Fetal Care Team Shares New Findings at SMFM Annual Conference
Fetal interventions before birth provide life-changing care to the smallest patients. Two new studies from physicians at Cincinnati Children’s Fetal Care Center reveal methods to improve outcomes for babies who require amnioinfusion fluid during fetal therapy and those with cardiac dysfunction related to twin-to-twin transfusion syndrome.
At this year’s Society for Maternal-Fetal Medicine’s annual pregnancy meeting, Braxton Forde, MD—a maternal-fetal medicine specialist at the Fetal Care Center—presented his oral plenary, “Creation of a Synthetic Amniotic Fluid for Use in Fetal Therapy.” He received an abstract award for his work and presentation during the fellows plenary.
Fetal Care Center Maternal-Fetal Medicine Director Mounira Habli, MD, presented her poster “Prenatal Cardiac Predictors of Outcome in Severe Twin-Twin Transfusion (Stage IV TTTS): Largest Center Experience.” The meeting was held Feb. 5 to 11, in San Francisco.
Cincinnati Children’s was proud to be a major participant.
Building a Better Amniotic Fluid
Amnioinfusions, or instillation of fluid around the fetus, are often needed at the time of fetal interventions. One problem is that these amnioinfusion fluids are more acidic and nutrient poor than amniotic fluid. To reduce the risk of ruptured amniotic membranes and early labor, Forde and his team created a synthetic amniotic fluid for use in fetal therapy that more closely resembles natural amniotic fluid.
The question of amnioinfusion fluids has been gnawing at Forde since his maternal-fetal medicine fellowship at the University of Cincinnati, he says.
“Fetal therapy is a small field, so we’ve used what’s been available from other areas of medicine,” Forde says. “Originally, we used saline for amnioinfusions, and that did not have a bad effect on babies, so we kept using it. Eventually, we switched to lactated Ringer’s, but neither fluid is designed at all for the amniotic sac. Now we’re looking at how these fluids impact the amniotic membrane with a goal of keeping the pregnancy going as long as possible.”
The synthetic fluid, called “amnio-well” (AL), closely models human amniotic fluid with equivalent pH, electrolyte, albumin and glucose concentrations.
Amnioinfusion Fluids Versus ‘Amnio-well’
Their study evaluated the impact of different amnioinfusion fluids on amniotic epithelium in vitro. Using placentas from unlabored cesareans, the team isolated and cultured amniotic epithelium.
The cultured amniotic epithelium was exposed to normal saline (NS), lactated Ringer’s (LR) or AL. Culture media was a control. Researchers simulated the normal turnover of amniotic fluid by replacing the fluid with culture media after six, 12, 18 and 24 hours at 25%, 50%, 75% and 100% (respectively).
Cells were evaluated for rates of early and late apoptosis and necrosis. Cells were also tested for "rescue" after amnioinfusion.
The results? The percentage of cells alive after 24 hours:
- 89% exposed to AL
- 44% exposed to NS
- 52% exposed to LR
The percentage of cells alive after exposure and rescue:
- 94% exposed to AL
- 21% exposed to NS
- 44% exposed to LR
Forde says the current fluids used for amnioinfusion in fetal cases are toxic to human amnion in vitro and may impact the rate of membrane rupture post-surgery. He believes the use of synthetic fluid that closely resembles amniotic fluid should be considered.
He’s preparing for amnio fluid exchange studies in rats to further test how the synthetic fluid impacts fetal membranes, lungs and gastrointestinal tracts.
Forde also continues to refine the synthetic amniotic fluid. He’s conducting RNA sequencing to improve the substance and find naturally occurring antioxidants and anti-inflammatory agents. Forde’s goal is to make the most optimal fluid that has as little stress as possible on amniotic membranes after fetal surgery.
“This is not a magic bullet, as we can never fix the hole in the membrane when we do these interventions,” Forde says. “But if we can get extra weeks of pregnancy by making the fluid better, that is a huge benefit.”
Risk of Water Breakage
Forde’s amnioinfusion fluid study also led to additional research for a poster presentation, “Gestational age-related risk of rupture of membranes in the setting of fetoscopy for twins,” outlining the risk of water breakage from fetal surgery at each week of pregnancy.
The average delivery of babies who receive fetal surgery for twin-twin transfusion is between 31 and 32 weeks. However, Forde and his team found:
- Fetal surgery at an early gestational age has a higher risk of breaking water before 34 weeks.
- Fetal surgery at 21 weeks significantly decreases the risk of rupture of membranes.
“We expected it would be a little better each week, but it’s not,” Forde says. “Once the pregnancy hits 21 weeks, the risk is no different.”
These findings emphasize the need for closer surveillance and more data collection when fetal surgery is performed early in pregnancy, Forde says. Ongoing findings will help physicians provide individualized counseling to patients so they can make informed decisions.
Understanding Cardiac Dysfunction in TTTS
Parents of fetuses with twin-to-twin transfusion syndrome (TTTS)—and the physicians who treat them—need more information to make the right treatment decisions. Habli wanted to know more about cardiac predictors of survival for the most severe cases.
The abnormal blood vessel connections between babies with TTTS cause one fetus to donate blood to the other. The recipient baby produces more urine and amniotic fluid and can overwork the heart. The donor fetus becomes malnourished, makes too little amniotic fluid and experiences stalled development. The severity of TTTS is categorized in stages I to IV.
A laser surgery called selective fetoscopic laser photocoagulation (SFLP) coagulates the abnormal blood vessel connections between babies, so each receives the blood it needs from the placenta.
Habli completed a retrospective study of stage IV TTTS cases from 2004-2019 treated with SFLP. Her review included 75 stage IV TTTS patients who received fetal echocardiography before or within 24 hours after SFLP.
The findings show that recipient non-survivors, when compared to recipient survivors, had:
- Significantly higher cardiothoracic ratios (0.48± 0.04 vs. 0.41± 0.07, p=0.005)
- Higher incidences of moderate to severe left ventricular systolic dysfunction (55% vs. 15%)
- Higher rates of functional pulmonary atresia (64% vs. 18%)
Making Improved Treatment Decisions
Habli says her results are important in counseling patients about their outcome and treatment options. Her work shows that as compared to other treatment modality, stage IV treated with SFLP had a similar survival outcome as earlier TTTS stages. Recipient cardiac dysfunction is a major predictor of fetal demise despite SFLP.
This makes echocardiography tests an important diagnostic tool for patient counseling especially for stage IV TTTS patients, Habli says.
Other reported treatment options for TTTS include pregnancy termination or radiofrequency ablation of the abnormal blood vessels.
Having cardiac health data allows the care team to create a more accurate picture of the risk of fetal death and expected outcomes after birth.
Study results also open the door to “look at any adjustments in medical therapy in addition to SFLP to improve outcomes,” Habli says. “Knowing the high prevalence of cardiac dysfunction in these stage IV patients means we need more research on the long-term outcomes and cardiac development after SFLP.”
(Published November 2022)
