Diana Bianchi, M.D.

Senior Investigator

Medical Genetics Branch




Building 31, Room 2A03
31 Center Drive
Bethesda, MD 20892



Research Topics

Dr. Bianchi's laboratory seeks to advance understanding of fetal and placental biology through sequence analysis of nucleic acids that circulate within the pregnant woman's blood. The information acquired is used to improve counseling and prenatal care. The laboratory has a long-term commitment to developing prenatal treatments for Down syndrome. We hypothesize that giving safe and efficacious medications to pregnant women who are carrying fetuses diagnosed with trisomy 21 will reduce oxidative stress and inflammation, promote the production of new fetal nerve cells, and lead to improvement in brain growth, all of which will ultimately improve brain function, learning and memory after birth.

Noninvasive Prenatal Genomic Testing
Since its incorporation into clinical care in the US in October 2011, analysis of circulating cell-free (cf) DNA in the plasma of pregnant women -- non-invasive prenatal testing (NIPT) - has revolutionized prenatal screening and diagnosis for fetal chromosome abnormalities. It is the largest and fastest growing assay in genomic medicine, and over six million tests have been performed globally as of late 2017. Compared to the current biochemical standard serum screen, NIPT has better sensitivities, specificities, positive and negative predictive values, and significantly lower false positive rates (FPRs). Due to the improved screening test performance for the common autosomal aneuploidies, there has been up to a 70% decrease in the number of diagnostic procedures such as amniocentesis and chorionic villus sampling (CVS) performed in the United States, with an associated decrease in procedure-related miscarriages.

Minimal scientific evidence is currently available upon which to base professional practice guidelines following a positive NIPT screen that is discordant with the results of the recommended diagnostic follow-up procedure (amniocentesis or CVS). An increasing body of literature has demonstrated many potential biological reasons for discordance between NIPT results and the fetal karyotype. Chromosomal etiologies for these variances can be characterized broadly into two groups: feto-placental and maternal. They include confined placental or true fetal mosaicism, maternal autosomal or sex chromosome aneuploidies, and maternal copy number variants (CNVs). More recently it has been shown that maternal conditions, such as a prior solid organ transplant from a male donor or a disorder of sexual differentiation, can explain discordant sex chromosome NIPT results.

Our laboratory hypothesizes that by collecting additional clinical information and sequencing the DNA in relevant biomaterials, we will be able to determine a biological explanation for the discordant results between the cell-free DNA in maternal blood and the diagnostic fetal karyotype. We have a particular interest in pregnant women whose DNA sequencing results demonstrate genome-wide imbalance, which suggests that there may be a clinically asymptomatic tumor that may or may not merit treatment.

The Prenatal Transcriptome as a Means of Developing Novel Therapies
In prior work we have performed gene expression microarray analyses of the cell-free RNA that floats in amniotic fluid, a maternal biofluid that is routinely accessed for clinical prenatal testing. Comparing samples from living fetuses matched for gestational age and sex, we have examined differences between typically developing fetuses with normal chromosomes, and fetuses with trisomies 21 or 18, Turner syndrome (45, X), Fragile X, twin to twin transfusion syndrome, and myelomeningocele. We have also explored the effects of maternal obesity on fetal gene expression in fetuses with normal chromosomes. All of the transcriptome data that we generated are publicly available on the Gene Expression Omnibus. We are currently performing secondary analyses to determine developmental pathways that are affected by these different genetic, developmental and environmental conditions, and using that information to test hypotheses regarding novel prenatal therapies. To determine the extent that alternate transcription plays a role in phenotype variation, we are expanding our knowledge using RNA sequencing.

Prenatal Therapy for Down Syndrome
Down syndrome is the focus of prenatal screening programs worldwide. The only treatment option available for affected infants is delivery in a specialized medical center. Primarily due to three copies of chromosome 21, Down syndrome causes functional alterations of the developing brain resulting from abnormalities of neurogenesis, neuronal differentiation, myelination, dendritogenesis, and synaptogenesis. Based on strong supporting preliminary human data derived from our laboratory's extensive study of the amniotic fluid transcriptome, we have shown that the cell-free RNA in human mid-trimester amniotic fluid supernatant contains multiple fetal brain transcripts. Functional analyses of transcripts from individuals with Down syndrome compared to gestational age and sex-matched controls have demonstrated significant oxidative stress, cell cycle defects and neuroinflammation that manifests in utero. Our central hypothesis, supported by these preliminary data, is that prenatally treating the oxidative stress and neuroinflammation will improve neurogenesis and synaptic plasticity, thereby improving postnatal cognition and behavior.

Our immediate goal is to test the candidate therapies previously identified from an integrated analysis of the human amniocyte and amniotic fluid transcriptomes and brain tissue from three different mouse models of Down syndrome, the Ts65Dn, the Ts1Cje and the Dp(16)1Yey. We wish to determine whether there is improvement in brain development, learning and memory in affected pups when given to their mothers during their pregnancies. The overall goal is to improve postnatal infant cognition by discovering novel and safe pharmacologic therapies that can be given to pregnant women following a prenatal diagnosis of Down syndrome.


Diana W. Bianchi, M.D., is the director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and head of the Prenatal Genomics and Therapy Section for the Medical Genetics Branch at NHGRI. She oversees the research on pediatric health and development, maternal health, reproductive health, intellectual and developmental disabilities, and rehabilitation medicine, among other areas. These efforts include managing a staff of approximately 1,400 people and an annual budget of approximately $1.3 billion. Dr. Bianchi serves as an ambassador and spokesperson for NICHD.

Dr. Bianchi received her B.A. magna cum laude from the University of Pennsylvania and her M.D. from Stanford University School of Medicine. She completed her residency training in pediatrics at the Children's Hospital, Boston, and her postdoctoral fellowship training in medical genetics and Neonatal-Perinatal Medicine, both at Harvard. She is board-certified in all three specialties and is a practicing medical geneticist with special expertise in reproductive genetics. Dr. Bianchi's translational research focuses on two broad themes: prenatal genomics with the goal of advancing noninvasive prenatal DNA screening and diagnosis, and investigating the fetal transcriptome to develop new therapies for genetic disorders that can be given prenatally.

Dr. Bianchi has published over 300 peer-reviewed articles, and she is one of four authors of Fetology: Diagnosis and Management of the Fetal Patient. This book won the Association of American Publishers award for best textbook in clinical medicine in 2000. The second edition was published in April 2010 and is in its third printing. It has been translated into Japanese, Mandarin and Spanish.

Dr. Bianchi is recognized widely for her leadership roles. She spent 23 years at Tufts Medical Center, where she was the founding executive director of the Mother Infant Research Institute, as well as the Natalie V. Zucker Professor of Pediatrics, Obstetrics and Gynecology at Tufts University School of Medicine. Dr. Bianchi also was the vice chair for Pediatric Research at the Floating Hospital for Children, Boston. From 2011 through 2015, she served on the National Advisory Council of NICHD. She is currently editor-in-chief of the international journal Prenatal Diagnosis and is a past president of the International Society for Prenatal Diagnosis and the Perinatal Research Society. She is a former member of the Board of Directors of the American Society for Human Genetics and a former council member of both the Society for Pediatric Research and the American Pediatric Society. She was elected to membership in the National Academy of Medicine (formerly the Institute of Medicine) in 2013.

Dr. Bianchi has received three major lifetime achievement awards. The Colonel Harland D. Sanders Lifetime Achievement Award in Genetics, given in 2017 by the March of Dimes, recognized her pioneering work on maternal and fetal cellular communication, including their significance in disease and diagnostics, and for exploring treatments of fetal disorders. The Maureen Andrew Award for Mentoring, given in 2016 by the Society for Pediatric Research, recognized her commitment to mentoring the next generation of clinician-scientists. The Landmark Award, from the American Academy of Pediatrics, was given in 2015 in recognition of her research and contributions to genetics and newborn care.

Selected Publications

  1. Bianchi DW, Chiu RWK. Sequencing of Circulating Cell-free DNA during Pregnancy. N Engl J Med. 2018;379(5):464-473.

  2. Pertile MD, Halks-Miller M, Flowers N, Barbacioru C, Kinnings SL, Vavrek D, Seltzer WK, Bianchi DW. Rare autosomal trisomies, revealed by maternal plasma DNA sequencing, suggest increased risk of feto-placental disease. Sci Transl Med. 2017;9(405).

  3. Aziz NM, Guedj F, Pennings JLA, Olmos-Serrano JL, Siegel A, Haydar TF, Bianchi DW. Lifespan analysis of brain development, gene expression and behavioral phenotypes in the Ts1Cje, Ts65Dn and Dp(16)1/Yey mouse models of Down syndrome. Dis Model Mech. 2018;11(6).

  4. Bianchi DW. Cherchez la femme: maternal incidental findings can explain discordant prenatal cell-free DNA sequencing results. Genet Med. 2018;20(9):910-917.

  5. Antonarakis SE, Skotko BG, Rafii MS, Strydom A, Pape SE, Bianchi DW, Sherman SL, Reeves RH. Down syndrome. Nat Rev Dis Primers. 2020;6(1):9.

This page was last updated on September 4th, 2020