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

Toward more predictable birthdays Low-cost methods for monitoring fetal development could improve prenatal care, especially in low-resource settings. By measuring the levels of certain placental RNA transcripts in maternal blood, Ngo et al. developed two noninvasive blood tests that provide a window into the progression of individual pregnancies. In a small proof-of-concept study, the first blood test predicted fetal age and delivery date with an accuracy comparable to that of ultrasound. The second blood test, also examined in a small pilot study, discriminated women at risk of preterm delivery from those who delivered at full term. The next step will be to assess the reliability of the tests in large, blinded clinical trials. Science, this issue p. 1133 In pilot studies of pregnant women, RNA-based tests of maternal blood predicted delivery date and risk of early childbirth. 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 (25 full-term and 13 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.

[1]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[2]  P. A. Lee,et al.  Serum gonadotropins before, at the inception of, and following human pregnancy. , 1969, The Journal of clinical endocrinology and metabolism.

[3]  Hanson Ae The eight months' child and the etiquette of birth: obsit omen! , 1987 .

[4]  A. Hanson The eight months' child and the etiquette of birth: obsit omen! , 1987, Bulletin of the history of medicine.

[5]  N. Rose,et al.  Maternal serum screening for neural tube defects and fetal chromosome abnormalities. , 1993, The Western journal of medicine.

[6]  A. E. Hanson Paidopoiïa: metaphors for conception, abortion, and gestation in the Hippocratic Corpus. , 1995, Clio medica.

[7]  D. Altman,et al.  New charts for ultrasound dating of pregnancy , 1997, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[8]  H. Parker Greek embryological calendars and a fragment from the lost work of Damastes, On the Care of Pregnant Women and of Infants , 1999, The Classical Quarterly.

[9]  D. Savitz,et al.  Comparison of pregnancy dating by last menstrual period, ultrasound scanning, and their combination. , 2002, American journal of obstetrics and gynecology.

[10]  W. Barr,et al.  Last menstrual period versus ultrasound for pregnancy dating , 2004, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[11]  D. Duan,et al.  Altered properties of volume‐sensitive osmolyte and anion channels (VSOACs) and membrane protein expression in cardiac and smooth muscle myocytes from Clcn3‐/‐ mice , 2004, The Journal of physiology.

[12]  J. Copel,et al.  First trimester ultrasound screening is effective in reducing postterm labor induction rates: a randomized controlled trial. , 2004, American journal of obstetrics and gynecology.

[13]  F. Malone,et al.  Quad Screen as a Predictor of Adverse Pregnancy Outcome , 2005, Obstetrics and gynecology.

[14]  K. Ward,et al.  The Heritability of Preterm Delivery , 2005, Obstetrics and gynecology.

[15]  H. Sasaki,et al.  Human MOB1 expression in non-small-cell lung cancer. , 2007, Clinical lung cancer.

[16]  K. Spencer,et al.  First‐trimester ultrasound and biochemical markers of aneuploidy and the prediction of preterm or early preterm delivery , 2008, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[17]  M. Berridge,et al.  Smooth muscle cell calcium activation mechanisms , 2008, The Journal of physiology.

[18]  M. Robinson,et al.  Small-sample estimation of negative binomial dispersion, with applications to SAGE data. , 2007, Biostatistics.

[19]  Max Kuhn,et al.  Building Predictive Models in R Using the caret Package , 2008 .

[20]  M. Neale,et al.  Estimating Fetal and Maternal Genetic Contributions to Premature Birth From Multiparous Pregnancy Histories of Twins Using MCMC and Maximum-Likelihood Approaches , 2009, Twin Research and Human Genetics.

[21]  A. Marshall,et al.  The PH domain adaptor protein Bam32/DAPP1 functions in mast cells to restrain FcɛRI-induced calcium flux and granule release. , 2010, Molecular immunology.

[22]  Louis J Muglia,et al.  The enigma of spontaneous preterm birth. , 2010, The New England journal of medicine.

[23]  Mark D. Robinson,et al.  edgeR: a Bioconductor package for differential expression analysis of digital gene expression data , 2009, Bioinform..

[24]  Jamie Perin,et al.  Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000 , 2012, The Lancet.

[25]  Davis J. McCarthy,et al.  Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation , 2012, Nucleic acids research.

[26]  J. Guibourdenche,et al.  Comparative expression of hCG β-genes in human trophoblast from early and late first-trimester placentas. , 2012, American journal of physiology. Endocrinology and metabolism.

[27]  Steven P Lund,et al.  Detecting Differential Expression in RNA-sequence Data Using Quasi-likelihood with Shrunken Dispersion Estimates , 2012, Statistical applications in genetics and molecular biology.

[28]  M. Yayla,et al.  Transvaginal Sonographic Evaluation of the Cervix in Asymptomatic Singleton Pregnancy and Management Options in Short Cervix , 2012, Journal of pregnancy.

[29]  Bernadette A. Thomas,et al.  Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 , 2012, The Lancet.

[30]  Joy Lawn,et al.  Born Too Soon: The global epidemiology of 15 million preterm births , 2013, Reproductive Health.

[31]  S. Fisher,et al.  Preterm labor: One syndrome, many causes , 2014, Science.

[32]  W. Koh,et al.  Noninvasive in vivo monitoring of tissue-specific global gene expression in humans , 2014, Proceedings of the National Academy of Sciences.

[33]  Robert N. Taylor,et al.  Rac1 Regulates Endometrial Secretory Function to Control Placental Development , 2015, PLoS genetics.

[34]  Ultrasound for fetal assessment in early pregnancy. , 2015, The Cochrane database of systematic reviews.

[35]  Zhihui Xie,et al.  R4 Regulator of G Protein Signaling (RGS) Proteins in Inflammation and Immunity , 2015, The AAPS Journal.

[36]  Roberto Romero,et al.  Vaginal progesterone to prevent preterm birth in pregnant women with a sonographic short cervix: clinical and public health implications. , 2016, American journal of obstetrics and gynecology.

[37]  Matthew K Hoffman,et al.  Development and validation of a spontaneous preterm delivery predictor in asymptomatic women. , 2016, American journal of obstetrics and gynecology.

[38]  Z. Nachum,et al.  Predictive Value of Second-Trimester Biomarkers and Maternal Features for Adverse Pregnancy Outcomes , 2017, Fetal Diagnosis and Therapy.

[39]  Xiaoting Chen,et al.  Genetic Associations with Gestational Length and Spontaneous Preterm Birth , 2017, The New England journal of medicine.

[40]  Francesco Vallania,et al.  Methods to increase reproducibility in differential gene expression via meta-analysis , 2016, Nucleic acids research.