Gastroenterology. 2021 Mar;160(4):1118-1130.e3. doi: 10.1053/j.gastro.2020.11.050.Epub 2020 Dec 9.

Eun Soo Kim ¹, Leonid Tarassishin ², Caroline Eisele ², Amelie Barre ³, Nilendra Nair ⁴, Alexa Rendon ², Kelly Hawkins ², Anketse Debebe ², Sierra White ², Anne Thjømøe ⁵, Einar Mørk ⁵, Mario Bento-Miranda ⁶, Hinaben Panchal ⁷, Manasi Agrawal ⁸, Anish Patel ⁹, Ching-Lynn Chen ¹⁰, Asher Kornbluth ⁸, James George ⁸, Peter Legnani ⁸, Elana Maser ⁸, Holly Loudon ¹⁰, Maria-Teresa Mella ¹¹, Joanne Stone ¹¹, Marla Dubinsky ¹², João Sabino ¹³, Joana Torres ¹⁴, Jean-Frederic Colombel ⁸, Inga Peter ², Jianzhong Hu ¹⁵, Mount Sinai Road to Prevention Study Group

Author information

• ¹Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.
• ²Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
• ³Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Cochin Hospital, Université de Paris, Paris, France.
• ⁴Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
• ⁵CALPRO AS, Lysaker, Norway.
• ⁶Division of Gastroenterology, Hospital and University Center of Coimbra, Coimbra, Portugal.
• ⁷Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
• ⁸The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
• ⁹Division of Gastroenterology, Brooke Army Medical Center, San Antonio, Texas.
• ¹⁰Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York.
• ¹¹Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York.
• ¹²Department of Pediatric Gastroenterology and Nutrition, Icahn School of Medicine at Mount Sinai, New York, New York.
• ¹³Department of Gastroenterology, University Hospitals of Leuven, Leuven, Belgium.
• ¹⁴The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Surgical Department, Hospital Beatriz Ângelo, Loures, Portugal.
• ¹⁵Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: jianzhong.hu@mssm.edu.

Abstract

Background & aims: The effect of pregnancy on inflammatory bowel disease (IBD) remains poorly understood. We aimed to monitor intestinal inflammation using fecal calprotectin (FC) in pregnant women and their babies during early life.

Methods: Pregnant women with or without IBD and their infants were prospectively enrolled. FC levels were measured at each trimester of pregnancy and in babies throughout the first 3 years of life. Repeated-measures analysis was applied to investigate changes in FC levels while adjusting for confounders. The FC levels were correlated with the bacterial abundance in both mothers and babies.

Results: Six hundred and fourteen fecal samples from 358 mothers (98 with IBD) and 1005 fecal samples from 289 infants (76 born to IBD mothers) were analyzed. Pregnant Patients with IBD maintained higher FC levels through pregnancy compared with controls (P = 7.5 × 10^-54). FC gradually increased in controls and declined in Patients with IBD throughout pregnancy (P for interaction = 5.8 × 10^-7). Babies born to mothers with IBD presented with significantly higher FC levels than those born to controls up to 3 years of age, after adjusting for sex, delivery mode, feeding behavior, and antibiotics exposure (2 weeks to 3 months of age, P = .015; 12-36 months of age, P = .00003). Subdoligranulum, Roseburia, Fusicatenibacter, and Alistipes negatively correlated, and Streptococcus, Prevotella, Escherichia-Shigella, and Bifidobacterium positively correlated with maternal FC levels at T3. Faecalibacterium, Bifidobacterium, and Alistipes showed negative correlations, and Streptococcus were positively correlated with FC levels within 3 months of birth.

Conclusions: Pregnancy is associated with decreased inflammatory activity in mothers with IBD. Higher FC levels in babies born to mothers with IBD suggest subclinical inflammation in early life, the long-term consequences of which are uncertain.