By Erin Digitale
Photography by Leslie Williamson
Before her third son was born in 2010, Maya Adam had to face a possibility modern medicine has made almost obsolete: She could bleed to death before or during delivery. A rare defect in her placenta left both Adam and her fetus vulnerable to sudden, fatal hemorrhage.
“We made a video for our two older boys in case they needed it as their final memory,” Adam says, recalling the compilation of family photos and video that she and her husband, Lawrence Seeff, assembled for sons Kiran, then 5, and Misha, then 2, near the end of her pregnancy. The family lives in Menlo Park, Calif., where Seeff invests in startup companies and Adam, a physician by training, teaches child health and nutrition at Stanford. Months earlier, when they decided to have a third child, Adam and Seeff never considered that Kiran and Misha might be left without a mother. “We had plenty of love and resources to give,” Adam says. “You just don’t think that you’re playing roulette with the stability of the older children’s lives.”
Adam’s situation, unusual as it is, reflects a growing problem in obstetric medicine. She had placenta accreta, in which the placenta, the organ that connects the pregnant woman to her fetus, attaches with dangerous tenacity to the uterus. Sometimes — as in Adam’s case — it grows through the uterine wall and invades other organs. Once vanishingly rare, with only one in 30,000 pregnancies affected in the 1950s, placenta accreta now hits around one in 500 pregnancies. Up to 7 percent of placenta accreta patients die of the disease. Scientists have linked the increase in cases to rising caesarean rates, but the exact mechanism of the disease — a conversation gone awry between the placenta and the uterus — remains profoundly mysterious.
Treatment is daunting: Doctors often must remove the entwined placenta and uterus immediately after delivery, a procedure that is both technically challenging for surgeons and potentially devastating for women who want other children. Such a surgery, a combined caesarean-hysterectomy, is difficult because the interior of the pelvis looks different just after birth than it usually does — the enlarged uterus has pushed other tissues out of their typical locations. Add to that a welter of blood vessels growing from the abnormal placenta, and the result is that, in spite of recent advances in the technology used to diagnose placenta accreta, the surgery remains unpredictable and challenging.
“Even though we have better imaging than we’ve ever had before, it’s still difficult to assess how bad the actual bleeding will be,” says Edward Riley, MD, professor of anesthesia at the School of Medicine. Before delivery, surgeons treating a placenta accreta patient typically have a sense of where the abnormal blood vessels are located, says Riley, who is also the Packard Children’s obstetric anesthesiologist who cared for Adam during her delivery. “But it’s really hard to know, will they just peel off nicely or cause real problems?” he says.
“It can be very scary,” says high-risk obstetrician Deirdre Lyell, MD, who is the medical director of the Program for Placental Disorders within the Division of Maternal-Fetal Medicine at Lucile Packard Children’s Hospital, which now treats 15 to 20 placenta accreta patients per year. Lyell, who is also an associate professor of obstetrics and gynecology at the School of Medicine, and her colleagues are among a handful of researchers tackling the disease nationwide. “Women with accreta can bleed very quickly.”
“The placental tissue is kind of remarkable: It behaves like cancer, invading into the uterus,” says placenta accreta researcher Robert Silver, MD, professor of obstetrics and gynecology at the University of Utah. He’s describing the normal process by which a pregnancy takes hold, beginning when the new embryo implants in the uterus and the placenta begins to form about a week after the egg is fertilized. “Then there’s a signal — we don’t know what it is — that puts a brake on and stops the invasion,” says Silver.
The placenta is supposed to attach only to the uterine lining, a temporary layer, distinct from the uterine muscle, that is shed at delivery. If the placenta grows into the muscle, it sticks. Small adhesions — what scientists call “focal accretas” — may cause chunks of placenta to stay in the uterus after delivery, increasing a woman’s risk for postpartum infection or hemorrhage. In more serious cases of accreta, the whole placenta adheres to the uterine muscle and invades deeply into the uterine wall (“placenta increta”) or grows completely through the wall (“placenta percreta”).
Scientists aren’t sure if the problem originates from a too-invasive placenta or a defect in the ability of the uterus to stop it. As Lyell puts it, “Is the placenta or the uterus driving?”
Her team is part of a multi-institution effort to look for clues. Researchers at Stanford Medicine, Columbia and the University of Utah are creating a tissue bank of normal and adhesive placenta samples, which Stanford’s Julie Baker, PhD, an associate professor of genetics, is testing for genetic or molecular signatures of abnormal invasiveness. Early results from other research suggest overly invasive placentas over-produce growth factors and signals associated with formation of new blood vessels, and make too little of certain proteins that act in other situations to curb the growth of cancers. Such findings hint that the placenta partly drives excess invasion.
But epidemiologic data about placenta accreta patients imply that the uterus also plays a role. Accreta risk increases if a woman has uterine scarring, such as that left by caesarean sections, surgeries to remove uterine fibroids, or dilation and curettage (D&C) procedures used to empty the uterus after a miscarriage. If the placenta attaches to a scar, where the uterine lining may already be defective, it’s a recipe for trouble. The risk of developing placenta accreta is 0.3 percent for women with one prior C-section, for instance; it rises to 2.4 percent for those with three prior caesareans.
‘We were doing what everyone said we shouldn’t do, which was to look online and see how dangerous it was and what to expect. It was quite frightening... .’
The position of the placenta is even more important: Lower in the uterus, where the uterine lining is less robust, the placenta is more likely to stick. And if the placenta implants across the exit from the uterus — a condition called complete or central placenta previa — the woman’s risk of developing placenta accreta rises enormously. Five percent of women with placenta previa and no uterine scars get placenta accreta. Women who have placenta previa and have had one prior caesarean have an 11 to 25 percent risk of developing placenta accreta, while those with placenta previa and two prior C-sections have a 40 percent risk of developing placenta accreta. Patients who had both placenta previa and a history of three prior C-sections, face an accreta risk of as much as 60 percent. Physicians have also noted that, in rare cases, women with no obvious risk factors can get placenta accreta, too.
Beyond understanding how an overly adhesive placenta forms, researchers also want to know if the condition could be prevented. “Maybe something as simple as a change in C-section technique could reduce the risk,” Silver says.
While physician-scientists conduct research to understand the science of placenta accreta, they are also making strides to help patients. Early, accurate diagnoses are enabling tightly planned care.
Often, as in Adam’s case, the condition shows up on a routine prenatal ultrasound. After the diagnosis, says Seeff, “we were doing what everyone said we shouldn’t do, which was to look online and see how dangerous it was and what to expect. It was quite frightening just reading some of the experiences.” For her part, Adam’s medical training helped to reassure her that her doctors knew how to manage her situation. Even so, she says, “I’m glad I’m not a specialist in that area; I would not have wanted to know exactly how bad things could get.”
Physicians begin to get a sense of how bad things are from their first ultrasound views of the affected placenta. An abnormally adherent placenta has “a Swiss-cheese-like appearance,” Lyell says. Her team has specialized tools, such as a near-field ultrasound probe for visualizing placental tissue, to gather as much diagnostic information as possible. A thin muscle wall or poor borders between the placenta and uterine muscle are other telltale signs. If the placenta invades nearby organs, the doctor may also see blood vessels at odd angles around another organ, such as the bladder. “It’s very disconcerting,” Lyell says.
After Adam was diagnosed at 20 weeks’ gestation, her obstetrician, Christie Coleman, MD, of the Palo Alto Medical Foundation, prescribed bed rest beginning at 30 weeks. Adam’s placenta extended across the uterine opening and down into her cervix, sending blood vessels into the muscles that kept her uterus closed. This was a hazardous situation because the lower portion of the uterus expands so much in late pregnancy. The growth could shear a major placental blood vessel, causing both the mother and fetus to quickly bleed to death. “If I had any bleeding, I was supposed to get to the ER as quickly as possible,” Adam says.
It’s risks like this that cause some women with severe cases of placenta accreta to end their pregnancies. “I have one patient who recently terminated her pregnancy at 11 weeks because the placenta had implanted all the way through her C-section scar,” says Daniela Carusi, MD, assistant professor of obstetrics, gynecology and reproductive biology at Harvard Medical School. Such an early, extreme placental defect can rupture the uterus during pregnancy. “This patient said, ‘I just don’t want to die,’” says Carusi, who is also director of the Program for Surgical Obstetrics at Brigham and Women’s Hospital in Boston. “She had a little boy at home, and wanted to keep herself healthy and her family intact.” Many patients in this situation have subsequent normal pregnancies, Carusi adds.
Adam and Seeff wanted to continue her pregnancy. “When the condition was first diagnosed, we didn’t imagine that our case would become so life-threatening. It was only later, during the third-trimester imaging, that the results suggested that ours could be a much more serious case,” Adam says. And bed rest was extremely challenging. In addition to their worries about her health, and the fact that they had two young children to care for, Adam had a new job at Stanford as a lecturer in human biology. (“I had to tell Stanford, ‘I can’t teach spring quarter,’ and that was the hardest thing I had ever done,” she says.) And she’s not one to sit still, even while pregnant — during her prior pregnancies, she was in medical school and worked until delivery. But nor is she easily daunted. (In the spring of 2013, she developed and taught an online Stanford course on child nutrition and cooking. More than 22,000 people signed up.) To stay sane through the long weeks of inactivity, she kept a blog. “We were holding our breath to see how long we could keep the fetus inside,” Adam says. She made it to 37 weeks’ gestation; at that point, her medical team called for a scheduled C-section to avoid risking the possibility that she would go into labor.
Coleman planned for a complicated delivery, warning Adam that a hysterectomy would probably be necessary, and enlisting both Riley, an experienced Packard Children’s obstetric anesthesiologist, and a gynecologic oncologist to assist. In some cases, specialists from other disciplines also participate in placenta accreta surgeries, including vascular surgeons, who operate on blood vessels, and interventional radiologists, who help block off blood vessels to prevent hemorrhaging.
On June 16, 2010, before Adam was wheeled into one of the main operating rooms at Stanford Hospital “they put hoses, basically, in my arms in preparation for giving large amounts of blood fast,” Adam remembers. As Seeff stood near her head, the surgeons delivered baby Milan with an incision made high on Adam’s uterus to avoid her placenta. While the couple got their first glimpse of the new baby, the doctors got their first in-person view of the entwined placenta and uterus.
“I had been at a few C-sections during my medical training, and they’re usually pretty happy occasions,” Adam says. During a routine caesarean, the medical staff chats easily, the baby is born, the chatter continues. “This time, after the baby was delivered, there was silence behind the curtain.”
After a pause, Coleman told Adam and Seeff, “We’re going to go ahead with the hysterectomy now.” Seeff and the baby were ushered out, and Adam received general anesthesia. The physicians began their struggle to control her bleeding.
It was fortunate, Coleman says now, that she and Adam could plan for a hysterectomy beforehand — and fortunate, too, that Adam and Seeff felt their third child would complete their family.
‘I had been at a few c-sections during my medical training and they’re usually pretty happy occasions. This time, after the baby was delivered, there was silence behind the curtain.’
“We had talked about it, and I had the opportunity to say, ‘If it looks bad, how aggressively do you want me to save your uterus?’” Coleman says. “It’s much harder when you’re trying to make those decisions in the moment.”
Even with excellent prenatal imaging of placenta accreta, physicians often don’t decide whether to do a hysterectomy until they’ve delivered the baby. In less-severe cases, massaging the exterior of the uterus sometimes prompts the placenta to detach, perhaps leaving small uterine tears that can be sewn closed. And in very severe cases such as Adam’s, where blood vessels from the placenta can be seen growing through the uterus at delivery, there’s little question that a hysterectomy is required. But difficult decisions fall in the middle of the severity scale, where patients and doctors may want to save the uterus but question if it is safe to try.
“The desire to preserve the uterus and preserve fertility is terrific,” says Utah’s Silver. “It deserves research.” Some teams, particularly in Europe, leave either the entire placenta or adherent portions in place after delivery in the hope that they will later detach, Silver notes, or they take active steps to help the retained placenta disengage, such as blocking blood vessels to retained segments, using radiofrequency ablation to destroy the retained placenta, or giving the chemotherapy drug methotrexate to destroy its blood supply. All of these approaches, however, require waiting days or weeks for the placenta to disintegrate and be reabsorbed.
After trying about 10 cases with such approaches, Silver is wary: “In several of those cases the patients had major complications with bleeding or infection and ultimately required hysterectomy. I’m not very enthusiastic about it other than in very experimental circumstances.”
But Boston’s Carusi, recalling a case she saw during her training that inspired her to study placenta accreta, cautions against a too-aggressive approach to removing a placenta that sticks unexpectedly. “From that case years ago, the lesson for me was ‘Respect the placenta,’” she says. “If it won’t come out, don’t fight it. You can end up doing a hysterectomy in someone who didn’t want one, or having a severe hemorrhage to control.”
For now, says Lyell, Packard Children’s placental disorders team avoids leaving pieces of the placenta behind inside the uterus. Before resorting to a hysterectomy, they sometimes try a combination of drugs that contract the uterus and a D&C procedure to try to remove pieces of placenta that are reluctant to detach. But they are also closely watching research from groups attempting alternate methods that involve leaving pieces of the placenta in place for longer periods.
‘A number of patients have post-traumatic stress disorder after pregnancy because the delivery is so stressful. ... It makes them feel very mortal — it’s often the first time they’ve had to think about death.’
Meanwhile, the Packard Children’s team is taking a new approach for another category of difficult cases. They’re staging post-delivery surgery over two days — a technique borrowed from trauma surgeons treating combat wounds in Iraq — for some patients whose placentas have grown through the uterus to invade other organs. In these cases, even a hysterectomy isn’t enough to get rid of the net of placental blood vessels, so the Packard Children’s team, in conjunction with David Spain, MD, the chief of trauma and surgical critical care at Packard Children’s and a professor of surgery at the School of Medicine, decided to try something different.
“When patients have bled so heavily and received so much blood that they’ve become unstable, there comes a point at which you can’t keep trying to get the placenta out,” Lyell says. Transfusing large amounts of blood can cause coagulopathy, in which the signals that trigger blood clotting stop working. When this happens, instead of continuing surgery, the team clamps everything that is bleeding, transfers the patient to the intensive care unit overnight and resumes surgery the next day. In the interim, the hormonal and vascular shifts that normally follow childbirth can occur, the patient is monitored closely and transfused as needed, and coagulopathy resolves. “When we’ve gone back the next day, it’s a completely different surgery,” Lyell says. “It’s a lifesaving move.”
For Adam, such extreme measures were fortunately unnecessary. But her surgery was far from simple. Coleman was glad for the assistance of Palo Alto Medical Foundation gynecologic oncologist Alfred Pisani, MD, who is an expert at distinguishing normal from abnormal pelvic tissues. As Coleman and Pisani operated, they knew that getting the placental blood vessels out would cause unavoidable bleeding, so they warned obstetric anesthesiologist Riley to be ready to transfuse blood each time they approached a vessel that looked difficult to remove. “We did get into really tremendous hemorrhaging, with her blood pressure going down quickly and her heart rate up,” Riley recalls. In each instance, with meticulous teamwork between the doctors, nurses and the blood bank, the team was soon able to bring Adam’s vital signs back under control.
During her two-hour operation, as Seeff went back and forth between the nursery where baby Milan was being cared for and the spot outside the operating room where Adam’s parents and sister also waited, he grew increasingly concerned about his wife. “It was very unnerving; the longer it kept going, the more worried we became,” he says. “But we were lucky that we were at a very sophisticated hospital with very experienced surgeons and doctors.”
Adam received 22 units of blood, more than 7 liters total. “She lost more than two times her normal blood volume,” Riley says.
When Adam was finally transferred to the intensive care unit at Stanford Hospital where she spent the next 24 hours on a ventilator, she had two thoughts: relief that the baby was OK and a desperate desire to get home to her older sons. After her breathing tube was taken out, the nurses gave her an incentive spirometer to blow into; receiving so much transfused blood had caused fluid to pool in her lungs, and the blowing action exercised her lungs and helped clear the fluid. But it also put a painful strain on her surgical incisions.
Her daily visits with Milan, who was being cared for in the hospital nursery, were incredibly motivating.
“I blew into that machine day and night,” she says. “They could not believe how determined I was, but I had two kids at home and I had told them I would only be in the hospital for a few days.”
Two days after she had entered the hospital, she was well enough to be transferred to Packard Children’s regular maternity ward, where she wept when the implications of her experience began to hit. “I realized how close I had come to not being here for my children.”
Complicated reactions in the aftermath of placenta accreta are common, the experts say. “The difference between making a choice to no longer have your fertility and having that choice thrust upon you is very difficult emotionally,” says Silver.
Yet some women, after months of worry about delivery, are relieved to know that a hysterectomy means they’ll never be pregnant again.
Still, even if they feel some relief, “a number of patients have post-traumatic stress disorder after pregnancy because the delivery is so stressful,” Carusi says. “We’ve struggled to find help for them because people don’t think of new mothers as PTSD patients. It makes them feel very mortal — it’s often the first time they’ve had to think about death, and that has huge impacts on them.”
For Adam, focusing on keeping things normal at home for Kiran and Misha helped pull her through. She was in intense pain from the surgery and, like many placenta accreta survivors, she produced insufficient milk to breastfeed. Her sister and parents helped Seeff to care for her and for Milan, and the boys’ cousins were on hand to play with Kiran and Misha. “We kept it light,” Adam says. “We have video footage of them blow-drying my hair while I was resting on the couch. They understood that something was wrong, but we made it seem as if ‘After the baby comes, the mother has to lie down all the time.’ We didn’t want to scare them.”
Today, Adam and Seeff are taking joy in watching their three sons grow and develop distinct personalities. Kiran is a fan of the sciences and enjoys building things; Misha is the family comic. And little Milan, now 3, loves sports. “He’ll run after anything that looks like a ball,” as Seeff puts it. “The most rewarding thing about seeing them grow up is how well they interact with each other, seeing the creation of a family.”
Now, looking back, Adam says, “I tell my kids there are ‘big bads’ and ‘little bads.’ The ‘big bads’ are things you never completely recover from. We’ve had one big scare in our family history and come through that without lasting scars. I put that in the category of ‘little bads.’” And the harrowing experience has given her a new appreciation for life. “I feel that I need to find a way to make every day meaningful,” she says. “These days were given to me for a reason. It’s my job to find ways to use them well.”
Explore the amazing placenta in three dimensions. In our interactive simulation, you’ll observe and control the development of the placenta, and see what can go wrong. You’ll also experience a new form of digital storytelling: Producer David Sarno built this “journey through the placenta” using the tools of modern video game design.