Transcription:
Apnea of Prematurity- Management

Dr. Julie Weiner:  Hello everyone. And welcome back to our podcast for today. This is Neonatal Review: Isolette to Crib. The purpose of this podcast is to review high-yield common topics in neonatology. While our focus is geared towards the perinatal neonatal boards, anyone learning or studying neonatology will find this podcast helpful.

I will be one of your hosts for this podcast. I am Dr. Julie Weiner, one of the neonatologists and current Medical Director for the NICU at Children's Mercy Hospital in Kansas City, Missouri. We're located here in the Heartland. So thank you for joining us today.

To help prepare for boards, we have a collection of neonatologists to help us along the way. All have either passed boards, been there, done that, or are currently studying for boards, same boat as you. Today, we are going to be joined again by Dr. Joti Sharma, who will be the other host for this podcast. She is the Fellowship Program Director here at Children's Mercy Hospital. Tell everybody hi, Dr. Sharma.

Dr. Jotishna Sharma: Hello!

Dr. Julie Weiner: She is joining us again today to talk about the management of apnea of prematurity and what we need to know. So hopefully everybody refilled their big cup of caffeine, so just keep breathing and here we go.

So Dr. Sharma, do you want to get us started talking about how do we manage apnea of prematurity?

Dr. Jotishna Sharma: Yes, Dr. Weiner, we'll talk about the management of apnea of prematurity today. One of the important aspects before we jump into the management is the monitoring of infants who have apnea. So let's talk about that first. As all of us who work in the NICU, monitoring is a common practice in our NICUs. And it is generally agreed that for infants who are less than 35 weeks gestation, they should be monitored for apnea due to the high prevalence of apnea in this group.

In most NICUs, cardiac monitors, pulse oximeters are used to monitor the apnea and associated bradycardia and hypoxemia. Some centers actually do use impedance pneumography, but I just want to talk a little bit about that because the accuracy of pneumography is limited by movement artifacts and the inability to detect obstructive apneic episodes. Therefore, it is not recommended to be used as the sole technique.

Dr. Julie Weiner: So Dr. Sharma, as we know, there's a lot of variability that can be normal with heart rate and oxygen levels. Is there a standard threshold settings for monitors?

Dr. Jotishna Sharma: Dr. Weiner, while there are no established data on the optimal threshold settings to determine significant apneic events, we do have widely accepted common thresholds that we use. And the most commonly used thresholds are apnea more than or equal to 20 seconds, heart rate less than or equal to 100 beats per minute and actually, for convalescing pre-term infants, you can use heart rate less than or equal to 70 to 80 beats per minute, and oxygen saturation less than 85%. So these three parameters are usually the common threshold settings that are used on the monitors.

Dr. Julie Weiner: Thank you. That helps us kind of have an idea what settings and monitoring is needed for these infants. So let's move on to discussing treatment. So when do you treat apnea of prematurity?

Dr. Jotishna Sharma: Yes, Dr. Weiner. It's usually difficult to decide which patient needs treatment and which we can just kind of need to observe. So for treatment of apnea of prematurity, there are two different scenarios. One is apneic spells that are frequent, prolonged or associated with bradycardia and oxygen desaturation. Or the second scenario is when the infant requires intervention with bag mask ventilation or has multiple episodes needing tactile stimulation. What's important to realize is that therapy often is needed for several weeks until the apnea resolves as the respiratory control of the infant matures.

Dr. Julie Weiner: Since we know who to treat, what are some of the treatment options? How do we treat it?

Dr. Jotishna Sharma: So the management or the treatment of apnea of prematurity is a combination of three factors. One is the general supportive measures that reduce their risk of apnea or its associated hypoxemia, number two is nasal CPAP and number three is methylxanthine therapy. It's only when these three treatment fails then we intervene with intubation and mechanical ventilation.

Dr. Julie Weiner: Will you discuss a little more about the general measures or supportive treatment that you discuss for apnea of prematurity?

Dr. Jotishna Sharma: It's so important to realize that the general supportive measures are usually preventive in nature and they are the most common entities that we use to take care of our preemie babies in the NICU. And the intervention should be directed towards eliminating factors that, one, increase the risk of apnea and, two, reduce the prevalence of associated hypoxia. So supportive measures include the environmental temperature control, head and neck position, maintenance of nasal patency and oxygen supplementation.

Dr. Julie Weiner: Thank you for that. Dr. Sharma. Will you just take us into a little bit more depth into these general measures?

Dr. Jotishna Sharma: So Dr. Weiner, as I mentioned, four general measures important for the care of any preterm infant. So environmental temperature control is very important because you need to provide a stable environment which eliminates temperature fluctuations that precipitate apneic episodes. Therefore, most of our preemie babies either need to be in an incubator for the extreme preemies or in servo-controlled radiant warmers.

The second entity, neck and head position is very important for maintenance of the upper airway. Therefore, avoiding extreme flexion or extension is important.

Maintaining nasal patency. Again, we should always prevent vigorous sectioning and prolonged use off nasogastric tubes. It is also important to avoid continued hypoxemia. Therefore, some of these babies will need oxygen supplementation to keep their sats around 90 to 95%.

Now, the last thing that we need to consider is that if you have a patient, even if they are a preterm infant with continued apnea, you still need to consider underlying causes for the onset of apnea, is neonatal sepsis. That's something that we should always think about.

Dr. Julie Weiner: So when the supportive treatment is failing or not helping with apnea of prematurity, a lot of times we'll use nasal CPAP for treatment. Can you just walk us through how that helps or works in relation to apnea of prematurity?

Dr. Jotishna Sharma: Nasal CPAP is very helpful and it actually does help decrease apneic spells. And it does this by, one, decreasing the incidence of mixed and obstructive apnea. It maintains the functional residual capacity and it also alters the timing of breathing in preterm infants. It's thought that CPAP is effective through splinting the pharyngeal airway with positive pressure, which decreases the upper airway collapse and obstruction.

Nasal CPAP decreases respiratory rate through prolongation of expiratory time without altering the ventilatory response to carbon dioxide. And CPAP also increases oxygenation by improving the V/Q matching and provides continuous distending pressure that optimizes the functional residual capacity.

Dr. Julie Weiner: So Dr. Sharma, now that you've walked us through how CPAP helps with apnea of prematurity, when do you make that decision to use nasal CPAP for treatment?

Dr. Jotishna Sharma: So, as I mentioned earlier, the supportive measures are always your first line. And if those fail, then you should consider nasal CPAP for preterm infants who are having clinically significant apneas with continued oxygen desaturation with or without bradycardia. But you also have to remember that most of these preterm infants may already need CPAP for other reasons such as respiratory distress syndrome.

Usually, the CPAP is initiated around 4 to 6 centimeters of water pressure. So in practice, some clinicians may increase CPAP pressure in an attempt to optimize the functional residual capacity based on estimating lung volume on chest x-ray. But many of these infants have good lung compliance and pressures above 8 centimeters may overdistend the lungs and impair circulatory function. It's also important to note that data are lacking for practice of increasing CPAP to optimize functional residual capacity.

Dr. Julie Weiner: So what I take is CPAP may be helpful, but we just have to be mindful on how high the pressures that we're using. So are there other respiratory interventions that may also be useful for the treatment of the apnea of prematurity?

Dr. Jotishna Sharma: Yes. CPAP of above 8 will not be beneficial. So moving on, yes, there are other non-invasive modes of respiratory support that we can provide for apnea of prematurity. And the two that I think most centers use are the humidified high-flow nasal cannula. And again, it's important to note that while high-flow nasal cannula is an effective method to provide oxygen supplementation and deliver CPAP and it does minimize the patient discomfort, but we do have to realize that high flow through nasal canula may provide unpredictable levels of CPAP. So I think that's something important to realize.

The other method of noninvasive support that can be provided is noninvasive positive pressure ventilation, which basically just augments your CPAP. And if all else fails, then you may consider mechanical ventilation.

Dr. Julie Weiner: Okay, now that we've talked about kind of supportive measures to prevent apnea of prematurity and we've talked about some respiratory strategies for apnea of prematurity, let's move on and talk a little bit about pharmacological therapies. Can you tell us a little bit more about caffeine? I mean, I know I really love my caffeine, but can you tell us how this helps the babies?

Dr. Jotishna Sharma: Yes. And we always ask the question, "Is the baby caffeinated?" Isn't that what we always do?

Dr. Julie Weiner: Yes. And we may need to ask all the attendings to make sure we're all a little caffeinated.

Dr. Jotishna Sharma: Yes, that's true too. So before we discuss caffeine, I just wanted to talk about the methylxanthines in general. So methylxanthines are the primary pharmacological therapy for treatment of apnea of prematurity. The two methylxanthines that I use for treatment of apnea are caffeine and theophylline. Caffeine is not the preferred drug of choice and it is the one that's almost exclusively used now. And this is due to his longer half-life, wider margin of safety and less adverse effects. Methylxanthines work through inhibition of the adenosine receptors centrally.

Dr. Julie Weiner: So you mentioned methylxanthines work through inhibition of adenosine receptors centrally. Can you talk a little bit more about its mechanism of action?

Dr. Jotishna Sharma: So adenosine is an inhibitory neuromodulator of the respiratory drive. The main mechanism of action of caffeine and essentially all methylxanthines is the inhibition of the adenosine receptors in the central nervous system. So blockage of the adenosine receptors by caffeine results in, one, improved respiratory drive; two, increased ventilatory responsiveness to carbon dioxide; three, reversal of central hypoxic depression of breathing; four, enhanced diaphragmatic contraction; five, leading to increased minute ventilation; and six, it does improve the pharyngeal muscle tone. All these ultimately leads to resolution or prevention of apneic events.

Dr. Julie Weiner: So, can you talk a little bit about the impact of caffeine on the action of apnea of prematurity kind of in clinical practice? And how we've moved to really starting at for every baby less than 28 to 32 weeks to prevent or treat the apnea of prematurity?

Dr. Jotishna Sharma: Yes, that's correct, Dr. Weiner. And we'll talk more about it in just a little bit later. But I wanted to tell you, did you know that when we give a loading dose of caffeine citrate at 20 milligrams per kg intravenously within five minutes, your central respiratory drive, it increases. Well, that's what happens in babies.

Dr. Julie Weiner: I did not know that. So what I'm hearing is to get your biggest bang, we need some IV caffeine.

Dr. Jotishna Sharma: Well, I won't recommend that for us. No. Because I know there are some of us who would want to do that.

So there was a study of 51 preterm infants with a gestational age of 29 weeks. Two hours after caffeine administration, they found that there was increased cerebral cortical activity, decreased transcutaneous carbon dioxide and increase in the mean arterial pressure, which is just interesting after two hours of off caffeine therapy, Caffeine also reduces the effects of hypoxia on the perinatal white matter injury. And it is thought that this effect is because of its ability to inhibit pro and anti-inflammatory factors, which is mediated by adenosine receptor subtypes.

Dr. Julie Weiner: So, are there any other data on the effectiveness on methylxanthine therapy?

Dr. Jotishna Sharma: Yes, Dr. Weiner. Several trials have established that methylxanthines both caffeine and theophylline are effective in the treatment of apnea of prematurity. Actually in 2010, there was a systematic review which included five trials, I think three were caffeine trials and two were theophylline trials that studied the short-term effects of methylxanthine therapy. And it demonstrated that patients treated with methylxanthines compared to those who received placebo were less likely to have apneic episode and require assisted 2entilation.

Dr. Julie Weiner: So I know in the early 2000, there was a big trial that looked at caffeine for apnea of prematurity or the CAP trial. Can you talk a little bit about that?

Dr. Jotishna Sharma: So the CAP trial was a randomized control trial of about 2000 preterm infants with birth weights between 500 to 1250 grams. And they reported no differences in the rate of death, abnormal brain ultrasound and necrotizing enterocolitis between the treated and control groups. However, this is important. Caffeine therapy was associated with reduced risk of PDA ligation and bronchopulmonary dysplasia. It also led to earlier discontinuation of supplemental oxygen and a lower age at the time of last endotracheal tube use, in other words earlier extubation.

Dr. Julie Weiner: So it sounds like that trial showed some pretty important findings related to caffeine. Did it report anything else?

Dr. Jotishna Sharma: So there was actually a followup report of the CAP trial, and they also revealed a few important findings. For infants who required positive pressure ventilation, caffeine benefit was associated with shorter duration of mechanical ventilation compared with placebo. The earlier discontinuation of positive pressure support with caffeine indirectly suggests a decrease in the frequency of apnea. The reduction of bronchopulmonary dysplasia suggests that caffeine might have a preventive role in the development of this disorder.

Dr. Julie Weiner: So with these dramatic findings from the CAP trial and the benefit of caffeine, is that why we've moved into some prophylactic treatment with caffeine?

Dr. Jotishna Sharma: You are correct, Dr. Weiner. So given the safety profile of caffeine and after the CAP trial, it has become common practice now that we give prophylactic caffeine therapy to our extremely low birth weight babies or infants who are less than 28 weeks of gestation to avoid intubation and mechanical ventilation or to enhance extubation.

Dr. Julie Weiner: Is there any kind of data or literature that helps support prophylactic use of caffeine?

Dr. Jotishna Sharma: So there is this large retrospective study that came out from the Canadian Neonatal Network of infants less than 29 weeks gestation. And what they did was they compared early administration of caffeine that is within the first two days of life with late administration of caffeine greater than three days of life, 75% of these patients actually received early caffeine.

When they did multi-variate analysis, they found that infants in the early caffeine group had a small, but statistically significant lower risk of a composite outcome of death or BPD. However, most of this effect was due to a reduction in the incidence of BPD, as there was no difference in mortality. They also found that the early caffeine group had less PDA and were less likely to undergo surgical intervention for PDA. There was no difference in the necrotizing enterocolitis rates, severe neurological injury or retinopathy of prematurity.

They did a followup of this cohort at 18 to 24 months corrected age and they reported better neurodevelopmental outcome with early versus late administration of caffeine, supporting early use of caffeine. So this is some data that suggests actually early use of caffeine may have effect on the neurodevelopmental outcome. Having said that, I just want to note that actually there were two other studies that did not note any additional benefit of caffeine when it was given earlier.

Dr. Julie Weiner: So it sounds like caffeine has shown some real benefit. Can you discuss the side effects if there are any with caffeine and theophylline?

Dr. Jotishna Sharma: So the main adverse effects of methylxanthines, which includes caffeine treatment, is tachycardia. And again, this is less frequent with caffeine compared to theophylline. Theophylline can cause gastroesophageal reflux due to delayed gastric emptying, but this is not clinically significant. Methylxanthines increase the metabolic rate, but the long-term impact is unknown.

So in a study of metabolic rate and oxygen consumption, caffeine significantly increased oxygen consumption and energy expenditure. During the four-week study period, infants that received caffeine required a lower incubator temperature to maintain normal body temperature and had less weight gain with similar caloric intake than untreated patients.

Dr. Julie Weiner: Are there any long-term neurodevelopmental outcome studies with caffeine therapy?

Dr. Jotishna Sharma: So Dr. Weiner, the CAP trial does have some followup data, but it is limited. In their followup, the neurobehavioral outcome is not affected by caffeine therapy. Overall, similar cognitive outcome and academic performance between the two groups at age five and 11 years of age were noted, but neonatal caffeine therapy reduced rates of developmental coordination disorder at five years of age and motor impairment at 11 years of age.

The caffeine treated group at 11 years of age performed better than the control group on tests for fine motor coordination, visual motor integration, visual perception, and visual-spatial organization. So this data supports the long-term safety and potential efficacy of caffeine therapy for apnea of prematurity. The neurodevelopmental outcome at 18 to 24 months corrected age is better with early versus late administration of caffeine. Again, the CAP trial also suggests that caffeine therapy may have some impact on Better neurodevelopmental outcome.

Dr. Julie Weiner: Dr. Sharma, you mentioned a little earlier that caffeine is the preferred treatment over theophylline. Can you discuss the reason for this?

Dr. Jotishna Sharma: Caffeine has therapeutic advantages over theophylline for several reasons. One, it has a longer half-life ranging from 60 to 100 hours. Caffein can be given once daily instead of the more frequent dosing for theophylline. Also it's enteral absorption is more reliable and it has a wide therapeutic index, which minimizes the side effects. Monitoring serum levels is generally not required for caffeine as opposed to theophylline.

The systematic review in 2010, which I had mentioned earlier, reported similar rates of reduction of apnea and bradycardia during the first week between caffeine and theophylline. Adverse reactions were lower in the group treated with caffeine compared to theophylline in the systematic review. Therefore, now, caffeine has become the preferred methylxanthine for the treatment of apnea of prematurity.

Dr. Julie Weiner: Okay. So now we know that caffeine is the drug of choice for apnea of prematurity. Can you just tell us a little bit more about its use?

Dr. Jotishna Sharma: So, as I mentioned, it's the preferred prophylactic agent to prevent apnea of prematurity due to it's longer half-life, wide safety margin and lower frequency of adverse effects. The initial dose is a loading dose of 20 milligrams per kg of caffeine citrate, which is equivalent to 10 milligrams per kg of caffeine base. You can give it either intravenously or enterally. The daily maintenance dose is 5 to 10 milligrams per kg per dose, which again is equivalent to 2.5 to 5 milligrams per kg of caffeine base, which should be started 24 hours after the loading dose. And it again can also be given either intravenously or enterally.

The efficacy and safety of higher doses are unknown. I think it's also important to note that additional postnatal increased dosing after the first week of therapy may be needed due to the faster metabolism with advancing maturation.

Dr. Julie Weiner: So since people's tolerance and excretion of caffeine differs, is there any need to monitor caffeine levels?

Dr. Jotishna Sharma: So routine measurement of serum caffeine concentration is not necessary. Drug levels are usually only measured if there are concerns for toxicity, because as I mentioned earlier, it has a wide therapeutic margin and the dose-response relationship has not been established. The steady state concentration of caffeine is attained about five to seven days after starting therapy. The therapeutic trough serum concentration is about 5 to 25. So routine caffeine levels is of no benefit in clinical practice.

Dr. Julie Weiner: Okay. So now that we know caffeine works. We've started it on our patient, the apnea has resolved. How do know when it's time to stop the caffeine?

Dr. Jotishna Sharma: Very important question. So basically, the data is lacking for when to discontinue caffeine therapy. In practice, usually based on the natural cause of apnea of prematurity, most clinicians will discontinue caffeine when the patient reaches a postmenstrual age of about 32 to 34 weeks gestation and there are no apneic episodes requiring intervention for approximately five days.

Important to remember it takes about seven days for caffeine to be eliminated from the system. Therefore, cardiorespiratory monitoring is continued until the infant is discharged home because the mean half-life of caffeine is approximately 87 hours at 35 weeks postmenstrual age. Also important to remember that caffeine really needs to be re-instituted. But if there are frequent episodes of apnea, bradycardia, and oxygen desaturation or if the infant requires intervention with a bag and mask, caffeine therapy may be restarted.

Dr. Julie Weiner: Okay, Dr. Sharma. I want to broach a little bit different, difficult topic for the NICU. The relationship between gastroesophageal reflux and apnea of prematurity, can you comment on this?

Dr. Jotishna Sharma: You are correct. At the bedside, this is a common concern, right? Usually, we are asked to start antireflux medications. But evidence suggests that gastroesophageal reflux is not associated with apnea of prematurity and treatment of presumed or proven gastroesophageal reflux solely for the reduction in apnea events is not supported by current available evidence. So that's important to remember.

Dr. Julie Weiner: Thank you, Dr. Sharma, for that clarification. Now, while we're talking about controversies or related topics on apnea of prematurity, can you address if there's any effect of blood transfusions on apnea of prematurity?

Dr. Jotishna Sharma: Yes, this is another controversial topic that comes up in the NICU. In 2012, they continuously monitored 67 preterm infants for apnea, bradycardia and oxygen desaturation. And they found that patients had decreased apnea for three days after a blood transfusion compared to three days before. The author has also noted that the probability of an apnea event in a 12-hour period was higher with a lower hematocrit adjusted for postmenstrual age.

So these results suggest that anemia may increase the likelihood of apnea of prematurity and that blood transfusions may result in a short-term reduction in apnea. Again, there is no data to indicate that blood transfusion results in any long-term reduction in apnea.

Dr. Julie Weiner: Thank you for that clarification, Dr. Sharma. Okay, back to our preterm infant, who is now older and better and is ready for discharge. Is there any considerations for this infant with the history of apnea of prematurity that we need to consider before sending him home or her?

Dr. Jotishna Sharma: So Dr. Weiner, I think the question in this kind of scenario usually comes up is the question of home monitoring. So home cardiorespiratory monitoring is not needed for infants who are otherwise ready for discharge and free of any episode of apnea, bradycardia or oxygen desaturation for more than five to seven days as the risk of subsequent clinically significant apnea is very low.

Dr. Julie Weiner: How about if caffeine had just been discontinued, do we need to watch for a little bit after we stopped caffeine?

Dr. Jotishna Sharma: So if caffeine has only recently been discontinued, it is generally advised that the infant not be discharged home unless there is an event-free period of about seven days. This allows caffeine to be either eliminated or reach low subtherapeutic levels given its long half-life.

Dr. Julie Weiner: Are there discharge criteria for infants with a history of the apnea of prematurity?

Dr. Jotishna Sharma: Dr. Weiner, there are no standard discharge criteria. Brief isolated bradycardic episodes that spontaneously resolve and are feeding-related events that resolve with interruption of feeding are common in convalescent preterm infants and generally should not delay discharge.

Discharge criteria does vary by center. Most centers will wait until the infants are free of apnea and off caffeine therapy before discharge, while some centers do discharge patients home with cardiorespiratory monitoring with or without caffeine. It's important to know that if an infant is to be monitored at home, prior to discharge, all parental teaching should take place and they should be able to demonstrate proficiency in managing the monitor, providing appropriate intervention in an event with stimulation and performing cardiorespiratory resuscitation. Most home monitors, they can be discontinued around 43 to 44 weeks postmenstrual age.

Dr. Julie Weiner: Thank you, Dr. Sharma. So now that we've walked through the management of apnea of prematurity, can you just summarize or sum up what we've been talking about on this podcast so far?

Dr. Jotishna Sharma: Yes, Dr. Weiner, we did cover a lot of aspects of the management of apnea of prematurity and I'll try to summarize it. So initial cardiorespiratory monitoring is provided for all infants admitted to the NICU due to the risk for apnea. The management is a combination of general supportive measures, nasal CPAP and xanthine therapy with caffeine. If these treatment options fail, then we may require to intubate and provide mechanical ventilation.

The general and supportive measures should be focused on eliminating factors that increase the risk of apnea and this include a stable environmental temperature, nasal patency, avoiding extreme neck flexion or extension, and identifying any underlying causes such as sepsis.

Nasal CPAP reduces the risk of upper airway collapse and obstruction and increases oxygenation. For medical treatment of apnea of prematurity, caffeine is the preferred agent because of its long a half-life, wider margin of safety and lower incidence of side effects. Early prophylactic caffeine therapy within the first two days of life can be used for extremely low birth weight infants to avoid intubation and mechanical ventilation or to facilitate early extubation.

If a preterm baby has been on caffeine, you should consider discontinuation around 32 to 34 weeks for infants who have a five-day apnea-free period.

A little summary on discharge readiness. A clinically significant apnea-free event period before discharge is about five to seven days, but it varies by center. Infants have complete resolution of apneic events by 43 to 44 weeks gestational age.

Dr. Julie Weiner: Dr. Sharma, thank you for that summary. Now, to wrap up, let's go through a couple of questions to test our knowledge.

Dr. Jotishna Sharma: So I think we have two questions. The first question is a seven-day old 33 weeks gestational age infant has developed increasing apneic spells. The following general supportive measures should be undertaken prior to initiation of other treatment, except, so the choices are A, vigorous nasopharyngeal suctioning; B, consideration for sepsis as a cause of increased apneic spells; C, avoidance of extreme flexion or extension of the neck; D, oxygen supplementation to maintain saturations around 90 to 95%.

Dr. Julie Weiner: Okay. I think I know the answer. Is it A?

Dr. Jotishna Sharma: You are correct, Dr. Weiner. It is A. So all of them are correct and you should not provide vigorous nasopharyngeal suctioning because they actually will end up with more edema of the airways. So yes, the correct answer except is A. And the other supportive measure is the environmental temperature control.

The next question is a two-day old 25 weeks gestation infant is on low mechanical ventilator settings and FiO2 of 21% is ready to be extubated and she was loaded with caffeine citrate at 20 per kg shortly after birth and was started on maintenance caffeine citrate at 8 per kg per day 24 hours ago. All the statements below are effects of caffeine in premature infants, except, so A, a randomized control trial has shown that caffeine therapy can reduce the risk of bronchopulmonary dysplasia; B, enhances diaphragmatic contraction; C, a randomized controlled trial has shown that caffeine therapy can reduce the risk of necrotizing enterocolitis; D, it causes reversal of central hypoxic depression of breathing.

Dr. Weiner, you want to take a guess, which is the correct answer in this case?

Dr. Julie Weiner: Yeah, I think if I remember right from when you were talking that caffeine actually showed no difference between the treatment and the control groups related to necrotizing enterocolitis. So I think C is the incorrect answer.

You are correct. Yes, it did

Dr. Jotishna Sharma: not show a difference with regards to death and necrotizing enterocolitis. It did reduce the risk of BPD, which I think is a great benefit to our extreme preterm infants.

Dr. Julie Weiner: I would agree. Thank you, Dr. Sharm, for leading us through all the things that we need to know about apnea of prematurity. Hopefully, this information will give you all a better understanding of apnea of prematurity. This is Neonatology Review: Isollete to Crib. I'm Dr. Julie Weiner. Thank you for listening.