Case 7682299: Aug. 1, 2010. A mother gives her toddler three homeopathic pills to relieve her teething pain. Within minutes, the baby stops breathing.

“My daughter had a seizure, lost consciousness, and stopped breathing about 30 minutes after I gave her three Hyland’s Teething Tablets,” the mother later told the Food and Drug Administration. “She had to receive mouth-to-mouth CPR to resume breathing and was brought to the hospital.”

The company, Hyland’s, promotes “safe, effective, and natural health solutions” that appeal to parents seeking alternative treatments. But the agency would soon hear much more about Hyland’s teething products. Staff at the FDA would come to consider Case 7682299 one of the luckier outcomes.

A review of FDA records shows that some babies who were given Hyland’s teething products had repeated seizures, became delirious or turned blue and died. (Photo from FDA)

A review of FDA records obtained by STAT under the Freedom of Information Act paints a far grimmer picture: Babies who were given Hyland’s teething products turned blue and died. Babies had repeated seizures. Babies became delirious. Babies were airlifted to the hospital, where emergency room staff tried to figure out what had caused their legs and arms to start twitching.

Over a 10-year period, from 2006 to 2016, the FDA collected reports of “adverse events” in more than 370 children who had used Hyland’s homeopathic teething tablets or gel, a similar product that is applied directly to a baby’s gums. Agency records show eight cases in which babies were reported to have died after taking Hyland’s products, though the FDA says the question of whether those products caused the deaths is still under review.

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(The agency is also investigating two other deaths tied to teething remedies but declined to confirm the manufacturer of the products or provide the case reports.)

Following an FDA warning in September, Hyland’s said that it would no longer manufacture the teething products. But they remained on some store shelves for months, and are still available on the internet. They likely continue to be used in homes nationwide.

Hyland’s, a 114-year-old private company based in Los Angeles, is the nation’s largest homeopathic business. It insists its products are safe and says the FDA has failed to show there is a scientific link between them and infant seizures or other complications.

“That doesn’t mean that children don’t have a sensitivity to a product. There is a lot of sensitivity on kids’ parts and we have to watch carefully,” said a spokeswoman, Mary Borneman. “It’s not something that condemns the entire product line.”

Behind each of the FDA case numbers are angry and, in some cases, heartbroken parents. But a STAT examination — and the first detailed look at the case reports — also raises questions over the response of regulators.

It took four years until the FDA pushed Hyland’s to reformulate its remedies, in 2010. In the seven years since then, there has been a steady stream of reports of adverse events tied to Hyland’s homeopathic teething products.

“The FDA could bring the hammer down on them,” said Sarah Sorscher, an attorney for the nonprofit Public Citizen Health Research Group. “But it doesn’t. At the point where you have infants being hospitalized and deaths reported, it’s simply not acceptable for the agency to delay in taking action.”

An FDA spokeswoman defended the agency’s handling of the matter.

“It is important to note that while adverse event reports give us some information about a product and serious injuries or deaths related to use of a particular product, they often indicate situations that require additional analysis and do not constitute conclusive evidence of a problem with the product,” the spokeswoman, Lyndsay Meyer, said in a statement.

Despite the FDA’s difficulty in proving Hyland’s products harmed children, some doctors had no doubt.

In case 462749, dated Sept. 15, 2011, a physician sent Hyland’s a handwritten note, stating his patient, a 5-month-old girl, was unresponsive for 45 minutes after taking its teething tablets.

“I am sure this was not an allergic reaction,” he wrote. “I would like you to report it, find a contact at the FDA, so we can start an investigation and pull this dangerous, unregulated product from the shelves.”

One mother wrote the company to say her son’s pupils dilated “like marbles with big black eyes.” Another described seizures her daughter continued to have after taking the tablets and told the company, “I hate hate hate u for this.”

homeophathadverse — Adverse event report on Hyland' teething tablets, sent to FDA. (Photo by STAT)

An Industry Giant in a Giant Industry

Hyland’s and its parent company, Standard Homeopathy Co., are considered major players in the homeopathic market. CEO John P. Borneman comes from a family that has been in the business for generations, and is president of the industry group that publishes the Homeopathic Pharmacopeia, a compendium that serves as the bible of the industry.

The company sells dozens of products for pain relief, stress, sleep problems, allergies, flu, and other maladies.

As with all homeopathic treatments, Hyland’s products are based on a theory that patients can benefit from highly diluted natural substances that, in their original form, might make people sick.

Despite a lack of scientific evidence that homeopathic remedies work, they are ubiquitous.

Homeopathy has become a multibillion-dollar industry. Its products are big sellers around the world, and popular with adherents from Cher to Prince Charles. The industry also has political clout: It has been able to exempt itself from many rules proposed by Congress and the FDA over the years.

Unlike pharmaceutical company-produced drugs, homeopathic products don’t have to prove that they are effective at treating anything in particular before going on the market. It is left to the FDA’s drug division to determine whether they are unsafe after they are on the market — a difficult task since the adverse event reports are generally considered to represent only a fraction of the actual incidents and may lack sufficient information to allow for thorough investigations.

“If I’m working in the emergency room and I have a family that comes in with a seizing infant, I may not have the wherewithal to get the history of homeopathic use,” said Dr. Edward W. Boyer, a toxicologist in Harvard Medical School’s emergency medicine department.

In some cases, parents assume that products described as natural remedies, as is the case with Hyland’s tablets and gels, could not possibly result in complications, and never mention their use to a doctor. Without sufficient evidence of a problem, the FDA lacks what it needs to use the enforcement tools it does have.

For Karinna Talbott, a 26-year-old mother in Colorado Springs, the fact that Hyland’s teething products were labeled “natural” made her lower her guard.

“When our fourth kiddo comes around and starts teething at three months, we were like, ‘OK, what can we do to give him some relief?’” Talbott said. “Someone told us about the teething tablets and we thought, ‘give them a try.' ’’

Shortly after her son began taking the tablets, she said, his hands began twitching.

“We didn’t correlate it to the teething tablets,” Talbott said. “And his symptoms got worse, went to his arms and his feet. Sometimes they all happened together.”

Talbott said her doctor was at first uncertain as to the cause. But when they stopped giving him the tablets, the seizures also stopped.

“The neurologist said, maybe he was a little sensitive to the products in the teething tablet.”

‘Deadly nightshade’

In investigating Hyland’s teething products, the FDA focused on an ingredient known as atropa belladonna, an herb known colloquially as “deadly nightshade.”

In diluted form, the substance is not expected to pose any health risk. In 2010, however, FDA inspectors who examined Hyland’s facilities criticized the company for substandard manufacturing practices and found inconsistent levels of atropa belladonna in its products.

The agency issued a public warning, noting “reports of serious adverse events in children taking this product that are consistent with belladonna toxicity.”

It also noted that “infants are very susceptible to the neurotoxicity of drugs” because of how the body distributes and responds to drugs, and noted that “absorption of belladonna from the skin and mouth was fairly rapid.”

The company voluntarily took the products off shelves and agreed to reformulate them, although it insisted they were safe.

“We felt it was the right thing to do so that parents didn’t have to be concerned about the product,” said Borneman, the spokeswoman.

But the number of serious adverse events tied by the FDA to the products kept climbing. Some pediatricians and neurologists concluded the tablets and gels were the cause. Many parents wrote to the FDA, accusingly, asking why the pills were still on the market.

“My son had 3 of Hyland’s Teething Tablets,” a mother told FDA on Feb. 13, 2012, noting that the product appeared to have caused several seizures. “I am shocked at the popularity of this product, which is growing, and the lack of knowledge among parents, as well as the lack of warnings on the labels. Parents desperately need to be warned about this product if it is going to stay on the shelves!!!! Please do something!”

In September 2016, the FDA announced that it was investigating more adverse events reports and recommended that consumers stop using Hyland’s and other homeopathic teething products and dispose of any in their possession. Some stores, including Target and CVS, which sold Hyland’s and other homeopathic teething products, pulled them in response.

The FDA also asked Hyland’s to recall its products again. But this time Hyland’s stood its ground, and the agency has no authority to enforce a recall of homeopathic products.

Borneman said the company’s “pharmacovigilance program,” a product safety review system launched after 2010, offers proof that the treatments are safe.

“Homeopathic medicine has a very large margin of safety,” she said. “Our testing ensures there’s not too much belladonna in any bottle” of tablets.

At the same time, the company decided to stop manufacturing the teething tablets. In an open letter to customers, Hyland’s said the FDA warning had “created confusion among parents.”

“Putting you in a position of having to choose who to trust in the face of contradictory information is burdensome and undermines the FDA,” the company said, while insisting Hyland’s products, “including those you already have, are safe for use.”

Several weeks ago, on Jan. 27, the FDA issued another warning, saying that laboratory analysis of Hyland’s teething tablets found levels of belladonna “sometimes far exceeding the amount claimed on the label.” The agency warned consumers not to use the products and to seek medical care immediately if their child has seizures, difficulty breathing, lethargy, muscle weakness, or other problems after using homeopathic teething products.

The FDA also said there was no evidence that they actually worked.

homeopathicevent — Report sent to FDA by a physician. (Photo by STAT)

Cracks in the FDA’s Authority

With concerns about toxic levels of belladonna, and the sheer number of cases of adverse events, some critics — and parents — say the FDA should have moved faster in the case of Hyland’s.

But they also acknowledge that the episode underlines the cracks in the agency’s regulatory power when it comes to homeopathic products. There is no set mathematical formula or official standard that spells out how many sick or deceased children must be reported before the FDA seizes a company’s inventory or levies fines or shuts it down.

Critics say the fact that homeopathic products are generally highly diluted has kept them on the FDA’s back burner.

“It’s low on their priority list,” said Dr. Aaron S. Kesselheim, who coauthored a paper in the New England Journal of Medicine last year on the subject. “FDA for a long time just kind of deferred on homeopathic products because they are mostly inert and so diluted. The harm comes from people wasting their money, or diverting them from things that do work.”

In the case of some of Hyland’s products, however, Kesselheim believes that the toxic levels of belladonna show a substantial safety problem, putting a responsibility on FDA to respond.

One problem the FDA has in doing so is a matter of staffing: The agency has a medical officer review each report from manufacturers, but it doesn’t have someone who can routinely follow up with the patient, the patient’s family, or physician for missing records necessary to take a serious enforcement action.

“Is it fair to criticize FDA for the time lag between 2010 and now?” says Patricia Zettler, a former FDA counsel and associate law professor at Georgia State University. “I think the agency is in a tough position, with these kinds of products and with adverse event reports in general. They are not necessarily a perfect indication of something happening with a drug.”

“That said,” Zettler added, “it does sound like this is a product the agency was concerned about. It’s tough to parse out whether two reports of seizures should have been enough, or three or 10. There’s a balance the agency has to strike between acting quickly on safety information and not overreacting to something that may not actually be caused by the product.”

Public Citizen’s Sorscher said criminal cases take years to pursue, so the FDA would much prefer voluntary compliance.

“They don’t have a mechanism to say, ‘this ingredient is unsafe, nobody should sell it,’” she said. “It might be time for Congress to give FDA a standard and say, you can issue a regulation saying no one can make it anymore.”

Outraged by the standoff between FDA and Hyland’s, Connecticut Democratic Representative Rosa DeLauro introduced a bill last week called the Recall Unsafe Drugs Act. The proposal would give the FDA mandatory recall authority over homeopathic products and drugs.

“Hyland’s refusal to recall its teething tablets, despite numerous health and safety warnings from the FDA, is downright shameful,” DeLauro said, adding that the company “is choosing instead to prioritize the company’s profits and reputation before the safety of our children.”

“As it stands the FDA would have to go through an arduous legal process to take action against manufacturers such as Hyland’s. This is unacceptable and threatens the health and safety of American families.’’

For the parents of Case 10723317, any action would come too late. A mother reported that on July 9, 2014, her 9-month-old daughter died after being given two teething tablets, crushed, for the first time. She gave her infant the tablets, then a bottle, and then left her to sleep. When she checked on her 45 minutes later, she was dead in her crib, beside a puddle of vomit.

Five months later, after reading online reports suggesting babies may experience seizures after taking belladonna, she contacted Hyland’s.

“Customer did not request a refund or replacement,” noted the Hyland’s staffer who filed the report with the FDA. Hyland’s also noted that it was not able to test the bottle, because the customer threw it away.

“Due to the limited information provided by the reporter no further investigation is possible at this time of this incident,” the company concluded.

Ike Swetlitz contributed reporting.

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This story was originally published by STAT, an online publication of Boston Globe Media that covers health, medicine, and scientific discovery.

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Hundreds of Babies Reported Harmed by Homeopathic Product