For babies to develop and grow normally inside the womb, they must get enough energy. This is supplied in blood through the placenta (afterbirth). If the placenta does not work properly then babies don’t grow as they should. They are more likely to have problems when they are being born and develop long-term health problems, including diabetes and heart disease.

One reason for the placenta not to work properly is an illness called pre-eclampsia. This only happens in pregnancy, where the placenta does not attach properly, leading to less blood flow to the baby. This can cause pregnant mothers to become very unwell and throughout the world remains a main cause of maternal death. It also causes problems for babies, with many being born small and/or needing to be born early to improve their mother’s health.

If the placenta stops working, then babies can die inside the womb before birth (stillbirth). Having a stillborn baby is devastating for women and their families. Unfortunately, nearly one in every 200 pregnancies in the UK ends in stillbirth and in about half of these cases, the placenta was not working properly. It is very difficult to work out which women are at highest risk of having a stillbirth with no test available to tell us which women will be affected.

A test which tells us how the placenta is working could help show which women are at greatest risk of having pre-eclampsia, a small baby or stillbirth. Research has shown that some proteins, which can be measured in a blood sample taken from pregnant women, can tell us how the placenta is working. Two of these proteins are called placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt). Measuring these proteins in the second half of pregnancy in women who are assessed for suspected pre-eclampsia can help to show which women will develop this disease. Some studies have found that measuring these proteins towards the end of pregnancy in a large group of women may help find those at most risk of developing pre-eclampsia. One of these studies also suggested that this test may help show which women are at risk of stillbirth but this only included a small number of pregnancies resulting in stillbirth (23 pregnancies). More work is now needed to check whether this test can be used to find women more likely to have a stillbirth.

If we can find which women are most at risk by using a simple blood test then we can monitor these pregnancies more closely and deliver the baby before complications occur.

In this study, we want to see if measuring PlGF/sFlt in blood samples from pregnant women around 28 weeks through their pregnancy can help to show which women are at risk of pre-eclampsia, having a small baby and/ or having a stillbirth. It has been difficult to work out whether this test is useful in predicting stillbirth, as it is relatively rare in the UK and therefore numbers within individual studies have not been big enough to prove an effect. We have calculated that we need to measure PlGF/sFlt in at least 80 pregnancies experiencing a stillbirth to get accurate results. To get enough samples to achieve this, we plan to look at pregnancies resulting in stillbirth within the ALSPAC cohort and other large UK and European cohorts, including Born in Bradford. We have already had permission to use samples collected at 28 weeks of pregnancy from 11 women in the POPs study who experienced a stillbirth. We plan to use this information, with data gained from the ALSPAC and Born in Bradford cohorts to help reach the number of cases we need for this study to work. Whilst the number of stillbirths within the ALSPAC cohort with samples available around 28 weeks is small, these can be added to data from samples measured in the POPs study and Born in Bradford cohort to help us reach our target of 80 cases. We plan to compare these measurements with measurements on other women who gave samples to the ALSPAC study around 28 weeks of pregnancy and who did not have problems with their placentas.

Of all women who delivered a small baby, not all of these will be due to a problem with the placenta. Some of these babies are just naturally (constitutionally) small. These babies are not at as high risk of complications as small babies who have not reach their full growth potential i.e. those that are growth restricted. We plan to look at the whole placentas from women who had a small baby to help to show which pregnancies had an abnormal placenta. This would help identify which pregnancies had a small baby due to growth restriction secondary to an abnormal placenta. We would look at how well PlGF/sFlt picked up these pregnancies in a subgroup analysis as these are the group most at risk.