Maternal aim

Maternal and Fetal Metabolomics and Genomics

Maternal-Fetal Interface Dysfunction

Proper placental development is key to the gestational development of the fetus, as well as long-term maternal and child health. Placental dysfunctions underlie pregnancy pathologies, including recurrent pregnancy loss, fetal growth restriction, pre-eclampsia, and placenta accreta. Our knowledge of human placental structure, function, and development remains limited, a critical knowledge gap that restricts our ability to understand and treat diseases of pregnancy.

Metabolic profiling in the maternal-fetal interface will provide essential information in faulty placentation that can lead to placenta accreta (both Increta and Percreta), early pregnancy loss, and stillbirth. To improve maternal and fetal outcomes we need a deeper understanding of the early phases of placental development, when the extraembryonic tissues of the embryo invade and cross talk with the maternal uterine tissue and set up the further progression of the placenta. Placental trophoblasts are critical to in utero development and a successful pregnancy outcome. Little is known about the early stages of human differentiation due to limited in vivo access and a historical lack of experimental models, i.e. stem cells.

Perinatal Outcomes

The Metabolic Health Center is working to develop a prenatal blood test examining the fetal metabolic profile prior to delivery. The objective of these studies is to derive increased understanding of the impact of maternal conditions on fetal- newborn health, to monitor progression in those pregnancies complicated by common conditions (maternal hypertension, preeclampsia, diabetes) that can affect both or either the health of the mother and or her developing fetus.

The Center is also developing blood tests of metabolic profiles at birth from pregnancies complicated with maternal diseases to provide a unique personalized approach for perinatal risk estimation and treatment.

We anticipate that metabolic profiling of pregnancies, and the newborn at birth will facilitate a more precise understanding of newborn health and risk of disease. These tests will help providers mitigate risks and anticipate possible preventive or therapeutic interventions to avoid disease onset or alter its course for overall improved health outcomes. As an example, common acquired conditions of the premature newborn that may benefit from this approach include respiratory distress, retinopathy of prematurity, necrotizing enterocolitis and neurodevelopmental impairment.

Taken together, we anticipate that these novel metabolic profiles will build on the critical importance of the first 1000 days in setting a life-course trajectory for improved health.

Telomere Study

Telomeres are the protective caps at the ends of DNA strands, much like the tip of a shoelace. Telomeres shorten over time with age, and there is evidence that telomere shortening may be linked to increased risk of disease including heart attack, stroke, and cancer.

In the United States, perinatal complication rates are rising, and the diverse nature of comorbidities among an aging pregnant population makes risk stratification difficult. By studying telomere length in pregnant women and comparing to telomere length in non-pregnant women, we hope to gain insight into the biology behind adverse pregnancy outcomes such as preterm birth. A reduction in telomere length during pregnancy may allow us to quantify cumulative biologic stress (i.e. cellular aging), and combined with comorbidities, has the potential to help clinicians determine which mothers are at greatest risk.

Fetal Development and Pregnancy

In order to better understand pregnancy and impact human health, we’re studying the metabolism of pregnant women and neonates. We want to increase our understanding of the biomolecular drivers that are associated with fetal abnormalities and pregnancy complicated by fetal aneuploidy, birth defects, or genetic syndromes. In addition, we aim to develop novel molecular approaches and improve the existing ones, in order to improve the field of non-invasive prenatal screening and diagnosis. We will also investigate the telomere lengths of the mother and infant complicated by these birth defects.

Chromosomal Abnormalities

The detection of circulating cell-free fetal DNA (cfDNA) in maternal blood by next- generation sequencing is rapidly becoming the preferred method to screen for chromosomal abnormalities, birth defects and perinatal maternal syndromes such as preterm labor and preeclampsia. As the market for these screening tests continues to grow and more laboratories begin offering these services, there is a need for reliable reference materials to ensure the accuracy of results. This is especially critical as labs scale up their operation and need to train, validate, optimize and monitor ongoing performance of their next-generation sequencing or microarray assays. Our goal is to advance non-invasive prenatal diagnostics by developing a series of reference materials and controls for multiple genetic disease states that will be used with the growing number of next generation prenatal screening assays. We also intend to work toward improving the scientific basis and medical understanding of disease-driven bio-molecular alterations.

The Maternal-Fetal branch of the Metabolic Health Center studies the promise of precision medicine by advancing the understanding of disease and providing assurance of the diagnostic result. Our innovative proposal utilizing top notch tools and technologies not only ensure the safe, effective, and accurate performance of diagnostic assays but also, establish a framework for regulating, compiling, and interpreting data from precision diagnostics that will ultimately translate into improved medical care.