After having three children, Kenyatta Coleman was no stranger to weird pregnancy symptoms. But when she began experiencing an intense itching on her leg while 28 weeks pregnant with her fourth child, she knew something wasn’t right.
She called her local obstetrician’s office in Louisiana for guidance. It was probably pregnancy hormones, they told her, suggesting that she try some over-the-counter antihistamines for relief.
But a mother’s intuition told Kenyatta that it was more serious, and she insisted on being seen for an appointment.
It was a decision that would not only save her baby’s life but also lead them both to make history.
During that prenatal visit — which ultimately led to a diagnosis of cholestasis of pregnancy, a serious liver condition that can develop in the second or third trimester — her provider noticed something else. It appeared that Kenyatta was measuring smaller than expected, raising concerns about the baby’s growth and development. Her doctor recommended weekly ultrasounds and appointments to monitor Kenyatta and her baby more closely.
An ultrasound at 30 weeks revealed an enlarged fetal heart, as well as a rare and deadly blood vessel abnormality inside the baby’s brain. That same day, Kenyatta was referred to a maternal-fetal medicine specialist to confirm the finding.
About three weeks later, Kenyatta and her husband, Derek, were on a plane to Boston to participate in a clinical trial to treat their baby’s condition with in-utero brain surgery. Performed in March by a multidisciplinary team of specialists from the Brigham and Boston Children’s Hospital, it was the first procedure of its kind ever done in North America.
With seemingly impossible precision, the team repaired a high-flow vascular malformation deep in the baby’s brain while still in the womb. The benefits were almost immediately apparent.
“We didn’t know if we’d be bringing our baby home. Now, here we are holding her in our arms and watching her meet her milestones,” Kenyatta said. “The outcome is mind-blowing. I spend hours just looking at her in awe and saying, ‘Wow, you really are a miracle.’ She fought to be here.”
The landmark procedure, which was described in a paper published in Stroke this month, was a collaborative effort by a team that included a maternal anesthesiologist, maternal-fetal medicine specialist, obstetrical radiologist, pediatric anesthesiologist and pediatric neuro-interventional radiologist. It was performed as part of a clinical trial performed with oversight from the U.S. Food and Drug Administration.
“In every fetal surgery, there are two patients — the baby and the mother — and caring for both the fetus and the mother is an important aspect of fetal procedures,” said co-author Carol Benson, MD, co-director of High-Risk Obstetrical Ultrasound and radiology director of the Vascular Laboratory at the Brigham. “You need to make sure that everything is aligned perfectly, and we couldn’t do anything without the precise communication and teamwork of everyone involved.”
Fellow co-author Louise Wilkins-Haug, MD, PhD, division director of Maternal-Fetal Medicine and Reproductive Genetics, who has been collaborating with Benson for 20 years on fetal cardiac procedures, also emphasized the importance of this approach for such complex and delicate interventions.
“There may be three or four people at the table, but behind them there’s another dozen or so people assisting, and even more outside of the operating room who have been thinking about this from all angles,” Wilkins-Haug said.
A Novel Approach
While still in the womb, Denver was diagnosed with vein of Galen malformation (VOGM), a rare condition that occurs when arteries in the fetus’ brain connect directly to veins instead of capillaries.
VOGM can lead to high-pressure blood flowing into the veins, causing widespread brain injury or severe loss of brain tissue. The current standard of care is to treat infants with VOGM after they are born, but in many cases, brain damage has already occurred. Additionally, because of the abnormally high blood flow, babies with VOGM often experience life-threatening heart failure soon after birth, in some cases leading to inability to survive more than a few days.
The novel approach used to treat Denver in-utero involved placing tiny metal coils into the blood vessels in her brain through a catheter — inserted into the womb through a needle via ultrasound — to slow the blood flow and reduce pressure in the veins. Before the procedure began, a pediatric anesthesiologist administered medication for pain relief and to prevent her from moving during the procedure.
After she was born, Denver stayed in the Neonatal Intensive Care Unit (NICU) for four weeks as the team closely monitored her progress. Soon enough, she was off medication, eating normally and gaining weight.
Now 2 months old, Denver continues to do well, and her brain shows no signs of any negative effects from VOGM, said lead study author Darren B. Orbach, MD, PhD, co-director of the Cerebrovascular Surgery and Interventions Center at Boston Children’s Hospital.
“We were thrilled to see that the aggressive decline usually seen after birth simply did not appear,” said Orbach, who inserted the coils through a catheter during the procedure. “While this is only our first treated patient, and it is vital that we continue the trial to assess the safety and efficacy in other patients, this approach has the potential to mark a paradigm shift in managing vein of Galen malformation — where we repair the malformation prior to birth and head off the heart failure before it occurs, rather than trying to reverse it after birth. This may markedly reduce the risk of long-term brain damage, disability or death among these infants.”
While it is exciting to be part of a medical milestone, the greatest joy comes from seeing the impact on patients and families, said several members of the team.
“The malformation was growing so fast, but her brain was still OK, so this was a case where we could really help this little girl,” Benson said. “It’s very rewarding to know we are developing methods to help babies in ways that weren’t possible before.”
Having their unborn baby participate in an experimental surgery might give many parents-to-be pause, but the Colemans said they never once doubted they were making the best decision — one they say was guided equally by science and their strong religious faith as Baptists.
“We knew based on her scans that the size of the malformation, as well as how fast it was growing, meant that there was a very high chance of her going into immediate heart failure within the first two days of her life, so we were willing to do whatever was necessary,” Kenyatta said. “We’re deeply rooted in our faith, and because of that we had people praying for us and we were also praying together. We told the team from the beginning, we’re here for a reason.”
As Kenyatta and Derek soak up this precious moment with the latest addition to their family, they also hope their story shines a light on the importance of more third-trimester imaging to detect complications that develop late in pregnancy.
“I learned from my doctor later that I would have only had one ultrasound during my third trimester at 36 weeks,” Kenyatta said. “Based on the size of Denver’s malformation and what we knew about her heart function prior to the procedure, time was of the essence. Had we gone beyond 30 weeks, there is a possibility we might not have qualified for the intervention.”
How Did They Do It?
While the coiling part of the procedure itself only took 25 minutes, it was an achievement five years in the making.
In 2018, Orbach, an international expert in neurovascular diseases in children, approached Benson and Wilkins-Haug with a proposal to treat VOGM in utero, based on their expertise and two decades of experience in ultrasound-guided fetal cardiac interventions.
As part of their exhaustive planning, the team developed multiple 3D fetal-brain imaging phantoms and fetal skull-bone phantoms to simulate the procedure — an essential step that informed details such as where to place the needle, at what angle and the precise amount of pressure to use to enter the fetal brain without causing harm.
“You need to be lined up exactly for the needle insertion, so the majority of the time in the procedure is actually spent on positioning,” explained Wilkins-Haug, who was responsible for inserting the needle and monitoring both mom and baby. “The simulation ended up being remarkably true to reality.”
Benson, who provided the imaging necessary for the team to complete the intervention, said the case required a surprising amount of physical strength and coordination.
“With one hand, I was holding the baby’s head in position without moving for 25 minutes, while moving the ultrasound probe with the other hand as the intervention was occurring,” she said.