Intense heat is a particular hazard in pregnancy. New studies are probing why.
SYDNEY—Jem Cheng was soaked with sweat by the time she climbed off the stationary bike at the University of Sydney last month. The work of pedaling wasn’t the problem; the 30-year-old pushes herself much harder during her own regular workouts. But this ride took place in a “climate chamber,” a large, high-ceilinged room that on this day was heated to 36°C. During Cheng’s 86 minutes of pedaling, the humidity in the chamber gradually ramped up from 38% to a deeply uncomfortable 56%, making the air feel more like 46°C.
“I feel like I could have stayed in there for a little bit longer,” she said later, after weighing in to discover she had sweated off nearly 1 kilogram. “But I probably wouldn’t have wanted to.”
Cheng is a postdoc at the university’s Heat and Health Research Incubator (HHRI), and her ride was just a demonstration. But starting soon, dozens of pregnant women will be pedaling in the same climate chamber. The groundbreaking study seeks to replicate what tens of millions of pregnant people experience every day in a warming world: physical exertion in intense heat. The trial is funded by £2 million from the Wellcome Trust, which awarded £16.5 million this year to projects probing why heat is a risk during pregnancy.
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That risk is already undeniable. Dozens of epidemiological studies have linked heat exposure to poor outcomes including preterm birth, low birth weight, stillbirth, and congenital anomalies in the fetus. Premature birth is the most commonly documented: A 2020 literature review found that each 1°C increase brought a 5% increase in the risk of prematurity in hot areas or seasons—and a 16% increase during heat waves. That means climate change could exacerbate a major risk: Globally, prematurity is already the leading cause of death for children younger than 5.
A smaller number of studies, almost all from high-income countries, has suggested heat exposure also imperils the pregnant person: It has been associated with gestational diabetes and preeclampsia, a dangerous condition marked by high blood pressure. And a study of more than 400,000 pregnancies in Southern California published this month in JAMA Network Open found long-term heat exposure during pregnancy increased the risk of severe maternal illness during labor by 27%. The impacts may be worse in low-income countries in the Global South that face the greatest threats from climate change—and where pregnant people are more likely to be exposed to prolonged physical labor in hot environments. But, “there is very little data from regions we know are particularly vulnerable,” says Ana Bonell, a clinician and epidemiologist at the Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine. Bonell has studied heat stress in pregnant Gambian subsistence farmers and has Wellcome funding to expand her work there.
Even in wealthy nations that are investing heavily to prepare for climate change, specific risks to pregnant people are rarely acknowledged in heat or disaster plans and related documents. There is little research to go on. How pregnant people respond biologically to heat stress, how fetal risk varies across the weeks of pregnancy, and the safe limits for heat exposure are all uncertain.
Those unknowns helped inspire the new application for the HHRI climate chamber, which the Sydney researchers have used to study heat exposure among athletes, children, and the elderly, and to simulate conditions on garment factory floors in Bangladesh. Having finished a small initial trial, the team will spend the next several years recruiting pregnant participants to cycle in the chamber. “We’re very passionate about trying to get evidence that is applicable to women in pregnancy,” says Adrienne Gordon, a neonatologist and stillbirth researcher at Sydney and the Royal Prince Alfred Hospital, who is co–lead investigator on the climate chamber study.
The Sydney team will combine its data with measurements from a companion study of pregnant women wearing temperature sensors, run by collaborators in urban India and rural Bangladesh. The result will be a first-of-its-kind model aimed at designating safe limits for heat exposure during pregnancy. Such concrete advice is vital, says the study’s other co-lead, Ollie Jay, a thermal physiologist at Sydney who directs HHRI. “Otherwise, all we have is: ‘Avoid extreme heat,’ or ‘Avoid hot weather,’ or ‘Avoid exercise,’” he says. “That’s very difficult for many of the most vulnerable.”
PREGNANT OR NOT, humans normally maintain their core temperature—the temperature of their internal organs—at about 37°C. To keep that temperature from rising, we must lose heat as fast as it is produced by the body and absorbed from the environment. Our most efficient mechanism for losing heat is sweating.
Much of what scientists know about the body’s response to heat comes from studying men. “Healthy, young, white males [are] the classic sort of test subjects for understanding thermoregulatory response,” says Caitlin Wyrwoll, a reproductive physiologist at the University of Western Australia who is also embarking on a Wellcome-funded study of extreme heat and pregnancy complications. For instance, a model called the Universal Thermal Climate Index (UTCI) is widely used to gauge heat stress in different environmental conditions—including for studies of pregnancy. But it’s based on a 73.5-kilogram man with 14% body fat. In the U.S., women of reproductive age who aren't overweight or obese typically carry between 20% and 31% body fat, a percentage that bumps up during pregnancy, making the model’s assumptions far from fit for purpose.
This matters because it’s vital that pregnant people maintain normal core temperatures. The evidence comes not just from data linking heat exposure and poor pregnancy outcomes, but also from studies showing that running a high fever in pregnancy, especially in the first trimester, is linked to fetal abnormalities, including neural tube defects, heart malformations, and oral clefts. These studies helped establish 39°C as the “teratogenic” threshold. (Teratogens are factors that cause fetal malformations.) Yet studies of core temperature regulation in pregnancy are scarce. What’s more, virtually all research on heat and pregnancy has involved only cisgender women.
Scientists have long assumed that pregnant people don’t thermoregulate as well as others. They gain substantial weight, which means that relative to their body mass, they have less skin surface to dissipate heat. More than one-quarter of that additional weight is fat, which, compared with other tissues, requires less heat to raise its temperature. Fat also insulates the body, making it harder to offload heat. And the task of building another human being is itself an energy-intensive process that generates a lot of internal heat.
Yet pregnant people have additional tools that apparently aid thermoregulation. By the third trimester, the volume of plasma, the noncellular, fluid component of blood, has increased by 50% or more. That allows more fluid to be shunted to vessels in the skin that dilate in response to heat stress, releasing heat into the environment to cool the blood. (This works as long as the air is cooler than the body; if not, sweating kicks in.) Small arteries and arterioles in the limbs also relax over the course of pregnancy, enhancing blood flow and cooling. One 32-year-old study suggested pregnancy also lowers the body’s threshold for sweating. That study and others also found a woman’s core temperature ticks steadily downward during pregnancy. And the Sydney researchers’ smaller study, of 15 pregnant women who cycled at 32°C in the HHRI climate chamber during their second and third trimesters, showed that they safely regulated their internal temperatures, performing as well as or better than nonpregnant controls. None of their core temperatures even hit 38°C.
UNCOMFORTABLE INDOOR cycling hardly captures the kinds of heat exposure facing women in rural Kilifi County in Kenya, one site in a multicountry study called Climate, Heat and Maternal and Neonatal Health in Africa, better known as CHAMNHA. There, a team led by medical anthropologist Adelaide Lusambili of Africa International University conducted interviews with dozens of pregnant women, new mothers, male partners, mothers-in-law, community health care workers, and community leaders in 2021.
In this drought-ridden region where high temperatures average 31°C for months at a time, most women have no choice but to work in direct sun, collecting firewood, farming, and walking daily to ever-scarcer water holes, while trying to avoid those shared with animals for fear contaminants will harm their fetuses. (That reluctance puts both mother and fetus at risk of dehydration.) Pregnant women experienced sleeplessness, racing hearts, and faintness, and described their bodies as “boiling” or “on fire.” Some men said they had seen their wives having difficulty breathing because of the heat. Anecdotally, community health workers reported, pregnancies in the hottest months were more likely to be complicated by high blood pressure, or to end in miscarriages or premature birth.
Lusambili found that extreme heat also has indirect effects on pregnant women’s health, because it is “likely to compromise safe behaviors.” For example, her team learned that pregnant women are less likely to use bed nets when it’s hot, increasing their exposure to mosquitoes that can transmit malaria. The heat makes them fearful of walking kilometers across nearly shadeless terrain to health facilities for prenatal care or delivery. “With climate change we are going to have to rethink some of these behaviors that are harmful to the mom in the heat,” Lusambili says. “These women need help.”
Gordon, Jay, and their group hope to delineate where behaviors cross into danger. For the new study, they aim to recruit 270 pregnant women and 90 age-matched, nonpregnant women as controls. Pregnant women’s participation will stretch from late in their first trimester—when the risk of fetal malformations has largely passed—to late in the third. They will ride the cycle ergometer for up to 1 hour during each trimester, one-third of the participants at 30°C, another third at 35°C, and the rest at 40°C. After 30 minutes of exercise, the chamber’s relative humidity will gradually increase.
Several hours before the study, the women will swallow a temperature-sensing pill that sits in their intestines during the ride, wirelessly conveying core temperature to an external recorder every 15 seconds and later leaving their bodies by the usual route. These measurements will enable the scientists to identify the crucial inflection point when a participant can no longer maintain a steady state and their core temperature begins to climb steeply. (The researchers will halt the session then.)
They will then analyze how various factors—including temperature, pregnancy stage, maternal age, heart rate, and body shape and size—influence that inflection point. Those data will inform a biophysical model and, ultimately, a prototype online tool that will use the weather forecast at a pregnant person’s location and other individual metrics such as their age and week of pregnancy “to then say … ‘The maximum temperature that you can be exposed to is X for X number of minutes, exercising at this intensity,’” Gordon says. “It will have that level of detail.” The researchers hope the tool will eventually be used in the Global South, to protect pregnant people like those in Lusambili’s survey from excessive heat stress.
“It’s admirable that they are trying to do this study,” says Anne Drapkin Lyerly, an obstetrician and bioethicist at the University of North Carolina School of Medicine. “So much of pregnancy advice is based on fear and a ‘better safe than sorry’ sort of framework.” Admonitions such as “don’t exercise” and regimes of bed rest to avoid premature labor have shown no benefit and carry risks of their own, she says.
Still, Lyerly notes the sensitivities that come with studying pregnant people. “I think the jury is likely out on whether pregnant women would be willing to participate and who these pregnant women are,” she says. “This is a context where it would be extremely important to make sure that women were given every opportunity to say ‘No.’”
Jay and Gordon say they’re prioritizing safety. As with any research study, participants will be able to drop out at any time for any reason. Anticipating defections, the team is recruiting three times as many pregnant women as controls. The women must have low obstetrical risk; recent, normal fetal ultrasound scans; and be cleared by their doctors to participate. A participant’s session will be halted if her core temperature reaches 38°C. That leaves a 1°C buffer between her temperature and the 39°C teratogenic threshold, which Jay calls “very conservative.” Throughout the trial, a research midwife will be present to answer participants’ questions and monitor the fetal heart rate. Any pregnant woman who does drop out, or whose fetus’ heart rate raises concern, will be offered an immediate ultrasound scan to gauge fetal well-being at the nearby Royal Prince Alfred Hospital. The pregnant participants “are probably safer in our lab than they are just on a regular summer day,” Jay says.
“We’re very conscious that we need to make it extremely safe,” Gordon adds, “but we’re also very conscious that these things are happening to pregnant women all over the world in terms of exercise and heat exposure, and nobody’s measuring anything.”
A FEW PIONEERS are trying. Bonell and her team recently conducted the first field study probing the physiological impacts of heat stress on mother and fetus, published in December 2022. Her team tracked 92 pregnant women who were subsistence farmers in The Gambia and found they were frequently exposed to extreme heat. It led directly to fetal strain, which the scientists defined as reduced blood flow in the umbilical artery—indicating a placenta not functioning properly—or a fetal heart rate outside the normal range of 115 to 160 beats per minute. Bonell and her team found that the likelihood of the fetus experiencing strain grew by 17% for each 1°C increase in temperature as measured by the UTCI, which adjusts for the effects on the body of air temperature, humidity, wind speed, and heat radiating off nearby objects.
How such effects lead to outcomes such as premature birth, stillbirth, and low birth weight isn’t clear. “There is very limited definitive evidence,” a 2022 review concluded. But hypotheses are plentiful. High temperatures may prompt embryonic or fetal cells to switch key genes off or on at the wrong times, as suggested by studies in embryonic mice and newborn piglets. Cells under stress also produce heat shock proteins, which help stabilize the cells. But these proteins may go into overdrive, causing inflammation; and some also regulate the coordinated, forceful uterine muscle contractions during labor. Both mechanisms, it’s hypothesized, could lead to preterm birth. Another pair of possible culprits is oxytocin, the primary hormone triggering labor, and prostaglandins, which speed it along. Studies from the 1990s showed that they are secreted in pregnant farm animals exposed to heat stress.
... We are going to have to rethink some of these behaviors that are harmful to the mom in the heat. These women need help.
ADELAIDE LUSAMBILI, AFRICA INTERNATIONAL UNIVERSITY
Perhaps highest on the list of potential causes is reduced blood flow to the placenta. Studies in pregnant ewes have shown that chronic heat stress leads to smaller placentas and smaller, ill-nourished fetuses. It also reduces uterine blood flow, which feeds the placenta, by up to 30%, potentially triggering preterm labor or stillbirth. The picture is much the same in pregnant cows.
Bonell hopes her new Wellcome-funded study will help clarify what’s happening in humans. Her team will recruit 762 pregnant women in The Gambia and compare levels of chronic heat stress between those living on the country’s relatively cooler coast and those in the much hotter interior. She and her team will measure placental blood flow at regular check-ins. They will track maternal physiology and pregnancy outcomes including the health of the mothers and conduct neurodevelopmental tests on the newborns. Placental tissue samples will be shipped to physiologist Amanda Sferruzzi-Perri at the University of Cambridge, who will study whether differences in the organ’s vasculature or gene expression correlate with poor outcomes.
Jay and Gordon’s team will also add to the evidence base from women’s on-the-ground lives in the Global South. Working with partners at the Sitaram Bhartia Institute of Science and Research and the International Centre for Diarrhoeal Disease Research, they hope to enroll nearly 6000 women in urban India and rural Bangladesh, early in their pregnancies, for a prospective study that will use wearable temperature sensors to regularly track their levels of heat exposure. The primary outcome measure will be premature birth, though the team will also examine rates of other severe consequences such as stillbirth and low birth weight, as well as maternal complications including gestational diabetes and preeclampsia.
In a subset of 1000 women, the team will periodically assess heart rate, dehydration, and core temperature. These measurements will strengthen the model the Sydney group develops using the climate chamber. As a whole, the field study will offer “much more accurate data on the effect of individual level heat exposure on pregnancy outcomes,” says Camille Raynes-Greenow, a perinatal epidemiologist at Sydney who is co-leading the Bangladeshi arm of the study.
Ultimately, she would like to see effective and culturally acceptable measures available everywhere to protect pregnant people and their newborns from extreme heat. These might include education about the most sensitive weeks of pregnancy, trees planted where shade is most needed, and changes in building regulations to require insulation and cooler construction. But untangling the mechanisms of harm will be critical to these efforts, she says. “If we don’t know what is causing harm, how can we ever develop interventions to mitigate it?”