Heated and humidified high flow therapy (HHHFT) in extreme and very preterm neonates with respiratory distress syndrome (RDS): a retrospective cohort from a tertiary care setting in Pakistan.

OBJECTIVE: To determine the role of heated humidified high flow therapy (HHHFT) as primary respiratory support in spontaneously breathing moderate-late, very and extreme preterm neonates with respiratory distress syndrome (RDS) at a tertiary care hospital from a developing country. DESIGN: Retrospective cohort study. SETTING: Neonatal intensive care unit of Indus Hospital and Health Network, Karachi, Pakistan. PATIENTS: All preterm neonates with RDS and who received HHHFT as primary respiratory support were included retrospectively, while neonates with orofacial anomalies, congenital heart and lung diseases other than RDS, abdominal wall defects, encephalopathy, congenital pneumonia and received continuous positive airway pressure or invasive ventilation were excluded. INTERVENTIONS: HHHFT as primary respiratory support for RDS. MAIN OUTCOME MEASURES: Effectiveness, duration, failure rate and complications of HHHFT as a primary respiratory support in moderate-late, very and extremely preterm neonates were evaluated. RESULTS: The cohort included 138 neonates during a period of 12 months. The median gestational age was 32 weeks, and the median birth weight was 1607 g. Grade 1-2 RDS was seen in 97%, surfactant instillation was done in 10.8% and HHHFT was provided in all the neonates as primary respiratory support. The total duration of HHHFT support was <1 week in 94% of neonates. Bronchopulmonary dysplasia and pneumothorax until discharge or death were observed in one neonate, haemodynamically significant Patent Ductus Artriosus (HsPDA) in two neonates and intraventricular haemorrhage Grade ≥2 in five neonates, while only one neonate died. CONCLUSION: This study appears to show that HHHFT is a simple, safe, efficient and cheap mode of primary respiratory support that can be given to spontaneously breathing moderate-late, very and extremely preterm neonates with RDS, especially in low- or middle-income countries.

Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates.

BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015. OBJECTIVES: To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference abstracts.   SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M-enriched intravenous immunoglobulin (IgM-enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM-enriched IVIG with antibiotics. DATA COLLECTION AND ANALYSIS: We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed-effect model of meta-analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD. MAIN RESULTS: We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain. Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-certainty evidence) and may decrease length of hospital stay (LOS) (MD -7.74, 95% CI -11.72 to -3.76; 2 studies, 157 participants, low-certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low-certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low-certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low-certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low-certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low-certainty evidence) in neonates with sepsis. Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low-certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low-certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM-enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low-certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low-certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons. AUTHORS' CONCLUSIONS: Low-certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG, or PTX with antibiotics compared to IgM-enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well-designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.

Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates.

BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotizing enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline, a phosphodiesterase inhibitor, is one such agent. OBJECTIVES: Our primary objectives were :1.To assess the effect of intravenous pentoxifylline as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis.2.To assess the effect of intravenous pentoxifylline as an adjunct to antibiotic therapy on mortality and morbidity in neonates with NEC. SEARCH METHODS: We searched the Cochrane Neonatal Review Group Specialized Register, CENTRAL (The Cochrane Library Issue 2, 2014), EMBASE (January 1980 to May 2014), PubMed (January 1966 to May 2014), CINAHL (January 1982 to May 2014), Science Citation Index (January 1990 to May 2014), and BIOSIS (January 1992 May 2014) in May 2014. We checked references and cross-references from identified studies. We handsearched abstracts from the proceedings of the Pediatric Academic Societies Meetings (from January 1990 to May 2014). We placed no restrictions on language. SELECTION CRITERIA: We included randomised or quasi-randomised trials assessing the efficacy of pentoxifylline as an adjunct to antibiotics for treatment of suspected or confirmed sepsis or NEC in neonates. DATA COLLECTION AND ANALYSIS: We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) using fixed-effect model for dichotomous outcomes and mean difference (MD) for continuous outcomes. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD. MAIN RESULTS: Pentoxifylline used as an adjunct to antibiotics in neonates with sepsis decreased all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-quality evidence). Subgroup analyses revealed decrease in mortality in preterm infants, infants with confirmed sepsis, and infants with gram-negative sepsis (low-quality evidence, four studies). Pentoxifylline decreased length of hospital stay (MD -7.59 days, 95% CI -11.65 to -3.52; 2 studies, 148 participants, low-quality evidence). Pentoxifylline did not change the risk of development of NEC, chronic lung disease, severe intraventricular haemorrhage, retinopathy of prematurity, or periventricular leukomalacia in neonates with sepsis (one to two studies, very low-quality evidence). Pentoxifylline therapy compared to pentoxifylline and immunoglobulin M-enriched intravenous immunoglobulin or immunoglobulin M-enriched intravenous immunoglobulin alone did not change mortality or development of NEC in neonates with sepsis (one study, very low-quality evidence). We noted no adverse effects due to pentoxifylline. We identified no trials evaluating pentoxifylline treatment for NEC. AUTHORS' CONCLUSIONS: Low-quality evidence from six small studies suggests that pentoxifylline therapy as an adjunct to antibiotics in neonatal sepsis decreases mortality without any adverse effects. We encourage researchers to undertake large, well-designed multicentre trials to confirm or refute the effectiveness of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.

Oral immunoglobulin for the prevention of rotavirus infection in low birth weight infants.

BACKGROUND: Rotavirus is a common neonatal nosocomial viral infection and epidemics with the newer P(6)G9 strains have been reported. Local mucosal immunity in the intestine to rotavirus is important in the resolution of infection and protection against subsequent infections. Oral administration of anti-rotaviral immunoglobulin preparations might be a useful strategy in preventing rotaviral infections, especially in low birth weight babies. OBJECTIVES: To determine the effectiveness and safety of oral immunoglobulin preparations for the prevention of rotavirus infection in hospitalized low birthweight infants (birthweight < 2500 g) SEARCH METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE, CINAHL, biological Abstracts (BIOSIS), Science Citation Index for articles citing Barnes 1982 and the proceedings of the Pediatric Academic Societies from 1991 onwards were searched in July 2011. Ongoing trials were also searched at clinicaltrials.gov and controlled-trials.com SELECTION CRITERIA: The criteria used to select studies for inclusion were: 1) design: randomized or quasi-randomized controlled trials; 2) participants: hospitalized low birthweight infants; 3) intervention: oral immunoglobulin preparations for prevention of rotavirus infection compared to placebo OR no intervention; 4) at least one of the following outcomes were reported: all cause mortality during hospital stay, mortality due to rotavirus infection during hospital stay, rotavirus infection , duration of diarrhea, need for rehydration, duration of viral excretion, duration of infection control measures, length of hospital stay in days, recurrent diarrhea or chronic diarrhea. DATA COLLECTION AND ANALYSIS: The two review authors independently abstracted data from the included trials. MAIN RESULTS: One published study (Barnes 1982) was eligible for inclusion in this review. Barnes 1982 found no significant difference in the rates of rotavirus infection after oral gammaglobulin versus placebo in hospitalized low birthweight babies [RR 1.27 (95% CI 0.65 to 2.37)]. In the subset of infants who became infected with rotavirus after receiving gammaglobulin or placebo for prevention of rotavirus infection, there was no significant difference in the duration of rotavirus excretion between the group who had gammaglobulin (mean 2 days, range 1 to 4 days) and the group who had placebo (mean 3 days, range 1 to 6 days). Barnes 1982 reported no adverse effects after administration of oral immunoglobulin preparations. AUTHORS' CONCLUSIONS: Current evidence does not support the use of oral immunoglobulin preparations to prevent rotavirus infection in low birthweight infants. Researchers are encouraged to conduct well-designed neonatal trials using the newer preparations of anti-rotaviral immunoglobulins (colostrum, egg yolk immunoglobulins) and include cost effectiveness evaluations.

Oral immunoglobulin for the treatment of rotavirus diarrhea in low birth weight infants.

BACKGROUND: Rotavirus infection is the most common neonatal nosocomial viral infection. It is a major health problem worldwide. Epidemics with the newer P(6)G9 strains have been reported in neonatal units globally. These strains can cause severe symptoms in most infected infants. Infection control measures become necessary and the utilization of hospital resources increase. Local mucosal immunity in the intestine to rotavirus is important in the resolution of infection and protection against subsequent infections. Boosting local immunity by oral administration of anti-rotaviral immunoglobulin preparations might be a useful strategy in treating rotaviral infections, especially in low birth weight babies. OBJECTIVES: To determine the effectiveness and safety of oral immunoglobulin preparations for the treatment of rotavirus diarrhea in hospitalized low birth weight infants (birth weight less than 2500 g) SEARCH STRATEGY: Electronic databases including The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), MEDLINE, EMBASE and CINAHL, Biological Abstracts (BIOSIS) were searched by the strategy outlined in the protocol. Science Citation Index search for all articles that referenced Barnes 1982 were searched. The proceedings of the Pediatric Academic Societies published online at 'Abstracts Online' were searched. Ongoing registered trials at www.clinicaltrials.gov and www.controlled-trials.com were searched. Authors prominent in the field were contacted for any unpublished articles and more information on published articles was sought. Reference lists of identified clinical trials and personal files were also reviewed. The above search was updated in July 2011. SELECTION CRITERIA: The criteria used to select studies for inclusion were: 1) DESIGN: randomized or quasi-randomized controlled trials 2) Hospitalized low birth weight infants with rotavirus diarrhea 3) INTERVENTION: Oral immunoglobulin preparations compared to placebo or no intervention 4) At least one of the following outcomes were reported: All cause mortality during hospital stay, mortality due to rotavirus infection during hospital stay, duration of diarrhea, need for rehydration, duration of viral excretion, duration of infection control measures, length of hospital stay in days, recurrent diarrhea or chronic diarrhea DATA COLLECTION AND ANALYSIS: The two reviewers were to independently abstract data from eligible trials. No data were available for analysis. MAIN RESULTS: No eligible randomized controlled trials were found. AUTHORS' CONCLUSIONS: No randomized controlled trials that assessed the effectiveness or safety of oral immunoglobulin preparations for the treatment of rotavirus diarrhea in hospitalized low birth weight infants were found. Clinical trials that address the issue of oral immunoglobulin treatment of rotavirus infection are needed.

Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates.

BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotizing enterocolitis (NEC) is high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline, a phosphodiesterase inhibitor, is one such agent. OBJECTIVES: The primary objectives were 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 and NEC. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2011), MEDLINE, EMBASE and CINAHL, Science Citation Index for articles referencing Lauterbach 1996, proceedings of the Pediatric Academic Societies (1990 to 2011), BIOSIS (1992 to 2011), conference proceedings (1992 to 2011), ongoing trials and reference lists of identified RCTs were searched in July 2011. SELECTION CRITERIA: Randomised or quasi-randomised trials assessing the efficacy of pentoxifylline as an adjunct to antibiotics for treatment of suspected or confirmed sepsis or NEC in neonates were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted information for the outcomes of interest. Typical relative risk (RR) and risk difference (RD) with 95% confidence intervals (CI) using fixed effects model are reported for dichotomous outcomes and mean differences for continuous outcomes. NNT was calculated for outcomes for which there was a statistically significant reduction in RD. MAIN RESULTS: In four randomised controlled trials, 227 neonates with suspected or confirmed sepsis were randomised to pentoxifylline or placebo. Pentoxifylline therapy significantly decreased "all cause mortality during hospital stay" in the overall population of infants with sepsis [typical RR 0.40 (95%CI 0.20 to 0.77); typical RD -0.15 (95%CI -0.26 to -0.05); NNT 7 (95%CI 4 to 20)]. Subgroup analyses revealed significant reduction in mortality in preterm infants, infants with confirmed sepsis and gram-negative sepsis. Pentoxifylline treatment significantly decreased length of hospital stay [mean difference -11.20 [95%CI -22.09 to -0.31] but not development of NEC in neonates with sepsis [typical RR 0.29 (95%CI 0.07 to 1.24); typical RD -0.20 (95%CI -0.41 to 0.01)]. No adverse effects due to pentoxifylline were noted. No completed trial of treatment with pentoxifylline for treatment of NEC was identified. AUTHORS' CONCLUSIONS: Current evidence from four small studies suggests that the use of pentoxifylline as an adjunct to antibiotics in neonatal sepsis decreases mortality without any adverse effects. Researchers are encouraged to undertake large well-designed multicenter trials to confirm or refute the effectiveness of pentoxifylline in reducing mortality and adverse outcomes in neonates with suspected or confirmed neonatal sepsis and NEC.

Caesarean or vaginal delivery for preterm very-low-birth weight (< or =1,250 g) infant: experience from a district general hospital in UK.

OBJECTIVE: To determine whether delivery by caesarean is associated with a better neuro-developmental outcome at two years for preterm infants born weighing 1,250 g or less. SETTING: District General Hospital, United Kingdom. DESIGN: All inborn infants weighing <1,250 g born at St Helier University Hospital between January 1995 and December 2003 were identified from contemporaneously collected computer database. All hospital records were retrieved. Details of the mother, delivery route, Apgar score, details of resuscitation and details of the baby, neonatal progress and neuro-developmental status at two years was transcribed on a pre-designed proforma. Neuro-developmental status assessment at two years of age was carried out by an independent neurodevelopmental paediatrician. Neuro-developmental status was classified as normal, severe, moderate or mild disability. STATISTICAL ANALYSIS: Analysis was done by creating a simple two by two table. Statistical significance was set at p = 0.05. Multivariate and univariate analysis was carried out for a number of confounding variables. SAMPLE: Total of 411 babies were identified from the data-base. Of these 59 were still born and fourteen though born alive died in the delivery suit. 125 (37%) were excluded from analysis as they were returned to their referring hospitals prior to discharge from hospital. Information about their two-year follow-up was either incomplete or not robust enough to be included in the analysis. Analysis was carried out on 213(63%) for whom we had complete data set at two years of age (103 infants born via vaginal delivery and 110 infants were born by caesarean section). OUTCOME MEASURE: Primary outcome measure was to compare survival at discharge and neurodevelopmental status at two years of age of this cohort. Secondary outcome included determining the incidence of grade III or IV intraventricular haemorrhage (IVH), chronic lung disease and necrotising enterocolitis (NEC). RESULTS: The overall caesarean delivery rate for this cohort was 51.6% while the overall caesarean rate for all births at our hospital during the study period varied between 20 and 23%. Neonatal mortality for those delivered by caesarean was 12.7% compared to 14.5% for those delivered vaginally (p = ns). Overall incidence of any neuro-disability at two years of age was 46.8% for those delivered by caesarean compared to 47.7% for those delivered vaginally (p = ns). There was no difference in those with severe (23.5% vs. 25.0%), moderate (10.4% vs. 9%) or mild (12.5% vs. 13.6%) neuro-disability between the groups nor was there any difference in the number of babies with IVH, chronic lung disease and NEC. Neuro-disability was equally greater in both groups for babies born weighing 750 grams or less and/or born at 26 weeks or less gestation. CONCLUSION: Despite the increasing tendency to deliver extremely preterm babies by caesarean, we did not find that it was associated with either reduced mortality or neuro-disability at two years of age. Therefore the method of delivery of very-low-birth weight premature infants should be based on obstetric or maternal indications rather than the perceived outcome of the baby.

Definitions of bloodstream infection in the newborn.

OBJECTIVE: To develop definitions of bloodstream infections in the newborn that would enable clinicians to identify infection early, so patients can be enrolled in clinical trials. The definitions should be useful for surveillance and epidemiologic purposes. METHOD: Search of EMBASE, MEDLINE, and Cochrane Library using age and English language limited key words sepsis, septicemia, and shock. Extensive study of textbook of neonatology and discussions with experts in the field. RESULTS: The search identified >2,000 references. The most appropriate were selected and reviewed. Definitions of bloodstream infection were developed after consultation with an international faculty. CONCLUSION: Current definitions of neonatal infection (and associated categories) used by neonatal clinicians and researchers have been either adapted/modified from definitions developed for adults or generated by individuals to suit their local needs or the needs of a particular study. It is clear that definitions generated for adults are not applicable to children or to newborn infants. In addition, developing and using unique definitions to suit individual or local needs make comparisons of outcome data and result of studies very difficult. This article proposes a set of definitions that are based as much as possible on current evidence. These definitions may be applicable widely for daily management of an infant with an infection and for research and epidemiologic studies.

Pattern of culture-proven neonatal sepsis in a district general hospital in the United Kingdom.

OBJECTIVE: To determine the incidence, clinical characteristics, and risk factors associated with the first culture-proven episode of sepsis among neonates in a neonatal intensive care unit (NICU). SETTING: Level-II NICU in the United Kingdom. PATIENTS: Neonates with their first culture-proven sepsis between January 1, 1996, and December 31, 2000. METHODS: Demographic data were obtained from the NICU database and chart review. Sepsis was considered early (EOS; < 72 hours old) or late (LOS; > 72 hours old). Data were also collected on potential risk factors. RESULTS: Among 14,767 live births, 1,612 (11%) neonates were admitted to the NICU during the study period. Nine hundred eight were screened for sepsis. One hundred twenty-four had at least one positive culture (overall sepsis rate of 8.4 per 1,000 live births [1%] or 77 per 1,000 NICU admissions). Twenty-four neonates had EOS and 100 had LOS. Coagulase-negative staphylococci (CoNS) and group B Streptococcus were the most frequent organisms causing EOS, whereas CoNS and Escherichia coli most frequently caused LOS. Birth before 30 weeks' gestation and birth weight less than 1,500 g were risk factors for sepsis. Resuscitation at birth was the leading risk factor for EOS and respiratory support prior to sepsis, presence of a central or peripheral catheter, and total parenteral nutrition were leading risk factors for LOS. CONCLUSIONS: A strong inverse relationship existed between gestational age of 30 weeks or younger and birth weight of 1,500 g or less and LOS. Resuscitation and indwelling intravenous catheters were also risk factors.