UNIVERSITY OF UTAH: STILLBIRTH RESEARCH FOR PREVENTION

Through support from The Riley Fund for Stillbirth Research, the University of Utah focus has been on unexplained stillbirth and umbilical cord accidents. This work has resulted in one published paper, one paper about to be submitted, and additional ongoing work and research.

Through the study, they noted that about 19% of stillbirths in a large U.S. cohort of stillbirths were attributable to umbilical cord abnormalities using rigorous criteria. This work is the largest published study of stillbirths associated with umbilical cord problems and was published in the leading journal in Obstetrics and Gynecology. This work underscores the need to focus on cord accidents and cord abnormalities in order to prevent stillbirths and can be seen here Umbilical Cord Abnormalities and Stillbirth.

A novel biomarker was assessed that could be measured in maternal blood to determine if it is associated with stillbirth. It is a protein, DLK1, that is made by the baby in response to stress. The marker was associated with poor fetal growth but not stillbirth. A manuscript is being finalized for publication.

The results of this study analyzed 234 stillbirths and 234 live births. 246 DLK1 values were quantifiable within the standard curve and comparisons of case and control DLK1 geometric means within the standard curve did not reveal any significant differences between groups.

In exploratory analysis of all data, adjusted analysis showed a significant difference for the live birth comparison only. In exploratory analysis of the proportion of “low DLK1,” there was a significant difference between the odds ratio of having “low DLK1” between preterm cases and controls for both stillbirths and live births.

There were no significant differences in geometric means nor “low DLK1” between stillbirths and live births. The conclusion of the study suggests more placental insufficiency cases in preterm stillbirths and live births had “low DLK1” and lower values of DLK1 compared to normal placenta controls but low DLK1 levels were not associated with stillbirth. DLK1, however, warrants evaluation as a marker for placental insufficiency.

Additional research at The University of Utah will focus on a study using novel measurements on ultrasound in term pregnancies to determine if they can predict umbilical cord problems. This study is a “pilot.” If results are promising, a larger study will focus on more pregnancies.

This clinical research will focus on third trimester ultrasound to identify pregnancies at risk of umbilical cord accident, i.e., ultrasonographic umbilical cord assessment.

Stillbirth remains a common and traumatic pregnancy complication, occurring in approximately 1 in 160 pregnancies in the United States. Up to 20% of stillbirths are attributable to spontaneous umbilical cord occlusion by fetal parts, knots, or torsion leading to fetal death (“umbilical cord accidents”). These stillbirths are particularly devastating since they often occur at term in otherwise normal babies and could be prevented by earlier delivery. Because delivery prior to 39 weeks is associated with a small but measurable increase in perinatal morbidity, routine early delivery is not justified by the empiric risk of a cord accident at term. Currently, however, cord accidents are not considered to be preventable because no strategies exist to identify fetuses at risk of umbilical cord accidents to guide consideration of early delivery. This represents a critical obstacle to reducing potentially preventable stillbirths.

The study aims to establish a standardized and reproducible umbilical cord accident risk assessment through an observational pilot study of 70 women with low-risk pregnancies to undergo ultrasound at 36 weeks gestation using state-of-the-art Samsung obstetric ultrasound machines. This ultrasound examination will assess a variety of umbilical cord parameters at three sites along the umbilical cord: the placental insertion, mid-cord, and fetal insertion, along with assessments of umbilical cord morphology and location. This data will be used to generate normal ranges and establish the characteristics of the parameters, such as inter- and intra-observer variability, which will then be used in a larger, more definitive study assessing the use of these parameters to identify pregnancies at risk of cord accident and stillbirth.

While the precise timing of a cord accident is unpredictable, cord accident stillbirths may be preceded by intermittent compression of the umbilical cord. Evidence of such compression may be detectable by Doppler assessment of the umbilical artery and vein waveforms at various sites within the cord and fetal circulation. Risk factors for cord compression, such as nuchal cord, also may be routinely detectable via ultrasound.

The long-term goal of this study is to develop surveillance strategies to identify fetuses at risk of cord accident stillbirths. The overall objective of this project is to establish the reproducibility of ultrasonographic cord assessments of assess whether ultrasound evidence of cord compression in the late third trimester is associated with evidence of fetal hypoxia and thereby could be an antecedent to cord accidents.