Dr. Rebecca Baergen has devoted her career to placental pathology

About five years ago, an abnormally small placenta arrived in the surgical pathology laboratory at NewYork-Presbyterian/Weill Cornell Medical Center. A patient had suffered a miscarriage well into her second trimester, and she craved an explanation for what had gone wrong. Because the placenta controls life inside the womb — providing nutrients to the growing fetus and acting as its lungs, kidneys and immune system — many issues can be traced back to it after birth. Dr. Rebecca Baergen, chief of obstetric and perinatal pathology, was asked to see if it offered any clues.

Because the fetus had short limbs, doctors had earlier suspected skeletal dysplasia, a type of genetic dwarfism, but X-rays and other analyses had disproved this hypothesis. When Dr. Baergen inspected the placenta — which is ideally soft, spongy and beefy red — she noticed a severe loss of blood supply. This had caused some of the placenta's cells and tissue to die and indicated that the fetus hadn't received enough nutrients and oxygen.

While the placenta's appearance suggested preeclampsia, a serious pregnancy complication characterized by high blood pressure, it was ruled out because the mother had no history of the condition. So Dr. Baergen, a professor of pathology and laboratory medicine, recommended that the woman's doctors check her for autoimmune diseases and blood disorders — and they found that she had Protein S deficiency, a genetic condition that causes over-clotting. In the placenta, this meant that the blood vessels were abnormal, which impeded the transfer of blood and nutrients to the fetus and kept it from growing properly. Doctors treated the mother with a blood thinner, and she went on to have two healthy children. "Most pathologists don't get to talk to patients, but I work with a lot of mothers," says Dr. Baergen, author of the "Pathology of the Human Placenta," the preeminent clinical text on the subject. "It makes a big impression on me when I'm able to help somebody in that way."

Dr. Baergen is one of only a hundred or so pathologists across the country who focus on the placenta, a complex, temporary organ that develops early in pregnancy and is expelled immediately after birth. As recently as five years ago, it was thrown away post-delivery without a second thought. But in her decades-long work, Dr. Baergen has seen the organ gain importance and significance. Today, every placenta that's delivered at NewYork-Presbyterian/Weill Cornell is stored in a labor and delivery unit refrigerator for one week. This procedure, which Dr. Baergen implemented soon after arriving 18 years ago, ensures that any pregnancy-, birth- or newborn-related issue can be properly investigated. Information uncovered from that research has meant improvements to maternal and neonatal care. And on a larger scale, thanks to the new $41.5 million National Institutes of Health-supported Human Placenta Project, scientists are now studying the organ in a major way. "The placenta is the chronicle of intrauterine life, and it can tell you so much," Dr. Baergen says. "It can be the problem, it can reflect the problem — or even if it's normal, it can help doctors rule things out. It's really important."

About six or seven days after fertilization, the placenta starts forming when the hundred or so cells that form the pre-embryonic mass, called a blastocyst, start differentiating. At that time, the outer layer of cells (called trophoblasts) invades the uterine wall and by day nine develop a primitive support network of vessels, which ultimately becomes the placenta.

Microscopic analysis: Evidence of maternal vascular disease (above). Right: Overly small chorionic villi, the functional units of the placenta. Photo credit: Dr. Rebecca Baergen

As the blastocyst grows and becomes an embryo, then a fetus, the placenta grows too. By the end of the first trimester, a seamless exchange of nutrients and oxygen takes place between mother and child. Deoxygenated blood is pumped from the fetus through two umbilical arteries to the placenta; there, the arteries subdivide and burrow deep within it, where they continue to spread and multiply — "like branches on an upside-down tree," Dr. Baergen says. Eventually, they become tiny capillaries, which feed into the functional units of the placenta, called chorionic villi. The villi control the nutrient, fluid and oxygen exchange, which takes place between fetal blood from the capillaries and maternal blood being pumped into the placenta from underneath it. This process happens naturally throughout pregnancy; after delivery, contractions force the placenta, which weighs about a pound, to detach from the uterine wall to be delivered as well. "But there are a million things that can go wrong," Dr. Baergen says, and if they do, the health of the fetus and the mother are at stake.

Dr. Baergen came to Weill Cornell Medicine in 1997 from the University of California, San Diego, where she worked with her mentor, Dr. Kurt Benirschke, known as the father of placental pathology. At NewYork-Presbyterian/Weill Cornell, she sees the placentas of every patient who has experienced complications during pregnancy or delivery, or whose babies had problems immediately after birth. Through her work, she has uncovered genetic disorders, infections, and a host of other conditions that impede the transfer of nutrients within the organ. She also studies physical problems that can cause fetal death, including cords that are too long, twisted restricted, or inserted into the wrong part of the placenta. Some of these are just random flukes; others, like clotting issues, can be better managed in future pregnancies once discovered; still others are of unknown origin and require further study before they can impact clinical decisions. "Because this discipline is relatively new, there are still so many basic aspects of the placenta to study," Dr. Baergen says. "It's an amazing organ."

—Anne Machalinski

This story first appeared in Weill Cornell Medicine, Vol. 15, No.1.

Dr. Sing Sing Way's Research on How Mother's Immune Cells Respond to Infection During Pregnancy Unveils New Strategies for Protection Against Stillbirth, Preeclampsia and Premature Birth

NEW YORK, NY (March 17, 2016) — Dr. Sing Sing Way, the Pauline and Lawson Reed Chair in Infectious Disease at Cincinnati Children's Hospital and an associate professor of pediatrics at the University of Cincinnati College of Medicine, has been awarded the inaugural Gale and Ira Drukier Prize in Children's Health Research, Weill Cornell Medicine announced today.

The Drukier Prize honors an early-career pediatrician whose research has made important contributions towards improving the health of children and adolescents. Dr. Way was recognized for his groundbreaking research on how a woman's immune system naturally tolerates the developing fetus and placenta during pregnancy, preventing rejection of these genetically foreign tissues. Many pregnancy complications — including stillbirth, prematurity and preeclampsia — are associated with disruptions in fetal tolerance, and children born following these pregnancy complications are highly susceptible to infection, breathing disorders, deafness and blindness, along with learning and behavior disabilities. With a better understanding of immune cells that maintain healthy pregnancy, doctors may be able to provide more effective therapies against these complications to improve the health of infants and children.

Dr. Way formally accepted the award, which carries a $10,000 unrestricted honorarium, and delivered a public lecture on March 16 about reinforcing maternal immune tolerance during pregnancy.

"We are thrilled to honor Dr. Way with this inaugural award, and to formally recognize the quality of his vital work and his dedication to improving children's health," said Dr. Gale Drukier and Weill Cornell Medicine Overseer Ira Drukier, who together established the prize. "Dr. Way exemplifies just why we created this prize: We could not think of a more deserving individual, or someone who is a greater exemplar for the importance of pediatric research."

The Gale and Ira Drukier Prize in Children's Health Research was established as part of a $25 million gift to Weill Cornell Medicine in December 2014, which also created the Gale and Ira Drukier Institute for Children's Health. As part of its mission, this premier, cross-disciplinary institute, dedicated to understanding the causes of diseases that are devastating to children, will award this prize annually.

"An accomplished physician-scientist and leader, Dr. Way is deeply committed to driving advances in pediatric research and patient care," said Dr. Laurie H. Glimcher, the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine. "His groundbreaking basic and translational research has the power to profoundly improve the health of each and every pregnancy — and generations of children along with it. Weill Cornell Medicine is delighted to honor Dr. Way with the inaugural Gale and Ira Drukier Prize in Children's Health Research."

"There is still so much we don't know about how the maternal immune system functions during pregnancy, and what role it plays in devastating outcomes like early-term miscarriage, spontaneous abortion, stillbirth and infant mortality," said Dr. Gerald Loughlin, the Nancy C. Paduano Professor and chairman of Weill Cornell Medicine's Department of Pediatrics. "Dr. Way is dedicated to answering these fundamental scientific questions and investigating how researchers can bolster women's immune systems to ensure that they and their children are healthy. For that reason, he is an ideal awardee."

"I have enormous gratitude toward the Drukier family for creating this recognition, and toward Weill Cornell Medicine and the Department of Pediatrics for using this award to put pediatric research in the national spotlight," Dr. Way said. "Reproductive immunology and prenatal infection are specialized research areas, and I am excited for this award to draw more attention to these understudied clinical problems that carry profound medical and emotional repercussions for families."

Dr. Way has shown that expanded immunological tolerance during pregnancy weakens a woman's ability to fend off infection-causing microbes. Once infection takes hold in women during pregnancy, the maternal immune cells' tolerance of the developing fetus, which bears genetically foreign tissues, is overturned, causing a rejection-like reaction.

Dr. Sing Sing Way. Photo credit: Stephanie Diani

"If the root cause of pregnancy complications stems from maternal immune cells unintentionally attacking the baby, immune-based therapies may be the key to help mothers better tolerate their pregnancies," said Dr. Way, who published a series of papers on these findings in Cell, Nature and The Journal of Clinical Investigation. This might involve somewhat counterintuitively weakening the responsiveness of maternal immune components, he continued, so that they do not reject the baby.

"Another interesting idea is developing vaccines that reinforce fetal tolerance. While most vaccines work by priming the immune system to become activated, this vaccine would tell the immune system to be more tolerant," he said.

Dr. Way also discovered why newborn infants in the first weeks after their birth are more susceptible to infection. His research showed that immune cells in newborn babies are actively suppressed. These findings, published in Nature, profoundly change the conceptual framework for how scientists view newborns' susceptibility to infection, which may lead to improved strategies for preventing infection when children are most vulnerable.

"Children are most susceptible in the first month after birth, and in fact, more than 40 percent of childhood deaths occur in this critical developmental window," Dr. Way said. Some of these infants are born too early and their medical issues are a direct reflection of pregnancy complications, while others acquire life-threatening illness soon after birth. "By better understanding how maternal and neonatal immune cells are uniquely regulated during pregnancy and the early postnatal period, we hope to develop more effective therapies for reducing infant mortality and improving the health of surviving children."

Dr. Way received both his medical degree and a doctorate in microbiology and immunology from the Albert Einstein College of Medicine in the Bronx. He completed his residency in pediatrics at the University of California, San Francisco, a fellowship in infectious disease at the Children's Hospital and Regional Medical Center in Seattle, and post-doctorate research training at the University of Washington. He is outspoken about the need for pediatricians to develop research careers to optimally address the clinical problems unique to infants and children.

"Many times, parents will ask me why their child got sick, and what can be done to prevent their child from getting sick again," Dr. Way said. "While the answers pediatricians provide in response to these practical, real-life questions are often disguised in medical jargon and complex laboratory testing, the root cause in most cases remains undefined."

"Physicians like me who struggle to find acceptable ways to say ‘I don't know,' to sick children and their parents have an enormous motivation to perform research, so that one day, we can eliminate the need for these questions to be asked in the first place," he continued. "Caring for sick children day in and day out should drive us to find ways to make things better. After all, our future is in the hands of today's children, and accordingly, there is nothing more important than their health and wellbeing."

Weill Cornell Medicine

Weill Cornell Medicine is committed to excellence in patient care, scientific discovery and the education of future physicians in New York City and around the world. The doctors and scientists of Weill Cornell Medicine — faculty from Weill Cornell Medical College, Weill Cornell Graduate School of Medical Sciences, and Weill Cornell Physician Organization — are engaged in world-class clinical care and cutting-edge research that connect patients to the latest treatment innovations and prevention strategies. Located in the heart of the Upper East Side's scientific corridor, Weill Cornell Medicine's powerful network of collaborators extends to its parent university Cornell University; to Qatar, where Weill Cornell Medicine-Qatar offers a Cornell University medical degree; and to programs in Tanzania, Haiti, Brazil, Austria and Turkey. Weill Cornell Medicine faculty provide comprehensive patient care at NewYork-Presbyterian/Weill Cornell Medical Center, NewYork-Presbyterian/Lower Manhattan Hospital and NewYork-Presbyterian/Queens. Weill Cornell Medicine is also affiliated with Houston Methodist. For more information, visit weill.cornell.edu.

Physiatrist Dr. Jaclyn Bonder specializes in the rare field of rehab for women with pelvic floor disorders and other ob/gyn-related issues

By Beth Saulnier

Portraits by John Abbott

Carter Bisso was about 20 weeks pregnant when the pain started — an ache on the right side of her lower back, between her hip and spine. It got worse and worse, to the point where she couldn't sleep at all. "I would lay down and the pain was absolutely agonizing," recalls Bisso, a marketing professional who lives in the West Village. "When you're in that much pain, the nights are endless. Sitting also hurt, so I would stand and kind of sway at the kitchen counter and try to stay awake. I was almost delirious."

An assistant professor, Dr. Bonder is one of just a dozen physicians nationwide who specialize in women's health rehabilitation with a pelvic floor and ob/gyn focus. She treats numerous pregnant and postpartum patients with musculoskeletal problems, as well as those with other conditions related to pelvic floor muscle dysfunction and weakness including chronic pelvic pain, urinary and bowel issues, pain following gynecologic surgery, pain during intercourse, and pain in the lower back, groin, abdomen and hips. Zeroing in on diseases and conditions using specialized exam techniques as well as conventional diagnostic methods, she treats patients using a wide range of modalities including physical therapy, oral medications, injections of pain drugs, hormone therapy, and topical medications.Bisso's ob/gyn said she could try an over-the-counter sleep aid, but it didn't help; neither did a visit to a pain-management specialist. When she went for an ultrasound at 31 weeks, she recalls, "the tech was trying to be supportive, and he said, 'Only nine weeks to go,' and I burst into tears. When you're in that kind of pain, any amount of time is too long." Finally, she called her ob/gyn's practice again to ask for a referral to a physical therapist. But one of the nurses had a different suggestion, someone she'd seen during her own pregnancy: Dr. Jaclyn Bonder, medical director of women's health rehabilitation in the Division of Rehabilitation Medicine at Weill Cornell Medicine and the Department of Physical Medicine and Rehabilitation at NewYork-Presbyterian/Weill Cornell Medical Center.

Happy ending: Carter Bisso with her son, Cal.

"When I went to her, it was remarkable," Bisso recalls. "I told her roughly where the pain was, and she pointed to a spot on my back and asked, 'Is it right here?' — and it was the dead-on spot that was hurting." Dr. Bonder had Bisso lie down and raise each leg; the right one was harder to lift. "Then she leaned over and squeezed in on my hips and told me to lift my right leg again," Bisso says. "And it was almost as if it was air, it lifted so easily."

It turned out that Bisso's problem was primarily related to the sacroiliac joint, a pelvic joint in her buttock. Dr. Bonder explained the importance of wearing a pregnancy support garment commonly known as a "belly band" — which, despite its name, is more about reinforcing the joints of the pelvis as they loosen and the muscles stretch in preparation for birth. She also cautioned her against exercises that stretch and open the hips, which Bisso had been doing avidly in the mistaken belief that they might help, and offered advice for modifying her prenatal yoga routine. "Seeing her, that one visit, my life turned around," Bisso says. "I was so scared about my pregnancy, not being able to sleep. I didn't know how I was going to make it through to my delivery date, living in that kind of pain. One visit made such a difference, and now I've told all my pregnant friends about her. She was so patient and attentive and professional. It really was a wonderful experience."

Bisso — who gave birth to a healthy baby boy, Cal, in June — is just one of many patients who credit Dr. Bonder with helping them overcome pain and restore their physical function. For Dr. Bonder, who contemplated a career in physical therapy before applying to medical school, such outcomes are immensely satisfying. "When patients come to me, they've often lost hope," she says. "I find it really gratifying to keep digging, to think outside the box to try to figure it out. I put myself in their shoes and think how upset and miserable I'd be if I couldn't sit on the floor to play with my son or lift him out of the bath. Like any doctor, it feels great to make a patient feel better — to help give them back parts of their lives."

Dr. Bonder's path to her unusual specialty began with a postcard. During her residency in rehab medicine (also known as physiatry) at NYU, she got notice of a continuing medical education course at the Rehabilitation Institute of Chicago on rehab for women with pain and other musculoskeletal issues related to pregnancy and birth. Since she'd loved her ob/gyn clerkship during medical school and had a strong interest in women's health, it felt perfect for her — and her residency director agreed. In Chicago, she learned to perform a specialized procedure known as a musculoskeletal pelvic floor exam, an internal and external exam in which the physician assesses the status of the pelvic floor — the muscular base of the abdomen, attached to the pelvis — and related joints, muscles and nerves. Although it takes just 10 minutes or so, the exam is not routinely taught in medical school or post-graduate training.

'So relieved': Dr. Jaclyn Bonder with patient Julia Buldo-Licciardi

After doing additional training in Chicago during her residency, Dr. Bonder became one of the only physiatrists in New York who address conditions related to pelvic floor pain and dysfunction. She now gets referrals to treat patients, including men, with a wide range of symptoms and conditions. "She's a very caring physician and a wonderful colleague to work with," says Dr. Bilal Chughtai, an assistant professor of urology who specializes in treating women. "These are difficult cases in general, because these patients are often silent sufferers who've had their conditions for a long time. You've got to be very good at speaking to them and bringing it to the surface, because a lot of times they won't really talk to you about it. So it's important that you make patients comfortable."

One patient who struggled for years was Julia Buldo-Licciardi, a 26-year-old instructor who teaches undergrads at NYU. Years ago, when she was a ballet dancer, she tore a muscle in her hip — and that injury may or may not have contributed to a constellation of symptoms that started plaguing her three years ago including constipation, abdominal numbness, and vaginal pain.

Since all of Buldo-Licciardi's test results were unremarkable, she says, "everybody kept telling me I was fine," and she eventually sought mental health treatment on the assumption that the symptoms must be related to stress following the death of a close relative. "When I got Dr. Bonder's name, I was so relieved," says Buldo- Licciardi, who was referred by Dr. Orli Etingin, the Lisa and Sanford B. Ehrenkranz Professor in Women's Health and medical director of the Iris Cantor Women's Health Center. "When I got to her office, I felt like I was finally being taken care of. She actually knew what I was talking about, and she was completely in tune with all my symptoms. It wasn't like it was foreign dialogue to her."

Dr. Bonder and Buldo-Licciardi, herself an aspiring physician

Dr. Bonder prescribed a course of physical therapy — a combination of at-home exercises and sessions with a specialist in pelvic floor rehab — and the results have been excellent. Buldo-Licciardi's pain and numbness have abated and her gastrointestinal function is now normal. "I'm gaining more sensation in my abdomen and we're releasing the vaginal muscles in the pelvic floor, and that's alleviating a lot of the pain, so it's been incredible," she says. "I feel very lucky."

In the future, more patients may not need to count on luck to feel better. Dr. Bonder and a colleague at Columbia are surveying ob/gyn residents throughout the New York metro area on their knowledge of lower back and pelvic pain during pregnancy and after delivery, including their thoughts on when and how they'd offer treatment. The ultimate goal is to devise educational tools to make clinicians more aware of such conditions and their possible remedies. "Most obstetricians are not trained in what to do with these patients, because the symptoms are muscle and joint related, not necessarily gynecologic," Dr. Bonder says. "The natural inclination is to tell them, 'You've just delivered a baby, you've got some pain, it's normal, it's going to get better, just give it some time.' But that's not always the case. If you take 10 patients, it's probably true that most of them are going to get better — but if you don't do anything, the others may not, and may get worse. And the earlier you treat them, the likelier they are to get better."

Bisso improved so much from following Dr. Bonder's advice that she canceled a follow-up appointment. But she went back to see her about three months after giving birth, when she started to feel pain in the same area of her back. "I wanted to be preemptive," says Bisso, "and not wait until I couldn't sleep at night." It turned out to be just muscle strain, and the pain abated after Dr. Bonder suggested Advil and some stretching exercises. "I wish more women didn't just accept that we're supposed to suffer — and that there were more doctors like Dr. Bonder," Bisso says. "Especially in the third trimester, everyone says you're not going to sleep, you're counting down the days, you're almost expecting it to be rough. But in the end, that's not what it had to be for me."

This story first appeared in Weill Cornell Medicine, Vol. 14, No.3.

Dr. Steven Gabbe '69, the senior vice president for health sciences at Ohio State University and emeritus CEO of OSU Wexner Medical Center, has been awarded the Weill Cornell Medical College Alumni Association Award of Distinction.

Established in 1949, the annual accolade recognizes a Weill Cornell alum who has demonstrated outstanding achievement in research, education or patient care, and has brought acclaim to the medical college. Dr. Gabbe received the award at the Alumni Award of Distinction dinner on May 27.

"It was an incredibly meaningful surprise winning this award, especially when I think of all the Weill Cornell alums that I've known and worked with over the years who are so accomplished and have done so much," said Dr. Gabbe, who is also a professor of obstetrics and gynecology at Ohio State University.

Dr. Gabbe is one of the world's leading experts on the complications of diabetes and pregnancy. He has helped define the glucose treatment protocols for pregnant women with type 1 diabetes. He was also involved in an international study funded by the National Institutes of Health that led to new diagnostic criteria for gestational diabetes. The study was devoted to defining the criteria for fetal risk associated with maternal glucose levels and pregnancy.

Dr. Gabbe served on the faculty of six universities: the University of Southern California, University of Colorado, University of Pennsylvania and the University of Washington. He spent nine years as the chair of Ohio State University's Department of Obstetrics and Gynecology. He was also dean of the Vanderbilt University School of Medicine for seven years, and is currently a member of the Institute of Medicine and senior editor of Obstetrics: Normal and Problem Pregnancies, a leading obstetrics textbook.