It’s hard to imagine a more common stressor for new parents than the recurring riddle: Why is the baby crying? Did she just rub her eyes—tired? Is he licking his lips—hungry? The list of possible culprits and vague signs, made hazier by brutal sleep deprivation, can sometimes feel endless. But for one family in New England, the list seemed to be swiftly coming to an end as their baby continued to slip away from them.
According to a detailed case report published today in the New England Journal of Medicine, it all started when the parents of an otherwise healthy 8-week-old boy noticed that he started crying more and was more irritable. This was about a week before he would end up in the pediatric intensive care unit (PICU) of the Massachusetts General Hospital.
His grandmother, who primarily cared for him, noticed that he seemed to cry more vigorously when the right side of his abdomen was touched. The family took him to his pediatrician, who could find nothing wrong upon examination. Perhaps it was just gas, the pediatrician concluded—a common conclusion.
Rapid decline
But when the baby got home from the doctor’s office, he had another crying session that lasted hours, which only stopped when he fell asleep. When he woke, he cried for eight hours straight. He became weaker; he had trouble nursing. That night, he was inconsolable. He had frantic arm and leg movements and could not sleep. He could no longer nurse, and his mother expressed milk directly into his mouth. They called the pediatrician back, who directed them to take him to the emergency room
There, he continued to cry, weakly and inconsolably. Doctors ordered a series of tests—and most were normal. His blood tests looked good. He tested negative for common respiratory infections. His urinalysis looked fine, and he passed his kidney function test. X-rays of his chest and abdomen looked normal, ultrasound of his abdomen also found nothing. Doctors noted he had high blood pressure, a fast heart rate, and that he hadn’t pooped in two days. Throughout all of the testing, he didn’t “attain a calm awake state,” the doctors noted. They admitted him to the hospital.
Four hours after he first arrived at the emergency department, he began to show signs of lethargy. Meanwhile, magnetic resonance imaging of his head found nothing. A lumbar puncture showed possible signs of meningitis—high red-cell count and protein levels—and doctors began courses of antibiotics in case that was the cause.
Six hours after his arrival, he began losing the ability to breathe. His oxygen saturation had fallen from an initial 97 percent to an alarming 85 percent. He was put on oxygen and transferred to the PICU. There, doctors noted he was difficult to arise, his head bobbed, his eyelids drooped, and he struggled to take in air. His cry was weak, and he made gurgling and grunting noises. He barely moved his limbs and couldn’t lift them against gravity. His muscles went floppy. Doctors decided to intubate him and start mechanical ventilation.
Process of elimination
Doctors worked to decipher a diagnosis. They started with an assumption that the irritability, lethargy, and muscle floppiness were all caused by the same thing. Without any obvious leads, they went from head to toe to go through the possibilities, starting with an invasive infection. Infants are particularly susceptible to infections, given their underdeveloped immune systems and lack of immunizations early in life. But there were no clear signs of infection on any of his tests, besides the lumbar test, which could have just been caused by a traumatic lumbar puncture. They next went down his whole body, ruling out neurological problems, eye problems, heart and lung problems, gastrointestinal problems, genital and urinary problems, skin and soft-tissue problems, cancer, metabolic disorders, and poisoning.
With the riddle of why he was crying unanswerable, they moved to the muscle floppiness. In infants, muscle tone loss (hypotonia) is generally caused by conditions that either affect the central nervous system (CNS) or the peripheral nervous system (PNS) There are two notable exceptions, tick paralysis and paralytic shellfish poisoning, but the baby boy had no evidence for either of those possibilities. He also did not have any evidence of a CNS-related disease—his muscles and movement had been normal previously, he had no spinal cord injury, and had no preceding fever that would suggest a post-infection paralyzing condition, such as acute flaccid myelitis.
That left just PNS diseases, which generally include much of the boy’s symptoms—his weak cry, drooping eyelids, and poor feeding. The process of elimination then led them to botulism—a condition that explained all of his symptoms. Botulism is a disease of the neuromuscular junction that causes irritability, constipation, autonomic disturbances such as high blood pressure and fast heart rate, a weak cry, drooping eyelids, poor feeding, lethargy, weakness, and respiratory difficulties. It most often strikes infants between 2- and 26-weeks old.
Riddle solved
In infant botulism, spores of Clostridium botulinum colonize the gastrointestinal tract after accidental ingestion and start producing toxin type A. The toxin makes its way into nerve cells and cleaves a critical protein complex necessary for the release of the neurotransmitter acetylcholine, halting nerve signaling. Upon further investigation, the family revealed the baby seemed to have abdominal discomfort prior to falling ill and they had soothed him with honey—a known source of C. botulinum spores and botulism in infants.
With the strong possibility that the boy had botulism, the doctors immediately ordered BabyBIG (Botulism Immune Globulin Intravenous), the only FDA-approved anti-botulism toxin antibodies used to treat infant botulism. It was developed by and is distributed from a unique program run by the California Department of Public Health. The faster infants with botulism get BabyBIG, the better, because the antibodies cannot get into nerve cells—they can only prevent the toxin from going into them. Once the toxin is in the nerve cell and cleaves its target protein complex, it takes four weeks for that protein complex to regenerate and reverse the toxin’s actions.
The BabyBIG arrived from California, and doctors administered it to the baby 31 hours after he first went to the emergency room. About six days later, stool tests confirmed the presence of C. botulinum toxin type A. With the antibody blocking the toxin, the baby boy spent 10 days intubated until he started moving again on his own. He opened his eyes and could cough. He was discharged after 21 days and spent eight days in a rehabilitation facility. Three months later, he had fully recovered and was developmentally on track. And at his recent three-year checkup, he continued to do well.
In this case, the boy’s exposure to honey gave a tidy explanation for why he developed botulism—the diagnosis that finally solved the riddle of his crying. But in most cases, the exposure isn’t so obvious. Infant botulism is rare in the US, with an average of around 80 cases each year, according to the Centers for Disease Control and Prevention. Clear exposure to honey or corn syrup only occurs in a minority of the cases, the doctors of the case report note. Instead, the condition is often linked to environmental exposures, such as rural living, dust production, or nearby soil perturbation. Its sporadic nature can make it yet more difficult to spot.