Stillbirth and fetal free haemoglobin

Researchers supported by Tommy’s have found that the substance that usually carries oxygen around our blood may have harmful effects on the baby when it escapes from red blood cells.

  • Author's list

    Dr Ian Crocker, Dr Paul Brownbill, Professor Alexander Heazell, Anna Hoaksey

Many babies that are stillborn show signs that there isn’t enough blood flow in the placenta. Sometimes, the blood vessels in the placenta can become too narrow, stopping the baby from getting the nutrients and oxygen it needs. If this goes on for too long, the baby might not be able to grow properly. In the worst cases, the baby’s blood supply can be completely cut off.

Researchers supported by Tommy’s have found that something called cell free fetal haemoglobin might be involved in restricting the blood supply in the placenta. Haemoglobin is a protein that exists in all of our red blood cells. It’s the substance that picks up oxygen so that our blood can transport it around the body. While the baby is growing in the womb, it makes a type of haemoglobin that is slightly different to an adult’s: it binds to oxygen more strongly. This helps the baby to get all the oxygen it needs from the mother’s blood.

If a baby’s haemoglobin is not contained in red blood cells – cell free fetal haemoglobin – it can remove substances in the blood that help the blood vessels to widen. Usually, free haemoglobin is taken out of the blood by an enzyme called HO-1. However, if there is not enough of this enzyme, free haemoglobin is left in the blood, causing the blood vessels to narrow. In turn, this will decrease the flow of blood in the placenta.

To understand better how this can increase the risk of stillbirth, Tommy’s are funding PhD student Anna Hoaksey, to carry on looking at the role of fetal haemoglobin. She will try to find out how levels of HO-1 can get low enough to be harmful, as well as studying potential ways of stopping the blood vessels from becoming too narrow. 

In her recent work, Anna has confirmed that babies with weakened circulation do have the highest levels of cell free fetal haemoglobin. We have identified a drug called hydroxychloroquine (HCQ) that could be used to counteract this problem. Our experiments have shown that HCQ can stop fetal haemoglobin from making the blood vessels too narrow. As HCQ can safely cross the placenta, our next steps are to test this in clinical trials for the treatment of fetal growth restriction and stillbirth.

In the future, this vital work has the potential to find new drugs that will prevent stillbirth. 

Get our research updates

Tommy's funds research across the UK investigating the reasons for pregnancy complications and loss. We can keep you updated on our research news.  If you're interested in being kept updated about our research and news from Tommy's, click here.

This study is fully funded by Tommy's and takes place in a Tommy's centre

Read more on this topic

  • Research into stillbirth

    When a baby dies after 24 weeks of gestation, it is called a stillbirth. Nearly 3000 families a year get the devastating news that their baby is not alive. Our research is helping to change this.
    Research into stillbirth

  • ReMIT-2 – a feasibility study for spotting the early signs of complications

    We need better ways to spot the early signs of pregnancy complications. The ReMIT-2 study laid the foundations for a large clinical trial of a blood test which could predict which women need urgent care to prevent stillbirth.
    ReMIT-2 – a feasibility study for spotting the early signs of complications

  • Can steroid injections improve blood flow to babies at risk of stillbirth?

    Finding out whether steroids can improve the blood flow through the placenta
    Can steroid injections improve blood flow to babies at risk of stillbirth?

  • Older mothers and the ageing placenta

    Consistent with ageing, the placenta in older mothers does not work as effectively. Researchers supported by Tommy’s are investigating why this happens.
    Older mothers and the ageing placenta

  • Assessing how healthy babies are when they start moving less than normal (FEMINA2)

    Reduced fetal movements are a common reason for women to go to hospital in the last 12 weeks of pregnancy. There is currently no way to know which women will have a normal pregnancy and which have problems.
    Assessing how healthy babies are when they start moving less than normal (FEMINA2)

  • Comparing 2D and 3D MRI to study the placenta

    Our scientists are developing new ways to use MRI scans to study the placenta, so that we can understand how it works and how its structure and function change during pregnancy. This will help us prevent complications like stillbirth and miscarriage.
    Comparing 2D and 3D MRI to study the placenta

  • Older mothers and the risk of stillbirth

    Women over 35 are more likely to have a stillbirth. Researchers supported by Tommy’s are looking at how the placenta may play a role in this, and are testing how we can stop stillbirths by making sure the placenta is healthy.
    Older mothers and the risk of stillbirth

  • Viagra: is it an effective treatment for stillbirth (STRIDER)

    Viagra works by increasing blood flow. Fetal growth restriction is often caused by poor flow of blood through the placenta. This trial is looking at whether Viagra is effective in increasing blood flow to the baby.
    Viagra: is it an effective treatment for stillbirth (STRIDER)

  • Assessing how healthy babies are when they start moving less than normal (FEMINA3)

    Reduced fetal movements are a common reason for women to go to hospital in the last 12 weeks of pregnancy. But there is still no way to accurately tell which women will have a normal pregnancy, and which will have problems.
    Assessing how healthy babies are when they start moving less than normal (FEMINA3)

  • Improving support in a pregnancy after stillbirth or neonatal death (the IMPS study)

    Many parents who have suffered a stillbirth embark on another pregnancy, often within a relatively short time after their loss. We currently know very little about women’s experiences of care and what extra support they would find helpful.
    Improving support in a pregnancy after stillbirth or neonatal death (the IMPS study)

  • Testing for microRNAs to find out when the placenta isn’t working

    Scientists have been looking to see if fragments of DNA-like material in a mother’s blood could be used as a sensitive test to find women at risk of stillbirth.
    Testing for microRNAs to find out when the placenta isn’t working

  • Is fetal growth restriction caused by failure of the placenta to adapt to nutrient demand?

    In this study we will compare placentas from normal and Fetal Growth Restricted-affected pregnancies to identify what the important signals might be.
    Is fetal growth restriction caused by failure of the placenta to adapt to nutrient demand?