Boonshoft researcher Thomas L. Brown is making strides in preeclampsia research.
Here in the Neonatal Intensive Care Unit of a Dayton hospital, tiny Jaxon John Baldasare struggles in his Isolette ® , a modern-day incubator. A ventilator does the work of his underdeveloped lungs, a feeding tube delivers nutrition, and various monitors track his vital signs.
His mother, Tiffany Baldasare, looks on with a mixture of love and anguish.
“I just want to walk him out of here, take him home and snuggle him, but you can’t do that,” said Tiffany, who visits Jaxon daily when she’s not working full time at another hospital nearby, raising two other children with husband Andy, and commuting back and forth to their home in Troy, some 20 miles north of Dayton.
It’s late July and Jaxon shouldn’t be here, not yet anyway, but his life depended on it. So did his mother’s. Just 26 weeks into her pregnancy (and with 14 to go), Tiffany developed preeclampsia, a life-threatening condition marked by a rapid rise in blood pressure and high levels of protein in the mother’s urine, symptoms that can lead to seizure, stroke, multiple organ failure, and, in the worst of cases, death of the mother and/or baby. Triggering the crisis was Tiffany’s defective placenta, the nutrition pipeline that joins mothers to their developing babies.
There’s no way to stop preeclampsia but to deliver the baby. So on June 6 Tiffany’s doctor delivered Jaxon via cesarean section. Born at 6:30 p.m., the third son of Tiffany and Andy Baldasare weighed 1 pound 13 ounces and stretched 13.5 inches head to toe.
“I really didn’t think he was going to make it,” reflected Tiffany, still carrying a hint of uncertainty in her voice.
It’s scenes like this one that drive Wright State’s Thomas L. Brown, Ph.D., and his research team to work long hours in his laboratory in the Medical Sciences Building. Brown, a professor and vice chair for research in the Department of Neuroscience, Cell Biology, and Physiology, has dedicated the bulk of his career to the study of embryonic development and prevention of pregnancy-associated disorders that lead to premature birth.
What is preeclampsia?
Preeclampsia (pre-e-CLAMP-si-a) is a condition unique to human pregnancy. It is diagnosed by the elevation of the expectant mother’s blood pressure, usually after the 20th week of pregnancy, combined with the appearance of excessive protein in her urine. Important symptoms include headaches, abdominal pain, visual disturbances, shortness of breath or burning behind the sternum, nausea and vomiting, confusion, and a heightened state of anxiety. Preeclampsia and related hypertensive disorders of pregnancy impact 5-8 percent of all births in the United States.
Who gets preeclampsia?
The most significant risk factors include:
- Previous history of preeclampsia
- Multiple gestation (i.e., pregnant with more than one baby)
- History of chronic high blood pressure, diabetes, kidney disease, or organ transplant
- First pregnancy
- Obesity, particularly with body mass index (BMI) of 30 or greater
- Over 40 or under 18 years of age
- Family history of preeclampsia
- Polycystic ovarian syndrome
- Lupus or other autoimmune disor - ders, including rheumatoid arthritis, sarcoidosis, and multiple sclerosis
- In-vitro fertilization
- Sickle cell disease
Source: Preeclampsia Foundation (preeclampsia.org)
In 2011, the promise and quality of his research garnered Brown a five-year grant of more than $1.5 million to investigate the underlying factors that cause preeclampsia, a disease that strikes five to eight out of every 100 births in the United States. The grant was funded by the Eunice Kennedy Shriver National Institutes of Child Health and Human Development, a division of the National Institutes of Health.
Two years later, Brown said the grant is paying off.
“Many pregnancy-associated disorders, including preeclampsia, stem from abnormal placental development,” he said. “We’ve identified a protein that plays a crucial role in placental stem cell development, and when that protein is altered and not working properly, the placenta doesn’t develop as it should.”
Brown said the protein, called “hypoxia inducible factor-1 alpha,” or HIF-1a, is an oxygen sensor that regulates trophoblast differentiation and maturation, the process in which early placental cells become more specialized in form and function. He explained that in a normal, healthy pregnancy, HIF-1a is active for most of the first trimester, when oxygen levels surrounding the developing embryo are very low. But as the embryo grows and moves closer to the mother’s blood supply, oxygen levels rise, and the protein becomes inactivated, allowing the placenta to develop properly. In preeclamptic pregnancies, however, something goes wrong with HIF-1a and it stays “on” for too long, throwing a wrench into what should otherwise be an orderly, precise process where timing is everything.
“If you blow through the red light, some bad things can happen,” said Brown, who injected a modified HIF-1a gene into pregnant mice for his study. “We believe the prolonged presence of the HIF-1a protein prevents maternal arteries in the placenta from being remodeled. This prevents the placenta from maturing at the right time and decreases blood flow to the baby. Sensing the baby isn’t getting enough oxygen, the mother’s body responds by cranking up its blood pressure, and that can cascade into a bunch of problems for mother and baby both.”
Those troubles almost always involve a preterm birth, and when that birth is especially early, such as Jaxon’s, the baby and family are in for a long slog in a neonatal intensive care unit, if the baby survives. Even after that, Brown noted, research shows the baby could face an increased risk for hypertension, cardiovascular disease, diabetes, and stroke later in life. He added that recent research further suggests the mothers, too, are at an increased risk of stroke later in life, even though their high blood pressure quickly resolves after delivery.
In 2007, the Preeclampsia Foundation estimated the combined short- and long-term financial costs related to preeclampsia and related pregnancy disorders at approximately $7 billion per year in the United States alone. Globally, preeclampsia and other hypertensive disorders of pregnancy are a leading cause of maternal and infant illness and death. By conservative estimates, these disorders are responsible for 76,000 maternal and 500,000 infant deaths each year.
Brown said HIF-1a probably isn’t a factor in all cases of preeclampsia — like cancer and other diseases, there could be many causes. He said he and his team now are studying what causes HIF-1a to misbehave in the first place. Finding answers could help scientists identify new tools and therapies for early diagnosis and treatment. “Every day we don’t get closer is another day babies, moms, and entire families are going to suffer from this devastating disorder,” Brown said from his office. “I think about that every day I walk in here, ‘Are we one step closer? What can we do today to be one step closer tomorrow?’ That’s what motivates us to work as hard as we do around here.”
At press time for this publication, Jaxon Baldasare remained in intensive care, though now at Dayton Children’s Hospital, with “severe chronic lung disease,” according to his mother. “We still have a long road ahead of us, but he will eventually come home,” she said. VS
For information on how you can help support research in pregnancy associated disorders at Wright State, visit the website www.wright.edu/give/pregnancyassociateddisorders or contact Dr. Brown via email at thomas.L.firstname.lastname@example.org