The Science Behind a Cure to Preterm Birth
In January 2017, CUIMC launched The Preterm Birth Prevention Center, in order to improve outcomes for mothers and their babies by providing personalized, multidisciplinary medical care for women at high risk for preterm birth and conducting cutting-edge research to develop novel, safe and more effective therapies to prevent babies from being born too soon. The Preterm Birth Prevention Center, co-directed by Drs. Joy Vink and Cynthia Gyamfi-Bannerman, focuses on this area of obstetrics because preterm birth still affects 1 in 10 (about 500,000) pregnancies in the U.S. every year.
Babies who are born premature, especially those that are born at the cusp of viability, are at significant risk of neonatal demise. Babies that do survive are at increased risk for complications of prematurity, which include breathing problems, neurodevelopmental delay, seizures, cerebral palsy, blindness, deafness and feeding problems. Complications of prematurity do not end in childhood. Recent studies show babies who are born premature have an increased risk of dying in young adulthood mainly due to heart problems. Preterm survivors also have higher rates of depression, anxiety, and inattention/hyperactivity. Preterm birth remains an enormous social and financial dilemma; in 2015, more than $30 billion in excess medical costs and social services in the U.S. were attributed to prematurity.
In addition, no dollar amount could begin to reflect the heartbreaking emotional trauma that families endure when they lose their baby due to prematurity. Despite decades of research, the preterm birth rate is rising. It is estimated that even if all pregnant women were screened and offered appropriate available intervention, 95% of preterm births would still occur.
Obstetricians are failing to effectively prevent preterm birth for two main reasons. Primarily, studies focusing on women’s reproductive health have largely been underfunded. This disparity has led to our current frustration with the fact that while there has been progress in curing various diseases, we still cannot answer one of the most basic and vital question - when and how does a pregnant woman go into labor? Additionally, obstetricians lack a fundamental understanding of how tissues important in pregnancy (uterus, cervix, amniotic sac) enlarge and change to accommodate a growing baby in pregnancy. They do understand that the role of each of these pregnancy tissues is incredibly complex. As a pregnancy develops, the cervix (just like a knot that keeps a balloon filled with air) must remain closed despite an increasing mechanical load from the developing fetus. The uterus (which is a large muscle) must remain relaxed and quiet despite massive enlargement as pregnancy progresses. The amniotic sac must remain intact despite significant expansion. When a baby is born, in a brilliant reversal of roles, the cervix must dilate, the uterus contracts, and the amniotic sac ruptures to allow the baby to deliver. A detailed understanding of how these tissues work together to accomplish this miracle is lacking.
Since obstetricians do not understand how this process happens “normally”, it is thus impossible to tease out the mechanisms and pathways that lead to “malfunction” of these tissues (premature cervical failure, preterm labor, premature rupture of the amniotic sac) and ultimately preterm birth. As such, finding effective therapies to prevent preterm birth remains elusive. This fundamental knowledge gap of how pregnancy tissues change and function as a human pregnancy develops inspired two women at Columbia University, Dr. Joy Vink (Co-Director of the Preterm Birth Prevention Center and Maternal Fetal Medicine physicianscientist) and Dr. Kristin Myers (mechanical engineer with expertise in soft tissue mechanics) to work together to finally fill this knowledge gap.
Their goal is to establish how the human cervix, uterus, and fetal membranes change and develop in pregnancy and understand how each of these tissues work together to create a symbiotic environment that is required for a successful, healthy pregnancy. This dynamic duo of women scientists are breaking barriers in women’s reproductive health as they start understand how tissue properties (cellular and protein content) of the cervix, uterus and fetal membranes influences each tissue’s mechanical strength and function in pregnancy. Drs. Vink and Myers are rapidly beginning to understand how the cervix remodels and softens in preparation for delivery of a baby. Their findings about how the cervix functions in pregnancy are exciting because although there are various risk factors that may trigger the pathway to preterm birth, the final common pathway must involve premature dilation of the cervix to allow for a baby to be born too early. Once Dr. Vink and Myers understand how the cervix softens and dilates too early in pregnancy, their goal is to develop novel, safe, and effective therapeutic interventions to keep the cervix closed and ultimately prevent preterm birth. To date, Dr. Vink’s findings have challenged the existing paradigm of cervical tissue structure, which was established in the 1940s, as she found that the cervix may contain a specialized sphincter that functions to keep the cervix closed in pregnancy. In order to understand how this sphincter functions and “malfunctions” leading to premature cervical dilation, Drs. Vink and Myers are working together to create personalized, patient-specific computer models of pregnancy that incorporate anatomically-correct, geometric ultrasound measurements of a woman’s pregnant uterus and cervix and a woman’s specific tissue properties. This clinical and engineering team at CUIMC has the only pregnancy model of this kind in the world. These models calculate and visualize how pregnancy tissues ‘hold the weight” of a growing baby. The model allows us to gain Preterm Birth Cervix Dilates Amniotic Sac Ruptures Uterus Contracts Cervix Softens Risk factors: Smoking Vaginal bleeding Uterine stretch Infection Trauma Race/ethnicity Genetic factors Socioeconomic OTHER Figure 2: insight into how a woman’s uterus and cervix function in pregnancy given her specific anatomic and tissue-specific properties and will help determine the potential for a biomechanical imbalance or malfunction that could lead to preterm birth (Figure 3). Ultimately Drs. Myers and Vink are striving to develop this computer modeling platform into an easy-to-use, personalized, patient friendly electronic application which will 1) accurately predict when a patient’s baby will deliver, 2) stratify her risk for preterm birth, and ultimately, 3) design personalized therapeutic interventions to optimize her best pregnancyoutcome. The Vision for the Preterm Birth Prevention Center at Columbia University Irving Medical Center Our Preterm Birth Prevention Center provides the best outcomes possible for mothers and babies, through a patient-centered approach that is comprehensive, multidisciplinary, and built on Columbia’s leading research. Our mothers and babies benefit tremendously from the very latest innovations in care as our clinicians collaborate with our researchers to bring safe and effective discoveries from the “laboratory bench” to our patients’ bedsides as quickly as possible.
The vision for the Center is to bring together clinician experts providing multidisciplinary care for women at risk of preterm birth and the world’s leading researchers in molecular biology, bioinformatics, engineering, genetics and tissue remodeling in one location at CUIMC. This would allow our physicians and scientists to pursue their goal to cohesively focus on delineating the mechanisms that lead to preterm birth. This environment of seamless crosstalk between clinicians and scientists who are all focused on preventing preterm birth and bringing the best possible therapies to women at risk of preterm birth is the multidisciplinary approach and future that is currently needed for progress to be made in the field of women’s reproductive health. Thank you Philanthropic support for this work is essential. We invite you to join us in our effort to bring countless lives safely into the world and to make Columbia the leader in preterm birth prevention. Please see our supplemental materials for the giving opportunities that would most support the Center. Every gift has a great impact, and additional opportunities are available upon request. Thank you for your consideration. Growing Baby Cervix Maternal Abdomen Computer simulation showing how a cervix will function/open in pregnancy based on a woman’s specific anatomic measurements of her uterus and cervix. Pregnant Uterus Figure 3:
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