VLBW Neonates Research Articles

Updated Meta-analysis of Probiotics for Preventing Necrotizing Enterocolitis in Preterm Neonates

Systematic reviews of randomized, controlled trials (RCTs) indicate lower mortality and necrotizing enterocolitis (NEC) and shorter time to full feeds after probiotic supplementation in preterm (<34 weeks' gestation) very low birth weight (VLBW; birth weight <1500 g) neonates. The objective of this study was to update our 2007 systematic review of RCTs of probiotic supplementation for preventing NEC in preterm VLBW neonates. We searched in March 2009 the Cochrane Central register; Medline, Embase, and Cinahl databases; and proceedings of the Pediatric Academic Society meetings and gastroenterology conferences. Cochrane Neonatal Review Group search strategy was followed. Selection criteria were RCTs of any enteral probiotic supplementation that started within first 10 days and continued for > or =7 days in preterm VLBW neonates and reported on stage 2 NEC or higher (Modified Bell Staging). A total of 11 (N = 2176), including 4 new (n = 783), trials were eligible for inclusion in the meta-analysis by using a fixed-effects model. The risk for NEC and death was significantly lower. Risk for sepsis did not differ significantly. No significant adverse effects were reported. Trial sequential analysis) showed 30% reduction in the incidence of NEC (alpha = .05 and .01; power: 80%). The results confirm the significant benefits of probiotic supplements in reducing death and disease in preterm neonates. The dramatic effect sizes, tight confidence intervals, extremely low P values, and overall evidence indicate that additional placebo-controlled trials are unnecessary if a suitable probiotic product is available.

Safety and efficacy of Vinyl bags in prevention of hypothermia of preterm neonates at birth

The present study was planned to evaluate the safety and efficacy of vinyl bags in prevention of hypothermia during resuscitation at birth in very low birth weight neonates. Sixty neonates of gestational age ≤32 weeks and birth weight ≤ 1500gm were randomised to either study group, or control group. Study group neonates were put in vinyl bags up to neck and the head was covered with a cap after drying immediately following delivery and resuscitated under radiant warmer. Control group neonates were resuscitated by conventional drying under radiant warmer. Mean axillary and rectal temperature recorded immediately after admission to NICU were significantly higher in the study group compared to control group. Temperature recorded after 1 hour of admission to NICU were however comparable between the two groups. As temperature maintenance in these VLBW neonates is of tremendous importance, it would make sense to recommend the use of vinyl bags during their resuscitation.

Aminoacid-based formula as a rescue strategy for feeding VLBW SGA infants

Whenever breast milk is unavailable, preterm formula is chosen to start and progress enteral feeding in VLBW infants; when these neonates have an associated growth retardation, the achievement of full enteral feeding can be particularly difficult. Consecutively, inborn VLBW neonates with weight centile < 5th, free from major malformations for whom breast milk was not available were enrolled in the study from January 2007 to June 2008. Cases were classified as feeding intolerant after at least 72 h on the basis of a sudden significant increase in gastric residuals and/or an abnormal abdominal examination and fed an Aa-based formula (AAF) with the same schedule. Cases were compared to A) VLBW infants exclusively fed on SPF; and B) themselves before the introduction of AAF. 22 infants were rescued on Aa-based formula; 42 control infants were enrolled. VLBW cases had a shorter number of gastric residual volume > 5 ml/kg at 48 h (3/20) than VLBW controls (15/42), shorter gastric residual volume at 72 h (0.6 ± 1.2) than VLBW controls (0.9 ± 1.5) and shorter residuals/total formula at 72 h (22.4 ± 38.1) than VLBW controls (51.2 ± 104.5) after the introduction of the FE. In the present clinical setting, the use of AAF: • improves feeding tolerance in VLBW cases = 10° of BW; • equalizes the time of parenteral nutrition and the time to reach 150 ml/kg enteral feeding in VLBW cases, compared to VLBW controls, without affecting growth.

Neonatal Sepsis of Vertical Transmision. An epidemiological study from the “Grupo de Hospitales Castrillo”

Neonatal sepsis of vertical transmission occurs as a result of colonization of the fetus before or during labor by microorganisms from the maternal genital tract. Group B streptococcal (GBS) infection is the most frequent cause of vertical sepsis and a leading cause of neonatal mortality. In Spain, national guidelines for the prevention of perinatal GBS infection were issued in 1998. To assess the epidemiology of neonatal vertical sepsis in our country (Spain). From 1996 the neonatal services of 34 acute-care teaching hospitals in Spain (“Grupo de Hospitales Castrillo”) carries out a prospective surveillance of the epidemiology of vertical neonatal sepsis. In the study period (1996-2008) a total of 1,109.669 live birth were analyzed. The incidence of vertical confirmed sepsis declined by 55%, from 2.4/1000 live birth in 1996 to 1.08/10000 in 2008 (p < 0.001), without significant variation in vertical clinical sepsis (3.5/1000 and 2.5/1000 live birth respectively). The incidence of both confirmed sepsis and clinical sepsis was significantly higher in the group of VLBW neonates than in those weighing > 500 . The incidence of GBS vertical sepsis declined significantly by 73.6%, from 1.25/1000 live birth in 1996 to 0.33/1000 IN 2008 (p < 0.001). There were fluctuations in the incidence of E. coli infection and no significant variations of other gram negative bacteria. The mortality rate of proven sepsis ranged between 8-11% in the study period and was significantly higher in the VLBW cohort. The global mortality per 1000 live birth decreased from 0.33 to 0.18 per 1000 live birth. There was a substantial decline in the incidence of vertical confirmed sepsis with significant reduction in the incidence of GBS sepsis in the study period, as consequence of the impact of antimicrobial intrapartum prophylaxis. Fluctuations in the incidence of E. coli infection suggest the need for continuing epidemiological surveillance.

Antistaphylococcal immunoglobulins to prevent staphylococcal infection in very low birth weight infants

Nosocomial infection is a major problem affecting the immediate health and long-term outcome of preterm and very low birth weight neonates. More than half of these infections are caused by staphylococci. Various type specific antibodies targeted at different antigenic markers of Staphylococcus have been developed and have shown promise in animal studies. To evaluate the efficacy and safety of antistaphylococcal immunoglobulins in the prevention of Staphylococcal infection in very low birth weight infants. Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials (The Cochrane Library) were searched from their inception until February 2009. In addition, abstracts of major pediatric meetings of last seven years were searched. Randomized and quasi-randomized studies of antistaphylococcal immunoglobulins for the prevention of staphylococcal infections in preterm or very low birth weight neonates were reviewed by both authors for their eligibility for inclusion. Studies of any dose and/or route were included. Quality of studies was evaluated using criteria of masking of randomization, masking of intervention, completeness of follow-up and masking of outcome assessment by both review authors. Data from the primary author were obtained where published data provided inadequate information for the review or where relevant data could not be abstracted. Data were abstracted independently by both review authors. Statistical methods included calculation of relative risk (RR), risk difference (RD), number needed to treat (NNT) and weighted mean difference (WMD) when appropriate. Ninety five percent confidence intervals (CI) was used for these estimates of treatment effects. A fixed effect model was used for meta-analyses. Three eligible studies were included (two studies of INH A-21 and one study of Altastaph involving a total of 2,701 neonates). Three reports of Pagibaximab were published as abstracts and will be considered for inclusion when further information is obtained. There were no significant differences noted in the risk of Staphylococcal infection between INH A-21 vs. placebo (typical RR 1.07, 95% CI 0.94, 1.22) or Altastaph vs. placebo (RR 0.86, 95% CI 0.32, 2.28); the risk of other bacterial infection between INH A-21 vs. placebo (typical RR 0.87, 95% CI 0.72, 1.06) or Altastaph vs. placebo (RR 0.93, 95% CI 0.53, 1.64); or the risk of any infection between INH A-21 vs. placebo (RR 1.00, 95% CI 0.91, 1.09) or Altastaph vs. placebo (RR 0.93, 95% CI 0.54, 1.62). There was no significant difference in the incidence of relevant secondary outcomes (chronic lung disease at 28 days, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, retinopathy of prematurity or duration of antibiotic and vancomycin use). Antistaphylococcal immunoglobulins (INH A-21 and Altastaph) are not recommended for prevention of staphylococcal infections in preterm or VLBW neonates. Further research to investigate the efficacy of other products such as Pagibaximab is needed.

Efficacy and safety of surgical treatment of PDA in VLBW neonates. Warsaw region multicenter collaboration

Efficacy and safety of surgical treatment of PDA in VLBW neonates. Warsaw region multicenter collaboration

Early insulin for VLBW neonates: little clinical benefit

Early insulin for VLBW neonates: little clinical benefit

Routine Use of Fluconazole Prophylaxis in a Neonatal Intensive Care Unit Does Not Select Natively Fluconazole-Resistant Candida Subspecies

We have previously demonstrated efficacy against fungal colonization and infection of fluconazole prophylaxis that was routinely administered since 2001 in our ICU for preterm infants <1500 g at birth (VLBW). With prolonged use, concerns exist for the emergence of acquired fungal resistance and of Candida subspecies that are natively fluconazole-resistant (NFR), mostly Candida glabrata and Candida krusei. We evaluated retrospectively all clinical and surveillance fungal isolates obtained from VLBW infants in our NICU during a 10-year period (1997-2006). Each fungal isolate was speciated, infants colonized or infected with NFR-Candida spp were identified and the incidence rates of colonization and infection by these fungal species were calculated. A comparison was made of the 6-year (2001-2006) prophylaxis period with the 4-year (1997-2000) preprophylaxis period. Overall, colonization by NFR-Candida spp ranged between 2.8% and 6.6% of VLBW infants yearly admitted, without any increasing trend during the study period. There were 18 of 434 (4.1%) neonates colonized by these species. Five episodes of systemic fungal infections caused by NFR-Candida spp occurred (incidence rate, 1.1%). No significant differences were detected when compared with the preprophylaxis period, when 11 of 295 infants (3.7%) were colonized by NFR-Candida spp and 4 episodes of infection occurred (1.4%) (P = 0.84 and 0.76, respectively). Fluconazole prophylaxis administered to VLBW neonates in 4- to 6-week courses after birth does not lead to the emergence of natively fluconazole-resistant Candida spp.

Escaping With VLBW Neonates

Escaping With VLBW Neonates

Association of BPD and IVH with early neutrophil and white counts in VLBW neonates with gestational age &lt;32 weeks

To investigate associations between early low neutrophil count from routine blood samples, white blood count (WBC), pregnancy complications and neonatal outcomes for very low birth weight infants (VLBW <or=1500 g) with gestational age <32 weeks. Information was abstracted on all infants admitted to level III neonatal intensive care units in Wisconsin 2003 to 2004. A total of 1002 VLBW neonates (78%) had differential and corrected total white counts within 2 (1/2) h of birth. Data analyses included frequency tables, binary logistic, ordinal logistic and ordinary regression. Low neutrophil count (<1000 per microl) was strongly associated with low WBC, pregnancy complications and antenatal steroids. Low neutrophil count predicted bronchopulmonary dysplasia severity level (odds ratio, OR: 1.7, 95% confidence interval, CI: 1.1 to 2.7) and intraventricular hemorrhage grade (OR: 2.2, 95% CI: 1.3 to 3.8). Early neutrophil counts may have multiple causes interfering with their routine use as an inflammatory marker. Nonetheless, low neutrophil count has consistent independent associations with outcomes.

Relationship Between Perinatal and Neonatal Indices and Intelligence Quotient in Very Low Birth Weight Infants at the Age of 6 or 8 Years

The majority of children born with very low birth weight (VLBW; < 1500g) enter mainstream schools. They experience significant neurodevelopmental disabilities during childhood. The specific aims of our study were to evaluate the neonatal outcomes of VLBW infants and whether they would influence intelligence quotient (IQ), cognitive function and learning disabilities at the age of 6 or 8 years. We enrolled VLBW neonates who weighed less than 1500g and who were delivered at Shin-Kong Wu Ho-Su Memorial Hospital in 1996 and 1999. The psychological assessments were applied with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) for age 6 and Wechsler Intelligence Scale for Children-Third Edition (WISC-III) for age 8. We recorded their demographic data, ventilation duration by days, length of stay, use of surfactant, respiratory distress syndrome (RDS), and other complications. According to whether the full scale intelligence quotient (FSIQ) was above or below the average score (FSIQ = 90), we divided VLBW children into two groups (< 90, n = 17; > or = 90, n = 21). The children with lower gestational age had lower FSIQ (p = 0.013). The higher FSIQ group (> or = 90) showed more prenatal steroid use (5/17, 29.4% vs. 14/21, 66.7%; p = 0.049). There were more boys in the lower FSIQ group (< 90, 13/17, 76.5% vs. > or = 90, 7/21, 33.3%; p = 0.011). The average IQ scores were 78.11 +/- 9.05 and 102.57 +/- 8.89 in the FSIQ < 90 and FSIQ > or = 90 groups, respectively. The groups were similar in ventilation duration by days, use of surfactant, frequency of sepsis, RDS, bronchopulmonary dysplasia, patent ductus arteriosus, intraventricular hemorrhage and retinopathy of prematurity. In our study, the children with lower gestational age had lower FSIQ. There was no significant association between small for gestational age and IQ performance. The neonatal outcomes of VLBW infants did have less impact on IQ performance later in life.

Assessment of serum interleukin-6 with a rapid test. The diagnosis of neonatal sepsis can be established or ruled out

The mortality rate from sepsis is high and the risk of sepsis increases in prematurity in proportion to the decrease in birth weight. The authors report the assessment of serum interleukin-6 levels in 12 term, at-risk newborn infants after birth and 60 VLBW neonates after detection of non-specific signs of infection or sepsis, treated in NICU at the Semmelweis University, 1st Department of Obstetrics and Gynecology in 2005-2006. The serum IL-6 level with a rapid test (Milenia Quickline IL-6 and PicoScan system) was investigated. The simultaneous assessment of C-reactive protein levels was analysed as well. The assessment of serum interleukin-6 and CRP levels for the early diagnosis of sepsis can be established or ruled out. The sensitivity of serum IL-6 level assessment was 100%. There were no false negative cases. The positive predictive value was 93%. There was a significant difference between the sepsis and infection group of VLBW infants in the serum Il-6 levels ( p = 0.048), and between the infection and non-infection groups in the interleukin-6 levels ( p < 0.005). In comparing the diagnostic value of IL-6 measurement in VLBW infants with signs of infection to the diagnostic methods currently in use, results showed that a combination of early assessment of IL-6 and CRP seems to increase diagnostic accuracy in attempting to differentiate between septic and nonseptic patients. Such increased accuracy will decrease neonatal morbidity as well as the financial cost of treatment.

EN ROUTE STABILITY OF VERY LOW BIRTH WEIGHT PREMATURE INFANTS USING HIGH-FREQUENCY VENTILATION.

Background Mechanical ventilation is required for survival of very low birth weight (VLBW; ≤ 1,250 g) premature infants. However, mechanical ventilation is also a common cause of chronic lung injury, also known as bronchopulmonary dysplasia (BPD), the primary cause of morbidity and mortality among surviving VLBW infants. High-frequency ventilation (HFV) differs from conventional modes in that it allows ventilation and oxygenation of the infant using higher mean airway pressures and smaller tidal volumes. Experimentally, HFV has been shown to improve lung function and protect against ventilator-induced injury in animal models. However, human studies are divergent as to whether HFV demonstrates a clinically significant advantage, and there are no large studies published to date evaluating the en route stability of neonates in whom HFV is used during transport. Therefore, we sought to describe our local experience using a newly implemented HFV transport ventilator, the Bronchotron®-I, in the transport of premature VLBW infants. Methods VLBW neonates who were transported within the first 3 days of life by the Intermountain Health Care (IHC) LifeFlight program on HFV were evaluated by medical chart review for en route physiologic stability. All neonates were evaluated for physiologic stability and en route markers of deterioration. Results Fifty-eight patients met the inclusion criteria (mean transport time 2.38 hours). All neonates tolerated the HFV ventilator en route. There were two instances of barotrauma during transport, neither of which was attributable to placement of the device. Arterial blood gases overall remained stable or improved during transport. For the majority of transports, mean blood pressure (MBP) also remained stable (n = 31; 54%) or showed a clinically significant (> 20%) improvement (n = 23; 40%). Conclusions In our local experience, VLBW neonates in whom HFV was used during transport remained physiologically stable en route and did not appear to experience adverse sequelae attributable to use of the HFV device. We therefore conclude that the Bronchotron®-I appears to be a safe and effective method of ventilation during transport of VLBW neonates. Larger multicenter trials may help compare differences in en route stability for VLBW infants transported on conventional ventilation versus HFV.

Escaping With VLBW Neonates: Caring for and Transporting Very Low Birth Weight Infants During a Disaster

August 29: Hurricane Katrina Landfall: I am a neonatologist in private practice and had been at the hospital for >24 hours along with 40 other physicians. I had volunteered to take care of the patients at Memorial Medical Center (MMC) during Hurricane Katrina. There were 16 infants in the NICU, ∼260 patients in total at the hospital, 500 essential employees, and >1200 family members of the patients and employees with their pets taking refuge from the storm. An additional 50 patients were in an acute care ward for adults with chronic conditions run by LifeCare within the hospital premises. Like most people, I thought Katrina would be just like other hurricanes that had threatened the city in the last few years. We would be at the hospital for a few days, and then we would return home. I had no idea what we were about to encounter. As Katrina approached New Orleans, Louisiana, the NICU staff moved the infants to an inside room because of the many windows that could endanger their safety. When Katrina made landfall in the early morning, the strong 125-mph winds did blow in several of the hospital's windows, including some in the NICU. As soon as the electrical power was lost, the backup generators started and restored the emergency electrical services. After enduring several hours of severe winds and rain, there was a general feeling of relief because the storm was over. Many windows were shattered, there was glass and water in many places, but apparently there was little structural damage to the main hospital building. In the ensuing hours we heard that the storm surge had breached the levee system, and the waters from Lake Pontchartrain were flooding the city. Still, we had no awareness of the impending severity of the situation. It soon … Address correspondence to Juan J. Gershanik, MD, FAAP, Medical Director, Neonatal Intensive Care Unit, West Jefferson Medical Center, 1101 Medical Center Blvd, Marrero, LA 70072. E-mail: jgershanik{at}aol.com

Very Low Birth Weight Baby: Review of Outcome and Personal Experience

Very low birth weight baby (VLBW) the limit for intact survival 15 years ago, has been replaced with extremely low birh weight babies (ELBW) as the neonatal intensive care unit(NICU) responds to these challenges. There are several risk factors associated with VLBW babies and the goal of management is to reduce mortality as well as the long term morbidity. The outcome varies depending on the level of care provided in the perinatal period. On comparative analysis we found that small babies in developing countries were more mature as compared to a similar birth weight baby in western countries. Hence, we see lower incidence of respiratory distress syndrome and associated complications. We can expect a reasonable outcome in babies >800 g birth weight and 28 weeks gestation and therefore all efforts should be made for providing adequate care to this group of VLBW neonates.

Prophylactic Fluconazole Is Effective in Preventing Fungal Colonization and Fungal Systemic Infections in Preterm Neonates: A Single-Center, 6-Year, Retrospective Cohort Study

Despite the promising preliminary results observed in extremely low birth weight (ELBW) populations, the use of fluconazole to prevent fungal colonization and infection in preterm neonates in the NICU is still an open question and not yet recommended as a standard of care. We have reviewed our 6-year series to assess the effectiveness and safety of this form of prophylaxis. This retrospective study consisted of 465 neonates who weighed < 1500 g at birth and were admitted to our NICU in the period 1998-2003. Those who were born between 1998 and 2000 and did not receive fluconazole prophylaxis (group A, n = 240) were compared with those who were born between 2001 and 2003 and treated with fluconazole until the 30th day of life (45th for neonates < 1000 g at birth; group B, n = 225). Weekly surveillance cultures were obtained from all patients. Incidence of fungal colonization, incidence of systemic fungal infection (SFI), rate of progression from colonization to infection, and mortality rates attributable to fungi were calculated for both groups and separately for neonates who were < 1000 g (ELBW) and were 1001 to 1500 g (NE-VLBW) at birth. Overall fungal colonization was significantly lower in group B (24.0%) than in group A (43.8%; relative risk [RR]: 0.406; 95% confidence interval [CI]: 0.273-0.605). The same was true of neonates with colonization in multiple sites (2.6% vs 5.8%) and of those with colonization from high-risk sites (5.8% vs 19.2%). SFI incidence was significantly lower in group B (10 of 225 cases; 4.4%) than in group A (40 of 240 cases; 16.7%; RR: 0.233; 95% CI: 0.113-0.447). Reduction of both colonization and SFI in group B was greater in the ELBW neonates and also significant in the NE-VLBW neonates. Rate of progression from colonization to infection was significantly lower in group B (0.17 vs 0.38; RR: 0.369; 95% CI: 0.159-0.815). Crude mortality rate attributable to Candida species was 1.7% (4 of 240) in group A vs 0% (0 of 225) in group B. Overall mortality rate (any cause before hospital discharge) was similar in the two groups (11.2% vs 10.6%), but in colonized infants (n = 159), it was significantly lower in group B (3.7% vs 18.1%; RR: 0.174; 95% CI: 0.039-0.778). The incidence of natively fluconazole-resistant fungal species did not increase over the years, and patterns of sensitivity to fluconazole remained the same. No adverse reaction related to fluconazole occurred. Prophylactic fluconazole significantly reduces the incidence of colonization and systemic infection by Candida species in both ELBW and NE-VLBW neonates and decreases the rates of progression from initial colonization to massive colonization and to systemic infection. All VLBW neonates may benefit from fluconazole prophylaxis.

206 Thymus Size as a Prognostic Size in Bronchopulmonary Dysplasia

BDP is major cause of premature neonates mortality and morbidity. Causes of BDP are oxygen toxicity, injuries caused by ventilators and respiratory volumes, perinatal inflammations. Chorioamnionitis is related to thymus functions through the intrauterine actions of cytokines. The purpose is to check the reliability of the chest X-Ray as prognostic sign in the development of BDP. Method: 34 chest X-Rays, taken from VLBW neonates, within the first 6 hours after birth, were reviewed. The following criteria were taken into account: 1 Mechanical ventilation = or > 3 days within the first week after birth. 2 Need for O2 administration for 28 days after birth. 3 Radiological findings of BDP in the chest X-Ray. Moreover, 34 chest X-Rays of VLBW neonates who did not develop BDP were reviewed. Thymus size was measured as a ratio between thymus diameter on the level of velum and thorax diameter(CT/T). Statistic analysis was performed by using ANOVA and t-test. Results: ANOVA method:34 neonates complied with the criteria of the study. Another 34 neonates were considered as witnesses. The mean CT/T of the first group was 0,33 and of the second group was 0,42. We found F=15,5>rate criterium F=7,035 with freedom degrees 1/66. Error probability was 1%. By this mean CT/T of the witnesses is statistically higher than the one of the patients with BDP. T-test: t=-3,93 with t-crucial double-sided=2,66. This method confirms that CT/T of witnesses is higher than CT/T of the patients. Discussion: The results show that the chest X-Ray within the first hours of life of VLBW premature neonates has prognostical value in the development of BDP. Small thymus size at birth shows that all mechanisms related to BPD have been activated intrauterus.

Enteral Administration of a Simulated Amniotic Fluid to Very Low Birth Weight Neonates

To reduce feeding intolerance among very low birth weight neonates. A total of 10 neonates with birth weights of 750 to 1250 g were given oral-gastric boluses (2.5 ml/kg every 3 hours) of a solution patterned after amniotic fluid. When milk feedings were begun the milk was mixed with the test solution. The solution was given at a constant daily dose of 20 ml/kg/day while the volumes of milk feedings were gradually increased. When milk feedings reached 80 ml/kg/day the test solution was discontinued. A comparison group consisted of neonates who met study criteria but were cared for during the period immediately preceding the study. The outcome was the number of calories taken enterally over the first 21 days of life. The test solution was begun an average of 27 hours after birth (range, 4 to 45). In the test group the first milk feedings were introduced 74 hours after birth (range, 18 to 144), which was similar to the time milk was introduced in the comparison subjects (79 hours; range, 18 to 168). After milk feedings were started, the test patients had a total of four NPO days (0.4 NPO days per patient) during their first 21 days, while the comparison group had 34 NPO days (3.4 NPO days per patient). During the first 14 days of life the test solution recipients had a median of 26.5 enteral cal/kg/day (range, 4.3 to 68.9), while the comparison neonates had 8.5 (range, 0.2 to 25; p < 0.05). During the first 21 days of life the test solution recipients had a median of 56.9 enteral cal/kg/day (range, 11.5 to 89.4), while the comparison neonates had 19.2 (range, 0.9 to 52.8; p < 0.05). In all, 10 VLBW infants tolerated the test solution for periods up to 14 days with no significant adverse effects. A randomized trial to determine whether this solution reduces feeding intolerance among VLBW neonates should be conducted.

Hospital survival of very-low-birth-weight neonates from 1977 to 2000.

To determine patterns of survival for very low birth weight (VLBW, birth weight 501 to 1500 g) neonates over 23 years. Data for 4873 VLBW neonates born from 1977 to 2000 were divided into five epochs. The primary outcome was survival to hospital discharge. Birth weight-specific survival rates were estimated by race and gender for each epoch. Presence of comorbidities and congenital anomalies, delivery mode, and provision of artificial ventilation were investigated to determine whether they could explain observed survival patterns. From 1977 to 1995, survival increased from 50.2% to 81.0% as the proportion of VLBW neonates receiving artificial ventilation rose from 59.0% to 80.9%. Survival was unchanged between 1990 to 1995 and 1996 to 2000. Black females maintained a survival advantage over the entire study period. Survival improved for neonates with congenital anomalies over time, but had little impact on race/gender survival patterns. Survival patterns also could not be explained by comorbidity status, delivery mode, or access to artificial ventilation. The survival advantage of VLBW black females persists and remains unexplained.

Effect of beginning recombinant erythropoietin treatment within the first week of life, among very-low-birth-weight neonates, on "early" and "late" erythrocyte transfusions: a meta-analysis.

Erythrocyte transfusions to neonates can be categorized as "early" if given during the first 3 weeks of life and "late" if given thereafter. We used a meta-analysis to determine whether recombinant erythropoietin (rEpo) administration to very-low-birth-weight (VLBW, <1500 g) neonates, beginning in the first week of life, reduces either "early" or "late" transfusions. Studies that used a randomized, placebo-controlled, double-masked design were deemed acceptable. We identified 12 acceptable, relevant, clinical trials. Additional data not provided in the publications were obtained from two of the authors. The acceptable studies involved an aggregate of 561 rEpo and 529 placebo recipients. If rEpo was begun in the first week of life, the summary odds ratio (OR) for receiving any transfusion ("early" or "late") was 0.52, 95% confidence interval (CI): 0.34 to 0.79 (p=0.001). The OR for receiving an "early" transfusion was 0.54 (95% CI: 0.25 to 1.15; p=0.055), and the OR for receiving a "late" transfusion was 0.56 (95% CI: 0.37 to 0.83; p=0.036). Heterogeneity among studies was too great to estimate the effect of rEpo on the number of transfusions received or the volume of blood transfused (p<0.001 for the Q-test statistic). Subgroup analysis suggested that when rEpo is begun in the first week of life, neonates 1000 to 1500 g and >29 weeks are more likely to completely avoid transfusion than are extremely low-birth-weight (ELBW, <1000 g) neonates. No dose-response relationship was apparent between rEpo dose or iron dose and transfusion. No difference was apparent depending on whether the rEpo was given subcutaneously vs intravenously. If rEpo is begun in the first week of life, a moderate reduction can be expected (p=0.001) in the proportion of VLBW neonates transfused. Reduction is less significant in "early" transfusion (p=0.055) than in "late" transfusion (p=0.036). Such treatment is not likely to eliminate transfusions among ELBW neonates completely.