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Introduction Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs). Methods Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria. Results Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: • Two interventions prevent preterm births—smoking cessation and progesterone • Eight interventions prevent stillbirths—balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery • Eleven interventions improve survival of preterm newborns—prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome Conclusion The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions.

Almost one million prematurely born infants die annually from respiratory insufficiency, predominantly in countries with limited access to respiratory support for neonates. The primary hypothesis tested in the present study was that a modified device for bubble nasal continuous positive airway pressure (Bn-CPAP) would provide lower work of spontaneous breathing, estimated by esophageal pressure-rate products. Infants born <32 weeks gestation and stable on Bn-CPAP with FiO2 <0.30 were studied within 72 h following delivery. Esophageal pressures during spontaneous breathing were measured during 2 h on standard Bn-CPAP, then 2 h with Bn-CPAP using a modified bubble device presently termed Seattle-PAP, which produces a different pattern of pressure fluctuations and which provided greater respiratory support in preclinical studies, then 2 h on standard Bn-CPAP. All 40 infants enrolled completed the study and follow-up through 36 wks post menstrual age or hospital discharge, whichever came first. No infants were on supplemental oxygen at completion of follow-up. No infants developed pneumothoraces or nasal trauma, and no adverse events attributed to the study were observed. Pressure-rate products on the two devices were not different, but effort of breathing, assessed by areas under esophageal pressure-time curves, was lower with Seattle-PAP than with standard Bn-CPAP. Use of Seattle-PAP to implement Bn-CPAP lowers the effort of breathing exerted even by relatively healthy spontaneously breathing premature neonates. Whether the lower effort of breathing observed with Seattle-PAP translates to improvements in neonatal mortality or morbidity will need to be determined by studies in appropriate patient populations.

Background At birth, the majority of neonates born at <30 weeks of gestation require respiratory support to facilitate transition and ensure adequate gas exchange. Although the optimal approach to the initial respiratory management is uncertain, the American Academy of Pediatrics endorses noninvasive respiratory support with nasal continuous positive airway pressure (nCPAP) for premature neonates with respiratory insufficiency. Despite evidence for its use, nCPAP failure, requiring intubation and mechanical ventilation, is common. Recently, investigators have described a novel method to deliver bubble nCPAP, termed Seattle-PAP. While preclinical and pilot studies are encouraging regarding the potential value of Seattle-PAP, a large trial is needed to compare Seattle-PAP directly with the current standard of care for bubble nCPAP (Fisher & Paykel CPAP or FP-CPAP). Methods/design We designed a multicenter, non-blinded, randomized controlled trial that will enroll 230 premature infants (22 0/7 to 29 6/7 weeks of gestation). Infants will be randomized to receive Seattle-PAP or FP-CPAP. The primary outcome is respiratory failure requiring intubation and mechanical ventilation. Secondary outcomes include measures of short- and long-term respiratory morbidity and cost-effectiveness. Discussion This trial will assess whether Seattle-PAP is more efficacious and cost-effective than FP-CPAP in real-world practice among premature neonates. Trial registration ClinicalTrials.gov, NCT03085329 . Registered on 21 March 2017.

Reduction of glutathione disulfide (GSSG) to glutathione (GSH) by glutathione reductase (GR) enhances the efficiency of GSH-dependent antioxidant activities. However, GR-deficient (a1Neu) mice are less susceptible to acute lung injury from continuous exposure to > 95% O(2) (96 h: 6.9 +/- 0.1 g right lung/kg body versus room air 3.6 +/- 0.3) than are C3H/HeN control mice (10.6 +/- 1.3 versus 4.2 +/- 0.3, P < 0.001). a1Neu mice have greater hepatic thioredoxin (Trx)1 and Trx2 levels than do C3H/HeN mice, suggesting compensation for the absence of GR. a1Neu mice exposed to hyperoxia for 96 hours showed lower levels of inflammatory infiltrates in lungs than did similarly exposed C3H/HeN mice. Pretreatment with aurothioglucose (ATG), a thioredoxin reductase (TrxR) inhibitor, exacerbated the effects of hyperoxia on lung injury in a1Neu mice (11.6 +/- 0.8, P < 0.001), but attenuated hyperoxic lung edema and inflammation in C3H/HeN mice (6.3 +/- 0.4, P < 0.001). No consistent alterations were observed in lung GSH contents or liver GSH or GSSG levels after ATG pretreatment. The data suggest that modulation of Trx/TrxR systems might provide therapeutically useful alterations of cellular resistance to oxidant stresses. The protective effects of ATG against hyperoxic lung injury could prove to be particularly useful therapeutically.

ObjectiveTo test the hypothesis that infants born <30 weeks’ gestation supported by Seattle-PAP will have lower rates of continuous positive airway pressure (CPAP) failure than infants supported with conventional, Fisher&Paykel-CPAP (FP-CPAP).Study designRandomized trial (3/2017-01/2019) at 5 NICUs. The primary outcome was CPAP failure; subgroup analyses (gestational age, receipt antenatal corticosteroids) were performed.ResultsA total of 232 infants were randomized. Infants in the Seattle-PAP and FP-CPAP groups had mean gestational ages of 27.0 and 27.2 weeks, respectively. We observed no differences in rates of treatment failure between Seattle-PAP (40/112, 35.7%) and FP-CPAP (38/120, 31.7%; risk difference, 4.1%; 95% CI, −8.1–16.2; P = 0.51). Subgroup analysis indicated no differences in rates of CPAP failure. We observed no differences between the two groups in frequencies of adverse events or duration of respiratory support.ConclusionsAmong infants born <30 weeks’ gestation, rates of CPAP failure did not differ between Seattle-PAP and FP-CPAP.

To recruit and train the next generations of pediatric clinician-scientists, the American Pediatric Society and Society for Pediatric Research initiated a program in 1991 to support medical students with interests in research and pediatrics to conduct research at institutions other than their respective medical schools. Since 1991, the American Pediatric Society-Society for Pediatric Research Medical Student Research Program (MSRP) has funded 732 of 2209 applicants from 132 US or Canadian medical schools for 8–12 wk of research under the direction of experienced investigators. PubMed-attributable publications tabulated in 2001 for MSRP applicants through 2000 indicated that participants had published more actively than had nonparticipant applicants. Male nonparticipants exhibited greater publication activities than did female nonparticipants, but female and male participants published equally. Of all MSRP participants between 1991 and 1996, as of 2008, 36% were in pediatrics, and a remarkable 29% were in academic pediatrics.

Antifreeze proteins (AFPs) are extremely efficient at inhibiting ice recrystallization in frozen solutions. Knight and Duman [Knight, C. A. \\& Duman, J. G. (1986) Cryobiology 23, 256-263] have proposed that this may be an important function of the proteins in freeze-tolerant organisms. We have tested this proposal in vitro by characterizing the influence of AFP on the recovery of cryopreserved cells, which often can survive cooling and yet subsequently be damaged by ice crystal growth during warming. Relatively low concentrations (e.g., 5-150 μg/ml) of winter flounder (Pseudopleuronectes americanus) AFP enhance survival of red blood cells cryopreserved in hydroxyethyl starch solutions. This effect is most apparent in samples warmed at suboptimal rates, i.e., where ice recrystallization would be exaggerated. Cryomicroscopy demonstrates that AFP inhibits ice recrystallization in the extracellular regions during the latter stages of the warming cycle. AFP concentrations that enhance survival of red cells confer partial inhibition of recrystallization. Relatively high concentrations of AFP (e.g., 1.54 mg/ml) are much more effective at inhibiting extracellular recrystallization. However, extensive growth of ice around the cell, and concomitant cell damage, is noted. The mechanism for this AFP-induced ice growth is unknown. We propose that there is a delicate balance between AFP-induced enhancement of cell preservation and AFP-induced enhancement of cell damage and that this balance hinges on the degrees of inhibition of ice recrystallization and of preferential growth of ice around the cells. We conclude that, under appropriate conditions, one of the proposed functions of AFPs in nature can be emulated, and perhaps have application, in cryopreservation of materials of biomedical interest.

Background: At birth, the majority of neonates born at <30 weeks of gestation require respiratory support to facilitate transition and ensure adequate gas exchange. Although the optimal approach to the initial respiratory management is uncertain, the American Academy of Pediatrics endorses noninvasive respiratory support with nasal continuous positive airway pressure (nCPAP) for premature neonates with respiratory insufficiency. Despite evidence for its use, nCPAP failure, requiring intubation and mechanical ventilation is common. Recently, investigators have described a novel method to deliver bubble nCPAP, termed Seattle-PAP. While preclinical and pilot studies are encouraging with regard to the potential value of Seattle-PAP, a large trial is needed to compare Seattle-PAP directly with the current standard of care for bubble nCPAP (Fisher Paykel-CPAP; FP-CPAP). Methods: We designed a multicenter, non-blinded, randomized controlled trial that will enroll 230 premature infants (220/7 to 296/7 weeks of gestation). Infants will be randomized to receive Seattle-PAP or FP-CPAP. The primary outcome is respiratory failure requiring intubation and mechanical ventilation. Secondary outcomes include measures of short and long-term respiratory morbidity and cost effectiveness. Discussion: This trial will assess whether Seattle-PAP is more efficacious and cost effective than FP-CPAP in real-world practice among premature neonates. Trial Registration: This trial has been registered with the United States National Library of Medicine (www.clinicaltrials.gov, Trial Identifier #NCT03085329). Registered on 21 March 2017.

Some reports in the literature have suggested that endotracheal intubation may increase the risk for chronic lung disease (CLD) in preterm infants. Stern and co-workers noted that bronchopulmonary dysplasia (BPD) was rare in infants ventilated using negative-pressure respirators and concluded that, in addition to exposure to high oxygen, chronic lung disease in infants required exposure to positive pressure or an endotracheal tube (1). More recently, in a retrospective study of nursery practices, Avery and co-workers found that the incidence of chronic lung disease appeared to be lowest in intensive care units that relied on nasal application of continuous positive airway pressure (NCPAP), rather than endotracheal intubation (2). Although there are multiple ways in which endotracheal intubation might contribute to chronic lung disease in infants, this chapter will concentrate on two:1. Interference with normal warming and humidification of inspired gas by the nose and upper pharynx2. Increased risk of aspiration210 Gomez and HansenBecause there is a considerable amount of information about the first of these, warming and humidifying inspired gas, much of this chapter focuses on this important issue.

In 1971, Sinha et al. described a patient with isochromosomes arising from a C-group autosome. This patient had the phenotypic appearance of C-trisomy mosaicism. Six years later she presented with complaints of polydipsia and polyuria and was documented to have nephrogenic diabetes insipidus and renal tubular acidosis. The abnormal cell line of the patient had disappeared at the time of this observation.