Side Effects of 1918 Flu Seen Decades Later

Runny nose, persistent chill, fever, fatigue — these symptoms are all familiar evidence of influenza. But what about a heart attack, suffered 60 years later?

Researchers suggest that such distant health problems may be linked to early exposure to the flu — as early as in the womb — according to a new study that analyzed federal survey data collected from 1982 to 1996. Researchers found, for instance, that people who were born in the U.S. just after the 1918 flu pandemic (that is, people who were still in utero when the disease was at its peak) had a higher risk of a heart attack in their adulthood than those born before or long after the pandemic.

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The new findings, published in the Journal of Developmental Origins of Health and Disease, are based largely on survey data available on some 100,000 Americans who were born between 1915 and 1923. Overall, these populations had roughly the same rate of heart attack year to year — about 200 heart attacks per 1,000 people — when they were studied some 60 years later. But among the subset of people born between October 1918 and June 1919, when the flu pandemic was at its worst, the number of heart attacks increased more than 20%.

The study’s authors, including Caleb Finch, a professor of gerontology at the University of Southern California, also combed through U.S. Army enlistment data for about 2.7 million men born between 1915 and 1922 and found other trends among flu babies. “Men born in 1919 were shorter by about 0.05 in. relative to surrounding cohorts,” says Finch. That’s only about a millimeter’s difference, or the thickness of a credit card, but he thinks that’s significant and somehow related to maternal flu exposure. “I am confident because it’s only restricted to that one year,” Finch says.

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In the past decade, there have been several similar studies in the U.S., Britain, Brazil and elsewhere that have come to comparable conclusions. Children born just after flu pandemics have higher rates of physical disability, perform worse in academic tests and have lower income compared with babies born before or after pandemics. “The cohort [born in 1919] has shorter height and lower weight as teenagers, a higher percentage of various health issues,” wrote economist Ming-Jen Lin of National Taiwan University in a soon-to-be-published paper looking at the long-term effects of the 1918 flu in Taiwan.

Perhaps the most commonly cited paper is one by researchers at Columbia University, which associated a mother’s influenza with her child’s risk of mental illness. In that landmark study, researchers collected blood samples from 12,000 pregnant women in Alameda County, California, between 1959 and 1966 and monitored their sons and daughters for more then three decades. Children born to women who had been infected with flu were three to seven times more likely to develop schizophrenia later in life, the study concluded.

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So what is the link between a mother’s influenza and her child’s cardiac health, physical stature or risk of mental illness? Well, we don’t really know. What we do know is that it’s probably not the flu virus itself. There is no known biochemical mechanism that links heart disease or other health outcomes to prenatal exposure to flu. And the flu virus, unlike the pathogens that cause herpes, German measles and syphilis, is not teratogenic — that is, it doesn’t cause malformations in the fetus, says Dr. Ellen Harrison, the director of obstetrical medicine at the Montefiore Medical Center in the Bronx, N.Y.

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Researchers’ best guess is that a flu infection causes stress in the mother, which might in turn affect fetal development. During pregnancy, a woman’s heart and lungs are working substantially harder than usual, and her immune system is compromised, so a few infections (like influenza) may potentially become more intense. Although most pregnant women who get the flu survive with no serious problems, they are still more likely than other healthy adults to also develop respiratory failure and secondary bacterial infections like pneumonia — potentially fatal conditions that may require hospitalization and mechanical ventilation. “It is these severe cases that are dangerous for both the mother and her baby,” said Harrison in an e-mail message.

The idea that environmental conditions in the womb may have lifelong effects on the fetus is certainly not new. British epidemiologist D.J. Barker first proposed his theory of fetal origins in 1992, arguing that when the fetus doesn’t get enough nutrition in utero, for example, an increased risk of future heart disease and diabetes somehow gets “programmed” into his or her development. There wasn’t very much data to back Barker’s theory at the time, but over the decades, a wealth of animal and human data has suggested it’s true. Maternal conditions like high blood pressure and diabetes and behaviors like smoking and drinking have all been identified as factors that can harm the fetus. Each risk factor may lead to various long-term consequences, including mental retardation, low birth weight or an increased risk of heart disease, diabetes or schizophrenia.

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But the flu-stress theory is still just a theory. There is only epidemiological evidence to support it; a clinical trial measuring the effects of flu-induced maternal stress would, of course, be unethical. And the link could involve any number of unknown variables: in the new study co-authored by Finch, it’s not even clear which of the survey respondents’ mothers actually caught the flu, because that information was not available.

Still, the study’s authors argue that there are few other immediately obvious alternative hypotheses, given the cluster of outcomes among babies born at certain times. “Why is it that only those born in 1919 showed the spike [in heart disease]?” asks study author Douglas Almond, a professor of economics at Columbia University and a pioneer in applying the fetal-origins theory to economics. “People who were born just before and after the flu should be affected as well.”

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Whatever the exact biological pathway, for doctors like Harrison, the findings have practical relevance: they reinforce the importance of getting a flu shot, especially for pregnant women, many of whom say they are reluctant to receive the new 2009 H1N1 vaccine. “I am already 37 weeks into my pregnancy and haven’t fallen sick and have been healthy all along, and I don’t see the point of introducing a foreign body into my body,” says first-time mother Laurie Koch-Smith, 41, in Westchester County, New York, who says she thinks the risk of H1N1 infection has been overhyped.

But even if pregnant moms avoid catching the H1N1 flu, the vaccine has other benefits, says Harrison. “The baby of a woman who got the influenza vaccine [during pregnancy] will be born with antibodies to influenza,” she says, adding that immunity — albeit temporary — would greatly reduce the chances of the infant coming down with the flu during the first few months of life.

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