Mithal (Leena) Laboratory

Research Highlights

NOVEL DIAGNOSTICS TO GUIDE TREATMENT OF NEONATAL SEPSIS

Clinicians lack optimal tools to identify newborns with neonatal sepsis. The Mithal Laboratory is developing novel diagnostics, including detection of new biomarkers in umbilical cord blood and advanced placental diagnostics, that will allow precise decisions about the need for antibiotics in the first few days of a baby’s life. In the process, the team is also studying the immune development of infants across gestational development.

INFANT MICROBIOME AND NEUROBEHAVIORAL DEVELOPMENT

One topic of study includes examining the role of the early life microbiome in predisposing children to conditions. In particular, Dr. Mithal and collaborators are studying the role of the infant nasal microbiome in olfaction and neurodevelopment. A retrospective study found decreased diversity and differential abundance of particular bacterial taxa associated with early childhood irritability, a marker of mental health risk. Subsequently, data collection for an innovative pilot study using functional olfactory MR imaging in the context of infant microbiome and behavior was recently completed, with analysis in progress.

THE IMPACT OF COVID-19 IN PREGNANCY

An important area of research focus has been the impact of SARS-CoV-2 infection on pregnancy, the placenta, and infants. The Studying Novel Infectious Pathogens in Pregnancy (SNIPP) research group at Northwestern University Feinberg School of Medicine, which Dr. Mithal co-leads, has published research on COVID-19 in healthy infants, increased risk of placental abnormalities with SARS-CoV-2 infection during pregnancy, safety, antibody response, and transplacental antibody transfer following mRNA COVID vaccination during pregnancy, among others.

PERINATAL COLONIZATION OF DRUG-RESISTANT BACTERIA

In a prospective study aimed to determine the burden of drug-resistant Enterobacteriaceae colonization and rate of perinatal transmission in healthy mother-infant dyads in the US, research from the Mithal Lab found a high rate of maternal colonization with extended-spectrum beta-lactamase producing Enterobacteriaceae (14%) and a 42% perinatal transmission rate to infants. The team is now conducting comparative genomics analysis on strains and the impact of early ESBL colonization on the developing gut microbiome.

CHICAGO PERINATAL ORIGINS OF DISEASE COHORT AND THE FOUNDERS 400

The Chicago Perinatal Origins of Disease Cohort will follow pregnant parents and their infants longitudinally from early pregnancy to age two years to collect social, environmental, and medical data along with biospecimens to address questions related to early life exposures and health trajectories among children. Within CPOD, the Founder's 400 aim will ensure high representation of brown and black individuals who are typically underrepresented in medical research. The cohort will provide the foundation for understanding genetic and environmental influences on childhood health in a diverse population.

Oral abstracts

• Smith G, Jones M, Akel M, Barrera L, Heffernan M, Seed P, Macy M, Fisher S, Mithal LB. Parental Perceptions Surrounding Perinatal Research Studies: A Qualitative Investigation. Pediatric Academic Societies Annual Meeting, Washington D.C., April 29, 2023
• Sunderraj A, Otero S, Miller ES, Shanes ED, Goldstein JA, Mithal LB. Maternal and cord blood cytokine levels following SARS-CoV-2 infection during pregnancy. Late Breaker Oral Abstract Session, IDWeek 2022, Washington D.C. October 21, 2022
• Otero S, Scholtens D, Hultquist J, Lancki N, Hu TL, Cullather E, Goo YA, Grobman WA, Mestan KG, Seed PC, Mithal LB. Characterization of the cord blood proteome across gestational development. Pediatric Academic Societies Annual Meeting. Denver, CO. April 23, 2022.

Invited platforms

• “Impact of Maternal COVID-19 on Pregnancy and the Neonate”, Perinatal Transmission of Potential Pathogens: Managing the Mother Infant Dyad, IDWeek, September 30, 2021
• “A Precision Approach to the Management of Early Onset Sepsis.” IDWeek, October 2-6, 2019; Washington, DC.

Featured publications

• Mithal LB, Palac HL, Yogev R, Ernst LM, Mestan KK. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants. PLoS One. 2017 Jan 3;12(1):e0168677. doi: 10.1371/journal.pone.0168677. PMID: 28045978
• Ernst LM, Mithal LB, Mestan K, Wang V, Mangold KA, Freedman A, Das S. Umbilical Cord miRNAs to Predict Neonatal Early Onset Sepsis. PLoS One. 2021 May 7;16(5):e0249548. doi: 10.1371/journal.pone.0249548. eCollection 2021. PMID: 33961620.
• Shanes E, Mithal LB, Otero S, Azad HA, Miller ES, Goldstein JA. Placental Pathology in COVID-19,
  American Journal of Clinical Pathology. 2020 July;154(1):23–32. doi: 10.1093/ajcp/aqaa089. PMID: 32441303.
• Mithal LB, Otero S, Simons LM, Hultquist JF, Miller ES, Ozer EA, Shanes ED, Goldstein JA. Low-level SARS-CoV-2 Viremia Coincident with COVID Placentitis and Stillbirth. Placenta. 2022;121:79-81.Doi: 10.1016/j.placenta.2022.03.003. PMID: 35290925
• Otero S, Miller ES, Sunderraj A, Shanes ED, Sakowicz A, Goldstein HA, Mithal LB. Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy. Clinical Infectious Diseases, Nov 9 2022, https://doi.org/10.1093/cid/ciac793. PMID: 36348510

Media

• Leena Mithal named MSCI Co-Director - Northwestern University, November 11, 2022
• Illinois Covid Update - ABC 7 News, February 7, 2022
• Dr. Leena Mithal of Northwestern joins WGN News to discuss COVID-19 vaccines for pregnant women - WGN, April 2, 2021 

Principal Investigator

Leena B. Mithal, MD

Leena Mithal, MD, is a pediatric infectious diseases specialist with an academic focus and clinical expertise in neonatal and congenital infections. Dr. Mithal is passionate about understanding microbial exposures in utero, perinatally, and in the first months of life; the interaction of microbes (viruses, bacteria) and the developing immune system; and the role of the microbiome in health outcomes.

Lab Members