Last week an article published by the New York Times entitled “Scrutiny for Laxatives as a Childhood Remedy” made the rounds. The article raised the question of a possible link between the use of a popular over-the-counter laxative, PEG (polyethylene glycol) 3350, and neurological or psychiatric problems in children. This wasn’t the first time this particular journalist wrote a piece on this topic, however. In 2012, she wrote about the popularity of the treatment among pediatricians despite a lack of FDA approval for use by children, a fact which applies to many if not most of the drugs commonly prescribed by pediatricians.
PEG 3350, perhaps more commonly known as Miralax or by one of many similar generic product names, has long been known to potentially result in loose stools or even frank diarrhea with excessive dosing, as well as abdominal cramping. But both of the New York Times articles mention the fact that there have been a number of anecdotes blaming PEG 3350 for a variety of non-gastrointestinal symptoms, with varying degrees of plausibility in my opinion. They also point out that many of these unproven anecdotes were made via the FDA Adverse Event Reporting System (FAERS).
The FAERS can provide pivotal post-marketing surveillance. It can generate hypotheses, thus allowing the FDA, researchers, and healthcare professionals in the trenches, to hone in on potential toxicities not picked up during clinical trials because of low prevalence, delayed onset, or some other unexpected variable. But like the VAERS, the federal vaccine specific reporting system, the FAERS has significant limitations such that data mined from it should be used cautiously. Now the FDA is funding research at Children’s Hospital of Philadelphia that will specifically address these concerns.
The word autism wasn’t used in these articles, but that is the leap being made by many in the lay community. I’ve already been asked about this by a number of parents, and they are worried. Just search “miralax AND autism” on the Googles or your search engine of choice. I’m not surprised folks are worried considering some of the information available online, like this terrifying nonsense from Gutsense.org:
Adding insult to injury, after getting nuked with an abdominal CT scan to “diagnose” constipation and, then hooked on MiraLAX by the very doctors expected to protect her health, she may end up autistic and cancer-prone for the rest of her life.
You can conveniently order their “Colorectal Recovery Program” for $119.95 in order to avoid and/or repair the damage from these synthetic chemicals. Here is a good rebuttal of the Gutsense post. I’ll cover some of the same ground, and go into more detail about childhood constipation and why we need drugs like PEG 3350, but it’s a good read nonetheless.
Constipation is an extremely common, and often underrated problem in kids, and many children use the remedy in question for acute episodes or for long-term prevention. Some children, my daughter being one of them, have required weeks, months and even years of daily dosing at some point in their lives. So if PEG 3350 is harmful, many children might be affected. Of course there are significant harms that can result from poorly-managed constipation also.
I can’t possibly explain in complete detail such a complex topic as childhood constipation, as it has many causes and a variety of management approaches. But before discussing the potential dangers of PEG 3350, I would like to at least give a solid basic overview of the problem and how it presents in the bulk of children as a functional condition unrelated to any anatomic or biochemical derangement. And it is a problem. One which is extremely under-appreciated. Warning: I’m going to say poop a lot.
What is constipation and why is it so common in children?
Simply put, constipation is defined as trouble with defecation, with having stools that are hard to pass or infrequent fitting the bill for older kids and adults. But as younger children develop, what is considered normal in regards to the frequency and consistency of stools changes – so there must be some fluidity to the definition. We can’t just lump all kids into the same group. It is not uncommon for a parent to believe that their perfectly healthy child is constipated because of an inaccurate understanding of the range of normal stooling patterns and behaviors.
True constipation is very common though, with as many as a third of children affected at any given time, and related complaints from kids and caregivers are the impetus for 3-5% of pediatric sick visits. These complaints cover a lot of ground, ranging from nervous mothers worried about infrequent bowel movements, to severe abdominal pain and the need for inpatient or even surgical management, to significant psychosocial sequelae. The most common presentations, however, involve bowel movements that are hard and uncomfortable, and cramping abdominal discomfort. But trust me, there are piles of additional potential problems associated with untreated constipation.
Mild to moderate constipation occurs throughout childhood, likely as a result of poor dietary choices/options resulting in a less-than-optimal intake of fruits, vegetables and fiber, with incidence tending to peak during the preschool years. It has spikes at three distinct periods of development: the introduction of solid foods during infancy, toilet training and starting school. The most severe cases of functional constipation, which again implies that there is not something structurally or biochemically amiss such as a spinal cord lesion or cystic fibrosis, tend to occur in the setting of purposeful withholding of stool.
Why would a child purposefully hold his poop in? There are actually a number of reasons, and it doesn’t always begin as intentional withholding. An understanding of why a child would do this helps to explain why we see increased incidence of constipation at certain periods of development.
Kids who are afraid to have a bowel movement will actually do whatever they can to not have a bowel movement, including all manner of muscular contortions. These behaviors can be quite impressive and mimic other issues. I once had parents worried about unusual seizure activity or other problem with the nervous system because their horribly constipated toddler would frequently drop whatever he was doing and writhe on the ground with his legs crossed like scissors.
Here is how this can happen. If a child with mild to moderate constipation, or just bad luck, develops a small but very painful tear in the anal tissue, something called a fissure, they might begin to associate pooping with pain. If they are yelled at or punished for having an accident during potty training, they might begin to associate emotional discomfort with pooping. Sometimes kids will refuse to use the bathroom at school because of anxiety or because the toilets are nasty, or they may be unable to even reach the bathroom because of overly-strict school policies on bathroom breaks.
Once the pattern of holding stools in has begun, whether voluntary or not, it can become a vicious cycle. The longer that a child withholds, the larger and harder the accumulated stool becomes, and the likelihood that subsequent bowel movements will be painful increases. Painful defecation in turn leads to more intentional withholding, or to the initiation of intentional withholding in kids who simply weren’t allowed to go at school or had worsening constipation simply because of a poor diet. As the process continues, stool can become impacted and a host of new difficulties can begin to occur. In addition to the sequelae discussed above, chronic severe constipation can also lead to voiding dysfunction with resulting urinary tract infections as well as bedwetting.
Impaction of stool can even lead to fecal incontinence, and I’ve had a few families present with complaints of diarrhea completely unaware that their child was severely constipated. As the mass of stool in the rectum enlarges, the normal functioning of the nerves that signal the need to defecate or delay defecation is impaired because of constant stretching. These children also may lose the ability to even produce enough pressure to move stool from the rectum into the anal canal, thus purposeful withholding of stool can eventually become automatic. At this point, the child may be unaware when the leading edge of hard stool emerges enough to soil their underwear, and liquid stool from above the impaction can leak around the blockage and pass through the anus uncontested.
How is constipation in kids diagnosed?
The official diagnosis of constipation is based on the Rome III criteria, an international consensus for functional gastrointestinal disorders, although in practice we tend to use more of a clinical gestalt, for better or worse. With either approach, a number of factors come into play: stool frequency, hardness, size, fecal incontinence, purposeful retention, and pain with passing stools. To diagnose a child over four years of age, the Rome III criteria require two months of at least two of the previous factors being an issue (one month for infants and toddlers). Treatment should generally begin long before a child might fit this criterion, and prevention should be discussed even earlier than that.
Use of strict criteria like this can be helpful but doesn’t replace clinical skill because they don’t take into account the range of normal stooling behavior or the complexity of information gathering. A parent can usually tell me how many dirty diapers they might change each week but not how often their 7-year-old poops. And good luck getting the kid to tell you anything about frequency and consistency of stool. Even teenagers will often respond with “I don’t know.” Kids will frequently not even localize pain in any way other than “my stomach hurts.”
If parents don’t know that something is a helpful clue, they may not point it out. They may not realize, for example, that “skid marks” observed when doing the laundry are probably not because Timmy doesn’t wipe well enough, or that the “weird thing he does sometimes” is withholding behavior. And I’ve encountered many families that joke about their toddler’s “man-sized toilet cloggers.” Without asking the right questions, sometimes in a variety of ways, all that some parents of chronically and even severely constipated children might offer up is “he complains about his tummy and he’s missed a lot of school lately.”
How is constipation in children managed?
The first and most important step in managing childhood constipation is recognizing that it is a problem that needs management in the first place. Many kids with severe constipation that eventually require inpatient treatment spent months with unrecognized mild-to-moderate symptoms. Despite the fact that pediatric interns generally learn early on in training to respect constipation while managing their first hospital “clean out“, we still often drop the ball and fail to provide appropriate anticipatory guidance and early intervention.
Prevention is the key, so discussing diet and bowel habits should be a standard part of well-child visits. Particular focus should be given to the high risk transitional periods I mentioned earlier. Parents can ensure that their infant’s diet includes adequate fiber and water as they start solid food intake at around 6 months of age, and hopefully they will continue to model and provide a healthy diet containing plenty of fruits and vegetables. Excessive intake of cow’s milk beyond what is required for nutrition is unfortunately common in toddlers and can also lead to constipation.
The common approach to toilet training can be overly aggressive for many children, potentially leading to failure, frustration and withholding behaviors. It should be delayed until a child is developmentally ready and should never involve punishment for accidents. Unfortunately, pushing potty training is often hard to avoid for working parents when preschools and daycare facilities require it.
As kids age and go off to school, parents should be counseled to maintain a working knowledge of their child’s bathroom failures and successes. They should be on the lookout for any difficulties pooping at school and make sure that children have time and are encouraged to go at home. I usually recommend at least 15 minutes, twice a day, for potty time. Sometimes a reward system can help. And diet remains an important factor as children grow as well, with fiber, fruits and vegetables being a key component of normal bowel movements and future health.
But what about when a child presents with signs or symptoms of constipation? The earlier it is recognized and treatment begun, the more successful management tends to be. In many instances, dietary intervention is all that is necessary, particularly when the constipation is mild to moderate.
Infants can be given fruit juices or purees that contain sorbitol, which pulls water into the lumen of the intestines and softens stools, and higher fiber cereals can be given in place of the more typical rice variety. Older kids can simply increase their intake of fruits and vegetables, which is frequently a lot easier said than done. These interventions don’t always work, and tweaking the diet by adding fiber and fluid is usually not enough when children come in with severe constipation, withholding, or incontinence. But it is still important as a means of preventing future occurrences.
For significant short-term constipation in children over 6 months of age, the best treatment on the market is PEG 3350. Like sorbitol, polyethylene glycol is osmotically active. It pulls water into the gut and softens the stool. Furthermore it is the iocane powder of pharmaceutical interventions, being completely without taste, smell, color, or texture when mixed in liquid, and it can be mixed in anything. PEG 3350 is extremely easy to dose and it’s relatively inexpensive since becoming over-the-counter a few years ago. It is recommended by the overwhelming majority of pediatricians and pediatric gastroenterologists, and has an excellent safety record even with use over months to years. Another benefit to PEG 3350 is that it isn’t habit-forming like stimulant laxatives, which can play a role in management but tend to be avoided when possible.
Another major component of constipation management is disimpaction, frequently in the form of suppositories in young infants and enemas in older children. Sometimes surgical disimpaction is even necessary, but thankfully it rarely gets to that point. The reason that this aspect of treatment is so important, particularly in severe cases of impaction, is because treating from above, so to speak, can actually makes things worse if the blockage is not removed.
I have admitted more kids than I can count for severe constipation who have failed outpatient management. Inpatient management involves the administration of a slow-but-steady infusion of PEG 3350 via a tube placed into the stomach through the nose, but only after one or more enemas has removed the impacted fecal mass. Sadly, although quite rare, there are kids out there with such severe, persistent constipation that they have required surgical placement of a tube into their colon for ease of administering laxative solutions at home in order to avoid frequent hospitalizations.
Management of severe constipation is usually thought of as a marathon as opposed to a sprint. Children usually come in having had issues for months to years, and it can take as long for them to return to having soft and comfortable bowel movements. For one thing, changing a child’s diet sounds easy on paper but it can be a challenge for parents who find themselves with a picky toddler or who are in need of dietary interventions themselves. Also, as I mentioned earlier, chronic impaction can impair the ability to evacuate stool even when it is softened. Thus it is extremely common for children to become constipated and symptomatic recurrently, which is why so many remain on PEG 3350 for so long. It just takes time for things to reset.
Does PEG 3350 increase the risk of autism or any other neuropsychiatric symptoms?
PEG is an extremely versatile compound with different chemical properties depending on the form used. It can be found in use in a variety of industries, one of which is in the formulation of various medications. It has been used in some drugs to reduce toxicity and slow clearance from the blood so that the dosing interval can be spaced out. One example is PEG-interferon alfa, a medication for hepatitis C. PEG is also used in the production of liquid medications and soft capsules, as a lubricant in eye drops, and as a base for ointments.
It has a wide range of uses in biological research and industry. It is used in rocket fuel, paintball rounds, and to preserve historical objects recovered from underwater. You can even find it in toothpaste and as an anti-foaming agent in food. Frankly I’m surprised that the Food Babe hasn’t gotten around to PEG yet.
PEG is produced by putting ethylene oxide in a big pot with water and ethylene glycol. I think maybe there is an incantation said over the pot and an acid or base is used as a catalyst, but the incantation is the key in producing a polymer of identical ethylene glycol subunits. What has everyone upset about PEG 3350 is the fact that its production involves ethylene glycol, which is a major component of antifreeze and tastes great, making it a common cause of poisoning in kids. So if you learn nothing else from this post, please keep your antifreeze out of the reach of young children.
Ethylene glycol is used in the production of PEG 3350, but PEG 3350 isn’t ethylene glycol, perhaps because of the incantation used during production, or maybe even science. Ethylene glycol toxicity is serious, potentially resulting from ingestion of just a few milliliters in small children and manifesting as alcohol poisoning with symptoms like altered mental status, rhythm disturbances of the heart, and kidney injury. Treatment is available if recognized quickly enough, but it can be fatal. Ethylene glycol poisoning is similar to autism in the way that mercury poisoning is. In other words, it isn’t. It also isn’t really similar to the anecdotal reports of behavior changes and movement disorders reported to the FDA.
We actually already have an understanding of what happens to PEG in the body. We have a good grasp of how much is absorbed depending on the molecular weight and how it is metabolized. We even have data on whether or not it is broken down into ethylene glycol and potentially able to wreak havoc on the brain, heart and kidneys. We know, for instance, that of the PEG 3350 ingested by humans less than 10% is absorbed and none of it is broken down into individual ethylene glycol monomers. Yes, this wasn’t specifically studied in children but there is no reason at all to think that a child would metabolize PEG into antifreeze while an adult wouldn’t.
What is adding fuel to the fire, in addition to the very questionable FAERS data, is that the FDA apparently did find some ethylene glycol in some test batches a few years ago. But follow-up testing of a larger sample size in 2013, involving five different manufacturers, didn’t reproduce those results. Taking into account what we already know about PEG, the untrustworthy nature of FAERS data, and the long track record of safety in clinical use in children, I believe that this is a non-issue.
But, and I mean this, I understand why the FDA is doing what they are doing. I don’t think it is completely unreasonable to investigate further and hopefully answer this question once and for all. Of course even if the results of the additional research on the safety of PEG 3350 in kids are reassuring, the damage has already been done. It will always be a concern for some parents, particularly parents of children who have already been diagnosed with autism.
Constipation is common in all kids, but it is even more prevalent in children with autism. It makes sense to me that children who may have nutritional and/or sensory issues might be predisposed to problems with defecation and have an increased risk of withholding behaviors. I hate to think that because of implausible concerns about the safety of such an effective treatment there may be children who will have poorly-managed constipation which might exacerbate other behavioral problems. There are other laxatives that can be used, they just aren’t as good.
Ultimately, however, I will follow the science where it leads. Despite the fact that I am highly skeptical of these concerns regarding PEG 3350, and that I will continue to recommend its use in the meantime, I will drop it in a heartbeat should I be wrong. That is, after all, the essence of science-based medicine.