Active inflammatory bowel disease (IBD) during pregnancy increases the risk for adverse events including spontaneous abortion, low birth weight, and preterm birth.1 Pregnant women with IBD are also more likely than pregnant women without IBD to have Cesarean section and to give birth to infants who are small for their gestational age.2   Therefore, detecting IBD early may facilitate early clinical remission and improved outcomes for mothers with IBD and their babies. In a new study published in Journal of Clinical Gastroenterology, researchers reviewed the role of noninvasive fecal tests in assessing IBD in pregnancy.

Challenges With Assessing IBD in Pregnancy

At present, researchers consider endoscopy and radiologic confirmation to be key elements in assessing activity in IBD in the general population.1 However, these procedures present challenges in pregnant women.

Researchers of a 2017 study published in Gastroenterology found that rates of preterm birth and small size for gestational age were higher in women who had an endoscopy during pregnancy compared with those who did not (7.6% vs 4.8% and 3.6% vs 2.5%, respectively).3 Current guidelines suggest that lower gastrointestinal endoscopic evaluations in pregnant women be limited to the second trimester only when possible.1

Additionally, imaging techniques such as magnetic resonance imaging may be associated with teratogenesis during the first trimester, with eye malformations having been documented in studies in which animals were exposed to this imaging technique.4 Computed tomography scans that use iodine-based contrast agents have been found to negatively affect thyroid function in fetuses.1

Alternative Methods of Assessing IBD in Pregnancy

Using noninvasive tools such as the Harvey-Bradshaw Index, Simple Clinical Colitis Activity Index, and partial Mayo scores to monitor IBD during pregnancy may reduce the risk for adverse outcomes.1 However, these tools may not be entirely useful in pregnancy, since routine serum biomarkers such as C-reactive protein (CRP), albumin, and hemoglobin are altered during pregnancy and may not correlate with IBD activity in this population.1

Researchers have proposed using fecal calprotectin (FCP) to monitor IBD in pregnant patients since its use in nonpregnant IBD patients was shown safe and effective at ruling out active IBD. Researchers of a 2017 study published in Inflammatory Bowel Diseases found that when combined with physician global assessment, FCP may be an optimal way to assess activity in IBD during pregnancy.5 Up until recently, this finding was limited on behalf of small sample size and lack of standardized methods for using FCP to assess IBD in pregnancy.5

The latest study from Journal of Clinical Gastroenterology evaluates the role of FCP and other noninvasive serum and fecal biomarkers in monitoring and assessing disease activity in pregnant women with IBD. Researchers used multiple electronic databases including Medline and Cochrane Central Register of Controlled Trials to identify all studies that reported levels of stool and blood tests in assessing disease activity in IBD in the pregnant population.

Role of Serum CRP

In 3 studies, serum CRP levels were evaluated in pregnant women with IBD stratified by disease activity and gestational period.

In the first study, CRP was found to be significantly higher in clinically active disease during the second trimester compared with inactive disease (8.9 mg/L [range 0.6-40.0 mg/L] vs 2.3 mg/L [range 0-12.2 mg/L]; P =.0001), but there were no other significant differences in CRP levels during other gestational periods. During the second trimester, CRP correlated with higher FCP levels (r=0.57, P =.0007).1

In the second study, researchers reported significant differences in median CRP between clinically active disease and inactive disease in all gestational periods, with the greatest difference observed during the second trimester (14 mg/L [range 10-22 mg/L] vs <10 mg/L [range <10 to <10 mg/L], P <.02].1

In the third study, researchers evaluated 23 women with either ulcerative colitis or Crohn’s disease and reported median CRP levels that were numerically higher in active disease vs inactive disease during the first trimester (24.75 vs 6 mg/L; P =1.0). During the second and third trimesters, there were no differences in median CRP levels between ulcerative colitis (n=13) and Crohn’s disease (n=10).1

Role of Serum Albumin and Hemoglobin

In the 1 study that compared serum albumin and hemoglobin levels in pregnant women with clinically active and inactive IBD, researchers detected no difference in these levels when patients were stratified by gestational age and the presence of clinically active disease. In women with inactive disease, serum albumin and hemoglobin levels declined naturally between the first and third trimesters.1

Role of Fecal Lactoferrin

There were 2 studies that assessed the role of fecal lactoferrin (FL) in pregnant women with IBD. In the first study, researchers found FL levels to be significantly higher in pregnant women with IBD at each trimester compared with healthy pregnant controls. During the third trimester only, FL was found to significantly correlate with physician global assessment (Spearman r=0.41, P =.001), partial Mayo score (Spearman r=0.41, P =.04), Harvey-Bradshaw Index (Spearman r=0.36, P =.25), and FCP (Spearman r=0.78, P <.0001).1

In the second study, researchers found that the median FL was significantly higher in pregnant women with IBD compared with healthy pregnant controls (median 9.5 vs 2.0 μg/mL, P =.035). FL was found to correlate with FCP only.1

Although Fl levels correlate with clinical scores such as the Harvey-Bradshaw Index and FCP, the data is limited, and the sample sizes are small. Therefore, the precise role of FL in evaluating IBD during pregnancy remains to be elucidated with larger, prospective studies.

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Role of FCP

The role of FCP in pregnant women without IBD was evaluated in 4 studies, with 2 of these studies directly comparing FCP between pregnant women with IBD to healthy pregnant controls. Overall, the median FCP in healthy pregnant patients (n=162) ranged from 0 to 25 μg/g, and the mean FCP ranged from 19.7 to 36.9μg/g.1

In the first of 2 studies comparing pregnant women with IBD to healthy controls, the overall median FCP was significantly higher in pregnant patients with IBD compared with healthy counterparts (131 μg/g, range 0-3600 μg/g vs 0 μg/g, range 0-84 μg/g; P <.0001). Commercially available sandwich enzyme-linked immunosorbent assay FCP kits were used in the first study. In the second study, the median FCP was found to be significantly higher in pregnant patients with IBD compared with healthy counterparts (416 μg/g, interquartile range [IQR] 516 μg/g vs 15 μg/g, IQR 38 μg/g; P <.001). Researchers used a Quantum Blue Fecal Calprotectin High Range Rapid Test for the second study.1

Researchers of additional studies that evaluated FCP in pregnant women with IBD produced similar results, showing that FCP levels were significantly higher in pregnant women with IBD compared to those without IBD, and in patients with active disease compared with those with inactive disease across all gestational periods.

Conclusion

Researchers found that only FCP appeared to correlate with disease activity in IBD in every gestational stage of pregnancy. They concluded that fecal tests like FCP do not appear to be affected by physiological changes that occur during pregnancy and that these tests may be useful in predicting IBD activity across all gestational periods, including conception. Furthermore, use of FCP tests may lead to optimization of therapy, improved outcomes for mother and baby, and improved chances of achieving remission.

References

1. Tandon P, Leung K, Yusuf A, Huang VW. Noninvasive methods for assessing inflammatory bowel disease activity in pregnancy: a systematic review. J Clin Gastroenterol. 2019;53(8):574-581.

2. Shand AW, Chen JS, Selby W, Solomon M, Roberts CL. Inflammatory bowel disease in pregnancy: a population-based study of prevalence and pregnancy outcomes. BJOG. 2016;123(11):1862-1870.

3. Ludvigsson JF, Lebwohl B, Anders E, et al. Outcomes of pregnancies for women undergoing endoscopy while they were pregnant: a nationwide cohort study. Gastroenterology. 2017;152(3);554-563.

4. Patenaude Y, Pugash D, Lim K, et al; Diagnostic Imaging Committee; Society of Obstetricians and Gynaecologists of Canada. The use of magnetic resonance imaging in the obstetric patient. J Obstet Gynaecol Can. 2014;36(4);349-363.

5. Julsgaard M, Hvas CL, Gearry RB, et al. Fecal calprotectin is not affected by pregnancy: clinical implications for the management of pregnant patients with inflammatory bowel disease. Inflamm Bowel Dis. 2017;23(7):1240-1246.