"About 40 per cent of women who give birth prematurely are primarily what we call the idiopathic pre-term births where we don't understand why they went into labour early," says Dr. John Challis, professor of medicine and physiology at the University of Toronto, and one of the senior authors of a paper in the April 25 issue of Science. "Our research with sheep in this paper suggests that a proportion of those idiopathic pre-term births could be associated with maternal undernutrition before the start of pregnancy."
In normal pregnancy, the fetus triggers the onset of its own birth, explains Dr. Frank Bloomfield, lead author of the paper and now a senior lecturer at the University of Auckland. In animals, it is well known that the fetus does this through activation of its adrenal gland to produce a surge of cortisol in the blood. The surge of cortisol is the catalyst for the chain of events that eventually lead to its birth. It is believed that human labour follows the same type of process.
The problem is when birth occurs prematurely, adds Challis, who is also scientific director of the Institute of Human Development, Child and Youth Health of the Canadian Institutes of Health Research. "Those born prematurely have less opportunity for their lungs and organs to develop in utero in preparation for life outside the womb. The nature of these experiments prevented us from exploring the longer term viability of the premature lambs. But we believe that the cortisol from the adrenal gland of the offspring, which provides the stimulus to the birthing process, also assists in maturing organ systems like the lungs, which the baby needs to breathe air once it's been born. If there has not been enough cortisol to cause lung maturation in utero, then the offspring develops respiratory distress and may succumb and die outside the womb. That is always a big concern with premature deliveries."
Using about 40 sheep, Challis, Bloomfield and colleagues from New Zealand and Australia divided ewes into two groups. The control group of 20 ewes was fully nourished prior to mating and during the entire gestational period. In the experimental group, ewes were underfed and maternal body weights were reduced by approximately 15 per cent (about 15 lbs) 60 days prior to mating and for an additional 30 days after conception. Fifteen per cent is considered a mild to moderate nutrient restriction for sheep, says Bloomfield; after that time, nourishment levels were increased and ewes were allowed to eat as much as they desired.
The normal gestational period for sheep is about 145 to 150 days. However, the researchers found that even after nutrition was returned to normal, fetuses of undernourished ewes had accelerated maturation of their adrenal glands, prompting their premature delivery by about one week, on average. In some cases, the ewes delivered as much as 15 to 20 days early.
"Even after adequate nutrition is reintroduced, months later there's been an effect on the fetus," says Bloomfield, who conducted this research as part of his post-doctoral fellowship in physiology at U of T.
Still, Bloomfield and Challis say they were surprised to find that the undernourishment of ewes did not create growth restrictions in the offspring. Lambs delivered early by underfed mothers were the appropriate weight and size for their gestational development, although naturally smaller than full-term lambs. The researchers are involved in a new study that will examine long-term health consequences of lambs born prematurely from underfed ewes.
While pre-term birth is a problem throughout the world, Challis and Bloomfield note that the incidence of pre-term birth in affluent Western societies has increased over the past decade and remains the number one cause of perinatal illness and death. Challis suggests the problem may have to do with women who diet prior to pregnancy for fear they'll be unable to shed the excess weight afterwards.
"Women need to think about proper diet and food intake before they even know they're pregnant because proper nutrition after pregnancy may not compensate for the lack of it beforehand. Even a modest restriction around the time of conception could have far-reaching consequences," says Challis. "We know now that this period of undernutrition could impact on the development of the pituitary and adrenal glands of the baby and may well affect the development of other organ systems. So if you're intending to get pregnant, do not diet substantially before the start of pregnancy because it's not necessarily a good thing for your pregnancy and you may cause your baby to be born prematurely."
Bloomfield also points to evidence that more and more women are having children later in life in addition to the rising incidence of conception via artificial techniques, both of which lead to an increase in the pre-term birth rate. "Some data from the U.K. suggests that many women (up to 40 per cent) of child-bearing age do not eat a good, well-balanced diet, as recommended by various food guides, and that may certainly be a strong factor in premature delivery."
Challis and Bloomfield conducted the work with Mark Oliver, Paul Hawkins, Bernhard Breier, Peter Gluckman and Jane Harding of the University of Auckland in New Zealand; Melanie Campbell, a graduate student in physiology at U of T; and David Phillips of Monash University in Australia. This research was funded by the Canadian Institutes of Health Research, the Health Research Council of New Zealand, the Royal Australian College of Physicians and the National Health and Medical Research Council of Australia.
CONTACT:
Janet Wong
U of T Public Affairs
416-978-5949
jf.wong@utoronto.ca
Dr. John Challis
U of T Department of Physiology, CIHR Institute of Human Development, Child and Youth Health
416-946-7979
j.challis@utoronto.ca
Dr. Frank Bloomfield
University of Auckland
011 64 9 3737599, ext. 86107
f.bloomfield@auckland.ac.nz
Journal
Science