How experiencing famine in the womb may shape people’s health as adults

Hunger killed an estimated 4 million people in Ukraine between 1932 and 1933 — the result of Holodomor, a famine inflicted by the Stalin-led Soviet regime. New research shows how the harm experienced during famines can extend even to people who haven’t yet been born.

The study, published Thursday in Science, strengthens the link between fetal exposure to famine and increased risk for type 2 diabetes later on in life. It found that people who had been exposed to the peak famine period in early gestation (defined as the first three months) had double the risk of developing diabetes as adults compared to those who had not been exposed. People born in areas hit harder by famine — Kyiv, Cherkasy, and Poltava — were also at greater risk.

The study looked at diabetes diagnoses between 2000 and 2008 among more than 10 million people born in Soviet Ukraine between 1930 and 1938. It marks an important step in addressing questions about the long-term health effects of undernutrition and starvation, according to L.H. Lumey, a professor of epidemiology at Columbia University and the study’s lead author. This research comes as a more comprehensive follow-up to his 2015 study, which used more limited geographical and population data.

“Because of the unusual combination of factors, the high-quality demographic data, the sudden onset of the famine, the limited duration of the famine, the huge numbers exposed — this makes it like a laboratory study from the point of view of the medical science, that is unlikely to be ever repeated,” Lumey said.

Type 2 diabetes occurs when the pancreas does not produce enough insulin, the hormone that manages blood sugar levels. The study does not identify the mechanism underlying the link between prenatal exposure to famine and adult onset of type 2 diabetes. But Simin Liu, a professor of epidemiology, medicine, and surgery at Brown University, said epigenetics — how environmental factors affect gene expression — is likely at play. He has studied the same phenomenon in the Chinese famine that began in 1959, widely considered the deadliest famine in human history.

“The short answer is epigenetic modifications may link prenatal exposure to famine to an increased risk of cardiometabolic diseases later in life,” Liu, who was not involved in the study, wrote in an email to STAT. He added that additional experimental studies of animals, as the authors suggest, would be necessary to further understand the reasons for the link.

The fetal programming hypothesis — which suggests stimuli at a critical period of fetal development can influence metabolism into adulthood — might offer an explanation, according to Peter Klimek, an associate professor at the Medical University of Vienna who studies disease in the context of complex socioeconomic systems. In the Ukraine study, fetuses exposed to famine in early gestation saw an increase in diabetes risk as adults, while those exposed at later gestational times as well as infants in the first years following birth did not have an increased risk.

“The hypothesis basically is that the metabolism is still malleable in early forms of gestation, and it will particularly respond to environmental influences,” said Klimek, who wrote an accompanying perspective on the study. The body prepares for and adopts metabolism in accordance with a nutritionally-poor environment — but if, by the time the baby is born, the famine is over, their metabolism has adjusted to the wrong environment. However, famine exposure might not always mean higher diabetes risks, Klimeck said, noting that there are many risk factors for diabetes.

One challenge faced by the study authors was that the 1939 census was falsified by the Soviet government, according to Oleh Wolowyna, a study co-author and fellow at the Center for Slavic, Eurasian and Eastern European Studies at the University of North Carolina.

“The population of Ukraine was inflated by almost 3% to hide the effect of the famine,” Wolowyna said. “In the case of births and deaths, especially in 1933, the peak of the famine, there was an extraordinary amount of under-registration — about 30% of the births were not registered, and more than half of all the deaths were not registered.”

The study’s authors used a demographic balancing equation with data from the 1926, 1937, and 1939 censuses as inputs to obtain accurate yearly population estimates, accounting for births, deaths, and net migration.

One in three Ukranians today are experiencing hunger as a result of the ongoing Russia-Ukraine war, according to a 2023 United Nations report. Prior to the war, Ukraine was one of the largest suppliers of agricultural products to parts of Africa and Asia. “Hunger in other countries has increased due to the war, and these effects of the war — they are not constrained anymore to Ukraine alone,” Klimek said.

Liu said that this research, alongside other famine studies, emphasizes the importance of prenatal and early childhood nutrition in shaping long-term health outcomes at both individual and population levels.

“From a public policy perspective, targeting at-risk populations to ensure adequate nutritional support during critical developmental periods should be prioritized,” Liu wrote. He said this encompasses policies ensuring food security for pregnant women and young children in famine-vulnerable regions, as well as support in detecting and managing metabolic disorders for individuals exposed to these conditions.