The human fetal liver: development and response to maternal drug use
It is well known that if a woman smokes while pregnant it has adverse consequences for the resulting offspring including reduced birthweight, an impaired immune system (e.g. increased asthma), poorer educational performance and a raised chance of developing obesity, diabetes and heart disease (called metabolic syndrome). Many of these effects also happen if the mother regularly drinks alcohol while pregnant. Currently, we do not know exactly how much maternal smolking/drinking affects the chance of somebody developing metabolic syndrome although a recent study of 74,000 women found that if their mother smoked while pregnant, the woman had a 53% higher chance of becoming obese.
In the UK smoking and/or alcohol use during pregnancy continues in 20-40% of women and overall is likely to be a major added drain on the NHS. In 2006-07 costs to the English NHS of lifestyle and related conditions were: smoking £3.3 billion, alcohol £3.3 billion, overweight/obesity £5.1 billion and diabetes £3.5 billion annually.
Adult health is partly programmed by events during fetal life and an individual may be adversely affected for life if the mother uses recreational drugs. Growth restriction is important in this process and the liver is one of the organs most affected by disturbed growth before birth. The fetal liver is a key organ, protecting the fetus from harmful chemicals and controlling fetal growth.
Progress in understanding the effects of maternal drug use on fetal development suffers from two problems:
- firstly, our ignorance of the levels of drugs to which the fetus is exposed and,
- secondly, the mechanisms by which these drugs affect development.
This ignorance comes about partly because very little research uses normal human fetuses, but also because there is no low-cost means with which to measure how much/which chemicals (nicotine, alcohol, cannabis etc.) are getting into the human fetus during pregnancy.
The project aims
To resolve these issue novel methods developed at the National Institute on Drug Abuse (USA) will be used to measure chemicals from tobacco, cannabis, cocaine and alcohol in the fetal liver and in matched pairs of fetal livers and placentas. This will tell us how much of the drugs taken by the mother gets to the fetus and also whether the placenta can be used to measure the fetal burden of drugs and chemicals from the mother. This would allow us to carry out much larger studies of newborn babies to measure exposure levels in the placenta and their contribution to adult ill-health.
At the same time as measuring drug levels in the fetal liver we will work out how those drugs have affected liver function. Then, by using cell culture, it will be possible to re-create the effects of drug exposure in the culture dish with a view to understanding the long-term consequences.
We will also be able to find out more about how liver function develops and how it differs between male and female babies. Overall, our aim is to relate changes in the control of fetal liver development to the effects of chemicals in cigarette smoke. This will allow us to start to understand how liver mal-development relates to development of metabolic syndrome.
The information from this study will also allow us to measure, and to understand, the effects of exposing the developing fetus to recreational drug use by the mother. This will enable treatments to be designed to reverse these effects and to lower the incidence of metabolic syndrome.
First published: 12 September 2014