This major population study examines maternal factors during pregnancy and their impact on the subsequent development of PCOS, and is the first to reconcile previous conflicting research on the developmental origins of the syndrome.
Dr Michael Davies, senior research fellow at the Research Centre in Reproductive Health at the University of Adelaide, Australia, told the 21st annual conference of the European Society of Human Reproduction and Embryology today (Wednesday 22 June): "Our research suggests that, during pregnancy and birth, there are several different factors working through different pathways that are implicated in the overlapping and varying symptoms of PCOS that emerge in the offspring's later life".
"Existing research has already established links between foetal growth restriction, postnatal growth and metabolic disorders such as diabetes in adulthood. The idea that events in very early life can have an enduring, complex and important influence on subsequent disease is referred to as developmental programming, and this research theme has been applied to PCOS recently. Different studies have produced conflicting evidence that shows that large babies grow to become heavier adults with polycystic ovaries, but that the most severe symptoms of PCOS are associated with growth restriction as a foetus."
"Our research examines the relationship between symptoms of PCOS in adulthood and foetal conditions in women born in a major hospital in Adelaide in the 1970s. Our findings support the proposition that there is an inter-generational growth path leading to menstrual irregularity, while, at the same time, other symptoms may be one of number of consequences of restricted foetal growth."
Dr Davies and his team are studying a group of young women born between 1973 and 1975. They went back to maternity hospital records and first traced the mothers so that they could then contact and interview the daughters. So far they have interviewed 544 women who were born between 1973 and 1974 and who are aged between 30 and 32 at present.
They took a medical history of the young women and compared it with information about their births, including birth weight, placental weight, and weight of their mothers at their last clinical examination before giving birth.
Dr Davies said: "Symptoms of PCOS were relatively common. One in five women had more facial and/or body hair than normal, and one in four reported menstrual irregularity of greater than four days. Five per cent of women reported that they had an existing diagnosis of PCOS.
"We examined maternal weight in late pregnancy, birth weight and placental weight in relation to the symptoms of PCOS, or an existing or putative diagnosis of PCOS. Compared with their counterparts, young women without a diagnosis of PCOS but with irregular periods were heavier at birth, with larger placentas, and they tended to have mothers who were heavier in late pregnancy. In contrast, women with an existing diagnosis of PCOS tended to have birth weights that were, on average, 196g lighter than women without PCOS and smaller placentas.
"Therefore, our data suggest that different developmental pathways are implicated in the overlapping symptoms of PCOS. One pathway may be mediated by high maternal weight in late pregnancy, which is linked to irregular periods in the daughter, and possibly obesity and weight-related reproduction problems. A second pathway may involve reduced placental and foetal growth, which is linked to the more severe symptoms of PCOS in the daughter, usually resulting in an early clinical diagnosis of the syndrome. A foetus that has been affected by restricted growth is more likely to have problems with insulin metabolism in later life due to an underlying metabolic problem. In women this problem appears to be associated with PCOS, and is most evident where there is a constellation of symptoms of increasing severity. Hence, I suspect there are at least two pathways that can give rise to overlapping symptoms."
Dr Davies said that events that occurred not only to the mother, but possibly also the grandmother, could have a bearing on the development of a foetus. "To understand the growth of a child, we need to also understand the growth of the parents and possibly the grandparents. A good predictor of one's own birth weight is the birth weight of one's mother."
The study shed light on three aspects of the developmental origins of PCOS, he concluded. "There are reproductive consequences of metabolic programming events that occur during foetal development; we may need to look further back up the generations and look at more factors than previously considered; and finally, adverse events for one generation may have reproductive implications for the next."
Notes * PCOS is the commonest cause of ovarian dysfunction in women of reproductive age. It consists of numerous cysts in the ovaries, which are normally detected by ultrasound scanning. A woman with PCOS may have one or more of various symptoms such as menstrual irregularity, hirsutism, acne, obesity and difficulty conceiving. The condition is also linked with an increased risk of diabetes and heart disease.