Tuesday, April 11, 2023

Scheduled childbirth may greatly reduce preeclampsia, a leading cause of maternal death

Scheduled labor inductions or Cesarean deliveries may prevent more than half of at-term preeclampsia cases, according to new research published in Hypertension journal

Peer-Reviewed Publication

AMERICAN HEART ASSOCIATION

Research Highlights:

  • Analysis found that more than half of preeclampsia cases that occur during weeks 37-42 of pregnancy (called at-term preeclampsia) may be prevented with timed birth, such as a scheduled induction or Cesarean delivery.
  • Planned labor inductions and Cesarean deliveries are already widely practiced for a range of reasons, however, they are seldom considered as an intervention to prevent at-term preeclampsia, which may be life-threatening.

DALLAS, April 10, 2023 — More than half of all preeclampsia cases that occur during weeks 37-42 of pregnancy (at-term) may be prevented with timed birth, such as a scheduled induction or Cesarean delivery, according to new research published today in Hypertension, a peer-reviewed journal of the American Heart Association.

Preeclampsia is the most dangerous form of high blood pressure (≥140/90 mm Hg) during pregnancy, and it is a leading cause of maternal death worldwide. Preeclampsia is potentially life-threatening and affects 1 in 25 pregnancies in the United States. The condition is typically diagnosed after 20 weeks of pregnancy. Symptoms include headaches, vision changes and swelling of the hands, feet, face or eyes for the mother; or a change in the well-being of the baby. Preeclampsia also indicates that there is an increased risk of developing heart health complications for women later in life.

Preterm delivery may be considered an option for women who develop preeclampsia during weeks 20-36 of pregnancy; however, most preeclampsia occurs during the time frame called at-term, which is between 37-42 weeks of pregnancy. While screening for preeclampsia is routine during pregnancy, there are limited treatment options that are proven safe and effective. Low-dose aspirin more than halves the risk of preterm preeclampsia among women at risk, however, aspirin does not affect the risk of at-term preeclampsia , which is three times more common than preterm preeclampsia and associated with more complications for mothers and babies.

Timed birth strategies, including induced labor and Cesarean deliveries that are planned in advance, are already widely practiced for various reasons. However, they are seldom used as an intervention to prevent at-term preeclampsia.

“Timed birth is achievable in many hospitals or health centers,” said lead study author Laura A. Magee, M.D., a professor of women’s health at King’s College in London, “so our proposed approach to prevent at-term preeclampsia has huge potential for global good in maternity care.”

Researchers examined more than 10 years of health records for nearly 90,000 pregnancies at two hospitals (King’s College Hospital, London and Medway Maritime Hospital, Gillingham) in the U.K. There were 57,131 pregnancies with health records at 11 to 13 weeks (between 2006 and 2017), in which there were 1,138 cases of at-term preeclampsia; and 29,035 pregnancies at 35 to 36 weeks (between 2016 and 2018), in which there were 619 cases of at-term preeclampsia. In the analysis, researchers evaluated risk of preeclampsia and potential benefits of timed birth for both groups with standard clinical criteria for preeclampsia and a risk prediction model (computer program that predicts risk of preeclampsia based on various individual factors, such as maternal history, blood pressure, ultrasound and blood tests).  

The majority of women in the dataset were in their early 30s, self-identified as white and had a body mass index at the upper limits of normal. About 10% of the women in the analysis also self-identified as smokers; fewer than 3% had a medical history of high blood pressure, Type 2 diabetes or an autoimmune disease; and only 3.9% reported a family history of preeclampsia.

At-term preeclampsia occurred with similar frequency when participants screened during the first trimester were compared with those screened during the third trimester. On average, women included in the study delivered at 40-weeks, and two-thirds of all participants experienced spontaneous onset of labor. About one-fourth of the women included in the analysis had Cesarean deliveries.

The analysis indicates that, when utilizing risk-modeling in place of standard clinical screening, timed birth may prove to be an effective intervention for reducing by more than half the risk of at-term preeclampsia.

“Our findings suggest that over half of the cases of at-term preeclampsia may be prevented by timed (planned) birth,” said Magee. “It is important to note that being at higher risk of at-term preeclampsia was associated with earlier spontaneous onset of labor, so women at the highest risk were already less likely to deliver close to their due date.”

 Limitations for the research included that no interventions were provided to participants; researchers calculated potential risk only through risk modeling. In addition, the study did not examine the potential for preeclampsia after delivery. Although this was an observational study using modeling to predict risk reduction for at-term preeclampsia, the researchers noted that strengths of the study include the large population of women represented and that labor induction and Cesarean delivery are widely available options. However, randomized clinical trials, studies where individuals are chosen at random to receive treatment versus no treatment or an alternate treatment, are needed to evaluate the safety and effectiveness of timed birth as an appropriate intervention to reduce at-term preeclampsia.

In February 2023, the American Heart Association released a scientific statement, Optimizing Prepregnancy Cardiovascular Health to Improve Outcomes in Pregnant and Postpartum Individuals and Offspring, which details the benefits of early interventions to support pre- and interpregnancy (during pregnancy) cardiovascular health. The statement highlighted interventions related to diet, smoking cessation and weight reduction that may reduce the frequency of adverse pregnancy outcomes at birth (such as hypertensive disorders of pregnancy, pre-term birth, small-for-gestational-age birth or gestational diabetes). Additional research is needed to better understand the relationship between comprehensive prepregnancy cardiovascular health care and the frequency of adverse pregnancy outcomes.

Co-authors are David Wright, Ph.D.; Argyro Syngelaki, Ph.D.; Peter von Dadelszen, D.Phil.; Ranjit Akolekar, M.D.; Alan Wright, Ph.D.; and Kypros H. Nicolaides, M.D. Authors’ disclosures are listed in the manuscript.

The study was funded by grants from the Fetal Medicine Foundation in the U.K. Support was also provided by PerkinElmer, Life Analytical Sciences, Roche Diagnostics and Thermo Fisher Scientific.

Studies published in the American Heart Association’s scientific journals are peer-reviewed. The statements and conclusions in each manuscript are solely those of the study authors and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Association’s overall financial information are available here. 

Additional Resources:

About the American Heart Association

The American Heart Association is a relentless force for a world of longer, healthier lives. We are dedicated to ensuring equitable health in all communities. Through collaboration with numerous organizations, and powered by millions of volunteers, we fund innovative research, advocate for the public’s health and share lifesaving resources. The Dallas-based organization has been a leading source of health information for nearly a century. Connect with us on heart.org, Facebook, Twitter or by calling 1-800-AHA-USA1.

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JOURNAL

Hypertension

DOI

10.1161/HYPERTENSIONAHA.122.20565 

ARTICLE TITLE

Preeclampsia Prevention by Timed Birth at Term


Protein Beclin-1 is a major player in uterine remodeling and the establishment of pregnancy


Peer-Reviewed Publication

BAYLOR COLLEGE OF MEDICINE

Throughout a woman's reproductive life, the endometrium, the mucous membrane lining the uterus, goes through cyclical remodeling. It thickens during the menstrual cycle in preparation for embryo implantation, and it is shed during menstruation when there is no fertilization.

Researchers at Baylor College of Medicine and collaborating institutions are investigating little-known factors directing uterine remodeling to advance the understanding of this process and provide new insights into fertility-associated gynecological conditions. They report today in the journal Developmental Cell that autophagy protein Beclin-1 governs endometrial remodeling and the establishment of pregnancy in animal models by regulating autophagy, a natural process that digests and recycles cellular components.

“One of our main goals is to understand biological processes that might be associated with pregnancy loss,” said corresponding author Dr. Rama Kommagani, associate professor in the Departments of Pathology and Immunology and Molecular Virology and Microbiology at Baylor. “In this study, we looked to understand the role Beclin-1 plays in endometrial reprogramming for the successful establishment of pregnancy.”

In the first part of this study, Kommagani and his colleagues found that Beclin-1 is essential for the establishment of pregnancy in mouse models. When they removed Beclin-1 specifically from uterine cells, the uteri did not develop properly, and this led to infertility caused by reduced uterine receptivity and failed embryo implantation.

In addition, molecular analysis of uteri revealed that Beclin-1 is necessary for endometrial programming of stem cells that leads to the development of uterine glands and other structures that are essential for uterine maturation.

“We also studied the mechanism by which Beclin-1 regulates uterine development,” Kommagani said. “Beclin-1 is known to regulate two distinct natural processes called autophagy and apoptosis that help maintain many normal functions in organisms. We investigated whether one of these two processes or both were involved.”

The team found that disabling apoptosis in the presence of Beclin-1did not alter the normal remodeling of the uterus and gland development. Importantly, restoring only Beclin-1-driven autophagy, but not apoptosis, promoted normal uterine remodeling.

“After birth, the uterus goes through a multistep process of development that is required for successful pregnancies in the future. Any deficiencies along this process can have a ripple effect on the ability to conceive and for the pregnancy to succeed,” Kommagani said. “We discovered that one of the steps involves Beclin-1-mediated autophagy, which acts as a molecular switch that governs uterine reprograming by maintaining the endometrial progenitor stem cells that support uterine remodeling.”

The findings have encouraged the researchers to explore the possibility of developing practical applications both in the field of contraceptives and infertility.

Other contributors to this work include Pooja Popli, Suni Tang, Sangappa B. Chadchan, Chandni Talwar, Edmund B. Rucker III, Xiaoming Guan, Diana Monsivais, John P. Lydon, Christina L. Stallings and Kelle H Moley. The authors are affiliated with Baylor College of Medicine, University of Kentucky or Washington University School of Medicine.

This work was funded, in part, by National Institutes of Health/National Institute of Child Health and Human Development (grants R01HD102680, R01HD104813, 454 R01HD065435, R01HD105800). A Next Gen Pregnancy Award (NGP10125) from the Burroughs Wellcome Fund, NIH Awards NIAID R01 AI132697 and U19 AI142784, the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the CPRIT Core Facility Support Award (CPRIT-RP180672) and the NIH (CA125123 and RR024574).

JOURNAL

Developmental Cell

DOI

10.1016/j.devcel.2023.03.013 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Beclin-1-Dependent Autophagy but Not Apoptosis Is Critical for Stem Cell Mediated-Endometrial Programming and the Establishment of Pregnancy

ARTICLE PUBLICATION DATE

10-Apr-2023

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