Delayed cord clamping in preterm twin infants: a systematic review and meta-analysis.

OBJECTIVE: To compare the effects of delayed cord clamping (DCC) versus early cord clamping (EDD) on all-cause in-hospital mortality and selected morbidities among preterm twin neonates. DATA SOURCES: A search of PubMed, Ovid Medline, Embase, Cochrane database, Web of Science and CINAHL was conducted in December 2023 for studies comparing DCC to ICC in preterm twin neonates. STUDY ELIGIBILITY CRITERIA: Studies were deemed eligible if they included preterm twin neonates (< 37 weeks of gestation), compared delayed (≥ 30 seconds) vs early (<30 seconds) umbilical cord clamping at delivery and described at least one outcome of interest. Outcomes of interest were mortality, maternal hemorrhage, transfusion, severe interventricular hemorrhage (grade III or IV), bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity (stage IV or receiving treatment) and length of hospital stay. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently selected the studies, assessed bias and extracted data. Risk ratio and mean difference with 95% confidence intervals were determined by fixed effects models, heterogeneity by I2 statistics. RESULTS: Five studies compared DCC vs ECC in 2075 infants. Meta-analysis showed a significant reduction in mortality [(RR) 0.70 (95% CI 0.53-0.93)], a significant decrease in the risk of red blood cell transfusion [(RR) 0.42 (95% CI 0.28 - 0.64)] as well as a lower risk of retinopathy of prematurity [(RR) 0.50 (95% CI 0.26-0.96)] with DCC in twin population. DCC had no impact on the incidence of intraventricular hemorrhage [(RR) 1.01 (95% CI 0.79, 1.28)], of bronchopulmonary dysplasia [(RR) 0.67 (95% CI 0.36, 1.24)], of necrotizing enterocolitis [(RR) 1.02 (95% CI 0.60, 1.73)]. There was no significant effect on length of hospital stay [-0.10 (-0.20, -0.00)]. None reported maternal hemorrhage. CONCLUSION: DCC may decrease mortality risk in preterm twin infants without affecting major neonatal morbidities. Further evidence is needed to support its safety in preterm twins.

Pulmonary important outcomes after extremely preterm birth: Parental perspectives.

AIM: To describe pulmonary important outcomes (PIO) reported by parents of children born extremely preterm. METHODS: Over 1-year, all parents of children aged 18 months-7-years born <29 weeks' GA were asked regarding their perspectives. The proportion of parents who described PIO and the themes they invoked were examined. Results were analysed using mixed methods. RESULTS: Among parental responses (n = 285, 98% participation rate), 44% spoke about PIO, invoking 24 themes pertaining to NICU hospitalisation and/or long-term respiratory health. Some themes had an impact primarily on the child (e.g. exercise limitation), while the majority had an impact on the whole family (e.g. hospital readmissions). None mentioned oxygen at 36 weeks nor bronchopulmonary dysplasia (BPD). The proportion of responses invoking PIO were statistically similar between parents of children with and without BPD, born before or after 25 weeks or with birthweight < or ≥750 g. PIO were more likely to be mentioned in males and among those readmitted for respiratory problems. CONCLUSION: Parents describe many PIO, most related to the functional impact of lung disease on their child (and family), rather than the diagnosis of BPD itself. Most of these PIO are not primary outcomes in large neonatal trials nor collected in neonatal databases.

Avoidance of routine endotracheal intubation and general anesthesia for primary closure of gastroschisis: a systematic review and meta-analysis.

PURPOSE: Over the last few decades, several articles have examined the feasibility of attempting primary reduction and closure of gastroschisis without general anesthesia (GA). We aimed to systematically evaluate the impact of forgoing routine intubation and GA during primary bedside reduction and closure of gastroschisis. METHODS: The primary outcome was closure success. Secondary outcomes were mortality, time to enteral feeding, and length of hospital stay. RESULTS: 12 studies were included: 5 comparative studies totalling 192 patients and 7 descriptive case studies totalling 56 patients. Primary closure success was statistically equivalent between the two groups, but trended toward improved success with GA/intubation (RR = 0.86, CI 0.70-1.03, p = 0.08). Mortality was equivalent between groups (RR = 1.26, CI 0.26-6.08, p = 0.65). With respect to time to enteral feeds and length of hospital stay, outcomes were either equivalent between the two groups or favored the group that underwent primary closure without intubation and GA. CONCLUSION: There are few comparative studies examining the impact of performing primary bedside closure of gastroschisis without GA. A meta-analysis of the available data found no statistically significant difference when forgoing intubation and GA. Foregoing GA also did not negatively impact time to enteral feeds, length of hospital stay, or mortality.

Building trust and improving communication with parents of children with Trisomy 13 and 18: A mixed-methods study.

BACKGROUND: Trisomy 13 and trisomy 18 are common life-limiting conditions associated with major disabilities. Many parents have described conflictual relationships with clinicians, but positive and adverse experiences of families with healthcare providers have not been well described. AIM: (1) To investigate parental experiences with clinicians and (2) to provide practical recommendations and behaviors clinicians could emulate to avoid conflict. DESIGN: Participants were asked to describe their best and worse experiences, as well as supportive clinicians they met. The results were analyzed using mixed methods. SETTING/PARTICIPANTS: Parents of children with trisomy 13 and 18 who were part of online social support networks. A total of 503 invitations were sent, and 332 parents completed the questionnaire about 272 children. RESULTS: The majority of parents (72%) had met a supportive clinician. When describing clinicians who changed their lives, the overarching theme, present in 88% of answers, was trust. Parents trusted clinicians when they felt he or she cared and valued their child, their family, and made them feel like good parents (69%), had appropriate knowledge (66%), and supported them and gave them realistic hope (42%). Many (42%) parents did not want to make-or be part of-life-and-death decisions. Parents gave specific examples of supportive behaviors that can be adopted by clinicians. Parents also described adverse experiences, generally leading to conflicts and lack of trust. CONCLUSION: Realistic and compassionate support of parents living with children with trisomy 13 and 18 is possible. Adversarial interactions that lead to distrust and conflicts can be avoided. Many supportive behaviors that inspire trust can be emulated.

Correlations between near-infrared spectroscopy, perfusion index, and cardiac outputs in extremely preterm infants in the first 72 h of life.

Haemodynamic assessment during the transitional period in preterm infants is challenging. We aimed to describe the relationships between cerebral regional tissue oxygen saturation (CrSO2), perfusion index (PI), echocardiographic, and clinical parameters in extremely preterm infants in their first 72 h of life. Twenty newborns born at < 28 weeks of gestation were continuously monitored with CrSO2 and preductal PI. Cardiac output was measured at H6, H24, H48, and H72. The median gestational age and birth weight were 25.0 weeks (24-26) and 750 g (655-920), respectively. CrSO2 and preductal PI had r values < 0.35 with blood gases, lactates, haemoglobin, and mean blood pressure. Cardiac output significantly increased over the 72 h of the study period. Fifteen patients had at least one episode of low left and/or right ventricular output (RVO), during which there was a strong correlation between CrSO2 and superior vena cava (SVC) flow (at H6 (r = 0.74) and H24 (r = 0.86)) and between PI and RVO (at H6 (r = 0.68) and H24 (r = 0.92)). Five patients had low SVC flow (≤ 40 mL/kg/min) at H6, during which PI was strongly correlated with RVO (r = 0.98). CONCLUSION: CrSO2 and preductal PI are strongly correlated with cardiac output during low cardiac output states. What is Known: • Perfusion index and near-infrared spectroscopy are non-invasive tools to evaluate haemodynamics in preterm infants. • Pre- and postductal perfusion indexes strongly correlate with left ventricular output in term infants, and near-infrared spectroscopy has been validated to assess cerebral oxygenation in term and preterm infants. What is New: • Cerebral regional tissue oxygen saturation and preductal perfusion index were strongly correlated with cardiac output during low cardiac output states. • The strength of the correlation between cerebral regional tissue oxygen saturation, preductal perfusion index, and cardiac output varied in the first 72 h of life, reflecting the complexity of the transitional physiology.

Fluid restriction for treatment of preterm infants with chronic lung disease.

BACKGROUND: Fluid restriction is often recommended as part of the management of infants with early or established bronchopulmonary dysplasia (BPD). OBJECTIVES: To determine whether fluid restriction as part of the therapeutic intervention for early or established BPD improves clinical outcomes. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1) in the Cochrane Library (searched 16 February 2016), MEDLINE via PubMed (1966 to 16 February 2016), Embase (1980 to 16 February 2016), and CINAHL (1982 to 16 February 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Prospective randomised clinical trials comparing two distinct fluid administration volumes in preterm infants with early or established BPD. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. For the included trial, we extracted data and assessed the risk of bias, and used GRADE methods to assess the quality of the evidence. The outcomes considered in this review are effects on mortality or requirement for oxygen at 36 weeks' postmenstrual age (primary outcome measure), the duration of supplemental oxygen therapy, proportion of infants discharged from hospital on oxygen, duration of assisted ventilation, duration of hospitalisation, weight gain, feeding tolerance, apnoea, necrotizing enterocolitis, renal dysfunction or nephrocalcinosis, lung mechanics, and use of diuretic therapy (secondary outcome measures). MAIN RESULTS: One trial was found, including 60 preterm infants at 28 days of age with persistent oxygen requirements. Infants were randomised to either 180 mL/kg/day of standard formula or 145 mL/kg/day of concentrated formula. This single study did not provide data regarding our primary outcome. No effects of the intervention were found on any of our secondary outcomes. The quality of the evidence from this study was graded low. AUTHORS' CONCLUSIONS: There is no evidence to support the practice of fluid restriction in infants with early or established BPD.

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide (iNO) is effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure and the potential risks of iNO differ substantially in preterm infants, necessitating specific study in this population. OBJECTIVES: To determine effects of treatment with inhaled nitric oxide (iNO) on death, bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH) or other serious brain injury and on adverse long-term neurodevelopmental outcomes in preterm newborn infants with hypoxic respiratory failure.Owing to substantial variation in study eligibility criteria, which decreases the utility of an overall analysis, we divided participants post hoc into three groups: (1) infants treated over the first three days of life because of defects in oxygenation, (2) preterm infants with evidence of pulmonary disease treated routinely with iNO and (3) infants treated later (after three days of age) because of elevated risk of BPD. SEARCH METHODS: We used standard methods of the Cochrane Neonatal Review Group. We searched MEDLINE, Embase, Healthstar and the Cochrane Central Register of Controlled Trials in the Cochrane Library through January 2016. We also searched the abstracts of the Pediatric Academic Societies. SELECTION CRITERIA: Eligible for inclusion were randomised and quasi-randomised studies in preterm infants with respiratory disease that compared effects of iNO gas versus control, with or without placebo. DATA COLLECTION AND ANALYSIS: We used standard methods of the Cochrane Neonatal Review Group and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. MAIN RESULTS: We found 17 randomised controlled trials of iNO therapy in preterm infants. We grouped these trials post hoc into three categories on the basis of entry criteria: treatment during the first three days of life for impaired oxygenation, routine use in preterm babies along with respiratory support and later treatment for infants at increased risk for bronchopulmonary dysplasia (BPD). We performed no overall analyses.Eight trials providing early rescue treatment for infants on the basis of oxygenation criteria demonstrated no significant effect of iNO on mortality or BPD (typical risk ratio (RR) 0.94, 95% confidence interval (CI) 0.87 to 1.01; 958 infants). Four studies examining routine use of iNO in infants with pulmonary disease reported no significant reduction in death or BPD (typical RR 0.94, 95% CI 0.87 to 1.02; 1924 infants), although this small effect approached significance. Later treatment with iNO based on risk of BPD (three trials) revealed no significant benefit for this outcome in analyses of summary data (typical RR 0.92, 95% CI 0.85 to 1.01; 1075 infants).Investigators found no clear effect of iNO on the frequency of all grades of IVH nor severe IVH. Early rescue treatment was associated with a non-significant 20% increase in severe IVH.We found no effect on the incidence of neurodevelopmental impairment. AUTHORS' CONCLUSIONS: iNO does not appear to be effective as rescue therapy for the very ill preterm infant. Early routine use of iNO in preterm infants with respiratory disease does not prevent serious brain injury or improve survival without BPD. Later use of iNO to prevent BPD could be effective, but current 95% confidence intervals include no effect; the effect size is likely small (RR 0.92) and requires further study.

Measuring and communicating meaningful outcomes in neonatology: A family perspective.

Medium- and long-term outcomes have been collected and described among survivors of neonatal intensive care units for decades, for a number of purposes: (1) quality control within units, (2) comparisons of outcomes between NICUs, (3) clinical trials (whether an intervention improves outcomes), (4) end-of-life decision-making, (5) to better understand the effects of neonatal conditions and/or interventions on organs and/or long-term health, and finally (6) to better prepare parents for the future. However, the outcomes evaluated have been selected by investigators, based on feasibility, availability, cost, stability, and on what investigators consider to be important. Many of the routinely measured outcomes have major limitations: they may not correlate well with long-term difficulties, they may artificially divide continuous outcomes into dichotomous ones, and may have no clear relationship with quality of life and functioning of children and their families. Several investigations, such as routine term cerebral resonance imaging for preterm infants, have also not yet been shown to improve the outcome of children nor their families. In this article, the most common variables used in neonatology as well as some variables which are rarely measured but may be of equal importance for families are presented. The manner in which these outcomes are communicated to families will be examined, as well as recommendations to optimize communication with parents.

Parental hopes, interventions, and survival of neonates with trisomy 13 and trisomy 18.

Trisomy 13 and 18 are life-limiting conditions for which a palliative approach is frequently recommended. The objective of this study was to examine parental goals/decisions, the length of life of their child and factors associated with survival. Parents of children who lived with trisomy 13 or 18 that were part of English-speaking social networks were invited to participate in a questionnaire study. Participants answered questions about their hopes/goals, decisions regarding neonatal interventions, and the duration of their children's lives. The participants were 332 parents who answered questions about their 272 children (87% response rate based on site visits; 67% on invitations sent). When parents were asked about their hope after the diagnosis, the main themes invoked by parents were the following: meet their child alive (80% of parents with a prenatal diagnosis), spend some time as a family (72%), bring their child home (52%), and give their child a good life (66%). Parents wanted to give them a chance, but also reported their fears were medical complexity, pain and/or life in the hospital (61%). Healthcare providers recommended comfort care at birth to all parents. Life-sustaining interventions "as for any other child" was chosen as a plan of care by 25% of parents. Of the 216 children with full trisomy, 69% were discharged home after birth and 40% lived >1 y. The presence of a prenatal diagnosis was the strongest independent factor negatively associated with longevity: 36% of children with a prenatal diagnosis lived <24 hr and 47% were discharged home compared to 1% and 87%, respectively for children with a postnatal diagnosis (P < 0.01). Male gender, low-birth weight, and cardiac and/or cerebral anomaly were also associated with decreased survival (P < 0.05). After a prenatal diagnosis, palliative care at birth consisted of limited interventions, whereas after a postnatal diagnosis (median age of 6 days) it consisted of various interventions, including oxygen, ventilation, tube feeding and intravenous fluids, complicating the analysis. In conclusion, the goals of parents of children with trisomy 13 or 18 were to meet their child, be discharged home and be a family. Having a postnatal diagnosis was the independent factor most associated with these goals. Children with a postnatal diagnosis were treated "as any other children" until the diagnosis, which may give them a survival advantage, independent of palliative care. Rigorous transparency regarding specific interventions and outcomes may help personalize care for these children. © 2016 Wiley Periodicals, Inc.

Management during the first 72 h of age of the periviable infant: an evidence-based review.

After NICU admission the extremely immature newborn (EIN) requires evaluation and support of each organ system, and the integration of all those supports in a comprehensive plan of care. In this review, I attempt to analyze the evidence for treatment options after the initial transition, during the first 3 days of life, which have been shown to improve survival or short- or long-term morbidity. This review revealed several things: there is little available evidence from studies that have included significant numbers of EINs; interventions affecting different organ systems need to be co-ordinated as any intervention will have multiple effects; and future advances in treatment of this group of patients will require the installation of permanent research networks to have enough power to perform many studies needed to improve outcomes.

End-of-life decisions for extremely low-gestational-age infants: why simple rules for complicated decisions should be avoided.

Interventions for extremely preterm infants bring up many ethical questions. Guidelines for intervention in the "periviable" period generally divide infants using predefined categories, such as "futile," "beneficial," and "gray zone" based on completed 7-day periods of gestation; however, such definitions often differ among countries. The ethical justification for using gestational age as the determination of the category boundaries is rarely discussed. Rational criteria used to make decisions regarding life-sustaining interventions must incorporate other important prognostic information. Precise guidelines based on imprecise data are not rational. Gestational age-based guidelines include an implicit judgment of what is deemed to be an unacceptably poor chance of "intact" survival but fail to explore the determination of acceptability. Furthermore, unclear definitions of severe disability, the difficulty, or impossibility, of accurately predicting outcome in the prenatal or immediate postnatal period make such simplistic formulae inappropriate. Similarly, if guidelines for intervention for the newborn are based on the "qualitative futility" of survival, it should be explicitly stated and justified according to established ethical guidelines. They should discuss whether newborn infants are morally different to older individuals or explain why thresholds recommended for intervention are different to recommendations for those in older persons. The aim should be to establish individualized goals of care with families while recognizing uncertainty, rather than acting on labels derived from gestational age categories alone.

Common hemodynamic problems in the neonate.

Hemodynamic problems are common in neonatal intensive care. They occur in the context of incomplete myocardial and vascular development and in cardiovascular responses to interventions which are, as a result, limited and often uncertain and unpredictable. In this review, I outline the hemodynamic features of 4 neonatal conditions which often require intervention: (1) persistent pulmonary hypertension of the newborn, (2) cardiogenic shock (most commonly in the context of hypoxic ischemic injury), (3) sepsis and (4) low blood pressure in the transitional period of the extremely preterm infant. I also look at the evidence which exists for effective interventions and the most important research questions for the future.

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide (iNO) is effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure and the potential risks of iNO differ substantially in preterm infants, necessitating study in this population. OBJECTIVES: To determine the effect of treatment with iNO on death, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and neurodevelopmental disability in preterm newborn infants with respiratory disease. SEARCH STRATEGY: Standard methods of the Cochrane Neonatal Review Group were used. MEDLINE, EMBASE, Healthstar and the Cochrane Central Register of Controlled Trials (The Cochrane Library) were searched covering the years from 1985 to 2010. In addition, the abstracts of the Pediatric Academic Societies were also searched. SELECTION CRITERIA: Randomized and quasi-randomized studies in preterm infants with respiratory disease that compared the effects of iNO gas to control, with or without placebo were eligible. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Neonatal Review Group were used. MAIN RESULTS: Fourteen randomized controlled trials of inhaled nitric oxide therapy in preterm infants were found. The trials have been grouped post hoc into three categories depending on entry criteria; entry in the first three days of life based on oxygenation criteria, routine use in preterm babies with pulmonary disease, and later enrolment based on an increased risk of BPD. No overall analyses were performed.Nine trials of early rescue treatment of infants based on oxygenation criteria demonstrated no significant effect of iNO on mortality or BPD. Three studies with routine use of iNO in infants with pulmonary disease also demonstrated no significant reduction in death or BPD [typical RR 0.93 (95% CI 0.86 to 1.01)] although this small effect approached significance. Later treatment with iNO based on the risk of BPD (two trials) demonstrated no significant benefit for this outcome in analyses which are possible using summary data.There is no clear effect of iNO on the frequency of all grades of IVH or of severe IVH. Early rescue treatment was associated with a non-significant 20% increase in severe IVH.No effect on the incidence of neurodevelopmental impairment was found. AUTHORS' CONCLUSIONS: iNO as rescue therapy for the very ill preterm infant does not appear to be effective. Early routine use of iNO in preterm infants with respiratory disease does not affect serious brain injury or improve survival without BPD. Later use of iNO to prevent BPD might be effective, but requires further study.

Inhaled nitric oxide for preterm infants: a systematic review.

OBJECTIVE: Our goal was to determine whether, for preterm newborn infants with respiratory disease, inhaled nitric oxide reduced the rates of death, bronchopulmonary dysplasia, intracranial hemorrhage, or neurodevelopmental disability. METHODS: We searched Medline, Embase, Healthstar, and the Cochrane Central Register of Controlled Trials using the search terms "nitric oxide," "clinical trial," and "newborn" and covering 1985-2006. We also searched abstracts of the Pediatric Academic Societies. RESULTS: Eleven randomized, controlled trials of inhaled nitric oxide therapy for preterm infants were found. The trials were grouped into 3 categories according to the entry criteria, that is, entry in the first 3 days of life on the basis of oxygenation criteria (early rescue), enrollment after 3 days on the basis of elevated risk of bronchopulmonary dysplasia, and routine use for intubated preterm infants. Early rescue treatment based on oxygenation criteria did not seem to affect mortality or bronchopulmonary dysplasia rates. Routine use for intubated preterm infants showed a barely significant reduction in the incidence of the combined outcome of death or bronchopulmonary dysplasia (relative risk [RR]: 0.91 [95% confidence limits (CLs): 0.84, 0.99]). Later treatment based on the risk of bronchopulmonary dysplasia showed no significant effect on this outcome. Early rescue treatment showed a trend toward increased incidence of severe intracranial hemorrhage, whereas routine use for intubated preterm infants seemed to show a reduction in the incidence of either severe intracranial hemorrhage or periventricular leukomalacia (RR: 0.70 [95% CLs: 0.53, 0.91]). CONCLUSIONS: Inhaled nitric oxide as rescue therapy for very ill preterm infants undergoing ventilation does not seem to be effective and may increase severe intracranial hemorrhage. Later use of inhaled nitric oxide to prevent bronchopulmonary dysplasia does not seem to be effective. Early routine use of inhaled nitric oxide for mildly sick, preterm infants seems to decrease the risk of serious brain injury and may improve rates of survival without bronchopulmonary dysplasia.

Prevention and management of pain in the neonate: an update.

The prevention of pain in neonates should be the goal of all caregivers, because repeated painful exposures have the potential for deleterious consequences. Neonates at greatest risk of neurodevelopmental impairment as a result of preterm birth (ie, the smallest and sickest) are also those most likely to be exposed to the greatest number of painful stimuli in the NICU. Although there are major gaps in our knowledge regarding the most effective way to prevent and relieve pain in neonates, proven and safe therapies are currently underused for routine minor yet painful procedures. Every health care facility caring for neonates should implement an effective pain-prevention program, which includes strategies for routinely assessing pain, minimizing the number of painful procedures performed, effectively using pharmacologic and nonpharmacologic therapies for the prevention of pain associated with routine minor procedures, and eliminating pain associated with surgery and other major procedures.

Caffeine therapy for apnea of prematurity.

BACKGROUND: Methylxanthines reduce the frequency of apnea of prematurity and the need for mechanical ventilation during the first seven days of therapy. It is uncertain whether methylxanthines have other short- and long-term benefits or risks in infants with very low birth weight. METHODS: We randomly assigned 2006 infants with birth weights of 500 to 1250 g during the first 10 days of life to receive either caffeine or placebo, until drug therapy for apnea of prematurity was no longer needed. We evaluated the short-term outcomes before the first discharge home. RESULTS: Of 963 infants who were assigned to caffeine and who remained alive at a postmenstrual age of 36 weeks, 350 (36 percent) received supplemental oxygen, as did 447 of the 954 infants (47 percent) assigned to placebo (adjusted odds ratio, 0.63; 95 percent confidence interval, 0.52 to 0.76; P<0.001). Positive airway pressure was discontinued one week earlier in the infants assigned to caffeine (median postmenstrual age, 31.0 weeks; interquartile range, 29.4 to 33.0) than in the infants in the placebo group (median postmenstrual age, 32.0 weeks; interquartile range, 30.3 to 34.0; P<0.001). Caffeine reduced weight gain temporarily. The mean difference in weight gain between the group receiving caffeine and the group receiving placebo was greatest after two weeks (mean difference, -23 g; 95 percent confidence interval, -32 to -13; P<0.001). The rates of death, ultrasonographic signs of brain injury, and necrotizing enterocolitis did not differ significantly between the two groups. CONCLUSIONS: Caffeine therapy for apnea of prematurity reduces the rate of bronchopulmonary dysplasia in infants with very low birth weight. (ClinicalTrials.gov number, NCT00182312.).

Clinical outcomes following institution of universal leukoreduction of blood transfusions for premature infants.

CONTEXT: Leukocytes present in stored blood products can have a variety of biological effects, including depression of immune function, thereby increasing nosocomial infections and possibly resulting in organ failure and death. Premature infants, given their immature immune state, may be uniquely predisposed to the effects of transfused leukocytes. OBJECTIVE: To evaluate the clinical outcomes following implementation of a universal prestorage red blood cell (RBC) leukoreduction program in premature infants admitted to neonatal intensive care units (NICUs). DESIGN AND SETTING: Retrospective before-and-after study conducted in 3 Canadian tertiary care NICUs from January 1998 to December 2000. PATIENTS: A total of 515 premature infants weighing less than 1250 g who were admitted to the NICU, received at least 1 RBC transfusion, and survived at least 48 hours were enrolled. The intervention group consisted of infants admitted in the 18-month period following the introduction of universal leukoreduction (n = 247) and the control group consisted of infants admitted during the 18 months prior to the introduction of universal leukoreduction (n = 268). MAIN OUTCOME MEASURES: Primary outcomes were nosocomial bacteremia and NICU mortality, compared before and after implementation of universal leukoreduction using multivariate regression. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intraventricular hemorrhage. RESULTS: The proportion of infants who acquired bacteremia after an RBC transfusion was 79/267 (29.6%) in the nonleukoreduction period and 63/246 (25.6%) in the leukoreduction period. For NICU mortality, there were 45 deaths (16.8%) in the nonleukoreduction period and 44 deaths (17.8%) in the leukoreduction period. The adjusted odds ratio (OR) for bacteremia was 0.59 (95% confidence interval [CI], 0.34-1.01) and for mortality was 1.22 (95% CI, 0.59-2.50). The adjusted ORs for bronchopulmonary dysplasia and retinopathy of prematurity were 0.42 (95% CI, 0.25-0.70) and 0.56 (95% CI, 0.33-0.93), respectively. The adjusted ORs for necrotizing enterocolitis and grade 3 or 4 intraventricular hemorrhage were 0.39 (95% CI, 0.17-0.90) and 0.65 (95% CI, 0.35-1.19), respectively. The adjusted OR for a composite measure of any major neonatal morbidity was 0.31 (95% CI, 0.17-0.56). Crude and adjusted rates for all secondary outcomes suggest that leukoreduction was associated with improved outcomes. CONCLUSION: Implementation of universal prestorage leukoreduction was not associated with significant reductions in NICU mortality or bacteremia but was associated with improvement in several clinical outcomes in premature infants requiring RBC transfusions.