About

Karen Marie Puopolo, MD, PhD, is a Professor of Pediatrics specializing in Neonatology and Newborn Services at the Children's Hospital of Philadelphia. She serves as an Attending Physician in Neonatology at the same institution and is the Medical Director of the NICU and Well Nursery at Pennsylvania Hospital. Dr. Puopolo has over 25 years of experience practicing neonatology in large perinatal centers and has conducted significant research in neonatal infectious diseases, sepsis risk assessment, and neonatal health outcomes. Her research career began with laboratory investigations into the virulence mechanisms of Group B Streptococcus, a key neonatal pathogen. She then focused on neonatal sepsis risk assessment, developing models and practical tools such as a Sepsis Risk Score that have been widely adopted and have changed national perinatal practices. Her work includes studies on infection epidemiology, antibiotic practices, and the long-term health effects of perinatal antibiotic exposure. During the COVID-19 pandemic, her team leveraged existing infrastructure to study maternal COVID seroepidemiology and transplacental antibody transfer. Dr. Puopolo is also actively involved in medical research training, mentoring multiple fellows and junior faculty, and serving as a primary mentor for investigators with NIH grants.

Research topics

• Medicine
• Internal medicine
• Pediatrics
• Psychiatry
• Intensive care medicine

Selected publications

• Anti-cytomegalovirus medications among very low birth weight infants in the United States from 2016 to 2023

  Journal of Perinatology · 2026-04-20

  articleOpen access
  PublisherOA PDFDOI

• Blood cultures to define neonatal early-onset sepsis: why not enough for clinical care?

  Pediatric Research · 2026-03-07

  articleOpen access
  PublisherOA PDFDOI

• Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants

  UNC Libraries · 2026-03-18

  articleOpen access

  Importance: The management of patent ductus arteriosus (PDA) in preterm infants is controversial. Objective: To determine whether expectant management compared with active treatment of a protocol-defined PDA in preterm infants decreases the incidence of death or bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: A randomized clinical trial including infants born at 22 to 28 weeks' gestation and diagnosed with a protocol-defined PDA between the age of 48 hours and 21 days at screening. The trial was conducted from December 2018 to December 2024 at 33 hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. The final date of follow-up was June 2025. Interventions: Infants with PDA were randomized to expectant management (n = 242) or active treatment (n = 240; acetaminophen, ibuprofen, or indomethacin) to close the PDA. Main Outcomes and Measures: The primary outcome was death or BPD at 36 weeks' postmenstrual age. The secondary outcomes included the components of the primary outcome and other morbidities of prematurity. Results: A total of 482 infants were randomized (median gestational age, 25 weeks [IQR, 24 to 27 weeks]; median birth weight, 760 g [IQR, 620 to 935 g]). The trial was stopped for futility and safety after the 50% interim analysis for the primary outcome due to higher survival in the expectant management group. The incidence of death or BPD was 80.9% (195/241) of infants in the expectant management group vs 79.6% (191/240) of infants in the active treatment group (adjusted risk difference, 1.2% [95% CI, -5.7% to 8.1%]; P = .73). The incidence of death before 36 weeks' postmenstrual age was 4.1% (10/241) of infants in the expectant management group vs 9.6% (23/240) of infants in the active treatment group (adjusted risk difference, -5.6% [95% CI, -10.1% to -1.2%]; P = .01). Infections resulting in death occurred in 0.8% (2/241) of infants in the expectant management group vs 3.8% (9/240) of infants in the active treatment group. Conclusions and Relevance: In extremely preterm infants with a protocol-defined PDA, death or BPD did not differ between the expectant management group and the active treatment group. Survival was substantially higher with expectant management. Trial Registration: ClinicalTrials.gov Identifier: NCT03456336.

  PublisherDOI

• Long-term sustainability and safety of a delivery-based early-onset sepsis evaluation strategy for very low birth weight infants

  Journal of Perinatology · 2026-03-13

  articleOpen access
  PublisherOA PDFDOI

• Group B Streptococcal Disease

  New England Journal of Medicine · 2026-02-25 · 2 citations

  article1st authorCorresponding

  Group B streptococcus commonly colonizes the human gastrointestinal and genitourinary tracts and is the single most common bacterial cause of invasive infection among newborns in the United States. Intrapartum antibiotic prophylaxis is currently used to reduce the risk of group B streptococcal disease among pregnant persons and newborns. No strategies are currently available to prevent disease in later infancy or among nonpregnant adults. Vaccines against group B streptococcal disease that consist of capsular polysaccharides linked to protein antigens are in development and may provide a means of prevention for all at-risk populations.

  PublisherDOI

• Lymphocytic Choriomeningitis Virus Seroprevalence among Urban Pregnant Women and Newborns, Philadelphia, Pennsylvania, USA, 2021

  Emerging infectious diseases · 2026-02-25 · 1 citations

  articleOpen access

  Lymphocytic choriomeningitis virus (LCMV) is a globally distributed rodentborne pathogen that can cause severe congenital infections. We conducted a retrospective cross-sectional seroepidemiologic study using remnant serum samples from pregnant women and newborns at 2 hospitals in Philadelphia, Pennsylvania, USA. We tested samples for LCMV IgG and IgM in 3 phases: a high-risk group determined by neighborhood deprivation index scores, a random sample of all birthing women, and a group with prenatally diagnosed neurologic malformations. We found LCMV IgG seroprevalence was 2.4% among 700 high-risk and 2.7% among 300 randomly selected pregnant women. Seroprevalence varied by hospital site, maternal race or ethnicity, and neighborhood deprivation level. All seropositive maternal samples were IgM-negative. Thirty-seven pregnant women carrying fetuses with neurologic malformations were seronegative. Our findings highlight the risk for LCMV exposure in urban settings and emphasize the need for pregnant women to avoid contact with rodents to prevent this rare but serious congenital infection.

  PublisherDOI

• Rapid dissemination of Staphylococcus aureus in the neonatal intensive care unit is associated with invasive infection

  Nature Communications · 2026-02-09 · 2 citations

  articleOpen access

  Staphylococcus aureus is a leading cause of severe infections in neonatal intensive care units (NICUs). We present results of precision surveillance of S. aureus carriage and invasive infection in a cohort study of high-risk infants in the NICU with the goal of identifying novel strategies for prevention and control. Using whole genome sequence guided epidemiology over a 3-year timeframe, we identify spatial and temporal links for transmission between babies, suggesting shared spaces, caregivers, and physical proximity as major risks for transmission in the NICU. Moreover, environmental surveillance reveals potential environmental reservoirs of S. aureus. Remarkably, specific clusters of S. aureus strains that are associated with invasive infection are also detected in more infants over time during routine surveillance, suggesting a strong link between the rate of dissemination and disease in this vulnerable population. Overall, our findings demonstrate a strong association amongst colonization, transmission, persistence, and the development of invasive infections, underscoring the importance of targeted measures to prevent S. aureus infections in the NICU setting. In this work, authors use whole genome tracking in a neonatal intensive care unit to reveal a strong link between Staphylococcus aureus colonization and invasive infection, pinpointing critical new targets for infection prevention in high-risk infants.

  PublisherOA PDFDOI

• Vancomycin Concentrations in Umbilical Cord Blood After Intrapartum Exposure

  Obstetrics and Gynecology · 2025-02-06 · 1 citations

  articleSenior author

  Little is known about the fetal-neonatal pharmacokinetics of maternally administered, weight-based vancomycin dosing for group B streptococcus (GBS) intrapartum antibiotic prophylaxis. Our objective was to quantify vancomycin concentrations in umbilical cord blood at birth after weight-based maternal intrapartum vancomycin administration and to assess cord blood vancomycin levels relative to the established GBS clinical minimum inhibitory concentration (MIC) breakpoint. Using a convenience sample of stored sera from our biorepository, we measured vancomycin levels in umbilical cord blood from 26 neonates after maternal intrapartum vancomycin exposure. Most neonates (24/26, 92.3%; 95% CI, 74.9-99.1%) had vancomycin cord blood levels above the MIC breakpoint (1 microgram/mL or higher) for GBS.

  PublisherDOI

• Vancomycin Concentrations in Umbilical Cord Blood After Intrapartum Exposure

  Obstetric Anesthesia Digest · 2025-08-20

  articleSenior author

  ( Obstet Gynecol . 2025;145:435–438 DOI: 10.1097/AOG.0000000000005843) A study investigated the presence of vancomycin (VANC) in umbilical cord blood following maternal intrapartum administration using current weight-based dosing guidelines for group B Streptococcus (GBS) prophylaxis. The objective was to assess whether these concentrations reached or surpassed the established minimum inhibitory concentration (MIC) needed to prevent neonatal GBS infection. Moreover, GBS colonization affects nearly 30% of pregnant individuals in the United States, and standard intrapartum antibiotic prophylaxis (IAP) involves beta-lactam antibiotics such as penicillin or ampicillin. However, for those with severe beta-lactam allergies and clindamycin-resistant GBS strains, weight-based VANC is recommended. Unlike beta-lactams, VANC transfers less efficiently through the placenta and is rapidly cleared during pregnancy due to increased kidney filtration. Concerns persist about whether VANC reaches effective fetal concentrations. Existing guidelines from the American Academy of Pediatrics suggest VANC is insufficient for GBS IAP, and data on fetal exposure using updated dosing remains limited.

  PublisherDOI

• The Contributions of delivery mode and intrapartum antibiotic exposure to body mass index among children through 5 years of age

  European Journal of Obstetrics & Gynecology and Reproductive Biology · 2025-04-20

  articleOpen access

  <h2>Abstract</h2><h3>Objective</h3> To investigate independent effects of group B Streptococcus (GBS) intrapartum antibiotic prophylaxis (IAP) and cesarean delivery (CD) on body mass index (BMI) during early childhood. <h3>Study design</h3> Retrospective cohort study of infants (n = 157,820) born 2007–2015 in an integrated healthcare system. Exposures were delivery mode (CD or vaginal delivery [VD]) and GBS IAP exposure. CD was further divided into elective CD (without labor or rupture of membrane [ROM]) or unscheduled CD (following labor and/or ROM). BMI over 5 years was compared using non-linear multivariate models with B-splines, adjusted for demographics, maternal medical and obstetrical factors, and childhood antibiotic exposure. <h3>Results</h3> At age 5 years, unscheduled CD without GBS IAP (Δ BMI 0.11 kg/m², 95 % CI 0.06 to 0.16, p < 0.0001) and unscheduled CD with GBS IAP (Δ BMI 0.24 kg/m², 95 % CI 0.11 to 0.36 kg/m², p = 0.0002) were positively associated with higher BMI compared to their VD counterparts, respectively. No BMI difference was observed between children born by elective versus unscheduled CD. GBS IAP exposure was positively associated with increased BMI compared to non-exposed births in both VD (Δ BMI 0.07 kg/m², 95 % CI 0.02 to 0.13 kg/m², p = 0.0125) and CD (Δ BMI 0.22 kg/m², 95 % CI 0.09 to 0.35 kg/m², p = 0.0009). <h3>Conclusions</h3> Based on our findings, the widespread administration of GBS IAP and birth by cesarean delivery independently contribute to a significant upshift in body weight early in life that compares to or is higher than the annual increase in BMI in U.S. children on a population level.

  PublisherDOI

Recent grants

• NIH Grant M01RR002635

  NIH · $27.3M · 2010

• NIH Grant K08HD041534

  NIH · $668k · 2007

Frequent coauthors

• Sagori Mukhopadhyay

  253 shared

• Dustin D. Flannery

  Children's Hospital of Philadelphia

  158 shared

• Jeffrey S. Gerber

  Children's Hospital of Philadelphia

  111 shared

• Brenda B. Poindexter

  74 shared

• Eric C. Eichenwald

  Eunice Kennedy Shriver National Institute of Child Health and Human Development

  72 shared

• Miren B. Dhudasia

  Children's Hospital of Philadelphia

  55 shared

• Lawrence C. Madoff

  48 shared

• Gabriel J. Escobar

  Kaiser Permanente

  44 shared