A new report details a sharp spike in cases of situs inversus found on ultrasounds in China during the first seven months of 2023.
Researchers speculate that the spike could be linked to a late 2022 increase in COVID-19 cases in China.
The report is not conclusive, and more research is needed.
In a report published last week in the New England Journal of Medicine, Chinese physicians reported a sharp increase in cases of fetal situs inversus. This condition causes the reverse placement of major internal organs. Data from January 2014 through July 2023 was compiled from clinical data from two obstetrics centers in China, according to ultrasound records.
Ultrasounds were conducted between 20 and 24 weeks of pregnancy. Researchers found that, when broken down month by month, the highest surge occurred between April and June 2023, with rates falling back in line with historic numbers in July. For context, between 2014 and 2022, there were about six situs inversus cases (per 10,000 births. In 2023, the rate jumped to nearly 24 cases (per 10,000 births).
The study notes that there was no clear reason for this increase, and it is not explained by factors such as any changes to diagnostic protocols or physician training related to situs inversus.
Researchers speculate that the spike in cases could be connected to a late 2022 spike in COVID-19 that occurred when China lifted many of its COVID-19 safety regulations. Shortly after regulations were lifted, China experienced a COVID-19 surge that lasted from December 2022 to February 2023, infecting an estimated 82% of the population in China. Since the spike in fetal situs inversus cases began about four months after this spike in COVID-19 cases, study authors theorize that the two could be connected through direct infection or an immune response.
However, there is no evidence that any cases of situs inversus included in the study were pregnancies in people who had been infected with COVID-19.
Additionally, there have not been any similar observed spikes in situs inversus following other COVID-19 surges in China or any other location.
There are also multiple known risk factors that can lead to situs inversus, including exposure to pesticides and other chemicals during pregnancy, use of cigarettes or cocaine during pregnancy, and diabetes mellitus. Genetics can also play a role; at least 20 genetic mutations have been identified in people with the condition. It’s unknown which, if any, of these risk factors and genetic links were present in any pregnancies in this study.
The study authors acknowledge these limitations. They also acknowledge that although cases quadrupled, situs inversus is still rare. The report does not make any conclusions but calls for further research into this spike and emphasizes that COVID-19 could have played a role.
The complexities of situs inversus
The overall incidence of situs inversus worldwide is unclear. The incidence of all conditions that cause abnormal organ placement, heterotaxy syndrome, is reported to be about one in 10,000 people worldwide. However, researchers believe that the condition is underdiagnosed. Situs inversus is reported to be as common as 1 in 6,500 births and as rare as 1 in every 8,000 to 25,000 births. Additionally, situs inversus with levocardia is rarer than situs inversus with dextrocardia.
This ambiguity is largely because symptoms can be so varied. In some cases, situs inversus causes severe birth defects affecting the heart and other organs.
Chronic conditions are also common. Typical conditions linked to situs inversus include heart conditions, valve and vein issues, and respiratory conditions like primary ciliary dyskinesia. In other cases, however, the condition can go completely undetected. People can be unaware for decades that they have situs inversus and might only discover it when imaging for another condition or concern reveals their abnormal organ placement.
“Because it doesn’t always cause symptoms, and because it’s so rare, a person might not always know they have it,” surgeon Douglas Warriner, MD, explains. “The organs can be functional in these positions. So it’s very possible for a person to have no complications, but then other patients will experience cardiac dysfunction or lung dysfunction.”
In a notable case from 2018, situs inversus with levocardia was discovered during the autopsy of an Oregon woman, Rose Marie Bentley, who died of natural causes. Bentley lived to be 99 with no major health issues, and reportedly never knew about her situs inversus. She is the longest-living known person to have the condition.
Even when situs inversus doesn’t cause any symptoms or complications, knowing that one has the condition can be important. For treatments ranging from surgery to emergency care and diagnostics, it can be critical for medical providers to be aware of a patient’s organ placement.
“They should be aware, and it should be made known for the future. Especially for any surgeries they might have,” Dr. Warriner says.