August 16, 2010
By Carolyn Gutierrez
For The Record
Vol. 22 No. 15 P. 24
A doctor’s groundbreaking procedure has had untold effects on babies suffering from twin-to-twin transfusion syndrome.
Twin-to-twin transfusion syndrome (TTTS) is a disease involving the placenta shared by identical twins in which the two fetuses receive a disproportionate amount of blood and nutrients due to abnormal blood vessels. About two thirds of identical twins are randomly monochorionic (share one placenta), and 15% of those will develop TTTS. Though the syndrome varies in severity, it can cause complications for the fetuses ranging from anemia to heart failure to neurologic damage. Left untreated, TTTS has a mortality rate of 80% to 100%, usually due to premature delivery.
In TTTS, the fetus known as the recipient receives too much blood through the connecting blood vessels of the placenta, while the donor fetus receives too little. For the recipient, this imbalance causes excessive urination, leading to an overabundance of fluid in the amniotic sac. Conversely, the donor fetus urinates infrequently and is surrounded by little or no fluid. Neither hereditary nor genetic, this blood flow imbalance between otherwise normal, healthy fetuses can result in a dramatic size difference between the twins, with the smaller twin’s growth restricted due to its insufficient “placental share” and limited access to nutrients.
A Trailblazing Surgeon
Before the refinement and widespread use of ultrasound technology in the early 1980s, TTTS treatment was negligible at best. But in October 1988, Julian E. De Lia, MD, FACOG, FACS, performed the first fetoscopic laser occlusion of the connecting vessels in the placenta, a procedure in which a 3.5-mm scope identifies connecting blood vessels between the twins that are then coagulated by a laser, restoring normal blood flow between the fetuses. This procedure gave new hope to countless expectant parents whose pregnancies were complicated by TTTS.
The founder and current medical director of the International Institute for the Treatment of Twin-to-Twin Transfusion Syndrome at Wheaton Franciscan-St. Joseph in Milwaukee, De Lia is the 2010 winner of the Pacesetter Award from New York Hospital Queens for his groundbreaking surgery and research in aiding TTTS patients.
The case that inspired De Lia’s innovative TTTS treatment occurred in Utah in the early 1980s. A previous patient of De Lia’s came to see him during her second pregnancy. A radio newscaster, her schedule had been so hectic that she hadn’t planned a prenatal checkup until midway through her pregnancy.
“She was about 23 weeks when we saw her for the first time, and clearly her uterus was too large for someone who was 23 weeks pregnant,” he recalls. “Either her dates were very much off as to when she had conceived or she was pregnant with twins. And so we set up an ultrasound almost immediately, which found the twins, and found that they were identical twins that shared a single placenta and were showing manifestations of TTTS. These manifestations in her case were that one of the fetuses [the recipient fetus] was in heart failure and was also surrounded by an excess amount of amniotic fluid and considerably less fluid surrounded the donor fetus. This was 1983. The physician who did the ultrasound scan looked at this mother, and I was standing there because she was my patient and I wanted to see what the ultrasound looked like, and he said to her, ‘There’s no way these babies will survive. This is TTTS.’”
A pharmacist recommended that the team try digoxin, a medication that had been somewhat successful in treating fetal arrhythmias. “Miraculously, it seemed to work,” says De Lia, “and we were able to get these twins to 33 weeks. So the heart failure seemed to go away and we delivered the babies. The good news is they both lived; the bad news is that the recipient twin had mild cerebral palsy and some degree of mental insufficiency. So it was a bittersweet victory, but for the parents who lived through this, it was spectacular.”
For De Lia, the wheels started turning. “By the time these babies were born, I knew everything there was to know about the placenta and TTTS,” he says. “By the time these babies were born, I was already a member of the laser laboratory at the University of Utah where they were looking for applications. And by the time these babies were born, I already knew that if the placenta looked the way I thought it was going to look and if this tool was really what it was made out to be, namely the laser, I thought I had a solution to this problem.”
Influence of Pathologists/Placental Studies
In his acceptance speech for the Pacesetter Award, De Lia spoke of how his work was “below the radar” because it involved an often-disregarded organ—the placenta. “At delivery, parents typically ask about fingers and toes and never the placenta,” he notes. “We keep the medical records, the 9 lbs of fetal heart monitor tracings, and throw the placenta away.”
In the early 1980s, it was thought there was not much that could be done for TTTS patients. “The literature was predominantly pathology,” says De Lia, “because so many of the twins didn’t survive. Most of the literature was written by pathologists who had done the autopsies on these fetuses along with the examination of the placenta.”
The study of placentas—each of which is unique—was key to the research conducted by De Lia, who cites the influence of pediatric pathologists in the early days of fetal surgery. “The pathologists are the physicians who live in basements. They’re not on the main floors of the hospitals. Nobody sees them and nobody gives them a heck of a lot of respect,” he says. “The pediatric pathologists were the ones who were not only my mentors but also the individuals who really encouraged me to go forward with [the laser surgery] rather than the obstetricians.”
De Lia generally performs the laser surgery midway through the pregnancy at approximately 20 weeks. Twenty-five weeks is the surgery’s cut-off point because at that stage the babies can be delivered.
“The specialty of fetal surgery came about pretty much when ultrasound became sophisticated enough to make these diagnoses. That was probably the late 1970s. Fetal surgery in general should be undertaken if it’s bioethically acceptable, if it’s feasible, and if it’s necessary—those are the three criteria for fetal therapy,” he notes. “And certainly my operation fulfills those three characteristics. But you have to understand that there was a great deal of resistance to the laser surgery once I introduced it back in 1988. There are some centers and some people in this country who still do not support the surgery.”
Today De Lia’s procedure is the most commonly performed fetal surgery, most likely because more cases of TTTS are being seen as advances are made in reproductive technology. “The IVF [in vitro fertilization] procedure is associated with an almost 20 times greater incidence of monozygotic twinning, or identical twinning,” he says. “About one in 150 of the IVF patients have a risk of developing TTTS.”
A TTTS Mother
Katie O’Connor Fast is one mother whose life was changed by TTTS and De Lia’s groundbreaking surgery. The San Francisco mother laughs as she talks about her “mischief makers,” 7-year-old identical twin daughters Sophie and Sara who keep O’Connor Fast on her toes with telephone pranks to their classmates and other day-to-day hijinks. She lists the twins’ myriad activities: swimming, soccer, basketball, horseback riding, skiing, riding scooters, and “playing” school. Their world is a bright and spirited one, and O’Connor Fast is grateful yet reflective about her experience with TTTS, fully aware that she is fortunate to have had a happy ending to her high-risk pregnancy.
When asked about De Lia, who performed her laser surgery, O’Connor Fast says, “He is pretty much single-handedly responsible for us being able to keep our kids, so he has a very special place in our lives.”
During her pregnancy, O’Connor Fast suffered from extreme morning sickness but was thrilled nonetheless at the prospect of becoming a first-time mom to twins. At an appointment with her perinatologist, Carl Otto, MD, an ultrasound revealed manifestations of TTTS. The news took a serendipitous turn, according to O’Connor Fast, as “Dr. Otto had just two weeks before seen a woman who was pregnant with identical twins who it turned out had TTTS, which I think in all of his years of practicing perinatology, that was an odd occurrence for him—two back-to-back situations of the exact same type. So we benefited from the research that he had done two weeks before in terms of learning about Dr. De Lia.”
O’Connor Fast and her husband Spencer researched De Lia and called him that day. “[De Lia] called me from his home in Milwaukee late that same night and spoke to Spencer and me for nearly an hour about TTTS, its treatment, and the efforts we ourselves could take to combat our helplessness in battling this deadly disease,” she recalls. “He was fantastic, extraordinarily hands-on.”
Because of the uniqueness of each case and the varying degrees of severity in TTTS, De Lia carefully monitors each patient he sees. “He’s very conservative in his approach,” says O’Connor Fast. “He’s very conservative in terms of who becomes a candidate for his surgery. The babies have to be within certain parameters in order to qualify for his surgery. I think some people grouse about that because it means that not everybody’s going to get to the point where they’re going to need the surgery, but I understand why he does it. He doesn’t want to endanger the mother; he doesn’t want to endanger the babies.”
Maternal Warning Signs
According to the TTTS Foundation’s website, warning signs in the mother of twins with TTTS include the following:
• the sensation of rapid growth of the womb;
• a uterus that measures large for the dates;
• abdominal pain or tightness, or uterine contractions;
• sudden increases in body weight; and
• swelling of the hands and legs during early pregnancy.
Excessive weight gain in a TTTS mother stems from the disproportionate amount of amniotic fluid surrounding the recipient twin. Reduction amniocentesis can stem the excess fluid and relieve symptoms. In mild cases, this may be all that is needed to address the imbalance, but a comprehensive treatment plan is usually recommended for the best outcome. This includes a combination of amnio reduction, bed rest, and nutritional therapy.
Four Paradigms of TTTS
According to De Lia, there are four paradigms in the treatment of TTTS. Two are placental: the presence of blood vessel anastomoses connecting the twins’ circulatory systems and the tendency for a shared placenta to be partitioned unequally.
The other two paradigms, metabolic abnormalities and cervical insufficiency, are maternal and still under study. As De Lia’s laser surgery has gained more mainstream acceptance, he would like to focus more on researching the mother’s nutrition and cervical instability. In his study “Maternal Metabolic Abnormalities in Twin-to-Twin Transfusion Syndrome at Mid-Pregnancy-II,” De Lia found that all TTTS patients at midpregnancy were malnourished.
“This protein calorie malnutrition is really a significant finding because it can take a very mild transfusion between the twins and make it look much worse,” he says. “In mild cases of TTTS, we start patients on aggressive nutritional supplements … and horizontal rest because it turns out that we have yet to see a woman with manifestations of TTTS who did not have protein calorie malnutrition. They all have it.”
In the last 10 years, an emphasis has also been placed on the cervix and the potential for cervical insufficiency in TTTS mothers. Using ultrasound, physicians discovered that cervical insufficiency could occur due to the tremendous pressure on the uterus resulting from the excessive amniotic fluid produced by the recipient twin. In these cases, cerclage is performed on the mother to stabilize the cervix. “A third of all the losses, a third of all of the sick kids [from TTTS] came about as a result of a woman having a short cervix that no one was aware of at midpregnancy,” notes De Lia. “Cerclage has revolutionized the postoperative period for our patients where I do not get the call from one in five that the babies were lost. It just doesn’t happen that way anymore.”
De Lia expresses a desire to share his knowledge with other surgeons so more twins with TTTS may survive. “The only thing I would like to do is leave a little bit better legacy for the patient,” he says. “I would like to teach other laser surgeons what my learning curve was like—in other words, things to try to avoid, things to do. In all honesty, no one has ever asked me personally to help them do this operation or teach them to do it. And so it looks like my only recourse is to kind of force myself into these centers that are popping up—almost every four months—in this country and worldwide. I think that would be the best course to take given my limited amount of time left on this earth, figuratively speaking.”
For O’Connor Fast, thanks to De Lia, she has two vivacious daughters. But having gone through TTTS, she knows that not every mother with the condition is so fortunate. Besides working with the TTTS Foundation and counseling newly diagnosed mothers, O’Connor Fast wants to give back something more: hope.
“I’ve talked to a lot of expectant mothers who are going through this and I know that our outcome was really an outlier, which breaks my heart so much and part of it is, I think, the lack of education about what this condition is and the fact that it is actually treatable,” she says. Other than their small build and a slight weight difference between them, Sophie and Sara have not experienced any long-term effects from TTTS. “They’re string beans, but they’re here and they’re great,” she says.
Every August on the anniversary of her TTTS laser surgery, O’Connor Fast and her family have a celebration for the twins. “That gets me emotional because it’s just such a special thing,” she says. “We call it their second-chance day.”
— Carolyn Gutierrez is a freelance writer based in New York City.