Dr. Jessica Duis gave the 1-hour presentation below at the 2019 FPWR Family Conference. In it, she shares current standards of care for people with PWS who are ages 0 to 2.

Dr. Duis is a geneticist at Vanderbilt University with an unbridled passion for people with PWS. Trained in both pediatrics and genetics at Johns Hopkins Hospital, she also spent a year specializing in epigenetics research, focusing her bench and clinical work on PWS. She has established a multidisciplinary clinic for PWS at Vanderbilt and has authored “A Multidisciplinary Approach to the Clinical Management of Prader–Willi Syndrome" in which she documents comprehensive medical care considerations for individuals with PWS.

Timestamps and topics are provided below the video for easy viewing of specific content. A partial transcription of the session is also available below.

2019-Conference-Standards-of-Care-Ages-0-2-Jessica-Duis

 

Presentation Sections With Timestamps

Time Presentation
01:30 Diagnosing PWS
03:00 Message to newly diagnosed families – finding your support team
06:00 Lets get started – other than growth hormone (GH) there is no 1 prescription
06:30 Skin to skin care, postpartum depression
07:20 Undescended testes, use of HCG
08:10 Monitoring for hip dysplasia 
10:00 Nutritional phases of PWS
11:30 A fed baby is a healthy baby – feeding tips and tube recommendations
13:43 Positioning can be key [video]
14:45 Aspiration is common (90% of infants) – may need to thicken formula and pay attention!
17:11 Nipple flow rate and bottle recommendations
17:50 NG tube feeding scarring caution
18:50 Formula vs breastmilk – adjusting calories
20:30 Reflux
20:50 A caution on Nissen fundoplication 
21:51 Introducing of solids
23:40 Liquids and cup recommendations
24:48 Starting solids
26:30 Starting supplements
27:26 Supplements (coq10, levocarnitine, MCT oil, B vitamins, DHA, multivitamin, biotics)
35:10 Early intervention (speech, PT, OT recommendations)
44:35 Behavior and childcare
47:00 GH makes a difference!
48:45 Sleep and sleep studies for GH therapy
50:00 Obstructive sleep apnea – often improves with GH treatment
50:50 Central sleep apnea 
51:10 Other treatment considerations: scoliosis, constipation, allergies, viscous saliva
53:00 Oxytocin – benefits and considerations/cautions
56:40 Multidisciplinary Clinic at Vanderbilt University
57:25 Q&A

 

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Partial transcript from the FPWR 2019 Family Conference: Standards of Care for Ages 0-2 by Jessica Duis

Dr. Jessica Duis:           

I started really focusing on seeing patients with PWS 5 years ago, but I've been seeing kids with PWS for about 20 years. When I began there was nothing in the literature on standards of care. I wanted to set up a situation in which everybody could get the same care that they were getting, wherever they were going. I wanted to have a document or published papers to say ‘this is something you should at least think about trying cause it's safe’. And so that's how I started on this journey. And it did start with a conversation with Dr. Miller, because she does a lot of treatments and therapies and has a lot of things in her toolbox that aren't really well documented out there. I started with talking with her, and then other experts throughout the country, interviewing parents about therapies they were getting, and interviewing experts in the field who work every day with individuals with PWS, to really understand the breath of tools that we can use to treat these kids. And why does it feel like there's nothing out there to really guide us to be able to do that?

I don't have to explain to this audience what usually helps us pick up that a child has PWS, but usually it's picked up in the neonatal intensive care unit, a child who's not feeling well, who also has low muscle tone. And that is the typical thing that we think about when we think about Prader Willi. But one thing to realize is that that's not true across the board. It is true in about 90% of individuals. But there are people out there whose parents have managed at home, they got through the feeding years, the children have some delays but are still undiagnosed with PWS.

Diagnosing PWS

I know there was also a genetic talk earlier so I'm not going to go through this in too much detail, but Prader Willi is caused by missing expression of the paternal critical region on chromosome 15. And this is just to emphasize that even now we get a lot of individuals who are transferred to our NICU who have had, for example, testing to look for that deleted region of chromosome 15 and families will come to us saying, ‘Oh no, they ruled out Prader Willi’ even when they have been at other medical institutions. Therefore, it really is the methylation test that tells you which genes are turned on in the region, that will pick up 99% of individuals with PWS.

The Importance of Building Your team

I can't emphasize enough how important it is for you to take some time at that point [of diagnosis] to really find your team. You really do. You need to give yourself some time to really absorb what that means. And it's hard not to think about what the future looks like. And at a time like this, that can be so challenging to get past. So I encourage you to really find a support team for you. And give yourself some time, try to just take some time to find your support team. I can't emphasize enough how important that is because there are good days and there are bad days. You need that team on good days to brag, and you need that team on bad days to really hear what you're going through and say, ‘I've been through the same thing.’ And it doesn't have to be someone in the PWS community.

I can't emphasize enough how careful you should be on Facebook. One of the most disappointing things about being in the rare disease community is some of the things that I hear that people get said to them on Facebook really make them feel bad. We need to be more aware, as a community, of what we're saying to each other. There isn't one way to do things. And there are going to be bad days and I don't want anyone to ever forget that these kids are warriors. They're determined. They are strong in ways you can't even imagine as parents of young kids. They

They have a diagnosis that doesn't define them, that doesn't limit them. You still should have the same goals that you have for your other kids. But like someone who said to me, you, it may change what your expectations are for the future, but you should still have those same goals and want your child to get involved in things that they enjoy. It shouldn't hold them back. And so your job as a parent in this situation is to give them all the power and empower them to proceed with the things they want to pursue. So remember you got this.

The Only FDA Approved Standard of Care: Growth Hormone

So I'm going to go through a long list of things. The main thing to remember is that there is no one way to take care of an individual with PWS. We have one thing that's FDA approved that's a standard of care that I feel very strongly every child should be on, and that's growth hormone. Outside of that, all of this may not pertain to your child, and may not be something your child went through. And there are no randomized control trials to say that there's other therapies or things that we should be doing right now.

Skin to Skin Care

So one of the things that there is a lot of literature about, not necessarily in PWS but particularly in the NICU, would be skin to skin care. So you know, getting the diagnosis of course is very challenging. There's high rates of postpartum depression. I really want families to remember is the benefit of holding your baby. Skin to skin care really helps with all these things. And this has been shown in the literature to be beneficial for kids with low muscle tone or other medical problems that bring them to the NICU. And bonding is very important. So this also comes back to find your support team because if there are, it's very common for people to have postpartum depression and you want to recognize that in yourself, and take care of yourself so that you can take care of your baby.

Undescended Testes

Undescended testes are very common and can sometimes help us diagnose Prader-Willi in boys who have low muscle tone. There is some data that HCG can be helpful, particularly in enlarging the scrotal sack to allow for surgery to be a little bit easier when they go in to bring the testes down. We do have some cases where actually HCG treatment is enough that they don't need to go on to have surgery, which is a big deal for these kids who have some anesthesia considerations. So we do encourage people to use HCG, at least try it. It doesn't seem to have any true negatives or huge risks to using it.

Hip Dysplasia

Developmental Dysplasia of the hip is more and more common and we're recognizing it more in individuals with low muscle tone, including those with PWS. There was a recent paper in 2018 that said that we should be getting hip ultrasounds on all individuals with PWS at six-weeks of age to rule out  developmental dysplasia of the hip. If you catch it early, then you can put something called a Pavlik harness on which is a brace as opposed to having to go on to do surgery. So we try to follow this guideline. The risk of doing a hip ultrasound obviously is very low. It's just like when your baby was in your belly and they were taking a look to see how things were going. So very easy to do and noninvasive. If a child gets past that six-week age, then we can get x-rays instead of an ultrasound and look at the hips to make sure they look normal. Once you rule out dysplasia of the hip, you don't need to have any additional imaging as they won’t develop it later.

Nutritional Stages of PWS

There's a lot of published information about the nutritional stages of PWS and this is not something that I necessarily say worry about at this 0 to 2 years age. The nutritional stages published for Prader Willi are really a loose guideline. Not every child with PWS follows these nutritional stages at these ages. These are averages and I will tell you, we do see kids in this age range, the zero to two age range where they start to have more interest in food and more anxiety around food. So this is just a rough guideline, but in this age range [ 0 to 2 years], you're going to see this failure to thrive. As kids get closer to two, usually over two, there is some weight gain without a change in appetite or changing diet. And there's mixed reviews about what the cause of that is. Truthfully, from a standpoint of management, I don't know that it matters what the cause is. It could be that they're slowing in metabolism and decrease needs. It could be because these kids have low muscle tone and they move less, so they burn less calories. It's unclear why this happens, but it's interesting because they always have had that low muscle tone. In fact, over time the low muscle tone gets better. And so I am in the camp of thought that there is a slowing of the metabolism that they have less caloric needs than other individuals.

A Fed Baby is A Healthy Baby

It's really important when you're going through all the feeding issues to just remember a fed baby is a healthy baby, a baby gaining weight is a healthy baby. It doesn't matter how they're getting their nutrition. Now from a bonding standpoint, I know it's very challenging, but at the end of the day, if you're feeding your baby and holding your baby, you're bonding with your baby just as you would if you are feeding them another way. And feeding difficulties are common so when you're thinking about your support team, people who have been through that, it's really important.

 

Tube Feeding

There are strategies to try to get your child to wake up more for feeding: feed them without clothes on, try different positioning, try different bottles, and if you're going to support your child with a way to give nutrition that's not by mouth, we strongly recommend doing it through an NG tube. We strongly recommend that hospitals become more comfortable sending kids home with NG tubes and training families on them. So if hospitals reach out to us, we say to them, in this case it is better for these children to go home with an NG tube, if the family feels comfortable. Now if parents don't feel comfortable, then of course we want to do what feels most comfortable to the family, because like I said, a fed baby is a healthy baby. But if families feel comfortable, we strongly encourage being able to go home with an NG tube. About a quarter of kids still end up with gastrostomy tubes and that's okay. There is no data in the literature about what type of tube feeding is better. No one has ever done a study where they looked at the safety considerations. If someone has the G-tube, how long is too long? If you're on an NG tube, how long is too long to feed your child through an NG tube? And are there other risks that we need to be aware of when we're thinking about that?

Positioning While Feeding

This is a video. [see video timestamp] So positioning is key. A side lying position is a position that we use frequently. Even if you're bottle feeding or breastfeeding, putting the baby on the side, providing neck support, sometimes providing chin support can help too. She is saying in the video that he can take a break if he needs to and if he stops feeding it's not still squirting into his mouth. In the side lying position the milk will leak out of his mouth, which will allow him not to choke on what's sitting in his mouth. Sometimes we also keep a hand on the back and we'll have them try to push the jaw forward to help as well.

Aspiration

Aspiration is really common in kids with PWS. There was a presentation at the PWSA-USA meeting and then this was recently published to say there's a high number of aspiration events, which means that there's a high number of kids who get some of this formula that goes down the wrong airway. The liquid should be going down the trachea and it's coming down the pharynx right here, which can go into the lung. And that's very common. About 90% of individuals with PWS have this. There was a study by Roxanne Gross that showed that this occurs throughout life. Even in adolescence, with Prader Willi, there's a high rate of aspiration.

So what does this mean? It means we need to be aware of it. If your child is sick, we need to think about whether there could have been an aspiration event that could have led to that child's illness. And that could be why they're not getting better. They do tend to aspirate more if they're sick. Kids who have a lot of congestion sometimes end up in the hospital with Prader Willi. That may be because they're aspirating. There are things we can do about this. It doesn't mean the child may need a tube. It may mean that we need to thicken formula's or liquids that they're getting, and just pay more attention to it. The hard part is we don't know how much typically developing infants aspirate. They probably do to some extent. And similarly, how many of us have been drinking something and start coughing and choking? I mean that happens to me all the time. So all of us have some of these events. The challenge with Prader Willi, because low muscle tone is being able to clear it. So it's something to pay attention to.

Bottles and Nipples

Another thing to think about is nipple flow rate. And this is from the literature as well, looking at what are the nipple flow rates and it does show that in kids who have low muscle tone, it is important to consider this. Here are some of the bottles that work really well. We really like the Doctor Brown's feeding system because for one thing, there's a valve that you can put in there that will slow the flow and then you can also take the valve out. If the child's sick and more likely to aspirate, we may put the valve back in or when they're really young they need the valve. But as they get bigger they don't need it anymore. So that's the one that we liked. But there's lots of stuff out there.

And then I talked about this already. You know, we have all postulated for a long time that there are theoretical risks to having a tube placed. When you have a tube placed, even after you pull it out, you have a scar there. As kids get older, if they have a lot of weight gain, weight loss, weight gain, weight loss, and they have an episode where they intake a lot of food, then we think that the stomach might be weaker at that position and that it could be a challenge for that child. But I have to tell you, there is no data about that. When we've anecdotally collected data on the kids who have had rupture, which is rare, very rare. It seems to be there's more important contributing factors then when they had to G-tube.

Weight Monitoring

We monitor the growth curves closely and we may increase calories and I do recommend that you have a dietician or a good pediatrician making sure that they're following weight and increasing calories. But we have this group of families coming to us recently who have kids with PWS where the pediatricians are worried they're gaining too much weight, and they're putting them on lower calorie formulas than is safe for a child that age, and they're trying to get them to lose weight as infants. This is not appropriate. So if anybody hears anyone or sees anyone on Facebook, please direct them to someone who can really help them because the kidney is not ready to process that caloric density and the amount of fluids that that child might be getting.  It can be very dangerous for many reasons. All babies have some fat on them and there are still other factors for kids with PWS. There's no fat babies. There's well fed babies, normally healthy fed babies. And I can't emphasize that enough because I think some people hear PWS, think it starts the, hyperphagia starts from the beginning and then automatically want to calorie restrict from the beginning. I can't believe how much it happens.

Reflux

Reflux is really common and can contribute to not wanting to feed because things come up. They're uncomfortable. This is what we call dysphasia. And there's behavioral things you can do, maybe not medication based. So holding kids upright for 30 minutes after feeding, and then medications and maximizing medications may be the right thing for your child. Again, there's no data, but if your child is getting a tube, avoid doing the procedure for gastro esophageal reflux, where they wrap the top of the fundus of the stomach back around itself to prevent things from refluxing up. We think that it does impact gastric emptying later. So these kids are at risk for slow gastric emptying called gastro-paresis and so we think that this procedure contributes and could increase the risk of gastric rupture. So avoid getting this procedure even though they will try to get you to have this procedure when they put the G-tube in because it's a common procedure for kids with low muscle tone.

Introducing Solids

As soon as your child has good head control, it's okay to introduce solids. Just make sure that they're in a supportive chair. There are some really great chairs that can also help with preventing scoliosis. This is one of the ones we like [see video]. It is a serious chair but it does collapse and is relatively easy to travel with.

Kids with PWS seem to have an increased risk of allergies so you want to give a good amount of time every time you introduce a new food. We say three days. We don't think you have to wait a whole week, but just pay attention.  Even from this age, we say avoid added sugar. Look at labels and see if there's any added sugars. The reason is that there was one paper that showed sugar seems to impact the brain similarly to someone who's getting a drug, who's addicted to drugs. The brain lights up with what we call the reward pathway of the brain.

As soon as you start to incorporate solids, you should start incorporating liquid water, plain water if you can. There’s lots of different ways to incorporate water. We try to have people make stuff at home: infused water with fresh fruits or vegetables. There's also a lot of stuff on the market now, like hint waters. I've had some success with kids liking Hint waters and they have no added sugar, no calories, and they're pretty flavorful if you've tried them.

At this time you should also start to incorporate cups. There are different types of cups. We often start with the honey bear cup, which allows you to help the child get the fluid through the straw. But it is also great because it starts to get them used to what the technique would be, what you're trying to accomplish, to learn. Another reason we say to incorporate a straw cup early is that it is tremendously helpful with the low muscle tone in the cheeks and the muscles of the face and helps with them chewing later. You want to make sure your child chews well because of the aspiration risk and using a cup with a straw early helps them develop those muscles.

We'd like you to start solids with non-starchy vegetables. Broccoli and celery for example.  All of this is pureed. Nothing solid. There are certain fruits that are better than others because they have a lot of fiber. Typically these are berries. Avocado is great if your child will eat it because it has a lot of medium chain triglycerides and good fat. When you begin meats, again everything should be pureed when you're first starting solids, but really focusing on lean meats.

Supplements

Supplenents is a whole talk in and of itself. There is very little data to say we should be using any supplements in PWS. So if families are interested in supplements, we encourage people to try them, because we want to do anything that could be beneficial. Don't ever start two at once. Only start one at a time.

Try to systematically collect data about whether you think it’s helping your child. Most of your children are in therapies. Ask the therapist, don't tell them that you've changed anything you're doing, but ask the therapist, if they notice any changes.  Try to collect systematic data, or see if people comment because you don't want to end up with your child on 40 supplements and have no idea if they are doing anything.  We don’t want them taking a lot of stuff into their body if we don't know if it has benefit. We also don't know if it has risks to it.

Coenzyme Q10

The basis for use of Coenzyme Q10 is that there may be a problem with the powerhouse of the cell, called the mitochondria. That is really important for the production of energy that our body uses, called ATP. Coenzyme Q10 is part of that chain of events that allows that part of the body to make energy. And theoretically where the benefit of CoQ10 comes from. There've been some studies that have looked at levels of Coenzyme Q10 in PWS and, for the most part, they're normal. So, it doesn't seem that there's a deficiency in this particular vitamin but there is a little bit of data that it may impact development, primarily motor development. There was one study that looked at kids who were on growth hormone versus Coenzyme Q10. It seemed to have the same benefits as growth hormone in that one study. We do try it COQ10 in our clinic. You know, a lot of people have different philosophies about dosing. We typically start at hundred milligrams, but then some people do milligram per kilogram dosing, and there's no randomized controlled trials to say that this is beneficial. And the side effects are that it can cause reflux so be aware of that in a child who's not feeding well. One might prioritize the getting the feeding under control before they incorporate something that may make reflex worse.

Carnitine

Carnitine is similar to COQ10 in that it is important for how our body gets energy from our fat to our muscle. That's simplified, but that's how we'll explain it. There is some conflicting data about whether there's low carnitine levels in individuals with PWS. And I think that is something that's worth checking, or having your doctor check, because we are seeing that some people have low levels of Carnitine. And in that case, absolutely it should be given back to help your child. Carnitine may be helpful for alertness and daytime energy. There was a paper that came out from Art Beadet's lab that showed Carnitine may play a role in non-syndromic Autism. So that renewed some interest in this particular supplement as well. And again, no randomized controlled trial of actually using this in Prader Willi.

MCT Oil

MCT oil is Medium Chain Triglyceride oil. It's really helpful in augmenting some of the diets that we do recommend which are higher protein, higher fat diets, no added sugar, and less carbs or non-nutritious carbs in the diet. There have been some recent papers that MCT may impact ghrelin. So of all the supplements, MCT has the most data to suggest that it may have some mechanism pertinent specifically to PWS, although there's no trials of MCT in PWS. There's also lot of data about MCT in the overweight and obese population, not the hyperphagic population, but the overweight population that it may be helpful for appetite. And it is definitely a source of fuel for the brain. So it may be helpful also for that alertness. And so MCT is something that we try and recommend.

B Vitamins

B vitamins are really hard, in particular B12. Individuals with PWS across the board have high levels of B12, if you check them. And we inject them in a lot of our patients. It's not published, but the levels are in the thousands even though parents don't have their kids on any supplements when we're doing those levels. There was this school of thought in the community that maybe people with PWS don't have enough active B12. There is no data to support anything like that. And so it's hard because a lot of people are interested in getting B12 injections. B12 injections are a little bit different than giving growth hormone injections. B12 injections go into the muscle and it's a volume you have to give your child into the muscle. So it's a little bit different from the subcutaneous injection that growth hormone is down to a science in giving. So it's just something to consider. It's something where we definitely need more data. We certainly see patients who are on it and if they feel like it's helping, we encourage people to continue it. The levels in these kids who are on it are in the hundred-thousands, they're really high. And I just don't know what the impact of that is. So it's one of those risk benefit things. I don't feel as comfortable using B12 in our clinic.

DHA

DHA has a lot of data in the literature about its use for developmental disabilities and autism, and there are some good studies that show that it could help with neuropsychiatric development. So we do encourage use of DHA, or using a formula that has DHA, and continuing a milk that has DHA. And when your child turns 12 months, we recommend transitioning to whole milk.

Multivitamin

We do recommend children be on a multivitamin and there's some good multivitamins out there. In particular if you're using only breast milk, you want to make sure that your child's on vitamin D.

Probiotics and the Microbiome

There's a huge body of research going on in terms of the microbiome and what does the microbiome look like in PWS and does this contribute to some of the features of PWS? There's still a long way to go in terms of research in this area, not just for PWS but also autism and other neurodevelopmental disabilities. We think that the gut microbiome plays a huge role in the development and function of the central nervous system. There's not overwhelming systematic data to say that's for sure, but there's enough suggesting that that could be the case.

There are probiotics out there that try to reestablish the gut flora. So there's all the different types of bacteria you might have in your gut that you take as a powder form or a pill form to reestablish a new colony. Then there's prebiotics. It's kind of like fertilizer for those bacteria. So it's food for them to try to encourage the healthy type of gut microbiome to grow over the not as good. There's a book that came out by someone who's interested in autism but again, there no systematic study to say this is what we should be doing. So we encourage people to be on either prebiotics or probiotics. Some people are on both because it does seem to help with keeping things going through the gut. It does seem to be, potentially, a natural way to help with constipation. But this is another area of we just don't know.

Early Intervention

Early intervention is key. One thing that's really important is that feeding consultation. We encourage everybody to do a feeding consultation. Getting involved in state programs is really important. And then you also just really have to do a lot of advocacy because a lot of the state programs will say your child's in developmental therapy and they stay in developmental therapy for months and months and months, and they don't progress to physical therapy. They don't progress to specific types of therapies.

We want kids in PT by about three months. It is important to meet kids where they are in terms of their physical therapy. If a child's just starting to hold their head up, we don't recommend just taking that child and say and working only on sitting. You should try to slowly work through things. That said, there is no regimen or program that's been studied to say that there's any risk of scoliosis. You know, you have to be comfortable with the providers who are providing your physical therapy. Lots of things with balance balls, we definitely think it's so important to build core strength. I can't emphasize that enough. You need someone who will think outside the box about how do I build core strength. So balance balls can be fantastic for these kids, but there's no clear evidence to say if you do it this way, that is why your child has scoliosis. And so we need to be careful about putting that out in the community. Right. Because that's where families feel like ‘I listened to my physical therapist.’ I mean I have families come see me in clinic in tears saying to me, I put my child in physical therapy, I trusted this physical therapist and look, my child has scoliosis, it has to be their fault. They were sitting my child up before they were ready. That's bananas. That makes parents feel awful. So bottom line is there's no data to suggest that, you have to have someone you feel comfortable with and if they don't work well with your child, switch. We advocate for these kids to have the best therapies. We're on board, but if you like who you're working with and your child's making progress, most likely the scoliosis has nothing to do with it. They have Prader Willi, they have a high risk of scoliosis. They have low muscle tone. They have a high risk of scoliosis.

OT can be really important for some of the sensory things very early on. Exposing your child to lots of textures and working with someone who's familiar with that, who again will think outside the box about what can we do.

Speech is also a really important piece. A lot of kids don't talk till they're older and we think that that's because of something called apraxia. It’s in there cognitively, they can speak, they want to speak. It's a problem with motor planning. So if that's the case, one of the families that I work with, about five years ago actually, in a different community told me their child started prompt speech therapy. And the mom has actually worked on a book because it was life changing for her child! So prompt speech therapy, which has to do with also working with the child, manipulating the mouth, helping with placement of the tongue, communicating in multiple different modalities. Using hand gestures and talking to the child all can be really helpful. There are some great YouTube videos if you want to learn to do prompt with your child. I watched them and I even just try it in clinic with families to kind of give them a sense of what it is because it's pretty easy to learn.

And then we've had a lot of people go for neuromuscular electrical stimulation to help with swallow. You know, there's no data out there. I don't know if that's one of those things that if parents want to try, they pay out of pocket for it. It's not something we recommend necessarily. Because it, it's basically providing an external stimulation to the Pharynx to help kids with swallow.

Behavior

Behavior is really normal in this age range. Every parent should teach with praise. Be proud of your child. No matter what it is they do. No matter how small the accomplishment. Kids with PWS are people pleasers. They want to make people happy. They want to make people proud of them. So the more praise you can give, the better. Rewards can begin to be used around the age of 18 months. Reward charts work really well. Competitive reward charts work really well. So if you have other children having a reward chart with a number of stickers for all the other kids and doing the same things as you do for your child with PWS as you do for other kids.

You may start to see rigidity at this age. Now they're going to be stubborn, they're going to have tantrums at this age, that's going to continue for a few years. That's normal. So there's a balance, but you do want to be paying attention to some rigid behaviors. You might notice communication concerns, not making eye contact. And the reason for that is we want to help them develop those skills. So when we notice that there might be some concern, we want to get in there and get them the right therapies and sometimes that requires the right ICD10 code for the insurance. And that's just the reality of what we do in medicine. I am constantly working on that. So these are things to pay attention to cause we might be able to help.

And then I can't emphasize enough to do the normal things you do with your other kids. Gymboree, you know, all the mothers-days-out, all of the activities you would do with other kids his age. You know, you want to do that with these kids too. And don't feel bad for putting your child in daycare. They do not need a nanny. They can go to daycare like other kids. At some point your child's going to go to school and they're going to be exposed to all of the same things that they might be exposed to when they go to daycare. So don't feel bad about having to put your child in daycare because they may have special needs.

Growth Hormone

I can't emphasize this enough, the only standard of care we have for Prader Willi is growth hormone. We recommend you get your kids on growth hormone right off the bat from birth. We have a protocol in our NICU. We give kids growth hormone in the NICU. During pregnancy, growth hormone is made in the placenta and the child does not have any growth hormone at birth.

If your child has PWS and they're not producing growth hormone, then they don't have any growth hormone right from birth. If your child makes some of their own growth hormone, and many kids with PWS do make some of their own growth hormone, in fact a lot of them do, then there are still all these other benefits of growth hormone that we know about in this population. So we want kids on growth hormone right from the beginning. The problem is there's very little data about this. There was a recent randomized control trial, that included kids less than 24 months, but those kids were closer to one year old. But it did show that GH is safe. That's the number one thing we worry about. Is it safe? It is. That trial showed that it is safe. It also showed that it has some benefits at that young age. So we want to get kids on growth hormone right off the bat. There is also some data coming out now from multiple different labs that is showing that kids may have some IQ improvements on growth hormone so we are recommending as early as possible that you get on growth hormone.

The biggest challenge with growth hormone is sleep. Sleep apnea and sleep disorders are all very common in this age group. Central sleep apnea as well as obstructive sleep apnea. The FDA requires we get sleep data on these kids. If your child is in the NICU, which a lot of kids with PWS are, and they're on a monitor, that is enough for your first sleep study. So if kids have been in the NICU a week with enough data to say they had that first sleep study, we can get them on growth hormone. Then you still need the follow up evaluation, and kids do tend to have more sleep apnea on that second evaluation. There's data in adults to say that growth hormone has no impact on sleep apnea. There's no data in kids. I suspect that the bigger concern at this age is the low muscle tone that's contributing. Growth hormone actually helps the low muscle tone, which helps the sleep apnea.

There was a study from Dr. Miller's group that showed a lot of people got better when they started growth hormone in terms of their sleep. What we recommend is that we send you to an ENT and we try to continue the growth hormone in our clinic. We fight really hard sometimes and we have some discussions about it, but we try to continue growth hormone in our clinic. And then we do send you for a drug induced sleep endoscopy (the current gold standard) to look to see if there's any surgical intervention. But most of the time in the age range that your kids are, there's not that much we can do about it. They don't have huge tonsils yet. They don't have huge adenoids. So it just requires that discussion and balance.

Central sleep apnea is also really common in this age range. Basically, your brain doesn't have the normal drive to breathe and the only treatment for that would be to go on oxygen.

Scoliosis

When your child can sit up from lying down to sit up on their own, we recommend getting an x-ray of the spine. That's because we miss a lot of scoliosis in these kids because it's hard to see because of low muscle tone, but also because sometimes all we see is a tiny bit of asymmetry in the shoulders and that's hard to see. So we recommend getting an x-ray of the back.

Constipation

Constipation is really common. It's under-recognized too. If you're noticing your child ever gets a balloon belly, gassy, it's most likely that they have bad constipation. We've had several parents come in and say, look, my child poops normally and we get an x-ray and they're totally backed up. So in PWS, this seems to be a really common. Keeping them on some of these supplements, that's where MCT does have benefit, it helps keep things moving in the gut. You want to be aggressive about treating constipation.

Allergies

Allergies are common. We recommend getting evaluations for allergies.

Thick Saliva

Kids with PWS do have really thick saliva and they don't have the right salt content in their saliva. It doesn't coat the teeth. So kids with PWS, even at this age, start to get cavities. So the American Academy of Pediatric Guidelines say these kids should be getting evaluations of their teeth every three months, starting at age one. It's really hard to get the dentist to listen, but it's in the guidelines. I encourage you to take those guidelines which are widely available online and show them that that is necessary for your child's medical care.

Oxytocin

I could spend a whole lecture talking on Oxytocin. There's some data that Oxytocin might be beneficial for a couple of things. One of them is feeding early on. The other thing is bonding with parents. As kids get older it may have other benefits for social behavior and hyperphagia.

In Europe, they're a big believer in using Oxytocin. Dr. Tauber's group is using it widely. I know people are getting it in the community widely. At the doses used in the most recent studies, which would be four international units in one spray, we think it's definitely safe. The studies that have showed that it's not safe have been using really high doses, as high as 48 units a day. That's more than 10 times what most people are using right now. Those studies showed that it may increase the risk of aggression in older kids. So it's one of those risk-benefit issues.

Oxytocin is widely available. It's one of those things that if it's really beneficial at this age, we don't want this group of patients to miss getting it. We feel like if there's data to suggest something is helpful, but most importantly if there's data to suggest something's not harmful, of course we don't know long-term what that looks like, we want to help people who are interested and have educated themselves. The challenges: there's no consensus on whether it needs to be re-dosed and all of us have a different school of thought about that. How many of you reduce your growth hormone every day? Anybody in here give growth hormone every day? Growth hormone is a hormone that our body produces. Oxytocin is a hormone our body produces. If the hypothesis is that our child does not produce Oxytocin, then why isn't it something that they need every day? We know that people produce Oxytocin throughout life. Truthfully, we don't know what the benefits are in Prader-Willi. Lots of people are working on that. The bottom line is everything we know about Oxytocin outside of PWS says it's produced throughout life. We're saying our kids don't produce it. So everyone has a little different school of thought about this. But I think it's a lifelong therapy. If we're saying it's a therapy for PWS, it's not a one-time therapy. So it depends what the benefits are, but you can see from these studies, these are benefits that affect people throughout life. Social behavior affects people throughout life. Cognition, everyone would agree, affects people throughout life. So we're not sure what we should be doing with it, but it's out there.

And so we do have a paper out and I mention this because it can be helpful to take to your Doctors that talks about growth hormone and Oxytocin. Some people have been able to take it to their local providers and get them interested enough to help their child get Oxytocin.