Infectious Disease and Pregnancy: Contributions of Kristina Adams-Waldorf, MD by Phyllis Leppert, MD, PhD
For many years it has been known that bacterial and viral infections affect pregnancy outcomes and cause fetal injury. Traditionally, the TORCH pathogens of toxoplasmosis, others (syphilis, hepatitis B, varicella, mumps and HIV), rubella, cytomegalovirus, and herpes simplex were considered to cause birth defects, stillbirth and chronic postnatal infection. However, current research leads to the conclusion that many other pathogens are cause fetal injury. A study from the laboratory of Kristina Adams-Waldorf of the University of Washington demonstrates that Zike Virus infection during pregnancy has long term consequences affecting children after birth even if there is no evidence of microcephaly. Normocephalic infants have documented delays in neurodevelopment. Adams-Waldorf and her colleagues conducted a cohort study of six Zika Virus challenged pregnant pigtail macaques who received Zika Virus injections on day 60-121 of gestation and compared them to six control pigtail macaques. Offspring were studied after c/section delivery. None were microcephalic. The scientists analyzed the offspring brain tissue transcriptome from deep gray matter, superficial white matter and deep white matter. Downregulation of genes fundamental to the formation and maintenance of myelin surrounding axons was found with the deep white matter showing the largest change in the downregulation. Decompaction of myelin in oligodendrocytes was demonstrated by electron microscopy. There findings led to the conclusion that changes in neural function and signaling leads to developmental delay in offspring of Zika infected gestations(1).
In a review article Adams-Waldorf and others discuss the impact of infections during pregnancy on the long-term mental health of children born following these gestations. They state that while there are genetic risks for disease such as schizophrenia, bipolar disease, autism spectrum disorders and depression many studies from a number of laboratories point to perinatal infection as a contributing cause to later mental disease in children and adults(2).
SARS-CoV-2 is the virus that causes Covid-19 and in pregnancy has led to maternal mortality, ICU admission, mechanical ventilation, gestational hypertension, preterm and still birth. SARS-CoV-2 placental infection demonstrates syncytiotrophblast necrosis, increased perivillous fibrin depositions, and chronic histiocytic intervillositis. However, Adams-Waldorf published a current review article reporting that many studies of COVID -19 infections in pregnancy a comprehensive reporting of clinical outcomes, and laboratory testing of placentas and fetuses is lacking. Taken all together the reported studies are inconclusive. This does not mean that COVID-19 in pregnancy is not a serious disease. It means that further study is needed(3).
These cited articles are three of the numerous studies that Adams-Waldorf has conducted in her outstanding professional life. Kristina Adams-Waldorf, MD, is Professor of Obstetrics and Gynecology at the University of Washington and has spent her research career focusing on pregnancy infections and how they relate to fetal injury and to preterm birth. She has conducted numerous studies of how Group B Streptococcus, E coli, the Zika Virus and SARS-CoV-2 impacts pregnancy, preterm birth, and the fetus. She states on her lab website that she is actively investigating these areas: 1. Pathogen virulence and host factors that are involved in bacterial and viral trafficking into the amniotic fluid and into the fetus 2. How the activation of innate immune response by pathogens in the placenta and fetus leads to pregnancy complications and fetal injury and 3. How a disruption by pathogens of the maternal-fetal tolerance necessary for the success of pregnancy contributes to preterm birth and 4. How novel therapeutics may prevent preterm birth and fetal injury. Like all excellent scientists she utilizes multiple techniques from many disciplines, including those of current molecular biology, genetics as well as analysis of large data bases. She also has been involved in conduiting clinical research. Admas-Waldorf has a number of outstanding collaborators including scientists in Sweden. Her research has extended our understanding of the role infections and immunity in the outcomes of pregnancy and birth.
Dr Adams-Waldorf obtained her BS from the University of Washington, an MD from Mayo Medical School and completed her residency in obstetrics and gynecology at the University of Washington, Seattle. As a faculty member she continues the tradition of excellence in infectious disease and immunological research that has long existed in the Department of Obstetrics and Gynecology at the University of Washington School of Medicine. She is Director of the North America Branch of the Preterm Birth International Collaboration (PREBIC). It is through this organization that I as the President of the Campion Fund got to know her.
References:
(1) Tisoncik-Go J, Stokes C, Whitmore LS, Newhouse DJ, Voss K, Gustin A, Sung CJ, Smith E, Stencel-Baerenwald J, Parker E, Snyder JM, Shaw DW, Rajagopal L, Kapur RP, Adams Waldorf KM, Gale M Jr. Disruption of myelin structure and oligodendrocyte maturation in a macaque model of congenital Zika infection. Nat Commun. 2024 Jun 18;15(1):5173. doi: 10.1038/s41467-024-49524-2. PMID: 38890352; PMCID: PMC11189406.
(2)Al-Haddad BJS, Oler E, Armistead B, Elsayed NA, Weinberger DR, Bernier R, Burd I, Kapur R, Jacobsson B, Wang C, Mysorekar I, Rajagopal L, Adams Waldorf KM. The fetal origins of mental illness. Am J Obstet Gynecol. 2019 Dec;221(6):549-562. doi: 10.1016/j.ajog.2019.06.013. Epub 2019 Jun 15. PMID: 31207234; PMCID: PMC6889013.
(3)Li A, Schwartz DA, Vo A, VanAbel R, Coler C, Li E, Lukman B, Del Rosario B, Vong A, Li M, Adams Waldorf KM. Impact of SARS-CoV-2 infection during pregnancy on the placenta and fetus. Semin Perinatol. 2024 Jun;48(4):151919. doi: 10.1016/j.semperi.2024.151919. Epub 2024 Jun 6. PMID: 38897829; PMCID: PMC11288977.