The search for what causes SIDS

When a healthy baby has either too little oxygen or too much carbon dioxide, Goldstein explains, their breathing stops (“pause apnea”) before they start gasping. “These breaths usually cause the heart rate to increase in a healthy baby,” says Goldstein. “These babies wake up and have reflexes associated with excitement: they squirm, yawn, turn, wake up and cry, and this relieves most babies of relatively modest obstacles and they survive.

“And babies with SID didn’t do that. They didn’t wake up and remained ‘untethered’ between these agonal gasps, which are triggered by certain centers in the brain, and the cardiac response.”

That means a “vicious circle” where the feedback system doesn’t work, it ends in coma and death, Rognum says.

Why? In Norway, Rognum, together with pediatrician and neuroscientist Ol Didrik Saugstad, came up with the theory of “fatal triangle”, which they defined as “a vulnerable period after birth, some genetic predisposition and a trigger event”. Around the same time in the US, a team led by Goldstein and Hannah Kinney at Boston Children’s Hospital came up with a similar idea: “triple risk model”.

It is the latter label that has taken hold and that theory is now the leading explanation among SIDS researchers. It gets to the heart of what scientists suspected at least since the 1970s: SIDS is not caused by a single event, but by several factors that come together. “There’s not just one reason,” says Goldstein. “We put it more in the category of expressing a rare undiagnosed disease where at least for a while, at initial presentation, it is incompatible with survival.”

Rognum noted that the period of greatest risk for death from SIDS, between the second and fifth months after birth, is also the time when the immune system is rapidly developing. “When something develops very quickly, it is also unstable,” he says. It is a vulnerable period after birth. A trigger event can be a seasonal respiratory infections or sleeping on your stomach, or both together – a pairing that increases the risk of SIDS 29-fold.

However, what the “predisposition” is may be the most enduring puzzle at the heart of SIDS. However, in recent years this aspect has also become less of a mystery.

Researchers, including Kinney, thought it might be a problem with serotonergic system – neurotransmitters located in the brain stem that regulate a number of automatic processes, including sleep and breathing. Over the past 20 years, Kinney’s team has honed their hypothesis more studies. An increase of serotonin (5-HT) in the blood, in particular, a biomarker for SIDS in about 30% of cases. Their findings were confirmed by other teams. One study of autopsies, for example, found that serotonin levels were 26% lower in SIDS cases than in healthy infants – a biomarker discovered before Harrington’s discovery.

Similarly, Rognum thought that the genetic element could be due to variants, or polymorphismsin the genes that make up interleukin – which can be anti-inflammatory or pro-inflammatory molecules. They are usually produced in response to damage caused by infection or injury, so variants in these genes can make this part of the immune response weaker or stronger than it should be.

“We found it in the cerebral spinal fluid that SIDS cases had significantly higher levels of interleukin-6. It’s the interleukin that gives us a fever,” says Rognum. “Half of the SIDS cases have levels in the same range as children who died of meningitis and septicemia without having those illnesses.”