins, haematopoetic colony stimulating factors among others) in reducing mortality and morbidity due to neonatal sepsis.

Anti-Bacterial Agents↗
PubMed2006

Intravenous in-line filters for preventing morbidity and mortality in neonates.

BACKGROUND: Venous access is an essential part of caring for the sick neonate; however, problems such as contamination of fluids with bacteria, endotoxins and particulates have been associated with intravenous infusion therapy. Intravenous in-line filters claim to be an effective strategy for the removal of bacteria, endotoxins and particulates associated with intravenous therapy in adults and are increasingly being recommended for use in neonates. OBJECTIVES: To assess whether in-line filters on intravenous lines prevent morbidity and mortality in neonates. SEARCH STRATEGY: Searches were made of the electronic databases MEDLINE (from 1966 to September 2005), EMBASE (from 1980 to September 2005), CINAHL (from 1982 to September 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3 2005 ). There was no language restriction. Further searching included cross references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that compared the use of intravenous in-line filters with placebo or nothing in neonates were included in the review. DATA COLLECTION AND ANALYSIS: The procedures of the Cochrane Neonatal Review Group (CNRG) were followed throughout. Titles and abstracts identified from the search were checked by the review authors. The full text of all studies of possible relevance were obtained. The review authors independently assessed the trials for their methodological quality and subsequent inclusion in the review. Statistical analysis followed the procedures of the Cochrane Neonatal Review Group. Dichotomous data is expressed as relative risk and 95% confidence intervals, and risk difference and 95% confidence intervals. MAIN RESULTS: There were three eligible studies, which recruited a total of 262 neonates. For most of the outcomes for this review, only one study of 88 neonates contributed eligible data. This review found no significant effect of in-line filters in any of the reported outcomes of overall mortality, proven and unproven septicaemia, phlebitis, necrotizing enterocolitis, duration of cannula patency, number of catheters inserted and financial costs. AUTHORS' CONCLUSIONS: There are insufficient data to determine whether or not the use of intravenous in-line filters prevent morbidity and mortality in neonates. The wide confidence intervals on outcomes indicate the imprecise estimates of treatment effect due to the small numbers of patients and events.

Catheterization, Peripheral↗
PubMed1992

Antigen presentation for T cell interleukin-2 secretion is a late acquisition of neonatal B cells.

The ability of B lymphocytes to process and present antigen to helper T cells is essential to initiate T cell-B cell interactions in humoral immune responses. Here we describe the developmental acquisition of the antigen-presenting function of B cells as measured by the ability of B cells to stimulate a T cell hybrid to interleukin (IL)-2 secretion. Neonatal splenic B cells are not adult-like in their ability to process and present the model protein antigen pigeon cytochrome (Pc), which enters the B cell through fluid-phase pinocytosis, until 21 to 28 days of life. The ability of neonatal B cells to process and present antigen which enters the cell bound to surface Ig is not adult-like until 28 days of age. When neonatal B cells acquire antigen-presenting cell (APC) function, surface IgM facilitates antigen processing. The delayed acquisition of APC function cannot be accounted for solely by a deficiency in major histocompatibility complex MHC class II, ICAM-1, or LFA-1 as neonatal B cells express adult levels of these molecules by 7-14 days after birth. Moreover, the ability of neonatal B cells to present a peptide fragment of Pc which does not require processing is adult like by day 14. Furthermore, neonatal B cells are capable of binding, internalizing and degrading radiolabeled antigen, suggesting a more subtle level of regulation. In contrast to neonatal B cells, immature B cells in the adult bone marrow and adult B cells undergoing antigen-driven differentiation to memory B cells, as defined by the loss of the J11D marker, are competent to process and present antigen resulting in T cell IL-2 secretion. Thus, developing B cell subpopulations in the adult and in the neonate can be distinguished. Only neonatal B cells are deficient in their ability to stimulate T cells to IL-2 production.

Animals↗
PubMed1994

Enhanced growth capacity of neonatal pulmonary artery smooth muscle cells in vitro: dependence on cell size, time from birth, insulin-like growth factor I, and auto-activation of protein kinase C.

Based on the unique susceptibility of the neonatal pulmonary circulation to hypoxia-induced structural alteration in vivo, we hypothesized that pulmonary artery (PA) smooth muscle cells (SMC) from the neonate would demonstrate enhanced growth capacity in vitro compared to adult cells. To test this hypothesis, matched neonatal and adult bovine SMC were tested for differences in size, serum-stimulated proliferation, susceptibility to senescence, resistance to serum withdrawal, autocrine growth capacity, and responsiveness to a locally important growth factor (insulin-like growth factor I; IGF-I) and an activator of protein kinase C (PKC) (phorbol 12-myristate 13-acetate; PMA). Neonatal PA SMC were smaller, grew faster, reached a higher plateau density, and were less susceptible to senescence. They were more resistant to serum withdrawal, had spontaneous autocrine growth capacity, and were more responsive to IGF-I, PMA, and the combination. Acquisition of increased growth factor responsiveness occurred between d5 and d14 after birth. Increased neonatal growth to IGF-I was associated with reduced IGF-I binding activity, implicating a post-receptor mechanism in enhanced responsiveness. Increased membrane-bound PKC catalytic activity was found in serum-deprived neonatal SMC. This basal increase was equal to that stimulated by 1 nM PMA in adult SMC, a pretreatment that caused these cells to become as responsive to IGF-I as untreated neonatal ones. We conclude that neonatal bovine PA SMC have marked enhancement of growth capacity in vitro, the acquisition of which is dependent on time from birth and is associated with auto-activation of PKC, These increased growth properties detected in vitro may contribute to the striking hyperplasia of neonatal PA SMC found in vivo following hypoxic exposure.

Aging↗
PubMed2003

Regulation of the proliferation of cocultured gonocytes and Sertoli cells by retinoids, triiodothyronine, and intracellular signaling factors: differences between fetal and neonatal cells.

The regulation of early fetal germ cell growth has not been studied in cell culture, probably due to the poor survival of these cells. However, cell culture is the only system in which the control of cell growth can be studied independently of the influence of secreted testicular factors, which are diluted in the medium. We successfully cultured dispersed testicular cells from 16.5-day-old rat fetuses in defined medium and compared the growth of these cells with that of cells from 3-day-old neonates. In this system, fetal gonocytes displayed low levels of mitotic activity and their numbers remained stable. In contrast, neonatal gonocytes displayed high levels of mitotic activity and increased in number, these characteristics resembling those observed in vivo. We found that retinoic acid had deleterious effects on the number of gonocytes but did not affect Sertoli cell proliferation in fetal and neonatal cell cultures. Moreover, in fetal cell cultures, the decrease in the number of gonocytes resulted from a decrease in mitotic activity, probably due to a direct effect of retinoids on fetal gonocytes. Among the selective agonists for the retinoic acid receptor (RARalpha agonist, RARbeta agonist, and RARgamma agonist) and the retinoic X receptor (pan-RXR agonist) tested, only the RARalpha agonist reproduced the effects of retinoic acid at concentrations lower than its Kd value in both fetal and neonatal cell cultures. As both RARalpha and RXRalpha are present in fetal and neonatal gonocytes, we suggest that retinoic acid exerts its effects on gonocytes via a RARalpha-RXRalpha heterodimer, with RARalpha functioning as an active partner and RXRalpha as a passive partner. In this culture system, we show for the first time that triiodothyronine (T3) inhibits testicular fetal Sertoli cell and germ cell growth. We also tested intracellular signaling factors and found that a cAMP analog increased Sertoli cell proliferation and germ cell survival in both fetal and neonatal cells whereas phorbol esters (PMA) strongly inhibited the proliferation of fetal but not of neonatal gonocytes. None of the tested factors (T3, dbcAMP, and PMA) seemed to interact with the all-trans retinoic acid pathway. Thus, fetal gonocytes and neonatal gonocytes differ in intrinsic properties, and their growth is not regulated in the same manner. Despite their low level of mitotic activity, fetal gonocytes were more sensitive to various factors than neonatal gonocytes.

Animals↗