Researchers are trying to close the knowledge gap

Megan Hanson was eight weeks pregnant in 2019 when she experienced a miscarriage — her sixth consecutive loss in as many years. It felt particularly cruel after a second IVF transfer. She and her husband, Ben Burnham, were devastated, physically and financially drained — and deeply frustrated by the lack of answers or support for people like them who had experienced recurrent miscarriages.

Driving to a Seattle clinic for surgery to remove fetal tissue, the two felt the heaviness of the moment. They knew they were done trying. Over the previous six years they had become medical sleuths, reading studies, speaking to doctors, and examining all treatments possible. Most doctors pinned Hanson’s losses on fetal abnormalities, but she felt there was more to it. The fact that her miscarriages were unexplained, she says now, was “unacceptable.”

Lack of research into miscarriage in the U.S. — its prevalence, its causes, and how best to treat people who’ve experienced pregnancy loss — has helped to reinforce what has long been a culture of silence and shame around miscarriage. That knowledge gap means that people who miscarry, and miscarry repeatedly, like Hanson, aren’t given the emotional support they need at a time when they are most vulnerable. Equally important, they aren’t given the medical treatment, screening, and support from the health care system that might help them avert future miscarriages. And research into the possible reasons for recurrent pregnancy loss has been limited and siloed, several experts told STAT. 

The dearth of knowledge about pregnancy loss and miscarriage is far greater in the United States than in other industrialized countries, according to physicians, policymakers, and researchers who spoke with STAT. Countries with national health systems such as the United Kingdom have standardized medical records and better aggregate health data, enabling medical researchers to conduct studies and trials more readily, and to examine the physical, emotional, and economic toll of pregnancy loss. Nordic countries, too, have national health systems that provide more open access to data, enabling researchers to study the impact of loss to a greater extent than it is studied in the U.S.

One U.K. estimate of the economic devastation of miscarriage there pegged it at £471 million, or $611 million, per year. Yet no such estimate of the economic cost of miscarriage in the U.S. — generally defined as a loss in the first 20 weeks of pregnancy — exists. The Centers for Disease Control and Prevention does not publish data on miscarriage, but estimates suggest that 10% to 25% of all pregnancies in the U.S. end in miscarriage. The American College of Obstetricians and Gynecologists says that fewer than 5 in 100 people have two miscarriages in a row.

Hanson now has two children. But she knows from her own experience the pain of miscarriage, the mental health cost, and the urgent need for better data and more research in the U.S. “I wish that the system had been better set up to support that piece of it for me,” Hanson said. “It’s like you’re grieving this imagined future that you had.” 

Funding research to ‘find answers faster’

Reflecting on their many losses some years ago, Hanson and her husband stepped boldly into the information void: In 2019, after consulting extensively with doctors and researchers, they set up the Recurrent Pregnancy Loss Association (RPLA), focused on eliminating recurrent pregnancy loss and preventing unnecessary losses. 

The nonprofit offers support and resources to individuals and couples who’ve experienced the trauma of recurrent miscarriages. And it’s partnering with the medical and scientific communities to “find answers faster,” said Hanson, who worked for several years at the pharmaceutical company Baxter and witnessed fruitful partnerships between industry researchers and patient groups. While there are a few organizations that focus on stillbirth — defined as pregnancy loss after 20 weeks of gestation — the RPLA is the first to focus exclusively on recurrent miscarriage research.

So far, the RPLA has distributed $133,000 to reproductive endocrinologists, experts in maternal-fetal medicine, and others to explore how various factors — from sperm DNA fragmentation to endometrial “notch signaling” to abnormal responses in the mother’s immune system — may play a role in pregnancy loss. 

Some of the few experts in the U.S. leading research on miscarriage and pregnancy loss are funded by the RPLA, including Winifred Mak at the University of Texas at Austin; Abey Eapen, at the University of Iowa Health Care; and Ruth Lathi, at Stanford University’s School of Medicine. All three are reproductive endocrinologists and infertility researchers.

Historically, the National Institutes of Health underfunded miscarriage research in the United States and there was limited private funding, said Mak. In recent years, that’s started to shift. The NIH has funded studies into recurrent miscarriage at Yale and Stanford and Mak’s research on sperm DNA fragmentation, which was also supported by the RPLA. 

Mak hopes to discover the precise type of damage to sperm DNA — single-stranded or double-stranded — that is implicated in losses. In cases where it’s double-stranded, Mak will do additional molecular analysis to determine the region where the damage is located. Mak, who completed medical school in the U.K., says that it’s critical to do research in the United States because European research doesn’t always translate to the diverse and heterogeneous population of the U.S. Greater funding for miscarriage research holds the promise of providing “patients with more answers and hopefully more therapeutic options,” she said. 

Before Eapen went to the University of Iowa, he trained at Tommy’s National Centre for Miscarriage Research in the U.K. There he witnessed how collaboration among researchers and funding for women’s health made large-scale clinical trials possible. “To finish that type of research in a timely fashion [in the U.S.] would be a big hurdle at this point in time,” he said.  

Today Eapen is using funding from the RPLA to test selected patients’ various biomarkers for inflammation and their telomere length for epigenetic changes that may be associated with miscarriage. These are not considered standard tests for miscarriage. The goal is to produce high-quality research using consistent techniques and the same laboratory to ensure accuracy in their results. 

At Stanford University’s School of Medicine, reproductive endocrinologist Lathi has seen how “life-altering” miscarriage can be for patients. Fetal tissue, she says, can offer answers in pregnancy loss just as an autopsy would provide clarity after death. But unlike in Europe, where systems are standardized and early pregnancy centers can provide care and capture fetal tissue when a miscarriage is actually happening, the U.S. doesn’t have that level of focused care — leaving many patients without answers. 

Together with partners across multiple universities, Lathi is recruiting participants for the HOPE study, which uses genome sequencing of parental and fetal DNA to determine which genes contribute to pregnancy loss. That is in addition to her research supported by a grant from RPLA, which examines endometrial tissue for notch signaling — a process that is an evolutionary pathway for communication between cells. That work could clarify if the signaling is dysregulated during a miscarriage or recurrent miscarriage.  

Researchers like Mak, Eapen, and Lathi say there is potential for more research in the U.S. But collaboration among researchers, which involves coordinating efforts across multiple universities, requires significant resources. The U.S. would have to vastly increase funding for women’s health — which has been historically deprioritized — to produce the type of large-scale clinical trials on  miscarriage and recurrent miscarriages involving thousands of participants like their European counterparts, they said.

A U.K. study to assess the impact of pregnancy loss

Before starting RPLA, Hanson had looked to the United Kingdom for inspiration. 

For decades, the U.K. has been at the forefront of research and advocacy on pregnancy loss. Tommy’s, founded in 1992 by two obstetricians at London’s St. Thomas’ Hospital, leads research on pregnancy loss under the umbrella of the Tommy’s National Centre for Miscarriage Research. The center, a partnership between three universities and four hospital systems, supports people experiencing loss while also enabling an educational and cultural shift through public campaigns in an effort to save lives. Similar resources and research support are harnessed by the Pregnancy Loss Research Group in Ireland and The Pink Elephants Support Network in Australia.

Among their important findings is that the use of progesterone in women who have early pregnancy bleeding and a history of miscarriage can lead to 8,450 more babies born each year; that the drug sitagliptin (used to treat diabetes) can increase the number of stem cells in a person’s womb and reduce their risk of miscarriage; and that physiological processes may explain maternal selection of embryos during early gestation.

Six years ago, the British government made it a priority to examine how care was delivered to people experiencing loss before 24 weeks of gestation (the U.K. definition of miscarriage) across the National Health Service (NHS), the U.K.’s publicly funded health care system. 

Then-Secretary of State for Health and Social Care Jeremy Hunt initiated a nationwide independent “pregnancy loss review,” which was co-authored by Zoe Clark-Coates and Samantha Collinge, a grief specialist and midwife, respectively. 

Believed to be the first of its kind, the review offers broad lessons on how countries around the world, including the United States, can improve care for those who experience miscarriage and pregnancy loss, take it seriously as a medical problem that needs investigation, and provide governments and health systems with tangible insights on how to better care for grieving families. 

Clark-Coates and her husband waited several years before trying to conceive, and she had two pregnancy losses in a row. The second time, “We were actually asked whether we were so upset because we paid for the baby — was it because we had IVF — which was really shocking,” Clark-Coates reflected about the treatment she and her husband, Andy Clark-Coates, received at the hospital.

The response of many to pregnancy loss — invisible but often creating physical, mental and economic strain for couples, said Clark-Coates — is to grieve in silence. “The actual cost on society is so huge that if you actually put in some of this cost in early days of bereavement support you save as a country so much more money down the line,” she said.  

After eventually experiencing five losses, and the birth of two living daughters, Clark-Coates knew that uncompassionate care was common. She and her husband founded Mariposa Trust to support people going through pregnancy loss regardless of gestational age. 

Initially the nonprofit focused on offering emotional support. But, in response to hearing thousands of “really traumatic stories of poor and uncompassionate care,” Clark-Coates said the organization changed its focus to address the impact of fetal loss on individuals, families, the health system, and society overall. It sought to understand what it would take to shift the culture of silence and indifference that accompanied fetal loss.

Remembrance ceremonies and non-viable birth certificates

When Hunt, the U.K. health secretary, made his request in 2018, working on the pregnancy loss review was a natural next step for Mariposa Trust, which had tried to change cultural practices that influence how families experience their loss. One is the 12-week rule whereby couples keep pregnancy a secret until completing the first trimester, after the highest risk of miscarriage has passed. “It tells people that they shouldn’t ever be talking about loss which is creating this huge taboo around the subject,” Clark-Coates said. “It’s also giving people a false sense of security.” 

While the risk of loss indeed decreases after the first trimester, there is always a risk. The 12-week rule, said Clark-Coates, means that pregnancy loss and support for those who experience it during that period isn’t normalized.

Miscarriage comes with little opportunity for closure, as providers usually urge their patients to move on and try again. Mariposa Trust holds remembrance ceremonies for people to honor their loss, regardless of the gestational age of the fetus — thereby avoiding the damaging “grief hierarchy” that suggests a loss later in pregnancy somehow is more significant than one that occurs early in a pregnancy. 

As another way to promote closure, the pregnancy loss review suggested that the U.K. government issue a voluntary, non-legal certificate that would formally document a non-viable birth. The program launched earlier this year. 

In preparing the review for the U.K. government, Clark-Coates and Collinge met with emergency services, maternity and gynecology departments, sonography units, and clinics that specialized in miscarriage prevention and research. Based on their findings, the review recommended that if a person has more than two losses, they be referred for additional blood tests and other investigations to detect any underlying problems, something often ignored by clinicians unless a person had three or more losses.

The recommendations — all 73 of which were accepted by the U.K. government in July 2023 — were comprehensive, spanning everything from pain relief, mental health, and palliative care to the sensitive handling of fetal remains. The review recommended that hospitals with maternity care also have a clinic for those who experience pregnancy after a loss, recognizing people may need extra support to avert another loss and experience a successful pregnancy. It further recommended mental health support for both parents, given the increased risk of PTSD and suicide among families that have experienced loss.

Estimating the economic impact of pregnancy loss

When Priti Kalsi, a labor economist at the Rochester Institute of Technology looked for data on the impact of a miscarriage on a woman’s income in the United States, she discovered that no aggregate national statistics exist on which to base any analysis.

Researchers in European countries have been able to draw on such national data for their analyses thanks to integrated public health systems. In the Netherlands, researchers Sara Rellstab, Pieter Bakx, and Pilar Garcia-Gomez used hospital data from Statistics Netherlands that showed a 16% increase in women seeing a psychiatrist or psychologist in the first year following a miscarriage. Their paper suggests that a decline in mental health triggered by a miscarriage “may lead to short term lower probability of promotion and/or salary stagnation.” Researchers in Norway sourced data from a Norwegian pregnancy loss registry in a working paper that showed that women tend to make greater investments in their health following pregnancy loss, by increasing their use of supplements, switching physicians, and taking other measures.

Kalsi, in trying to apply economic analysis to pregnancy loss in the U.S. with co-author Maggie Y. Liu, had to turn to data compiled in the National Longitudinal Surveys by the Bureau of Labor Statistics. Their work, which examines the financial impact of a first miscarriage up to seven years after the event, suggests that a decline in mental health triggered by a miscarriage, “may lead to short-term lower probability of promotion and/or salary stagnation.” 

Kalsi and Liu compared samples of women who have the same number of children to one another, but in one group, the women had experienced a miscarriage along the way. They carefully matched the sample so that the group that didn’t miscarry and the group that did miscarry had their first child at a similar age.

Beginning in the late ’90s, the BLS surveys interviewed teenagers annually to assess how their life experiences with developing careers and growing families may have affected their earning power. Kalsi and Liu focused on the data about women as they got pregnant and experienced pregnancy losses. The data were not explicitly designed to study miscarriages, but offered detailed fertility and labor market outcomes.

Kalsi and Liu’s working paper shows that women who experienced a first miscarriage (the data looked at up to two losses) withdrew from the workforce substantially. They worked fewer hours the year of the miscarriage and after that, about 200 fewer hours per year. That translated to an annual income reduction of approximately $5,000 per year in the seven years after the loss.  

“The most striking thing is just a magnitude of the effect. It is not a small effect. It is a big effect. The pattern is very convincing,” Kalsi said. “These women look very similar economically to women who don’t have a miscarriage until they have a miscarriage.” 

Kalsi said that further analysis showed that grief is a driver of the results. After a miscarriage, women and their partners were more likely to break up, decrease cohabitation, and complete fewer years of education, and their mental health deteriorated. Their European colleagues found a similar impact on a person’s mental health after a miscarriage.

“It’s important to focus on the United States because compared to Europe, we don’t have a universal health care system,” Kalsi said. “Women don’t have access to fertility care, we don’t have access to the kind of economic cushion that we would have access to after any kind of health event.”

Addressing the gaps in U.S. data collection

When Carol Gilbert, an assistant professor at the University of Nebraska Medical Center College of Public Health, examined CDC data for her 2021 Ph.D. dissertation on perinatal periods of risk, she realized that she needed more complete data for losses before 20 weeks. For public health researchers like Gilbert, incomplete data prevents them from making accurate comparisons between states. When she examined the data, she understood why the CDC doesn’t publish statistics on fetal losses before 20 weeks of gestation. 

The individual case data on pregnancy losses are collected by hospitals, assembled by states, and then forwarded to the CDC. But a trifecta of quality problems may explain why the CDC does not publish what data it does receive on losses before 20 weeks of gestation. First, laws regarding the gestational age at which fetal losses need to be reported vary across states. The second problem Gilbert found was that states were inconsistent in their reporting, failing to follow their own laws. This was especially true for fetal deaths between 20 and 24 weeks.

The third problem was that not all states fill forms completely, leaving out data elements like birthweight and basic maternal characteristics. Some of this is inevitable because it is difficult to weigh fetal tissue in the early stage of pregnancy loss. A CDC spokesperson told STAT that “information regarding early pregnancy losses before 20 weeks gestation, including ectopic pregnancies and miscarriages, is challenging to obtain as these outcomes are not routinely reported to CDC.”

There aren’t many ways to fix national or state-level data problems without the introduction of new reporting requirements across the nation, along with standardized, universally accepted dates and definitions for pregnancy loss — something unlikely to happen anytime soon. In each state, says Gilbert, hospital staff, data entry workers and coroners would have to be trained properly, and time would have to be devoted to ensuring that record keeping is complete and accurate. All of this would require, she said, “more funding or huge efficiency gains.”

Meanwhile, researchers will have to adapt, and make do with the data available in their search for answers as to why miscarriages happen.

And they may continue to depend on individual efforts, such as those of Hanson. When she was wondering how the Recurrent Pregnancy Loss Association could advance research, she knew that addressing the data problem was key. 

So in 2022 the RPLA started a patient registry, compliant with privacy regulations, that collects information and data on pregnancy history and diagnoses. It can’t compare, of course, with a national data registry. But Hanson hopes the registry can help researchers access detailed information about more people who have experienced miscarriages. With enough data, it could potentially contribute to a natural history study in the future.

“Then you can really start to say, ‘here are the things that worked’ or you can start to ask better questions about what might be related underlying factors here that we haven’t maybe thought of before,” Hanson said. “My goal is really to get to that place of preventing unnecessary losses.”

This story is part of ongoing coverage of reproductive health care supported by a grant from the Commonwealth Fund. Our financial supporters are not involved in any decisions about our journalism.