World-first trial at Monash Health targeting fetal growth restriction

Photo left to right: Harriet Dinning, Associate Professor Kirsten Palmer and Ebony LaPosta. 

A world-first trial at Monash Health could change how a pregnancy complication is treated to support better outcomes for unborn babies.

The PROTECT Me Trial, led by Monash Health, and Monash University School of Clinical Sciences dedicated to finding an effective treatment for a pregnancy complication called fetal growth restriction.

If successful, this trial will lead the way in finding the first treatment for fetal growth restriction, changing how clinicians treat this condition, which will give hope to many people worldwide.

What is fetal growth restriction?

Fetal growth restriction (FGR) is a condition in which an unborn baby is smaller than expected for the number of weeks in a pregnancy.

This condition complicates 1 in 14 Australian pregnancies and over 30 million globally and is one of the leading risk factors for early birth, labour complications and stillbirth.

FGR can occur when something is impairing the baby’s growth, such as infection, genetics, or the most common cause: a poorly functioning placenta.

When the placenta is not able to provide the amount of oxygen or nutrients needed to support the unborn baby, it can lead to inflammation and injuries in the developing brain. This can have long-term effects on the brain, leading to problems later in life, such as delayed milestones, learning difficulties, cerebral palsy, and behavioural disorders.

There is currently no cure for FGR, and management involves careful monitoring of the baby with ultrasound to guide the timing of birth if there are signs of distress.

However, nothing currently can be done to protect the brain from the inflammatory effects of FGR and even with close monitoring, too many babies show problems later in life.

This is something that the PROTECT Me Trial is aiming to change.

The PROTECT Me Trial

The core of the PROTECT Me Trial is introducing melatonin supplements into the pregnancy to reduce the effects of brain inflammation.

This is a world-first trial to see if melatonin makes a difference in pregnancies with FGR.

Melatonin is a natural hormone produced by the brain which regulates our sleep-wake cycle. However, new research shows that melatonin can reduce inflammation in the brain.

Associate Professor Kirsten Palmer is a consultant obstetrician and maternal fetal medicine subspecialist and the chief investigator of the PROTECT Me Trial.

A/Prof Palmer explains that early studies using melatonin at The Ritchie Centre, led by Professor Suzie Miller and Professor Euan Wallace, underpinned the basis of the PROTECT Me Trial.

“The thought was that melatonin, as an antioxidant, would work really effectively at helping to counteract the effects of a poorly functioning placenta in FGR and protect the babies from damage. These early studies produced incredibly promising findings that melatonin protects the developing brain and normalises brain development,” A/Prof Palmer said.

These early studies showed that unborn babies exposed to melatonin when the placenta was not working well had fewer brain injuries than babies with FGR who did not receive melatonin.

These findings, combined with melatonin appearing safe and well tolerated and easily able to cross to the placenta and into the fetal brain, make it a promising treatment for use in pregnancy.

As part of the trial process, participants are randomised and given either melatonin or a placebo supplement.

Nicoletta said she had no hesitations in joining after reading information about the trial.

Although participants may not receive melatonin during the trial, receiving the placebo supplement can also benefit the pregnancy.

A/Prof Palmer explains, “there are clinical benefits for patients that participate in clinical trials, so even those on placebo will often have some benefits.”

“Participants can have better outcomes just due to the continuity of care they receive from the team, as we are with them throughout their entire journey and support them along the way,” she said.

Nicoletta is a participant in the trial and gave birth to baby Nicholas at 29 weeks gestation.

Nicoletta was introduced to the PROTECT Me Trial team after a scan early in her pregnancy indicated complications in Nicholas’s growth.

Nicoletta explains that while she didn’t know whether she received melatonin or a placebo, she was going to try anything to ensure that her baby would survive.

“I was advised that it wasn’t certain if Nicholas would get past 24 weeks due to his weight. However, I was so positive that we had the melatonin that I believe with my positive outlook, Nicholas was able to grow and stay in my tummy longer.”

“You’ve got nothing to lose. If anything, you have something to gain because if you do have the melatonin, it’s doing something for your child,” she said.

She also highlighted the excellent care she received from the PROTECT Me Trial midwifery coordinators, Ebony LaPosta and Harriet Dinning, at Monash Health.

Nicoletta said, “I’m a positive person and paired with meeting Ebony and her putting me at ease made me even more positive than I was previously. I felt like that really helped me go through the program and the pregnancy.”

Both Harriet and Ebony have a background in complex clinical maternity care and chose to combine their clinical midwifery roles with clinical trial research to try and improve outcomes for mothers and their babies experiencing pregnancy complications.

Ebony, who joined the trial team in 2020, explains that participants in the trial share the same focus as the team in changing the outcomes for babies with FGR.

“For many women, the driving factor for participating in the trial is not only for themselves or their baby but the possibility that they can spare a woman and her child in the future from going through this,” Ebony said.

The basis of the PROTECT Me Trial is the relationships formed with the participants as they share their pregnancy journey with the team.

Ebony explains, “The continuity of care and the relationship building with the participants is really important and travelling the journey of their pregnancy and getting them home with their baby is something special.”

Lorena and her daughter Mimi have just completed their two-year follow-up as part of the PROTECT Me Trial.

Lorena joined the trial late in her pregnancy in 2020, weeks before she gave birth to Mimi at 26 weeks gestation, where she became the smallest baby ever delivered at Monash Medical Centre.

Looking back on this time, Lorena reflects on the fantastic care she received from midwifery coordinator Harriet Dinning.

“During Mimi’s birth, my husband couldn’t be there with me, but Harriet was with me all the way. We first met when I was getting ready to go into theatre, so it was a moment where I didn’t know what was happening, I had no family members with me, and my life and my child’s life were on the line. Her approach was really calming, and to have her there with her positivity was crucial to us, and I will never forget that,” Lorena said.

At Mimi’s two-year assessment, her results were slightly below average but considering her size at birth and all the challenges she faced; the results are extremely positive.

Lorena believes taking the supplements in the week leading up to Mimi’s birth contributed significantly to where she is today.

“Even though the time that I took the supplements wasn’t very long, I believe it impacted the way Mimi is now. I didn’t know if I was taking the melatonin, but my mindset in thinking that I was taking something that was helping her was really important,” she said.

Lorena said the PROTECT Me Trial team assisted her with any worries or questions during and after Mimi’s birth.

“If you are scared or have questions, the midwives are open to explain the trial to you to discuss and respect your decisions. I think it’s important to give the trial a go if you can, as you aren’t taking a medication that can harm your baby; it actually can help.”

For more information, you can watch this video explaining the trial.

If you are interested in participating in the PROTECT Me Trial, speak to your obstetrician about how you can get involved.