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Urine Test to Identify Pregnancy Outcome after Threatened Miscarriage

Researchers at Nanyang Technological University, Singapore (NTU Singapore) and clinicians at KK Women’s and Children’s Hospital (KKH) have developed a urine test that within 30 minutes, can gauge pregnancy outcomes for women presenting with signs of threatened miscarriage.

Threatened miscarriage is characterised by abdominal pain with vaginal bleeding, it is one of the most common gynaecological emergencies worldwide.

Based on a previous study by Duke-NUS, NTU and KKH, one in five pregnancies in Singapore shows signs of threatened miscarriage within the first trimester. Among pregnant women with such symptoms, one in four of them end up losing their baby within two weeks.

With no non-invasive way of predicting the risk of miscarriage, clinicians are only able to assess a pregnant woman’s miscarriage risk through a lab-based method. This method uses a serum progesterone test to measure progesterone level in the blood within a few hours.

The new test developed by NTU scientists in collaboration with doctors from KKH uses an innovative surface-enhanced Raman scattering (SERS) chip that requires a droplet of urine to screen for urine molecules associated with miscarriage risk. This is done through the chemical 4-mercaptophenylboronic acid (MPBA) which is coated on the chip. MPBA probes and selectively captures the miscarriage-related molecules pregnane and tetrahydrocortisone (THC) from the urine.

From a case-control study of 40 pregnant women attending the Urgent O&G Centre at KKH who display symptoms of threatened miscarriage, were tested retrospectively to identify accurately the pregnancy outcomes of the participants.

Led by Associate Professor Ling Xing Yi and Associate Professor Tan Nguan Soon from NTU, in collaboration with KKH’s Dr Ku Chee Wai, the study findings were published in the peer-reviewed journal ACS Nano in February 2020.

The researchers believe their initial success points the way towards a non-invasive, fast, and accurate approach for triaging pregnant women with a threatened miscarriage, identifying those who are at higher risk of a spontaneous miscarriage.

Associate Professor Tan, a metabolic disorder expert at NTU’s Lee Kong Chian School of Medicine, explained that the unparalleled sensitivity offered by the SERS test and the small sample volume required make it attractive for clinical use.

“This is even more so for cases where large amounts of sample are hard to obtain, such as tear sampling for eye disorders or breath vapour for lung diseases. Our diagnostic platform could revolutionise metabolite detection for medical conditions that are normally challenging to detect and bring testing for them out of the lab and into the clinic,” said Associate Professor Tan.

The researchers also shared that a reliable and non-invasive diagnostic test would be invaluable for miscarriage risk management.

Dr Ku Chee Wai, Division of Obstetrics and Gynaecology, KKH, said, “This non-invasive toolkit will enable clinicians to predict risk of a spontaneous miscarriage in women who presents with a threatened miscarriage. Early detection will also allow these pregnant women to receive counselling, medical interventions, or be under close medical management for adverse pregnancy outcomes throughout the rest of their pregnancy. It can also allay the fears and worries of pregnant women who are at low risk of miscarriage and improve their pregnancy experience”.

The team has patented the new diagnostic test and is looking to evaluate the performance of the toolkit in hospital settings, with the aim of commercialising the product in the future. [APBN]