Rationale: Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, and do not adequately predict childhood morbidity.Objectives: To determine which of 18 prespecified, revised definitions of bronchopulmonary dysplasia that variably define disease severity according to the level of respiratory support and supplemental oxygen administered at 36 weeks’ postmenstrual age best predicts death or serious respiratory morbidity through 18–26 months’ corrected age.Methods: We assessed infants born at less than 32 weeks of gestation between 2011 and 2015 at 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.Measurements and Main Results: Of 2,677 infants, 683 (26%) died or developed serious respiratory morbidity. The diagnostic criteria that best predicted this outcome defined bronchopulmonary dysplasia according to treatment with the following support at 36 weeks’ postmenstrual age, regardless of prior or current oxygen therapy: no bronchopulmonary dysplasia, no support (n = 773); grade 1, nasal cannula ≤2 L/min (n = 1,038); grade 2, nasal cannula >2 L/min or noninvasive positive airway pressure (n = 617); and grade 3, invasive mechanical ventilation (n = 249). These criteria correctly predicted death or serious respiratory morbidity in 81% of study infants. Rates of this outcome increased stepwise from 10% among infants without bronchopulmonary dysplasia to 77% among those with grade 3 disease. A similar gradient (33–79%) was observed for death or neurodevelopmental impairment.Conclusions: The definition of bronchopulmonary dysplasia that best predicted early childhood morbidity categorized disease severity according to the mode of respiratory support administered at 36 weeks’ postmenstrual age, regardless of supplemental oxygen use.

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. 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 FI O 2 , 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.Keywords: bronchopulmonary dysplasia; prematurity; low-birth-weight infant AT A GLANCE COMMENTARY Scientific Knowledge on the SubjectBronchopulmonary dysplasia is the most common serious pulmonary morbidity in premature infants. Although accurate predictive models of bronchopulmonary dysplasia risk are sometimes used in research, none are currently used in common clinical practice for a variety of reasons. What This Study Adds to the FieldIn this study, we identified the change in the relative contributions of a variety of risk factors to the prediction of bronchopulmonary dysplasia with advancing postnatal age. This tool may help identify patients most likely to benefit from postnatal treatment and assist in the design of clinical trials to assess the efficacy of preventive therapies in high-risk populations.

Background-Previous studies have suggested that the incidence of retinopathy is lower in preterm infants with exposure to reduced levels of oxygenation than in those exposed to higher levels of oxygenation. However, it is unclear what range of oxygen saturation is appropriate to minimize retinopathy without increasing adverse outcomes.Methods-We performed a randomized trial with a 2-by-2 factorial design to compare target ranges of oxygen saturation of 85 to 89% or 91 to 95% among 1316 infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. The primary outcome was a composite of severe retinopathy of prematurity (defined as the presence of threshold retinopathy, the need for surgical ophthalmologic intervention, or the use of bevacizumab), death before discharge from the hospital, or both. All infants were also randomly assigned to continuous positive airway pressure or intubation and surfactant.Results-The rates of severe retinopathy or death did not differ significantly between the loweroxygen-saturation group and the higher-oxygen-saturation group (28.3% and 32.1%, respectively; relative risk with lower oxygen saturation, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P = 0.21). Death before discharge occurred more frequently in the lower-oxygen-saturation group (in 19.9% of infants vs. 16.2%; relative risk, 1.27; 95% CI, 1.01 to 1.60; P = 0.04), whereas severe retinopathy among survivors occurred less often in this group (8.6% vs. 17.9%; relative risk, 0.52; 95% CI, 0.37 to 0.73; P<0.001). There were no significant differences in the rates of other adverse events.Conclusions-A lower target range of oxygenation (85 to 89%), as compared with a higher range (91 to 95%), did not significantly decrease the composite outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors. The increase in mortality is a major concern, since a lower target range of oxygen saturation is increasingly being advocated to prevent retinopathy of prematurity. (ClinicalTrials.gov number, NCT00233324.) Retinopathy of prematurity is an important cause of blindness and other visual disabilities in preterm infants. The incidence of retinopathy of prematurity was increased with exposure to unrestricted oxygen supplementation in preterm infants in randomized, controlled trials NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript performed in the 1950s. 1 In the 1960s, this increase resulted in the practice of restricting the fraction of inspired oxygen (FiO 2 ) to no more than 0.50, which was estimated to result in an excess of 16 deaths per case of blindness prevented. 2 More recent data suggest that levels of oxygen saturation previously thought to be at the upper end of the normal range may increase the risk of retinopathy of prematurity as compared with levels at the lower end of the normal range. [3][4][5] Oxygen toxicity may also increase the risk of death, 6,7 bronchopulmonary dysplasia, 8-...

Probability of mesh erosion at 7 years (estimated by the Kaplan-Meier method) was 10.5% (95% CI, 6.8% to 16.1%). Conclusions and Relevance During 7 years of follow-up, abdominal sacrocolpopexy failure rates increased in both groups. Urethropexy prevented SUI longer than no urethropexy. Abdominal sacrocolpopexy effectiveness should be balanced with longterm risks of mesh or suture erosion. Trial Registration clinicaltrials.gov Identifier: NCT00099372

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.

IMPORTANCE Over 300,000 surgeries are performed annually in the United States for pelvic organ prolapse. Sacrospinous ligament fixation (SSLF) and uterosacral ligament suspension (ULS) are commonly performed transvaginal surgeries to correct apical prolapse. Little is known about their comparative efficacy and safety, and it is unknown whether perioperative behavioral therapy with pelvic floor muscle training (BPMT) improves outcomes of prolapse surgery. OBJECTIVE To compare outcomes between 1) SSLF and ULS and 2) perioperative BPMT and usual perioperative care in women undergoing surgery for vaginal prolapse and stress urinary incontinence. DESIGN, SETTING AND PARTICIPANTS Multi-center, 2×2 factorial randomized trial of 374 women undergoing surgery to treat both apical vaginal prolapse and stress urinary incontinence was conducted between 2008 and 2013 at 9 U.S. medical centers. Two-year follow-up rate was 84.5%. INTERVENTIONS Surgical intervention: Transvaginal surgery including mid-urethral sling with randomization to SSLF (n = 186) or ULS (n=188); Behavioral intervention: Randomization to perioperative BPMT (n = 186) or usual care (n=188). MAIN OUTCOME MEASURES The primary outcome for the surgical intervention (surgical success) was defined as: 1) no apical descent greater than one-third into vaginal canal or anterior or posterior vaginal wall beyond the hymen (anatomic success); 2) no bothersome vaginal bulge symptoms and 3) no retreatment for prolapse at 2 years. For the behavioral intervention, primary outcome at 6 months was urinary symptom scores (Urinary Distress Inventory; range 0–300, higher scores worse), and primary outcomes at 2 years were prolapse symptom scores (Pelvic Organ Prolapse Distress Inventory; range 0–300, higher scores worse) and anatomic success. RESULTS At 2 years, surgical group was not significantly associated with surgical success rates [ULS 59.2% (93/154) vs. SSLF 60.5% (92/152), OR 0.9 (95% CI 0.6, 1.5)] or serious adverse event rates [ULS 16.5% (31/188) vs. SSLF 16.7% (31/186), OR 0.9 (95% CI 0.5, 1.6)]. BPMT was not associated with greater improvements in urinary scores at 6 months [treatment difference −6.7 (95% CI −19.7, 6.2)], prolapse scores at 24 months [treatment difference −8.0 (95% CI −22.1, 6.1)] or anatomic success at 24 months. CONCLUSIONS AND RELEVANCE Two years after vaginal surgery for prolapse and stress urinary incontinence, neither ULS nor SSLF was significantly superior to the other for anatomic, functional, and or adverse event outcomes. Perioperative BPMT did not improve urinary symptoms at 6 months or prolapse outcomes at 2 years.

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-Priorantibiotics, 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. KeywordsCandidiasis; premature infant; risk factors In the extremely low-birth-weight (ELBW; <1000g) infant, invasive candidiasis is common, often fatal, and frequently leads to poor neurodevelopmental outcomes. 1,2 Invasive candidiasis (Candida infections of the blood and other sterile body fluids) is the second most common cause of infectious disease-related death in the extremely premature infant. Despite antifungal treatment, 20% of infants who develop invasive candidiasis die, and neurodevelopmental impairment occurs in nearly 60% of survivors. 1,2 Rates of invasive candidiasis vary 10-fold among similar academic tertiary care neonatal intensive care units (NICUs). 3 This variation among nurseries is found throughout the world 4-9 and has not been explained, but exposure to environmental risk factors (e.g., incubator humidity), third-generation cephalosporins, and foreign bodies such as catheters have all been associated with development of disease. 3,10,11 The high morbidity related to invasive candidiasis leads to the consideration of empirical anti...

OBJECTIVE. We sought to determine if an association exists between the use of histamine-2 receptor (H2) blockers and the incidence of necrotizing enterocolitis (NEC) in infants of 401 to 1500 g in birth weight. STUDY DESIGN. Data from the National Institute of Child Health and Human Development Neonatal Research Network very low birth weight (401–1500 g) registry from September 1998 to December 2001 were analyzed. The relation between the diagnosis of NEC (Bell stage II or greater) and antecedent H2-blocker treatment was determined by using case-control methodology. Conditional logistic regression was implemented, controlling for gender, site of birth (outborn versus inborn), Apgar score of &lt;7 at 5 minutes, and postnatal steroids. RESULTS. Of 11072 infants who survived for at least 12 hours, 787 (7.1%) developed NEC (11.5% of infants 401–750 g, 9.1% of infants 751–1000 g, 6.0% of infants 1001–1250 g, and 3.9% of infants 1251–1500 g). Antecedent H2-blocker use was associated with an increased incidence of NEC (P &lt; .0001). CONCLUSIONS. H2-blocker therapy was associated with higher rates of NEC, which is in agreement with a previous randomized trial of acidification of infant feeds that resulted in a decreased incidence of NEC. In combination, these data support the hypothesis that gastric pH level may be a factor in the pathogenesis of NEC.