Finding what caused pregnancy loss through a blood test

Breaking new ground 2. mar 2023 3 min Professor Henriette Svarre Nielsen Written by Kristian Sjøgren

Researchers can determine why a woman lost a pregnancy by analysing fetal DNA in the woman’s blood. For some women, this can be a positive result, giving them clarity and an optimistic outlook on becoming pregnant again. For other women, the result may prompt lifestyle changes aimed at increasing the chances of success next time.

Of the 120 million pregnancies annually worldwide, 25% end in pregnancy loss. Doctors have traditionally told women that they miscarried because the fetus is not developing normally and is not viable.

However, doctors have not had much more than guesswork to rely on and have not investigated the reasons because they did not have the optimal tools.

However, this will probably change in the future now that researchers have developed a way to analyse a blood test taken within 24 hours of a pregnancy loss that can determine whether the pregnancy was lost because of a major chromosomal defects or whether no such defect is present and therefore pointing toward factors associated with the woman’s body.

“Pregnancy loss has been a taboo for decades. Many women have therefore experienced that they have not been able to share their great sadness with other people. This is now changing, and more women want to know why they lost their fetus. Until now, doctors, including me, have told the women that the fetus was not developing normally and was not viable, without basing our answers on examining the individual fetus. This study showed that analysing the woman’s blood can tell her whether the loss resulted from a fetal gross genetic cause or could have resulted from factors related to the woman herself,” explains Henriette Svarre Nielsen, Clinical Professor, Department of Obstetrics and Gynaecology, Amager and Hvidovre Hospital and Department of Clinical Medicine, University of Copenhagen.

The research has been published in The Lancet.

Cell-free fetal DNA in the mother’s blood

In recent years, researchers and doctors have tried to determine how to identify the cause of a pregnancy loss. So far, this has required access to the fetus itself or parts of the placenta.

Pregnancy tissue is mainly expelled from the uterus through drug treatment or spontaneously – for example as heavy menstruation at home – and is an impractical source of information.

The researchers therefore wanted to investigate whether blood samples from the woman within 24 hours following the loss can determine whether something was wrong with the fetus or not. This method has revolutionised fetal diagnostics in viable pregnancies.

This is possible because fetal DNA is present in the woman’s blood during pregnancy, and researchers can use this to investigate whether something is abnormal in the fetal DNA.

1,000 women studied

The researchers examined blood samples from 1,000 women who had experienced pregnancy loss. The blood was collected while pregnancy tissue was still in place or within 24 hours after the pregnancy tissue had passed.

The researchers also examined DNA extracted from pregnancy tissue collected by surgical evacuation or collected at home and brought to the hospital.

The women experienced pregnancy loss between 5 and 21 weeks (average 10 weeks) into the pregnancy.

A result in 90% of pregnancy losses

The results show that methods independent of pregnancy tissue are needed.

Although the women had agreed to participate and were dedicated to the task, they could only provide pregnancy tissue from 70% of the lost fetuses, so this is probably not a feasible clinical way to determine the reason for loss.

In contrast, the part of the study focusing on blood tests showed that this is a good method to obtain information about what might have been wrong with the fetus.

The researchers obtained a result for 90% of the women who experienced pregnancy loss after 7 weeks from the blood sample.

In some cases, the researchers obtained a useful result as early as week 5 of the pregnancy.

Henriette Svarre Nielsen says that these figures make the method suitable clinically, since about half of pregnancy losses occur before week 10 of the pregnancy.

The study also showed that the researchers only found serious genetic defects in 50% of the losses.

“We gave the women a result they otherwise would not have received. Normally, we would have just told the women that there was probably something wrong with the fetus, but otherwise they would not have received any further details. With the blood test results, we could tell them something that helped them to move onward,” says Henriette Svarre Nielsen.

Results help in looking towards the future

According to Henriette Svarre Nielsen, the results can have great clinical significance. This also applies whether a pregnancy loss results from a chromosomal defect or not.

If the blood test shows that the fetus perished because of a chromosomal defect, this would not affect the woman’s chances of having a viable fetus next time and giving birth, and the doctors can tell the woman this.

Conversely, the risk of subsequent pregnancy loss increases with euploid losses (with correct number of chromosomes) and underlying genetic causes are more unlikely.

“If the fetus is otherwise viable, the cause is probably factors related to the woman. If the fetus does not have any serious chromosomal defects but still perishes, we could investigate the possible cause. The woman might smoke, have obesity or have a metabolic or immune disorder. Today, we do not investigate women before three consecutive pregnancy losses, but a blood test for the first loss immediately shows whether intervening earlier is warranted,” explains Henriette Svarre Nielsen.

She also emphasises that attempting to prevent repeated pregnancy losses may be appropriate for the women’s health. Previous studies have shown that women who experience repeated pregnancy losses have an increased risk of cardiovascular disease or type 2 diabetes 10–15 years later.

Expertises (Recurrent) Pregnancy Loss; Infertility; women’s health Main research areas Reproductive and female “omics”, immunology, epidemiology...

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