Improving the prediction of pregnancy outcomes

Breaking new ground 13. feb 2021 3 min Postdoc David Westergaard, Physician and Part-time Lecturer Astrid Marie Kolte Written by Morten Busch

Pregnancy loss is not just a huge blow for parents. In both high-income countries and globally, an increasing number of people are involuntarily childless or have fewer children However, there are significant gaps in knowledge of the reasons for pregnancy loss. A new study of data on pregnancies in Denmark over 40 years shows that, although previous pregnancy loss negatively affects the chance of a live birth, it is far from being the only factor. The new knowledge can lead to better counselling and treatment for the many affected people.

For most people, losing an unborn child is as profound as the miracle of creating life itself. In fact, pregnancy loss is the most common severe complication of pregnancy, affecting one in four pregnancies. Some women have recurrent pregnancy losses, and the decision to go through the stress and grief once again can be difficult. New research has analysed the chance of a woman achieving a live birth based on previous pregnancy loss, age and other factors and may therefore help to provide answers.

“Our results clearly show that a woman’s pregnancy history greatly influences the chance of the next pregnancy resulting in a live birth. However, only considering the woman’s age and the number of losses is insufficient to predict whether a pregnancy will end with a live birth. The new model may provide far better answers, but we still need to improve understanding of the biological determinants to provide clear answers and thus be able to help the affected people better,” explains co-first author Astrid Marie Kolte, physician and Part-time Lecturer, Department of Clinical Medicine, University of Copenhagen and Postdoctoral Fellow, Recurrent Pregnancy Loss Unit, Capital Region of Denmark.

Data on more than 1 million women

Based on data from Denmark’s population over the past 40 years, the researchers analysed the chance of live birth – based not only on previous pregnancy losses but also on the woman’s age, ectopic pregnancies, previous molar pregnancies and obstetric complications in previous births.

“I have had many discussions with pregnant women who had a pregnancy loss and have been asked whether that loss would influence whether they can give birth to a child next time. I have often thought that we lack information on the effects of previous pregnancy complications, so our study aimed to qualify these discussions and focus on those who really need help,” says Astrid Marie Kolte.

To analyse the factors that determine whether a pregnancy leads to a live birth or pregnancy loss, the researchers designed an algorithm to enable them to predict this based on data from more than 1 million women who were pregnant at least once. The procedure was iterative and continued until the factors that were not decisive were removed from the prediction system.

“The figures clearly show that previous pregnancy outcomes and the order of events affect the chance of live birth. For a 25-year-old woman who has not had a pregnancy loss, the chance of live birth exceeds 90%, but three previous pregnancy losses reduces the chance to 75%, and if the woman is 35 years old with three previous pregnancy losses, the chance of live birth declines to nearly 50%,” explains co-first author David Westergaard, Postdoctoral Fellow at the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen and the Recurrent Pregnancy Loss Unit, Capital Region of Denmark.

Not enough to say try again

Although the new models provide a clear picture, the data also clearly show that pregnancy history and a mother’s age are insufficient to predict the outcome of a given pregnancy, even considering the effects of birth complications.

“Solely considering age and the number of losses does not predict whether a pregnancy will end as a live birth . The new model shows that the exact sequence of events is important, but the model cannot explain everything, which reminds us that the biological determinants that affect pregnancy outcomes are insufficiently understood,” says Astrid Marie Kolte.

Research has repeatedly shown that pregnancy loss is associated with an increased risk of subsequent loss. The more losses, the greater the risk becomes. In this respect, the new study confirms previous results but is also nuanced so that physicians in the future can give earlier and clearer answers to hopeful parents, and according to Astrid Marie Kolte, this is very important.

“Pregnancy loss is the most common serious pregnancy complication, with 20,000 annual cases in Denmark, and significantly affects health. Studies have shown an increased risk of illness, especially among women, with serious effects such as stress and depression, so taking the problems and these people seriously is important. We cannot just say ‘try again’ and send them home. We want to be able to give them a realistic, scientifically based view of their chance of having a successful outcome in their next pregnancy,” she explains.

Genetics can provide vital answers

Physicians can use the new prediction model to give clear advice based on an individual’s exact history, giving women justified hope. Another ongoing study will nuance and back this up and will determine how many children women with a history of pregnancy loss actually end up having. The researchers also hope that research over the coming years can provide better explanations. Smoking, alcohol, changes in the uterus, blood clotting disorders and hormones are currently known risk factors.

“An estimated half of pregnancy losses are associated with genetic abnormalities, and the other half result from other conditions, including women’s immune systems. Remember that pregnant women provide a womb to someone who is typically 50% genetically different from themselves. Women’s immune systems markedly change during pregnancy, and this probably explains some pregnancy losses,” says David Westergaard.

Immunomodulatory drugs can therefore help women with recurrent pregnancy loss, and examinations include thorough medical history, blood tests, examination of the uterus and genetic testing of the couple.

“The genetic tests are probably one of the keys to understanding the many pregnancy losses. Unfortunately, we do not have information on the father’s DNA, since he is not registered until the birth. However, as we develop more genetic knowledge, we will probably be able to determine which genetic factors recur in a mother and her unborn child. This will enable us to better identify the pregnant women at higher risk of pregnancy loss and enable them to receive optimal help,” concludes Astrid Marie Kolte.

Chance of live birth: a nationwide, registry-based cohort study” has been published in Human Reproduction. In 2019, the Novo Nordisk Foundation awarded a grant to co-author Henriette Svarre Nielsen for the project Prognosis for Live Birth in Women with Explained Recurrent Pregnancy Loss Compared to Women with Unexplained Recurrent Pregnancy Loss. David Westergaard is employed under the BRIDGE – Translational Excellence Programme, which is funded by the Novo Nordisk Foundation. Several co-authors are employed at Novo Nordisk Foundation Center for Protein Research, University of Copenhagen.

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