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1.  Effect of inborn vs. outborn delivery on neurodevelopmental outcomes in infants with hypoxic–ischemic encephalopathy: secondary analyses of the NICHD whole-body cooling trial 
Pediatric research  2012;72(4):414-419.
The effect of birth location on hypothermia-related outcomes has not been rigorously examined in the literature. In this study, we determined whether birth location had an impact on the benefits of whole-body cooling to 33.5 °C for 72 h in term infants (n = 208) with hypoxic–ischemic encephalopathy (HIE) who participated in the Neonatal Research Network (NRN) randomized controlled trial.
Heterogeneity by birth location was examined with respect to cooling treatment for the 18-mo primary outcomes (death, moderate disability, severe disability) and secondary outcomes (death, components of disability), and in-hospital organ dysfunction. Logistic regression models were used to generate adjusted odds ratios.
Infants bom at a location other than an NRN center (outborn) (n = 93) experienced significant delays in initiation of therapy (mean (SD): 5.5 (1.1) vs. 4.4 (1.2) h), lower baseline temperatures (36.6 (1.2) vs. 37.1 (0.9) °C), and more severe HIE (43 vs. 29%) than infants born in an NRN center (inborn) (n = 115). Maternal education <12 y (50 vs. 14%) and African-American ethnicity (43 vs. 25%) were more common in the inborn group. When adjusted for NRN center and HIE severity, there were no significant differences in 18-mo outcomes or in-hospital organ dysfunction between inborn and outborn infants.
Although limited by sample size and some differences in baseline characteristics, the study showed that birth location does not appear to modify the treatment effect of hypothermia after HIE.
PMCID: PMC3730811  PMID: 22914450
2.  Association Between Blood Spot Transforming Growth Factor-β and Patent Ductus Arteriosus in Extremely Low-Birth Weight Infants 
Pediatric cardiology  2012;34(1):149-154.
Permanent ductal closure involves anatomic remodeling, in which transforming growth factor (TGF)-β appears to play a role. Our objective was to evaluate the relationship, if any, between blood spot TGF-β on day 3 and day 7 of life and patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Prospective observational study involving ELBW infants (n = 968) in the National Institute of Child Health and Human Development Neonatal Research Network who had TGF-β measured on filter paper spot blood samples using a Luminex assay. Infants with a PDA (n = 493) were significantly more immature, had lower birth weights, and had higher rates of respiratory distress syndrome than those without PDA (n = 475). TGF-β on days 3 and 7 of life, respectively, were significantly lower among neonates with PDA (median 1,177 pg/ml [range 642–1,896]; median 1,386 pg/ml [range 868–1,913]) compared with others without PDA (median 1,334 pg/ml [range 760–2,064]; median 1,712 pg/ml [range 1,014–2,518 pg/ml]). The significant difference persisted when death or PDA was considered a composite outcome. TGF-β levels were not significantly different among subgroups of infants with PDA who were not treated (n = 51) versus those who were treated medically (n = 283) or by surgical ligation (n = 159). TGF-β was not a significant predictor of death or PDA (day 3 odds ratio [OR] 0.99, 95 % confidence interval [CI] 0.83–1.17; day 7 OR 0.88, 95 % CI 0.74–1.04) on adjusted analyses. Our results suggest that blood spot TGF-β alone is unlikely to be a reliable biomarker of a clinically significant PDA or its responsiveness to treatment.
PMCID: PMC3704212  PMID: 22684193
Transforming growth factor; Patent ductus arteriosus; Preterm; Neonate
3.  Outcomes of Extremely Low Birth Weight Infants with Bronchopulmonary Dysplasia: Impact of the Physiologic Definition 
Early human development  2012;88(7):509-515.
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).
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.
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.
PMCID: PMC3686277  PMID: 22236557
Outcome; preterm; bronchopulmonary dysplasia; physiologic definition
4.  Circulating β chemokine and MMP 9 as markers of oxidative injury in extremely low birth weight infants 
Pediatric research  2010;67(1):77-82.
Matrix metalloproteinases (MMP) and chemokines appear to be induced by hyperoxia in preclinical studies. We hypothesized that O2 exposure immediately after birth is associated with altered blood spot MMP 9 and β chemokine concentrations. The following analytes were measured on blood spots on days 1 and 3 of life, using luminex technology in 1059 infants (birth weights < 1000 grams) in the NICHD Neonatal Research Network: MMP 9, monocyte chemoattractant protein 1 (MCP 1), macrophage inflammatory proteins (MIP 1α and β), and Regulated upon Activation, Normal T-cell Expressed and Secreted (RANTES). Infants administered O2 continually from 6 to 24 hours of life (n=729), when compared to those with < 6 hours exposure (n=330), had significantly lower mean birth weight and higher rate of respiratory distress syndrome (p≤ 0.002). On day 3, MCP 1 was higher and RANTES lower among infants with early prolonged O2 exposure. After adjusting for covariates, prolonged early O2 exposure retained a statistically significant association with higher MCP 1 on day 3 (p=0.003). The consistent association between O2 exposure and MCP 1 among extremely preterm infants suggests that further investigation of its role in oxidative injury is warranted.
PMCID: PMC2831535  PMID: 19755933
5.  Real-Time Polymerase Chain Reaction for the Rapid Detection of Group B Streptococcal Colonization in Neonates 
Pediatrics  2006;118(1):14-22.
Group B streptococcal (GBS) infection remains a leading cause of neonatal sepsis. Currently, the management guidelines of neonates born to women with unknown GBS status at delivery are unclear. In this cohort, who undergo at least a 48-hour observation, a rapid method of detection of GBS colonization would allow targeted evaluation and treatment, as well as prevent delayed discharge.
The goal of this research was to evaluate the validity of rapid fluorescent real-time polymerase chain reaction in comparison with standard culture to detect GBS colonization in infants born to women whose GBS status is unknown at delivery.
Neonates at > 32 weeks’ gestation born to women whose GBS status was unknown at delivery were included. Samples were obtained from the ear, nose, rectum, and gastric aspirate for immediate culture and real-time polymerase chain reaction after DNA extraction using the LightCycler. Melting point curves were generated, and confirmatory agar gel electrophoresis was performed.
The study population (n = 94) had a mean ± SD gestational age of 38 ± 2 weeks and birth weight of 3002 ± 548 g. The rates of GBS colonization by culture were 17% and 51% by real-time polymerase chain reaction. The 4 surface sites had comparable rates of GBS. The overall sensitivities, specificities, and positive and negative predictive values of real-time polymerase chain reaction were: 90%, 80.3%, 28%, and 98.9%.
Real-time polymerase chain reaction resulted in a threefold higher rate of detection of GBS colonization and had an excellent negative predictive value in a cohort of neonates with unknown maternal GBS status at delivery. Thus, real-time polymerase chain reaction would be a useful clinical tool in the management of those infants potentially at risk for invasive GBS infection and would allow earlier discharge for those found to be not at risk.
PMCID: PMC1513630  PMID: 16818544
group B streptococcus; rapid diagnostic tests; polymerase chain reaction; newborn; GBS—group B streptococcus; PCR—polymerase chain reaction; CI— confidence interval

Results 1-5 (5)