To examine factors affecting center differences in mortality for extremely low birth weight (ELBW) infants.
We analyzed data for 5418 ELBW infants born at 16 Neonatal Research Network centers during 2006–2009. The primary outcomes of early mortality (≤12 hours after birth) and in-hospital mortality were assessed by using multilevel hierarchical models. Models were developed to investigate associations of center rates of selected interventions with mortality while adjusting for patient-level risk factors. These analyses were performed for all gestational ages (GAs) and separately for GAs <25 weeks and ≥25 weeks.
Early and in-hospital mortality rates among centers were 5% to 36% and 11% to 53% for all GAs, 13% to 73% and 28% to 90% for GAs <25 weeks, and 1% to 11% and 7% to 26% for GAs ≥25 weeks, respectively. Center intervention rates significantly predicted both early and in-hospital mortality for infants <25 weeks. For infants ≥25 weeks, intervention rates did not predict mortality. The variance in mortality among centers was significant for all GAs and outcomes. Center use of interventions and patient risk factors explained some but not all of the center variation in mortality rates.
Center intervention rates explain a portion of the center variation in mortality, especially for infants born at <25 weeks’ GA. This finding suggests that deaths may be prevented by standardizing care for very early GA infants. However, differences in patient characteristics and center intervention rates do not account for all of the observed variability in mortality; and for infants with GA ≥25 weeks these differences account for only a small part of the variation in mortality.
mortality rates; outcome; NICU; preterm infants; extremely preterm infants
Purpose of review
Clinicians’ adherence to AAP and CDC Guidelines to prevent Group B Streptococcal (GBS) early onset sepsis (EOS) have reduced GBS EOS. While evidence-based testing and empirical antibiotic initiation is likely saving lives, clinicians have less compelling data to guide duration of empirically initiated antibiotics when cultures remain sterile and clinical signs resolve quickly. Our purpose is to review current opinions and evidence influencing clinicians’ choices for duration of empirically initiated antibiotics in newborns with sterile cultures.
Retrospective cohort studies indicate potential for harm with longer duration of empirical antibiotics for EOS when cultures are sterile. Cohort studies indicate timing of widely used tests used to estimate EOS risk affects their predictive value, and tests acquired 24 – 48 hours postnatally may provide reassurance for safe discontinuation.
Every day clinicians caring for thousands of neonates in the US stop antibiotics which were started empirically to treat EOS on the first postnatal day. Evidence is lacking to support a universal approach to decisions on duration of empirical antibiotics when cultures remain sterile. Reviewing predictive value relative to timing of laboratory testing can help clinicians develop locally appropriate antimicrobial duration decision-making guidelines.
empirical antibiotics; early onset sepsis
To describe and compare incidence of late-onset sepsis (LOS) and demographic and clinical characteristics associated with LOS in very low birth weight (VLBW) infants from singleton and multiple births and to examine the heritability in susceptibility to LOS among VLBW twins by comparing same-sex with unlike-sex twin pairs.
We studied infants with birth weight 401–1500 grams cared for at clinical centers of the NICHD Neonatal Research Network 2002–2008. Only the first episode of LOS was examined. Stepwise logistic regression models were fitted separately for singleton and multiple pregnancies to examine the maternal and neonatal factors associated with LOS. LOS due to only gram-negative bacteria among singleton and multiple pregnancies was also examined in separate models. The heritability of LOS was estimated by examining concordance of LOS between twins from same-sex and unlike-sex pairs.
LOS occurred in 25.0% (3797/15,178) of singleton and 22.6% (1196/5294) of multiple VLBW infants. Coagulase-negative staphylococci were the most common infecting organisms, accounting for 53.2% of all LOS episodes in singletons and 49.2% in multiples. E. coli and Klebsiella species were the most commonly isolated gram-negative organisms, and Candida albicans was the most commonly isolated fungus. Concordance of LOS was not significantly different between same-sex and unlike-sex twin pairs.
LOS remains a common problem in VLBW infants. The incidence of LOS is similar for singleton and multiple infants. Similar concordance of LOS in same-sex and unlike-sex twin pairs provided no evidence that susceptibility to LOS among VLBW infants is genetically determined.
Heredity; preterm infants; twins
Myo-inositol given to preterm infants with respiratory distress has reduced death, increased survival without bronchopulmonary dysplasia (BPD) and reduced severe retinopathy of prematurity (ROP) in 2 randomized trials. Pharmacokinetic (PK) studies in extremely preterm infants are needed prior to efficacy trials.
Infants of 23–29 weeks gestation were randomized to a single intravenous (IV) dose of inositol at 60 or 120 mg/kg or placebo. Over 96 h, serum levels (sparse sampling population PK) and urine inositol excretion were determined. Population PK models were fit using a nonlinear mixed effects approach. Safety outcomes were recorded.
A 1-compartment model that included factors for endogenous inositol production, allometric size based on weight, gestational age (GA) strata and creatinine clearance fit the data best. The central volume of distribution was 0.5115 l/kg, the clearance 0.0679 l/kg/h, endogenous production 2.67 mg/kg/h and the half life 5.22 h when modeled without the covariates. During the first 12 h renal inositol excretion quadrupled in the 120 mg/kg group, returning to near baseline after 48 h. There was no diuretic side-effect. No significant differences in adverse events occurred between the 3 groups (p > 0.05).
A single compartment model accounting for endogenous production satisfactorily described the PK of IV inositol.
To examine whether preterm very low birth weight (VLBW) infants have an increased risk of late-onset sepsis (LOS) following early-onset sepsis (EOS).
Retrospective analysis of VLBW infants (401-1500 g) born September 1998 through December 2009 who survived >72 hours and were cared for within the NICHD Neonatal Research Network. Sepsis was defined by growth of bacteria or fungi in a blood culture obtained ≤72 hr of birth (EOS) or >72 hr (LOS) and antimicrobial therapy for ≥5 days or death <5 d while receiving therapy. Regression models were used to assess risk of death or LOS by 120d and LOS by 120d among survivors to discharge or 120d, adjusting for gestational age and other covariates.
Of 34,396 infants studied 504 (1.5%) had EOS. After adjustment, risk of death or LOS by 120d did not differ overall for infants with EOS compared with those without EOS [RR:0.99 (0.89-1.09)] but was reduced in infants born at <25wk gestation [RR:0.87 (0.76-0.99), p=0.048]. Among survivors, no difference in LOS risk was found overall for infants with versus without EOS [RR:0.88 (0.75-1.02)], but LOS risk was shorter in infants with BW 401-750 g who had EOS [RR:0.80 (0.64-0.99), p=0.047].
Risk of LOS after EOS was not increased in VLBW infants. Surprisingly, risk of LOS following EOS appeared to be reduced in the smallest, most premature infants, underscoring the need for age-specific analyses of immune function.
Very low birth weight; early-onset sepsis; late-onset sepsis
Determine predictors of neurocognitive outcome in early school age congenital diaphragmatic hernia (CDH) survivors.
Prospective study of infants with CDH at Duke University Medical Center. Neurocognitive delay (NCD) at school age (4 to 7 years) was defined as a score < 80 in any of the following areas: Verbal Scale IQ, Performance Scale IQ, Expressive Language, or Receptive Language. Logistic regression, Fisher’s exact, and the Wilcoxon rank sum test were used to examine the relationship between NCD at early school age and 6 demographic and 18 medical variables.
Of 43 infants with CDH, twenty seven (63%) survived to hospital discharge, and 16 (59%) returned for school age testing at a median age of 4.9 years. Seven (44%) of the children evaluated had NCD. Patch repair (p=0.01), extracorporeal membrane oxygenation (ECMO; p=0.02), days on ECMO (p=0.01), days of mechanical ventilation (p=0.049), and post-operative use of inhaled nitric oxide (p=0.02) were found to be associated with NCD at early school age.
CDH survivors are at risk for neurocognitive delay persisting into school age. Perinatal factors such as patch repair and ECMO treatment may aid in identifying CDH survivors at high risk for continued learning difficulties throughout childhood.
hernia, diaphragmatic; follow-up studies; neurobehavioral manifestations; growth & development; infant nutrition disorders
Very low birth weight neonates (≤1500 g, VLBWs) have a high rate of infection and distinct baseline immune function compared with more mature populations. In critically ill children and adults, sepsis increases subsequent infection risk. It is unknown whether sepsis modifies the risk of subsequent infection in VLBWs.
We conducted a retrospective cohort study of VLBWs ≤32 weeks gestation at birth cared for in 312 neonatal intensive care units in the United States from 1997–2011 (n=103,376). Early-onset sepsis (EOS, culture-positive only) and late-onset sepsis (LOS, culture-positive or clinical) cases were identified. Cox proportional hazards models were used to control for clinical variables between neonates with and without EOS to determine if EOS modified risk of LOS, necrotizing enterocolitis (NEC), or death.
LOS occurred in 12,112/102,317 (11.8%) neonates without EOS and in 133/1059 (12.6%) of those with EOS. After adjustment for clinical variables, the risk of LOS was not different between neonates with or without a history of EOS (hazard ratio [HR]=0.92; 95% confidence interval [CI] 0.74, 1.16). EOS increased the risk of 120-day mortality (HR=1.78; 95% CI 1.49, 2.13).
In contrast to findings in children and adults, EOS was not associated with an increased risk of LOS in this cohort. Age-specific investigations are needed to determine if post-sepsis immunologic alterations are present.
preterm; neonate; sepsis; immunoparalysis
Sepsis in older children and adults modifies immune system function. We compared serotype-specific antibody responses to heptavalent pneumococcal conjugate vaccine (PCV7) in very low birth weight infants (<1500g,VLBW) with and without blood stream infection (BSI) during their birth hospitalization.
Patients and Methods
Retrospective analysis of prospectively collected data for the Neonatal Research Network study of PCV7 responses among VLBWs. Infants received PCV7 at 2, 4, and 6 months after birth with blood drawn 4–6 weeks after 3rd dose. Serotype antibodies were compared between infants with or without a history of BSI. Regression models were constructed with birth-weight groups and other confounding factors identified in the primary study.
244 infants completed the vaccine series and had serum antibody available; 82 had BSI. After adjustment, BSI was not associated with reduced odds of serum antibody ≥0.35μg/mL.
BSI was not associated with reduced odds of WHO-defined protective PCV7 responses in VLBWs.
VLBW; immune response; vaccine; sepsis; blood stream infection
To assess the impact of emperic antifungal therapy of invasive candidiasis on subsequent outcomes in premature infants.
This was a cohort study of infants ≤1000 g birth weight cared for at Neonatal Research Network sites. All infants had at least 1 positive culture for Candida. Emperic antifungal therapy was defined as receipt of a systemic antifungal on the day of or the day before the first positive culture for Candida was drawn. We created Cox proportional hazards and logistic regression models stratified on propensity score quartiles to determine the effect of emperic antifungal therapy on survival, time to clearance of infection, retinopathy of prematurity, bronchopulmonary dysplasia, end-organ damage, and neurodevelopmental impairment (NDI).
136 infants developed invasive candidiasis. The incidence of death or NDI was lower for infants who received emperic antifungal therapy (19/38, 50%) compared with those who had not (55/86, 64%; odds ratio=0.27 [95% confidence interval 0.08–0.86]). There was no significant difference between the groups for any single outcome or other combined outcomes.
Emperic antifungal therapy was associated with increased survival without NDI. A prospective randomized trial of this strategy is warranted.
Candida; neonate; mortality; neurodevelopmental impairment
We sought to determine if a center’s approach to care of premature infants at the youngest gestational ages (22–24 weeks’ gestation) is associated with clinical outcomes among infants of older gestational ages (25–27 weeks’ gestation).
Inborn infants of 401 to 1000 g birth weight and 22 0/7 to 27 6/7 weeks’ gestation at birth from 2002 to 2008 were enrolled into a prospectively collected database at 20 centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Markers of an aggressive approach to care for 22- to 24-week infants included use of antenatal corticosteroids, cesarean delivery, and resuscitation. The primary outcome was death before postnatal day 120 for infants of 25 to 27 weeks’ gestation. Secondary outcomes were the combined outcomes of death or a number of morbidities associated with prematurity.
Our study included 3631 infants 22 to 24 weeks’ gestation and 5227 infants 25 to 27 weeks’ gestation. Among the 22- to 24-week infants, use of antenatal corticosteroids ranged from 28% to 100%, cesarean delivery from 13% to 65%, and resuscitation from 30% to 100% by center. Centers with higher rates of antenatal corticosteroid use in 22- to 24-week infants had reduced rates of death, death or retinopathy of prematurity, death or late-onset sepsis, death or necrotizing enterocolitis, and death or neurodevelopmental impairment in 25- to 27-week infants.
This study suggests that physicians’ willingness to provide care to extremely low gestation infants as measured by frequency of use of antenatal corticosteroids is associated with improved outcomes for more-mature infants.
low-birth weight infant; NICUs; treatment; patient outcome assessment
Neonatal sepsis causes significant morbidity and mortality, especially in preterm infants. Consequently, clinicians are compelled to treat with empirical antibiotics at the first signs of suspected sepsis. Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes including invasive candidiasis, increased antimicrobial resistance, necrotizing enterocolitis, late-onset sepsis, and death. Most common neonatal pathogens are susceptible to narrow-spectrum antibiotics. The choice of antibiotic and duration of empirical treatment are strongly associated with center-based rather than with individual patient risk factors, implying that these choices are modifiable across centers. Thus, clinicians should aim to treat with short courses of narrow-spectrum antibiotics whenever possible, choosing the appropriate antibiotics and treatment duration to balance the risks of potentially untreated sepsis against the adverse effects of treatment in infants with sterile cultures.
neonatal intensive care unit; empirical; antibiotic; sepsis; infection
Extremely low birth weight (ELBW) infants with candiduria are at substantial risk for death or neurodevelopmental impairment. Therefore, identification of candiduria should prompt a systemic evaluation for disseminated Candida infection and initiation of treatment in all ELBW infants.
Background. Candidiasis carries a significant risk of death or neurodevelopmental impairment (NDI) in extremely low birth weight infants (ELBW; <1000 g). We sought to determine the impact of candiduria in ELBW preterm infants.
Methods. Our study was a secondary analysis of the Neonatal Research Network study Early Diagnosis of Nosocomial Candidiasis. Follow-up assessments included Bayley Scales of Infant Development examinations at 18–22 months of corrected age. Risk factors were compared between groups using exact tests and general linear modeling. Death, NDI, and death or NDI were compared using generalized linear mixed modeling.
Results. Of 1515 infants enrolled, 34 (2.2%) had candiduria only. Candida was isolated from blood only (69 of 1515 [4.6%]), cerebrospinal fluid (CSF) only (2 of 1515 [0.1%]), other sterile site only (not urine, blood, or CSF; 4 of 1515 [0.3%]), or multiple sources (28 of 1515 [2%]). Eleven infants had the same Candida species isolated in blood and urine within 3 days; 3 (27%) had a positive urine culture result first. Most urine isolates were Candida albicans (21 of 34 [62%]) or Candida parapsilosis (7 of 34 [29%]). Rate of death or NDI was greater among those with candiduria (50%) than among those with suspected but not proven infection (32%; odds ratio, 2.5 [95% confidence interval, 1.2–5.3]) after adjustment. No difference in death and death or NDI was noted between infants with candiduria and those with candidemia.
Conclusions. These findings provide compelling evidence that ELBW infants with candiduria are at substantial risk of death or NDI. Candiduria in ELBW preterm infants should prompt a systemic evaluation (blood, CSF, and abdominal ultrasound) for disseminated Candida infection and warrants treatment.
To determine the dynamic morphological development of the human fovea in-vivo utilizing portable spectral domain optical coherence tomography (SDOCT).
Prospective, observational case series.
31 prematurely born neonates, nine children and nine adults.
Sixty-two neonates were enrolled in this study. SDOCT imaging was performed after examination for retinopathy of prematurity (ROP) at the bedside in non-sedated infants ages 31-41 weeks post-menstrual-age PMA (PMA=gestational age in weeks + chronological age) and at outpatient follow-up ophthalmic examinations. Thirty-one neonates met eligibility criteria. Nine children and nine adults without ocular pathology served as control groups. Semi-automatic retinal layer segmentation was performed. Central foveal thickness (CFT), foveal to parafoveal (FP) ratio (CFT divided by thickness 1000 μm from the foveal center), and 3D thickness maps were analyzed.
Main Outcomes Measures
In-vivo determination of foveal morphology, layer segmentation, analysis of sub-cellular changes, spatio-temporal layer shifting.
In contrast to the adult fovea, we observed several signs of immaturity in the neonates: a shallow foveal pit, persistence of inner retinal layers (IRL), and a thin photoreceptor layer (PRL) that was thinnest at the foveal center. Three-dimensional mapping showed displacement of retinal layers out of the foveal center as the fovea matured and the progressive formation of the inner/outer segment band in the opposite direction. The FP-IRL ratios decreased as IRL migrated prior to term and minimally after that, while FP-PRL ratios increased as PRL subcellular elements formed closer to term and into childhood. A surprising finding was the presence of cystoid macular edema in 58% of premature neonates which appeared to affect inner foveal maturation.
This study provides the first view into development of living cellular layers of the human retina and of subcellular specialization at the fovea in premature infant eyes using portable spectral domain optical coherence tomography. Our work establishes a framework of the timeline of human foveal development, allowing us to identify unexpected retinal abnormalities that may provide new keys to disease activity, and provide a method for mapping of foveal structures from infancy to adulthood that may be integral in future studies of vision and visual cortex development.
Rationale: Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment.
Objectives: To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death.
Methods: We assessed infants of 23–30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000–2004.
Measurements and Main Results: Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and FiO2, and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org.
Conclusions: The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.
bronchopulmonary dysplasia; prematurity; low-birth-weight infant
Variable approaches to the care of infants with congenital diaphragmatic hernia (CDH) by multiple providers may contribute to inconsistent care. Our institution developed a comprehensive evidence-based protocol to standardize the management of CDH infants. This report reviews patient outcomes prior to and after implementation of the protocol.
Retrospective chart review of CDH infants managed with individualized care (Pre-protocol group, January 1997–December 2001, n=22) or on the protocol (Protocol group, January 2002–July 2009, n=47). Survival and other categorical variables were compared by chi square analysis and continuous variables were compared using one-sided ANOVA analysis with significance defined as p<0.05.
Survival to discharge was significantly greater in the Protocol group (40/47 (85%)) than the Pre-protocol group (12/22 (52%) p=.006) although mean gestational age, mean birth weight, and expected survival were not statistically different between the two groups. The use of supportive therapies, including high frequency jet ventilation, inhaled nitric oxide, and extracorporeal life support was similar between groups as well.
Since implementation of a management protocol for infants with CDH, survival has improved significantly compared with expected survival and pre-protocol controls. Reduction in the variability of care through use of an evidence-based protocol use may improve the survival of CDH infants.
Congenital diaphragmatic hernia; variability; evidence-based care guidelines; protocolized care
We present a case of bilateral severe retinal edema with subretinal fluid in an infant diagnosed with neonatal hemochromatosis and liver failure. A macular cherry-red spot in each eye mimicked the clinical appearance of many metabolic storage diseases. Both the clinical retinal appearance and the anatomic abnormalities observed on spectral domain optical coherence tomography resolved after successful liver transplant.
Congenital diaphragmatic hernia (CDH) is associated with mortality of 10–50%. Several investigators have reported outcomes from centers using high-frequency oscillatory ventilation in their management of CDH, but there are no recent reports on use of high-frequency jet ventilation.
During the study period from January 2001 until August 2007, infants with CDH, who were cared for at Duke University Medical Center, received high-frequency jet ventilation as a rescue mode of high frequency ventilation. We compared actual survival with predicted survival for infants treated only with conventional ventilation versus those rescued with high-frequency jet ventilation after failing conventional ventilation.
Survival for the 16 infants that received high frequency jet ventilation was predicted to be 63%; actual survival was 75%. Survival for the 15 infants that received only conventional ventilation was predicted to be 83%; actual survival was 87%. We observed no significant survival benefit for high-frequency jet ventilation, 8.0% (95 confidence interval; −22.0%, 38.1%, p=0.59).
Although our sample size was small, we conclude with consideration of the absolute results, the degree of illness of the infants, and the biologic plausibility for the intervention, that high-frequency jet ventilation is an acceptable rescue ventilation mode for infants with CDH.
high frequency jet ventilation; congenital diaphragmatic hernia; survival
The purpose of this study is to examine the results of repeat lumbar puncture in infants with initial positive cerebrospinal fluid (CSF) cultures in order to determine the clinical characteristics and outcomes of infants with repeat positive cultures.
Cohort study of infants with an initial positive CSF culture undergoing repeat lumbar puncture between 1997 and 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical group. We compared the clinical outcomes of infants with repeat positive cultures and infants with repeat negative cultures.
We identified 118 infants with repeat CSF cultures. Of these, 26 infants had repeat positive cultures. A higher proportion with repeat positive cultures died compared to those with repeat negative cultures, 6/23 (26%) vs. 6/81 (7%), respectively (p=0.02).
Among infants with a positive CSF culture, a repeat positive CSF culture is common. The presence of a second positive culture is associated with increased mortality.
neonate; newborn; cerebrospinal fluid; infection; mortality
Report clinical response to recombinant factor VIIa in a cohort of critically ill infants.
We identified all infants who received factor VIIa in the Duke Neonatal Intensive Care Unit between January 2005 and July 2008. Hematologic data and volume of blood transfusions before and after factor VIIa treatment were compared. The precipitating diagnosis for each factor VIIa use and the ensuing clinical outcomes of bleeding, thrombosis, and mortality were noted.
We identified 18 infants with median birth weight of 880 g and median gestational age of 26 weeks. One to six doses of factor VIIa (90 mcg/kg/dose) were administered, with 13 (72%) infants receiving a single dose. Hemostasis was achieved in 13 (72%) of the infants. Prothrombin time and activated partial thromboplastin time significantly decreased following treatment with factor VIIa. Volume of plasma transfusions significantly decreased following treatment with factor VIIa (p=0.02). Thrombosis occurred in 1 (11%) infant. Six (33%) infants died within 72 hours of treatment, and overall mortality was 10/18 (56%).
Treatment with factor VIIa at doses of 90 mcg/kg improved coagulation studies and decreased the need for plasma transfusions in a group of critically ill infants without significant risk. Factor VIIa may be an effective addition to current treatment modalities for refractory hemorrhage in infants.
infants; blood products; transfusion; coagulation factors
Patent ductus arteriosus is a common occurrence among prematurely born neonates and is believed to play a role in the development of other complications of prematurity including intraventricular hemorrhage, bronchopulmonary dysplasia, and necrotizing enterocolitis. The clinical decision to treat the patent ductus arteriosus is complicated by the lack of evidence available regarding clinical conditions under which closure should be attempted.
To compare clinical outcomes for neonates who underwent treatment of patent ductus arteriosus exhibiting bidirectional blood flow versus those with flow that was left to right.
Cohort study of all neonates with patent ductus arteriosus in which medical closure was attempted at the Duke University between January 2002 and October 2007.
Death and other important clinical conditions.
We identified 20 neonates with bidirectional flow out of 317 cases in which medical closure of patent ductus arteriosus was attempted. There was no significant increase in overall complications due to closure of a bidirectional patent ductus arteriosus [40% (8/20)] versus ones with left to right shunting [38% (111/297) p=0.82]. Death occurred in 15% (3/20) with bidirectional PDA compared to 11% (34/297) in the left to right group, p=0.72.
The trend in mortality is worrisome but does not contraindicate an aggressive approach to the clinically significant PDA that has bidirectional flow at the time of the echocardiogram.
Ductal closure; Preterm infant; Echocardiography; Bronchopulmonary dysplasia
Intravenous vasopressin at 0.01 to 0.04 units/kg/h increased median mean blood pressure from 26 mm Hg (range 18-44) to 41 mm Hg (range 17-90) by 12 hours of infusion (P = .002) and allowed weaning of catecholamines in a group of extremely low birth weight infants with refractory hypotension.
Determine associations between left vocal cord paralysis (LVCP) and poor respiratory, feeding, and/or developmental outcomes in extremely low birth weight (ELBW) infants following surgical closure of a patent ductus arteriosus (PDA).
ELBW infants who underwent PDA ligation between January 2004 and December 2006 were identified. We compared infants with and without LVCP following ligation to determine relationships between LVCP and respiratory morbidities, feeding and growth difficulties, and neurodevelopmental impairment at 18-22 month follow-up. Student's t test, Fisher exact test, and multivariable regression analyses were used to determine associations.
60 ELBW infants with a mean gestational age of 25 weeks and mean birth weight of 725 g had a PDA surgically closed. Twenty-two of 55 survivors (40%) were diagnosed with LVCP post-operatively. Infants with LVCP were significantly more likely to develop bronchopulmonary dysplasia (82% vs. 39%, p = 0.002), reactive airway disease (86% vs. 33%, p<0.0001), or need for gastrostomy tube (63% vs. 6%, p<0.0001).
LVCP as a complication of surgical ductal ligation in ELBW infants is associated with persistent respiratory and feeding problems. Direct laryngoscopy should be considered for all infants who experience persistent respiratory and/or feeding difficulties following PDA ligation.
infant, premature; ductus arteriosus, patent; growth & development; infant nutrition disorders; bronchopulmonary dysplasia; asthma
Moderate to severe hypoxic–ischemic injury in newborn infants, manifested as encephalopathy immediately or within hours after birth, is associated with a high risk of either death or a lifetime with disability. In recent multicenter clinical trials, hypothermia initiated within the first 6 postnatal hours has emerged as a therapy that reduces the risk of death or impairment among infants with hypoxic–ischemic encephalopathy. Prior to hypothermia, no therapies directly targeting neonatal encephalopathy secondary to hypoxic–ischemic injury had convincing evidence of efficacy. Hypothermia therapy is now becoming increasingly available at tertiary centers. Despite the deserved enthusiasm for hypothermia, obstetric and neonatology caregivers, as well as society at large, must be reminded that in the clinical trials more than 40% of cooled infants died or survived with impairment. Although hypothermia is an evidence-based therapy, additional discoveries are needed to further improve outcome after HIE. In this article, we briefly present the epidemiology of neonatal encephalopathy due to hypoxic–ischemic injury, describe the rationale for the use of hypothermia therapy for hypoxic–ischemic encephalopathy, and present results of the clinical trials that have demonstrated the efficacy of hypothermia. We also present findings noted during and after these trials that will guide care and direct research for this devastating problem.
HIE; hyperthermia; hypothermia; hypoxic–ischemic encephalopathy; neonate; perinatal asphyxia
Preterm birth is increasing worldwide, and late preterm births, which comprise more than 70% of all preterm births, account for much of the increase. Early and late onset sepsis results in significant mortality in extremely preterm infants, but little is known about sepsis outcomes in late preterm infants.
This is an observational cohort study of infants < 121 days of age (119,130 infants less than or equal to 3 days of life and 106,142 infants between 4 and 120 days of life) with estimated gestational age at birth between 34 and 36 weeks, admitted to 248 neonatal intensive care units in the United States between 1996 and 2007.
During the study period, the cumulative incidence of early and late onset sepsis was 4.42 and 6.30 episodes per 1000 admissions, respectively. Gram-positive organisms caused the majority of early and late onset sepsis episodes. Infants with early onset sepsis caused by Gram-negative rods and infants with late onset sepsis were more likely to die than their peers with sterile blood cultures (OR 4.39, 95% CI 1.71–11.23, P=0.002; and OR 3.37, 95% CI 2.35–4.84, P<0.001, respectively).
Late preterm infants demonstrate specific infection rates, pathogen distribution, and mortality associated with early and late onset sepsis. The results of this study are generalizable to late preterm infants admitted to the special care nursery or neonatal intensive care unit.
blood culture; neonate; prematurity; infection; near term
Compare the rates of medical closure of the PDA and complications (renal dysfunction, necrotizing enterocolitis, spontaneous intestinal perforation, and intraventricular hemorrhage) between infants treated with indomethacin and ibuprofen.
A retrospective comparative cohort study of infants treated with indomethacin or ibuprofen for symptomatic patent ductus arteriosus at Duke University Medical Center between November 2005 and November 2007.
We identified 65 infants that received indomethacin and 57 that received ibuprofen. The rate of survival without surgical ductal ligation was 62% (40/65) in the indomethacin group and 58% (33/57) in the ibuprofen group, P=0.71. The rate of the composite of complications (death, necrotizing enterocolitis, or intestinal perforation) was 40% (26/65) in the indomethacin group and 32% (18/57) in the ibuprofen group, P=0.35. There was no significant difference between groups in elevation of serum creatinine during treatment.
In clinical practice, ibuprofen appears to be as effective as indomethacin for closure of patent ductus arteriosus with similar complication rates. The decision to use one agent over the other should be based on dose schedule preference and the currently published clinical trials until more safety and effectiveness data are available.
Ibuprofen; Indomethacin; Patent Ductus Arteriosus; Neonates; Nonsteroidal antiinflammatory drug