LONDON — The rapidly emerging theory that adult health is set to a significant degree before birth, by conditions in the womb, is getting its first major challenge with new research questioning the validity of some evidence supporting the idea.
In a critique published last week in the Lancet medical journal, scientists conclude that the reported link between low birth weight and higher blood pressure later in life, an early cornerstone of the theory, may not be as strong as previously thought. Because of flaws in the studies, it may not exist, the report said.
The theory, known as the fetal origins of adult disease hypothesis, postulates that when a fetus is undernourished, it diverts resources to areas it really needs at the time, such as the brain, at the expense of organs it will need later, such as the lungs.
Proponents believe that may permanently change the baby's structure, functioning and metabolism, setting it up to be more vulnerable than normal to the development in adulthood of heart disease and related disorders such as high blood pressure, stroke and diabetes.
The concept first emerged in 1986, but it has gained recognition among scientists in the last five years and has become a hot area of medical research. The field had its first international research conference last year.
"Surprisingly, this hypothesis doesn't seem to have gone through [rigorous scrutiny] very much. It seems to have been adopted very widely, very rapidly without too much in the way of critical appraisal," said Oxford University scientist Rory Collins, one of the lead investigators in the new analysis.
The critique involved a reanalysis of 103 studies that examined birth weight and blood pressure.
The larger studies showed a weaker link between blood pressure and birth weight than the smaller studies did.
One problem is that smaller studies are more likely to find more extreme results and positive results are more likely to be published. That means published evidence from the small studies might overestimate the true effect, Collins said. To counter that possibility, the new analysis gave more importance to the larger studies.
Proponents of the fetal hypothesis have estimated that a 2.2-pound higher birth weight is typically associated with a 2-to 4-point lower blood pressure.
After re-weighting the studies to eliminate any bias introduced by publishing only the small studies with strong results, the new analysis concluded that the 2.2-pound extra birth weight was linked to about a half-point lower blood pressure.
The earlier studies also adjusted their statistics to take into account the current weight of the patients when they had their blood pressure measured as adults. That obscures the real relationship between birth weight and blood pressure, Collins said.
"When we removed the adjustment for current weight, the relationship appeared to disappear," Collins said.
"It is a serious concern when something that is considered by the proponents to be their best evidence appears to have such serious problems," he said. "That's certainly not to say there's nothing in it, but it may mean that the strength of any association is much less than had been claimed, if at all."
Collins said other aspects of the theory should be similarly studied to prevent research money being wasted on dead ends.
Most proponents of the fetal theory said the new analysis was constructive criticism, but did not accept the interpretation. "The four largest studies completely dominate, and effectively they chuck away all the evidence apart from those," said Chris Martyn, an epidemiologist at Southampton University in England who conducted some of the studies that were reanalyzed.
"The four largest studies used the most primitive methods--people were asked to remember their birth weight and their most recent blood pressure measurement," he said. "If you weighted the studies not by their size but by their quality, you might come up with a completely different answer."
Proponent Kent Thornburg, director of the Heart Research Center at Oregon Health Sciences University, added that since experiments in a variety of animal species show a clear correlation between elevated blood pressure and fetal undergrowth, he has no doubt that the correlation is genuine.