PAPPA1

Labcorp's test combines readings of two blood-based proteins with measurements of mean arterial pressure and uterine artery pulsatility index. Labcorp has begun rolling out a new blood test that aims to predict the risk of a pregnant person developing preeclampsia, with screening results available as early as the first trimester. The test is designed to be performed between 11 and 14 weeks into pregnancy and delivers a risk score for developing the condition before 34 weeks. The clinical diagnostics giant said it can be used to screen people with low to average risk profiles as well as during first-time pregnancies.  Associated with high blood pressure and other potentially severe complications, including organ dysfunction and seizures, preeclampsia can develop into one of the main causes of maternal and fetal mortality if left untreated.  The condition affects about 1 in 25 pregnancies in the U.S., according to Labcorp, while risks are typically higher among non-Hispanic Black women, with cases reported at a 60% higher rate compared to white women. The test taps four blood-based biomarkers—including two chemical readouts measuring placental growth factor and pregnancy-associated plasma protein-A, plus readings of the patient’s mean arterial pressure and uterine artery pulsatility. Low levels of those two proteins can indicate poor placental development, while high pressure and pulsatility figures are associated with increased resistance to blood flow. Labcorp said its approach can deliver up to 90% sensitivity and can help identify a person’s risk earlier than traditional systems such as hypertension or the presence of proteins in urine, which tend to be found after 20 weeks of gestation. The new test follows up on Labcorp’s January launch of a blood test developed by Thermo Fisher Scientific for detecting the signs of severe preeclampsia in single-child pregnancies between about 23 and 34 weeks. With the latest offering, Labcorp said it “is now the only laboratory to offer tests that screen for preeclampsia risk across all trimesters of pregnancy.”

Labcorp is now the only lab that can detect preeclampsia risk across all pregnancy trimesters BURLINGTON, N.C., May 15, 2024 /PRNewswire/ -- LabCorp (NYSE: LH), a global leader of innovative and comprehensive laboratory services, announced today the launch of its first trimester preeclampsia screening test to be performed between 11 and 14 weeks gestation to determine the risk of developing preeclampsia before 34 weeks of pregnancy. It is the only test of its kind available in the United States and is relevant for all pregnant individuals, including those with a low- to average-risk for preeclampsia or first-time pregnancies. Preeclampsia is a high blood pressure disorder that can develop during pregnancy or postpartum and is a leading cause of maternal morbidity and mortality worldwide. Roughly one in 25 pregnancies in the U.S. is affected by preeclampsia, which poses an even greater risk for non-Hispanic Black women, who experience the condition at a 60% higher rate compared to white women. With this test launch, Labcorp is now the only laboratory to offer tests that screen for preeclampsia risk across all trimesters of pregnancy. In January, Labcorp announced the launch and availability of an FDA-cleared blood test for risk assessment and clinical management of severe preeclampsia during the second and third trimesters. "Our organization celebrates this innovative new test offering," said Eleni Tsigas, Chief Executive Officer of the Preeclampsia Foundation. "Research shows that patients and providers want access to more tools that better predict progression to preeclampsia, especially for those patients with low- to average-risk or those with first-time pregnancies for whom there is some uncertainty." The first trimester test uses four key early pregnancy biomarkers to provide a comprehensive risk assessment with up to 90% sensitivity, nearly twice the sensitivity of assessing typical maternal history or biophysical factors alone. The test results provide risk identification earlier than traditional symptoms such as hypertension or protein in the urine, which tend to develop around 20 weeks gestation. The blood-based test produces a risk score by measuring two biochemical markers – placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) – and two biophysical markers – mean arterial pressure (MAP) and uterine artery pulsatility index (UtAPI). Low levels of PlGF and PAPP-A indicate poor placental development and function, while high MAP and UtAPI levels indicate high blood pressure and elevated resistance to blood flow across the uterine artery. "Labcorp is committed to advancing maternal and fetal health through innovative diagnostic and screening solutions," said Dr. Brian Caveney, Labcorp's Chief Medical and Scientific Officer. "This new first trimester blood test is another significant milestone in our mission to improve health and improve lives. By giving healthcare providers another tool to assess preeclampsia risk in their pregnant patients with objective biomarkers, we're helping to advance prenatal care and improve outcomes for mothers and their babies." Labcorp's test is based on published data from two principal studies, demonstrating the significant benefits of combining maternal factors with biomarkers for early screening. The SPREE study (Screening Program for Pre-eclampsia), a large prospective multicenter study of 16,700 women, reported that the combination of MAP, UtAPI, PlGF and PAPP-A yielded substantially improved screening performance than standard screening guidelines. The ASPRE trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention), a first trimester multicenter study of screening for preterm preeclampsia among more than 25,000 pregnant women, validated the use of MAP, UtAPI, PlGF and PAPP-A as screening factors. The new first trimester test is the latest offering from Labcorp in its commitment to advance women's health by providing innovative tests, resources and services to support each stage of an individual's health journey. Among these services, Labcorp offers support to millions of women through its digital health platform, Ovia Health by Labcorp. Through its family of apps, Ovia offers evidence-based, clinically informed content and simple, convenient tools, including a preeclampsia prevention and management program, which provides members with clear, actionable guidance to help them understand their risk to make better health decisions that support a healthy pregnancy. For more information about Labcorp's offerings across women's health and its first trimester test, visit About Labcorp Labcorp (NYSE: LH) is a global leader of innovative and comprehensive laboratory services that helps doctors, hospitals, pharmaceutical companies, researchers and patients make clear and confident decisions. We provide insights and advance science to improve health and improve lives through our unparalleled diagnostics and drug development laboratory capabilities. The company's more than 67,000 employees serve clients in approximately 100 countries, provided support for 84% of the new drugs and therapeutic products approved in 2023 by the FDA, and performed more than 600 million tests for patients around the world. Learn more about us at . Company Codes: NYSE:LH

Researchers have determined the three-dimensional structure of the proteolytic enzyme PAPP-A. The results may allow us to better understand the basic biology that regulates linear growth of vertebrates. The same regulatory mechanisms are also involved in several age-related diseases, and thus, the research is an important step towards the development of novel types of drugs. The growth factor IGF plays a key role in human growth. In the absence of IGF signaling, we become dwarfs. Later in life, IGF is involved in age-related diseases, e.g. cancer and cardiovascular disease. In both cases, IGF must be converted from an inactive to an active form. This is what PAPP-A is able to do. "Seven years ago we discovered that the protein STC2 blocks the activity of PAPP-A, thus indirectly inhibiting the activity of the IGF growth factor. To block the activity, STC2 must form a complex with PAPP-A. We have studied this complex, and we now know its three-dimensional structure. It is fascinating to see what a molecule, we know biochemically very well, actually looks like. PAPP-A is heart-shaped with an inner 'chamber'. But from a research point of view, the shape is not the most interesting feature. Rather, it is the interactions between the different elements of the molecule," Professor Claus Oxvig explains. There are still many unanswered questions about the molecular mechanisms, which regulate how much IGF is converted into the active form. It is likely that complex formation between PAPP-A and STC2 is highly regulated. Such a hypothesis is supported by earlier findings showing that natural human variants of STC2, in which just a single amino acid is substituted, form the complex with PAPP-A slightly slower. The consequence of this is that slightly more IGF can be activated by PAPP-A, resulting in an increase in height of up to 2.1 cm. The first-author of the publication reporting the PAPP-A·STC2 structure, graduate student Sara Dam Kobberø, has used cryo-electron microscopy (cryo-EM) to determine the structure of the large protein complex. The Danish National Cryo-EM Research Infrastructure (EMBION, AU) has allowed this study, which has also involved participants from the University of Copenhagen.