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author:("Das, abik")
1.  Neurobehavioral Assessment Predicts Motor Outcome in Preterm Infants 
The Journal of pediatrics  2009;156(3):366-371.
To determine whether Neonatal Intensive Care Unit Network Neurobehavior Scales (NNNS) at 44 weeks predict motor outcome at 2 years in preterm infants from the Maternal Lifestyles Study (MLS).
Study design
Data were collected on all preterm infants (<36 weeks) in the MLS who had an NNNS at 44 weeks (n=395) and neurologic exam at 12–36 months or Bayley Psychomotor Development Index (PDI) at 24 months (n=270). Logistic regression analyzed NNNS summary scores associated with Cerebral Palsy (CP) or PDI <70, while controlling for birth weight 1250g.
Eighteen of 395 infants (5%) had CP; 24 of 270 infants (9%) had PDI <70. CP was associated with low quality of movement (OR 1.95, 95% CI 1.24–3.06, p=0.004) and high lethargy (OR 1.67, 95% CI 1.01–2.76, p=0.045). The model contributed 19% of the variance in CP diagnosis at 12–36 months (R2=0.19, p<0.001). Low PDI was associated with low handling (OR 1.83; 95% CI 1.12–2.99, p=0.017), low quality of movement (OR 2.16; 95%CI 1.38–3.38, p=0.001), and hypotonia (OR 1.63; 95% CI 1.14–2.32, p=0.007). The model contributed 26% of the variance in PDI <70 at 24 months (R2=0.26, p<0.001).
The neurobehavioral profile of underarousal in 44 week preterm infants may predict poor motor outcome.
PMCID: PMC3121326  PMID: 19880137
neurobehavior; outcomes; ELBW
2.  Infant Neurobehavioral Dysregulation Related to Behavior Problems in Children with Prenatal Substance Exposure 
Pediatrics  2009;124(5):1355-1362.
To test a developmental model of neurobehavioral dysregulation relating prenatal substance exposure to behavior problems at age 7.
The sample included 360 cocaine-exposed and 480 unexposed children from lower to lower middle class families of which 78% were African American. Structural equation modeling (SEM) was used to test models whereby prenatal exposure to cocaine and other substances would result in neurobehavioral dysregulation in infancy, which would predict externalizing and internalizing behavior problems in early childhood. SEM models were developed for individual and combined parent and teacher report for externalizing, internalizing, and total problem scores on the Child Behavior Checklist.
The Goodness of Fit Statistics indicated that all of the models met criteria for adequate fit with 7 of the 9 models explaining 18 to 60% of the variance in behavior problems at age 7. The paths in the models indicate that there are direct effects of prenatal substance exposure on 7-year behavior problems as well as indirect effects, including neurobehavioral dysregulation.
Prenatal substance exposure affects behavior problems at age 7 through two mechanisms. The direct pathway is consistent with a teratogenic effect. Indirect pathways suggest cascading effects where prenatal substance exposure results in neurobehavioral dysregulation manifesting as deviations in later behavioral expression. Developmental models provide an understanding of pathways that describe how prenatal substance exposure affects child outcome and have significant implications for early identification and prevention.
PMCID: PMC2874881  PMID: 19822596
Prenatal substance exposure; cocaine; neurobehavioral dysregulation; behavior problems
3.  Predicting Time to Hospital Discharge for Extremely Preterm Infants 
Pediatrics  2009;125(1):e146-e154.
As extremely preterm infant mortality rates have decreased, concerns regarding resource utilization have intensified. Accurate models to predict time to hospital discharge could aid in resource planning, family counseling, and perhaps stimulate quality improvement initiatives.
For infants <27 weeks estimated gestational age (EGA), to develop, validate and compare several models to predict time to hospital discharge based on time-dependent covariates, and based on the presence of 5 key risk factors as predictors.
Patients and Methods
This was a retrospective analysis of infants <27 weeks EGA, born 7/2002-12/2005 and surviving to discharge from a NICHD Neonatal Research Network site. Time to discharge was modeled as continuous (postmenstrual age at discharge, PMAD), and categorical variables (“Early” and “Late” discharge). Three linear and logistic regression models with time-dependent covariate inclusion were developed (perinatal factors only, perinatal+early neonatal factors, perinatal+early+later factors). Models for Early and Late discharge using the cumulative presence of 5 key risk factors as predictors were also evaluated. Predictive capabilities were compared using coefficient of determination (R2) for linear models, and AUC of ROC curve for logistic models.
Data from 2254 infants were included. Prediction of PMAD was poor, with only 38% of variation explained by linear models. However, models incorporating later clinical characteristics were more accurate in predicting “Early” or “Late” discharge (full models: AUC 0.76-0.83 vs. perinatal factor models: AUC 0.56-0.69). In simplified key risk factors models, predicted probabilities for Early and Late discharge compared favorably with observed rates. Furthermore, the AUC (0.75-0.77) were similar to those of models including the full factor set.
Prediction of Early or Late discharge is poor if only perinatal factors are considered, but improves substantially with knowledge of later-occurring morbidities. Prediction using a few key risk factors is comparable to full models, and may offer a clinically applicable strategy.
PMCID: PMC2951502  PMID: 20008430
Pediatrics  2009;124(2):517-526.
Current literature suggests that use of synchronized nasal intermittent positive pressure ventilation (SNIPPV), following extubation, reduces the rate of reintubation compared to nasal continuous positive airway pressure (NCPAP). However, there is limited information available on the outcomes of infants managed with SNIPPV.
To compare the outcomes of infants managed with SNIPPV (postextubation or for apnea) to infants not treated with SNIPPV at 2 sites.
Clinical retrospective data was used to evaluate the use of SNIPPV in infants ≤1250 g birth weight (BW); and 3 BW subgroups (500 –750, 751–1000, and 1001–1250 g, decided a priori). SNIPPV was not assigned randomly. Bronchopulmonary dysplasia (BPD) was defined as treatment with supplemental oxygen at 36 weeks’ postmenstrual age.
Overall, infants who were treated with SNIPPV had significantly lower mean BW (863g vs. 964g) and gestational age (26.4 weeks vs. 27.9 weeks), more frequently received surfactant (85% vs. 68%), and had a higher incidence of BPD or death (39% vs. 27%) (all p<0.01), compared to infants treated with NCPAP. In the subgroup analysis, SNIPPV was associated with lower rates of BPD (43% vs 67%, P = .03) and BPD/death (51% vs 76%, P = .02) in the 500- to 750g infants, with no significant differences in the other BW groups. Logistic regression analysis, adjusting for significant covariates, revealed infants with 500 –700-g BW who received SNIPPV were significantly less likely to have the outcomes of BPD (OR: 0.29 [95% CI: 0.11– 0.77]; P = .01), BPD/death (OR: 0.30 [95% CI: 0.11– 0.79]; P = .01), neurodevelopmental impairment (NDI) (OR: 0.29 [95% CI: 0.09–0.94]; P = .04), and NDI/death (OR: 0.18 [95% CI: 0.05– 0.62]; P = .006).
SNIPPV use in infants at greatest risk of BPD or death (500-750g) was associated with decreased BPD, BPD/death, NDI, and NDI/death when compared to infants managed with NCPAP.
PMCID: PMC2924622  PMID: 19651577
premature newborn; respiratory distress syndrome; non-invasive ventilation
5.  Cytokines Associated with Bronchopulmonary Dysplasia or Death in Extremely Low Birth Weight Infants 
Pediatrics  2009;123(4):1132-1141.
Inflammation mediated by cytokines may be important in the pathogenesis of bronchopulmonary dysplasia and the competing outcome of death in extremely low birth weight infants.
To develop multi-variable logistic regression models for the outcome of bronchopulmonary dysplasia and/or death at 36w post-menstrual age using clinical and cytokine data from the first 28 days.
1067 extremely low birth weight infants in the Neonatal Research Network of the National Institute of Child Health and Human Development had 25 cytokines measured from blood collected within 4 h of birth and on days 3, 7, 14, and 21. Stepwise regression using peak values of the 25 cytokines and 15 clinical variables identified variables associated with BPD/death. Multi-variable logistic regression was done for bronchopulmonary dysplasia/death using variables selected by stepwise regression. Similar analyses were also done using average cytokine values from days 0–21, days 0–3, and from days 14–21.
Of 1062 infants with available data, 606 infants developed bronchopulmonary dysplasia or died. Combining results from all models, bronchopulmonary dysplasia/death was associated with higher concentrations of interleukins-1β, -6, -8, -10, and interferon-γ and lower concentrations of interleukin-17, RANTES, and tumor necrosis factor-β. Compared to models with only clinical variables, addition of cytokine data improved predictive ability by a statistically significant but clinically modest magnitude.
The overall pattern of cytokines suggests bronchopulmonary dysplasia/death may be associated with impairment in the transition from the innate immune response mediated by neutrophils to the adaptive immune response mediated by T-lymphocytes.
PMCID: PMC2903210  PMID: 19336372
Logistic models; Infant; premature; Predictive value of tests
6.  Impact of Postnatal Corticosteroid (PNS) Use on Neurodevelopment at 18-22 Months Adjusted Age: Effects of Dose, Timing and Risk of Bronchopulmonary Dysplasia in Extremely Low Birthweight Infants (ELBW) 
Pediatrics  2009;123(3):e430-e437.
Postnatal steroid use in bronchopulmonary dysplasia (BPD) decreases lung inflammation but increases impairment (NDI). We hypothesized that increased dose is associated with increased NDI, lower postmenstrual age (PMA) at exposure increases NDI and risk of BPD modifies the effect of PNS.
Steroid dose and timing of exposure beyond 7 days was assessed among 2358 ELBW nested in a prospective trial, with 1667 (84%) survivors examined at 18-22 months PMA. Logistic regression tested the relationship between NDI (Bayley MDI/PDI < 70, disabling cerebral palsy (CP) or sensory impairment), total dose (tertiles < 0.9, 0.9-1.9, ≥ 1.9 mg/kg) and PMA at first dose. Separate logistic regression tested effect modification by BPD severity (Romagnoli Risk > 0.5 as high risk, n=2336 (99%) for days of life 4-7).
366 neonates (16%) were steroid treated (94% dexamethasone). Treated neonates were smaller and less mature. 72% of those treated were high risk for BPD. PNS exposure was associated with NDI/death (61 vs. 44%, p < 0.001). NDI increased with higher dose; 71% dead or impaired at highest dose tertile. Each 1 mg/kg was associated with a 2.0 point reduction in MDI and a 40% risk increase in disabling CP. (OR 1.4, 95% CI: 1.2-1.6). Older PMA did not mitigate the harm. Treatment after 33 weeks PMA was associated with greatest harm (NDI/death OR 2.5, 95% CI: 1.1-5.5) despite not receiving highest dose. The relationship of PNS to NDI was modified by BPD risk, (High risk OR 1.9, 95% CI: 1.4-2.6; Low risk OR 2.9, 95% CI: 1.8-4.8) with those at highest risk experiencing less harm.
Higher PNS dose was associated with increased NDI. There is no “safe” window for PNS use in ELBWs. Neonates with low BPD risk should not be exposed. A randomized trial of PNS for infants at highest risk is warranted.
PMCID: PMC2846831  PMID: 19204058
postnatal corticosteroids; neurodevelopmental impairment; extremely low birth weight infants
7.  Twin Gestation and Neuro-developmental Outcome in Extremely Low Birth Weight Infants 
Pediatrics  2009;123(2):e220-e227.
To compare the risk-adjusted incidence of death or neuro-developmental impairment at 18–22 months corrected age, between twin and singleton extremely low birth weight infants.
Twin gestation is independently associated with increased risk of death or adverse neuro-developmental outcomes at 18–22 months corrected age in extremely low birth weight infants.
Retrospective study of inborn extremely low birth weight infants (BW 401– 1000g) admitted to NICHD Neonatal Research Network units between 1997 and 2005, who either died or had follow-up data available at 18–22 months corrected age. Neuro-developmental impairment (NDI), the primary outcome variable, was defined as the presence of any one of the following: moderate or severe cerebral palsy, severe bilateral hearing loss needing amplification, bilateral blindness, Bayley Mental Developmental Index or Psychomotor Developmental Index of less than 70. Death was included with NDI as a composite outcome since it is a competing variable. Results were compared for both twins, twin A, twin B, same sex twins, unlike sex twins and singleton infants. Logistic regression analysis was done to control for demographic and clinical factors that were different among the groups.
The cohort of infants who either died or were assessed for NDI consisted of 7,630 singleton infants and 1,376 twins. Logistic regression adjusting for clinical and socio-demographic risk factors showed an increased risk of death or NDI for twins as a group when compared with the singletons (OR-1.39, 95% CI- 1.19–1.63). On analyzing twin A and B separately as well, risk of death or NDI was increased in both twin A (OR-1.32, 95% CI- 1.09–1.59) and for twin B (OR-1.47, 95% CI- 1.21–1.78), when compared with singleton infants.
Twin gestation in ELBW infants is associated with an independent increased risk of death or NDI at 18–22 months corrected age, compared to ELBW singleton gestation infants. Both first and second born twins are at increased risk of death or NDI when compared to singleton ELBW infants.
PMCID: PMC2842087  PMID: 19139085
twins; neuro-developmental impairment; extremely low birth weight infants
8.  Prediction of Early Childhood Outcome of Term Infants using Apgar Scores at 10 Minutes following Hypoxic-Ischemic Encephalopathy 
Pediatrics  2009;124(6):1619.
Death or severe disability is so common following an Apgar score of 0 at 10 minutes in observational studies that the Neonatal Resuscitation Program suggests considering discontinuation of resuscitation after 10 minutes of effective CPR.
To determine if Apgar scores at 10 minutes are associated with death or disability in early childhood following perinatal hypoxic-ischemic encephalopathy (HIE).
Design, Setting, and Patients
This is a secondary analysis of infants enrolled in the NICHD Neonatal Research Network hypothermia trial. Infants ≥ 36 weeks gestation had clinical and/or biochemical abnormalities at birth, and encephalopathy at < 6 hours. Logistic regression and classification and regression tree (CART) analysis was used to determine associations between Apgar scores at 10 minutes and neurodevelopmental outcome adjusting for covariates. Associations are expressed as odds ratios (OR) and 95% confidence interval (CI).
Main Outcome Measure
Death or disability (moderate or severe) at 18–22 months of age.
Twenty of 208 infants were excluded (missing data). More than 90% of infants had Apgar scores of 0–2 at 1 minute and Apgars at 5 and 10 minutes shifted to progressively higher values; at 10 minutes 27% of infants had Apgar scores of 0–2. After adjustment each point decrease in Apgar score at 10 minutes was associated with a 45% increase in the odds of death or disability (OR 1.45, CI 1.22–1.72). Death or disability occurred in 76, 82 and 80% of infants with Apgar scores at 10 minutes of 0, 1 and 2, respectively. CART analysis indicated that Apgar scores at 10 minutes were discriminators of outcome.
Apgar scores at 10 minutes provide useful prognostic data before other evaluations are available for infants with HIE. Death or moderate/severe disability is common but not uniform with Apgar scores < 3; caution is needed before adopting a specific time interval to guide duration of resuscitation.
PMCID: PMC2821195  PMID: 19948631
Apgar scores; Hypoxic-Ischemic Encephalopathy; cardiopulmonary resuscitation

Results 1-8 (8)