“We’re challenged in our ability to do good work on these questions of rare [health] outcomes and the environment,” Mendola said, because it’s not easy to gather enough cases, with enough detail, to do so. Her study with Ha drew its clinical data on about 1,000 stillbirths from the medical records of nearly 230,000 women giving birth that the National Institute of Child Health and Human Development collected to study risk factors for caesarean deliveries. The birth or death certificates that other studies relied on give only limited information.
Compared to factors like maternal complications, the effect of an environmental exposure on stillbirth risk is small, Ha said, so teasing it out of all the potential confounders is difficult. Some factors that could influence stillbirth risk are closely correlated to temperature, such as air-pollution levels and season of conception, said Tim Bruckner, a public-health researcher at the University of California, Irvine, who has studied the effects of exposure to cold temperatures on birth outcomes in Sweden. “That makes it hard to attribute a causal effect of the birth outcome to temperature.”
Ha and Mendola have also done research on the effects of air pollution on stillbirth, and did control for it as well as season of conception in their temperature study. The effects of air pollution and temperature appear to be independent of one another, Mendola said, “to the extent that the math works.”
But Gary Loy, an obstetrician at Rush University Medical Center in Chicago and advisor to a regional Pediatric Environmental-Health Specialty Unit who was not involved with the temperature- and pregnancy-outcomes research, issued a note of caution. “The strength of association is always in question,” he said, “because there are so many confounders and biases and potential influences.”
Even so, Loy added that, based on what’s been uncovered on temperature and pregnancy thus far, “I think it’s settled there’s an association.” He said, “I don’t think there’s any question.”
Perhaps the biggest caveat is that so far, all the research has been based on observational data. “Epidemiological studies in general have their difficulties,” Loy said. “They’re generally hypothesis-generating studies rather than confirmatory studies.” These studies can show associations but not prove one thing caused the other to happen—a major hurdle for research on the harms of being exposed to various aspects of the environment.
A key question to answer, then, if it’s suspected that outside temperature can impact a child in the womb: What’s the biological explanation for how that could happen?
As of yet, the necessary research to answer that question hasn’t been done, though there are “lots of plausible ties,” Mendola said. Pregnant women, for example, are less able to regulate the temperature of their bodies, which was one reason it made sense to Basu to study the effects of temperature on pregnancy in the first place. Stress from a rising body temperature could also trigger an inflammatory response that constricts a pregnant woman’s blood vessels, making it harder for blood carrying oxygen and other essentials to get to the placenta and putting the baby at risk, Loy said.