Being able to accurately identify which babies are at the highest risk of stillbirth or neonatal death means that treatments can be better targeted and families whose pregnancies are healthy can be reassured.

How well a baby is growing gives an idea of how healthy they are. Some babies are not able to grow as expected during pregnancy due to problems with the placenta. Unfortunately, for these babies it can mean they are more likely to die during pregnancy or around the time of birth or may experience complications. The POPS study set out to see if having additional ultrasound scans in the final part of pregnancy could help identify babies who are smaller than expected and to see if there are any scan or Doppler measurements that are more common in babies or are stillborn or born unwell. Researchers found that ultrasound scans can help identify babies who are small, but some still died after a reassuring scan. Research is now taking place to see if combining blood tests with ultrasound scans can give clearer, more accurate information.

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What is the aim of this study?

The study was designed to see whether having additional ultrasound scans in the third trimester of pregnancy helps to identify babies who are smaller than expected. It also looked at whether any scan or Doppler measurements are more common in babies in babies who are stillborn or very poorly at birth.


Why is this important?

Some babies are not able to grow as they should during pregnancy because the placenta isn’t working properly. This slow growth is called ‘fetal growth restriction’, and babies who have this are more likely to have problems at birth and also, sadly, are more likely to die before or around the time of birth compared with babies who have grown normally.

Unfortunately it isn’t easy to identify babies who have fetal growth restriction during pregnancy. In most pregnancies, the baby’s growth is estimated from the increase in size of the mother’s bump (or the symphysial fundal height to give it the proper name) during pregnancy. There is a real need to improve the identification of babies who would benefit from extra monitoring and perhaps early delivery, and there is much debate around whether additional ultrasound scans in the third trimester would be helpful.


Healthy small baby or growth restriction?

Babies with fetal growth restriction fall into a larger group of babies who are said to be ‘small for gestational age’ or SGA. Most SGA babies are healthy, but because the growth-restricted babies are also SGA, researchers sometimes look at SGA babies rather than growth-restricted babies. This is because there are more SGA babies so it is easier to study this group and get useful results.


What happened in the study?

A total of 4444 first-time pregnant women took part in the POP study, which was carried out at the Rosie Hospital in Cambridge. All the women had the normal pregnancy care they would expect in the NHS, with some women having additional ultrasound scans in the third trimester if there were concerns about the baby. The results of these scans were made known to the woman and her maternity team and were used to make decisions about the rest of the pregnancy, as would normally happen.

But as well as this ‘selective’ screening, all women in the study had ultrasound scans at 28 and 36 weeks of pregnancy. The results of these scans were not made known to the participants or their maternity team. (This was because knowing the result of the scans may have influenced the rest of the measurements in pregnancy, which could make the study results less reliable.)

Once the babies were born, the research team looked at the birthweight and the scan results to see how often the scans correctly identified an SGA baby. The team also looked at whether any differences in scan measurements or Doppler results were more commonly found in the babies who were or very poorly at birth or stillborn.


What did the study find?

The research team were able to analyse data for 3977 babies. They were able to compare the ability of the selective scans (current care) and research scans (scanning all women) to detect the live-born babies who were SGA or severely SGA.

In this study, the selective scans (so only scanning a woman if there was a clinical reason to) correctly identified 20% of SGA babies and 32% of severely SGA babies. In comparison, scanning all women correctly identified 57% of SGA babies and 77% of severely SGA babies.

Very roughly speaking, this means the selective scans picked up 2 in 10 SGA babies and 3 in 10 severely SGA babies, whereas the universal screening picked up around 6 in 10 SGA and 8 in 10 severely SGA babies.


Identifying babies who were stillborn or poorly

Seven babies were stillborn in this study, 26 babies either died shortly after birth or were seriously ill at birth, and 275 babies were poorly at birth. The research team looked at the scans of these babies and also the results of Doppler tests to see if there were any patterns in the results. The aim was to find something that could pick out those babies who were SGA and poorly from those who were small and healthy.

Only one of the measurement gave this additional information. The researchers  found that estimating the growth rate of the abdomen from the difference in its size at the 20 week scan and at the last scan before birth gave a measurement that was markedly lower  in the babies who were SGA and poorly, very poorly or stillborn at birth.

Babies who were identified as SGA by the scans but whose abdominal growth rate was normal were healthy. But SGA babies whose abdominal growth rate was very low were much more likely to be poorly, very poorly or stillborn: 18 times more likely to be SGA and poorly at birth and about 40 times more likely to be SGA and stillborn or seriously ill.


What do the researchers say about these results?

The team acknowledge that scans can sometimes mis-identify a normal-sized baby as SGA, causing the parents to worry unnecessarily. They also say that another study in pregnant women who aren’t in their first pregnancy should be carried out to see if the results are the same. But on the basis of the results published, the team conclude that “a programme of screening that includes universal ultrasonography and intervention following a care bundle based on the latest RCOG[Royal College of Obstetricians and Gynaecologists] guideline has the potential to reduce the number of adverse perinatal outcomes caused by FGR [fetal growth restriction].”


What’s next?

While the POP Study has shown that ultrasound can improve the detection of small babies, some babies still die after a reassuring scan. And while research to develop blood tests (looking at ‘biomarkers’ in blood) to highlight a risk of stillbirth has been promising, the tests don’t give clear enough information on their own to be helpful.

So the next question that the POP study is asking is whether ultrasound can be combined with blood tests to identify more of the babies who are becoming ill towards the end of pregnancy. The research team in Cambridge are looking at the results of their POP ultrasound scans and blood tests and matching these with the medical information on the babies born to mothers in the study to see if there’s a pattern. Find out more about POPS2.

Research Papers

Sovio, U. et al. (2015) ‘Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study’, Lancet (London, England), 386(10008), pp. 2089–2097. doi:10.1016/S0140-6736(15)00131-2

Further statistical analyses were carried out in following published papers:

Cleaton, M.A.M. et al. (2016) ‘Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction’, Nature Genetics, 48(12), pp. 1473–1480. doi:10.1038/ng.3699

Partap, U., Sovio, U. and Smith, G.C.S. (2016) ‘Fetal Growth and the Risk of Spontaneous Preterm Birth in a Prospective Cohort Study of Nulliparous Women’, American Journal of Epidemiology, 184(2), pp. 110–119. doi:10.1093/aje/kwv345

Salavati, N. et al. (2016) ‘The relationship between human placental morphometry and ultrasonic measurements of utero-placental blood flow and fetal growth’, Placenta, 38, pp. 41–48. doi:10.1016/j.placenta.2015.12.003

Sovio, U., Murphy, H.R. and Smith, G.C.S. (2016) ‘Accelerated Fetal Growth Prior to Diagnosis of Gestational Diabetes Mellitus: A Prospective Cohort Study of Nulliparous Women’, Diabetes Care, 39(6), pp. 982–987. doi:10.2337/dc16-0160


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