Stillbirth and fetal free haemoglobin

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

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.

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. 

Funding

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

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