Noninvasive blood tests for fetal development predict gestational age and preterm delivery

Thuy T M Ngo; Mira N Moufarrej; Marie-Louise H Rasmussen; Joan Camunas-Soler; Wenying Pan; Jennifer Okamoto; Norma F Neff; Keli Liu; Ronald J Wong; Katheryne Downes; Robert Tibshirani; Gary M Shaw; Line Skotte; David K Stevenson; Joseph R Biggio; Michal A Elovitz; Mads Melbye; Stephen R Quake

doi:10.1126/science.aar3819

Noninvasive blood tests for fetal development predict gestational age and preterm delivery

Science. 2018 Jun 8;360(6393):1133-1136. doi: 10.1126/science.aar3819.

Authors

Thuy T M Ngo¹, Mira N Moufarrej¹, Marie-Louise H Rasmussen², Joan Camunas-Soler¹, Wenying Pan¹, Jennifer Okamoto¹, Norma F Neff¹, Keli Liu³, Ronald J Wong⁴, Katheryne Downes⁵, Robert Tibshirani^{3

6}, Gary M Shaw⁴, Line Skotte², David K Stevenson⁴, Joseph R Biggio⁷, Michal A Elovitz⁵, Mads Melbye^{8

9}, Stephen R Quake¹⁰

Affiliations

¹ Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, Stanford, CA 94305, USA.
² Department of Epidemiology Research, Statens Serum Institute, Copenhagen 2300, Denmark.
³ Department of Statistics, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁵ Maternal and Child Health Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
⁶ Department of Biomedical Data Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁷ Center for Women's Reproductive Health, Department of Obstetrics and Gynecology, University of Alabama, Birmingham, AL 35294, USA.
⁸ Department of Epidemiology Research, Statens Serum Institute, Copenhagen 2300, Denmark. quake@stanford.edu mmelbye@stanford.edu.
⁹ Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
¹⁰ Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, Stanford, CA 94305, USA. quake@stanford.edu mmelbye@stanford.edu.

Abstract

Noninvasive blood tests that provide information about fetal development and gestational age could potentially improve prenatal care. Ultrasound, the current gold standard, is not always affordable in low-resource settings and does not predict spontaneous preterm birth, a leading cause of infant death. In a pilot study of 31 healthy pregnant women, we found that measurement of nine cell-free RNA (cfRNA) transcripts in maternal blood predicted gestational age with comparable accuracy to ultrasound but at substantially lower cost. In a related study of 38 women (23 full-term and 15 preterm deliveries), all at elevated risk of delivering preterm, we identified seven cfRNA transcripts that accurately classified women who delivered preterm up to 2 months in advance of labor. These tests hold promise for prenatal care in both the developed and developing worlds, although they require validation in larger, blinded clinical trials.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Blood Chemical Analysis / methods*
Cell-Free Nucleic Acids / blood*
Female
Fetal Development*
Fetal Monitoring / methods*
Gestational Age*
Humans
Pilot Projects
Pregnancy
Premature Birth / blood*
Premature Birth / diagnosis*
Prenatal Care
Young Adult

Substances

Cell-Free Nucleic Acids