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1.  Survival and major neurodevelopmental impairment in extremely low gestational age newborns born 1990–2000: a retrospective cohort study 
BMC Pediatrics  2007;7:20.
It is important to determine if rates of survival and major neurodevelopmental impairment in extremely low gestational age newborns (ELGANs; infants born at 23–27 weeks gestation) are changing over time.
Study infants were born at 23 to 27 weeks of gestation without congenital anomalies at a tertiary medical center between July 1, 1990 and June 30, 2000, to mothers residing in a thirteen-county region in North Carolina. Outcomes at one year adjusted age were compared for two epochs of birth: epoch 1, July 1, 1990 to June 30, 1995; epoch 2, July 1, 1995 to June 30, 2000. Major neurodevelopmental impairment was defined as cerebral palsy, Bayley Scales of Infant Development Mental Developmental Index more than two standard deviations below the mean, or blindness.
Survival of ELGANs, as a percentage of live births, was 67% [95% confidence interval: (61, 72)] in epoch 1 and 71% (65, 75) in epoch 2. Major neurodevelopmental impairment was present in 20% (15, 27) of survivors in epoch 1 and 14% (10, 20) in epoch 2. When adjusted for gestational age, survival increased [odds ratio 1.5 (1.0, 2.2), p = .03] and major neurodevelopmental impairment decreased [odds ratio 0.54 (0.31, 0.93), p = .02] from epoch 1 to epoch 2.
The probability of survival increased while that of major neurodevelopmental impairment decreased during the 1990's in this regionally based sample of ELGANs.
PMCID: PMC1876228  PMID: 17477872
2.  Impact of managed clinical networks on NHS specialist neonatal services in England: population based study 
Objective To assess the impact of reorganisation of neonatal specialist care services in England after a UK Department of Health report in 2003.
Design A population-wide observational comparison of outcomes over two epochs, before and after the establishment of managed clinical neonatal networks.
Setting Epoch one: 294 maternity and neonatal units in England, Wales, and Northern Ireland, 1 September 1998 to 31 August 2000, as reported by the Confidential Enquiry into Stillbirths and Sudden Deaths in Infancy Project 27/28. Epoch two: 146 neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit, 1 January 2009 to 31 December 2010.
Participants Babies born at a gestational age of 27+0-28+6 (weeks+days): 3522 live births in epoch one; 2919 babies admitted to a neonatal unit within 28 days of birth in epoch two.
Intervention The national reorganisation of neonatal services into managed clinical networks.
Main outcome measures The proportion of babies born at hospitals providing the highest volume of neonatal specialist care (≥2000 neonatal intensive care days annually), having an acute transfer (within the first 24 hours after birth) and/or a late transfer (between 24 hours and 28 days after birth) to another hospital, assessed by change in distribution of transfer category (“none,” “acute,” “late”), and babies from multiple births separated by transfer. For acute transfers in epoch two, the level of specialist neonatal care provided at the destination hospital (British Association of Perinatal Medicine criteria).
Results After reorganisation, there were increases in the proportions of babies born at 27-28 weeks’ gestation in hospitals providing the highest volume of neonatal specialist care (18% (631/3495) v 49% (1325/2724); odds ratio 4.30, 95% confidence interval 3.83 to 4.82; P<0.001) and in acute and late postnatal transfers (7% (235) v 12% (360) and 18% (579) v 22% (640), respectively; P<0.001). There was no significant change in the proportion of babies from multiple births separated by transfer (33% (39) v 29% (38); 0.86, 0.50 to 1.46; P=0.57). In epoch two, 32% of acute transfers were to a neonatal unit providing either an equivalent (n=87) or lower (n=26) level of specialist care.
Conclusions There is evidence of some improvement in the delivery of neonatal specialist care after reorganisation. The increase in acute transfers in epoch two, in conjunction with the high proportion transferred to a neonatal unit providing an equivalent or lower level of specialist care, and the continued separation of babies from multiple births, are indicative of poor coordination between maternity and neonatal services to facilitate in utero transfer before delivery, and continuing inadequacies in capacity of intensive care cots. Historical data representing epoch one are available only in aggregate form, preventing examination of temporal trends or confounding factors. This limits the extent to which differences between epochs can be attributed to reorganisation and highlights the importance of routine, prospective data collection for evaluation of future health service reorganisations.
PMCID: PMC3318112  PMID: 22490978
3.  Chorioamnionitis and Early Childhood Outcomes among Extremely Low-Gestational-Age Neonates 
JAMA pediatrics  2014;168(2):137-147.
Chorioamnionitis is strongly linked to preterm birth and to neonatal infection. The association between histological and clinical chorioamnionitis and cognitive, behavioral and neurodevelopmental outcomes among extremely preterm neonates is less clear. We evaluated the impact of chorioamnionitis on 18-22 month neurodevelopmental outcomes in a contemporary cohort of extremely preterm neonates.
To compare the neonatal and neurodevelopmental outcomes of three groups of extremely-low-gestational-age infants with increasing exposure to perinatal inflammation: no chorioamnionitis, histological chorioamnionitis alone, or histological plus clinical chorioamnionitis.
Longitudinal observational study.
Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.
2390 extremely preterm infants born <27 weeks' gestational age between January 1, 2006 and December 31, 2008 with placental histopathology and 18-22 months' corrected age follow-up data were eligible.
Main exposure
Main Outcome Measures
Outcomes included cerebral palsy, gross motor functional limitation, behavioral scores (according to the Brief Infant-Toddler Social and Emotional Assessment), cognitive and language scores (according to the Bayley Scales of Infant Development, 3rd-Edition) and composite measures of death/neurodevelopmental impairment. Multivariable logistic and linear regression models were developed to assess the association between chorioamnionitis and outcomes while controlling for important variables known at birth.
Neonates exposed to chorioamnionitis had a lower gestational age (GA) and had higher rates of early-onset sepsis and severe periventricular-intraventricular hemorrhage as compared with unexposed neonates. In multivariable models evaluating death and neurodevelopmental outcomes, inclusion of gestational age in the model diminished the association between chorioamnionitis and adverse outcomes. Still, histological+clinical chorioamnionitis was associated with increased risk of cognitive impairment as compared with no chorioamnionitis (Adjusted OR 2.4, [1.3- 4.3] without GA; Adjusted OR 2.0, [1.1-3.6] with GA as a covariate). Histological chorioamnionitis alone was associated with lower odds of death/neurodevelopmental impairment as compared with histological+clinical chorioamnionitis (Adjusted OR 0.68, [0.52-0.89] without GA; 0.66, [0.49-0.89] with GA). Risk of behavioral problems did not differ statistically between groups.
Conclusions and Relevance
Antenatal exposure to chorioamnionitis is associated with altered odds of cognitive impairment and death/neurodevelopmental impairment in extremely preterm infants.
PMCID: PMC4219500  PMID: 24378638
chorioamnionitis; preterm; neurodevelopmental impairment; outcome
4.  Neurodevelopmental Outcomes of Extremely Low Gestational Age Neonates with Low Grade Periventricular-Intraventricular Hemorrhage 
JAMA pediatrics  2013;167(5):451-459.
To compare neurodevelopmental outcomes at 18–22 months corrected age for extremely low gestational age infants with low grade (Grade 1 or 2) periventricular-intraventricular hemorrhage to infants with either no hemorrhage or severe (Grade 3 or 4) hemorrhage on cranial ultrasound.
Longitudinal observational study
Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
1472 infants born at <27 weeks gestational age between 2006–2008 with ultrasound results within the first 28 days of life and surviving to 18–22 months with complete follow-up assessments were eligible.
Main Exposure
Low grade periventricular-intraventricular hemorrhage
Outcome Measures
Outcomes included cerebral palsy, gross motor functional limitation, Bayley III cognitive and language scores, and composite measures of neurodevelopmental impairment. Regression modeling evaluated the association of hemorrhage severity with adverse outcomes while controlling for potentially confounding variables and center differences.
Low grade hemorrhage was not associated with significant differences in unadjusted or adjusted risk of any adverse neurodevelopmental outcome compared to infants without hemorrhage. Compared with low grade hemorrhage, severe hemorrhage was associated with decrease in adjusted continuous cognitive (−3.91, [95% Confidence Interval [CI]: −6.41, −1.42]) and language (−3.19 [−6.19, −0.19]) scores as well as increased odds of each adjusted categorical outcome except severe cognitive impairment (OR: 1.46 [0.74, 2.88]) and mild language impairment (OR: 1.35 [0.88, 2.06]).
At 18–22 months, the neurodevelopmental outcomes of extremely low gestational age infants with low grade periventricular-intraventricular hemorrhage are not significantly different from those without hemorrhage.
PMCID: PMC3953349  PMID: 23460139
5.  Low-Intensity Therapy in Adults with Burkitt’s Lymphoma 
The New England journal of medicine  2013;369(20):1915-1925.
Burkitt’s lymphoma is an aggressive B-cell lymphoma that occurs in children and adults and is largely curable with the use of intensive and toxic chemotherapy. Current treatments are less effective and have more severe side effects in adults and patients with immunodeficiency than in children.
We studied low-intensity treatment consisting of infused etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (EPOCH-R) in patients with untreated Burkitt’s lymphoma. Two EPOCH-R regimens were tested: a standard dose-adjusted combination in human immunodeficiency virus (HIV)–negative patients (DA-EPOCH-R group) and a lower-dose short-course combination with a double dose of rituximab in HIV-positive patients (SC-EPOCH-RR group).
A total of 30 consecutive patients were treated; 19 patients were in the DA-EPOCH-R group, and 11 in the SC-EPOCH-RR group. The overall median age of the patients was 33 years, and 40% were 40 years of age or older; 73% of the patients had intermediate-risk disease, and 10% had high-risk disease. The principal toxic events, fever and neutropenia, were observed during 22% of the DA-EPOCH-R treatment cycles and 10% of the SC-EPOCH-RR treatment cycles. The tumor lysis syndrome developed in 1 patient; no treatment-related deaths occurred. The median cumulative doses of doxorubicin–etoposide and cyclophosphamide administered in the SC-EPOCH-RR group were 47% and 57% lower, respectively, than those administered in the DA-EPOCH-R group. With median follow-up times of 86 months in the DA-EPOCH-R group and 73 months in the SC-EPOCH-RR group, the rates of freedom from progression of disease and overall survival were, respectively, 95% and 100% with DA-EPOCH-R and 100% and 90% with SC-EPOCH-RR. None of the patients died from Burkitt’s lymphoma.
In this uncontrolled prospective study, low-intensity EPOCH-R–based treatment was highly effective in adults with sporadic or immunodeficiency-associated Burkitt’s lymphoma. (Funded by the National Cancer Institute; numbers, NCT00001337 and NCT00006436.)
PMCID: PMC3901044  PMID: 24224624
6.  Impact of Changes in Perinatal Care on Neonatal Respiratory Outcome and Survival of Preterm Newborns: An Overview of 15 Years 
Survival and outcomes for preterm infants with respiratory distress syndrome (RDS) have improved over the past 30 years. We conducted a study to assess the changes in perinatal care and delivery room management and their impact on respiratory outcome of very low birth weight newborns, over the last 15 years. A comparison between two epochs was performed, the periods before and after 2005, when early nasal continuous positive airway pressure (NCPAP) and Intubation-SURfactant-Extubation (INSURE) were introduced in our center. Three hundred ninety-five clinical records were assessed, 198 (50.1%) females, gestational age 29.1 weeks (22–36), and birth weight 1130 g (360–1498). RDS was diagnosed in 247 (62.5%) newborns and exogenous surfactant was administered to 217 (54.9%). Thirty-three (8.4%) developed bronchopulmonary dysplasia (BPD), and 92 (23%) were deceased. With the introduction of early NCPAP and INSURE, there was a decrease on the endotracheal intubation need and invasive ventilation (P < 0.0001), oxygen therapy (P = 0.002), and mortality (P < 0.0001). The multivariate model revealed a nonsignificant reduction in BPD between the two epochs (OR = 0.86; 95% CI 0.074–9.95; P = 0.9). The changes in perinatal care over the last 15 years were associated to an improvement of respiratory outcome and survival, despite a nonsignificant decrease in BPD rate.
PMCID: PMC3539442  PMID: 23320153
7.  Neurodevelopmental Outcomes in the Early CPAP and Pulse Oximetry Trial 
The New England journal of medicine  2012;367(26):2495-2504.
Previous results from our trial of early treatment with continuous positive airway pressure (CPAP) versus early surfactant treatment in infants showed no significant difference in the outcome of death or bronchopulmonary dysplasia. A lower (vs. higher) target range of oxygen saturation was associated with a lower rate of severe retinopathy but higher mortality. We now report longer-term results from our prespecified hypotheses.
Using a 2-by-2 factorial design, we randomly assigned infants born between 24 weeks 0 days and 27 weeks 6 days of gestation to early CPAP with a limited ventilation strategy or early surfactant administration and to lower or higher target ranges of oxygen saturation (85 to 89% or 91 to 95%). The primary composite outcome for the longer-term analysis was death before assessment at 18 to 22 months or neurodevelopmental impairment at 18 to 22 months of corrected age.
The primary outcome was determined for 1234 of 1316 enrolled infants (93.8%); 990 of the 1058 surviving infants (93.6%) were evaluated at 18 to 22 months of corrected age. Death or neurodevelopmental impairment occurred in 27.9% of the infants in the CPAP group (173 of 621 infants), versus 29.9% of those in the surfactant group (183 of 613) (relative risk, 0.93; 95% confidence interval [CI], 0.78 to 1.10; P = 0.38), and in 30.2% of the infants in the lower-oxygen-saturation group (185 of 612), versus 27.5% of those in the higher-oxygen-saturation group (171 of 622) (relative risk, 1.12; 95% CI, 0.94 to 1.32; P = 0.21). Mortality was increased with the lower-oxygen-saturation target (22.1%, vs. 18.2% with the higher-oxygen-saturation target; relative risk, 1.25; 95% CI, 1.00 to 1.55; P = 0.046).
We found no significant differences in the composite outcome of death or neurodevelopmental impairment among extremely premature infants randomly assigned to early CPAP or early surfactant administration and to a lower or higher target range of oxygen saturation. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute; SUPPORT number, NCT00233324.)
PMCID: PMC4140695  PMID: 23268664
8.  Post-neonatal Mortality, Morbidity, and Developmental Outcome after Ultrasound-Dated Preterm Birth in Rural Malawi: A Community-Based Cohort Study 
PLoS Medicine  2011;8(11):e1001121.
Using data collected as a follow-up to a randomized trial, Melissa Gladstone and colleagues show that during the first two years of life, infants born preterm in southern Malawi are disadvantaged in terms of mortality, growth, and development.
Preterm birth is considered to be associated with an estimated 27% of neonatal deaths, the majority in resource-poor countries where rates of prematurity are high. There is no information on medium term outcomes after accurately determined preterm birth in such settings.
Methods and Findings
This community-based stratified cohort study conducted between May–December 2006 in Southern Malawi followed up 840 post-neonatal infants born to mothers who had received antenatal antibiotic prophylaxis/placebo in an attempt to reduce rates of preterm birth (APPLe trial ISRCTN84023116). Gestational age at delivery was based on ultrasound measurement of fetal bi-parietal diameter in early-mid pregnancy. 247 infants born before 37 wk gestation and 593 term infants were assessed at 12, 18, or 24 months. We assessed survival (death), morbidity (reported by carer, admissions, out-patient attendance), growth (weight and height), and development (Ten Question Questionnaire [TQQ] and Malawi Developmental Assessment Tool [MDAT]). Preterm infants were at significantly greater risk of death (hazard ratio 1.79, 95% CI 1.09–2.95). Surviving preterm infants were more likely to be underweight (weight-for-age z score; p<0.001) or wasted (weight-for-length z score; p<0.01) with no effect of gestational age at delivery. Preterm infants more often screened positively for disability on the Ten Question Questionnaire (p = 0.002). They also had higher rates of developmental delay on the MDAT at 18 months (p = 0.009), with gestational age at delivery (p = 0.01) increasing this likelihood. Morbidity—visits to a health centre (93%) and admissions to hospital (22%)—was similar for both groups.
During the first 2 years of life, infants who are born preterm in resource poor countries, continue to be at a disadvantage in terms of mortality, growth, and development. In addition to interventions in the immediate neonatal period, a refocus on early childhood is needed to improve outcomes for infants born preterm in low-income settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Being born at term in Africa is not necessarily straightforward. In Malawi, 33 of every 1,000 infants born die in the first 28 days after birth; the lifetime risk for a mother dying during or shortly after pregnancy is one in 36. The comparable figures for the United Kingdom are three infants dying per 1,000 births and a lifetime risk of maternal death of one in 4,700. But for a baby, being born preterm is even more risky and the gap between low- and high-income countries widens still further. According to a World Health Organization report in 2010, a baby born at 32 weeks of gestation (weighing around 2,000 g) in Africa has little chance of survival, while the chances of survival for a baby born at 32 weeks in North America or Europe are similar to one born at term. There are very few data on the longer term outcomes of babies born preterm in Africa and there are multiple challenges involved in gathering such information. As prenatal ultrasound is not routinely available, gestational age is often uncertain. There may be little routine follow-up of preterm babies as is commonplace in high-income countries. Data are needed from recent years that take into account both improvements in perinatal care and adverse factors such as a rising number of infants becoming HIV positive around the time of birth.
Why Was This Study Done?
We could improve outcomes for babies born preterm in sub-Saharan Africa if we understood more about what happens to them after birth. We cannot assume that the progress of these babies will be the same as those born preterm in a high-income country, as the latter group will have received different care, both before and after birth. If we can document the problems that these preterm babies face in a low-income setting, we can consider why they happen and what treatments can be realistically tested in this setting. It is also helpful to establish baseline data so that changes over time can be recorded.
The aim of this study was to document four specific outcomes up to the age of two years, on which there were few data previously from rural sub-Saharan Africa: how many babies survived, visits to a health center and admissions to the hospital, growth, and developmental delay.
What Did the Researchers Do and Find?
The researchers examined a group of babies that had been born to mothers who had taken part in a randomized controlled trial of an antibiotic to prevent preterm birth. The trial had previously shown that the antibiotic (azithromycin) had no effect on how many babies were born preterm or on other measures of the infants' wellbeing, and so the researchers followed up babies from both arms of the trial to look at longer term outcomes. From the original group of 2,297 women who took part in the trial, they compared 247 infants born preterm against 593 term infants randomly chosen as controls, assessed at 12, 18, or 24 months. The majority of the preterm babies who survived past a month of age (all but ten) were born after 32 weeks of gestation. Compared to the babies born at term, the infants born preterm were nearly twice as likely to die subsequently in the next two years, were more likely to be underweight (a third were moderately underweight), and to have higher rates of developmental delay. The commonest causes of death were gastroenteritis, respiratory problems, and malaria. Visits to a health center and admissions to hospital were similar in both groups.
What Do these Findings Mean?
This study documents longer term outcomes of babies born preterm in sub-Saharan Africa in detail for the first time. The strengths of the study include prenatal ultrasound dating and correct adjustment of follow-up age (which takes into account being born before term). Because the researchers defined morbidity using routine health center attendances and self-report of illnesses by parents, this outcome does not seem to have been as useful as the others in differentiating between the preterm and term babies. Better means of measuring morbidity are needed in this setting.
In the developed world, there is considerable investment being made to improve care during pregnancy and in the neonatal period. This investment in care may help by predicting which mothers are more likely to give birth early and preventing preterm birth through drug or other treatments. It is to be hoped that some of the benefit will be transferable to low-income countries. A baby born at 26 weeks' gestation and admitted to a neonatal unit in the United Kingdom has a 67% chance of survival; preterm babies born in sub-Saharan Africa face a starkly contrasting future.
Additional Information
Please access these Web sites via the online version of this summary at
UNICEF presents useful statistics on mother and child outcomes
The World Health Organization has attempted to analyse preterm birth rates worldwide, including mapping the regional distribution and has also produced practical guides on strategies such as Kangaroo Mother Care, which can be used for the care of preterm infants in low resource settings
Healthy Newborn Network has good information on initiatives taking place to improve neonatal outcomes in low income settings
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on research being conducted into preterm birth
Tommy's is a nonprofit organization that funds research and provides information on the risks and causes of premature birth
PMCID: PMC3210771  PMID: 22087079
9.  Trends in socioeconomic inequalities in risk of sudden infant death syndrome, other causes of infant mortality, and stillbirth in Scotland: population based study 
Objectives To compare changes in inequalities in sudden infant death syndrome with other causes of infant mortality and stillbirth in Scotland, 1985-2008.
Design Retrospective cohort study.
Setting Scotland 1985-2008, analysed by four epochs of six years.
Participants Singleton births of infants with birth weight >500 g born at 28-43 weeks’ gestation.
Main outcome measures Sudden infant death syndrome, other causes of postneonatal infant death, neonatal death, and stillbirth. Odds ratios expressed as the association across the range of seven categories of Carstairs deprivation score.
Results The association between deprivation and the risk of all cause stillbirth and infant death varied between the four epochs (P=0.04). This was wholly explained by variation in the risk of sudden infant death syndrome (P<0.001 for interaction). Among women living in areas of low deprivation, there was a sharp decline in the rate of sudden infant death syndrome from 1990 to 1993. Among women living in areas of high deprivation, there was a slower decline in sudden infant death syndrome rates between 1992 and 2004. Consequently, the odds ratio for the association between socioeconomic deprivation and sudden infant death syndrome increased from 2.04 (95% confidence interval 1.53 to 2.72) in 1985-90, to 7.52 (4.62 to 12.25) in 1991-6, and 9.50 (5.46 to 16.53) in 1997-2002 but fell to 1.78 (0.87 to 3.65) in 2002-8. The interaction remained significant after adjustment for maternal characteristics.
Conclusion The rate of sudden infant death syndrome declined throughout Scotland in the early 1990s. The decline had a later onset and was slower among women living in areas of high deprivation, probably because of slower uptake of recommended changes in infant sleeping position. The effect was to create a strong independent association between deprivation and sudden infant death syndrome where one did not exist before.
PMCID: PMC3307809  PMID: 22427307
10.  Severe retinopathy of prematurity in infants <30 weeks' gestation in New South Wales and the Australian Capital Territory from 1992 to 2002 
Retinopathy of prematurity (ROP) significantly increased in New South Wales (NSW) from 1986 to 1994, but more recent data suggest that there has now been a decrease.
To study the incidence and treatment of severe ROP (stage ⩾3) in NSW and the Australian Capital Territory (ACT) from 1992 to 2002.
Data collected prospectively from the Neonatal Intensive Care Units' (NICUS) Data Collection over an 11‐year period in infants <30 weeks' gestation were divided into four epochs and analysed retrospectively. The incidence and treatment of severe ROP were compared for gestational ages ⩽24 weeks', 25–26 weeks' and 27–29 weeks' gestation over the four epochs.
In infants ⩽24 weeks' gestation the incidence of severe ROP and those treated increased significantly (stage ⩾3: from 17 (41.5%) to 41 (53.9%), p = 0.052; treated: from 8 (19.5%) to 25 (32.9%), p<0.05 (first and fourth epoch)). In infants 25–26 weeks' gestation the incidence of severe ROP decreased significantly whereas there was a non‐significant increase in those treated (stage ⩾3: from 55 (26.2%) to 46 (19.3%), p<0.05; treated: from 19 (9.0%) to 32 (13.4%)). In infants 27–29 weeks' gestation, there was no significant change in the incidence of severe ROP or those treated (stage ⩾3: from 30 (4.1%) to 17 (2.4%); treated: from 14 (1.9%) to 8 (1.1%)).
In infants ⩽24 weeks' gestation there has been a significant increase in severe ROP, and in infants <27 weeks' gestation the numbers treated for severe ROP increased.
PMCID: PMC2675420  PMID: 17251225
retinopathy of prematurity; preterm infants; cryo‐therapy and laser therapy
11.  Phase II Study of Dose-Adjusted EPOCH-Rituximab in Untreated Diffuse Large B-cell Lymphoma with Analysis of Germinal Center and Post-Germinal Center Biomarkers 
To assess the clinical outcome and the influence of biomarkers associated with apoptosis inhibition (Bcl-2), tumor proliferation (MIB-1) and cellular differentiation on the outcome with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) infusional therapy in diffuse large B-cell lymphoma and analysis of germinal center B-cell (GCB) and post-GCB subtypes by immunohistochemistry.
Patients and Methods
Phase II study of 72 patients with untreated de novo DLBCL who were at least 18 years of age and stage II or higher. Radiation consolidation was not permitted.
Patients had a median age of 50 (range: 19-85) years and 40% had a high-intermediate or high International Prognostic Index (IPI). At five-years, progression-free (PFS) and overall survival (OS) were 79% and 80%, respectively, with a median potential follow-up of 54 months. PFS was 91%, 90%, 67% and 47%, and OS was 100%, 90%, 74% and 37%, for 0-1, 2, 3 and 4-5 IPI factors, respectively, at five-years. The Bcl-2 and MIB-1 biomarkers were not associated with PFS or OS. Based on DA-EPOCH historical controls, rituximab only benefited Bcl-2 positive tumors. Bcl-6 expression was associated with higher PFS whereas GCB exhibited a marginally significant higher PFS compared to post-GCB DLBCL.
DA-EPOCH-R outcome was not affected by tumor proliferation and rituximab appeared to overcome the adverse effect of Bcl-2. Bcl-6 may identify a biological program associated with a superior outcome. Overall, DA-EPOCH-R shows promising outcome in low and intermediate IPI groups. A molecular model of treatment outcome with rituximab and chemotherapy is presented.
PMCID: PMC2409217  PMID: 18378569
12.  Death in the neonatal intensive care unit: changing patterns of end of life care over two decades 
Death remains a common event in the neonatal intensive care unit, and often involves limitation or withdrawal of life sustaining treatment.
To document changes in the causes of death and its management over the last two decades.
An audit of infants dying in the neonatal intensive care unit was performed during two epochs (1985–1987 and 1999–2001). The principal diagnoses of infants who died were recorded, as well as their apparent prognoses, and any decisions to limit or withdraw medical treatment.
In epoch 1, 132 infants died out of 1362 admissions (9.7%), and in epoch 2 there were 111 deaths out of 1776 admissions (6.2%; p<0.001). Approximately three quarters of infants died after withdrawal of life sustaining treatment in both epochs. There was a significant reduction in the proportion of deaths from chromosomal abnormalities, and from neural tube defects in epoch 2.
There have been substantial changes in the illnesses leading to death in the neonatal intensive care unit. These may reflect the combined effects of prenatal diagnosis and changing community and medical attitudes.
PMCID: PMC2672727  PMID: 16790729
palliative care; withholding treatment; intensive care
13.  The nonimpact of gestational age on neurodevelopmental outcome for ventilated survivors born at 23–28 weeks of gestation 
It has long been known that survival of preterm infants strongly depends upon birth weight and gestational age. This study addresses a different question – whether the gestational maturity improves neurodevelopmental outcomes for ventilated infants born at 23–28 weeks who survive to neonatal intensive care unit (NICU) discharge.
We performed a prospective cohort study of 199 ventilated infants born between 23 and 28 weeks of gestation. Neurodevelopmental impairment was determined using the Bayley Scales of Infant Development-II at 24 months.
As expected, when considered as a ratio of all births, both survival and survival without neurodevelopmental impairment were strongly dependent on gestational age. However, the percentage of surviving infants who displayed neurodevelopmental impairment did not vary with gestational age for any level of neurodevelopmental impairment (MDI or PDI <50, <60, <70). Moreover, as a higher percentage of ventilated infants survived to NICU discharge at higher gestational ages, but the percentage of neurodevelopmental impairment in NICU survivors was unaffected by gestational age, the percentage of all ventilated births who survived with neurodevelopmental impairment rose – not fell – with increasing gestation age.
For physicians, parents and policy-makers whose primary concern is the presence of neurodevelopmental impairment in infants who survive the NICU, reliance on gestational age appears to be misplaced.
PMCID: PMC4528368  PMID: 22277021
Prematurity; Neurodevelopmental disability; Gestational age; Neonatal outcomes research; Neonatal ethics
14.  Neonatal Outcomes of Extremely Preterm Infants From the NICHD Neonatal Research Network 
Pediatrics  2010;126(3):443-456.
This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA).
Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22–28 weeks) and very low birth weight (401–1500 g) who were born at network centers between January 1, 2003, and December 31, 2007.
Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at ≤ 12 hours, with most early deaths occurring at 22 and 23 weeks (85% and 43%, respectively). Rates of prenatal steroid use (13% and 53%, respectively), cesarean section (7% and 24%, respectively), and delivery room intubation (19% and 68%, respectively) increased markedly between 22 and 23 weeks. Infants at the lowest GAs were at greatest risk for morbidities. Overall, 93% had respiratory distress syndrome, 46% patent ductus arteriosus, 16% severe intraventricular hemorrhage, 11% necrotizing enterocolitis, and 36% late-onset sepsis. The new severity-based definition of bronchopulmonary dysplasia classified more infants as having bronchopulmonary dysplasia than did the traditional definition of supplemental oxygen use at 36 weeks (68%, compared with 42%). More than one-half of infants with extremely low GAs had undetermined retinopathy status at the time of discharge. Center differences in management and outcomes were identified.
Although the majority of infants with GAs of ≥24 weeks survive, high rates of morbidity among survivors continue to be observed.
PMCID: PMC2982806  PMID: 20732945
extremely low gestation; very low birth weight; morbidity; death
15.  Neonatal cerebral blood flow velocity responses to changes in posture. 
Archives of Disease in Childhood  1993;69(3 Spec No):304-308.
Maintaining a constant cerebral blood flow during a change in cerebral perfusion pressure is known as autoregulation. The integrity of this phenomenon is considered to be important in preventing cerebral lesions in preterm infants. A study was carried out using Doppler ultrasound measurements of cerebral blood flow velocities (CBFV) as an indicator of alterations in cerebral haemodynamics. CBFV were recorded on a beat to beat basis over 60 second epochs, during which time the cerebral perfusion pressure was changed by rapidly altering the infants' posture from horizontal to either 20 degrees head up or head down. An informative response in CBFV was considered to be either (a) a uniphasic, immediate, passive alteration in velocity occurring with the change in posture and without a subsequent change or (b) a biphasic response of an initial change in CBFV followed within 20 seconds by a second response. This latter response is considered to be consistent with autoregulatory activity. A total of 501 epochs in 60 neonates of gestational age 24-41 weeks was analysed. It was shown that any one infant can make either response, but the reliability of making an active, biphasic response increases with increasing gestational age.
PMCID: PMC1029498  PMID: 8215571
16.  Relationship between 17-hydroxyprogesterone caproate concentrations and gestational age at delivery in twin gestation 
To evaluate in women with twin gestation the relationship between 17-hydroxyprogesterone caproate (17-OHPC) concentration and gestational age at delivery and select biomarkers of potential pathways of drug action.
Study Design
Blood was obtained between 24–28 weeks (epoch 1) and 32–35 weeks (epoch 2) in 217 women with twin gestation receiving 17-OHPC or placebo. Gestational age at delivery and concentrations of 17-OHPC, 17-hydroxyprogesterone, progesterone, C-reactive protein (CRP) and corticotrophin releasing hormone were assessed.
Women with higher concentrations of 17-OHPC delivered at earlier gestational ages than women with lower concentrations (p<0.001). Women receiving 17-OHPC demonstrated significantly higher (p=0.005) concentrations of CRP in epoch 1 than women receiving placebo but CRP values were similar in epoch 2 in both groups. A highly significant (p<0.0001) positive relationship was observed between 17-OHPC concentration and progesterone and 17-hydroxyprogesterone concentrations at both epochs. CRH concentrations did not differ by treatment group.
17-OHPC may adversely impact gestational age at delivery in women with twin gestation.
PMCID: PMC3484214  PMID: 22959763
17-hydroxyprogesterone caproate (17-OHPC); pharmacodynamics; twin gestation
17.  Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: A randomized clinical trial 
Invasive candidiasis in premature infants causes mortality and neurodevelopmental impairment. Fluconazole prophylaxis reduces candidiasis, but its effect on mortality and the safety of fluconazole is unknown.
To evaluate the efficacy and safety of fluconazole in preventing death or invasive candidiasis in extremely low-birth-weight infants.
This study was a randomized, blinded, placebo-controlled trial of fluconazole in premature infants. Infants weighing less than 750 g at birth (N = 361) from 32 neonatal intensive care units (NICUs) in the United States were randomly assigned to receive either fluconazole or placebo twice weekly for 42 days. Surviving infants were evaluated at 18 to 22 months corrected age for neurodevelopmental outcomes. The study was conducted between November 2008 and February 2013.
Fluconazole (6 mg/kg of body weight) or placebo.
The primary end point was a composite of death or definite or probable invasive candidiasis prior to study day 49 (1 week after completion of study drug). Secondary and safety outcomes included invasive candidiasis, liver function, bacterial infection, length of stay, intracranial hemorrhage, periventricular leukomalacia, chronic lung disease, patent ductus arteriosus requiring surgery, retinopathy of prematurity requiring surgery, necrotizing enterocolitis, spontaneous intestinal perforation, and neurodevelopmental outcomes—defined as a Bayley-III cognition composite score of less than 70, blindness, deafness, or cerebral palsy at 18–22-months corrected age.
Among infants receiving fluconazole, the composite primary end point of death or invasive candidiasis was 16% (95% CI, 11%–22%) vs 21% in the placebo group (95% CI, 15%–28%; odds ratio 0.73 [95% CI 0.43–1.23]; P=.24; treatment difference −5% [95% CI, −13%–3%]). Invasive candidiasis occurred less frequently in the fluconazole group (3% [95% CI, 1%–6%] vs the placebo group (9% [95% CI, 5%–14%]; P=.02; treatment difference −6% [95% CI, −11%–−1%]). The cumulative incidences of other secondary outcomes were not statistically different between groups. Neurodevelopmental impairment did not differ between the groups (fluconazole 31% [95% CI, 21–41%] vs placebo, 27% [95% CI, 18–37%]; P=.60; treatment difference 4% [95% CI, −10–17%]).
Among infants with a birth weight of less 750 g, 42 days of fluconazole prophylaxis compared with placebo did not result in a lower incidence of the composite of death or invasive candidiasis. These findings do not support the universal use of prophylactic fluconazole in extremely-low-birth-weight infants.
PMCID: PMC4110724  PMID: 24794367
18.  Changes in Perinatal Care and Predictors of In-Hospital Mortality for Very Low Birth Weight Preterm Infants 
Iranian Journal of Pediatrics  2012;22(3):326-332.
Mortality of very low birth weight premature infants is of great public health concern. To better guide local intervention program, it is essential that current and reliable statistics be collected to understand the factors associated with mortality of these infants.
Data of very low birth weight premature infants admitted to a neonatal unit during 2002-2009 was retrospectively collected. Changes in perinatal care between two halves of the study period (2002-2005 and 2006-2009) were identified. Factors associated with in-hospital mortality were found by logistic regression and a predictive score model was established.
A total of 475 cases were enrolled. In-hospital mortality decreased from 29.8% in 2002-2005 to 28.1% in 2006-2009 (P>0.05). More infants born <28 gestational weeks survived to discharge in the latter epoch (38.1% vs 8.3%, P<0.05). Persistent pulmonary hypertension of newborn, pulmonary hemorrhage, birth weight <000 grams, gestational age <33 weeks, feeding before 3 postnatal days and enteral feeding were found predictors of in-hospital mortality by logistic regression. The discriminating ability of the predictive model was 82.4% and the cutoff point was -0.56.
Survival of very low birth weight premature neonates was not significantly improved in 2006-2009 than 2002-2005. Infants with a score higher than -0.56 were assessed to be at high risk of in-hospital mortality. Multi-center studies of planned follow-up are needed to develop a comprehensive and applicable score system.
PMCID: PMC3564087  PMID: 23399925
Premature Infant; Very Low Birth Weight; Mortality; Predictive Score Model
19.  Validation of the Functional Status II questionnaire in the assessment of extremely-low-birthweight infants 
The increased survival of infants born at extremely low birthweight (ELBW) has been associated with significant morbidity, including higher rates of neurodevelopmental disability. However, formalized testing to evaluate these problems is both time-consuming and costly. The revised Functional Status questionnaire (FS-II) was designed to assess caregivers’ perceptions of the functional status of children with chronic diseases.
We evaluated the reliability and validity of the FS-II for ELBW infants at 18 to 22 months corrected age using data from the US Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN). Exploratory factor analyses were conducted using data from the network’s first follow-up study of 1080 children born in 1993 to 1994 (508 males, 572 females [53%]), and results were confirmed using data from the next network follow-up of 4022 children born in 1995 to 2000 (1864 males, 2158 females [54%]).
Results suggest that a two-factor solution comprising measures of general health and independence is most appropriate for ELBW infants. These factors differed from those found among chronically ill children, and new, more appropriate scales are presented for screening ELBW survivors. Both scales demonstrated good internal consistency: Cronbach’s α=0.87 for general health and α=0.75 for independence. Construct validity of the scales was assessed by comparing mean scores on the scales according to scores on the Bayley Scales of Infant Development, second edition (BSID-II), and medical conditions.
As hypothesized, infants with greater functional impairments according to their BSID-II scores or medical conditions had lower scores on the general health and independence scales, supporting the validity of the scales.
PMCID: PMC3031102  PMID: 19459909
20.  Developmental outcome of very low birth weight infants in a developing country 
BMC Pediatrics  2012;12:11.
Advances in neonatal care allow survival of extremely premature infants, who are at risk of handicap. Neurodevelopmental follow up of these infants is an essential part of ongoing evaluation of neonatal care. The neonatal care in resource limited developing countries is very different to that in first world settings. Follow up data from developing countries is essential; it is not appropriate to extrapolate data from units in developed countries. This study provides follow up data on a population of very low birth weight (VLBW) infants in Johannesburg, South Africa.
The study sample included all VLBW infants born between 01/06/2006 and 28/02/2007 and discharged from the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Bayley Scales of Infant and Toddler Development Version 111 (BSID) 111 were done to assess development. Regression analysis was done to determine factors associated with poor outcome.
178 infants were discharged, 26 were not available for follow up, 9 of the remaining 152 (5.9%) died before an assessment was done; 106 of the remaining 143 (74.1%) had a BSID 111 assessment. These 106 patients form the study sample; mean birth weight and mean gestational age was 1182 grams (SD: 197.78) and 30.81 weeks (SD: 2.67) respectively. The BSID (111) was done at a median age of 16.48 months. The mean cognitive subscale was 88.6 (95% CI: 85.69 - 91.59), 9 (8.5%) were < 70, mean language subscale was 87.71 (95% CI: 84.85 - 90.56), 10 (9.4%) < 70, and mean motor subscale was 90.05 (95% CI: 87.0 - 93.11), 8 (7.6%) < 70. Approximately one third of infants were identified as being at risk (score between 70 and 85) on each subscale. Cerebral palsy was diagnosed in 4 (3.7%) of babies. Factors associated with poor outcome included cystic periventricular leukomalacia (PVL), resuscitation at birth, maternal parity, prolonged hospitalisation and duration of supplemental oxygen. PVL was associated with poor outcome on all three subscales. Birth weight and gestational age were not predictive of neurodevelopmental outcome.
Although the neurodevelopmental outcome of this group of VLBW infants was within the normal range, with a low incidence of cerebral palsy, these results may reflect the low survival of babies with a birth weight below 900 grams. In addition, mean subscale scores were low and one third of the babies were identified as "at risk", indicating that this group of babies warrants long-term follow up into school going age.
PMCID: PMC3293066  PMID: 22296705
21.  The Effect of Red Blood Cell Transfusion on Intermittent Hypoxemia in ELBW Infants 
To test the hypothesis that the effect of red blood cell (RBC) transfusion on intermittent hypoxemia (IH) in extremely low birth weight (ELBW) infants is dependent on postnatal age.
Study Design
Oxygen saturation of 130 ELBW infants, who required transfusion, was monitored continuously for the first 8wks of life. We compared the characteristics of IH (SpO2 ≤ 80% for ≥4s and ≤3min), 24h before and both 24h and 24-48h after each RBC transfusion at three distinct time periods: Epoch 1, 1-7d; Epoch 2, 8-28d; and Epoch 3, >28d.
In Epoch 1, the frequency and severity of IH events were not significantly different before and after transfusion. In both Epochs 2 and 3 there was a decrease in IH frequency and severity 24h after RBC transfusion that persisted for 48h. In addition, there was a decrease in the overall time spent with SpO2 ≤ 80% which persisted for 24h after transfusion in Epochs 1 and 3, and for 48h in Epoch 3.
The benefit of RBC transfusion on IH is age dependent as improvement in the frequency and severity of IH after transfusion only occurs beyond the first week of life. These observations will aid clinician’s decision making by clarifying the benefit of RBC transfusions on patterns of oxygenation in preterm infants.
PMCID: PMC4245392  PMID: 24921411
Red Blood Cell Transfusion; Intermittent Hypoxemia; Apnea of Prematurity; Oxygen Saturation
22.  Cerebral blood flow velocity during neonatal seizures 
AIM—To determine if cerebral blood flow velocity increases during all types of neonatal seizure, and whether the effect is due solely to an increase in blood pressure, transmitted to the cerebral circulation when autoregulation is impaired.
METHODS—Seizures were diagnosed in 11 high risk neonates using cotside 16 channel video-EEG polygraphy. EEG, cerebral blood flow velocity (CBFV) using transcranial Doppler ultrasound, and arterial blood pressure (ABP) measurements were made. At least two 5-10 minute epochs of simultaneous measurements were performed on each infant. These epochs were then reviewed to eliminate artefacts, and one minute data periods containing a clear seizure onset were created. Each period contained 20 seconds before the seizure. Data periods without seizures from the same infants were also analysed and compared with seizure periods.
RESULTS—Four infants had purely electrographic seizures—without clinical manifestations. Six infants had electroclinical seizures. One infant displayed both seizure types. A random effects linear regression analysis was used to determine the effect of seizures on CBFV and ABP. A significant increase was found in mean CBFV in those periods containing seizures. The mean percentage change in velocity for all infants was 15.6%. Three infants showed a significant increase in mean ABP after seizures but the overall increase in ABP for all infants was not significant.
CONCLUSION—Electroclinical and electrographic neonatal seizures produce an increase in CBFV. In some infants the increase is not associated with an increase in blood pressure. These preliminary results suggest that electrographic seizures are associated with disturbed cerebral metabolism. Treatment of neonatal seizures until electrographic seizure activity is abolished may improve outcome for these infants. 

PMCID: PMC1720914  PMID: 10325785
23.  Approach to Infants Born at 22 to 24 Weeks’ Gestation: Relationship to Outcomes of More-Mature Infants 
Pediatrics  2012;129(6):e1508-e1516.
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.
PMCID: PMC3362905  PMID: 22641761
low-birth weight infant; NICUs; treatment; patient outcome assessment
24.  Phase 1 Trial of 4 Thyroid Hormone Regimens for Transient Hypothyroxinemia in Neonates of <28 Weeks' Gestation 
Pediatrics  2009;124(2):e258-e268.
Transiently low levels of thyroid hormones occur in ∼50% of neonates born 24–28 weeks' gestation and are associated with higher rates of cerebral palsy and cognitive impairment. Raising hormone levels shows promise for improving neurodevelopmental outcome.
To identify whether any of 4 thyroid hormone supplementation regimens could raise T4 and FT4 without suppressing TSH (biochemical euthyroidism).
Eligible subjects had gestational ages between 240/7 and 276/7 weeks and were randomized <24 hours of birth to one of six study arms (n = 20–27 per arm): placebo (vehicle: 5% dextrose), potassium iodide (30 μg/kg/d) and continuous or bolus daily infusions of either 4 or 8 μg/kg/d of T4 for 42 days. T4 was accompanied by 1 μg/kg/d T3 during the first 14 postnatal days and infused with 1 mg/mL albumin to prevent adherence to plastic tubing.
FT4 was elevated in the first 7 days in all hormone-treated subjects; however, only the continuous 8 μg/kg/d treatment arm showed a significant elevation in all treatment epochs (P < .002 versus all other groups). TT4 remained elevated in the first 7 days in all hormone-treated subjects (P < .05 versus placebo or iodine arms). After 14 days, both 8 μg/kg/d arms as well as the continuous 4 μg/kg/d arm produced a sustained elevation of the mean and median TT4, >7 μg/dL (90 nM/L; P < .002 versus placebo). The least suppression of THS was achieved in the 4 μg/kg/d T4 continuous infusion arm. Although not pre-hypothesized, the duration of mechanical ventilation was significantly lower in the continuous 4 μg/kg/d T4 arm and in the 8 μg/kg/d T4 bolus arm (P < .05 versus remaining arms). ROP was significantly lower in the combined 4 thyroid hormone treatment arms than in the combined placebo and iodine arms (P < .04). NEC was higher in the combined 8 μg/kg/d arms (P < .05 versus other arms).
Elevation of TT4 with only modest suppression of TSH was associated with trends suggesting clinical benefits using a continuous supplement of low-dose thyroid hormone (4 μg/kg/d) for 42 days. Future trials will be needed to assess the long-term neurodevelopmental effects of such supplementation.
PMCID: PMC2927485  PMID: 19581264
thyroxine; triiodothyronine; hypothyroxinemia; thyroid hormone; monodeiodinase; extremely low birth weight neonate; transient hypothyroxinemia; nonthyroidal illness; euthyroid sick syndrome; cerebral palsy; prematurity; randomized; controlled trial
25.  Risk Factors for Post-NICU Discharge Mortality Among Extremely Low Birth Weight Infants 
The Journal of Pediatrics  2012;161(1):70-74.e2.
To evaluate maternal and neonatal risk factors associated with post-neonatal intensive care unit (NICU) discharge mortality among ELBW infants.
Study design
This is a retrospective analysis of extremely low birth weight (<1,000 g) and <27 weeks' gestational age infants born in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network sites from January 2000 to June 2007. Infants were tracked until death or 18–22 months corrected age. Infants who died between NICU discharge and the 18–22 month follow-up visit were classified as post-NICU discharge mortality. Association of maternal and infant risk factors with post-NICU discharge mortality was determined using logistic regression analysis. A prediction model with six significant predictors was developed and validated.
5,364 infants survived to NICU discharge. 557 (10%) infants were lost to follow-up, and 107 infants died following NICU discharge. Post-NICU discharge mortality rate was 22.3 per 1000 ELBW infants. In the prediction model, African-American race, unknown maternal health insurance, and hospital stay ≥120 days significantly increased risk, and maternal exposure to intra-partum antibiotics was associated with decreased risk of post-NICU discharge mortality.
We identified African-American race, unknown medical insurance and prolonged NICU stay as risk factors associated with post-NICU discharge mortality among ELBW infants.
PMCID: PMC3366175  PMID: 22325187
extremely preterm infants; discharge; mortality; predictive model

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