Early identification of women at high risk for pregnancy complications

June 12, 2014

One in 200 babies dies before birth in the UK. A study aimed at determining how to reduce the risk of a pregnancy coming to a devastating end is now producing its first results.

"I've spoken to many bereaved parents and the loss of a baby has a profound and life-long impact," said Gordon Smith, Professor of Obstetrics and Gynaecology. "There's a whole life to be gained if you identify a baby who will die in the womb at 40 weeks of pregnancy, and this huge gain can be achieved relatively easily by early delivery of the baby at 38 or 39 weeks."

Smith leads the Pregnancy Outcome Prediction (POP) study, which aims to determine both the risk women face of losing their baby during their first pregnancy and how this can be reduced.

Although some women are identified as for pregnancy complications from their family or medical history – and might be offered ultrasound, biochemical screening and genetic analysis, as well as an early delivery if their baby should show signs of difficulty – most stillbirths occur in women with no known risk factors.

For these low-risk women, the current provision of antenatal care – established in 1929 – still relies on the use of a tape measure.

"We estimate that over half of the 4,000 stillbirths a year in the UK are the result of placental dysfunction, which is frequently associated with impaired growth of the fetus. Apart from urine and blood pressure monitoring for pre-eclampsia – one of the conditions that can cause stillbirth – the standard means of identifying a baby that's small for gestational age in low-risk women is measuring the mother's 'bump' with a tape measure," Smith explained.

Globally, every year 2.6 million babies are stillborn and 3.2 million live-born children die in the first month of life. "Growth-restricted and premature children can also suffer difficulties at delivery, childhood diseases, and educational, social and health problems in later life. The emotional cost to families, coupled with the associated healthcare and social costs, means that research into the prevention of these conditions is more crucial than ever."

Smith's approach in the Department of Obstetrics and Gynaecology, funded by the National Institute for Health Research (NIHR), was to monitor more than 4,500 women during their first pregnancy at several stages until the end of pregnancy. As well as regular ultrasound scans and blood sampling, maternal and paternal DNA samples were taken and, at the time of delivery, samples of placenta, fetal membranes and umbilical cord were collected, together with details of the delivery and baby.

Completed a few months ago, the study has been a massive undertaking, but one that Smith says has laid the basis for years of in-depth analysis: "With this core resource of data and biological samples we can now ask whether there are novel biomarkers to identify women at high risk of developing pre-eclampsia – something that would be especially useful in low – and middle-income countries where scanning may not be available. We can also ask questions such as is inflammation of the placenta more common in complicated pregnancies and can this be detected by measuring circulating markers?"

One of the first questions the team asked was how effective routine ultrasound scans are as a screening test for babies who are small for ; such babies are thought to account for about 30–40% of stillbirths.

"Although previously published research had shown no beneficial effect of routine screening for identifying small babies in the third trimester of pregnancy," said Smith, "it was unclear whether this was because ultrasound performed poorly as a screening test, or whether the associated interventions were ineffective." Smith and colleagues have now clearly shown that routinely scanning women during pregnancy increases the detection of the smallest babies from 32% to 77%.

"The problem with previous studies is that they were designed without any information on how well scanning performed as a screening test. We now know that ultrasound actually performs very well compared with used in other areas of medicine. We are now focusing on how to differentiate between healthy small babies and those who are small due to a pathological process. When we can achieve this, we will be able to identify the babies most likely to benefit from intervention."

"Practice only changes when guidelines change, and guidelines only change when the evidence to support change is strong," said Smith. "When we have refined our screening test, a next step may be large-scale trials of screening. The interventions will include more-intensive monitoring and earlier delivery."

The situation with stillbirth has parallels with sudden infant death syndrome (Sids), explained Smith: "In the 1980s, 1 in 500 died of Sids. But when research showed that sleeping on the front was a risk factor for the baby, this was followed by a public health campaign that reduced Sids by 80–90%. Although the strategy to reduce stillbirth is unlikely to be as simple, one area that we can look at is whether we can generate biomarkers for the antecedents of stillbirth, and use these for population-based screening."

Smith believes that placental dysfunction might result in 'a signature' of biomarkers that can be used to identify a problem with the placenta even in a mother showing no symptoms, and he and others have identified several potential candidates.

Many of these studies address identifying a failing placenta. However, what remains uncertain is why the placenta is dysfunctional in the first place. "One possible initiating factor is infection. Consistent with this, some studies have reported high rates of placental inflammation in pregnancies with adverse outcomes, but the evidence so far is poor."

The search for an infectious agent, possibly even a currently unrecognised bacterium or virus, has now begun, thanks to a new four-year £1.6 million project funded by the Medical Research Council using the data and biological samples gathered by the POP study. Smith and colleagues will be working with Professor Sharon Peacock from the Department of Medicine and Dr Julian Parkhill and Professor Paul Kellam from the Wellcome Trust Sanger Institute, as well as industrial partners.

It's an intriguing possibility that some hitherto unrecognised infectious agent might lead to a significant proportion of pregnancy complications. If so, there would be the possibility of treatment or vaccination to prevent complications, in the same way that women are now vaccinated against human papilloma virus to prevent cervical cancer.

"That said, the idea that we could come up with one magic solution for pre-eclampsia or stillbirth is beyond everyone's expectations at the moment. More realistically, it would seem plausible that diverse infectious agents could impair the function of the placenta, perhaps by activating some common pathway," he explained.

The overarching goal of the Department's research is to apply state-of-the-art approaches in clinical study design, biostatistics, molecular biology and sequencing to develop novel tools that will help differentiate between a healthy and an unhealthy pregnancy. "Our primary aim is to generate clinically useful screening tests that allow us to focus medical care on women who are truly high risk for complications, and to avoid 'medicalising' the experience of pregnancy and birth for the women who are at low risk."

Explore further: Delivering better ways of preventing stillbirth

Related Stories

Delivering better ways of preventing stillbirth

May 14, 2012
(Medical Xpress) -- Despite recent dramatic reductions in cot death rates in the UK, and the development of sophisticated screening for Down’s syndrome, preventing stillbirth is proving tougher to tackle. Now, a major ...

Half of pregnant women who have hypertension and snore unknowingly have a sleep disorder

June 2, 2014
One in two hypertensive pregnant women who habitually snore may have unrecognized obstructive sleep apnea, a sleeping disorder that can reduce blood oxygen levels during the night and that has been linked to serious health ...

Hyperemesis gravidarum during the second trimester is more likely to cause placental complications

January 29, 2013
Pregnancies complicated by hyperemesis gravidarum in the second trimester of pregnancy are at a much higher risk of associated placental dysfunction disorders such as placental abruption and small for gestational age babies ...

Why are girl babies winning in the battle for survival?

May 27, 2014
Sexual inequality between boys and girls starts as early as in the mother's womb – but how and why this occurs could be a key to preventing higher rates of preterm birth, stillbirth and neonatal death among boys.

Preterm delivery, low birth weight and neonatal risk in pregnant women with high blood pressure

April 15, 2014
Pregnant women with chronic hypertension (high blood pressure) are highly likely to suffer from adverse pregnancy outcomes such as preterm delivery, low birth weight and neonatal death, which highlights a need for heightened ...

Recommended for you

Negative birth outcomes linked to air pollution exposure early in pregnancy, study finds

July 27, 2017
Exposure to air pollution early in a pregnancy could increase risk for preterm birth and low birth weight, according to a study led by researchers at NYU School of Medicine, and published on July 27 in Environmental Health ...

Study shows a significant ongoing decline in sperm counts of Western men

July 25, 2017
In the first systematic review and meta-analysis of trends in sperm count, researchers from the Hebrew University-Hadassah Braun School of Public Health and Community Medicine and the Icahn School of Medicine at Mount Sinai ...

Women exposed to smoke while in womb more likely to miscarry

July 13, 2017
Women exposed to cigarette smoke while in their mothers' wombs are more likely to experience miscarriage as adults, according to new research from the University of Aberdeen.

Lack of a hormone in pregnant mice linked to preeclampsia

June 30, 2017
(Medical Xpress)—A team of researchers from Singapore, the Netherlands and Turkey has isolated a hormone in pregnant mice that appears to be associated with preeclampsia—a pregnancy-related condition characterized by ...

Aspirin reduces risk of pre-eclampsia in pregnant women

June 28, 2017
Taking a low-dose aspirin before bed can reduce the risk of pre-eclampsia, which can cause premature birth and, in extreme cases, maternal and foetal death.

The biology of uterine fluid: How it informs the fetus of mom's world

June 22, 2017
A developing fetus bathes in a mixture of cellular secretions and proteins unique to its mother's uterus. Before fertilization, the pH of uterine fluid helps create a conducive environment for sperm migration, and afterward, ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.