The Quiet Baby

Want to know What antidote is made from the blood of scientists? And what poisoning occurs due to a lack of bile acids and good bacteria in the GI tract? Listen to find out! 

Transcript

This is the Pick Your Poison podcast. I’m your host Dr. JP and I’m here to share my passion for poisons in this interactive show. Will our patient survive this podcast? It’s up to you and the choices you make. Want to know What antidote is made from the blood of scientists? And what poisoning occurs due to a lack of bile acids and good bacteria in the GI tract? Listen to find out!

Today's episode starts at your friend's house. You are visiting your friend and her new baby. You’ve been dying to meet him since he was born four months ago. You arrive with lots of gifts, cute outfits and colorful toys, you couldn’t resist buying. Your friend opens the door in sweatpants and a t-shirt, kicked in vomit. She has deep hollows under her eyes.

You ask how she's doing. Surviving she says with a tired smile. She passes you the baby, he’s cute, pink, chubby and bald. He grunts a few times. She says he’s been constipated since yesterday, but is overall doing well. In fact, he’s crying less than usual. The pediatrician said he’s reaching all of his growth milestones. 

You tell her you’ll watch the baby. She should rest, get a pedicure, take a walk or do something for herself. She says what she wants most is a shower and rushes off to the bathroom. 

You coo at the baby and show him the noisy new rattle you brought. He looks at the toy, and moves his arms, but doesn't make a real effort to reach out or grab it. His big blue eyes are wide open, watching as you wave it around. You notice his pupils are really large. It's kind of dark in this corner of the room, so you move over to the window where the sunlight is coming through, surprised his pupils don't constrict.

As I'm sure you know, our pupils dilate to let the light in when it's dark, and constrict when there's a lot of light to focus it on your retina. This is why when you go to the doctor we're shining a flashlight in your eyes checking the reflexes are working appropriately. An uneasy thought forms in your brain. You hear the shower water turn off as your friend finishes up, probably her first uninterrupted shower in weeks. 

You put a blanket on the floor and set the baby down on its tummy. By four months old, most babies can hold themselves up on their forearms, and hold up their head. He’s trying to push himself up but can't get up on his forearms and is moving his head on the blanket but not lifting it. Your friend said he was meeting his milestones, maybe this is just normal variation and nothing to be worried about. But, of course, you can never turn off your ER doctor and toxicologist brain, and the uneasy feeling becomes a bit of concern. 

Your friend comes out of the shower with a smile and clean clothes. She reaches for the baby to start breastfeeding. He doesn't immediately latch on. 

“How is he doing with tummy time?” You ask. 

She says, "Good. He's been able to hold his head up pretty good until yesterday. It seems kind of floppy again." He still hasn't latched on. She shifts trying to improve his position.

“How about reaching for and holding toys?” You ask. 

“He loves that rubber giraffe,” She says, pointing to a toy on the table. 

He's still not feeding yet, so you pick up the toy and ask if you could interrupt for a second. She turns the baby towards you. He cries, it’s a very weak sound. You wave the giraffe. Same as before, he sort of moves his arms but doesn't really reach for the toy. 

"I think we need to go to the emergency department." You blurt before you can think of a more sensitive way to say it.

Her eyes widen. She says, "I had a call in about the constipation to the pediatrician an hour or so ago, but I haven't heard back yet. I didn’t think it was an emergency." 

It’s not the constipation itself you’re worried about. You tell her you're concerned this might be more than the pediatrician can address in the office and take her and the baby to the emergency department. 

This is fiction, so of course, you're the baby's doctor. The nurse hooks him up to the monitor. His temperature is 98.6°F (37°C), so no fever. Heart rate is 150 beats per minute, normal for his age. It's difficult to get blood pressures in babies, so we don't often check them unless there’s a specific concern. Respiratory rate 50 breaths per minute, also normal. His oxygen saturation is 98% on room air. On physical exam, you check his fontanelles (soft spots on his head) to make sure there's no swelling, which could indicate increased intracranial pressure. They are normal. His pupils are large, and just like at the house, they don't constrict when you shine a light.

You check his skin, noting no rash. His heart and lungs sound normal. His abdomen is also normal, despite the history of constipation, he doesn’t have any pain when you press.  He isn’t moving his arms or legs much. 

Pediatricians, have a tough job, especially with neonatal patients and newborns. They can't talk, they can't tell us what's wrong, all they can do is cry. I always feel like it’s as much detective work as medicine when taking care of the little guys. 

Mom says he was a full-term baby born via vaginal delivery. He hasn't had any medical problems. Doesn't take any medicines. She hasn't given him anything over the counter. He's up to date on all of his vaccines. 

With our patient, what stands out as the main issue is the muscle weakness or hypotonia in medical terms. Parents love to talk about milestones and how their kids are doing. Some kids are slower developers than others, and generally speaking, a short delay is nothing to be concerned about. Here, it’s regression raising concern for a serious problem. He was able to hold his head, he was able to push himself up on his arms, and now he can’t. From an emergency standpoint, worrisome. In fact, if you hold him with your hand under his back and his butt, he’s floppy, meaning his limbs just kind of flop down.

Ok, so what do you want to do first?

On a positive note, his vital signs look good, so we have time to figure out what to do. You order and IV and basic labs. Next, we need to think about what types of things can cause muscle weakness in babies to further direct our care. We've talked about electrolyte disturbances. Do you remember what electrolyte can cause muscle weakness? Question #1. 

A.    Sodium

B.     Chloride

C.     Magnesium

Answer: C, high magnesium causes muscle weakness. As well as both high and low potassium. We'll get the electrolytes with the labs. But a breastfed baby, really shouldn’t have electrolyte disturbances.

Encephalitis and meningitis are the top of my list. These are caused by bacterial and viral infections. But he never had a fever, and mom denies any sort of cough or cold symptoms. We probably will need to do a spinal tap or a lumbar puncture to check, but it's certainly not a classic presentation for these diagnoses.

There's something called Guillain-Barré syndrome which we've touched on in the past. It's a neurological disease which sometimes occurs in association with viruses and sometimes without any known etiology, causing ascending paralysis. The Miller Fisher variant causes descending paralysis, though less often, extremity weakness. We'd have to consider these; they're clinical diagnoses, one clue is an elevated protein in the cerebral spinal fluid after a spinal tap.

Could he have polio? He's been vaccinated, so no. But these days we often have to consider historical diseases we didn't used to think about in the United States. Polio is a virus, so you'd expect a fever and, often, it causes asymmetric weakness. If you've ever met a person who had polio in the past, they usually have, for example, one leg that's weak.

One I want to mention is diphtheria. A lot of us have never treated these diseases from the 1800s and early 1900s. Interestingly, it can cause a demyelinating neuropathy with cranial nerve involvement. But first, the child would have to have the typical symptoms we expect of fever, sore throat, cough.  And he’s vaccinated, as I said. 

Could he have had a stroke? A baby with a stroke, did I hear you say? Unfortunately, it's not impossible. But typically, with a stroke or intracranial bleeding, you’d expect weakness on one side rather than both. Certainly, we'll consider brain imaging with a CT scan. 

We have a lot to think about, and what we really need here is help, specifically from an expert like a pediatrician or pediatric neurologist. Not only are babies difficult to get a history from, it's also difficult to evaluate them. The nurses are still having trouble getting the IV and the labs. We certainly don't want to do an unnecessary spinal tap, and if we do a CAT scan, we may need to consider sedation. So we need expert advice about which tests to do and which order to do them in.

The pediatric neurologist recommends both a head CT and a spinal tap. We discuss other diagnoses as well because, as you know, this is a toxicology podcast, not a pediatric neurology podcast, so let's focus in on the toxins.

We said he had big pupils. Could he have anticholinergic toxicity? From too much diphenhydramine or Benadryl, for example. It's easy to accidentally overdose a child. If he did have anticholinergic toxicity, he'd also have fever and a rapid heart rate, so it doesn’t fit. Eyedrops like you get at the eye doctor, but he hasn't been exposed to these. Sympathomimetics like cocaine and methamphetamine. I'd love to say exposure never occurs in babies, but that would be absolutely not true. Your friend would never do that, but to further support the issue from an objective standpoint, he doesn't have a rapid heart rate or a high blood pressure, which would go along with the sympathomimetic toxidrome. And those don't cause flaccid paralysis either.

So, what does cause flaccid paralysis? Some things we've talked about on the podcast before. Poisoned dart frogs. But we're not in the Amazon, so doubtful. Same with cone snails, elapid bites, like coral snakes. Paralytic shellfish poisoning caused by saxitoxin. Organophosphates and pesticides, but he doesn't have other symptoms of cholinergic toxicity, like a slow heart rate and breathing problems. We use paralytics in medicine, especially in the emergency department for intubation. But again, there's no way he really could have been exposed to any of these things. Some heavy metals, like lead. You can certainly get lead poisoning in kids, but this usually occurs in children a little bit older who can crawl and are old enough to put things in their mouths, like, say, paint chips for example. Also, this presentation doesn't fit with lead toxicity either.

Question # ***. Time to pick your poison. In infants, the combination of constipation and “floppy baby” is a classic description of which toxin. 

A. Thallium

B. Cyanide

C. Carbon monoxide

D. Botulism

Answer: D This is a classic case of infant botulism. Cyanide causes cardiovascular collapse. Thallium is a heavy metal, so it can cause muscle weakness, but he'd be screaming in excruciating pain. Carbon monoxide exposure can cause weakness and coma, but both you and mom would also be sick.

We talked about food bourne botulism the Hooch episode, so I recommend listening, if you haven't already, for more details about exposure from canned foods, fermented foods, and how you could be exposed in prison. The other kinds of botulism include: Wound botulism (where exposure occurs from a wound, often after injection of black tar heroin), and iatrogenic botulism, which occurs for example after Botox injections. 

And Infant botulism which is what we're going to talk about today. It's caused by the same toxin, but it's actually really interesting. It's a separate form of the disease and occurs via different mechanisms. Infant botulism is a type of botulism toxicity that occurs in infants under one year of age. It can be, but is definitely not always, associated with food. 

Question ***. What food is infant botulism often associated with

A. bananas

B. Peanuts

C. Honey

D. Artichokes

The answer is C honey. Some cases of botulism are associated with eating honey. the number is variable, but it's around 20% in the US. Definitely not all cases, and we'll come back to this in a few minutes. Cases of infant botulism declined after warnings from organizations like the CDC and the American Academy of Pediatrics to avoid honey in infants under one year of age in the 1970s and 1980s.

Interestingly, about 95% of infant botulism cases occur in the U.S. And in the US, infant botulism is the most common kind of botulism, accounting for 70% of all reported cases. There are seven different types botulinum toxin A through G. It's only A and B which cause toxicity in infants.

Question ***. Most cases of infant botulism come from two areas of the United States. Which are they?

A. California

B. The Gulf Coast, Mississippi, Alabama, and Texas.

C. Pennsylvania

D. Four Corners of Utah, Colorado, Arizona, and New Mexico.

The answer is A and C. California has the most cases followed closely by southeastern Pennsylvania, specifically around Philadelphia, Delaware, and New Jersey.

Back to our patient. You ask your friend if she's given the baby any honey, and she says no, absolutely nothing other than breast milk. So if the baby didn't get it from honey, then where did it come from? Well, we do know what some of the risk factors for exposure are, but in many cases, we never know exactly where it came from. Botulism toxin comes from the bacteria Clostridium botulinum, which can survive for a very, very long time as a spore. It's commonly found in dirt and high levels are noted in California and Pennsylvania, the likely reason the majority of the cases occur in these areas. In infant botulism, the spores get into the large intestine, and grow, causing colonization by Clostridium botulinum.

There is evidence that living near a construction site might be a risk factor, with the idea that it is stirring up the dirt and aerosolizing the spores. There are some interesting associations with parent's jobs, specifically if the parents work in construction, farming, or plant nurseries, the baby may be at an increased risk.

Wait a minute, did I hear you say? If botulism spores are all around in the soil, why aren't we all getting botulism and toxicity from this? Infant botulism occurs in children under one year old, and in fact mostly in children under six months old. This happens for specific reasons, First, babies have underdeveloped immune systems that don't work as well as ours. Second, they have low amounts of gastric acid and bile acid in their stomachs and GI tracts. This is actually what keeps the rest of us from becoming sick if we were to ingest a few botulism spores from the air. Also, as you're well aware, we have good bacteria in our gastrointestinal tracts. These help to keep down overgrowth of bad bacteria like Clostridium botulinum. But babies aren't born with good bacteria, and colonization takes some time. There is an association between breastfed infants and botulism toxicity, though the reasons are not entirely clear.

Okay, so we talked about it and where it comes from, let's touch on briefly what it does. Again, I discussed the mechanism in more detail on the previous episode, so go back and check that out if you want to hear more. 

The first sign of botulism toxicity in infants is usually constipation. This is followed by difficulty feeding and a weak cry. It progresses to the classic description of the floppy baby where when you hold up the baby, they can't hold up their own neck or their own arms and legs. In contrast to foodborne botulism, the symptoms typically progress more slowly. This is because with foodborne botulism you eat the toxin and it makes you sick. Over days, whereas with infants it progresses slowly, sometimes even over weeks.

If you remember Clostridium botulinum toxin works on the nerve terminals to prevent the release of acetylcholine. This in turn leads to a loss of muscle contraction and thus muscle weakness and flaccid paralysis. As with anything causing flaccid paralysis, it can progress to respiratory failure. 

You and the pediatric neurologist are in agreement about the concern that this could be infant botulism. The baby's head CT and lumbar puncture come back completely normal.

First and foremost, of course the baby needs to be admitted to the hospital, specifically to the ICU, for close monitoring of his breathing. It's pretty likely he'll develop complete respiratory failure, requiring intubation and mechanical ventilation. So, the pediatric intensivists will keep a close eye on his respiratory status. I'd get this started, but there is something you need to do in tandem.

How can we figure out if this really is botulism toxicity? We've done the initial workup, we've ruled out some reasonably common alternative diagnosis, and we have a classic presentation. Pediatrics and neurology are both in agreement about the likelihood that this is infant botulism. Is there a test? Yes. It's a stool test, but it takes several days to a week to come back, because in most areas you have to send it to the CDC for analysis.

At this point, I'd call the infant botulism hotline, which is a 24/7 number. You can call to discuss your concern and obtaining the treatment. It's run by the California Department of Health, you can look up the number online. 

What’s the treatment? It has a great brand name: BabyBIG. Its Immune globulin that's given IV. So, BabyBIG means baby botulism immune globulin. This is an antidote, human-derived, and its essentially antibodies against botulism toxin. Invented in 1997, by a scientist working for the California Department of Health. The mechanism is similar to digibind, the digoxin FAB fragments that we've talked about in the past, as well as snake antivenom. 

The sooner you start this, the better it works. Therefore, we don't wait for test results when the clinical suspicion is high. Because infant botulism is rare, and this treatment is very expensive, approximately $70,000, it's not stocked in hospitals. You have to get it from the California Department of Health, thus the hotline.

You call the hotline, speak to the physician on call, and discuss the case. She agrees with your assessment and confirms you've sent specimens off for confirmatory testing. She tells you she'll start working on the logistics immediately to get the antidote flown into your hospital.

How well does this antidote work? Well, first, in the past, mortality rates for infant botulism used to be 90%. Now, with mechanical ventilation, most babies would survive in modern times, even without the antidote. Before BabyBIG, patients stayed in the hospital on average for 5 weeks and on the ventilator on average for 17 days, which is a pretty long time. There's a definite risk of pneumonia and hospital-acquired infections. They often require feeding tubes because of poor feeding for up to 10 weeks.

Patients who are treated with the BabyBIG, have an average hospital stay of 2.2 weeks, less than half. Some don't even require mechanical ventilation. But if they do, time on the ventilator is reduced from 4 weeks to 1.8 weeks, and tube feeds from 10 weeks to 3.6 weeks, so that's pretty amazing.

It does matter how early it's given, as I said before. The biggest reduction in recovery time is if it's given within the first 3 days of hospitalization. It still has a benefit even given as far out as 10 days, but you start to see diminished effects.

            You tell your friend The baby BIG is on its way from California. A room is ready in the pediatric ICU, so he'll be transferred upstairs very shortly. She thanks you for recognizing the symptoms earlier than she would have. 

What are the side effects of the treatment? The main issue is it’s derived from human plasma, so just like with a blood transfusion, there's always a very small but potential risk of transmission of an infectious disease or an allergic reaction. Overall, it's pretty safe, and if your clinical suspicion is high, the risks by far outweigh the benefits. 

            The baby’s respiratory muscles become weak, and he does require intubation the following day. The next morning, the BabyBIG arrives from California and is started immediately. The results come back from the CDC confirming this is indeed infant botulism. Your friend is understandably devastated by this illness, but the good news is a week later, the baby starts to regain his muscle strength. You tell her it may take weeks to months for a full recovery, but reassure her that the vast majority of children recover without any neurologic sequelae.

This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings.

            As I said earlier, honey is the food that we often associate with botulism toxicity. However, just last month, there was an outbreak of infant botulism related to contaminated formula in the US. You may have heard about it in the news. The formula was recalled, about 51 infants in 19 states were believed to have had botulism toxicity, fortunately all survived. 

            It can be tough to diagnose infant botulism in the emergency department if the parents bring the patients in early with symptoms only of, say, constipation or difficulty feeding. So you have to maintain a high level of clinical suspicion, particularly if you work in areas like California. 

Interestingly, there was a study to see if infant botulism might explain cases of SIDS (Sudden Infant Death Syndrome). This is a devastating problem that we don't know very much about. It's a horrific, life-altering event for the parents and the family of the infants. It’s also traumatic for the physicians, nurses, and the entire hospital staff when these babies come in and cannot be revived. In a series of 250 infants, tragically post-mortem of course, botulism wasn't present in any of the babies.

I didn't know until I was doing research for this podcast that it's actually really amazing how the BabyBIG was invented. I mentioned earlier there was a research scientist at the California Department of Health, it took 15 years and $10 million to develop it. Under California state law, all of the funds used to buy the BabyBIG have to go back into the program itself. As I said, it's human-derived, so this means they rely on human volunteers, many of whom are also scientists. Batches are made every five years. 

For example, one was a woman who was a biochemist who happened to be vaccinated against botulism because she was studying the germ in the lab. She produced high levels of the antibody in her bloodstream as a result. Volunteers have had to undergo boosters of an investigational botulism vaccine which caused side effects like pain and welts in the area where it was given. Nevertheless, the volunteers are willing to undergo these side effects to help the babies.

The last question in today's podcast. Clostridium botulinum was named after a food it was often associated with in the 1700s and 1800s. Botulus is the Latin word for: 

A.    Sausage.

B, Olives.

C, Peaches.

D, Potatoes.

Follow the Twitter and Instagram feeds both @pickpoison1 for the answer. Remember, never try anything on this podcast at home or anywhere else. 

Thanks for listening. It helps if you subscribe, leave reviews and/or tell your friends. Transcripts are available at pickpoison.com. 

 While I’m a real doctor this podcast is fictional, meant for entertainment and educational purposes, not medical advice. If you have a medical problem, please see your primary care practitioner. Until next time, take care and stay safe.