Babies born prematurely are at risk for a variety of health problems, but for more than half of all preterm births, doctors don't know the cause. Now, a study of sheep suggests that modest undernutrition for a relatively brief time around conception can trigger an early surge of hormones in the fetus and lead to premature birth.
Researchers have suspected that a mother's nutrition plays an important role in gestation length. Proving that connection has been tough, in part because poor nutrition often goes hand in hand with confounding factors such as infections and stress. To avoid these complications, Frank Bloomfield and colleagues at the University of Auckland in New Zealand turned to sheep.
The researchers put 10 ewes on a restricted diet starting 60 days before they mated and lasting 30 days thereafter. This lowered their body weight by 15%, a moderate reduction for sheep, Bloomfield says. The formerly food-deprived ewes gave birth an average of 139 days after conception, compared to 146 days for eight ewes given all they wanted to eat, the team reports in the 25 April issue of Science. Although the preemie lambs weighed the same as their full-term counterparts, they were sickly, Bloomfield says.
The researchers also found that two hormones, cortisol and adrenocorticotropin (ACTH), surged earlier than normal in the fetuses carried by once undernourished ewes. All 10 had an early release of ACTH, a messenger from the fetal brain that tells the adrenal gland to pump out cortisol. Cortisol normally surges late in pregnancy, prompting the lungs, liver, and other organs to mature. In five of the 10 fetuses, the cortisol spike happened early. This suggests to Bloomfield that the pituitary and adrenal glands matured early in fetuses of ewes deprived of food. How conditions near the time of conception cause this is still a puzzle.
Bloomfield's findings mesh with the little work that's been done with humans, says Caroline Fall, a pediatric epidemiologist at the University of Southampton, U.K. For instance, she says, religious fasting has been blamed for small increases in premature deliveries--the so-called Yom Kippur or Ramadan effect. The new research has "potentially very interesting implications in human biology," agrees Jonathan Seckl, an endocrinologist at Western General Hospital in Edinburgh, U.K.