More than 800 women worldwide die from pregnancy-related causes every day, most of them in sub-Saharan Africa and parts of South Asia. The two regions also experience the highest levels of stunting among young children, a form of malnutrition associated with poor health and cognitive development for the remainder of their lives.
This year’s Rosenkranz Prize winners are both working to better understand these severe medical maladies and eventually find interventions to help those women and children survive their pregnancies and live healthier lives.
Ivana Marić, a research scientist at the Stanford Prematurity Research Center, will use machine learning to analyze metabolites in maternal blood from women in Zimbabwe, Kenya and Bangladesh — with the goal of eventually developing a simple blood test that could predict preeclampsia, one of the leading causes of maternal death in these countries.
“This could make a difference between life and death for both the mom and the baby,” she said.
Stunting, the most prevalent form of malnutrition in children under age five, impacts more than 150 million children worldwide. The condition renders those children more susceptible to infectious diseases and deficits in cognitive development.
Jessica Grembi, a postdoctoral researcher in the Division of Infectious Diseases and Geographic Medicine, will use the $100,000 prize money awarded to each Rosenkranz Prize winner to study T cell activation by the gut microbiome. She believes antigens from commensal microbiota can overstimulate immune system T cells, leading to chronic inflammation.
“When a child is malnourished, we see that their guts are more permeable — and that permeability can allow extensive contact between commensal microbiota and the immune system,” said Grembi, a former environmental engineer and company commander in the U.S. Army who worked on potable water and wastewater systems on military bases in Europe and was deployed twice to Iraq.
The Rosenkranz Prize given by the Freeman Spogli Institute for International Studies (FSI) and Stanford Health Policy goes to Stanford researchers in any discipline who are investigating innovative ways to improve health care and policy in developing nations.
“Both Ivana and Jess epitomize the legacy of Dr. George Rosenkranz. They each bring outstanding technical skill to bear, very creatively, on enormously important issues in global health,” said Grant Miller, a professor of medicine at Stanford Health Policy and chair of the committee that selects the winners.
The award’s namesake is George Rosenkranz, a chemist who first synthesized cortisone in 1951, and later progestin, the active ingredient in oral birth control pills. His family created the Rosenkranz Prize in 2009 with an award that embodies Rosenkranz’s belief that young scientists hold the curiosity and drive necessary to find alternative solutions to longstanding health-care dilemmas.
“Breakthroughs in either the prevention of preeclampsia or the understanding of how gut microbiota contribute to childhood stunting would be real global health breakthroughs — with very actionable implications,” Miller said. “The committee felt that the caliber of both Ivana’ and Jess’ proposed work clearly warranted making two awards this year.”
Ivana Marić’s research career began in the field of information theory, a mathematical discipline that aims at determining the fundamental laws of information processing. Partly inspired by her mother’s work on reproductive physiology in former Yugoslavia, she started using machine learning to predict preeclampsia risk early in pregnancy. She joined the Stanford Prematurity Research Center in 2017 and has been pursuing these research goals since.
Marić notes that the Stanford Prematurity Research Center — with a grant from the Bill and Melinda Gates Foundation in a project led by professors David Stevenson, Gary Darmstadt and Victoria Ward — already has a collection of maternal antenatal blood samples at 20-24 weeks of gestation from 375 women in Bangladesh and 325 in Kenya. The collection of another 500 samples in Zimbabwe is underway.
Using latest advances in machine learning — algorithms and statistical models that draw inferences from patterns in data — Marić intends to analyze thousands of measurable metabolites obtained from these collected blood samples to identify biomarkers that are strong predictors of preterm birth or preeclampsia. Once these biomarkers have been identified, a simple point-of-care test can be made available across health clinics in Zimbabwe, Kenya and Bangladesh.
In Zimbabwe, preeclampsia is the third leading cause of maternal death following AIDS-related deaths and postpartum hemorrhage. Only 22% of women receive first trimester prenatal care and only 59% receive urine tests during a prenatal visit.
“A simple, low-cost, accurate diagnostic test that is widely accessible and capable of informing a pregnant woman of her risk of preterm birth and pre-eclampsia could be crucial means to save lives in these settings,” she said.
After Surviving the Pregnancy
Women in these countries not only deal with much greater risks to their pregnancies, but once their children are born, their babies are now at risk of not reaching their full potential.
Grembi was a good six months into her PhD in the civil and environmental engineering program at Stanford when she read a paper on environmental enteric dysfunction (EED), an intestinal disorder that affects 50-90% of children in low-income countries. It outlined how children in some lower-income countries were getting nutritional supplements providing 100% of the daily recommended allowances — yet stunting remained prevalent. Nutrition researchers began looking at the small intestines of these persistently stunted children and realized they suffered from chronic low-grade inflammation and permeability.
“I read that paper and thought, wow, this is a really important problem, and we don’t really understand what’s behind it,” she said. And today, her research explores the interplay of gut microbiota, bacterial pathogens and the immune system.
Dietary protein and micronutrient interventions alone have made only a small impact on childhood stunting in low- to middle-income countries, Grembi said. These children are often exposed to high quantities of intestinal pathogens due to poor sanitary conditions, which can explain some of the inflammation of the small intestine, and some portion of the stunting because their bodies can’t absorb the nutrients and protein needed to grow properly. But that’s not the full story because many children without infections fail to respond to nutritional interventions.
Grembi is now a postdoctoral fellow in the lab of David Relman, a senior fellow at FSI and a professor of microbiology and immunology at FSI’s Center for International Security and Cooperation. She will be analyzing some, 5,500 fecal samples from the Gates-funded WASH Benefits project in Bangladesh, which she helped to collect.
She intends to establish the cellular profile of T cells stimulated by gut microbes in children with persistent stunting — with the long-term goal of designing interventions that would promote healthy interactions between the immune system and beneficial gut bacteria.
“I share Dr. Rosenkranz’s determination to improve the health of disadvantaged populations across the globe — with a specific passion for undernourished children,” she said.
The Rosenkranz Prize
"Our family continues to be marveled by the insightful and imaginative work of Rosenkranz Prize awardees,” said his son, Dr. Ricardo Rosenkranz. “This year we could not be happier that the committee has decided to award two prizes to well deserving Stanford Investigators for proposals in topics such as preeclampsia prediction and the identification of microbiome related factors in childhood stunting. Through their outstanding efforts, Drs. Marić and Grembi continue to honor the legacy of our father and his desire to advance healthcare everywhere and for everyone.”
Born in Hungary in 1916 and trained in chemistry by Nobel Prize winner Leopold Ruzicka, Dr. Rosenkranz helped first synthesize cortisone in 1951. This remarkable discovery — made in Mexico by Dr. Rosenkranz and a team of similarly youthful scientists — shaped Dr. Rosenkranz’s career of innovative work. In that same decade, Dr. Rosenkranz’s team would synthesize the active ingredient for the first oral birth control. Partnering with a Wall Street investor for further drug development, Dr. Rosenkranz became CEO of Syntex, a position he held until 1981.
Committed to the country where he started his career, Dr. Rosenkranz helped found the Mexican National Institute for Genomic Medicine. His work was honored by the President in Mexico in 2001 with the Eduardo Liceaga Medal. Dr. Rosenkranz lived with his wife in Menlo Park, CA, until his death in 2019 at age 102, and has three children.