Vivek Narendran

Early CPAP versus surfactant in extremely preterm infants

BACKGROUND 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. METHODS 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). RESULTS 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. CONCLUSIONS The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.)

Target ranges of oxygen saturation in extremely preterm infants.

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 lower-oxygen-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.)

Vernix Caseosa in Neonatal Adaptation

OBJECTIVES:To characterize vernix caseosa in newborn infants with respect to factors that influence vernix distribution on the skin surface, vernix effects on thermal stability, skin hydration, acid mantle development, and vernix antioxidant properties.STUDY DESIGN:Vernix distribution was determined for 430 infants. Thermal stability was assessed in parallel groups following vernix retention (n=66) and removal (n=64). The effects of vernix retention on skin hydration, pH, erythema, and dryness/scaling were determined. Samples were analyzed for vitamin E before and after UV exposure.RESULTS:Vernix distribution depended upon gestational age, delivery mode, gender, race, and meconium exposure. Retention had no effect on axillary temperatures. Skin hydration was significantly higher for vernix-retained skin. Skin pH and erythema were significantly lower with retention. Vitamin E levels were decreased by ultraviolet radiation.CONCLUSIONS:Vernix is a naturally occurring barrier cream with multiple salubrious effects, which support its retention on the skin surface at birth.

Interaction Between Pulmonary Surfactant and Vernix: A Potential Mechanism for Induction of Amniotic Fluid Turbidity

The development of amniotic fluid turbidity during the third trimester is a known marker of fetal lung maturity. We hypothesized that this turbidity results from detachment of vernix caseosa from the fetal skin secondary to interaction with pulmonary-derived phospholipids in the amniotic fluid. To test this hypothesis, we exposed vernix to bovine-derived pulmonary surfactant over a physiologically relevant concentration range. Ten milligrams of vernix was evenly applied to the interior walls of 1.5-mL polypropylene microfuge tubes. Surfactant phospholipids were added to the tubes followed by slow rotation at 37°C overnight. The liquid was decanted and spectrophotometrically analyzed at 650 nm to detect solution turbidity due to vernix detachment and/or emulsification. Increasing concentrations of surfactant phospholipids produced a dose-dependent increase in solution turbidity. A phospholipid mixture closely approximating natural pulmonary surfactant but devoid of surfactant-associated proteins yielded no increase. In other studies, the flow properties of vernix were studied in a Haake flow rheometer at 23°C and 37°C. There was a marked temperature-dependent effect with lower stress required to elicit flow at 37°C compared with 23°C. This temperature dependence was also demonstrated in the turbidity assay with a 124% increase in turbidity at body temperature compared with room temperature. We conclude that under in vitro conditions, pulmonary surfactant interacts with vernix resulting in detachment from a solid phase support. We speculate that in utero, this phenomenon contributes to the increase in amniotic fluid turbidity that is observed near term.

Biomarkers of epidermal innate immunity in premature and full-term infants.

Epidermal innate immunity is a complex process involving a balance of pro- and anti-inflammatory cytokines, structural proteins, and specific antigen presenting cells occurring against a background of neuroendocrine modulators such as cortisol. In this study, a multiplex array system was used to simultaneously determine multiple molecular factors critical for development of epidermal innate immune function from the skin surface of premature and term infants, healthy adults, and vernix caseosa. Samples were analyzed for Keratin 1,10,11, Keratin 6, involucrin, albumin, fibronectin and cortisol, and cytokines IL-1, TNFα, IL-6, IL-8, MCP1, IP10, IFNγ, and IL-1 receptor antagonist. Keratin 1,10,11 was decreased and involucrin was increased in infants versus adults. All infants had elevated IL1α and reduced TNFα versus adults. IL-6, IL-8, and MCP1 were significantly increased in premature versus term infants and adults. Skin surface cortisol and albumin were significantly elevated in premature infants. The biomarker profile in premature infants was unique with differences in structural proteins, albumin, and cytokines IL-6, IL-1β, IL-8, and MCP1. The higher infant IL1α may be associated with skin barrier maturation. The significant elevations in skin surface cortisol for preterm infants may reflect a neuroendocrine response to the stress of premature birth.

Economic Recession and Headache-Related Hospital Admissions

Abstract Incidence of headaches across different regions and its relationship to unemployment rates in the United States before and during an economic recession was evaluated. Years 2008 and 2009 were determined as recessionary period. Headache-related admissions, particularly the uncomplicated headaches, increased significantly during recession. Proportion of women with headaches has increased and the age group of 25–54 years was the most affected during the recession. The hospital charges have increased even though the average length and charge of stay decreased. These findings are consistent with our understanding of effects of stress and unemployment on psychological and physical health.

Morphological Characterization of Human Vernix: Analysis of Water Content and Comparison to Native Stratum Corneum

Morphological Characterization of Human Vernix: Analysis of Water Content and Comparison to Native Stratum Corneum

Contents Vol. 24, 2011

N. Ahmad, Madison, Wisc. P. Altmeyer, Bochum C. Antoniou, Athens H. Bachelez, Paris J.M. Baron, Aachen E. Benfeldt, Roskilde E. Berardesca, Rome D.R. Bickers, New York, N.Y. I. Bogdan Allemann, Zürich K. De Paepe, Brussels P. Elsner, Jena A. Farkas, Szeged A. Giannetti, Modena M.W. Greaves, London R.H. Guy, Bath J. Hadgraft , London E.M. Jackson, Bonney Lake, Wash. Y. Kawakubo, Chiba H.-C. Korting, Munich J. Krutmann, Düsseldorf R. Neubert, Halle D.R. Roop, Aurora, Colo. T. Ruzicka, Munich M. Schäfer-Korting, Berlin S. Seidenari, Modena J. Wohlrab, Halle S. Yamamoto, Hiroshima Journal of Pharmacological and Biophysical Research

Neonatal Morbidities of Prenatal and Perinatal Origin

The nature of obstetrics clinical practice requires consideration of two patients: mother and fetus. The intrinsic biological interdependence of one with the other creates unique challenges not typically encountered in other realms of medical practice. Often there is a paucity of objective data to support the evaluation of risks and benefits associated with a given clinical situation, forcing obstetricians to rely on their clinical acumen and experience. Family perspectives must be integrated in clinical decision making, along with the advice and counsel of other clinical providers. This chapter reviews how to best utilize neonatology expertise in the obstetric decision-making process.