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1.  Approach to Infants Born at 22 to 24 Weeks’ Gestation: Relationship to Outcomes of More-Mature Infants 
Pediatrics  2012;129(6):e1508-e1516.
OBJECTIVE:
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).
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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.
doi:10.1542/peds.2011-2216
PMCID: PMC3362905  PMID: 22641761
low-birth weight infant; NICUs; treatment; patient outcome assessment
2.  Prediction of Bronchopulmonary Dysplasia by Postnatal Age in Extremely Premature Infants 
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.
doi:10.1164/rccm.201101-0055OC
PMCID: PMC3136997  PMID: 21471086
bronchopulmonary dysplasia; prematurity; low-birth-weight infant
3.  Survival and Morbidity Outcomes of Very Low Birth Weight Infants with Down Syndrome 
Pediatrics  2010;126(6):1132-1140.
OBJECTIVE
Individuals with Down syndrome (DS) are at increased risk of several morbidities with lifelong health consequences. Little is known about mortality or morbidity risks in early infancy among very-low-birth-weight (VLBW) infants with DS. Our objective was to compare survival and neonatal morbidities between VLBW infants with DS and VLBW infants with other non-DS chromosomal anomalies, other non-chromosomal birth defects, and VLBW infants without major birth defects.
METHODS
Data were collected prospectively for infants weighing 401-1500 grams born and/or cared for at one of the study centers participating in the NICHD Neonatal Research Network from 1994 through 2008. Risk of death and morbidities including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD), were compared between VLBW infants with DS and infants in the other groups.
RESULTS
Infants with DS were at increased risk of death (adjusted relative risk [RR] 2.47, 95% confidence interval [CI] 2.00-3.07), PDA, NEC, LOS, and BPD relative to infants with no birth defects. Decreased risk of death (RR 0.40, 95% CI 0.31-0.52) and increased risks of NEC and LOS were observed when comparing infants with DS to infants with other non-DS chromosomal anomalies. Relative to infants with non-chromosomal birth defects, infants with DS were at increased risk of PDA and NEC.
CONCLUSION
The increased risk of morbidities among VLBW infants with DS provides useful information for counseling parents and for caretakers in anticipating the need for enhanced surveillance for prevention of these morbidities.
doi:10.1542/peds.2010-1824
PMCID: PMC3059605  PMID: 21098157
neonatal mortality; neonatal morbidity; preterm infants; Down syndrome; trisomy 21
4.  Identification of Extremely Premature Infants at High Risk of Rehospitalization 
Pediatrics  2011;128(5):e1216-e1225.
OBJECTIVE:
Extremely low birth weight infants often require rehospitalization during infancy. Our objective was to identify at the time of discharge which extremely low birth weight infants are at higher risk for rehospitalization.
METHODS:
Data from extremely low birth weight infants in Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers from 2002–2005 were analyzed. The primary outcome was rehospitalization by the 18- to 22-month follow-up, and secondary outcome was rehospitalization for respiratory causes in the first year. Using variables and odds ratios identified by stepwise logistic regression, scoring systems were developed with scores proportional to odds ratios. Classification and regression-tree analysis was performed by recursive partitioning and automatic selection of optimal cutoff points of variables.
RESULTS:
A total of 3787 infants were evaluated (mean ± SD birth weight: 787 ± 136 g; gestational age: 26 ± 2 weeks; 48% male, 42% black). Forty-five percent of the infants were rehospitalized by 18 to 22 months; 14.7% were rehospitalized for respiratory causes in the first year. Both regression models (area under the curve: 0.63) and classification and regression-tree models (mean misclassification rate: 40%–42%) were moderately accurate. Predictors for the primary outcome by regression were shunt surgery for hydrocephalus, hospital stay of >120 days for pulmonary reasons, necrotizing enterocolitis stage II or higher or spontaneous gastrointestinal perforation, higher fraction of inspired oxygen at 36 weeks, and male gender. By classification and regression-tree analysis, infants with hospital stays of >120 days for pulmonary reasons had a 66% rehospitalization rate compared with 42% without such a stay.
CONCLUSIONS:
The scoring systems and classification and regression-tree analysis models identified infants at higher risk of rehospitalization and might assist planning for care after discharge.
doi:10.1542/peds.2011-1142
PMCID: PMC3208965  PMID: 22007016
logistic models; infant; premature; predictive value of tests
5.  Risk Factors for Post-NICU Discharge Mortality Among Extremely Low Birth Weight Infants 
The Journal of Pediatrics  2012;161(1):70-74.e2.
Objective
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.
Results
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.
Conclusion
We identified African-American race, unknown medical insurance and prolonged NICU stay as risk factors associated with post-NICU discharge mortality among ELBW infants.
doi:10.1016/j.jpeds.2011.12.038
PMCID: PMC3366175  PMID: 22325187
extremely preterm infants; discharge; mortality; predictive model
6.  Vitamin A Supplementation in Extremely Low- Birth-Weight Infants: Subgroup Analysis in Small-for-Gestational-Age Infants 
American journal of perinatology  2013;30(9):771-780.
Objective
Preterm infants with intrauterine growth restriction are at increased risk of respiratory distress syndrome and bronchopulmonary dysplasia (BPD). A randomized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network demonstrated that vitamin A supplementation in extremely low-birth-weight (ELBW) preterm infants requiring early respiratory support decreased the risk of developing BPD.
Study Design
A subgroup analysis of small-for-gestational-age (SGA) infants from the original NICHD trial was performed to test the hypothesis that in infants requiring early respiratory support, vitamin A supplementation decreases the relative risk of BPD or death in premature SGA infants to a greater extent than in gestational age–equivalent vitamin A–treated appropriate-for-gestational-age (AGA) infants.
Results
Although vitamin A supplementation significantly increased serum retinol concentrations in AGA ELBW infants (median [5th percentile, 95th percentile]: 16.3 [−7.0, 68.8] versus 2.4 [−13.9, 55.1]; p < 0.001), no increases were noted in SGA ELBW infants.
Conclusions
Given the limited power of this analysis due to a low number of SGA infants, these data did not provide evidence to support the hypothesis that vitamin A supplementation in preterm SGA infants requiring early respiratory support decreases the relative risk of BPD or death as compared with preterm AGA infants.
doi:10.1055/s-0032-1333410
PMCID: PMC3923571  PMID: 23329565
vitamin A; IUGR–intrauterine growth restriction; BPD–bronchopulmonary dysplasia; SGA–small for gestational age; AGA–appropriate for gestational age
7.  Patent Ductus Arteriosus Therapy: Impact on Neonatal and 18-Month Outcome 
Pediatrics  2009;123(2):674-681.
OBJECTIVE
The purpose of this work was to evaluate therapy for patent ductus arteri-osus as a risk factor for death or neurodevelopmental impairment at 18 to 22 months, bronchopulmonary dysplasia, or necrotizing enterocolitis in extremely low birth weight infants.
METHODS
We studied infants in the National Institute of Child Health and Human Development Neonatal Research Network Generic Data Base born between 2000 and 2004 at 23 to 28 weeks’ gestation and at <1000-g birth weight with patent ductus arteriosus. Patent ductus arteriosus therapy was evaluated as a risk factor for outcomes in bivariable and multivariable analyses.
RESULTS
Treatment for subjects with patent ductus arteriosus (n = 2838) included 403 receiving supportive treatment only, 1525 treated with indomethacin only, 775 with indomethacin followed by secondary surgical closure, and 135 treated with primary surgery. Patients who received supportive therapy for patent ductus arteriosus did not differ from subjects treated with indomethacin only for any of the outcomes of interest. Compared with indomethacin treatment only, patients undergoing primary or secondary surgery were smaller and more premature. When compared with indomethacin alone, primary surgery was associated with increased adjusted odds for neurodevelopmental impairment and bronchopulmonary dysplasia in multivariable logistic regression. Secondary surgical closure was associated with increased odds for neurodevelopmental impairment and increased adjusted odds for bronchopulmonary dysplasia but decreased adjusted odds for death. Risk of necrotizing enterocolitis did not differ among treatments. Indomethacin prophylaxis did not significantly modify these results.
CONCLUSIONS
Our results suggest that infants treated with primary or secondary surgery for patent ductus arteriosus may be at increased risk for poor short- and long-term outcomes compared with those treated with indomethacin. Prophylaxis with indomethacin in the first 24 hours of life did not modify the subsequent outcomes of patent ductus arteriosus therapy.
doi:10.1542/peds.2007-2781
PMCID: PMC2752886  PMID: 19171637
patent ductus arteriosus; bronchopulmonary dysplasia; necrotizing enterocolitis; neurodevelopmental impairment; therapy ductus arteriosus
8.  Short-term outcome of very low-birth-weight infants in a tertiary care hospital in Saudi Arabia 
Annals of Saudi Medicine  2011;31(6):581-585.
BACKGROUND AND OBJECTIVE:
Published data on short-term outcomes of very low birth weight infants from Saudi Arabia are limited. In the present study, our objective was to describe and analyze the outcomes of very low birth weight infants admitted to our neonatal intensive care unit and to compare the results with data published by the National Institute of Child Health and Development.
DESIGN AND SETTING:
This study was a retrospective analysis of prospectively collected data from a single tertiary care center over a three years period.
PATIENTS AND METHODS:
Biodemographic data and data regarding multiple outcome measures were analyzed for infants with birth weight of 1500 g or less. Data were obtained from our neonatal intensive care unit database.
RESULTS:
Our results included a total of 186 infants with birth weights of 1500 g or less. Of these infants, 154 (82.8%) survived to discharge. Seventy-six (40.9%) were male, and mean (SD) gestational age (GA) was 29 (2.9) weeks with a range of 21 weeks, 6 days to 36 weeks, 2 days. Mean (SD) birth weight was 1062 (302) g with a range of 420 to 1495 g. Fifty-seven (30.6%) infants were characterized as small for gestational age. Antenatal steroids were given to 74.2% of mothers. Eighty-five percent of infants were born by cesarean section. The rate of bronchopulmonary dysplasia was 17.7%, patent ductus arteriosus 31.2%, intraventricular hemorrhage 12.9%, periventricular leukomalacia 3.8%, necrotizing enterocolitis 7.5%, retinopathy of prematurity 28.3%, and late-onset sepsis was 21.9%.
CONCLUSION:
In this population of very low birth weight infants, survival rates and complications of prematurity were comparable to international data.
doi:10.4103/0256-4947.87093
PMCID: PMC3221128  PMID: 22048502
9.  Methicillin-Resistant and Susceptible Staphylococcus aureus Bacteremia and Meningitis in Preterm Infants 
Pediatrics  2012;129(4):e914-e922.
BACKGROUND:
Data are limited on the impact of methicillin-resistant Staphylococcus aureus (MRSA) on morbidity and mortality among very low birth weight (VLBW) infants with S aureus (SA) bacteremia and/or meningitis (B/M).
METHODS:
Neonatal data for VLBW infants (birth weight 401–1500 g) born January 1, 2006, to December 31, 2008, who received care at centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were collected prospectively. Early-onset (≤72 hours after birth) and late-onset (>72 hours) infections were defined by blood or cerebrospinal fluid cultures and antibiotic treatment of ≥5 days (or death <5 days with intent to treat). Outcomes were compared for infants with MRSA versus methicillin-susceptible S aureus (MSSA) B/M.
RESULTS:
Of 8444 infants who survived >3 days, 316 (3.7%) had SA B/M. Eighty-eight had MRSA (1% of all infants, 28% of infants with SA); 228 had MSSA (2.7% of all infants, 72% of infants with SA). No infant had both MRSA and MSSA B/M. Ninety-nine percent of MRSA infections were late-onset. The percent of infants with MRSA varied by center (P < .001) with 9 of 20 centers reporting no cases. Need for mechanical ventilation, diagnosis of respiratory distress syndrome, necrotizing enterocolitis, and other morbidities did not differ between infants with MRSA and MSSA. Mortality was high with both MRSA (23 of 88, 26%) and MSSA (55 of 228, 24%).
CONCLUSIONS:
Few VLBW infants had SA B/M. The 1% with MRSA had morbidity and mortality rates similar to infants with MSSA. Practices should provide equal focus on prevention and management of both MRSA and MSSA infections among VLBW infants.
doi:10.1542/peds.2011-0966
PMCID: PMC3313632  PMID: 22412036
Staphylococcus aureus; methicillin resistant; infant; newborn
10.  Intercenter Differences in Bronchopulmonary Dysplasia or Death Among Very Low Birth Weight Infants 
Pediatrics  2010;127(1):e106-e116.
OBJECTIVES:
To determine (1) the magnitude of clustering of bronchopulmonary dysplasia (36 weeks) or death (the outcome) across centers of the Eunice Kennedy Shriver National Institute of Child and Human Development National Research Network, (2) the infant-level variables associated with the outcome and estimate their clustering, and (3) the center-specific practices associated with the differences and build predictive models.
METHODS:
Data on neonates with a birth weight of <1250 g from the cluster-randomized benchmarking trial were used to determine the magnitude of clustering of the outcome according to alternating logistic regression by using pairwise odds ratio and predictive modeling. Clinical variables associated with the outcome were identified by using multivariate analysis. The magnitude of clustering was then evaluated after correction for infant-level variables. Predictive models were developed by using center-specific and infant-level variables for data from 2001 2004 and projected to 2006.
RESULTS:
In 2001–2004, clustering of bronchopulmonary dysplasia/death was significant (pairwise odds ratio: 1.3; P < .001) and increased in 2006 (pairwise odds ratio: 1.6; overall incidence: 52%; range across centers: 32%–74%); center rates were relatively stable over time. Variables that varied according to center and were associated with increased risk of outcome included lower body temperature at NICU admission, use of prophylactic indomethacin, specific drug therapy on day 1, and lack of endotracheal intubation. Center differences remained significant even after correction for clustered variables.
CONCLUSION:
Bronchopulmonary dysplasia/death rates demonstrated moderate clustering according to center. Clinical variables associated with the outcome were also clustered. Center differences after correction of clustered variables indicate presence of as-yet unmeasured center variables.
doi:10.1542/peds.2010-0648
PMCID: PMC3010091  PMID: 21149431
logistic models; infant; premature; predictive value of tests; clustering
11.  Early-Childhood Neurodevelopmental Outcomes Are Not Improving for Infants Born at <25 Weeks' Gestational Age 
Pediatrics  2011;127(1):62-70.
OBJECTIVE:
We compared neurodevelopmental outcomes at 18 to 22 months' corrected age of infants born with extremely low birth weight at an estimated gestational age of <25 weeks during 2 periods: 1999–2001 (epoch 1) and 2002–2004 (epoch 2).
PATIENTS AND METHODS:
We conducted a multicenter, retrospective analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Perinatal and neonatal variables and outcomes were compared between epochs. Neurodevelopmental outcomes at 18 to 22 months' corrected age were evaluated with neurologic exams and Bayley Scales of Infant Development II. Logistic regression analyses determined the independent risk of epoch for adverse outcomes.
RESULTS:
Infant survival was similar between epochs (epoch 1, 35.4%, vs epoch 2, 32.3%; P = .09). A total of 411 of 452 surviving infants in epoch 1 and 405 of 438 surviving infants in epoch 2 were evaluated at 18 to 22 months' corrected age. Cesarean delivery (P = .03), surgery for patent ductus arteriosus (P = .004), and late sepsis (P = .01) were more common in epoch 2, but postnatal steroid use was dramatically reduced (63.5% vs 32.8%; P < .0001). Adverse outcomes at 18 to 22 months' corrected age were common in both epochs. Moderate-to-severe cerebral palsy was diagnosed in 11.1% of surviving infants in epoch 1 and 14.9% in epoch 2 (adjusted odds ratio [OR]: 1.52 [95% confidence interval (CI): 0.86–2.71]; P = .15), the Mental Developmental Index was <70 in 44.9% in epoch 1 and 51% in epoch 2 (OR: 1.30 [95% CI: 0.91–1.87]; P = .15), and neurodevelopmental impairment was diagnosed in 50.1% of surviving infants in epoch 1 and 58.7% in epoch 2 (OR: 1.4 [95% CI: 0.98–2.04]; P = .07).
CONCLUSIONS:
Early-childhood outcomes for infants born at <25 weeks' estimated gestational age were unchanged between the 2 periods.
doi:10.1542/peds.2010-1150
PMCID: PMC3375467  PMID: 21187312
extremely preterm; neurodevelopmental; outcome; cerebral palsy; Bayley Scales of Infant Development II
12.  Population based trends in mortality, morbidity and treatment for very preterm- and very low birth weight infants over 12 years 
BMC Pediatrics  2012;12:17.
Background
Over the last two decades, improvements in medical care have been associated with a significant increase and better outcome of very preterm (VP, < 32 completed gestational weeks) and very low birth weight (VLBW, < 1500 g) infants. Only a few publications analyse changes of their short-term outcome in a geographically defined area over more than 10 years. We therefore aimed to investigate the net change of VP- and VLBW infants leaving the hospital without major complications.
Methods
Our population-based observational cohort study used the Minimal Neonatal Data Set, a database maintained by the Swiss Society of Neonatology including information of all VP- and VLBW infants. Perinatal characteristics, mortality and morbidity rates and the survival free of major complications were analysed and their temporal trends evaluated.
Results
In 1996, 2000, 2004, and 2008, a total number of 3090 infants were enrolled in the Network Database. At the same time the rate of VP- and VLBW neonates increased significantly from 0.87% in 1996 to 1.10% in 2008 (p < 0.001). The overall mortality remained stable by 13%, but the survival free of major complications increased from 66.9% to 71.7% (p < 0.01). The percentage of infants getting a full course of antenatal corticosteroids increased from 67.7% in 1996 to 91.4% in 2008 (p < 0.001). Surfactant was given more frequently (24.8% in 1996 compared to 40.1% in 2008, p < 0.001) and the frequency of mechanical ventilation remained stable by about 43%. However, the use of CPAP therapy increased considerably from 43% to 73.2% (p < 0.001). Some of the typical neonatal pathologies like bronchopulmonary dysplasia, necrotising enterocolitis and intraventricular haemorrhage decreased significantly (p ≤ 0.02) whereas others like patent ductus arteriosus and respiratory distress syndrome increased (p < 0.001).
Conclusions
Over the 12-year observation period, the number of VP- and VLBW infants increased significantly. An unchanged overall mortality rate and an increase of survivors free of major complication resulted in a considerable net gain in infants with potentially good outcome.
doi:10.1186/1471-2431-12-17
PMCID: PMC3311070  PMID: 22356724
13.  Ten-Year Review of Major Birth Defects in VLBW Infants 
Pediatrics  2013;132(1):49-61.
OBJECTIVE:
Birth defects (BDs) are an important cause of infant mortality and disproportionately occur among low birth weight infants. We determined the prevalence of BDs in a cohort of very low birth weight (VLBW) infants cared for at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers over a 10-year period and examined the relationship between anomalies, neonatal outcomes, and surgical care.
METHODS:
Infant and maternal data were collected prospectively for infants weighing 401 to 1500 g at NRN sites between January 1, 1998, and December 31, 2007. Poisson regression models were used to compare risk of outcomes for infants with versus without BDs while adjusting for gestational age and other characteristics.
RESULTS:
A BD was present in 1776 (4.8%) of the 37 262 infants in our VLBW cohort. Yearly prevalence of BDs increased from 4.0% of infants born in 1998 to 5.6% in 2007, P < .001. Mean gestational age overall was 28 weeks, and mean birth weight was 1007 g. Infants with BDs were more mature but more likely to be small for gestational age compared with infants without BDs. Chromosomal and cardiovascular anomalies were most frequent with each occurring in 20% of affected infants. Mortality was higher among infants with BDs (49% vs 18%; adjusted relative risk: 3.66 [95% confidence interval: 3.41–3.92]; P < .001) and varied by diagnosis. Among those surviving >3 days, more infants with BDs underwent major surgery (48% vs 13%, P < .001).
CONCLUSIONS:
Prevalence of BDs increased during the 10 years studied. BDs remain an important cause of neonatal morbidity and mortality among VLBW infants.
doi:10.1542/peds.2012-3111
PMCID: PMC3691532  PMID: 23733791
birth defects; prematurity; Neonatal Research Network; low birth weight
14.  Short-Term Outcomes of Very Low Birth Weight Infants Born at a Tertiary Care Hospital, Istanbul, Turkey 
Iranian Journal of Pediatrics  2013;23(2):205-211.
Objective
To evaluate mortality and short-term outcomes in very low birth weight infants admitted to the tertiary neonatal intensive care unit, Istanbul, Turkey.
Methods
Study data were recorded prospectively from January 1, 2010, to December 31, 2010. The clinical findings in neonates with birth weights <1000g were compared with infants with birth weights of between 1000g and 1499g.
Findings
In the present study, survival rates were 40% and 86.2% for infants weighing <1000g and 1000g to 1499g, respectively. There was no difference between males and females with respect to mortality (P>0.05). The mean (±standard deviation) birth weight was 985.6±150.15 g and mean gestational age was 27.5±2.04 weeks. The antenatal steroid rate was 37.2%, and the Cesarean section rate was 73%. Respiratory distress syndrome was diagnosed in 89% of the infants, with a 69% surfactant administration rate. Severe intracranial hemorrhage (IVH) (grade >II) was 14%. Grade 4 periventricular leukomalacia was 10%. Twelve (24%) infants had evidence of bronchopulmonary dysplasia (BPD). Retinopathy of prematurity (stage >II) was 4%. The correlation between ROP rate and need for ventilation therapy was present (r=0.52). Proven necrotizing enterocolitis (stage >2) was not observed. Patent ductus arteriosus (PDA) was diagnosed in 67% of the neonates. BPD, IVH, and PDA were statistically higher in neonates with a birth weight <1000g.
Conclusion
Survival rate of VLBW infants increased with increasing BW. Sex was not a risk factor for mortality. The need for ventilatory therapy may be an important risk factor for ROP in infants <1500g.
PMCID: PMC3663314  PMID: 23724184
Mortality; Morbidity; Neonate; Very Low Birth Weight
15.  Using a Count of Neonatal Morbidities to Predict Poor Outcome in Extremely Low Birth Weight Infants: Added Role of Neonatal Infection 
Pediatrics  2009;123(1):313-318.
OBJECTIVE
A count of 3 neonatal morbidities (bronchopulmonary dysplasia, brain injury, and severe retinopathy of prematurity) strongly predict the risk of death or neurosensory impairment in extremely low birth weight infants who survive to 36 weeks’ postmenstrual age. Neonatal infection has also been linked with later impairment. We examined whether the addition of infection to the count of 3 neonatal morbidities further improves the prediction of poor outcome.
METHODS
We studied 944 infants who participated in the Trial of Indomethacin Prophylaxis in Preterms and survived to 36 weeks’ postmenstrual age. Culture-proven sepsis, meningitis, and stage II or III necrotizing enterocolitis were recorded prospectively. We investigated the incremental prognostic importance of neonatal infection by adding terms for the different types of infection to a logistic model that already contained terms for the count of bronchopulmonary dysplasia, brain injury, and severe retinopathy. Poor outcome at 18 months of age was death or survival with 1 or more of the following: cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness.
RESULTS
There were 414 (44%) infants with at least 1 episode of infection or necrotizing enterocolitis. Meningitis and the presence of any type of infection added independent prognostic information to the morbidity-count model. The odds ratio associated with infection or necrotizing enterocolitis in this model was 50% smaller than the odds ratio associated with each count of the other 3 neonatal morbidities. Meningitis was rare and occurred in 22 (2.3%) of 944 infants.
CONCLUSIONS
In this cohort of extremely low birth weight infants who survived to 36 weeks’ postmenstrual age, neonatal infection increased the risk of a late death or survival with neurosensory impairment. However, infection was a weaker predictor of poor outcome than bronchopulmonary dysplasia, brain injury, and severe retinopathy.
doi:10.1542/peds.2008-0377
PMCID: PMC2829863  PMID: 19117897
extremely low birth weight infant; infection; bronchopulmonary dysplasia; brain injury; retinopathy; neurosensory impairment
16.  Outcomes of small for gestational age micropremies depending on how young or how small they are 
Korean Journal of Pediatrics  2011;54(6):246-252.
Purpose
The outcomes of small for gestational age (SGA) infants especially in extremely low birth weight infants (ELBWIs) are controversial. This study evaluated the mortality and morbidity of ELBWIs, focusing on whether or not they were also SGA.
Methods
The medical records of 415 ELBWIs (birth weight <1,000 g), who were inborn and admitted to the Samsung Medical Center neonatal intensive care unit from January 2000 to December 2008, were reviewed retrospectively. Mortality and morbidities were compared by body size groups: very SGA (VSGA), birth weight ≤3rd percentile; SGA, 3rd to 10th percentile; and appropriate for gestational age (AGA) infants, >10th percentile for gestational age. For gestational subgroup analysis, groups were divided into infants with gestational age ≤24+6 weeks (subgroup I), 25+0 to 26+6 weeks (subgroup II), and ≥27+0 weeks (subgroup III).
Results
Gestational age was 29+2±2+6 weeks in the VSGA infants (n=49), 27+5±2+2 weeks in the SGA infants (n=45), and 25+4±1+4 weeks in AGA infants (n=321). Birth weight was 692±186.6 g, 768±132.9 g, and 780±142.5 g in the VSGA, SGA, and AGA groups, respectively. Cesarean section rate and maternal pregnancy-induced hypertension were more common in the VSGA and SGA than in AGA pregnancies. However, chorioamnionitis was more common in the AGA group. The mortalities of the lowest gestational group (subgroup I), and also of the lower gestational group (subgroup I+II) were significantly higher in the VSGA group than the SGA or AGA groups (P=0.020 and P=0.012, respectively). VSGA and SGA infants showed lower incidence in respiratory distress syndrome, ductal ligation, bronchopulmonary dysplasia, intraventricular hemorrhage than AGA group did. However, by multiple logistic regression analysis of each gestational subgroup, the differences were not significant.
Conclusion
Of ELBWIs, extremely SGA in the lower gestational subgroups, had an impact on mortality, which may provide information useful for prenatal counseling.
doi:10.3345/kjp.2011.54.6.246
PMCID: PMC3174360  PMID: 21949519
Small for gestational age; Extremely low birth weight infants; Mortality; Morbidity
17.  Chorioamnionitis and Early Childhood Outcomes among Extremely Low-Gestational-Age Neonates 
JAMA pediatrics  2014;168(2):137-147.
Importance
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.
Objective
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.
Design
Longitudinal observational study.
Setting
Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.
Participants
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
Chorioamnionitis
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.
Results
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.
doi:10.1001/jamapediatrics.2013.4248
PMCID: PMC4219500  PMID: 24378638
chorioamnionitis; preterm; neurodevelopmental impairment; outcome
18.  Early CPAP versus Surfactant in Extremely Preterm Infants 
The New England journal of medicine  2010;362(21):1970-1979.
Background
There are limited data to inform the choice between early treatment with continuous positive airway pressure (CPAP) and early surfactant treatment as the initial support for extremely-low-birth-weight infants.
Methods
We performed a randomized, multicenter trial, with a 2-by-2 factorial design, involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were randomly assigned to intubation and surfactant treatment (within 1 hour after birth) or to CPAP treatment initiated in the delivery room, with subsequent use of a protocol-driven limited ventilation strategy. Infants were also randomly assigned to one of two target ranges of oxygen saturation. The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks (with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30% oxygen).
Results
A total of 1316 infants were enrolled in the study. The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group (47.8% and 51.0%, respectively; relative risk with CPAP, 0.95; 95% confidence interval [CI], 0.85 to 1.05) after adjustment for gestational age, center, and familial clustering. The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks (rates of primary outcome, 48.7% and 54.1%, respectively; relative risk with CPAP, 0.91; 95% CI, 0.83 to 1.01). Infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia (P<0.001), required fewer days of mechanical ventilation (P = 0.03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P = 0.01). The rates of other adverse neonatal outcomes did not differ significantly between the two groups.
Conclusions
The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.)
doi:10.1056/NEJMoa0911783
PMCID: PMC3071534  PMID: 20472939
19.  Outcomes of Extremely Low Birth Weight Infants with Bronchopulmonary Dysplasia: Impact of the Physiologic Definition 
Early human development  2012;88(7):509-515.
Aims
We compared neurodevelopmental outcomes of extremely low birth weight (ELBW) infants with and without bronchopulmonary dysplasia (BPD), using the physiologic definition.
Study Design
ELBW (birth weights <1000 grams) infants admitted to the Neonatal Research Network centers and hospitalized at 36 weeks postmenstrual age (n=1,189) were classified using the physiologic definition of BPD. Infants underwent Bayley III assessment at 18-22 months corrected age. Multivariable logistic regression was used to determine the association between physiologic BPD and cognitive impairment (score < 70).
Results
BPD by the physiologic definition was diagnosed in 603 (52%) infants, 537 of whom were mechanically ventilated or on FiO2 > 30% and 66 who failed the room air challenge. Infants on room air (n=505) and those who passed the room air challenge (n=51) were classified as “no BPD” (n=556). At follow up, infants with BPD had significantly lower mean weight and head circumference. Moderate to severe cerebral palsy (7 vs. 2.1%) and spastic diplegia (7.8 vs. 4.1%) and quadriplegia (3.9 vs. 0.9%) phenotypes as well as cognitive (12.8 vs. 4.6%) and language scores < 70 (24.2 vs. 12.3%) were significantly more frequent in those with BPD compared to those without BPD. BPD was independently associated (adjusted OR 2.4; 95% CI 1.40-4.13) with cognitive impairment.
Conclusions
Rates of adverse neurodevelopmental outcomes in early childhood were significantly higher in those with BPD. BPD by the physiologic definition was independently associated with cognitive impairment using Bayley Scales III. These findings have implications for targeted post-discharge surveillance and early intervention.
doi:10.1016/j.earlhumdev.2011.12.013
PMCID: PMC3686277  PMID: 22236557
Outcome; preterm; bronchopulmonary dysplasia; physiologic definition
20.  Early Onset Neonatal Sepsis: The Burden of Group B Streptococcal and E. coli Disease Continues 
Pediatrics  2011;127(5):817-826.
BACKGROUND:
Guidelines for prevention of group B streptococcal (GBS) infection have successfully reduced early onset (EO) GBS disease. Study results suggest that Escherichia coli is an important EO pathogen.
OBJECTIVE:
To determine EO infection rates, pathogens, morbidity, and mortality in a national network of neonatal centers.
METHODS:
Infants with EO infection were identified by prospective surveillance at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network centers. Infection was defined by positive culture results for blood and cerebrospinal fluid obtained from infants aged ≤72 hours plus treatment with antibiotic therapy for ≥5 days. Mother and infant characteristics, treatments, and outcomes were studied. Numbers of cases and total live births (LBs) were used to calculate incidence.
RESULTS:
Among 396 586 LBs (2006–2009), 389 infants developed EO infection (0.98 cases per 1000 LBs). Infection rates increased with decreasing birth weight. GBS (43%, 0.41 per 1000 LBs) and E coli (29%, 0.28 per 1000 LBs) were most frequently isolated. Most infants with GBS were term (73%); 81% with E coli were preterm. Mothers of 67% of infected term and 58% of infected preterm infants were screened for GBS, and results were positive for 25% of those mothers. Only 76% of mothers with GBS colonization received intrapartum chemoprophylaxis. Although 77% of infected infants required intensive care, 20% of term infants were treated in the normal newborn nursery. Sixteen percent of infected infants died, most commonly with E coli infection (33%).
CONCLUSION:
In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease. GBS remains the most frequent pathogen in term infants, and E coli the most significant pathogen in preterm infants. Missed opportunities for GBS prevention continue. Prevention of E coli sepsis, especially among preterm infants, remains a challenge.
doi:10.1542/peds.2010-2217
PMCID: PMC3081183  PMID: 21518717
neonatal sepsis; group B streptococcal disease; Escherichia coli infection
21.  Very Low Birth Weight Preterm Infants With Surgical Short Bowel Syndrome: Incidence, Morbidity and Mortality, and Growth Outcomes at 18 to 22 Months 
Pediatrics  2008;122(3):e573-e582.
OBJECTIVES
The objective of this study was to determine the (1) incidence of short bowel syndrome in very low birth weight (<1500 g) infants, (2) associated morbidity and mortality during initial hospitalization, and (3) impact on short-term growth and nutrition in extremely low birth weight (<1000 g) infants.
METHODS
Infants who were born from January 1, 2002, through June 30, 2005, and enrolled in the National Institute of Child Health and Human Development Neonatal Research Network were studied. Risk factors for developing short bowel syndrome as a result of partial bowel resection (surgical short bowel syndrome) and outcomes were evaluated for all neonates until hospital discharge, death, or 120 days. Extremely low birth weight survivors were further evaluated at 18 to 22 months’ corrected age for feeding methods and growth.
RESULTS
The incidence of surgical short bowel syndrome in this cohort of 12 316 very low birth weight infants was 0.7%. Necrotizing enterocolitis was the most common diagnosis associated with surgical short bowel syndrome. More very low birth weight infants with short bowel syndrome (20%) died during initial hospitalization than those without necrotizing enterocolitis or short bowel syndrome (12%) but fewer than the infants with surgical necrotizing enterocolitis without short bowel syndrome (53%). Among 5657 extremely low birth weight infants, the incidence of surgical short bowel syndrome was 1.1%. At 18 to 22 months, extremely low birth weight infants with short bowel syndrome were more likely to still require tube feeding (33%) and to have been rehospitalized (79%). Moreover, these infants had growth delay with shorter lengths and smaller head circumferences than infants without necrotizing enterocolitis or short bowel syndrome.
CONCLUSIONS
Short bowel syndrome is rare in neonates but has a high mortality rate. At 18 to 22 months’ corrected age, extremely low birth weight infants with short bowel syndrome were more likely to have growth failure than infants without short bowel syndrome.
doi:10.1542/peds.2007-3449
PMCID: PMC2848527  PMID: 18762491
short bowel syndrome; preterm; necrotizing enterocolitis; nutrition
22.  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.
Background
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.
Conclusions
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
Background
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 http://dx.doi.org/10.1371/journal.pmed.1001121.
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
doi:10.1371/journal.pmed.1001121
PMCID: PMC3210771  PMID: 22087079
23.  The effects of designation and volume of neonatal care on mortality and morbidity outcomes of very preterm infants in England: retrospective population-based cohort study 
BMJ Open  2014;4(7):e004856.
Objective
To examine the effects of designation and volume of neonatal care at the hospital of birth on mortality and morbidity outcomes in very preterm infants in a managed clinical network setting.
Design
A retrospective, population-based analysis of operational clinical data using adjusted logistic regression and instrumental variables (IV) analyses.
Setting
165 National Health Service neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit and participating in the Neonatal Economic, Staffing and Clinical Outcomes Project.
Participants
20 554 infants born at <33 weeks completed gestation (17 995 born at 27–32 weeks; 2559 born at <27 weeks), admitted to neonatal care and either discharged or died, over the period 1 January 2009–31 December 2011.
Intervention
Tertiary designation or high-volume neonatal care at the hospital of birth.
Outcomes
Neonatal mortality, any in-hospital mortality, surgery for necrotising enterocolitis, surgery for retinopathy of prematurity, bronchopulmonary dysplasia and postmenstrual age at discharge.
Results
Infants born at <33 weeks gestation and admitted to a high-volume neonatal unit at the hospital of birth were at reduced odds of neonatal mortality (IV regression odds ratio (OR) 0.70, 95% CI 0.53 to 0.92) and any in-hospital mortality (IV regression OR 0.68, 95% CI 0.54 to 0.85). The effect of volume on any in-hospital mortality was most acute among infants born at <27 weeks gestation (IV regression OR 0.51, 95% CI 0.33 to 0.79). A negative association between tertiary-level unit designation and mortality was also observed with adjusted logistic regression for infants born at <27 weeks gestation.
Conclusions
High-volume neonatal care provided at the hospital of birth may protect against in-hospital mortality in very preterm infants. Future developments of neonatal services should promote delivery of very preterm infants at hospitals with high-volume neonatal units.
doi:10.1136/bmjopen-2014-004856
PMCID: PMC4091399  PMID: 25001393
24.  Community Supports After Surviving Extremely Low-Birth-Weight, Extremely Preterm Birth 
Objective
To determine special outpatient services (SOS) use, need, associated factors, and neurodevelopmental and functional outcomes among extremely preterm infants at 18 to 22 months’ corrected age.
Design
Retrospective analysis.
Setting
National Institute of Child Health and Human Development (NICHD) Neonatal Research Network.
Participants
Infants younger than 28 weeks’ gestational age who had been born weighing less than 1000 g at an NICHD Neonatal Research Network center from January 1, 1997, to December 31, 2000, and who were receiving follow-up at 18 to 22 months’ corrected age.
Interventions
Questionnaires were administered at the 18- to 22-month follow-up visit regarding SOS use since hospital discharge and the current need for SOS (social work, visiting nurse, medical specialty, early intervention, speech and language services, occupational therapy and physical therapy, and neurodevelopmental and behavioral services).
Main Outcome Measures
The use of and need for SOS were analyzed by gestational age. Logistic regression analysis identified factors independently associated with the use of more than 5 services and with the need for any services.
Results
Of 2315 infants, 54.7% used more than 3 SOS by 18 to 22 months, and 19.1% used 6 to 7 SOS. The need for any SOS was reported by approximately 37%. The following variables that were commonly associated with adverse neurodevelopmental outcomes were also associated with the use of more than 5 SOS: sepsis, birth weight, postnatal corticosteroid use, bronchopulmonary dysplasia, and cystic periventricular leukomalacia or grade 3 or 4 intraventricular hemorrhage. Male sex was associated with the need for any SOS. Although high SOS use was more likely among children with adverse neurodevelopmental outcomes, a reported need for SOS was common even among those with mild developmental impairment (39.7%) and mild cerebral palsy (42.2%).
Conclusions
High SOS use is common, has identifiable neonatal risk factors, and is associated with neurodevelopmental impairment. Extremely preterm survivors have substantial need for community supports regardless of their impairment level. Efforts to improve comprehensive delivery of family-centered community-based services are urgently needed.
doi:10.1001/archpedi.162.8.748
PMCID: PMC2748992  PMID: 18678807
25.  Trends in survival among extremely-low-birth-weight infants (less than 1000 g) without significant bronchopulmonary dysplasia 
BMC Pediatrics  2012;12:63.
Objective
The aim of this study was to analyze the evolution from 1997 to 2009 of survival without significant (moderate and severe) bronchopulmonary dysplasia (SWsBPD) in extremely-low-birth-weight (ELBW) infants and to determine the influence of changes in resuscitation, nutrition and mechanical ventilation on the survival rate.
Study design
In this study, 415 premature infants with birth weights below 1000 g (ELBW) were divided into three chronological subgroups: 1997 to 2000 (n = 65), 2001 to 2005 (n = 178) and 2006 to 2009 (n = 172).
Between 1997 and 2000, respiratory resuscitation in the delivery room was performed via a bag and mask (Ambu®, Ballerup, Sweden) with 40-50% oxygen. If this procedure was not effective, oral endotracheal intubation was always performed. Pulse oximetry was never used. Starting on January 1, 2001, a change in the delivery room respiratory policy was established for ELBW infants. Oxygenation and heart rate were monitored using a pulse oximeter (Nellcor®) attached to the newborn’s right hand. If resuscitation was required, ventilation was performed using a face mask, and intermittent positive pressure was controlled via a ventilator (Babylog2, Drägger). In 2001, a policy of aggressive nutrition was also initiated with the early provision of parenteral amino acids. We used standardized parenteral nutrition to feed ELBW infants during the first 12–24 hours of life. Lipids were given on the first day. The glucose concentration administered was increased by 1 mg/kg/minute each day until levels reached 8 mg/kg/minute. Enteral nutrition was started with trophic feeding of milk. In 2006, volume guarantee treatment was instituted and administered together with synchronized intermittent mandatory ventilation (SIMV + VG). The complications of prematurity were treated similarly throughout the study period. Patent ductus arteriosus was only treated when hemodynamically significant. Surgical closure of the patent ductus arteriosus was performed when two courses of indomethacin or ibuprofen were not sufficient to close it.
Mild BPD were defined by a supplemental oxygen requirement at 28 days of life and moderate BPD if breathing room air or a need for <30% oxygen at 36 weeks postmenstrual age or discharge from the NICU, whichever came first. Severe BPD was defined by a supplemental oxygen requirement at 28 days of life and a need for greater than or equal to 30% oxygen use and/or positive pressure support (IPPV or nCPAP) at 36 weeks postmenstrual age or discharge, whichever came first. Moderate and severe BPD have been considered together as “significant BPD”. The goal of pulse oximetry was to maintain a hemoglobin saturation of between 88% and 93%. Patients were considered to not need oxygen supplementation when it could be permanently withdrawn. The distribution of the variables was not normal based on a Kolmogorov-Smirnov test (p < 0.05 in all cases). Therefore, quantitative variables were expressed as the median and interquartile range (IQR; 25th-75th percentile). Statistical analysis of the data was performed using nonparametric techniques (Kruskal-Wallis test and Mann–Whitney U test). A chi-square analysis was used to analyze qualitative variables. Potential confounding variables were those possibly related to BPD in survivors (p between 0.05 and 0.3 in univariate analysis). Logistic regression analysis was performed with variables related to BPD in survivors (p < 0.05) and potential confounding variables. The forward stepwise method adjusted for confounding factors was used to select the variables, and the enter method using selected variables was used to obtain the odds ratios.
Results and conclusion
There was an increase in the rate of SWsBPD (1997 to 2000: 58.5%; 2001 to 2005: 74.2%; and 2006 to 2009: 75.0%; p = 0.032). In survivors, the occurrence of significant BPD decreased after 2001 (9.5% vs. 2.3%; p = 0.013). The factors associated with improved SWsBPD were delivery by caesarean section, a reduced endotracheal intubation rate and a reduced duration of mechanical ventilation.While the mortality of ELBW infants has not changed since 2001, the frequency of SWsBPD has significantly increased (75.0%) in association with increased caesarean sections and reductions in the endotracheal intubation rate, as well as the duration of mechanical ventilation.
doi:10.1186/1471-2431-12-63
PMCID: PMC3507706  PMID: 22682000
Bronchopulmonary dysplasia; Chronic lung disease; Extremely low birth weight infants; Preterm infants

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