Karius Research: Detecting Pathogen DNA in Maternal Plasma | Karius
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Karius Research: Detecting Pathogen DNA in Maternal Plasma

Intra-amniotic infections (IAI) can increase the risk of obstetric complications, including spontaneous onset of labor, neonatal sepsis and other inflammation-related morbidities.

But these infections may not always present with clinically significant symptoms like maternal fever or fetal tachycardia. Even when there is clinical evidence of infection, maternal blood cultures have low positive rates and microbiological diagnosis requires invasive procedures such as amniocentesis.

Several publications report that about ⅓ of pre-term deliveries have these subclinical intra-amniotic infections (IAI) present.

Being able to detect clinical and subclinical infections in a non-invasive way could help reduce complications and offer both mothers and their babies a healthier outcome.

We hypothesized that we could detect pathogen cell-free DNA in maternal plasma, and that this could be the basis for a non-invasive method to diagnose prenatal congenital infections.

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Karius Medical Director Dr. Simona Zompi and Karius bioinformatician Dr. Lily Blair recently presented this work at the 65th Annual Scientific Meeting of the Society for Reproductive Investigation.

A complete abstract is available online here.

For the study, next-generation sequencing of cell-free DNA (cfDNA) was performed on matched maternal plasma and umbilical cord plasma. Specimens were collected during delivery at gestational age 28 - 41 weeks from 18 cases suspected of IAI and 53 controls.

We found that pathogens that had been previously identified in the literature as causing IAI were enriched in patients that had histological evidence of IAI as compared to controls. An unbiased analysis of microbial signals of all 1251 pathogens detectable with this assay identified Streptococcus mitis, Ureaplasma spp., and Mycoplasma spp. as pathogens likely causing IAI in this cohort.

This is the first report showing a signal of relevant pathogen cfDNA in maternal plasma during intra-amniotic infection.

Based on this proof-of-concept, we aim to develop and validate a non-invasive method to detect congenital infections. Potential applications include diagnosis of infections that could lead to preterm labor or neonatal sepsis - with the promise of earlier targeted treatment for affected patients.

To learn more about this study or to inquire about partnering with Karius on your next study, please see the abstract online or write to us at medical@kariusdx.com.

References

  1. DiGiulio DB, Romero R, Amogan HP, et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One. 2008;3(8):e3056
  2. DiGiulio DB, Romero R, Kusanovic JP, et al. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol. 2010;64(1):38-57
  3. Viscardi RM. Ureaplasma species: role in diseases of prematurity. Clin Perinatol. 2010;37(2):393-409