Neonatal inflammation and its association with asthma and obesity in late childhood among individuals born extremely preterm

Crisma Emmanuel; Ali Oran; Elizabeth T Jensen; Raina N Fichorova; William A Gower; Eliana M Perrin; Keia Sanderson; Andrew M South; Semsa Gogcu; Jeffrey Shenberger; Rachana Singh; Kartikeya Makker; Amanda L Thompson; Hudson Santos; Rebecca C Fry; T M O'Shea; ELGAN-ECHO Study Investigators

doi:10.1038/s41390-024-03325-x

Neonatal inflammation and its association with asthma and obesity in late childhood among individuals born extremely preterm

Pediatr Res. 2024 Jun 24. doi: 10.1038/s41390-024-03325-x. Online ahead of print.

Authors

Crisma Emmanuel¹, Ali Oran², Elizabeth T Jensen³, Raina N Fichorova⁴, William A Gower⁵, Eliana M Perrin⁶, Keia Sanderson⁷, Andrew M South^{3

8}, Semsa Gogcu⁸, Jeffrey Shenberger⁹, Rachana Singh¹⁰, Kartikeya Makker⁶, Amanda L Thompson¹¹, Hudson Santos¹², Rebecca C Fry², T M O'Shea¹³; ELGAN-ECHO Study Investigators

Collaborators

ELGAN-ECHO Study Investigators:
Julie V Rollins, Bhavesh Shah, Rachana Singh, Ruben Vaidya, Linda Van Marter, Camilla Martin, Janice Ware, Caitlin Rollins, Cynthia Cole, Ellen Perrin, Christina Sakai, Frank Bednarek, Jean Frazier, Richard Ehrenkranz, Jennifer Benjamin, Angela Montgomery, T Michael O'Shea, Lisa Washburn, Semsa Gogcu, Carl Bose, Diane Warner, Steve Engelke, Amanda Higginson, Jason Higginson, Kelly Bear, Mariel Poortenga, Steve Pastyrnak, Padu Karna, Nigel Paneth, Madeleine Lenski, Michael Schreiber, Scott Hunter, Michael Msall, Danny Batton, Judith Klarr, Young Ah Lee, Rawad Obeid, Karen Christianson, Deborah Klein, Katie Wagner, Victoria Cobb, Shaula Paula, Andres Santana, Maureen Pimental, Collen Hallisey, Taryn Coster, Maddie Dolins, Maggie Mittleman, Hannah Haile, Julia Rohde, Kaysi Herrera Pujols, Susie Rodriquez, Kyla Waring, Ellen Nylen, Emily Neger, Kathryn Mattern, Catherine Ma, Deanna Toner, Elizabeth Vitaro, Allison Nolan, Lauren Venuti, Beth Powers, Ann Foley, Taylor Merk, Joanne Williams, Elaine Romano, Christine Henry, Debbie Hiatt, Nancy Peters, Patricia Brown, Emily Ansusinha, Jazmyne James, Nou Yang, Nicole Froelich, Kristi Lanier, Gennie Bose, Janice Wereszczak, Janice Bernhardt, Joan Adams, Donna Wilson, Nancy Darden-Saad, Bree Williams, Emily Jones, Hannah Morris, Taiara Williams, Isabella Carter, Dinah Sutton, Julie Rathbun, Stephanie Fagerman, William Boshoven, Jalen Johnson, Brandon James, Cynthia Gile, Megan Maynard, Emina Nakic, Duvonna Haynes, Karen Miras, Carolyn Solomon, Deborah Weiland, Chloe Caltrider, Grace Yoon, Rugile Ramoskaite, Suzanne Wiggins, Krissy Washington, Ryan Martin, Barbara Prendergast, Emma Lynch, Sabina Hajdarovic, Beth Kring

Affiliations

¹ University of North Carolina School of Nursing, Chapel Hill, NC, USA.
² Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina, Chapel Hill, NC, USA.
³ Department of Epidemiology and Prevention, Wake Forest University, Winston-Salem, NC, USA.
⁴ Brigham and Women's Hospital, Boston, MA and Harvard Medical School, Boston, MA, USA.
⁵ Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
⁶ Department of Pediatrics, Johns Hopkins University School of Medicine and School of Nursing, Baltimore, MD, USA.
⁷ Department of Medicine-Nephrology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
⁸ Departments of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁹ Connecticut Children's Hospital, Hartford, CT and University of Connecticut School of Medicine, Farmington, CT, USA.
¹⁰ Department of Pediatrics, Tufts University School of Medicine, Boston, MA, USA.
¹¹ Department of Anthropology, University of North Carolina, Chapel Hill, NC, USA.
¹² University of Miami School of Nursing, Miami, FL, USA.
¹³ Brigham and Women's Hospital, Boston, MA and Harvard Medical School, Boston, MA, USA. [email protected].

PMID: 38914762
DOI: 10.1038/s41390-024-03325-x

Abstract

Background: Asthma and obesity are frequent outcomes among individuals born extremely preterm and are associated with decreased lifespan. Neonatal inflammation is associated with chronic neurodevelopmental disorders; however, it is less studied in association with other later childhood chronic disorders in this population.

Methods: Fourteen hospitals in 5 U.S. states enrolled 1506 infants born before 28 weeks of gestation in the Extremely Low Gestational Age Newborn cohort in 2004-2014. Neonatal blood spots were collected on postnatal days 1, 7, 14, 21, and 28, and used to measure 14 inflammation-related proteins. Associations were evaluated between high (top quartile) levels of proteins and two chronic health disorders at ages 10 and 15 years: physician-diagnosed asthma and obesity (body mass index ≥95th percentile).

Results: Few associations were found between high levels of 14 inflammation-related proteins, either on a single day or on multiple days, and either asthma or obesity. Similarly, few associations were found in analyses stratified by sex or presence/absence of prenatal inflammation.

Conclusions: In extremely preterm newborns, systemic elevations of inflammation-related proteins during the neonatal period were not associated with childhood asthma and obesity outcomes at 10 or 15 years of age.

Impact: In the large multi-center Extremely Low Gestational Age Newborn (ELGAN) cohort, sustained elevation of neonatal levels of inflammation-related proteins was not consistently associated with asthma or obesity outcomes at 10 or 15 years of age. This finding contrasts with reported associations of perinatal inflammation with obesity at 2 years and neurodevelopmental disorders at 2-15 years in the ELGANs, suggesting that unlike neurodevelopment, peripubertal obesity and asthma may be driven by later childhood exposures. Future research on perinatal mechanisms of childhood asthma and obesity should account for both fetal and later exposures and pathways in addition to inflammation at birth.

Abstract

Grants and funding