JThe Medical Research Council (MRC) Max Perutz Scientific Writing Prize is open to MRC-funded doctoral students who are invited to write about the importance of their area of research. This year’s 10 shortlisted topics included cancer immune therapies, Scotland’s drug-related death rate and schistosomiasis, a neglected tropical disease. The high quality of the applications made judging difficult. Ultimately, the panel, made up of ObserverIan Tucker, the Science Museum’s Roger Highfield, journalist Samira Ahmed, science communication lecturer Andy Ridgeway, MRC’s Jennifer Anderson and award-winning young science writer Zara Hussan agreed that the £1,500 prize should go to Emily Cornish, PhD candidate at the EGA Institute for Women’s Health, University College London, for her essay on recurrent pregnancy loss. “I’m thrilled to have won this inspiring award,” says Emily.
The winning essay
Amy’s third baby was born in the middle of the night. In the split second before he cried, everyone in the operating room held their breath. I was crouched in a corner holding a huge bucket of ice, waiting to collect the placenta. The stakes seemed incredibly high. Both of baby William’s sisters were stillborn due to a placental disorder called chronic histiocytic intervillitis (CHI).
Most obstetricians have never heard of CHI. It is a rare disease that affects one in 2,000 pregnancies and can only be diagnosed after childbirth by examining the placenta under a microscope. The objective of my thesis is to discover the cause of this disease.
During a healthy pregnancy, the mother’s blood flows through the placenta into a channel called the intervillous space, where it comes into direct contact with tree-like structures called placental villi. This is where the vital gas and nutrient exchanges between mother and baby take place. In CHI, the channel is blocked by maternal immune cells, impairing the exchange process and causing serious consequences for the baby. Only half of these pregnancies end in a live birth and some babies must be delivered several months earlier by emergency caesarean section to give them a chance of survival.
CHI usually affects fit, healthy women with no medical conditions. It comes out of nowhere and has a devastating impact on couples hoping to have a baby. The cruelest thing about CHI is that eight out of 10 times it will recur in a subsequent pregnancy.
Any miscarriage or stillbirth is emotionally upsetting for parents, but for most it is unlikely to happen again. This is where CHI is different. When Amy was diagnosed after her second daughter was stillborn, she experienced ‘double grief’: not only for the loss of Grace, but for the loss of the future and family she had envisioned. . No test can reliably predict the recurrence of CHI, so these subsequent pregnancies require incredibly close monitoring. Many women will have scans fortnightly, struggling to suppress their fear as they return to the same ultrasound services where their previous losses were diagnosed.
The cause of CHI is unknown. However, when you look at a placenta with CHI through a microscope, at the cellular level it looks remarkably like a rejected kidney transplant. My hypothesis is that affected mothers make an antibody that attacks the developing placenta. This leads to inflammation of the placenta and an influx of maternal immune cells. Support for this theory comes from the fact that when couples affected by CHI undergo IVF using their own eggs and sperm, and transfer the embryo to a surrogate mother, the pregnancy progresses normally without any signs of CHI. This confirms that the problem stems from the mother’s immune system.
Initially, designing a research study focused on CHI seemed daunting – how could I expect to enroll a significant number of women when the disease is so rare? Fortunately, I was saved by a woman named Claudia and a Facebook group.
Claudia has lost four sons to CHI in the space of three years. As she went through the heartache of learning to live without her children, she became determined to spread awareness about this mysterious and brutal disease. Since then, she has been a tireless advocate for the advancement of CHI research and helps run a Facebook support group for affected women. The group has over 700 members and is a lifeline for parents struggling to come to terms with their diagnosis.
Despite its rarity, and thanks to Claudia’s group, I managed to recruit more than 30 women in my study. I take blood and placenta samples from them to look for any unusual immune cells, proteins or antibodies that might explain what is wrong with their pregnancy. I also analyze their DNA to look for variations in their genetic code that could predispose them to CHI.
By purifying antibodies from their blood and comparing them with women who had healthy, uncomplicated pregnancies, I showed that women with CHI react abnormally to placental proteins. My next challenge is to determine exactly what triggers this reaction and to unravel the molecular basis of how it leads to catastrophic placental damage. And the ultimate goal is to use this knowledge to develop new targeted treatments that can prevent recurrences.
My team is already making progress on the last question. Claudia lost her children 10 years ago and eventually resorted to surrogacy because nothing her doctors tried could stop the relentless recurrence of CHI. However, in recent months we have become cautiously optimistic about a new treatment protocol that involves suppressing the mother’s immune system during pregnancy. Once again, we have drawn parallels between CHI placentas and rejected transplants. This treatment is the same as that taken by people who have had an organ transplant to prevent their body from rejecting the donated organ. It is an intensive cocktail of drugs that requires regular blood tests and special vigilance for the first signs of potentially dangerous side effects. We have only treated a handful of women so far, but the majority have gone home with a healthy baby.
But until we discover the cause of CHI, these treatments are, at best, an educated guess. I am only nine months into my doctorate and I am well aware that finding a miracle cure is an unrealistic dream. However, my vision is to make concrete progress in our understanding of CHI so that future treatments can be tailored to the specific defect in the immune system of affected women.
After Amy lost her daughters, she felt like she was “kicked out of the motherhood club”. She couldn’t bear to lose another baby and although the prospect of a heavily medicated pregnancy filled her with anxiety, she decided to give it a shot. Amy took over 1,000 pills and injected blood thinner at least 200 times during her pregnancy with William. She traveled to the hospital on commuter trains during the pandemic, came to scans alone due to Covid’s restrictive visiting policy and underwent blood tests almost weekly.
I am inspired and moved by the extraordinary courage and determination of the women who embark on this diet. CHI has been overlooked by obstetrics researchers, but fortunately the women who have experienced it are highly motivated and desperate to educate us. If my research can draw attention to the massive impact of CHI and give affected families some hope, then spending my evenings crouching in an operating room with an ice bucket seems entirely worthwhile.
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