The Dische Fund Progress
July 2001

The Dische Fund is named in honor M. Renate Dische, MD, Ph.D., who, for over 50 years, has contributed to the understanding of causes of perinatal and pediatric illness. Friends of Alison Ivy Hime have chosen to support this fund to honor the memory of a very little girl who died too young. With your generous support, this fund was established two years ago with the goal of sponsoring clinical and pathologic investigations into the causes of perinatal and fetal illness or death, and to foster the development of improved approaches to clinical diagnosis, patient monitoring and treatment.

We'd like to update you on our progress to date, progress that would not have been possible without your generosity.

The Dische fund has supported:

1. The presentation of eight research abstracts at national and international meetings.
2. Four summer research student fellows.
3. One obstetric residency research thesis.
4. The development of a randomized clinical trial for a novel treatment for uterine vascular dysfunction.
5. A joint venture with Hypertension Diagnostics, Inc., in the diagnosis of vascular dysfunction in women with complicated pregnancies.
6. Thanks in part to Dische Fund supported research, the research team of Dr. Carolyn Salafia received a five year grant from the National Institutes of Health to study the structure of maternal blood vessels in women delivering at the University of North Carolina.

Let's take each of these in greater detail:

1. At the 2000 Meeting of the International Federation of Placental Organizations in Rochester NY, Dr. Salafia and her colleagues presented the following research topics:

Salafia, CM.
"Infant mortality and cardiovascular disease."

Salafia CM, Moretti M, Starzyk K, Bagiella E.
"Ethics of a randomized double-blinded trial for recurrent miscarriages: "stopping rules" in clinical practice."

Odom L, Barker A, Cleveland J, Salafia CM.
"Systemic arterial dysfunction and subfertility/recurrent miscarriage: Preliminary report of a case-control study."

Research abstracts were also accepted for presentation at the Society for Maternal Fetal Medicine. Topics included:

Ghidini A, Salafia CM, Patane L.
"Sexual origin of placental dysfunction in severe prematurity."

Ghidini A, Salafia CM, Silberman L, Patane L.
"Preterm PROM and placental abruptio."

Ghidini A, Salafia CM, Patane L.
"Preterm preeclampsia with fetal growth restriction is a more severe disease than preterm preeclampsia alone."

Ghidini A, Salafia CM, Patane L.
"Uteroplacental insufficiency: Does the presence of associated villous lesions make a difference?"

Klugman S, Carter S, Espinosa B, Crane M, S Gross S, Salafia C.
"Elevation of maternal serum hCG in the HIV+ women - implications for prenatal screening and placental immunology."

2. Our first summer Dische Fund Student was Ms. Maria Frias. Under the Dische Fund grant, she was able to assist Dr. Bialines Espinosa of the Bronx Lebanon Hospital with his residency research thesis titled: "Elevation of maternal serum hCG in the HIV+ women - implications for prenatal screening and placental immunology." (see item 3, below).

Our current Dische Sponsored Trainees include:

* Deepti Nagaraya, a student at the University of Connecticut who will spend the summer collecting information on placental and infant growth in healthy and complicated pregnancies. Poor fetal growth has been linked to increased risk of cardiovascular disease and diabetes in adult life. This study will improve our understanding of the interaction between growth of the placenta (the fetus's sole source of nutrients and oxygen) and fetal growth, and how maternal health can influence the normal relationship.

* Caroline Benkowitz, a rising sophomore at the University of Connecticut School of Medicine, will use her summer stipend to study, under the direction of Dr. Donald Maier, Reproductive Endocrinologist at UCSM, and Dr. Salafia, the effect of non-diabetic insulin resistance on IVF success rates.

* Rahul Magavi, also a rising sophomore at UCMS, will work with Dr. Gerard J. Foye, Chief of Maternal Fetal Medicine at Danbury Hospital, and Dr. Salafia in a study of why some diabetic patients who are very carefully controlled during pregnancy still have very large babies. Too-large babies may have more complications during delivery and in the newborn nursery. Dr. Foye says, "Clinically, we don't seem to be able to tell which patients will have problem-babies until after it is too late for us to treat them. This study will hopefully shed light on how we can better take care of the increasing number of women with diabetes who are having babies."

3. Dr. Bialines Espinosa of the Bronx Lebanon Hospital completed his residency research thesis titled: "Elevation of maternal serum hCG in the HIV+ women - implications for prenatal screening and placental immunology," under the guidance of Dr. Salafia and the Dische Fund, and with the support of Maria Frias, our first Dische Student. His research found that levels of HCG in the mother's blood stream rose as her CD4 cells, an important regulator of immune resistance, dropped.

The role of the immune system in pregnancy is hotly contested and extremely controversial, even after several decades of intense investigation. Dr. Espinosa's research found direct effect of maternal immune competence in HIV+ women on the placenta. A mother's immune competence, as measured by the number of CD4 + cells, appears to "place a lid" on the amount of HCG produced by the placenta and poured into the mother's bloodstream. As CD4 count decreases, serum HCG rises. This implies that the immune system may directly play into the balance of this critical aspect of placental cell/trophoblast function. To follow up on these results, we are beginning a prospective study of maternal HCG in HIV+ women in collaboration with colleagues at Columbia University.

4. Our randomized, double-blinded trial of a novel treatment to improve blood flow to the placenta (entitled "HCG Vascular Therapy and Prevention of Recurrent Early Pregnancy Loss: A Randomized Clinical Trial.") was approved by St. Vincent's (Staten Island) Hospital Institutional Review Board. The study is currently underway at St. Vincent's Medical Center. A second trial site at Mount Sinai Medical Center may be operational within the next few months, enabling us to amplify recruitment and achieve meaningful results more promptly. If it were determined that this treatment improves pregnancy outcome and is effective in improving blood flow in patients with prior miscarriages and tissue evidence of "stiff blood vessels," a step towards successful diagnosis and treatment would be achieved.

5. Hypertension Diagnostics Inc. has provided over $20,000 in state-of-the-art equipment to the Dische Fund for diagnosis of arterial stiffness. We have begun to apply this testing to women throughout pregnancy and after delivery. Our aims are:

* To improve prediction of risk of pregnancy complications before those complications develop (and when they are commonly too late to treat effectively).
* To improve recurrence risk assessment to help doctor and patient plan for a safest next pregnancy, once a complication has occurred.
* To test whether pregnancy is an effective point of triage for women for future cardiovascular disease risk.

The Dische Fund has been dedicated to improve our understanding of the causes and the cures of abnormal maternal blood vessel structure and function. Over the past two decades, this type of problem during pregnancy has been repeatedly identified as a cause of fetal and perinatal illness or death, and has recently been suggested by investigators to indicate an increased risk of future cardiovascular disease for the mother herself. Cardiovascular disease is the leading cause of death in older women, but is under- and frequently mis-diagnosed early in its course, when intervention can more be effective.

Again, restating the Dische Fund's goals, we recognize that community-based research remains often out of the scope of federal funding. Only the "continuity of care" provided at the community level allows questions of "what are my risks of complication in my next pregnancy?" and "what are my longer term cardiovascular risks?" to be fully addressed. The clinical protocols in place have drawn on the strengths of university and academic collaborators to approach the problems of how to improve fetal health, as well as women's long range health, with novel methods and cutting edge science. We thank you all, most sincerely, for your support.

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