Predicting women at risk of preeclampsia before clinical symptoms

Many of my female friends became pregnant with their first child in their late 30s or early 40s, which increased their risk of common complications such as high blood pressure, gestational diabetes and preeclampsia.

Affecting over 8 million women worldwide, preeclampsia can lead to serious, even fatal, complications for both the mother and baby. The clinical symptoms of preeclampsia typically start at 20 weeks of pregnancy and include high blood pressure and signs of kidney or liver damage.

“Once these clinical symptoms appear, irreparable harm to the mother or the fetus may have already occurred,” said Stanford immunologist Brice Gaudilliere, MD, PhD.  “The only available diagnostic blood test for preeclampsia is a proteomic test that measures a ratio of two proteins. While this test is good at ruling out preeclampsia once clinical symptoms have occurred, it has a poor positive predictive value.”

Now, Stanford researchers are working to develop a diagnostic blood test that can accurately predict preeclampsia prior to the onset of clinical symptoms.

A new study conducted at Stanford was led by senior authors Gaudilliere, statistical innovator Nima Aghaeepour, PhD, and clinical trial specialist Martin Angst, MD, and co-first authors and postdoctoral fellows Xiaoyuan Han, PhD, and Sajjad Ghaemi, PhD. Their results were recently published in Frontiers in Immunology.

They analyzed blood samples from 11 women who developed preeclampsia and 12 women with normal blood pressure during pregnancy. These samples were obtained at two timepoints, allowing the scientists to measure how immune cells behaved over time during pregnancy.

“Unlike prior studies that typically assessed just a few select immune cell types in the blood at a single timepoint during pregnancy, our study focused on immune cell dynamics,” Gaudilliere explained. “We utilized a powerful method called mass cytometry, which measured the distribution and functional behavior of virtually all immune cell types present in the blood samples.”

The team identified a set of eight immune cell responses that accurately predicted which of the women would develop preeclampsia — typically 13 weeks before clinical diagnosis.

At the top of their list was a signaling protein called STAT5. They observed higher activity of STAT5 in CD4+ T-cells, which help regulate the immune system, at the beginning of pregnancy for all but one patient who developed preeclampsia.

“Pregnancy is an amazing immunological phenomenon where the mother’s immune system ‘tolerates’ the fetus, a foreign entity, for nine months,” said Angst. “Our findings are consistent with past studies that found preeclampsia to be associated with increased inflammation and decreased immune tolerance towards the fetus.”

Although their results are encouraging, more research is needed before translating them to the clinic.

The authors explained that mass cytometry is a great tool to find the “needle in the haystack.” It allowed them to survey the entire immune system and identify the key elements that could predict preeclampsia, but it is an exploratory platform not suitable for the clinic, they said.

“Now that we have identified the elements of a diagnostic immunoassay, we can use conventional instruments such as those used in the clinic to measure them in a patient’s blood sample.” Aghaeepour said.

First though, the team needs to validate their findings in a large, multi-center study. They are also using machine learning to develop a “multiomics” model that integrates these mass cytometry measurements with other biological analysis approaches. And they are investigating how to objectively define different subtypes of preeclampsia.

Their goal is to accurately diagnose preeclampsia before the onset of clinical symptoms.

 “Diagnosing preeclampsia early would help ensure that patients at highest risk have access to health care facilities, are evaluated more frequently by obstetricians specialized in high-risk pregnancies and receive treatment,” said Gaudilliere.

Women with preeclampsia can receive care through the obstetric clinic at Lucile Packard Children’s Hospital Stanford.

Photo by Pilirodriquez

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

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Few California pharmacists prescribe birth control, a study finds

Photo by Anqa

It takes time and money to visit the doctor’s office to get birth control. This is particularly an issue for low-income women, those who live in rural areas and teenagers who feel uncomfortable seeing their family doctor.

So four states — California, Oregon, Colorado and New Mexico — are trying to make contraception cheaper and more readily available by allowing trained pharmacists to prescribe and dispense birth control pills, patches, injections and vaginal rings. However, pharmacists aren’t required to participate and few do, according to a new study.

University of California, Berkeley researchers investigated the availability and cost of pharmacist-prescribed contraception in California using a telephone audit survey of approximately 1000 community-based, retail pharmacies. Although randomly selected, most of the pharmacies were in urban areas and affiliated with retail chains, like CVS.

Posing as patients, they called the pharmacies and said, “I heard that you can get birth control from a pharmacy without a prescription from your doctor. Can I do that at your pharmacy?” If the answer was yes, then the researcher asked follow-up questions to identify the types of birth control available and the service fee.

The study found that pharmacy-prescribed birth control was available in only 11 percent of the surveyed pharmacies, with no availability differences between the rural or urban stores. They also determined that most participating pharmacies charged a service fee between $40 and $45.

“Our findings strongly suggest that more pharmacies need to offer this service to live up to the promise of widespread, easier access to birth control,” said lead author Anu Manchikanti Gómez, PhD, an assistant professor of social welfare at UC Berkeley, in a recent news release.

The authors noted that the current service fees may make birth control too expensive for some low-income women. They are hopeful this will improve once California’s Medicaid program starts reimbursing pharmacists for these services, which is required by July 2021.

They conclude the paper with a call for more research to identify the barriers to birth control accessibility.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Reducing cesarean delivery rates, without jeopardizing safety

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Approximately one-third of all babies born in the United States are currently delivered by cesarean section, according to the Centers for Disease Control and Prevention. Although cesarean delivery can be life saving for both the mother and child, the rapid increase in the cesarean birth rate between 1996 and 2011 raised significant concern that cesarean delivery is being overused.

This concern has led to initiatives to lower the c-section rates, including a new plan funded by the Oakland-based California HealthCare Foundation (CHCF) to lower California’s c-section rate for low-risk mothers to 23.9% in the next five years — in alignment with the Healthy People 2020’s national target.

A recent KQED Science article describes these efforts to reduce the state’s c-section rates. The story also explores the controversial issue that a healthy pregnant woman’s likelihood of having a cesarean birth varies depending on the hospital, based on a recent analysis of maternity care. For instance, the assessment report found that Lucille Packard Children’s Hospital Stanford has a c-section rate of 23.0 percent and the Coastal Communities Hospital in Santa Ana has a rate of 42.9 percent.

Deirdre Lyell, MD, professor of obstetrics and gynecology, clarified the issue in a recent email:

Nationally and internationally, there is concern that cesarean rates as a whole are too high. CHCF and others have shown a wide rage in cesarean rates by hospital around the country, and even within hospitals among individual physicians. Hospitals with very high rates should examine the underlying reasons. However, the “ideal rate” depends on the characteristics of the patient population, and it would be inappropriate to apply one goal to all women. For example, a pregnant, non-obese 25-year old who has had a prior vaginal delivery has a better likelihood of delivering her baby vaginally than does a pregnant, obese 45-year old first time mom.

At Stanford, we follow the “Safe Prevention of the Primary Cesarean Delivery” guidelines outlined by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine. We care for a higher-risk maternal and higher-risk fetal population, and share with our patients a common goal for delivery: a safe mom and a safe baby, while not performing cesareans unnecessarily. Avoidance of the first cesarean helps reduce the potential risks in the future.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.