Dr Emily Cornish – Immune Response in Recurrent Adverse Pregnancy Outcome

Scientists are investing a new treatment for a tragic yet little known condition that devastates the dreams and lives of couples trying for a baby.

Understanding why some babies are damaged by the mother’s immune system during pregnancy, leading to miscarriage and stillbirth

Scientists are investigating a new treatment for a tragic yet little known condition that devastates the dreams and lives of couples trying for a baby.

The MIRAPO study is investigating three rare placental disorders that cause recurrent miscarriage and stillbirth: Chronic histiocytic intervillositis (CHI), villitis of unknown etiology (VUE) and massive perivillous fibrin deposition (MPFD).

These conditions have significant long-term physical and psychological impact on affected families. As well as causing pregnancy loss, they have also been associated with chronic problems in surviving children including cerebral palsy.

The cause of CHI, VUE and MPFD is unknown, but they have been potentially linked to autoimmune diseases. Small studies have reported successful pregnancy after using treatments that suppress the mother’s immune system.

A Wellbeing of Women funded team at UCL have had promising early results with a drug used to prevent the rejection of kidney transplants which is safe in pregnancy.

Dr Emily Cornish said: “We believe these conditions may arise when a mother develops an antibody against the developing pregnancy, which damages the placenta and prevents it from supporting normal growth of the baby. If the damage is severe, the baby can be stillborn.

“We hope that discovering more about how these conditions that cause recurrent pregnancy loss will lead to the identification of new treatments that could benefit women with CHI, VUE, MPFD and other related conditions.

“We have prevented recurrence of CHI in two women by giving a medicine usually used to prevent immune rejection of kidney transplants. As it is safe in pregnancy, we believe it could also improve pregnancy outcome for women with related placental disorders or with unexplained recurrent pregnancy loss.”

CHI, VUE, MPFD can only be diagnosed once a pregnancy has ended by analysing the placenta. Apart from finding that a developing baby appears much smaller than expected on an ultrasound scans, there is no warning signs for recurrence and no reliable test that can predict whether a future pregnancy will succeed or result in loss of the baby.

Understanding why certain women develop these devastating conditions and exactly how they cause recurrent pregnancy loss should help us to identify new treatments that could improve pregnancy outcome. This could translate into wider benefits for women affected by other immune-mediated pregnancy disorders and women with unexplained recurrent pregnancy loss.

Case study:

Claudia Belardo suffered from four loses in two years. She was diagnosed with Chronic histiocytic intervillositis (CHI).

Claudia said: “I was told my baby was dying but I still had to go to scans. I was terrified of moving at night. You are causing the slow death of your child, it’s beyond your control.

“During my second pregnancy, I was told the baby wasn’t going to make it for 10 weeks, I thought I was having a break down. I begged to go to hospital for them to section me because I didn’t think I could cope.

“I had no problem conceiving or with fertility and the pathology didn’t indicate anything was wrong, so the message seemed to be getting was ‘these things happen, try again’. It was completely frustrating. I ended up going private and spending all my savings. I was referred to a consultant in Oxford, but he didn’t know much about the condition and there was no centre of excellence to refer me to.

“There wasn’t any mental health support either. You’re dealing with a bereavement, but you have other factors, it takes a toll on relationships and you can do nothing but blame yourself.

“I wasn’t coping for a long time. I was given maternity leave after I lost my twins. I expected to have the house filled with the sound of crying babies, but I was left at home in silence. I could hear my neighbour’s baby crying through the walls.

“We expected twins, and we were naïve that the outcome would be anything else but twins, we did not understand loss.

“I tried to bleed out my emotions in word form. I coped by writing my blog. The days were all hazy, I went through post-traumatic stress, trying to block it out.

“I am not the person I was. I think that it has changed me completely. I had a lot of anger. I was angry at the world in general. Grief never leaves you.

“I can’t bear the thought that there are other women going through what I went through. When your baby dies that the worst that happens, I always knew what the worst can be you can’t imagine unless you go through it.

“Although I have two boys that are now five, I would sincerely have loved to have had a successful pregnancy like my surrogacy.

“Right after the twins died, I started researching. No one was talking about the fact it could be the immune system. I wrote some papers and it was really only my work out there.

“I just wish there was a better, quicker way to diagnose CHI, and there needs to be more research to know if this is reversible.”

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