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Your idea of modulating growth factors that play a significant role in the pathogenesis of retinopathy of prematurity (ROP) is an intriguing one. As these growth factors and various cytokines play an extremely important role in early development of the fetus, and later in the neonate, how do you propose inhibiting their function at one site alone?
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Dr Saugstad: Yes, this issue is very complicated and we should not start using these factors now. However, the fascinating thing is, we understand more of the pathogenesis now and we have another option to consider. At present this is only a theoretical possibility.
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How much weight do you put on the role of Vitamin E in ROP?
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Dr Saugstad: The slide I showed on Vitamin E was a meta-analysis. Vitamin E has not gotten much attention in the neonatal community, although Cochran's review concluded that Vitamin E has a beneficial effect on ROP.
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The lower limit of oxygen saturation in one of the studies in your presentation was 83 to 89%. Do you have any information on their neurological outcomes?
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Dr Saugstad: The lower limit suggested in that study by Dr Tin was 83 to 89%. They have published 18-month outcomes from their observational study showing no increase in cerebral palsy or neurodevelopmental delay at 18 months. We really need randomized trials to test this hypothesis regarding optimal saturation in premature infants.
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I have concerns about fluctuating the arterial partial pressure of oxygen (PO2) in the delivery room during resuscitation of premature babies from 20 to several hundreds when we use 100% oxygen. Do you have any evidence on the impact of resuscitation with 100% oxygen and ROP?
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Dr Saugstad: We have no data on ROP and resuscitation. I suspect that using 100 or 80% in premature babies is worse than using it in term babies.
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You said that surfactant can be given in the condition of acute respiratory distress syndrome (ARDS), caused by pulmonary hemorrhage, but can't surfactant cause the condition to worsen? When is a good time to give surfactant?
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Dr Ramanathan: Surfactant treatment does not worsen pulmonary hemorrhage in premature babies, except in a subpopulation of males under 750 g and one with air leaks. If the infant develops pulmonary hemorrhage, the surfactant is inactivated by fibrinogen and protein in the blood. In this situation, increase the positive end-expiratory pressure (PEEP), suction as much blood as possible, and give a bolus of surfactant. Otherwise, you may have to use much higher ventilator pressures or switch the baby to an oscillator.
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Dr Speer: I would also suggest giving a higher dose of surfactant, maybe 200 mg/kg. This is needed as you have to overcome the inactivation and the inhibition of the surfactant system. Experimental data in meconium is indicative of this happening. This can be translated to serum and other inhibitor protein that can inactivate surfactant.
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What is the prevalence of the use of surfactant and extubation to continuous positive airway pressure (CPAP) in the United States? Also, what is the prevalence of reintubation after extubation to CPAP?
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Dr Ramanathan: If you look at the Columbia data, 100% of the babies are either extubated or never get intubated and stay on CPAP. The trend is toward early surfactant therapy and extubating as soon as possible. In Columbia, 73% of the babies less than 1250 g are managed only on CPAP, without intubation. The post extubation failure rate is 30 to 50%. Extubating to CPAP or nasal ventilation lowers that rate to <10%.
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Would you comment on the effectiveness of treating the mother with infection? What are you doing in your own nursery to reduce chronic lung disease?
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Dr Speer: There is good evidence showing that if you reduce the risk of infection you also reduce the risk of bronchopulmonary dysplasia (BPD). We are not fast enough or courageous enough to achieve this, which could avoid pulmonary inflammation and infection. We do not use corticosteroids except in life-threatening situations. This is very different from the practice 3 years ago. Babies now spend more time on oxygen and we try to keep their saturation in the lower ranges. It is very difficult to convince the nurses to do this. We do not use vitamin A. We do not give erythromycin routinely or prophylactically. Studies have shown that babies who have urea plasma infection have structural changes. By the time we have detected the bug, it may be too late to treat. This may be one of the reasons why all the meta-analysis has not shown any benefit in BPD reduction.
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Dr Ramanathan: It is very dangerous to resuscitate the baby without PEEP in the delivery room. Most units do not use PEEP in the delivery room. Resuscitation without PEEP may collapse the lung during resuscitation and harm the lung very early. We use gentle resuscitation with PEEP and extubate the infant as early as possible. Babies spent an average of seven days on the ventilator 10 years ago. Now, it is about 2 days. We extubate to CPAP very early and start feeds early.
Your idea of modulating growth factors that play a significant role in the pathogenesis of retinopathy of prematurity (ROP) is an intriguing one. As these growth factors and various cytokines play an extremely important role in early development of the fetus, and later in the neonate, how do you propose inhibiting their function at one site alone?