Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does ...not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity.
We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks' postmenstrual age.
We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks' postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes 4%) and 19 infants in the laser-therapy group (32 of 146 eyes 22%, P=0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P=0.003) but not for zone II disease (P=0.27).
Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. (Funded by Research to Prevent Blindness and others; ClinicalTrials.gov number, NCT00622726.).
Infants with stage 3+ retinopathy of prematurity (ROP) in zone I or zone II posterior were randomized to initial treatment with bevacizumab or laser in a multicenter trial (BEAT-ROP). The purpose of ...this study was to assess the effects of bevacizumab on nonophthalmologic outcomes.
At one study site, inborn infants of <27 weeks' gestational age underwent medical and standardized neurologic and developmental assessments at 18-22 months' corrected age (age after expected date of full-term delivery).
Of the 18 infants enrolled at our site, 16 (7 bevacizumab, 9 laser) were evaluated for medical and neurodevelopmental outcomes at 18-28 months' corrected age. For each of the groups, the medians and ranges of growth percentiles were low compared with norms for healthy infants. The ranges for Bayley III developmental scores were also low relative to expected norms for healthy infants. There were no significant differences between the bevacizumab and laser therapy groups in weight (median percentile: bevacizumab, 18; laser, 7), length, head circumference, cerebral palsy, or Bayley scores (median Cognitive Composite Score: bevacizumab, 85; laser, 65). There was a significant difference in length of hospital stay (median days, 98 vs 140 days) favoring the bevacizumab group.
In this patient cohort 2-year follow-up evaluation of infants treated with bevacizumab versus laser therapy for retinopathy of prematurity showed no adverse effects on medical or neurodevelopmental outcomes.▪
This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low ...birth weight infants, according to gestational age (GA).
Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22-28 weeks) and very low birth weight (401-1500 g) who were born at network centers between January 1, 2003, and December 31, 2007.
Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at <or=12 hours, with most early deaths occurring at 22 and 23 weeks (85% and 43%, respectively). Rates of prenatal steroid use (13% and 53%, respectively), cesarean section (7% and 24%, respectively), and delivery room intubation (19% and 68%, respectively) increased markedly between 22 and 23 weeks. Infants at the lowest GAs were at greatest risk for morbidities. Overall, 93% had respiratory distress syndrome, 46% patent ductus arteriosus, 16% severe intraventricular hemorrhage, 11% necrotizing enterocolitis, and 36% late-onset sepsis. The new severity-based definition of bronchopulmonary dysplasia classified more infants as having bronchopulmonary dysplasia than did the traditional definition of supplemental oxygen use at 36 weeks (68%, compared with 42%). More than one-half of infants with extremely low GAs had undetermined retinopathy status at the time of discharge. Center differences in management and outcomes were identified.
Although the majority of infants with GAs of >or=24 weeks survive, high rates of morbidity among survivors continue to be observed.
Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality.
To review 20-year trends in maternal/neonatal care, complications, and mortality among extremely preterm ...infants born at Neonatal Research Network centers.
Prospective registry of 34,636 infants, 22 to 28 weeks' gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012.
Extremely preterm birth.
Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex.
Use of antenatal corticosteroids increased from 1993 to 2012 (24% 348 of 1431 infants) to 87% (1674 of 1919 infants; P < .001), as did cesarean delivery (44% 625 of 1431 births to 64% 1227 of 1921; P < .001). Delivery room intubation decreased from 80% (1144 of 1433 infants) in 1993 to 65% (1253 of 1922) in 2012 (P < .001). After increasing in the 1990s, postnatal steroid use declined to 8% (141 of 1757 infants) in 2004 (P < .001), with no significant change thereafter. Although most infants were ventilated, continuous positive airway pressure without ventilation increased from 7% (120 of 1666 infants) in 2002 to 11% (190 of 1756 infants) in 2012 (P < .001). Despite no improvement from 1993 to 2004, rates of late-onset sepsis declined between 2005 and 2012 for infants of each gestational age (median, 26 weeks 37% {109 of 296} to 27% {85 of 320}; adjusted relative risk RR, 0.93 95% CI, 0.92-0.94). Rates of other morbidities declined, but bronchopulmonary dysplasia increased between 2009 and 2012 for infants at 26 to 27 weeks' gestation (26 weeks, 50% 130 of 258 to 55% 164 of 297; P < .001). Survival increased between 2009 and 2012 for infants at 23 weeks' gestation (27% 41 of 152 to 33% 50 of 150; adjusted RR, 1.09 95% CI, 1.05-1.14) and 24 weeks (63% 156 of 248 to 65% 174 of 269; adjusted RR, 1.05 95% CI, 1.03-1.07), with smaller relative increases for infants at 25 and 27 weeks' gestation, and no change for infants at 22, 26, and 28 weeks' gestation. Survival without major morbidity increased approximately 2% per year for infants at 25 to 28 weeks' gestation, with no change for infants at 22 to 24 weeks' gestation.
Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks' gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions.
clinicaltrials.gov Identifier: NCT00063063.
Four experiments showed that the decisions people make for future selves and other people are similar to each other and different from their decisions for present selves. Experiments involved ...decisions to drink a disgusting liquid for scientific purposes (Experiment 1), tutor peers during exam week (Experiment 2), receive e-mails for charity (Experiment 3), and defer a lottery prize for a larger one (Experiment 4). These findings seemed to be at least partially rooted in the tendency for decisions regarding the ongoing, present self to be uniquely influenced by internal subjective experience. Specifically, these effects emerged for real, but not hypothetical, decisions. Also, they were mitigated by manipulations that altered participants' attention to present or future subjective experience. In addition, when participants' subjective experience primarily involved empathy for others (Experiment 3), their decisions on behalf of present selves were more generous than their decisions for future selves and others. Applications are discussed.
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.
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.
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.
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.
The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.
The KDEL receptor retrieval pathway is essential for maintaining resident proteins in the endoplasmic reticulum (ER) lumen. ER resident proteins serve a variety of functions, including protein ...folding and maturation. Perturbations to the lumenal ER microenvironment, such as calcium depletion, can cause protein misfolding and activation of the unfolded protein response (UPR). Additionally, ER resident proteins are secreted from the cell by overwhelming the KDEL receptor retrieval pathway. Recent data show that KDEL receptors are also activated during the UPR through the IRE1/XBP1 signaling pathway as an adaptive response to cellular stress set forth to reduce the loss of ER resident proteins. This review will discuss the emerging connection between UPR activation and KDEL receptors as it pertains to ER proteostasis and disease states.
There are limited data to inform the choice between early treatment with continuous positive airway pressure (CPAP) and early surfactant treatment as the initial support for ...extremely-low-birth-weight infants.
We performed a randomized, multicenter trial, with a 2-by-2 factorial design, involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were randomly assigned to intubation and surfactant treatment (within 1 hour after birth) or to CPAP treatment initiated in the delivery room, with subsequent use of a protocol-driven limited ventilation strategy. Infants were also randomly assigned to one of two target ranges of oxygen saturation. The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks (with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30% oxygen).
A total of 1316 infants were enrolled in the study. The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group (47.8% and 51.0%, respectively; relative risk with CPAP, 0.95; 95% confidence interval CI, 0.85 to 1.05) after adjustment for gestational age, center, and familial clustering. The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks (rates of primary outcome, 48.7% and 54.1%, respectively; relative risk with CPAP, 0.91; 95% CI, 0.83 to 1.01). Infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia (P<0.001), required fewer days of mechanical ventilation (P=0.03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P=0.01). The rates of other adverse neonatal outcomes did not differ significantly between the two groups.
The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.)
Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and ...lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis.
The American Academy of Pediatrics stresses that NICUs should endorse and model the sudden infant deaths syndrome risk-reduction recommendations significantly before anticipated discharge of the ...infant. Medical personnel are critical role models for parents, and the way they position infants in the hospital strongly influences parental practices at home. The aims of this project were to increase the percentage of infants following safe sleep practices in the NICU before discharge and to determine if improving compliance with these practices would influence parent behavior at home.
An algorithm detailing when to start safe sleep practices, a "Back to Sleep" crib card, educational programs for nurses and parents, a crib audit tool, and postdischarge telephone reminders were developed as quality improvement intervention strategies.
NICU compliance with supine positioning increased from 39% to 83% (P < .001), provision of a firm sleeping surface increased from 5% to 96% (P < .001), and the removal of soft objects from the bed improved from 45% to 75% (P = .001). Through the use of a postdischarge telephone survey, parental compliance with safe sleep practices was noted to improve from 23% to 82% (P < .001).
Multifactorial interventions improved compliance with safe sleep practices in the NICU and at home.
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