The in utero impact of high stress during pandemic conditions may last for decades in some babies.
Erin Bascom's job in HIV prevention training shifted to work-from-home in mid-March 2020, around the same time that she and her husband decided to keep their daughter, then two, home from daycare out of concern over COVID-19. Initially, the plan was for the parents to take turns, one caring for the toddler while the other worked. But then Bascom’s husband, who serves in Maryland’s National Guard in the U.S., was called to active duty for pandemic response.
He was gone 12 hours a day at first. Then, to prevent disease transmission between soldiers and their families, his unit was assigned to stay at an area hotel. By that time, the daycare had closed its doors. Sending their daughter was no longer an option, even if the couple had wanted to risk it.
Then Bascom learned she was pregnant. She struggled to care for her two-year-old while keeping up with work but soon discovered that to fulfill one duty completely necessitated failing completely at the other. Stress was piling on top of stress, and Bascom was frequently nauseous.
For more than 18 months, current and expecting parents in the U.S. have found themselves whipsawed by work and child care, isolated from social supports, and worried about the virus, their children, and their future children. Obstetrician-gynecologists (OB-GYNs) have noticed.
“I see serious effects, like an uptick in severe mental health difficulties,” said Marta Perez, an OB-GYN in St. Louis who was herself pregnant for much of 2020. Though Perez noted that pregnancy is a risk factor for mood disorders, she said that pandemic stress may have compounded that effect. Some patients at her hospital who had a history of mild depression or anxiety experienced exaggerated symptoms; others without a mental health history developed symptoms. She noted that vulnerable populations with barriers to mental health care were particularly at risk.
Researchers are only now beginning to quantify the toll. An initial review of data from a survey of approximately 500 new mothers and pregnant people living in Oregon found high rates of pandemic-related stress. Severalpublished studies have also found higher rates of maternal depression and anxiety among pandemic cohorts compared to similar pre-pandemic cohorts.
COVID's effect on the next generation
And experts in the field point to another reason for concern. A large body of research going back decades indicates that stress of the type Bascom experienced can affect the fetus, causing physical and psychological harm that lingers throughout the child’s lifespan. With its chaotic response to the COVID-19 pandemic, the United States has unwittingly subjected more than a year’s worth of newborns to conditions resembling an enormous experiment on the long-term effects of stress during pregnancy.
Researchers note that no individual child born during the pandemic is necessarily doomed to a lifetime of poor health. Many babies will experience no harm from their mothers’ stress, and for those who do, the effect is likely to be slight. But small individual effects multiplied by 3.5 million — roughly the number of children born in the U.S. between March 2020 and March 2021 — can have a large societal impact. In fact, experts in the field warn that the U.S. may be facing a looming public health problem.
All doctors should be trained in childhood toxic stress
Examples of short- and long-term effects that pediatricians and psychiatrists might expect to see in at least some children exposed to the pandemic include “developmental delays, stunted acquisition of executive functions, changes in mental health, changes in metabolic states, and obesity,” Tom Boyce, a professor emeritus of pediatrics and psychiatry at the University of California, San Francisco, wrote in an email to Undark.
Jennifer Ablow, an associate professor of psychology at the University of Oregon and co-lead of the survey of new mothers and pregnant people in Oregon, predicts “a great increase in depression and anxiety” in COVID-era children resulting in part from their mothers’ pandemic-related excess stress.
That’s why experts say it’s important to identify affected kids as early as possible. Pediatricians already ask about a child’s health, diet and habits such as screen time. Adding a short set of screening questions about mental health could open doors to treatment at the first signs of anxiety or depression for even very young children. In addition, child development specialists say, the U.S. should follow the lead of other wealthy countries and implement policies that ease the burden on parents and poor families so that any gestational effects are not compounded by extreme stress during childhood. Doctors could also furnish parents with nutritional education and resources to reduce the risk of their child developing obesity and diabetes, which cost the U.S. health system hundreds of billions of dollars annually.
Work-life balance woes
Whether such a prescription will become widely accepted and followed is far from clear, but many experts insist that it would be foolish to ignore the potential impacts on a generation of children born to parents like Erin Bascom, whose pregnancies were buffeted by the unique and compounded anxieties of a global pandemic.
To balance parenting and work while her husband was away, Bascom redesigned her daily routine, taking her daughter outside each morning to play and burn off energy before returning home, where she would ask the toddler to sit quietly for hours — usually facilitated by more screen time than she felt appropriate. One morning, during COVID’s earliest months, she was running late for a virtual meeting as her daughter dawdled on their walk home from the park. When Bascom picked her up to hurry home, a tantrum ensued. By the time she showed up on Zoom, Bascom was sweating and still out of breath from carrying her wailing child into the house.
Bascom recalled her boss “nicely asked how I was doing, and I just lost it.” She said she broke down and began to weep. “I cried a lot during those few weeks.”
The developmental origins of health and disease
For more than 30 years, researchers have observed a link between a pregnant person’s external environment and the health of the developing fetus. Maternal exposure to stressful events like grief and marital strain, for example, can increase her offspring’s risk of long-term disease and of lower cognitive ability. The American Academy of Pediatrics asserted in a 2012 policy statement that all doctors should be trained in how childhood toxic stress can negatively affect physical and mental health in adults.
In 1989, British epidemiologist David Barker published a foundational study in The Lancet showing that among thousands of men born in Hertfordshire, England, between 1911 and 1930, those with the lowest weights at birth and at one year had the highest mortality rate from coronary heart disease. The following year, he hypothesized that slow fetal development, along with low birth weight and premature birth, which research would later show can all be influenced by the pregnant individual’s environment and circumstance, can cause high blood pressure, coronary heart disease and Type 2 diabetes.
Barker’s finding and subsequent theory set off a wave of research into what has become known as the developmental origins of health and disease. But it can be tricky to determine causality in this field: It wouldn’t be ethical to run an experiment in which some pregnant people are intentionally exposed to hardships that might harm their future children. So researchers began to study natural experiments — real life events experienced by only a portion of a given population — to see if one group fared better than another.
A calamity from World War II provided a disturbing example. When Nazi occupiers punished the Netherlands’ resistance with a blockade on food shipments to the country during the winter of 1944-45, a famine ensued. Five decades later, Hans W. Hoek, of the Parnassia Psychiatric Institute, and collaborators at Columbia University, compared the children of individuals who had been pregnant during the famine with those of women who gave birth just before the blockade, or more than 40 weeks after Allied troops drove out the German occupiers, ending the famine.
The findings were sobering. Rates of schizophrenia and central nervous system abnormalities in adults born during those months were nearly double those among people born just before or after. As a group, these children grew up to have higher rates of obesity. They also died younger. Some effects cascaded into their own children.
The long-term impact of fetal programming
Women pregnant during objectively stressful situations like famine, war or epidemics may see long-term effects in their childrenPhoto by engin akyurt on Unsplash
The process believed to be at work is known as fetal programming. “Recent findings suggest that many human fetuses have to adapt to a limited supply of nutrients and, in doing so, they permanently change their physiology and metabolism,” Barker noted in a 1994 lecture for the Wellcome Foundation, a charitable organization that supports scientific research. “These ‘programmed’ changes may be the origins of a number of diseases in later life.”
The programming occurs with the help of the placenta, an organ that develops during pregnancy and supplies oxygen, nutrients, hormones, antibodies and other substances that both nourish the fetus and provide it with information about the mother and the external environment into which it will be born. For example, a pregnant person living in a low-calorie environment may have lower levels of nutrients to pass on to the fetus. This scarcity sends a signal to the future child that it would be well served to hoard calories — to slow its metabolism.
Research on the influence of nutrient levels on fetal development got scientists wondering: to what extent could psychological stress contribute to behavioral and other health problems that developed in some children? In the 2000s, they started to find higher rates of behavioral and emotional problems in children of pregnant women with anxiety (even controlling for postpartum depression), suggesting that the fetus also receives signals about the mother’s psychological stress.
Hundreds of peer-reviewed papers have since substantiated the association between maternal stress during pregnancy and the risk for neurobehavioral or mental health problems in the children they will bear. Among the field’s most notable research projects is the Danish National Birth Cohort, a longitudinal study of approximately 100,000 mother-child pairs that began in 1996 and has observed the same set of variables in the subjects at repeated intervals. Scientists have used some of that data to show that increased stress during pregnancy is associated with a higher risk of the child developing an infectious disease or mental health disorder.
Cortisol could be key
In 2016, a group of researchers led by Catherine Monk, a professor of medical psychology at Columbia University Medical Center, explored a potential mechanism to help explain these negative outcomes. The researchers surveyed 61 women mid-pregnancy and collected salivary samples to measure cortisol, a hormone the body produces when the brain perceives a threat. A little cortisol can be beneficial, helping the body negotiate a stressful situation like giving a speech or taking a test. But too much, or too frequent, production of cortisol can negatively affect health. One reason is that cortisol triggers the release of glucose, increasing blood sugar levels and contributing to high blood pressure and increased risk for diabetes.
The fetus of an extremely stressed mother could be exposed to higher cortisol levels in the womb.
Monk’s team hypothesized that if the pregnant individuals experienced high levels of stress, then excess cortisol would pass through the placenta to the fetus. This, in turn, would cause changes to the expression of a fetal gene responsible for deactivating, or neutralizing, cortisol in the body.
Genes can be turned off or on through chemical processes known as methylation and demethylation. In adults, methylation patterns are influenced by environmental factors such as diet, stress, exercise and exposure to pollution. In fetuses, methylation patterns are influenced by the environment of the womb — the particular mix of nutrients, hormones and other substances that pass through the placenta from mother to child.
Monk’s study showed that in pregnant individuals, self-reported heightened stress (though not as measured by salivary cortisol) was associated with increased methylation, effectively turning off the gene responsible for deactivating cortisol. The fetus of an extremely stressed mother, therefore, could be exposed to higher cortisol levels in the womb, which might then affect its development and make the child less able to tolerate stress. This could then make them more susceptible to long-term behavioral and other health problems, such as obesity. Changes in such observable characteristics that do not involve changes to the underlying DNA sequence are referred to as epigenetic changes.
A natural experiment on the effects of hardship
According to Monk’s study, it was the first to link pregnant individuals’ stress with changes in the expression of placental genes. Separate research groups at National Institutes of Health and the University of Florida have since found associations between pregnancy stress and methylation changes in the placenta. Otherwork suggests that if a girl, for example, grows up to enter a pregnancy overweight, perhaps in part owing to her mother’s stress levels during pregnancy, that, along with a confluence of other factors, could make her own child more prone to obesity.
So some epigenetic changes, such as methylation patterns, might have intergenerational effects, even though the child’s DNA never changes. And while it remains a matter of debate whether the epigenetic changes themselves — the particular methylation patterns developed in utero, for example — can be passed down in humans, studies in animal models provide additional evidence that maternal stress can trigger in utero epigenetic changes that then influence the offspring’s health later in life.
One of the most robust studies of extreme stress during pregnancy focuses on children born during an ice storm that struck eastern Canada in 1998. In Quebec, more than three million people were without electricity, some for over a month. Like the Dutch famine, this provided an opportunity for a natural experiment: look at the children who were in utero during the power outage and compare them to those born just before or more than 40 weeks after electricity was restored.
Suzanne King, a professor in the Department of Psychiatry at McGill University in Montreal, followed ice storm kids for 20 years. She and colleagues have found that the more stress a person who was pregnant during the ice storm experienced, as measured by such factors as the number of days they went without electricity and loss of income, the greater the chance their child would have poor language, motor and intellectual development. Those children were also at a higher risk for obesity. PTSD symptoms while pregnant, meanwhile, predicted a greater likelihood that their child would have behavioral problems. What’s more, the methylation of the children’s genes, which tracked closely to the number of days their mothers went without electricity, affected the children’s immune systems, body mass index, and metabolism at age 13.
“Objective hardship predicted just about everything,” King said.
Other natural experiments have since validated the link between pregnancy stress and poor long-term health outcomes in children. Researchers at New York University found in 2012 that women who experienced earthquakes early in their pregnancies went on to have higher rates of preterm delivery. Israeli scientists, two years later, showed that women in a small city near the Gaza Strip that had experienced rocket attacks had more preterm births and lower birth-weights than women in a socioeconomically similar town without rocket attacks. Premature birth can set up a child for high blood pressure, chronic kidney disease and other conditions in adulthood.
The COVID-19 pandemic is another such natural experiment. “In all of our studies, when we look at objective hardship, we’re looking at the level of threat, the level of loss, the level of change and the scope — the duration and the percentage of the community that is affected,” King said. The pandemic has burdened the U.S. population with high degrees of all of these.
Social status matters — even for a fetusPhoto by Caleb Woods on Unsplash
The responses of Bascom’s, Lytle’s and Krin’s children are unlikely to resemble one another precisely. And earlier research suggests that because these babies are middle-class and not Black or Latino, they will probably face better odds than those from less privileged backgrounds. Boyce, of UCSF, said that because children respond differently to environmental exposures, “there will be tremendous variation in the impact of the epidemic” due to age, socioeconomic status, race and other factors.
Studies have shown that, as a group, Black Americans experience more stress than others, stemming from discrimination and racism. And data further suggest that chronic stress accounts for much of the disparities in birth weight, which can be a precursor to chronic disease, among White, Latino and Black infants.
Neisa Nelson, a 27-year-old Black woman, lives in Connecticut. Though she and her husband both held onto their jobs and never became sick from SARS-CoV-2, she still experienced elevated levels of stress during her pregnancy. During the pandemic, Black Americans have been more likely to serve as essential workers — one of the factors contributing to their elevated risk of exposure to the virus — and Nelson was among them: She works as a nurse in the pediatric ICU at Mount Sinai Hospital in Manhattan.
In the spring of 2020, when New York City became a global hotspot, averaging more than 5,000 cases per day, Nelson was in her third trimester. She came into close contact with colleagues who treated COVID patients, and she said her hospital saw some pregnant women die of the disease. Nelson feared the same fate for her and her future child.
“It was very, very stressful,” she said. “When the spikes were high, and people were getting symptoms and things of that sort, it was really, really bad.”
Then, on May 25 of last year, George Floyd, an African American man, was murdered in Minneapolis by police officer Derek Chauvin, and the nation erupted in protest. Nelson hadn’t felt racism among her colleagues before, but some of her White colleagues, she said, would “make little jokes about it, and sometimes it’s offensive because they don’t quite understand what they’re saying.”
Race, pandemic stress and fetal outcomes
Researchers are asking whether experiences like Nelson’s reflect a broader link between race, pandemic stress and fetal outcomes. Prior to the pandemic, the NIH had launched a program called ECHO (Environmental Influences on Child Health Outcomes), which includes one of the largest cohorts ever for studying the health of U.S. children. Six research groups won special funding for time-sensitive studies related to COVID-19, one of which is co-led by Johnnye Lewis, founder and director of the Community Environmental Health Program at the University of New Mexico’s College of Pharmacy. She and colleagues are comparing Indigenous, Black and white communities to understand how the various stressors of the pandemic, as well as racial and social inequality, affected mental health and neurodevelopment.“
“My poor child. It’s my first baby.”
The beauty of ECHO is it lets us compare across several different populations,” Lewis explained in an email. During the pandemic, Black and Latino communities have had higher rates of hospitalization and death than white communities. Meanwhile, Black communities were also more directly affected by police brutality and the anti-brutality protests. A preliminary review of the ECHO data used in Lewis’s study found that the Black and Indigenous communities surveyed reported more pandemic-related stressors compared with a rural White community. Based on the research linking stress to disease, behavioral health and neuro-developmental problems, this could mean poor outcomes for babies in those groups.
Nelson gave birth in June 2020 and described her new baby as “very much healthy.” (The other mothers interviewed by Undark also reported that their infants are healthy.) Still, she vividly recalls how difficult it was to cope in the final months of her pregnancy. During one period, she said, she cried every night.
“I was so stressed out to the point where I had to tell the doctor I wanted to go on bed rest,” she said. “My poor child. It’s my first baby.”
Policy changes could help
There is still time to ameliorate the effects of pregnancy stress on the millions of children born during the pandemic, but experts warn that it’s crucial to act quickly. With the right intervention at the right time, they maintain, children and populations can be healed. “If you can do interventions early when systems and organs are most plastic, then it’s easier,” said Matthew Gillman, program director of ECHO.
Monk, the psychiatric researcher at Columbia, said there’s no such thing as too early. “Babies are in utero right now. We could be paying attention to what’s happening to the pregnant person and their partner in this time,” she said. Post-partum depression, moreover, is associated with pregnancy distress, and babies can pick up on cues from depressed moms even when very young. Monk pointed to a program, HealthySteps, which pairs a childhood development expert with pediatric care and links those in need to services, as one successful model. Ablow, similarly, said pediatric visits could include screening for early signs of anxiety; it and other emotional disorders often begin very early in childhood.
A raft of studies have pointed toward other interventions worth trying. Data from randomized controlled trials — the gold standard in health research — show that simply providing cash to families reduces stress and boosts children’s school achievement. Parental training, psychotherapy and better health care can produce similar results. Hard data has demonstrated that the kinds of chronic diseases linked with toxic stress in utero are also associated with lower educational attainment, lost work days and income differentials, suggesting that early interventions may be cheaper than doing nothing.
Researchers are already finding effects of pandemic-related stress in infants. Elinor Sullivan, a psychologist and collaborator of Ablow’s, found that one-year-olds who were in utero during the pandemic had higher sadness scores as assessed by an infant behavior questionnaire, compared with one-year-olds born before the pandemic.
Meanwhile, Elizabeth Werner, an assistant professor of behavioral medicine at Columbia University, working with Monk and colleagues, has found that fetuses whose heart rate accelerated when the mother experienced stress went on, at 4 months old, to react with greater motor activity when confronted with something new. By school age, Monk said, “We might see some attention problems in part related to this jitteriness around the environment.” And such children, when they grow up, are at heightened risk for anxiety disorders.
King, Ablow and Monk each agreed that policy changes could ease the burden on pregnant women and new mothers — pandemic or no pandemic. The U.S. is alone among 41 countries of comparable wealth and culture in not requiring companies to provide new parents with paid time off to care for a newborn. Parental leave is linked to healthier children, Ablow added, so it ultimately results in less economic burden on the health care system.
Widespread, quality, affordable daycare might also help. Perez, the St. Louis OB-GYN, said she had patients leaving the hospital after childbirth against medical advice because they needed to care for other children. “Because they’re just trying to survive,” she said, “they had to sacrifice their own health or their pregnancy’s health to care for others.”
Looking on the bright side
Late last summer, Hurricane Ida tore through the eastern U.S., from New Orleans to New York. At the time Ida made landfall on the Gulf Coast, the Dixie wildfire had been burning for over six weeks across northeastern California, fueled by high temperatures and dry woodlands affected by an exceptional drought. Evacuations were ordered in four counties and smoke from the fire spread more than 1,000 miles.
Climate scientists expect a warming atmosphere to continue to bring stronger, more frequent storms to the Gulf Coast and Atlantic Coast regions, and continued drought conditions to the West, priming it for ever-greater firestorms threatening homes and lives.
This would suggest that even after the COVID-19 pandemic is brought to heel, Monk and other researchers might have plenty of opportunities to continue studying the effects of extreme stress on pregnancy.“When we think about this generation that was in utero during the pandemic, we also have to think about the Earth that they’re inheriting in 20 years,” she said. Climate change “is affecting the air their mothers breathe while they’re pregnant, and it’s going to be affecting their development in so many ways, and the quality of their lives in the future.”
Bascom knows those stressors, too. Her home in Northern Virginia was placed under a state of emergency during Hurricane Ida. Her family was out of town for most of it, but the storm killed 82 by some estimates and caused power outages in at least eight states. Nine days after coming on shore in Louisiana, more than 400,000 state residents were still without power.
Still, Bascom considers herself relatively fortunate. After the birth of her second child, she was able to take 18 weeks off, cobbling together the eight weeks of paid time off the District of Columbia requires her employer to provide, along with sick leave, disability leave and vacation days. (Parents in the European Union get a minimum of four months, paid).
She reports that she and her children — now 11 months and almost four — are doing well. “It was a nice reward at the end of it to have a baby to snuggle,” she said. She didn’t lose her job, like so many millions, and her employer was very supportive.
“I know that, despite the stress I was under,” she added, “I also was really, really lucky.”