Does ill health start in the placenta? This question lies at the heart of a new research project to find a simple blood test that can predict premature birth.(Photo: afterthird.com / Wikipedia) 
The socio-economic benefits of finding such a blood test and developing ways of preventing premature birth are incalculable.
The adverse effects that often come with premature birth are difficult for parents, and countries, to deal with – children born prematurely often suffer stunted growth, are more susceptible to viral and bacterial infections and often have long-term learning difficulties.
The more we can prevent premature birth the stronger, physically and mentally, societies can be. Wherever this is achieved, the need for government spending on disability grants will diminish, freeing state funds for other social goods. The effect, in South Africa specifically and sub-Saharan Africa more broadly, will be immense. South Africa and sub-Saharan Africa already carry a heavy burden of disease in terms of HIV, tuberculosis (TB) and malaria – all conditions that are linked to pregnant women delivering preterm.
So, do events leading to premature birth start in the placenta? The placenta is amazing. It is the only human organ that the female body builds when it needs it, and expels when its job is done at the end of a pregnancy. It serves as the life link between a mother and the developing baby ensconced in her womb.
Astonishing
Even more astonishing is the fact that it allows the mother and her foetus to remain tolerant of each other. The placenta belongs to the baby and shares 50% of its genetic material with its mother, and the other half from the father. So how does this organ, only lasting the lifetime of the growing baby, remain as a half-foreign body without being rejected? The acceptance of the placenta, or tolerance, is an active immunological process that is not yet fully understood, but we think that premature birth is linked with an early break of tolerance.
Our project to find out whether ill health begins in the placenta will focus on pregnant women living with HIV. These women make up a substantial vulnerable population in South Africa and they are at high risk of developing abnormalities in their placentas that raise their risk of delivering preterm, or delivering full-term babies who are small for their gestational age (very low weight at birth).
Read more: SA takes up US donations of anti-HIV jab before the end of the year
These women are also at risk of developing cardiovascular complications post-delivery, although we do not yet fully understand the link between complicated pregnancies and maternal cardiovascular complications. If we can relate maternal health complications back to poor placental development that would be another boost to maternal health, in South Africa and worldwide.
The major cardiovascular complication suffered by many of these women, post-delivery, is hypertension – high blood pressure. Again, South Africa and sub-Saharan Africa more broadly, face a hypertension epidemic that has a socio-economic cost in early deaths as well as lost productivity and its concomitant drop in household income, to name just two consequences.
Leading cause of death
Cardiovascular disease is a leading cause of death in South Africa, and it is estimated that around 30% – nearly a third – of South Africans suffer from hypertension, according to an article published in the Journal of Human Hypertension in October 2023. Only about half of people who live with hypertension are receiving treatment to control their high blood pressure.
Our project aiming to find a link between ill health and the placenta is highly collaborative, drawing on the expertise available in research universities in South Africa and the UK. We have assembled a consortium of immunologists, biochemists, cardiologists, and biostatisticians to tackle whether and how events in the placenta are predisposing adverse birth events and later sequelae of poor cardiovascular function in the mother. Together, we have already generated results that show that a specific molecule on a macrophage, a type of white blood cell, plays a role in premature birth.
Macrophages can play many roles in the body and in the placenta, which is packed with these cells. On the one hand, they can help kill and eliminate alien microorganisms, and on the other they can help the placenta grow. The particular macrophages that can help the placenta assemble in groups are known as Hofbauer cells.
We believe that when something goes wrong with the Hofbauer cells, there could be two catastrophic results: loss of tolerance, and/or poor placental blood vessel formation that causes a lack of oxygen and nutrients to pass from the mother to the developing baby through the placenta. In both cases, premature birth or a small, sickly baby is often the result.
About one-third of women who become pregnant in South Africa are living with HIV. One of our country’s greatest health successes is the prevention of mother-to-child HIV transmission through antiretroviral drugs. Making antiretrovirals available to HIV-positive people in South Africa has saved millions of lives. However, there are challenges, one of which is an association between long-term antiretroviral treatment and poor placental development in pregnant women who begin antiretroviral treatment prior to becoming pregnant.
Improving health outcomes
If we can find out how to improve the health outcomes of children born to mothers who are living with HIV and who are on antiretroviral drugs, and how to obviate these mothers developing cardiovascular complications after they have delivered, we will change lives.
Reducing South Africa’s disease burden from stunted growth and greater susceptibility to viral and bacterial infections, plus reducing the socioeconomic consequences of approximately one-third of all babies born in any given year suffering long-term learning difficulties, would have untold benefits.
This is worthwhile work and brings laboratory-based research directly into the public health arena. The R2.5-million this project has received from the 2023 Harry Oppenheimer Fellowship Award, through the Oppenheimer Memorial Trust, is an investment for a better, stronger South Africa.
What’s more, in this case, what is good for South Africa is good for the world. This research could save lives worldwide. It could also help the world achieve the United Nations’ Sustainable Development Goals. Sustainable Development Goal 3 calls on us to “ensure healthy lives and promote well-being for all at all ages” by 2030 through reducing the global maternal mortality rate and ending preventable deaths of newborns and children under five years of age.
There is another, equally important, effect of the Oppenheimer Memorial Trust’s investment in this research: it will help to develop South Africa’s pipeline of qualified and experienced research scientists, which is also an objective of this award.
I have dedicated my scientific life to developing new scientific research talent. For me, that is integral to everything I do as a research scientist.
Consortium of experts needed
One of the most powerful aspects of the Harry Oppenheimer Fellowship is the financial boost I have received for this vital part of my work. This is work that I cannot do alone. I need the consortium of experts that I have assembled if we are to reach our ambitious goals of establishing whether the placenta lies at the heart of maternal, newborn and child health, and discovering treatments for poor placental development. We will also be working with master’s degree and doctoral students, which will grow a new pipeline of clinical and lab-based researchers able to participate in highly sophisticated explorations.
As we continue on this scientific quest, which has the lives of all mothers who for whatever reason suffer poor placental development, and their unborn babies, at heart, we know this much: if we are successful, a healthier, stronger world awaits. DM
Professor Clive Gray, recipient of the 2023 Oppenheimer Memorial Trust's Harry Oppenheimer Fellowship Award, leads the Reproductive Immunology Research Consortium in Africa (RIRCA) as a Professor of Immunology in the Division of Molecular Biology and Human Genetics at Stellenbosch University. This is a consortium of immunologists and paediatricians conducting research into markers and mechanisms of poor birth and perinatal outcomes which have an immunology aetiology, with a focus on children who are born to mothers with HIV and other infectious diseases. In addition to his research, Professor Gray is involved in immunology education and capacity building on the African continent. Through the International Union of Immunology Societies (IUIS), the online education website, Immunopaedia, is run from the Immunopaedia Foundation. a not-for-profit company registered in South Africa. The aim is to advance global immunology by supporting courses and workshops held throughout Africa, Latin America and beyond.
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