Same PFAS Metabolites Tied to Maternal IBD Linked to Child Calprotectin

New data from 3 birth cohorts show that a small number of specific PFAS metabolites, rather than PFAS exposure in general, were the strongest contributors to the association between maternal inflammatory bowel disease (IBD) and elevated gut inflammation markers in children, according to a study published in Clinical Gastroenterology and Hepatology.¹

The analysis, led by Vishal Midya, PhD, and colleagues at the Icahn School of Medicine at Mount Sinai, measured per- and polyfluoroalkyl substances (PFAS) in cord blood, newborn dried blood spots, and maternal serum from mother-offspring pairs, then tracked fecal calprotectin—a standard biomarker of intestinal inflammation—in the children from birth through age 11. Earlier research linked PFAS exposure to later occurrence of IBD.²

HCPLive discussed the findings with Elizabeth A. Spencer, MD, a pediatric gastroenterologist at Mount Sinai who was enrolled as one of the mothers in the underlying cohort research and now runs the institution's IBD prevention clinic, which counsels people with a family history of IBD on modifiable risk factors, including PFAS exposure.

What Birth Cohorts Were Used in the PFAS-IBD Study?

Researchers drew on 3 separate cohorts: the MECONIUM and MELODY studies in New York, and the PROGRESS study in Mexico City. Dried blood spot and cord blood analyses each included samples from more than 80 mother-offspring dyads (84 and 93, respectively), with 55 dyads represented in both. PFAS were detectable across all three sample types, indicating exposure begins before birth.¹

Rather than testing for one or two individual PFAS compounds, the study modeled PFAS mixtures. The association between PFAS mixtures and elevated calprotectin held across both a U.S. population, where newer-generation PFAS predominate, and a Mexican population, where older "legacy" PFAS are more common.

How Strong Is the PFAS-Calprotectin Association?

The magnitude of the association varied by sample type and by the age at which calprotectin was measured. For each decile increase in PFAS mixture level, log-transformed fecal calprotectin at age 6 increased by an adjusted β of 0.44 (95% CI, 0.18–0.70) using dried blood spot data, and by 0.69 (95% CI, 0.53–0.85) using cord blood data. Maternal serum PFAS during pregnancy was associated with a smaller, but still statistically significant, increase in calprotectin later in childhood (β, 0.19; 95% CI, 0.05–0.33).¹

The cord blood and dried blood spot estimates are both drawn from samples collected within a day of birth. Elizabeth A. Spencer, MD, Associate Professor of Pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai and Mount Sinai Kravis Children's Hospital, who was not an investigator on the study but was enrolled as one of the mothers in the underlying cohort research, said prior research in this area has generally focused on individual PFAS compounds rather than mixtures. "Historically, researchers have often looked at just one or two PFAS compounds, but that's not how people are actually exposed," she said. "This study looked at broader PFAS mixtures, which better reflects real-world exposure, and the association held consistently across different populations and different PFAS profiles."

Which PFAS Metabolites Link Maternal IBD to Infant Gut Inflammation?

Beyond the mixture-level findings, the study identified specific metabolites as the top contributors to the calprotectin association. Mothers with IBD had greater levels of certain PFAS metabolites than mothers without IBD, and those same metabolites were the strongest contributors to their children's elevated calprotectin. Perfluoro-1-octane sulfonamide acetic acid was the metabolite most associated with maternal IBD status in dried blood spots, while 3-perfluorohexyl-2-hydroxypropyl acrylate carried that association in cord blood—and both were also the top contributors to offspring calprotectin in their respective sample types.¹

Does Elevated Calprotectin Mean a Child Will Develop IBD?

None of the children in the cohorts, now as old as 11, have been diagnosed with IBD. Spencer said a modestly elevated calprotectin level is not itself a clinical diagnosis, and whether these findings predict later IBD—or where a meaningful threshold might fall—remains an open question for longer-term follow-up.

"It's more likely one part of a broader environmental mixture that raises intestinal inflammation and, over time, contributes to IBD risk," Spencer said. "This is an association, not a proven causal pathway, and it shouldn't cause parents to panic."

Spencer also pointed to a broader implication of the mixture and metabolite-level approach: because most people who develop IBD do not have a family history of the disease, tools like existing newborn blood-spot cards could eventually help flag high PFAS exposure in the general population, not just in high-risk families, if combined with additional biomarkers in future research.

Editor's Note: Spencer reports no relevant disclosures.

References

1. Midya V, Maroli AS, Picker M, et al. Per- and Polyfluoroalkyl Substances in Early Life Are Associated With Childhood Intestinal Inflammation: Analyses of Three Birth Cohorts. Clin Gastroenterol Hepatol. Published online July 10, 2026. doi:10.1016/j.cgh.2026.07.001

2. Agrawal M, Midya V, Maroli A, et al. Per- and Poly-Fluoroalkyl Substances Exposure Is Associated With Later Occurrence of Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. Published online December 26, 2023. doi:10.1016/j.cgh.2023.12.020