Search tips
Search criteria

Results 1-9 (9)

Clipboard (0)
Year of Publication
Document Types
author:("Das, abik")
1.  Death or Neurodevelopmental Impairment at 18 To 22 Months in a Randomized Trial of Early Dexamethasone to Prevent Death or Chronic Lung Disease in Extremely Low Birth Weight Infants 
The Journal of pediatrics  2013;164(1):34-39.e2.
To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18 to 22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants.
Evaluation of infants at 18 to 22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI). NDI was defined as moderate or severe cerebral palsy, MDI or PDI less than 70, blindness, or hearing impairment.
Death or NDI at 18 to 22 months corrected age was similar in the dexamethasone and placebo groups (65 vs 66 percent, p= 0.99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50 vs 41 percent, p=0.42 for weight less than 10th percentile). Forty nine percent of infants in the placebo group received treatment with corticosteroid compared to 32% in the dexamethasone group (p=0.02).
The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group.
PMCID: PMC4120744  PMID: 23992673
neurodevelopmental outcome; growth; bronchopulmonary dysplasia; cerebral palsy; neonatal follow-up
2.  Immunogenicity of Haemophilus influenzae Type b Protein Conjugate Vaccines in Very Low Birth Weight Infants 
PMCID: PMC3960569  PMID: 24569312
Infant; premature; infant; very low birth weight; Haemophilus influenzae vacines; immunization; vaccines
3.  Cytokines and Neurodevelopmental Outcomes in Extremely Low Birth Weight Infants 
The Journal of pediatrics  2011;159(6):919-925.e3.
To determine if selected pro-inflammatory and anti-inflammatory cytokines/mediators of inflammation reported to be related to development of cerebral palsy predict neurodevelopmental outcome in extremely low birth weight infants.
Study design
Infants with birth weights ≤ 1000 g (n=1067) had blood samples collected at birth and on days 3±1, 7±1, 14±3, and 21±3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on five cytokines (IL-1β, IL-8, TNF-α, RANTES, and IL-2) reported to be most predictive of CP in term and late preterm infants.
IL-8 was higher on days 0–4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, TNF-β, SIL-rα, MIP-1β) were found to be altered on days 0–4 in infants who developed CP.
CP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin.
PMCID: PMC3215787  PMID: 21798559
4.  Is phototherapy exposure associated with better or worse outcomes in 501–1000 gram birth weight infants? 
To compare risk-adjusted outcomes at 18–22 months corrected age for extremely low birth weight (ELBW) infants who never received phototherapy (NoPTx) to those who received any phototherapy (PTx) in the NICHD Neonatal Research Network randomized trial of Aggressive vs. Conservative Phototherapy.
Outcomes at 18–22 months corrected age included death, neurodevelopmental impairment (NDI), and Bayley Scales Mental Developmental Index (MDI). Regression models evaluated the independent association of PTx with adverse outcomes controlling for center and other potentially confounding variables.
Of 1972 infants, 216 were NoPTx and 1756 were PTx. For the entire 501–1000 g BW cohort, PTx was not independently associated with death or NDI (OR 0.85, 95% CI 0.60 –1.20), death, or adverse neurodevelopmental endpoints. However, among infants 501–750 g BW, the rate of significant developmental impairment with MDI<50 was significantly higher for NoPTx (29%) than PTx (12%) (p=0.004).
Phototherapy did not appear to be independently associated with death or NDI for the overall ELBW group. Whether PTx increases mortality could not be excluded due to bias from deaths before reaching conservative treatment threshold. The higher rate of MDI<50 in the 501–750g BW NoPTx group is concerning, and consistent with NRN Trial results.
PMCID: PMC3505994  PMID: 21272067
5.  Predictive Value of an Early Amplitude Integrated Electroencephalogram and Neurologic Examination 
Pediatrics  2011;128(1):e112-e120.
To examine the predictive validity of the amplitude integrated electroencephalogram (aEEG) and stage of encephalopathy among infants with hypoxic-ischemic encephalopathy (HIE) eligible for therapeutic whole-body hypothermia.
Neonates were eligible for this prospective study if moderate or severe HIE occurred at <6 hours and an aEEG was obtained at <9 hours of age. The primary outcome was death or moderate/severe disability at 18 months.
There were 108 infants (71 with moderate HIE and 37 with severe HIE) enrolled in the study. aEEG findings were categorized as normal, with continuous normal voltage (n = 12) or discontinuous normal voltage (n = 12), or abnormal, with burst suppression (n = 22), continuous low voltage (n = 26), or flat tracing (n = 36). At 18 months, 53 infants (49%) experienced death or disability. Severe HIE and an abnormal aEEG were related to the primary outcome with univariate analysis, whereas severe HIE alone was predictive of outcome with multivariate analysis. Addition of aEEG pattern to HIE stage did not add to the predictive value of the model; the area under the curve changed from 0.72 to 0.75 (P = .19).
The aEEG background pattern did not significantly enhance the value of the stage of encephalopathy at study entry in predicting death and disability among infants with HIE.
PMCID: PMC3124102  PMID: 21669899
neonatal hypoxic-ischemic encephalopathy; amplitude integrated EEG
The heptavalent pneumococcal-CRM197 conjugate vaccine (PCV-7) has been incompletely studied in very-low-birth-weight (VLBW, ≤1500 grams) infants.
To assess PCV-7 immunogenicity in VLBW, premature infants. We hypothesized that the frequency of post-vaccine antibody concentrations ≥0.15 µg/mL would vary directly with birth weight.
This was a multi-center observational study. Infants 401–1500 grams birth weight and <32 0/7 weeks gestation, stratified by birth weight, were enrolled from 9 NICHD Neonatal Research Network centers. Infants received PCV-7 at 2, 4 and 6 months after birth and had blood drawn 4–6 weeks following the third dose. Antibodies against the 7 vaccine serotypes were measured by enzyme-linked immunosorbent assay.
Of 369 enrolled infants, 244 completed their primary vaccine series by 8 months and had serum obtained. Subjects were 27.8 ± 2.2 (mean ± standard deviation) weeks gestation and 1008 ± 282 grams birth weight. Twenty-six percent had bronchopulmonary dysplasia and 16% had received postnatal glucocorticoids. Infants 1001–1500 grams birth weight were more likely than those 401–1000 grams to achieve antibody concentrations ≥0.15 µg/mL against the least two immunogenic serotypes (6B: 96% v. 85%, P = 0.003 and 23F: 97% v. 88%, P = 0.009). In multiple logistic regression analysis, lower birth weight, postnatal glucocorticoid use, lower weight at blood draw and Caucasian race were each independently associated with antibody concentrations <0.35 µg/mL against serotypes 6B and/or 23F.
When compared with larger premature infants, infants weighing ≤1000 grams at birth have similar antibody responses to most, but not all, PCV-7 vaccine serotypes.
PMCID: PMC2949965  PMID: 20234331
Infant, premature; infant, very low birth weight; pneumococcal vaccines; immunization; vaccines
7.  Influence of Clinical Status on the Association Between Plasma Total and Unbound Bilirubin and Death or Adverse Neurodevelopmental Outcomes in Extremely Low Birth Weight Infants 
To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants.
Total plasma biirubin and unbound biirubin were measured in 1,101 extremely low birth weight infants at 5±1 day of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors.
Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants.
In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma and unbound bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.
PMCID: PMC2875328  PMID: 20105142
Plasma bilirubin; unbound bilirubin; Extremely low birth weight infants; Neurodevelopmental outcomes
8.  Aggressive vs. Conservative Phototherapy for Infants with Extremely Low Birth Weight 
It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less).
We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments.
Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 μmol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P = 0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g.
Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials. gov number, NCT00114543.)
PMCID: PMC2821221  PMID: 18971491
The Journal of pediatrics  2007;150(6):592-596.e5.
To assess interobserver reliability between two central readers of cranial ultrasound (CUS) and accuracy of local compared with central interpretations.
Study design
A retrospective analysis of CUS data from the NICHD trial of inhaled nitric oxide for premature infants. Interobserver reliability of two central readers was assessed by kappa or weighted kappa. Accuracy of local compared with central interpretations was assessed by sensitivity and specificity.
Cranial US from 326 infants had both central reader and local interpretations. Central reader agreement for grade 3/4 IVH, grade 3/4 IVH or PVL, grade of IVH, and degree of ventriculomegaly was very good (kappa=0.84, 0.81, 0.79, and 0.75, respectively). Agreement was poor for lower grade IVH and for PVL alone. Local interpretations were highly accurate for grade 3/4 IVH or PVL (sensitivity 87–90%, specificity 92–93%), but sensitivity was poor to fair for grade 1/2 IVH (48–68%) and PVL (20–44%).
Our findings demonstrate reliability and accuracy of highly unfavorable CUS findings, but suggest caution when interpreting mild to moderate IVH or white matter injury.
PMCID: PMC2757063  PMID: 17517240
intraventricular; hemorrhage; leukomalacia; central reader; neurodevelopmental; brain

Results 1-9 (9)