LC-MS/MS Uncovers Lipid Clues to Recurrent Pregnancy Loss

Doctors still do not have a reliable blood marker to identify cases of unexplained recurrent pregnancy loss (RPL; repeated miscarriages with no known cause). A study set out to examine the fat-related substances in the blood of patients with this condition, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile everything present in their blood serum. A paper based on this work was published in the journal Reproductive Medicine and Biology.¹

Why Might Fat Metabolism, Particularly Blood Lipid Levels, Play a Role in RPL?

Pregnancy causes major shifts in how the body processes and uses nutrients. Lately, researchers have become increasingly interested in how fat metabolism might be connected to RPL. One area of focus is unhealthy blood fat levels, especially high triglycerides and low levels of "good" cholesterol (HDL-C) which have been linked to blood vessel dysfunction and ongoing, low-level inflammation in the body.²These blood fat problems may interfere with how well the placenta functions, potentially reducing blood flow between the uterus and placenta. This, in turn, could raise the risk of repeated miscarriages.^3-5

The way the body handles fats changes over the course of pregnancy. During the first two trimesters, the body tends to store fat, leading to a buildup of triglycerides (a type of fat in the blood). Then, in the third trimester, the body shifts toward breaking down stored fat instead, which causes overall blood fat levels to rise.^6-8Recent research has also found a connection between a mother's blood fat levels during pregnancy and the risk of preterm birth, underscoring how important these fats may be to monitor.⁹ Triglycerides get broken down during metabolism into individual fatty acids. Some of these fatty acids then act as building blocks for substances that trigger inflammation in the body, called eicosanoids; this gives a clear biological explanation for how fat metabolism and inflammation are linked during pregnancy.¹⁰

Do Women with Recurrent Pregnancy Loss Have a Distinct Blood Lipid Profile That Could Serve As a Biomarker?

For this analysis, the researchers looked at blood samples from six groups of women: 31 healthy women who weren't pregnant, 15 healthy pregnant women, 32 non-pregnant women with recurrent pregnancy loss, and two groups of pregnant women with recurrent pregnancy loss—19 whose most recent miscarriage involved a chromosomally normal fetus and 30 whose miscarriage involved a chromosomally abnormal fetus. Compared to the healthy groups, non-pregnant women with recurrent pregnancy loss had higher levels of several substances linked to inflammation, including 11-dehydro-thromboxane B2 (11-dehydro-TXB2), 12-hydroxyeicosatetraenoic acid (HETE), and prostaglandin E2 (PGE2). Meanwhile, healthy pregnant women showed higher levels of substances derived from omega fats known to support pregnancy. When the researchers compared healthy pregnant women to those who suffered a miscarriage (whether the fetus was chromosomally normal or abnormal) they did not find any clear differences between these groups. Finally, a separate confirmatory test verified that one of the inflammation-related substances, 11-dehydro-TXB2, was indeed elevated in the blood of non-pregnant women with recurrent pregnancy loss.¹

“Patients with RPL,” write the authors of the paper,¹ “display a distinct serum lipid signature in the non-pregnant state, characterized by elevated levels of pro-thrombotic and pro-inflammatory eicosanoids, including 11-dehydro-TXB2, 12-HETE, and PGE2. Further studies are warranted to clarify the potential utility of 11-dehydro-TXB2 as biomarkers for RPL.”

That said, the researchers did not find major differences in blood chemistry among the pregnant groups (likely because the natural metabolic changes that come with pregnancy itself may have masked any underlying differences related to recurrent pregnancy loss). This means larger studies that follow patients forward in time are still needed to confirm these findings and figure out whether they could be useful in clinical care.¹

Read More on Similar Topics
Assessing Safety of Medications During Pregnancy and Breastfeeding with LC–MS/MS

References

1. Uchimura, Y.; Shen, L.; Goto, S. et al. Alteration in Lipid Metabolism Associated With Recurrent Pregnancy Loss: An Observational Case-Control Study. Reprod Med Biol. 2026, 25 (1), e70087. DOI: 10.1002/rmb2.70087
2. Chung, Y.; Melo, P.; Pickering, O. et al. The Association Between Dietary Patterns and Risk of Miscarriage: A Systematic Review and Meta-Analysis. Fertil Steril. 2023, 120 (2), 333-357. DOI: 10.1016/j.fertnstert.2023.04.011
3. Ball, E.; Bulmer, J. N.; Ayis, S. et al. Late Sporadic Miscarriage Is Associated with Abnormalities in Spiral Artery Transformation and Trophoblast Invasion. J Pathol. 2006, 208 (4), 535-542. DOI: 10.1002/path.1927
4. Brosens, I.; Pijnenborg, R.; Vercruysse, L. et al. The "Great Obstetrical Syndromes" Are Associated with Disorders of Deep Placentation. Am J Obstet Gynecol. 2011, 204 (3), 193-201. DOI: 10.1016/j.ajog.2010.08.009
5. Pijnenborg, R.; Vercruysse, L.; Brosens, I. Deep Placentation. Best Pract Res Clin Obstet Gynaecol. 2011, 25 (3), 273-285. DOI: 10.1016/j.bpobgyn.2010.10.009
6. Mulder, T.; Louwen, F.; van Poppel, M. et al. Lipid Metabolism During Pregnancy: Consequences for Mother and Fetus. Curr, Opin. Lipidol. 2024, 35, 123–131. DOI: 10.1097/MOL.0000000000000927
7. Bartels, Ä.; O'Donoghue, K. Cholesterol in Pregnancy: A Review of Knowns and Unknowns. Obstet Med. 2011, 4 (4), 147-151. DOI: 10.1258/om.2011.110003
8. Brizzi, P.; Tonolo, G.; Esposito, F. et al. Lipoprotein Metabolism During Normal Pregnancy. Am J Obstet Gynecol. 1999, 181 (2), 430-434. DOI: 10.1016/s0002-9378(99)70574-0
9. Lv, Y.; Xu, L.; He, Z. et al. The Association Between Pregnancy Levels of Blood Lipids and the Risk of Preterm Birth. Sci Rep. 2024, 14 (1), 10800. DOI: 10.1038/s41598-024-61119-x
10. Dichlberger, A.; Schlager, S.; Maaninka, K. et al. Adipose Triglyceride Lipase Regulates Eicosanoid Production in Activated Human Mast Cells. J Lipid Res. 2014, 55 (12), 2471-2478. DOI: 10.1194/jlr.M048553