598 Low fetal fraction associates with hypertensive disease of pregnancy in a low risk cohort

Abstract

Hypertensive disease in pregnancy (HDP) continues to rise and contribute to increased maternal mortality rates. Studies have established that a lower 1st trimester fetal fraction (FF) is associated with increased risk for HDP. However, obesity is a significant confounder for HDP and low FF. We have the novel opportunity to investigate whether 1st trimester FF determined via a standardized single institution NIPT platform among male and female fetuses associates with HDP independent of maternal obesity. We conducted a retrospective, single institution cohort study utilizing a previously validated cfDNA test using whole genome analysis on N=1097 women. Women with documented HDP status (including gestational hypertension and preeclampsia) with non-anomalous fetuses were included (n=981). Linear regression was used to evaluate the association between FF and HDP. The model was then adjusted for BMI. Next, the association between FF and HDP among obese (BMI≥30 kg/m2) and non-obese (BMI <30 kg/m2) women was investigated. We identified women with (n=116) & without (n=865) HDP with a FF in 1st trimester. Women with HDP had a significantly lower FF than women without HDP (9.9±4.2% vs 11.3±4.6%, p=0.01), but when adjusting for BMI the association lost significance (p=0.13). Interestingly, non-obese women with HDP had significantly lower FF than non-obese women without HDP (11.0±4.6% vs 12.3±4.8%, p=0.02), an association not noted among obese women with and without HDP (8.0±4.0% vs 9.1±4.4%, p=0.79) (Figure 1). Our study demonstrates that while a lower FF is associated with HDP development, this is primarily driven by obesity as a co-morbidity. However, we uniquely noted that among non-obese women, FF for those who develop HDP is lower than those without HDP. Therefore, while a low FF among women with obesity may not be able to differentiate those at risk for HDP, further studies need to evaluate the role of a 1st trimester FF in a low risk cohort as a potential biomarker for HDP development.