First evidence that preeclampsia can leave a persistent and potentially fatal imprint in the pulmonary circulation of the fetus

Children born of mothers who had preeclampsia during their pregnancy are more likely to have pulmonary hypertension than similar children born from normal pregnancies, according to a study conducted in Bolivia by Swiss and Bolivian researchers.

The findings provide the first evidence that preeclampsia (pregnancy-induced hypertension) can leave a persistent and potentially fatal imprint in the pulmonary circulation of the fetus, a physiological change that can predispose the offspring to exaggerated hypoxic pulmonary hypertension in later life.

The study also illustrates how field research at high altitudes can provide important clues in understanding a major clinical disease like pulmonary hypertension.

Dr. Pierre-Yves Jayet, a research fellow in the laboratory of Dr. Urs Scherrer, University Hospital, Lausanne, presented the study April 4 at The American Physiological Society scientific sessions during Experimental Biology 2005 in San Diego. The work was part of an ongoing project between Dr. Scherrer's group, the Swiss Cardiovascular Research Institute in Bern, and the Bolivian High Altitude Research Institute in La Paz.

Pulmonary hypertension is a relatively rare and potentially lethal blood vessel disorder of the lung in which the pressure in the pulmonary artery (the blood vessel leading from the heart to the lungs) rises above normal levels.

A related problem, high altitude sickness caused by lack of oxygen in the air, is familiar to many who travel to high altitudes. In mountaineers, classical high-altitude pulmonary edema (HAPE) is caused in part by dysfunction of the pulmonary blood vessels, leading to exaggerated pulmonary hypertension as the affected individuals climb higher, usually resolving if they return to a lower altitude. Untreated, it can be fatal.

Because of the work being conducted jointly in the surroundings of La Paz, capital of Bolivia and the highest major city in the Andes at 3600-4000 meters (12,000 – 13,000 feet), the research team was familiar with a particular form of high-altitude pulmonary edema that occurred to some native dwellers of high altitudes when they returned from sojourns at lower elevations. The cause was not known but the researchers speculated high-altitude dwellers who were susceptible to re-entry pulmonary edema would have a similar dysfunction of the pulmonary blood vessels as seen in classical HAPE. And indeed, when they compared pulmonary artery pressure at high altitude, they found markedly more elevated values in those who experienced re-entry pulmonary edema than in their counterparts who had never experienced this problem. The researchers also noticed that an unexpectedly high proportion of the group with re-entry pulmonary edema were offspring of mothers who had suffered from preeclampsia while carrying them.

To confirm this finding, the team measured systolic pulmonary artery pressure, using echocardiography, in eleven Bolivian children from La Paz (ages 6-8) whose mothers had had preeclampsia and in 13 age and sex matched offspring of normal pregnancies. The systolic pulmonary-artery pressure was roughly 33 percent higher in offspring of preeclamptic mothers.

Dr. Jayet is now trying to find the underlying mechanism leading to this pulmonary vascular damage. He believes this understanding will lead to new ways to prevent and treat primary pulmonary hypertension and perhaps other diseases as well.

Scientists already know that during preeclampsia the diseased placenta produces a number of circulating molecules known to interfere with the function of the mother's blood vessels. These vasotoxic molecules have the potential to cross the placental barrier, where they may damage the pulmonary circulation of the fetus. Such damage in turn may predispose the offspring to an exaggerated constriction of the pulmonary blood vessels later in life when triggered by certain conditions, such as life in the oxygen poor environment of high altitude.

The increased susceptibility to re-entry pulmonary edema of children of mothers with preeclampsia – children found to have higher systolic pulmonary-artery pressure – may have significant implications for people at any altitude, says Dr. Scherrer. Just as the low oxygen content at high altitudes triggers a response in these offspring, so may sustained lack of oxygen in the circulating blood affect patients suffering from other forms of heart or lung disease.

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