Treatment at the USF Health Center builds on leading translational research by Dr. Lockwood’s laboratory team
By Saundra Amrhein
The photographs arrive year after year: cherubic-faced babies, teetering toddlers, precocious kindergartners.
They are reminders to two USF Health doctors of the ultimate outcomes of years of research and struggles that often play out in their offices, the joyful results balanced against quiet frustration and painful loss.
Now, USF Health is announcing a major new initiative through which those doctors and a team of researchers hope to make a dent in the years of futile and heartbreaking attempts of expectant mothers to carry their pregnancy to full term – a hope to ensure that more efforts by area couples end in healthy childbirth.
Last month, USF Health launched The Pregnancy Loss Prevention Center — a clinic lodged at the USF Health South Tampa Center for Advanced Healthcare on the campus of Tampa General Hospital on Davis Islands.
Dr. Charles Lockwood and Dr. Stephanie Romero practice at the new Pregancy Loss Prevention Center, which is housed at the USF Health South Tampa Center for Advanced Healthcare.
At the helm is Dr. Charles Lockwood – the new dean of the USF Morsani School of Medicine and senior vice president for USF Health. His internationally renowned and award-winning research has long focused on preventing premature births, stillbirth, miscarriage and maternal thrombosis. While dean of Ohio State University’s College of Medicine, his institution was one of three Ohio universities and affiliated hospitals to receive a total of $10 million from the March of Dimes to fund the study and prevention of prematurity – which is the leading cause of infant death, blindness, mental disabilities and lung disorders in children.
At USF, he will run the new clinic with Dr. Stephanie Romero, a USF Health obstetrician and gynecologist and an assistant professor of obstetrics and gynecology and maternal fetal medicine. Dr. Romero, also an award-winning researcher, likewise has spent years studying factors – including genetic causes – that lead to pregnancy loss and premature birth.
The multi-disciplinary clinic – which will work with other USF departments and divisions, including genetics, and reproductive endocrinology – will first and foremost seek to give patients a clear and early understanding of what is happening to them so they can better chart a path through treatment or other options, like seeking an egg donor, that are realistic with their circumstances. In doing so, the doctors hope to offer extra office time and individualized care to cut through the uncertainty, anxiety and trauma that so many mothers, couples and families face, sometimes enduring multiple miscarriages and not knowing why or what to do.
“Time is a great resource we can provide, which a busy doctor in daily practice with thirty or forty patients a day can’t do,” says Dr. Lockwood, whose research team – among other accomplishments – has been credited with the development of “fetal fibronectin,” the first biochemical predictor of prematurity.
“That’s the most important ingredient we bring to the table,” he adds. “And also it brings a lot of psychological support, so they know what’s going on. That can have a magical effect on their ability to continue to pursue pregnancy.”
THE CENTER
Dr. Romero walked through the hushed and peaceful hallways of the maternal-fetal division on the fourth floor of the USF South Tampa Center, past examination and ultrasound rooms, stopping to greet and hug a staff member.
It is here where the Pregnancy Loss Prevention Center is based, initially starting out on two Monday mornings a month with plans to eventually expand to once a week as the center’s patient base grows, Dr. Romero said.
Likely to be referred here by physicians, gynecologists, infertility specialists or other medical personnel, patients will have experienced multiple miscarriages, stillbirths or premature births or the risk factors leading to them – from preeclampsia, diabetes and lupus to inflammation and infection.
While studies have shown that 50 percent of all fertile women trying to conceive suffer a miscarriage, about 10 percent of women suffer repeat miscarriages, a rate that increases with age, Dr. Romero said.
The clinic will run examinations on patients – and their partners, if necessary – and conduct laboratory tests to help determine problems or pre-dispositions for troubled pregnancies, she said.
Echoing Dr. Lockwood’s sentiments, Dr. Romero stressed one of the most important factors of the new clinic: quick communication. Patients will not only receive in-depth care, but they will have access to her personal email.
“You really want to get back to them as fast as possible,” she said, adding that the patient’s anxieties as well as physical symptoms need to be addressed right away. “Timeliness is such a big deal, especially at the beginning of pregnancy.”
High levels of anxiety dominate the conversations, she added, and run the risk of further impacting the mother and fetus’ health, as well as determining the patients’ willingness to even attempt another pregnancy.
“You are helping someone through a grieving process,” she said. “I’ve definitely had patients, more than one, say that if it happens again, I can’t go through this again.”
TREATMENT AND SUPPORT
The patients’ trauma from previous losses matched with years of searching in the dark with big unknowns and uncertain outcomes make it essential for the doctors to spend a lot of time with the expectant mothers.
“Some folks don’t even realize it’s a disease entity,” Dr. Romero said. Other times, patients endure multiple miscarriages not knowing they were due to uterine abnormalities, something the center could diagnose and get fixed right away.
“That’s something so easy to correct with surgery. Otherwise you would have no clue,” she said.
Depending on the patients’ conditions and causes for past losses, Dr. Lockwood added, approaches aside from surgery could include everything from heparin and aspirin therapy, to treatment of the immune system, hormone treatments, weight loss and bed rest. A team of researchers working with Dr. Lockwood in laboratories on the USF Tampa campus will be on hand for further investigation of maternal as well as fetal tissue following a miscarriage.
“What we’d like to be able to do is offer detailed genetic analysis, if that’s the explanation,” Dr. Lockwood said. “Or an evaluation for immunology abnormalities, if that’s the explanation.”
For instance, before the 10-week gestation point, most pregnancy losses are due to genetic factors, Dr. Lockwood says. That could include extra copies or deletions of chromosomes passed on to the embryo. The most common feature of such cases is advanced maternal reproductive age. Often such loses are a harbinger of the premature start of menopause – which is, in turn, most influenced by when her mother started menopause. The older her mother was before starting menopause, the longer the patient could likely go before showing higher rates of abnormal chromosomes and miscarriage. On average, if her mother started menopause at the age of 52, the patient could start showing higher chromosome abnormalities by age 35, and by age 40 a miscarriage rate of 50 percent, according to Dr. Lockwood. “However, if her mother was menopausal at 42, increased miscarriage rates may occur at age 30.”
“So it does vary significantly from a biological standpoint,” he added.
Another cause of genetic abnormality is when both parents carry a gene that is lethal to the developing embryo, Dr. Lockwood said.
Between 10 weeks and 20 weeks of gestation, genetic abnormalities are less frequently the cause for miscarriages, and other issues become more prevalent, such as Antiphospholipid antibody syndrome, lupus or other auto-antibody diseases and immunological disorders, he said.
After 20 weeks and before 32 weeks, inherited abnormalities in the cardiac conduction system can result in stillbirths. However, in this timeframe, the most common cause for stillbirths and premature delivery is inflammation and infection, something that can be diagnosed and addressed, Dr. Lockwood said. Other factors include hemorrhaging and stress on the fetus – including when there are twins and triplets.
With a clear diagnosis, he said, the patients can gain a sense of control and make an informed plan about the next step – whether that is with a positive prognosis for another pregnancy attempt or the practical necessity to try something else, such as IVF or an egg donor.
“They get closure,” Dr. Lockwood said. “It may not be good news, but it does provide closure and then helps them make some decisions.”
THE RESEARCH
Last spring when Dr. Lockwood left Ohio State University, where he was dean of the College of Medicine, to take over as dean of USF’s Morsani School of Medicine, he did not come alone. Joining him were three other researchers from his lab, including Dr. Frederick Schatz, who has worked with Dr. Lockwood for 35 years – from New York University to Yale University and then Ohio.
The new Pregnancy Loss Prevention Center at USF is modeled on similar practices Dr. Lockwood has run with his associates at NYU, and Yale and will build on his team’s laboratory research, much of which has been funded by grants from the National Institutes of Health and the March of Dimes Foundation.
A federally-funded Ob-Gyn translational research team working with Dr. Lockwood in laboratories on the USF Tampa campus complements the treatment provided to patients who have experienced multiple miscarriages, stillbirths or premature births or the risk factors leading to them. L to R: Ozlem Guzeloglu-Kayisli, PhD, assistant professor; Frederick Schatz, PhD, professor; Nihan Semerci, biological scientist; and Umit A. Kayisli, PhD, associate professor.
Dr. Schatz and his fellow researchers – Umit Kayisli and Ozlem Guzeloglu-Kayisli – called what they do “translational science” – the goal of taking their discoveries in the laboratory to the clinical level to treat patients.
Ultimately, Dr. Schatz said, their successes in preventing stillbirth and premature births will have a ripple effect that extends out from the immediate families to the entire medical industry and society.
“Statistically it’s a very serious problem,” Dr. Schatz said of prematurity and the disorders and millions of dollars in care it leads to over the course of a lifetime. “It creates a tremendous burden on the health care industry and society.”
In addition to being credited with discovering fetal fibronectin, Dr. Lockwood and his research team have more recently focused on such crucial conditions as preeclampsia – a disease marked by high blood pressure and abnormal protein levels in the urine. Preeclampsia affects between 6 percent and 8 percent of pregnancies in the United States. It is also a major indicator for premature birth, a leading cause of prenatal death and is responsible for 8 percent of maternal deaths, according to a research article by Dr. Lockwood and fellow researchers published in the American Journal of Pathology in September 2013.
Dr. Shatz holds a slide with sections of human placenta immunostained for the presence of the progesterone receptor, which may be related to preterm birth.
A major finding recorded in the research article identifies and describes a specific factor called IP-10 that was found at elevated levels in fluids of first-trimester women. The article calls it a new and “robust” early predictor of preeclampsia – a crucial discovery to help doctors confront a disease that becomes very dangerous in later stages of pregnancy or if left untreated.
Another important area of study for the researchers funded by the March of Dimes has centered on the mechanisms by which progesterone receptor levels suddenly drop during pregnancy, inducing a premature birth. The research has zeroed in on the correlation or role in these cases of spiking levels of thrombin – the enzyme that facilitates the clotting of blood – and interleukin-1beta, a hormone involved in inflammation.
And most recently, in promising research for which the team has applied to NIH for funding, the group is working with an Ohio State University researcher who has isolated a probiotic in laboratory cultures. The probiotic, incubated with maternal cells, leaves healthy bacteria alone while inhibiting bad bacterial growth. The hope is that the probiotic might one day be able to block in pregnant women the onset of infection and inflammation – the leading causes of premature deliveries between the second and third trimesters.
The probiotic is being used or taken in Europe, but it has not yet been tested on pregnant women, Umit Kayisli said.
While Dr. Lockwood is immersed in all these examples of cutting edge laboratory research, he said he also has drawers full of photographs, cards and letters from happy families that remind him of what is at stake.
“When you do have a healthy baby,” Dr. Lockwood said, “there’s nothing better than that.”
For more information on the Pregnancy Loss Prevention Center or to schedule an appointment, please call (813) 259-8500.
Photos by Eric Younghans, USF Health Communications
