Breakthrough in understanding and treating pregnancy disorder CHI

Using imaging software to count immune cells within placentas, our researchers at the Tommy’s Maternal and Fetal Health Research Centre in Manchester have made a major step forward in diagnosing and understanding a rare pregnancy condition which can cause miscarriage, stillbirth, restricted growth and neonatal death.

A standardised method of diagnosing Chronic Histiocytic Intervillositis (CHI) means a better understanding of whether experimental treatments to save babies’ lives are working.

​CHI is a pregnancy disorder in which the immune system floods the placenta with immune cells, damaging it and causing severe problems with baby’s growth, miscarriage or stillbirth.

Mothers who have CHI during pregnancy will often find that it returns in subsequent pregnancies.

Treatment in a subsequent pregnancy remains experimental, but our researchers are working hard to better understand, diagnose, and ultimately find a cure for this devastating condition.  

Improving and standardising diagnosis

Currently, diagnosing CHI can only be done by studying the cells and tissue of the placenta under a microscope after a birth. Diagnosing it varies between pathologists involved – there isn’t a standardised method of diagnosis and assessment.

Now, a unique new approach by our Manchester team, using computer software, is helping to more accurately diagnose the condition and see whether treatments have had an impact.

The imaging software, called QuPath, can be used to measure immune cells in placentas which had a diagnosis of CHI and compare them to healthy placentas. It can also look at placentas from subsequent pregnancies that were being treated with medication for CHI.

In a study published in the journal Archives of Pathology & Laboratory Medicine on Tuesday 25 July, Dr Chloe Brady and colleagues explain how this software shows that there is a 32-fold increase in the quantity of immune cells in placentas affected by CHI, compared to healthy placentas.  

While it was previously known that CHI causes increased inflammation, QuPath software has allowed the team to more accurately assess the amount of inflammation, and produce a threshold for making the diagnosis.  

Our researchers found evidence of CHI in subsequent pregnancy placentas that had not been initially diagnosed​. They were also able to exclude 4 placenta samples that originally had a CHI diagnosis as they did not meet the threshold for diagnosis by the software​. 

This new approach means that CHI can be better identified, and we can learn more about the impact of treatment.

Experimental treatments

Led by Tommy’s Centre Director, Professor Alex Heazell, researchers have recently been testing the effectiveness of a combination of medication including Hydroxychloroquine and Prednisolone, which has long been used to treat a wide range of health problems, including allergies, blood disorders, and to prevent organ rejection after a transplant.  

Other treatments such as aspirin and blood thinners are also being explored to see whether they can change the body’s immune response.

Software shows the impact of treatments

Dr Chloe Brady's study shows that when subsequent pregnancies are treated with a combination of medications to help blood flow and suppress the immune system, the amount of immune cells in the placenta reduces: a promising result for the future development of treatments.

8 of the 11 subsequent pregnancies for women whose placentas were studied for this research were treated with a combination of aspirin, heparin, prednisolone and hydroxychloroquine. 3 pregnancies were treated with aspirin, heparin and hydroxychloroquine.

Inflammation was significantly reduced in all pregnancies, with QuPath suggesting that CHI only came back in 18% of cases.  

Crucially, despite the condition’s usual prognosis, all pregnancies resulted in live births, and there were no stillbirths or neonatal deaths.

Dr Chloe Brady says:  

“CHI is hugely distressing condition but managing it is complicated by a lack of understanding into its cause, lack of standardisation in diagnosing it, and current treatments still being experimental.

“Our study shows that computer analysis of inflammation, alongside expertise from pathologists in grading how severe lesions are, is accurate in identifying the condition and in showing whether treatment affects its recurrence.  

“This is a really exciting breakthrough in improving our understanding, enabling medical professionals to more easily identify the condition, and helping to give parents who have lost their baby or babies the answers they need.”

Hannah and her husband Darren from Greater Manchester sadly lost their son, Billy, after 38 weeks of pregnancy due to CHI. Hannah has gone on to have 2 more children, Ozzy and Daisy, after being referred to Professor Heazell and team at the Tommy’s Rainbow Clinic at Saint Mary’s Hospital in Manchester.

Speaking about her pregnancy with Ozzy, Hannah says:  

“I had a scan at 6 weeks then so many scans and appointments, placenta scans at Tommy’s from 17 weeks where Prof Alex explained everything so clearly, never sugar-coating but always offering hope. I was on lots of medications including steroids, vitamin D and high doses of folic acid daily but I didn’t know if it would work and I was anxious until I got to hold him in my arms.

“Without Tommy’s, without Prof Alex and his research, neither Ozzy or Daisy would be here.”