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Heat waves are becoming more frequent and more intense, posing more of a health risk around the world. High temperatures can be deadly, and are especially dangerous for those with cardiovascular and chronic disease — but they begin affecting human lives even before birth.

Several studies have identified an increased risk of preterm delivery and stillbirth after heat exposure around the world. A new investigation, published on Friday in JAMA Network Open, confirmed the link to early deliveries at a massive scale, in a large cohort study capturing over half of the births that occurred in the United States between 1993 and 2017. Its results shed light on the way existing health inequities may be exacerbated by a worsening climate.

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The study looked at more than 53 million singleton births that occurred in the 50 most populous cities in the U.S. during the hottest months of the year. Looking back at heat waves between May and September, researchers counted preterm births (between 28 to 37 weeks of gestation) and early births (between 37 and 39 weeks) within four to seven days of the spike. During that period, there were 2.15 million preterm births, and 5.8 million early births.

After a heat wave, which the study defined as four consecutive days in which the mean temperature was higher than the local 97.5th percentile, preterm births increased by 2%, and early births by 1%. But the distribution of these adverse outcomes was uneven: Mothers who were 29 or younger, had a lower level of education, and belonged to a minority ethnic or racial group saw a 4% increase in preterm births, and a 3% increase in early deliveries.

“When we say people are experiencing a heat wave, well, only some people are truly physically experiencing that heat wave,” said Lyndsay Darrow, a professor of epidemiology at the University of Nevada, Reno, who led the study. Some people have better access to air conditioning and the financial resources to pay for higher electricity bills, for instance, or jobs that don’t require physical activity or working outdoors. “We worry about the within-population vulnerabilities, the inequities between people and the exposures they might be having,” she said.

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Though the data didn’t offer information about jobs or income of the mothers, said Darrow, indicators such as education, age, or race can be used as loose proxies to understand what factors may be at play. Generally, women who have lower education tend to be employed in more physically demanding jobs and earn lower wages, as do women who belong to minority racial and ethnic groups. And women of lower socioeconomic status tend to give birth earlier in life.

These inequities hold true across the world, said Jane Hirst, chair of global women’s health at Imperial College London, who was not involved in the research. “Those who are at the most disadvantaged place in society — which is often women full stop, and particularly women who have other intersectionality, like being from a non-dominant ethnic group or religious minority or lower caste — they’re often the ones who are particularly affected,” she said.

Preterm birth is a leading cause of infant deaths, and it can have long-term physical and developmental effects. “I think there’s concern amongst the maternal health community that, whilst a lot of gains have been made across saving mothers’ lives and babies, preterm births have been static in the last 10 years,” said Hirst. Studies like this, she said, shows “there’s a chance that actually things could start to get worse, despite all the efforts.”

Vulnerable populations are already more likely to experience preterm and early birth, regardless of heat exposure. Further research is necessary to understand whether the link between heat and preterm birth is determined by the temperature spikes alone, or whether heat exacerbates other existing risk factors.

A number of recent studies have also found strong links between high temperature and adverse pregnancy outcomes. A study published last May in the Lancet based on data from eight Chinese provinces found that the rates of preterm birth could have been reduced by about 15% had pregnant women been warned to protect themselves from impending extreme heat. Another study published in April found that the risk of miscarriage was double among women in the Indian state of Tamil Nadu who had high occupational heat exposure. They also experienced double the risk of adverse outcomes at birth.

Research hasn’t pinned down the physiological reactions heat may trigger in pregnant women that can lead to premature delivery. “Some studies recently have shown that extreme heat is related to an inflammatory cascade that might potentially trigger the induction of labor,” said Darrow.

Hirst, who with her team is investigating the physiological causes of preterm and early labor, is testing whether heat and dehydration may affect blood flow to the uterus, triggering labor. But that is only one of several working hypotheses. “Truth be told, we still don’t really understand how the exposure to a heat wave or extreme heat is causing these outcomes that we’re seeing,” she said.

Recent studies have shown extreme heat exposure can affect fetal development in other ways, too, note the authors of a commentary on the study also published on Friday in JAMA Network Open. Extreme heat is being associated with increased incidence of congenital abnormalities, for example. And it could cause issues in growth and development, including a shortened life span and poor reproductive health.

“There is a continuum from the burden of caring for a preterm infant to the impact on the earning potential for the parents of that preterm infant across their lifespan,” wrote commentary author Shruthi Mahalingaiah, an assistant professor of environmental, reproductive, and women’s health at Harvard, in an email to STAT. Quantifying this burden will require further research, she said, including following up on the infants to understand how their climate exposures could impact their behavioral health, milestones, and cognitive function.

Along with her co-authors, Mahalingaiah called for a more careful understanding and evaluation of the social and economic implications of climate change. “By failing to include these implications of preterm and early-term births in public health assessments,” they write, “we vastly underestimate the effects of heat on population health.”

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