In some women, the placenta does not develop normally and the growth of the fetus is affected. Now, researchers have found that this so-called 'placental insufficiency' can put a huge strain on the fetus. The result is a larger-than-normal heart that contains fewer muscle cells, irreversible architectural changes that could have long-term consequences.
In a sheep model of placental insufficiency, surgical constriction of the fetus' pulmonary artery to mimic a placental defect causes significant changes to the heart's right ventricle, says Kent Thornburg, professor of physiology and pharmacology at the Oregon Health and Science University. "The ventricle got heavier and thicker," he said. "What was most striking about it is that the cells matured much more quickly than they should have."
The idea that events during fetal development can predispose an individual to disease much later in life was first suggested in 1989 by David Barker of the University of Southampton. In it's original incarnation, 'Barker's Hypothesis' proposed that coronary heart disease originates through undernutrition in the womb.
"This was really earth-shattering," recalled Thornburg. Epidemiological studies reveal that a 5 lb baby has at least three times the risk of coronary disease in adulthood that does a 9 lb baby, he says. And because the placenta is often the culprit for causing low birth weight, Thornburg set out to explore the relationship between the placenta and the development of the fetal heart.
"Most people don't think of the baby before birth having to think about blood pressure, but it turns out that if the placenta doesn't form properly, it offers a very high resistance to the flow of blood coming out of the fetal circulation," he told BioMedNet News. "This is particularly stressful to the right ventricle, so the ventricle has to change its composition in order to adapt to this pressure," he said.
A crucial finding, says Thornburg, is that the cardiac muscle cells mature earlier than they normally would. This means that instead of dividing in the first few years of life, the myocytes just get bigger and bigger.
This 'cardiac hypertrophy' that Thornburg has found in his sheep has also been demonstrated in a rat model of placental insufficiency by Lubo Zhang, professor of pharmacology and paediatrics at Loma Linda University in California.
"If you treat a pregnant rat with six or seven days hypoxia during pregnancy, you cause an increased cell death in myocytes in the whole heart," said Zhang. Although the heart weight to body weight ratio is not increased, there is clear cardiac hypertrophy in the adult animals, he says.
And at six months, when these rats are in middle age, they are more likely than control animals to suffer a cardiac infarction when subjected to a hypoxic stress. Zhang reckons the hypertrophy is behind this. "I think that plays a significant role for this increased sensitivity to ischemia/reperfusion damage," he said.
A similar thing could be happening in humans, speculates Zhang. Thornburg too is keen to know if the placenta could have similar consequences for heart development in humans.
A project, currently in its planning stages, is being set up to answer this question. Mothers with slow-growing fetuses will be assigned to one group, says Thornburg, and compared with those that have the fastest growing fetuses.
Using a non-invasive approach, Thornburg's group, other US researchers, and an Indian team will use an ultrasound probe to measure the 'pulsatility index' in the umbilical artery. This index relates the systolic to diastolic pressures, and will indicate whether the fetal heart is working too hard, says Thornburg.
The pulsatility index should be highest in slow-growing fetuses, argues Thornburg. "We predict that in these babies, that they will have an abnormal right ventricle and that they will have fewer cells, and more mature cells, and a thicker wall," he said.
BioMedNet
24 July 2003
Original web page at BioMedNet
