Pregnancy Complications, Infectious

A new study challenges the prevailing view on the maternal death rate in the United States. The findings show that the rates of maternal death were stable between 1999-2002 and 2018-2021, instead of the dramatic upward trends previously reported. Additionally, the study indicates that direct obstetric causes of death declined over the last 20 years. A new study published in the American Journal of Obstetrics & Gynecology, published by Elsevier, challenges the prevailing view on the maternal death rate in the United States. The findings show that the rates of maternal death were stable between 1999-2002 and 2018-2021, instead of the dramatic upward trends previously reported by the National Vital Statistics System (NVSS), Centers for Disease Control and Prevention (CDC). Additionally, the study indicates that direct obstetric causes of death declined over the last 20 years. To determine whether the reported maternal death rates are accurate, a team of researchers took a deep dive into the underlying data and looked at the factors driving the increase, namely, changes in obstetric factors, maternal chronic conditions, and surveillance issues (i.e., changes in data collection methods). Maternal deaths refer to those occurring during pregnancy, childbirth, or the postpartum period from conditions directly related to pregnancy or those exacerbated by pregnancy and birth (accidental and incidental deaths in pregnancy are not included in the maternal death definition). Lead author K.S. Joseph, MD, PhD, Department of Obstetrics and Gynaecology, University of British Columbia and the Children's and Women's Hospital and Health Centre of British Columbia; and School of Population and Public Health, University of British Columbia, said "Our study showed that maternal mortality rates were low and stable between 1999-2002 and 2018-2021, which is very different from the high rates and dramatic increases reported by the NVSS in recent years. We found that exclusive reliance on the pregnancy checkbox on death certificates, without corroboration from the cause-of-death information, led to an overestimation of maternal mortality rates by the NVSS in 2018-2021." Researchers examined all deaths in the US between 1999 and 2021 using an approach that enables greater accuracy in how maternal deaths are identified and classified in the mortality database. The study uncovered several indications that the pregnancy checkbox was responsible for misclassifying nonmaternal and incidental deaths in pregnancy as maternal deaths. These included a 46-fold increase in maternal deaths among women with malignant neoplasms (which likely represent incidental deaths in pregnancy and not maternal deaths). Also, a substantially higher proportion of maternal deaths identified by the pregnancy checkbox had a single entry in the cause-of-death section, which requires a listing of all the immediate, intermediate, contributory, and underlying causes of death (thus suggesting a less thorough approach to death certification). Although the pregnancy checkbox was introduced on death certificates in 2003 to improve identification of maternal death, its use between 2003 and 2017 was associated with some substantial errors. A detailed investigation by the National Center for Health Statistics (NCHS), CDC showed that the checkbox was erroneously ticked in many cases, leading to misclassification and overestimation of maternal death. For example, hundreds of decedents, 70 years of age and older (including 147 women aged 85 years and older in 2013), were certified as pregnant at the time of death or in the year prior. The NCHS concluded that the entire increase in maternal mortality in the US between 2003 and 2017 was due to the pregnancy checkbox. In response, NCHS made specific changes regarding pregnancy checkbox use for deaths from 2018 onwards but NVSS reports show that maternal mortality rates have continued to increase (nearly doubling from 2018 to 2021). Roberto Romero, MD, DMedSci, Editor-in-Chief for Obstetrics of the American Journal of Obstetrics & Gynecology (AJOG), and Chief of the Pregnancy Research Branch of NICHD, NIH, stated, "Accurate assessment of the number and causes of maternal death is an important priority for countries and healthcare policymakers. Improving maternal mortality surveillance is key to formulating plans to improve maternal health. Comparisons of the rate of maternal death among countries should be interpreted with great caution because the methods of surveillance and accuracy differ. The article by Dr. Joseph and a distinguished group of epidemiologists and obstetricians published in AJOG calls attention to the need to improve surveillance in the United States and to thoughtful interpretation of reported statistics." Co-author Justin S. Brandt, MD, Director of the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, NYU Grossman School of Medicine, notes, "By not relying on the pregnancy checkbox, our approach avoided the misclassification that has given the false impression of increasing maternal mortality rates in the US. Identifying maternal deaths by requiring mention of pregnancy among the multiple causes of death shows stable maternal mortality rates and declines in maternal deaths from direct obstetric causes." The research team previously published a study on maternal mortality in the US in 2017, which also showed stable rates of maternal mortality from 1999 to 2014. As mentioned, their results were subsequently validated by a detailed investigation carried out by the NCHS and published in January 2020. Although the study's findings contradict the mainstream narrative of high and rising rates of maternal death in the US, the results are consistent with changes in maternal characteristics and improvements in obstetric practice. For instance, the increase in maternal deaths due to specific placental complications (i.e., placenta accreta spectrum disorder) observed in their study is consistent with increases in deliveries to women with a previous cesarean delivery. Similarly, the reduction in maternal deaths due to hypertensive disorders in pregnancy (i.e., preeclampsia/eclampsia), blood clot embolism (i.e., thromboembolism), and infection (i.e., puerperal sepsis) is consistent with advances in the obstetric management of these conditions. The study also showed a reduction in overall maternal mortality, and especially in maternal deaths from direct obstetric causes among non-Hispanic Blacks, which is encouraging. However, the disproportionately high rate of maternal death among Non-Hispanic Blacks in 2018-21 and the persistent racial/ethnic disparities are concerning, as is the small increase in direct obstetric deaths among non-Hispanic Whites. Co-author Cande Ananth, PhD, MPH, MD, Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences; Cardiovascular Institute of New Jersey and Department of Medicine; and Environmental and Occupational Health Sciences Institute, Rutgers, Robert Wood Johnson Medical School; and Department of Biostatistics and Epidemiology, Rutgers School of Public Health, elaborates, "Our analysis suggests that people who are Black remain at much higher risk of dying due to pregnancy complications compared with people who are White. The continuing disparities in maternal mortality rates are concerning and deserve strategic and focused efforts to combat structural racism and designed to address chronic conditions disproportionately represented in this subpopulation." The study provides important insights into cause- and race/ethnicity-specific maternal mortality and provides suggestions for the appropriate use of the pregnancy checkbox on death certificates. The authors hope that these findings will serve as the evidentiary basis for clinical and public health initiatives for reducing maternal mortality.

Commitment to make life-saving products to treat life-threatening hypovolemia due to sepsis and blood loss available in Sub-Saharan Africa where there is outsized demand. Targeted $20M Series B Round to include Sub-Saharan Africa in product development. Partnering with Propelevate to drive Sub-Saharan Africa strategy. KANSAS CITY, Mo., Feb. 22, 2024 /PRNewswire/ -- Life sciences company Vivacelle Bio today announced Sub-Saharan Africa as a priority region for its life-saving alternative to fluid resuscitation to treat hypovolemia caused by severe sepsis, septic shock, or blood loss. Vivacelle Bio's lifesaving cardiovascular support fluids (VBI-S and VBI-1), both comprised of phospholipid nanoparticles, can be used to treat the refractory hypovolemia and hypotension that occur in severe sepsis and septic shock, and used instead of blood to correct hypovolemia from blood loss such as after major vehicle collisions and postpartum hemorrhage. Vivacelle Bio is partnering with Propelevate to drive the Sub-Saharan Africa strategy, which is fully integrated into its Series B financing round. Globally, sepsis kills ~11M people each year. Young children in Sub-Saharan Africa have outsized rates of sepsis death from neonatal sepsis, and sepsis caused by respiratory infection, diarrheal disease, and malaria. A child born in sub-Saharan Africa is nearly 8 times more likely to die in the first month of life than a child born in the US. Likewise, seventy percent of pregnancy-related deaths globally occur in Sub-Saharan Africa. Annually more than 75,000 women in the region die from postpartum hemorrhage or maternal sepsis. Vivacelle Bio's use of phospholipid nanoparticles to raise the blood pressure in patients with life-threatening hypovolemia due to blood loss, sepsis and septic shock is unprecedented. A successful phase 2a clinical trial of VBI-S, the formulation designed for treating hypovolemia due to septic shock, was recently completed. The fluid restores intravascular volume and absorbs nitric oxide, a gas made by the body that is largely responsible for the drop in blood pressure that is not responsive to current therapy. The evidence from the clinical trial showed that VBI-S is safe for patients while it increases blood pressure and reverses organ failure even when standard therapy has failed. This is the first-time in 20 years that a phase 2 or phase 3 trial in septic shock has succeeded in meeting all of its efficacy endpoints. VBI-1, designed for blood loss, also absorbs nitric oxide, and protects vital organs from reperfusion injury. Pre-clinical studies show that VBI-1 has greater efficacy than blood or standard of care fluids in raising blood pressure after severe hemorrhagic shock. Blood and other fluids promote reperfusion injury to vital organs while VBI-1 prevents this organ damage. The current $20M Series B round includes funding for a Global Pediatric Phase III trial for VBI-S, and two Phase IIA trials for VBI-1, which will integrate sites in Sub-Saharan Africa to ensure the efficacy of both products in diverse contexts. Vivacelle Bio Co-Founder Dr. Cuthbert Simpkins, MD, Chief Innovation Officer of Vivacelle Bio and Sosland Missouri Endowed Chair in Trauma Services at the University of Missouri, Kansas City (UMKC) School of Medicine, says "VBI-S and VBI-1 can be used in any context where there is a health worker able to administer IV fluids. VBI-S has shown to be more effective than vasopressors at addressing septic shock, without the side effects such as gangrene of fingers and toes. Moreover, VBI-S carries oxygen and is shown to improve lung oxygenation, and reverse elevated creatinine in septic patients. Both VBI-S and VBI-1 are shelf stable for at least a year at room temperature with VBI-S currently having more than 2 years stability at room temperature. VBI-1 circumvents many of the challenges of blood transfusions: the challenges of securing blood donors, the need to type, to maintain cold chain, the short shelf-life, and the risk of disease transmission." Harven DeShield, JD, PhD, the CEO of Vivacelle Bio commented, "Being born in Liberia, and raised in Liberia, Côte d'Ivoire and Tanzania, the critical value proposition of VBI-S and VBI-1 being readily affordable and available in Africa is not only of immense personal importance, but also provides a holistic, strategic vehicle to address persistent health inequities in Africa related to treatment of shock and trauma." Dr. Angela James, Senior Advisor for 2Flo Ventures, a Chicago-based startup studio and venture capital firm, and investor in Vivacelle Bio, echoed the importance of the impact of addressing the global unmet need for people with sepsis and septic shock having equitable access to safe and effective treatments. "Vivacelle Bio is poised to bring life-changing drugs to patients and their families in a region which has not been given equitable access to effective therapies is a great opportunity from both a healthcare and business perspective." Through partnership with Propelevate, Vivacelle Bio will engage global health funders and stakeholders during final stages of product development, and Propelevate will drive Vivacelle Bio's go-to-market strategy for African markets upon regulatory approval. "We are excited to partner with Vivacelle Bio because of their commitment to Sub-Saharan Africa. Life sciences companies typically think about the region as an afterthought. Vivacelle Bio is already taking specific needs in the region into account in product development and laying the groundwork for eventual local manufacturing to ensure wide availability of its life-saving products," said Propelevate's Managing Director Krisila Benson. This work was supported by the Naval Medical Research Command (NMRC) - Naval Advanced Medical Development (NAMD) Program under MTEC award 20-02-NavyMultiTopic-002. About MTEC The Medical Technology Enterprise Consortium (MTEC) is a 501(c)(3) biomedical technology consortium collaborating under an Other Transaction Agreement (OTA) with the U.S. Army Medical Research and Development Command (USAMRDC) that serves those who serve our nation. For more information about MTEC, visit mtec-sc.org. About Vivacelle Bio: Vivacelle Bio () is a life sciences company that utilizes patented phospholipid nanoparticle technology to design products that increase the survivability of critically-ill patients. In addition to VBI-S and VBI-1, Vivacelle Bio has a pipeline of products at various stages of development applicable to a range of health areas including reperfusion injury, organ preservation and transplantation, multiple organ dysfunction syndrome and hyperprocalcitonemia. Vivacelle Bio has raised approximately $10.9M in seed and Series A1-A3 funding, including from the US Department of Defense, the US National Institutes of Health, and 2Flo Ventures. About Propelevate: Propelevate () is a consulting firm working at the intersection of the private sector and social impact. Propelevate has experience bringing new health products to market in Africa and Asia, raising tens of millions of dollars in global health financing, and brokering successful partnerships between commercial and development actors. SOURCE Vivacelle Bio

Medicines360 and DKT WomanCare are joining forces to increase availability and use of AVIBELA, an affordable, effective, long-acting hormonal IUD developed by Medicines360, across Africa, South and Southeast Asia, Central America, and the Caribbean.SAN FRANCISCO and PARIS, Jan. 31, 2024 (GLOBE NEWSWIRE) -- Medicines360, a global nonprofit pharmaceutical organization specializing in women’s health, and DKT WomanCare, a global marketing and distribution organization focused on increasing the availability and use of high-quality contraceptive and reproductive health products, have entered into a partnership to expand access to AVIBELA, an affordable, quality-assured, long-acting hormonal IUD that is more than 99% effective at preventing pregnancy.1 This important collaboration will help more women learn about, access, and use this highly effective, modern form of contraception. The 52 mg levonorgestrel-releasing intrauterine system (“hormonal IUD”) has been largely inaccessible in lower- and middle-income countries (LMICs) due to factors limiting availability and affordability. An estimated 218 million women in LMICs have an unmet need for modern contraception, resulting in approximately 111 million unintended pregnancies (nearly 1 in 2) each year. 2 With this strategic partnership, more women around the world will have the ability to choose from a broader mix of safe, effective, and affordable contraceptive methods, including AVIBELA. "As a global nonprofit pharmaceutical organization dedicated to expanding access to affordable reproductive health products for women, DKT WomanCare is an ideal partner for our organization," said Dr. Andrea Olariu, CEO of Medicines360. “With their proven track record of building markets for new high-quality contraceptives, DKT WomanCare will help us provide more women across the world with the contraceptive options they want and deserve. Together, we will make meaningful improvements in access to build a brighter future for women.” Leveraging their global marketing expertise and reach, DKT WomanCare will increase awareness of AVIBELA, build markets, and ensure broader access across the public and private sectors in Africa, South and Southeast Asia, Central America, and the Caribbean. DKT WomanCare will draw on the experience of its parent company, DKT International, to leverage the organization’s extensive network of national and regional offices alongside DKT WomanCare’s established partnerships with ministries of health, global procurement agencies, social marketing organizations, and commercial distributors. Lauren Archer, DKT WomanCare’s Managing Director, celebrated the partnership. “DKT WomanCare looks forward to leveraging our global partnerships and commercial relationships to ensure every woman, regardless of income, can access affordable, high-quality contraception. We look forward to working with Medicines360 to achieve these goals.” “This partnership is a wonderful opportunity to educate users and practitioners about the benefits of hormonal IUDs, expanding long-term contraceptive options to women everywhere with quality products like AVIBELA,” said Chris Purdy, President of DKT International. As the supplier of AVIBELA, Medicines360 will focus on providing quality assurance and regulatory oversight, as well as ensuring sustainable product supply to DKT WomanCare and global procurement agencies. Together, Medicines360 and DKT WomanCare will meet the growing demand for quality-assured, affordable hormonal IUDs and help build a robust and sustainable global contraceptive market. AVIBELA is a trademark of Medicines360 in countries across Africa, South and Southeast Asia, Central America, and the Caribbean. For more information about AVIBELA, please visit www.avibela.com. AVIBELA™ Important Safety Information Who is not appropriate for AVIBELAContraindications to use of AVIBELA include: pregnancy; use for post-coital contraception (emergency contraception); acute pelvic inflammatory disease (PID) or endometritis or a history of PID unless there has been a subsequent intrauterine pregnancy; infected abortion in the past 3 months; known or suspected uterine or cervical neoplasia; acute liver disease or liver tumor (benign or malignant); conditions associated with increased susceptibility to pelvic infections; congenital or acquired uterine anomaly, including fibroids, that distorts the uterine cavity and would be incompatible with correct intrauterine system (IUS) placement; uterine bleeding of unknown etiology; untreated acute cervicitis or vaginitis, including bacterial vaginosis, known chlamydial or gonococcal cervical infection, or other lower genital tract infections until infection is controlled; known or suspected breast cancer or other hormone-sensitive cancer, now or in the past; a previously inserted IUS that has not been removed; a history of hypersensitivity reaction to any component of AVIBELA (reactions may include rash, urticaria, and angioedema). Clinical considerations for use of AVIBELAUse AVIBELA with caution after careful assessment in patients with coagulopathy or who are taking anticoagulants; migraine, focal migraine with asymmetrical visual loss, or other symptoms indicating transient cerebral ischemia; exceptionally severe or frequent headache; marked increase of blood pressure; or severe arterial disease such as stroke or myocardial infarction. Consider removal of the IUS if any of these conditions arise during use. Also consider removing AVIBELA if uterine or cervical malignancy, or jaundice arise during use. IUSs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion. About 1/3 of women diagnosed with PID developed the infection within a week of AVIBELA insertion, while the remainder were diagnosed more than six months after insertion. PID is often associated with sexually transmitted infection (STI), and AVIBELA does not protect against STIs. PID or endometritis may be asymptomatic but still result in tubal damage and its sequelae. Pregnancy related risks with AVIBELAIn the case of pregnancy with AVIBELA in place, advise the woman of the increased risks for pregnancy complications, including miscarriage, premature delivery, infection and sepsis. Ectopic pregnancy should be excluded, and removal of the system should be considered. Removal of AVIBELA or probing of the uterus may result in spontaneous abortion. When a woman becomes pregnant with AVIBELA in place, the relative likelihood of ectopic pregnancy is increased. Ectopic pregnancy may require surgery and may result in loss of fertility. Women with a previous history of ectopic pregnancy, tubal surgery, or pelvic infection have a higher risk of ectopic pregnancy. Be aware of other serious complications and most common adverse reactionsSome serious complications with IUSs like AVIBELA are sepsis, perforation, and expulsion. Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of other LNG-releasing IUSs. Aseptic technique during insertion of AVIBELA is essential in order to minimize serious infections such as GAS. Perforation (total or partial, including penetration/embedment of AVIBELA in the uterine wall or cervix) may occur, most often during insertion, although the perforation may not be detected until sometime later. Perforation may reduce contraceptive efficacy and result in pregnancy. If perforation is suspected, the IUS should be removed as soon as possible. Delayed detection or removal of AVIBELA in case of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses, and erosion of adjacent viscera. Partial or complete expulsion of AVIBELA may occur, resulting in the loss of contraceptive protection. Ovarian cysts may occur and are generally asymptomatic but may be accompanied by pelvic pain or dyspareunia. Evaluate persistent ovarian cysts. In a large clinical trial of 1,751 women using AVIBELA for contraception, very common undesirable effects (occurring in more than 10% of users) include procedural bleeding, vaginal bacterial infections, vulvovaginal mycotic infections, nausea or vomiting, and acne. About Medicines360Located in San Francisco, California, Medicines360 is a nonprofit global women’s health pharmaceutical organization with a mission to accelerate the timeline from health innovation to access for all women. Medicines360 is committed to working with healthcare providers, advocacy groups, and patients to deliver innovative and meaningful treatments that help women around the world have greater access to the medicines they need. For more information, visit www.medicines360.org. About DKT WomanCare Together, non-profits DKT WomanCare and DKT International are among the largest providers of reproductive health products, services, and technology in the world. Operating in more than 100 countries, they leverage principles of social entrepreneurialism and focus on ensuring wide access and availability of products, building up the capacity of health providers, and empowering consumers. For more information, see www.dktinternational.org and www.dktwomancare.org. Contacts:Heidi GlasserDirector of Marketing and Communications, Medicines360hglasser@medicines360.org Lauren ArcherManaging Director, DKT WomanCarelauren@dktwomancare.org References: Avibela (levonorgestrel-releasing intrauterine system) 52 mg [Summary of Product Characteristics and Prescribing Information]. Impact RH360; 2022.Sully EA et al., Adding It Up: Investing in Sexual and Reproductive Health 2019, New York: Guttmacher Institute, 2020, https://www.guttmacher.org/fact-sheet/investing-sexual-and-reproductive-health-low-and-middle-income-countries