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Blizard Institute - Faculty of Medicine and Dentistry

Surviving and thriving – how the COMBI trial hopes to reverse the cycle of low birth weight in Zimbabwe

Zimbabwe women and children sitting under a tree

How can we increase babies’ birth weights and help them to thrive? Babies who are born too early or too small face a wide range of life challenges, particularly in low-income countries. Professor Andrew Prendergast is leading a study in Zimbabwe to intervene even before infants are born – treating pregnant mothers with a course of antibiotics to keep them healthy during pregnancy and to help their newborn infants survive and thrive.

Around a third of children around the world are stunted – which means they don’t grow as they should. The problem arises between conception and the age of two. This has long-term effects on their future prospects for learning and even future earning potential.

There are a wide range of reasons why children may not grow as they should, including low birth weight. If a child’s growth is delayed in early life, he or she is more likely to die early, or to do less well at school and have long-term health problems into adult life.

This cycle is perpetuated because mothers who were stunted as children often give birth to children who face the same issues − they are born with a low birth weight. This creates an intergenerational cycle of poverty which is hard to break.

Stunting syndrome graphic

Professor Prendergast and his colleagues at the Zvitambo Institute for Maternal and Child Health Research in Zimbabwe have explored many potential interventions to help children to grow and thrive. Their latest research project, Cotrimoxazole in Mothers to Improve Birthweight in Infants (COMBI), aims to intervene well before babies are even born.

What other initiatives have been attempted? 

The WHO set targets aiming to reduce stunting by 40% between 2010 and 2025. While some progress has been made, especially in Asia, the problem remains enormous, especially in Africa, where around 40% of children are still stunted. As populations expand, more and more children are affected.

Although stunting is usually attributed to poor diet or disease (especially diarrhoea), previous interventions have shown little improvement in the condition. In 2018, Professor Prendergast and colleagues published the results of the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial. This study tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in Zimbabwe. Between 2012, and 2015, 5280 pregnant women were enrolled onto the SHINE trial.

The researchers offered nutritional support in the form of lipid-based nutrient supplements for some babies aged six to 18 months, along with feeding counselling for parents. To improve sanitation for certain groups, an improved, ventilated pit latrine was built, along with handwashing stations and access to soap and chlorine. Some groups were given both feeding and WASH interventions.

The feeding initiative had some benefits in reducing the number of stunted children and those with anaemia, while the WASH intervention had no discernible impact on stunting or the prevalence of diarrhoea.

What does the COMBI trial aim to do?

COMBI hopes to break the intergenerational cycle of stunted growth, by helping babies to thrive even before they are born. By intervening when women are pregnant and improving the health of the mother, Professor Prendergast hopes to see as many babies as possible born at full term and at a good birth weight.

COMBI is enrolling 1000 pregnant women, whose pregnancies are dated by ultrasound.  The pregnant women then have a full health assessment, including details of their diet and medical history, analysis of urine, stool, blood, saliva, and high vaginal swabs. The participants also have their dental health assessed as there is increasing evidence that that harmful inflammatory processes and infections arising from the mother’s mouth and gums can cause babies to be born early or at lower birth weights.

The double-blind, placebo-controlled trial sees half of the women given 960mg of cotrimoxazole daily while the others receive a placebo. Cotrimoxazole is used to treat certain bacterial infections, such as pneumonia, bronchitis, urinary tract infections, ear infections and some intestinal problems. Some of the women may have ongoing infections, even infections of which they are not aware, and this broad-spectrum antibiotic is designed to treat these.

These antibiotics may also improve the health of the mothers after they give birth, and reduce the risk of their babies being exposed to pathogens during pregnancy or delivery. This may prevent neonatal sepsis, and help the new-born to develop a more robust immune system.  Thus this antibiotic intervention could have many benefits for both mother and baby.

We recognise that antibiotics are not going to be a silver bullet for the problem of small babies, however they could form part of a package of care for women during pregnancy.
— Professor Andrew Prendergast

What can this intervention achieve?

If the use of antibiotics makes a difference to the birth weights of babies, it will be an easy intervention to scale up and use in many antenatal environments. The antibiotic is low cost, and women will be able to receive the tablets from their clinic, as they would receive iron and folic acid.

Professor Prendergast is quick to say that COMBI is not a catch-all solution, but that along with infant feeding and other interventions will form a package of interventions in early life. He hopes that in time, more healthy babies will be born at a good weight and the cycle of stunted growth will be broken.

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