What is apnea of prematurity and will it ever end?
Our ability to breathe regularly is something most of us take for granted. We owe this function to a tiny area in the brain located in the medulla oblongata.
This area of the brain sends signals via nerves to the lung telling it to breathe in and out on a regular basis. For a preterm infant or even term baby this means there should be about 40-60 breaths per minute. Preterm infants are at risk for these events due to being neurologically premature but also due to a difference in the responsiveness of such infants to carbon dioxide levels in the bloodstream. In term infants and throughout life we are very responsive to higher levels of carbon dioxide. We like to keep it pretty tightly controlled which is why if you hold your breath and your carbon dioxide levels rise you feel like you need to take a breath. In preterm infants this response is blunted.
Pauses in breathing are called apnea and when they occur in a preterm infant they are known as apnea of prematurity. These are usually defined as stoppage of breathing for 20 seconds or longer or if shorter there is bradycardia (<100 heart beats per minute), cyanosis (bluish color to the skin), or pallor. They are so common under 37 weeks that I consider them a normal part of the preterm journey. You can see how common it is in the figure below. We also know that they are far more common as gestational age decreases so that a 24 week gestation preterm infant will be far more prone to apnea than the 35 week counterpart.
Parents often wonder if these drops in oxygen or heart rate are harmful. If the events are called spontaneous it means that your infant recovers quickly from these events without anyone stimulating your baby and so they are brief. We tend not to worry about these types of events as they brain is not likely to be affected. When events are happening more than a few times a day and require your nurse to either stimulate your infant or require support with a bag and mask to help your baby breathe this is where we become more concerned. Even then the presence of bradycardia during these events is more concerning than the oxygen levels as the poor heart rate means less blood is going to the brain. It is hard though to determine exactly how many events a day are actually harmful but intuitively if they are happening more than a few times a day and needing support to recover this is where we usually think about treatment.
The treatment of choice is caffeine. The same drug that is present in your soft drinks or coffee. It works by stimulating that centre in the brain that I talked about above. There are different dosing levels but you will see doses anywhere form 2.5 mg/g/d to sometimes 8 mg/kg/d for those babies with very resistant apnea. Some of those kids may need CPAP (mask on the nose) or intubation and a ventilator if they just won’t breathe. The good news is that they will grow out of it as shown in the next figure.
Most of our babies have their caffeine stopped sometime after they have reached the equivalent of 33 weeks (eg. born at 26 weeks this would be 7 weeks later). On rare occasion babies right up to term will have apnea as shown in the graph and for those kids if they are feeding well and otherwise ready for discharge we may choose to send you home on caffeine. Those kids though will need a follow-up study called a sleep study that will typically be done about 4 weeks later and require your child to come back for the appointment.
Blog posts of interest on apnea
What is Chronic Lung Disease and why does it matter?
By now if you have a preterm infant in particular who has been born before 36 weeks you will have heard people talking about chronic lung disease (CLD). Sometimes they may also refer to it as bronchopulmonary dysplasia (BPD). The terms are really for all intents and purposes the same from a parent’s point of view. If you google CLD or BPD you may find stories of very cystic and damaged lungs with babies needing tracheostomies due to long term need for ventilation. While this can still happen, thankfully this new type of CLD we see is not like the one of old but rather is a newer entity that is more uniform and has less of a cystic nature. The “New BPD” is really more of a lung that has less air sacs (alveoli) than usual but the lung is less damaged than the BPD of old.
When your infant was born they may have had immature lungs without enough surfactant. Surfactant is kind of like the engine oil of a car. It helps to make the lungs less sticky and allows breathing to be a lot easier. Some babies are treated with CPAP while others need intubation and ventilation. While this positive pressure can be lifesaving, it also exacts a cost. We humans prefer to breathe using negative pressure meaning that we suck air into the lungs rather than have it pushed in. With each delivered breath the lungs of these fragile infants can be injured leading to the type of picture shown above.
This becomes a concern at 36 weeks. You may hear doctors talking about 36 weeks as if it is scary deadline that is on the horizon. We tend to obsess about that date. The big reason for this obsession is that units compare themselves across Canada and in other countries using the need for oxygen, nasal prongs, CPAP or ventilation at this time point. If your unit has a rate of CLD of 10% and another has 20% it tells the higher one that they better do something with their medical practice to lessen the incidence. In other words the 36 weeks is a marker.
As I have written about in another blog post, in 2020, 40 weeks may be the more relevant number as written in the post “The New BPD That Matters” the reality is that your baby is more likely to stay in hospital due to inability to feed orally or from apnea of prematurity. I am not saying that we as a team should not try and reduce the risk as much as possible for CLD but in case you were wondering what we are talking about when we talk about this condition this is it.
Blog posts of interest on CLD
What is this NEC that everyone keeps talking about?
If you have an infant in the NICU and they were born at less than 2500g you probably have noticed that we tend to feed these babies very slowly. As you descend into the very early gestational ages and see babies under 750g or 1250g we feed these babies even more slowly. You may have heard your nurse or doctor talk about MEF or minimal enteral feedings. Typically these feeds are about 1 ml/kg of body weight given every couple of hours. If you have a 1kg baby then that would be about 1 mL of milk every couple hours. This is done for about 3-5 days and really “feeding” is a bit of a misnomer as what you are really doing is trying to “prime the pump”. By exposing the newborn gut to small amounts of breastmilk this MEF is really designed to help the bowel adapt to what is coming which is larger volumes of milk. We prefer that this milk is from humans as opposed to cow’s as the bowel tolerates this type of nutrition far better.
Once we start increasing feedings it may seem like it takes forever to get to what we call full feeds. We tend to increase the amount of oral feedings by anywhere from 20 – 30 mL/kg/day until we reach somewhere between 150-165 mL/kg/day of milk intake. During this time you may hear about us using TPN which stands for total parenteral nutrition. This is a combination of fats, sugars and protein plus important vitamins and minerals that we have in a liquid form (yellow and creamy white) that we give your baby so they get what they need while awaiting their feeds to reach the full point. While it may seem like a long time, it is not by accident. What we are trying to avoid is a condition called necrotizing enterocolitis (NEC). NEC is typically diagnosed on an x-ray but more recently people are using ultrasound to identify it. It can present clinically in a variety of ways but the one that usually triggers us to think about NEC as a possibility is blood in the diaper. This may be related to an intolerance to cow’s milk protein but if it is NEC we may also see other signs such as a distended belly, pain when we push on it or changes in vital signs such as temperature fluctuations and fast heart rates. Some babies may also present with failure to breathe and have pauses that may initially be thought to be just apnea of prematurity. NEC fortunately is less common than many years ago but it still occurs with varying frequency in babies under 33 weeks for the most part. The Canadian Neonatal Network is a group of 32 NICUs in Canada and tracks a number of conditions with NEC being one. Here is how the different sites compare across the country. What you can see from the graph is that the incidence varies but is generally abut 4-5% or about 1 in 20 babies in the NICU under 33 weeks.
The simplest way to think of it is that the lining of the bowel on its innermost surface absorbs nutrition but also has a dual role of keeping bacteria in the gut space and not allowing any to get into the tissues of the bowel. If the lining breaks down and allows bacteria to get into the tissues then we have the start of NEC. If this progresses we can ultimately see gas being produced in the bowel wall on x-ray and sometimes this gas escapes into the circulation of the liver and you will hear someone talk about “portal venous gas”.
NEC is a serious condition that if caught early may heal up but even in those cases on occasion the tissue damage can be permanent and lead to dead (necrotic) bowel being removed. When this happens the healthy bowel is typically brought up to the surface of the skin and a plastic pouch applied to the skin to catch the intestinal contents. This allows for the portion of bowel in the belly to heal and at some point many weeks later the bowel will be reconnected.
What can we do to prevent NEC?
- slow advancement of feeds
- exclusive human milk diet
- probiotics may be beneficial
Posts about NEC
Why does my baby need ultrasounds of their brain?
Sometime between a week to two weeks you will hear that an ultrasound of your baby’s brain has been ordered. What the team is looking for here is bleeding eithre within the fluid filled chambers of the ventricles (appear black in the picture below with blood that shows up as white). This early ultrasound is meant to pick up this type of injury while one done a few weeks later attempts to pick something else up.
Bleeding occurs due to the fragile naure of the brain tissue when born preterm. The more preterm an infant is the greater the risk of a signficant amount of bleeding. Bleeding tends to occur from an area of the brain just under the lining of the fluid filled ventricles that has a very rich blood supply. Anything that causes fluctuations in blood flow to this area of the brain can lead to injury and bleeding from this site. Blood in the ventricles of the brain is referred to as an Intraventricular hemorrhage or IVH for short.
Classically you will hear the team discuss the results of your baby’s head ultrasounds as having one of five possible categories.
- No IVH
- Grade 1 IVH – blood just under the lining of the ventricle
- Grade 2 IVH – blood has gotten into the ventricle but is not causing it to get signiicantly enlarged
- Grade 3 IVH – blood has entered the ventricle and is causing the chamber to grow as fluid that normally drains out is getting blocked by blood from leaving. As fluid (cerebral spinal fluid) continues to be produced, if it has trouble draining out it is like a kitchen sink with the tap turned on and something blocking the drain)
- Grade 4 IVH – this is actually a bit different and is blood within the tissues of the brain outside of the ventricles. This is caused by blood flow in the veins of the brain being too slow and then causing vessels to rupture from lack of flow and oxygen.
A grade 3 IVH is shown below with the chambers swelling (black).
What can happen if the bleeding is significant?
It is the Grade 3 and 4 bleeds that we really worry about. The grade 1 bleeds tend to resolve on their own. When we see a bleed you can expect to see a new ultrasound be done in 1-2 weeks to folllow up and make sure it doesn’t get worse. If a grade 3 bleed continues to cause the ventricles to increase in size we worry with time that this may put pressure on the brain and affect the amount of blood flow the brain receives. If this is happening you may hear that we are asking Neurosurgery to see your infant. They will work with us to determine whether your baby needs a drain put into the ventricle to help get rid of the excess fluid. Many times the ventricles as we watch them with additional ultrasounds get smaller with time but some do not and will need this plastic drain put in to allow the brain to have this pressure relieved.
With the Grade 4 bleeds with time the body will absorb this damaged tissue and your baby may be left with a hole in the brain where the injured tissue was. While this sounds frightening the ability of our ultrasounds to predict eventual outcome is not great. Such infants though will generally be followed in a high risk follow up clinic and carefully monitored for their development. If they are found to have any deficits, depending on your location a variety of services may be offered to help optimize the best chance for a good outcome. Such services might include involvement of an occupational therapist or physiotherapist.
Sometime between about 4-6 weeks after birth or in some cases near discharge another ultrasound will be done. This time the team is looking for something different. The risk of fresh bleeding has passed but now we are looking for evidence of a lack of blood supply at some point from the arteries that provide blood supply to the brain. Many weeks after being born if there has been a period of significant impairment of blood flow to the brain we may see evidence of this. The brain has both white and gray matter (tissue). The gray matter is all along the surface of the brain. Underneath though and right next to the ventricles is the white mattter. This white matter is where the injury we are looking for may have occurred. We call this injury periventricular leukomalacia. This means injury to the white matter. The white matter is where our neurological tissue for motor function travels so in these infants with such injury there can be problems with normal movement in the legs usually, more so than the arms. Assessments in babies with such injury may find increases in the muscle tone in the NICU. In such cases, referral to a physiotherapist early to teach families how to do stretching exercises as an example will be done. Similarly, positioning devices from an occupational therapist may also be recommended.
Post related to Imaging of the Brain
When can my baby go home? The “Big Four” Milestones.
If there is one question that is asked more than any other it is this one. As I have told countless parents, few really expect to have a stay in the NICU so when it happens you are caught off guard. The normal period of bonding after birth is disrupted and as many families will say, they just can’t wait to go home. When a baby is born preterm though they have to get through many obstacles such as dealing with respiratory distress syndrome, need for CPAP and perhaps problems related to the pesky patent ductus arteriosus. For sure these apply to the babies who are quite preterm but even those who are born later such as between 32-36 weeks or others who are born at term but quite small (we call those intrauterine growth restricted or IUGR infants) have a few milestones to achieve before they can go home. Knowing these are needed may help you on your journey and are summarized here. Please note this applies to my practice and although I suspect will be close to others, there may be some differences depending on where you are.
The “Big Four”
Feedings by mouth
We sometimes confuse families I think when we say on rounds that their infant is on full feeds. What we mean by this is that there is no longer a requirement for any intravenous fluid supplementation. In order to go home though in almost all cases your infant will need to be free of a plastic tube that is either passing from the nose or mouth to the stomach (NG or OG tubes). There are some instances where families may be trained to provide these “gavage” feeds at home but this is the exception rather than the rule. To enable full oral feeding there may be some different nipple and bottle options tried as well as strategies for different frequency of feeding. Typically, babies will be given feeds every 2 or 3 hours (q2 or 3H) and then with time given more flexibility (semi-demand or cue based feeds). When you hear “ad lib demand feeding” that means that they can feed as much as they want and as often as they want to and that means home is close.
When a baby leaves the NICU they will need to travel in a car seat for safety. In order to properly fit in a car seat you need to be about 4 lbs or 1800g. For this reason most centers keep infants until they are about this size. If you have a baby born at 1200g and they need to gain 600g they usually will lose weight for a few days and regain to birth weight by a week or two. Average weight gain for preterm infants is about 15-20g/kg/day which means that after the first couple weeks it would take on average about 30 days to reach the 1800g mark.
Small babies don’t have a lot of fat to keep them warm. As such your small infant starts off life in an isolette or what others call an incubator. Infants are all different but you can expect to begin seeing babies trialed out of isolettes as small as about 1500g. There are many babies who can’t successfully get out into an open crib even up to 4-5 lbs. Don’t be frustrated by this. It will happen but until they can maintain their body temperature outside of an isolette between about 36.3 – 37.4 degrees they will not be able to go home.
As discussed in another post, irregular breathing from apnea of prematurity can last for some time. Units across the globe vary in their approach to dealing with such “events”. On the short end there are units that like to see three days without an event at rest before stopping monitors while others use a five day period and others even longer at 7 or 8 days apnea free. These dips in oxygen saturation and/or heart rate can be VERY frustrating to families. Events that occur with feedings are less worrisome but still usually require a day or two of monitoring before your doctor will let you go. Sometimes they can last for weeks even when feeding seems to have gotten on track. The good news is that they will end eventually.
Of course there are other specific reasons why infants will need to remain in hospital but if you keep track of these “big four” it will give you a rough idea of when home might be around the corner.
These monitors are driving me crazy!
It’s not your fault. You come to the bedside often and there isn’t a
lot to do while your infant is asleep. There are only so many games,
news and social media posts to keep your attention and let’s face it the
monitor attached to your infant is a big distraction.
Typically, babies will have their blood oxygen saturation monitored
along with their heart rate and respiratory rate. Some babies will have
other physiological parameters monitored such as the amount of exhaled
carbon dioxide or the blood flowing through their brain (near infrared
spectroscopy) but the first three are the most common.
What you need to understand about these monitors is that we set
alarms for when we need to know if there is a problem. What you also
need to understand is that these alarms while necessary so we know when a
baby is in trouble, can also drive you crazy. Parents
may become slaves to the monitor where they spend a great deal of the
day staring at ever changing numbers. If your infant is a “swinger”
meaning that for example their heart rate or oxygen saturation tends to
fluctuate a lot this can mean a lot of noise all day long.
One of the things that influences the result on the monitor is something called the averaging time.
Typically for us this is 8 seconds which means that the number at any
given time being shown is not the number for that second but represents
the average number over the last 8 seconds. Sometimes your infant will
be referred for a special test called a sleep study to closely monitor
their apneic events. Sometimes families are shocked when their infant
who seemed to have one or two events a day suddenly is reported as
having 30. That is likely because the sophisticated lab is using a 2 or 4
second averaging time. Your baby in this case hasn’t changed. The
Some of the things that can be asked of the team when you have a baby with frequent events are trying to rule out causes of these alarms that are not due to your child themselves.
Is the nasogastric tube in the right place? Should it be changed if your infant’s problem is mostly low heart rate?
Could it be that the probe being used to measure oxygen saturation is in need of being changed to a different limb or altogether a new probe used?
Typically low heart rate limits are set to 100 BPM. Strictly speaking many would consider this bradycardia but another definition is having a heart rate that is >20% below a baby’s baseline. Some babies are born with a heart rate that is anywhere from 100-110 (normal is usually 120-160). Twenty percent below that could be 80 beats per minute. Should the alarm be lowered to that number from 100? If so many of these alarms will vanish.
Stop Thinking About The Day To Day
Lastly, I would encourage you to try and look at your baby’s progress every few days. The journey through the NICU has many ups and downs. It really is no different than a figure showing the stock market over the last many years. Individual days have their ups and downs but it is the trend over many days that matters. Try not to let the daily events ruin your day. Take a moment and ask your nurse to see how your baby is today compared to a few days or a week earlier. You might be reminded that a week earlier your baby was on CPAP and now is on room air. Overall if they are better try and let that balance out your thoughts and try to not stare at the monitor. It just might drive you crazy.