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1.  Emperic Antifungal Therapy and Outcomes in Extremely-Low-Birth-Weight Infants with Invasive Candidiasis 
The Journal of Pediatrics  2012;161(2):264-269.e2.
Objective
To assess the impact of emperic antifungal therapy of invasive candidiasis on subsequent outcomes in premature infants.
Study design
This was a cohort study of infants ≤1000 g birth weight cared for at Neonatal Research Network sites. All infants had at least 1 positive culture for Candida. Emperic antifungal therapy was defined as receipt of a systemic antifungal on the day of or the day before the first positive culture for Candida was drawn. We created Cox proportional hazards and logistic regression models stratified on propensity score quartiles to determine the effect of emperic antifungal therapy on survival, time to clearance of infection, retinopathy of prematurity, bronchopulmonary dysplasia, end-organ damage, and neurodevelopmental impairment (NDI).
Results
136 infants developed invasive candidiasis. The incidence of death or NDI was lower for infants who received emperic antifungal therapy (19/38, 50%) compared with those who had not (55/86, 64%; odds ratio=0.27 [95% confidence interval 0.08–0.86]). There was no significant difference between the groups for any single outcome or other combined outcomes.
Conclusions
Emperic antifungal therapy was associated with increased survival without NDI. A prospective randomized trial of this strategy is warranted.
doi:10.1016/j.jpeds.2012.01.053
PMCID: PMC3380169  PMID: 22424952
Candida; neonate; mortality; neurodevelopmental impairment
2.  An Integrated Randomized Intervention to Reduce Behavioral and Psychosocial Risks: Pregnancy and Neonatal Outcomes 
Maternal and Child Health Journal  2012;16(3):545-554.
Objective
While biomedical risks contribute to poor pregnancy and neonatal outcomes in African American (AA) populations, behavioral and psychosocial risks (BPSR) may also play a part. Among low income AA women with psychosocial risks, this report addresses the impacts on pregnancy and neonatal outcomes of an integrated education and counseling intervention to reduce BPSR, as well as the contributions of other psychosocial and biomedical risks.
Methods
Subjects were low income AA women ≥18 years living in the Washington, DC, metropolitan area and seeking prenatal care. Subjects (n=1044) were screened for active smoking, environmental tobacco smoke exposure (ETSE), depression, or intimate partner violence (IPV) and then randomized to intervention (IG) or usual care (UCG) groups. Data were collected prenatally, at delivery, and postpartum by maternal report and medical record abstraction. Multiple imputation methodology was used to estimate missing variables. Rates of pregnancy outcomes (miscarriage, live birth, perinatal death), preterm labor, Caesarean section, sexually transmitted infection (STI) during pregnancy, preterm birth (<37 weeks), low birth weight (<2,500 grams), very low birth weight (<1,500 grams), small for gestational age, neonatal intensive care unit (NICU) admission, and >2 days of hospitalization were compared between IG and UCG. Logistic regression models were created to predict outcomes based on biomedical risk factors and the four psychosocial risks (smoking, ETSE, depression, and IPV) targeted by the intervention.
Results
Rates of adverse pregnancy and neonatal outcomes were high and did not differ significantly between IG and UCG. In adjusted analysis, STI during the current pregnancy was associated with IPV (OR=1.41, 95% CI 1.04-1.91). Outcomes such as preterm labor/caesarian section in pregnancy and preterm birth, low birth weight, small for gestational age, NICU admissions and >2 day hospitalization of the infants were associated with biomedical risk factors including preexisting hypertension and diabetes, previous preterm birth (PTB), and late initiation of prenatal care, but they were not significantly associated with active smoking, ETSE, depression, or IPV.
Conclusions
Neither the intervention to reduce BPSR nor the psychosocial factors significantly contributed to the pregnancy and neonatal outcomes. This study confirms that biomedical factors significantly contribute to adverse outcomes in low income AA women. Biomedical factors outweighed psychosocial factors in contributing to adverse pregnancy and neonatal outcomes in this high-risk population. Early identification and management of hypertension, diabetes and previous PTB in low income AA women may reduce health disparities in birth outcomes.
doi:10.1007/s10995-011-0875-9
PMCID: PMC3288486  PMID: 21931956
3.  Enrollment of Extremely Low Birth Weight Infants in a Clinical Research Study May Not Be Representative 
Pediatrics  2012;129(3):480-484.
BACKGROUND AND OBJECTIVE:
The Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT) antenatal consent study demonstrated that mothers of infants enrolled in the SUPPORT trial had significantly different demographics and exposure to antenatal steroids compared with mothers of eligible, but not enrolled infants. The objective of this analysis was to compare the outcomes of bronchopulmonary dysplasia, severe retinopathy of prematurity, severe intraventricular hemorrhage or periventricular leukomalacia (IVH/PVL), death, and death/severe IVH/PVL for infants enrolled in SUPPORT in comparison with eligible, but not enrolled infants.
METHODS:
Perinatal characteristics and neonatal outcomes were compared for enrolled and eligible but not enrolled infants in bivariate analyses. Models were created to test the effect of enrollment in SUPPORT on outcomes, controlling for perinatal characteristics.
RESULTS:
There were 1316 infants enrolled in SUPPORT; 3053 infants were eligible, but not enrolled. In unadjusted analyses, enrolled infants had significantly lower rates of death before discharge, severe IVH/PVL, death/severe IVH/PVL (all < 0.001), and bronchopulmonary dysplasia (P = .003) in comparison with eligible, but not enrolled infants. The rate of severe retinopathy of prematurity was not significantly different. After adjustment for perinatal factors, enrollment in the trial was not a significant predictor of any of the tested clinical outcomes.
CONCLUSIONS:
The results of this analysis demonstrate significant outcome differences between enrolled and eligible but not enrolled infants in a trial using antenatal consent, which were likely due to enrollment bias resulting from the antenatal consent process. Additional research and regulatory review need to be conducted to ensure that large moderate-risk trials that require antenatal consent can be conducted in such a way as to ensure the generalizability of results.
doi:10.1542/peds.2011-2121
PMCID: PMC3289530  PMID: 22371462
antenatal steroids; clinical research/trials; informed consent; neonatal
4.  Outcomes Following Candiduria in Extremely Low Birth Weight Infants 
Extremely low birth weight (ELBW) infants with candiduria are at substantial risk for death or neurodevelopmental impairment. Therefore, identification of candiduria should prompt a systemic evaluation for disseminated Candida infection and initiation of treatment in all ELBW infants.
Background. Candidiasis carries a significant risk of death or neurodevelopmental impairment (NDI) in extremely low birth weight infants (ELBW; <1000 g). We sought to determine the impact of candiduria in ELBW preterm infants.
Methods. Our study was a secondary analysis of the Neonatal Research Network study Early Diagnosis of Nosocomial Candidiasis. Follow-up assessments included Bayley Scales of Infant Development examinations at 18–22 months of corrected age. Risk factors were compared between groups using exact tests and general linear modeling. Death, NDI, and death or NDI were compared using generalized linear mixed modeling.
Results. Of 1515 infants enrolled, 34 (2.2%) had candiduria only. Candida was isolated from blood only (69 of 1515 [4.6%]), cerebrospinal fluid (CSF) only (2 of 1515 [0.1%]), other sterile site only (not urine, blood, or CSF; 4 of 1515 [0.3%]), or multiple sources (28 of 1515 [2%]). Eleven infants had the same Candida species isolated in blood and urine within 3 days; 3 (27%) had a positive urine culture result first. Most urine isolates were Candida albicans (21 of 34 [62%]) or Candida parapsilosis (7 of 34 [29%]). Rate of death or NDI was greater among those with candiduria (50%) than among those with suspected but not proven infection (32%; odds ratio, 2.5 [95% confidence interval, 1.2–5.3]) after adjustment. No difference in death and death or NDI was noted between infants with candiduria and those with candidemia.
Conclusions. These findings provide compelling evidence that ELBW infants with candiduria are at substantial risk of death or NDI. Candiduria in ELBW preterm infants should prompt a systemic evaluation (blood, CSF, and abdominal ultrasound) for disseminated Candida infection and warrants treatment.
doi:10.1093/cid/cir800
PMCID: PMC3258271  PMID: 22144537
5.  Understanding the Association of Biomedical, Psychosocial and Behavioral Risks with Adverse Pregnancy Outcomes 
Maternal and child health journal  2011;15(Suppl 1):85-95.
Objectives
This study investigates the relationship between diabetes, hypertension, preeclampsia, and Body Mass Index (BMI) -- the most common and interrelated medical conditions occurring during pregnancy; sociodemographic and behavioral risk factors; and adverse pregnancy outcomes in high-risk urban African American women in Washington, DC.
Methods
Data are from a randomized controlled trial conducted in 6 prenatal clinics. Women in their 1st or 2nd trimester were screened for behavioral risks (smoking, environmental tobacco smoke exposure, depression, and intimate partner violence) and demographic eligibility. 1,044 were eligible, interviewed and followed through their pregnancies. Classification and Regression Trees (CART) methodology was used to: 1) explore the relationship between medical and behavioral risks (reported at enrollment), sociodemographic factors and pregnancy outcomes, 2) identify the relative importance of various predictors of adverse pregnancy outcomes, and 3) characterize women at the highest risk of poor pregnancy outcomes.
Results
Overall, the strongest predictors of poor outcomes were prepregnancy BMI, preconceptional diabetes, employment status, intimate partner violence, and depression. In CART analysis, preeclampsia was the first splitter for low birthweight; preconceptional diabetes was the first splitter for preterm birth (PTB) and neonatal intensive care admission; BMI was the first splitter for very PTB, large for gestational age, Cesarean section and perinatal death; and employment was the first splitter for miscarriage.
Conclusions
Preconceptional factors play a very important role in pregnancy outcomes. For many of these women, the risks that they bring into the pregnancy were more likely to impact their pregnancy outcome than events during pregnancy.
doi:10.1007/s10995-011-0856-z
PMCID: PMC3220795  PMID: 21785892
6.  Very Preterm Birth is Reduced in Women Receiving an Integrated Behavioral Intervention: A Randomized Controlled Trial 
Background
This study examines whether an integrated behavioral intervention with proven efficacy in reducing psycho-behavioral risks (smoking, environmental tobacco smoke exposure (ETSE), depression, and intimate partner violence (IPV)) in African-Americans is associated with improved pregnancy outcomes
Methods
A randomized controlled trial targeting risks during pregnancy was conducted in the District of Columbia. African-American women were recruited if reporting at least one of the risks mentioned above. Randomization to intervention or usual care was site and risk specific. Sociodemographic, health risk and pregnancy outcome data were collected. Data on 819 women, and their singleton live born infants were analyzed using an intent-to-treat approach. Bivariate analyses preceded a reduced logistical model approach to elucidate the effect of the intervention on the reduction of prematurity and low birth weight.
Results
The incidence of low birthweight LBW was 12% and very low birthweight VLBW was 1.6%. Multivariate logistic regression results showed that depression was associated with LBW (OR=1.71, 95%CI=1.12–2.62). IPV was associated with PTB and VPTB (OR 1.64, 95%CI=1.07–2.51, OR=2.94, 95%CI=1.40–6.16, respectively). The occurrence of VPTB was significantly reduced in the intervention compared to the usual care group (OR=0.42, 95%CI=0.19–0.93).
Conclusions
Our study confirms the significant associations between multiple psycho-behavioral risks and poor pregnancy outcomes, including LBW and PTB. Our behavioral intervention with demonstrated efficacy in addressing multiple risk factors simultaneously reduced VPTB within an urban minority population.
doi:10.1007/s10995-009-0557-z
PMCID: PMC2988881  PMID: 20082130
African-American; birth weight; pregnancy; gestational age
7.  Neonatal Candidiasis: Epidemiology, Risk Factors, and Clinical Judgment 
Pediatrics  2010;126(4):e865-e873.
OBJECTIVE
Invasive candidiasis is a leading cause of infection-related morbidity and mortality in extremely low-birth-weight (<1000 g) infants. We quantify risk factors predicting infection in high-risk premature infants and compare clinical judgment with a prediction model of invasive candidiasis.
METHODS
The study involved a prospective observational cohort of infants <1000 g birth weight at 19 centers of the NICHD Neonatal Research Network. At each sepsis evaluation, clinical information was recorded, cultures obtained, and clinicians prospectively recorded their estimate of the probability of invasive candidiasis. Two models were generated with invasive candidiasis as their outcome: 1) potentially modifiable risk factors and 2) a clinical model at time of blood culture to predict candidiasis.
RESULTS
Invasive candidiasis occurred in 137/1515 (9.0%) infants and was documented by positive culture from ≥ 1 of these sources: blood (n=96), cerebrospinal fluid (n=9), urine obtained by catheterization (n=52), or other sterile body fluid (n=10). Mortality was not different from infants who had positive blood culture compared to those with isolated positive urine culture. Incidence varied from 2–28% at the 13 centers enrolling ≥ 50 infants. Potentially modifiable risk factors (model 1) included central catheter, broad-spectrum antibiotics (e.g., third-generation cephalosporins), intravenous lipid emulsion, endotracheal tube, and antenatal antibiotics. The clinical prediction model (model 2) had an area under the receiver operating characteristic curve of 0.79, and was superior to clinician judgment (0.70) in predicting subsequent invasive candidiasis. Performance of clinical judgment did not vary significantly with level of training.
CONCLUSION
Prior antibiotics, presence of a central catheter, endotracheal tube, and center were strongly associated with invasive candidiasis. Modeling was more accurate in predicting invasive candidiasis than clinical judgment.
doi:10.1542/peds.2009-3412
PMCID: PMC3045840  PMID: 20876174
Candidiasis; premature infant; risk factors
8.  An Intervention to Reduce Environmental Tobacco Smoke Exposure Improves Pregnancy Outcomes 
Pediatrics  2010;125(4):721-728.
Objective
We tested the efficacy of a cognitive-behavioral intervention in reducing environmental tobacco smoke exposure (ETSE) and improving pregnancy outcomes among African-American women.
Methods
We recruited 1,044 women to a randomized controlled trial during 2001-2004 in Washington, DC. Data on 691 women with self-reported ETSE were analyzed. A subset of 520 ETSE women and salivary cotinine levels (SCLs) <20 ng/ml was also analyzed. Individually tailored counseling sessions adapted from evidence-based interventions for ETSE and other risks, were delivered to the intervention group. The usual care group received routine prenatal care as determined by their provider. Logistic regression models were used to predict ETSE before delivery and adverse pregnancy outcomes.
Results
Women in the intervention were less likely to self-report ETSE before delivery when controlling for other covariates (OR=0.50, 95%CI=0.35-0.71). Medicaid recipients were more likely to have ETSE (OR=1.97, 95%CI=1.31-2.96). With advancing maternal age, the likelihood of ETSE was less (OR=0.96, 95%CI=0.93-0.99). For women in the intervention the rates of very low birth weight (VLBW) and very preterm birth (VPTB) were significantly improved (OR=0.11, 95%CI=0.01-0.86; OR=0.22, 95%CI=0.07-0.68, respectively). For women with SCL <20 ng/ml, maternal age was not significant. Intimate partner violence at baseline significantly increased the chances of VLBW and VPTB (OR=3.75, 95%CI=1.02-13.81; OR=2.71, 95%CI=1.11-6.62, respectively). These results were true for mothers who reported ETSE overall and for those with SCL <20 ng/ml.
Conclusions
This is the first randomized clinical trial demonstrating efficacy of a cognitive-behavioral intervention targeting ETSE in pregnancy. We significantly reduced ETSE as well as VPTB and VLBW, leading causes of neonatal mortality and morbidity in minority populations. This intervention may reduce health disparities seen in reproductive outcomes.
doi:10.1542/peds.2009-1809
PMCID: PMC2923806  PMID: 20211945
behavioral intervention; environmental tobacco smoke; pregnant women; African-American; birth weight; preterm birth
9.  Antenatal Consent in the SUPPORT Trial: Challenges, Costs, and Representative Enrollment 
Pediatrics  2010;126(1):e215-e221.
OBJECTIVES
The purposes of this study were to quantify the time and effort involved in obtaining prenatal consent for the Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT) and to determine whether the enrolled infants were representative of the eligible population.
METHODS
Eligible subjects were likely to deliver in the SUPPORT gestational age window (24–27 6/7; weeks). Data included who approached the subjects for consent, how often they approached, the duration of each contact, whether consent was obtained, and whether subjects were enrolled in the trial. Eligible, nonenrolled infants entered into the Neonatal Research Network Generic Database throughout the period of SUPPORT enrollment were compared with enrolled infants.
RESULTS
A total of 2826 women were identified at 18 sites, 2228 were approached for consent, and 1219 (54.7%) agreed. For 76.9% of those approached, <3 visits (mean: 2.0 ± 1.2 visits) were required to complete the consent process. Of the 659 infants with consent who were delivered within the study window, 611 were enrolled. Mothers who received a neonatal consultation were more likely to give consent (P < .001). The proportion of infants not exposed to steroids was significantly greater in the nonapproached group than in the approached group (20.0% vs 3.4%; P < .0001).
CONCLUSION
In a trial that involved preterm infants and required prenatal consent, >5 women were identified as being likely to deliver in the SUPPORT gestational age window for each 1 who delivered an enrolled infant.
doi:10.1542/peds.2009-3353
PMCID: PMC3057215  PMID: 20587676
informed consent; prenatal; neonatal
10.  AN INTEGRATED INTERVENTION TO REDUCE INTIMATE PARTNER VIOLENCE IN PREGNANCY: A RANDOMIZED TRIAL 
Obstetrics and gynecology  2010;115(2 Pt 1):273-283.
OBJECTIVE
We estimated the efficacy of a psycho-behavioral intervention in reducing intimate partner violence (IPV) recurrence during pregnancy and postpartum, and in improving birth outcomes in African-American women
METHODS
We conducted a randomized controlled trial in which 1,044 women were recruited. Individually-tailored counseling sessions were adapted from evidence-based interventions for IPV and other risks. Logistic regression was used to model IPV victimization recurrence, to predict minor, severe, physical and sexual IPV.
RESULTS
Women randomized to the intervention were less likely to have recurrent episodes of IPV victimization (OR=0.48, 95%CI=0.29-0.80). Women with minor IPV were significantly less likely to experience further episodes during pregnancy (OR=0.48, 95%CI=0.26-0.86, OR=0.53, 95%CI=0.28-0.99) and postpartum (OR=0.56, 95%CI=0.34-0.93). Numbers needed to treat were 17, 12, and 22, respectively as compared to the usual care Women with severe IPV showed significantly reduced episodes at postpartum (OR=0.39, 95%CI=0.18-0.82) and number needed to treat is 27. Women who experienced physical IPV showed significant reduction at the first follow-up (OR=0.49, 95%CI=0.27-0.91) and postpartum (OR=0.47, 95%CI=0.27-0.82) and number needed to treat is 18 and 20, respectively. Intervention women had significantly fewer very preterm infants (p=0.03) and an increased mean gestational age (p=0.016).
CONCLUSION
A relatively brief intervention during pregnancy had discernable effects on IPV and pregnancy outcomes. Screening for IPV as well as other psychosocial and behavioral risks and incorporating similar interventions in prenatal care is strongly recommended.
doi:10.1097/AOG.0b013e3181cbd482
PMCID: PMC2917915  PMID: 20093899
11.  Prediction of Birth Weight By Cotinine Levels During Pregnancy in a Population of African American Smokers 
Pediatrics  2009;124(4):e671-e680.
Objective
The goal was to investigate the association between maternal salivary cotinine levels (SCLs) and pregnancy outcome among African Americans smokers
Methods
In a randomized controlled trial conducted in 2001-2004 in Washington, D.C. 714 women (126 active smokers (18%)) were tested for SCLs at the time of recruitment and later in pregnancy. Sociodemographic health risks and pregnancy outcomes were recorded.
Results
Birth weights were significantly lower for infants born to mothers with baseline SCLs of ≥20 ng/ml compared to <20 ng/ml (p=0.024), ≥50 ng/ml compared to <50 ng/ml (p=0.002), ≥100 ng/ml compared to <100 ng/ml (p=0.002), in bivariate analyses. In linear regression analyses adjusting for sociodemographic and medical factors, SCLs of ≥20 ng/ml were associated with a reduction in birth weight of 88 grams when SCLs were measured at baseline (p=0.042) and 205 grams when SCLs were measured immediately before delivery (p<0.001). Corresponding results were 129 grams (p=0.006) and 202 grams (p<0.001) for ≥50 ng/ml and 139 grams (p=0.007) and 205 grams (p<0.001) for ≥100 ng/ml. Gestational age was not affected significantly at any SCL, regardless of when SCLs were measured.
Conclusions
Elevated SCLs early in pregnancy or before delivery were associated with reductions in birth weight. At any cutoff level, birth weight reduction was more significant for the same SCL measured late in pregnancy. Maintaining lower levels of smoking for women who are unable to quit may be beneficial.
doi:10.1542/peds.2008-3784
PMCID: PMC2922025  PMID: 19786427
12.  An Integrated Intervention in Pregnant African Americans Reduces Postpartum Risk: A Randomized Trial 
Obstetrics and gynecology  2008;112(3):611-620.
Objective
To evaluate the efficacy of an integrated multiple risk intervention delivered mainly during pregnancy, in reducing such risks (smoking, environmental tobacco smoke exposure, depression and intimate partner violence) postpartum.
Design
Data from this randomized controlled trial were collected prenatally and on average 10 weeks postpartum in six prenatal care sites in the District of Columbia. African Americans were screened, recruited and randomly assigned to the behavioral intervention or usual care. Clinic-based, individually tailored counseling was delivered to intervention women. The outcome measures were number of reisks reported postpartum and reduction of these risks between baseline and postpartum.
Results
The intervention was effective in significantly reducing the number of risks reported in the postpartum period. In Bivariate analyses, the intervention group was more successful in resolving all risks (47% compared with 35%, p=0.007), number needed to treat=9, 95% confidence interval [CI] 5-31) and in resolving some risks (63% compared with 54%, p=0.009), number needed to treat=11, 95% CI 7-43) as compared with the usual care group. In logistical regression analyses, women in the intervention group were more likely to resolve all risks (OR=1.86, 95% CI: 1.25-2.75) and in resolving at least one risk (OR=1.6, 95% CI: 1.15-2.22).
Conclusions
An integrated multiple risk factor intervention addressing psychosocial and behavioral risks delivered mainly during pregnancy can have beneficial effects in risk reduction postpartum.
PMCID: PMC2935657  PMID: 18757660
13.  Environmental Tobacco Smoke Avoidance Among Pregnant African-American Nonsmokers 
Background
Environmental tobacco smoke (ETS) exposure during pregnancy contributes to adverse infant health outcomes. Limited previous research has focused on identifying correlates of ETS avoidance. This study sought to identify proximal and more distal correlates of ETS avoidance early in pregnancy among African-American women.
Methods
From a sample of low-income, black women (n=1044) recruited in six urban, prenatal care clinics (July 2001–October 2003), cotinine-confirmed nonsmokers with partners, household/family members, or friends who smoked (n=450) were identified and divided into two groups: any past-7-day ETS exposure and cotinine-confirmed ETS avoidance. Bivariate and multivariate logistic regression analyses identified factors associated with ETS avoidance. Data were initially analyzed in 2004. Final models were reviewed and revised in 2007 and 2008.
Results
Twenty-seven percent of pregnant nonsmokers were confirmed as ETS avoiders. In multivariate logistic regression analysis, the odds of ETS avoidance were increased among women who reported household smoking bans (OR=2.96; 95% CI=1.83, 4.77; p<0.0001), that the father wanted the baby (OR=2.70; CI=1.26, 5.76; p=0.01), and that no/few family members/friends smoked (OR=3.15; 95% CI=1.58, 6.29; p<0.001). The odds were decreased among women who had a current partner (OR= 0.42; 95% CI=0.23, 0.76; p<0.01), reported any intimate partner violence during pregnancy (OR= 0.43; 95% CI=0.19, 0.95; p<0.05), and reported little social support to prevent ETS exposure (OR= 0.50; 95% CI=0.30, 0.85; p=0.01). Parity, emotional coping strategies, substance use during pregnancy, partner/household member smoking status, and self-confidence in avoiding ETS were significant in bivariate, but not multivariate analyses.
Conclusions
Social contextual factors were the strongest determinants of ETS avoidance during pregnancy. Results highlight the importance of prenatal screening to identify pregnant nonsmokers at risk, encouraging household smoking bans, gaining support from significant others, and fully understanding the interpersonal context of a woman’s pregnancy before providing behavioral counseling and advice to prevent ETS exposure.
doi:10.1016/j.amepre.2008.10.012
PMCID: PMC2711691  PMID: 19215848
14.  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

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