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Background There are increasing data on changes in intestinal inflammation and microbiome diversity during pregnancy in women with inflammatory bowel disease (IBD) with implications towards individual and offspring immune function. However, differences in intestinal inflammation, as measured by fecal calprotectin (FC) and microbial a-diversity, in consecutive pregnancies are not known. Methods We prospectively enrolled a cohort of women, 37 with IBD and 39 without IBD, during two consecutive pregnancies, and their offspring. We collected serial stool samples and clinical data, and measured FC and bacterial abundance during each trimester of each pregnancy. We further performed correlation analysis between FC in consecutive pregnancies and between microbial a-diversity in consecutive pregnancies among women with and without IBD. Results Compared to healthy controls, IBD pregnancies had significantly lower gestational age at birth and higher frequency of Cesarean section. Mode of delivery, the status of Group B Streptococcus (GBS) infection and GBS infection prophylaxis were significantly associated with the pregnancy order in both IBD and controls (Table). Furthermore, we observed strong correlations of FC (r=0.56, p-value=0.093) and microbial alpha-diversity assessed as operational taxonomic unit (OTU) richness (r=0.88, p=0.0087) between paired consecutive pregnancies in women with IBD, but not in those without IBD (Figure). There were no differences in microbial alpha-diversity using the Shannon and Simpson indices when comparing consecutive pregnancies of women with and without IBD. Conclusion In this study, we demonstrate that intestinal inflammation and microbiome diversity are more conserved in consecutive pregnancies of women with IBD compared to healthy controls. These findings may have implications towards understanding the impact of pregnancy on host-microbiome interactions in IBD as well as the potential impact on offspring health.

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.

Background IBD often affects women during their reproductive years; however, the effect of pregnancy on disease course remains poorly understood. We aimed to assess intestinal inflammation in IBD patients compared with controls as measured by faecal calprotectin (FC). We also investigated whether maternal IBD diagnosis was associated with altered FC in the offspring and if there were particular bacterial taxa that correlated with FC levels. Methods Pregnant women with or without IBD and their infants were prospectively enrolled in the MECONIUM study during 2015–2018 years. FC levels at each trimester of pregnancy and in babies throughout the first 3 years of life were measured using a quantitative enzyme immunoassay (CALPRO AS, Norway). Multivariate regression analysis was applied to investigate FC levels. Stool microbiota composition in the maternal and baby stool was assessed using 16s rRNA sequencing. Results 617 faecal samples from 342 mothers (91 IBD, 251 control) and 1005 faecal samples from 288 infants (born to 76 mothers with and 212 without IBD) were analysed. FC levels in pregnant women with IBD were significantly higher than in control pregnant women regardless of IBD type (Crohn’s disease vs. ulcerative colitis). In IBD mothers FC levels showed a decline during pregnancy (µg/g, median (interquartile range); first trimester 130.8 (102.3–147.3) vs. third trimester 85.9 (44.5–125.4), p = 0.02) (Figure 1). Patients with flare at stool collection had the highest, while those treated with anti-TNF plus thiopurine showed the lowest FC at each trimester. Babies born to mothers with IBD presented higher FC levels than those born to control mothers at multiple time points between 2 and 36 months of age (Figure 2A); the median FC levels were the highest after 1 year up to 3 years in those babies whose mothers presented active disease during pregnancy (Figure 2B). Microbial α-diversity showed an inverse relationship with FC in both mothers (r = −0.25, p = 0.032) and babies (r = −0.31, p = 0.0035). Blautia and Streptococcus abundance were positively correlated with FC in babies. Conclusion FC levels in IBD patients decreased throughout pregnancy. Maternal IBD, lower microbiome diversity and the abundance of certain microbial genera were associated with higher FC in the offspring up to 3 years of life. These findings suggest a potential favourable impact of pregnancy on IBD activity and highlight a possible effect of IBD during pregnancy on the intestinal inflammation in offspring, which could be mediated through altered microbiome.