TORONTO — Adults who were exposed in-utero to the H1N1 influenza virus of 1918 were significantly more likely to have cardiovascular disease later in life, a U.S. study has found.
The study, published Thursday in the Journal of Developmental Origins of Health and Disease, also found that men exposed prenatally to the Spanish flu strain were shorter than peers born months before or months after the 1918 pandemic.
“If you were in-utero during the flu, if you were in that birth cohort, you were as a male a little shorter at World War II enlistment,” said senior author Caleb Finch, a professor of gerontology and neurobiology at the University of Southern California.
“And then 60 years after you were born, you had a higher risk of heart disease,” Finch said in an interview Wednesday from Los Angeles.
The findings, taken along with previous research, raise questions about possible effects on offspring exposed in-utero to the current pandemic swine flu, a different strain than the one that killed tens of millions worldwide at the close of the First World War.
“Our point is that during pregnancy, even mild sickness from flu could affect development with longer consequences,” Finch said.
The researchers analyzed data from the 1982-1996 National Health Interview Surveys, which included 100,000 individuals, aged 63 to 78, born during and around the time of the 1918-1919 influenza pandemic.
After first appearing in spring 1918 and all but disappearing in the summer, the flu pandemic “resurged to an unprecedentedly virulent October-December peak,” the researchers write. The outbreak killed two per cent of the U.S. population.
They found that men born in the first few months of 1919 (the height of the pandemic occurred when their mothers were in their second or third trimester) had a 23.1 per cent greater chance of having heart disease after age 60 than the overall population.
Women born in the first few months of 1919 were not significantly more likely to have cardiovascular disease, suggesting possible sex differences in the effects from flu exposure.
However, females born in the second quarter of 1919 — first trimester during the height of the epidemic — were 17 per cent more likely to have heart disease than the general population in later life, the researchers found.
The researchers also examined the heights of 2.7 million men born between 1915 and 1922 at the time of Second World War enlistment. They found that average height among men increased every successive year except for the period coinciding with in-utero exposure to the flu pandemic.
Men who were exposed to the 1918 strain in the womb were slightly shorter on average than those born just a year earlier or a year later. In their analysis, the researchers controlled for known season-of-birth effects and maternal malnutrition.
Still, Finch was careful about extrapolating conclusions from the data to the current swine flu pandemic.
“All we can say is here’s an example of such an effect,” he said. “The current H1N1 is a different H1N1. And although there have been increased numbers of secondary infections and mortality in pregnant women, there has not been any evidence of the terrible secondary infections that were part of the 1918 flu.”
“That was off the scale.”
Dr. Tina Chambers, a specialist in perinatal epidemiology at the University of California at San Diego, said the findings appear consistent with the fetal origins theory.
“In 1918, we know that just like now, pregnant women seemed to be more likely to have complications of the flu,” Chambers said by email. “Influenza in pregnancy has been linked to maternal complications such as serious respiratory problems, which could affect the fetus … High fever very early in pregnancy can increase the risk of certain birth defects, and fever at other times may also pose a risk to the fetus.”
She said the findings make sense “if you accept that prenatal growth restriction, or other prenatal events, can predispose individuals to adult diseases.”
Chambers said it highlights the importance for pregnant women to protect themselves by getting the H1N1 flu vaccination; treating fever with acetaminophen; and seeing their doctor immediately if they experience “flu-like symptoms or think they have been exposed so that antiviral medication can be initiated.”