Low-Dose Aspirin Use Does Not Increase Disease Activity in Pregnant Patients with Inflammatory Bowel Disease.

BACKGROUND: The adverse effects of non-steroidal anti-inflammatory (NSAID) drugs on the gastrointestinal system are well recognized, but the effect of NSAID use on disease activity patients with inflammatory bowel disease (IBD) remains unresolved. Low-dose aspirin (LDA) is recommended for all pregnant patients with risk factors for developing preeclampsia, including autoimmune conditions. As recognition of risk factors for preeclampsia improves, the preventative use of LDA is likely to increase. AIMS: To investigate if LDA use for prevention of preeclampsia increases the risk of disease activity in pregnant women with IBD. METHODS: Single-center retrospective cohort study of pregnant patients with IBD who delivered from 2012 to 2020, comparing those with and without LDA use. Primary outcome was odds of clinical IBD activity in patients in remission at time of conception. Secondary outcomes were rate of elevated inflammatory biomarkers, defined as C-reactive protein > 5 ug/mL or fecal calprotectin > 250 ug/g, and rate of preeclampsia. Univariate analyses tested for associations. RESULTS: Patients taking LDA were older (p = 0.003) and more likely to have chronic hypertension (p = 0.002), to have undergone in vitro fertilization (p < 0.001), and to be on biologics (p = 0.03). Among patients in remission at conception, there was no difference in clinical disease activity or biomarker elevation during pregnancy based on LDA use (OR 1.27, 95% CI [0.55-2.94], p = 0.6). Rates of preeclampsia were similar between groups. CONCLUSION: LDA use for preeclampsia prevention did not increase the incidence of disease activity in pregnant patients with IBD.

Longitudinal Changes in Fecal Calprotectin Levels Among Pregnant Women With and Without Inflammatory Bowel Disease and Their Babies.

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.

Identifying Patient Priorities for Preconception and Pregnancy Counseling in IBD.

BACKGROUND: Inflammatory bowel disease (IBD) commonly affects women of reproductive age. Many patients lacking knowledge about IBD and reproduction make uninformed decisions, such as voluntary childlessness and medication cessation. Education should be individualized to the patient's knowledge base and include topics of most importance to the patient. Our study aimed to describe the priority rankings of topics selected by patients seeking preconception and pregnancy counseling. METHODS: As part of an ongoing prospective study, patients with IBD were asked to rank, in order of importance, nine a priori preconception, pregnancy, and postpartum topics they would like addressed by our specialized care team, which includes an IBD physician and a high-risk obstetrician. χ2 and Fisher's exact tests were used to assess associations between clinical and demographic characteristics and priority rankings, and a p value cutoff for significance was set as .05. RESULTS: One hundred and fifty-eight women with IBD (mean (IQR) age; 32 (28-37) years) were seen in consultation, and 116 (70 (60%) CD, 43 (37%) UC, and 3 (3%) IBD-U) completed intake forms were analyzed. There were 78 (68%) women seen in the preconception stage, median age 31 (IQR 28-34), and 38 women (32%) were pregnant, median age 32 (IQR 28-33). Safety of IBD medications during pregnancy was most commonly ranked as top priority (40%) for all patients regardless of pregnancy status, followed by control of IBD disease activity and impact on pregnancy (31%), impact of IBD and surgery on fertility (19%), pregnancy outcomes for the baby (18%), mode of delivery (6%), inheritance of IBD (4%), breastfeeding (2%), nutritional health (2%), and vaccines and newborn care (1%). The impact of IBD and surgery on fertility was ranked as the number one priority more often in the preconception group (p value < 0.01) and mode of delivery in the pregnancy group (p value 0.04). CONCLUSION: Safety of IBD medications remains a priority topic for patients seeking preconception and pregnancy counseling.

Peripartum Exposure to Biologic Therapy Does Not Impact Postpartum Wound Healing in Women With IBD.

BACKGROUND: Inflammatory bowel disease (IBD) commonly affects women during childbearing years and often requires antepartum therapy. Data regarding effects of biologic exposure on delivery outcomes are limited. We explored whether peripartum biologic exposure impacts wound healing following cesarean section (C-section) and vaginal delivery (VD) in IBD patients. METHODS: Pregnancy and IBD data from the IBD Preconception and Pregnancy Planning (I-PrePP) Clinic database were collected and analyzed. Primary outcome was frequency of postpartum wound infection in women receiving peripartum biologics, defined as exposure in the third trimester and up to 2 weeks postdelivery relative to nonexposed patients. Secondary outcomes included effect of peripartum biologic timing and IBD phenotype on wound healing. Descriptive statistics summarized data using frequency for categorical variables and median for continuous variables. Univariate analyses tested associations when appropriate. RESULTS: Of 100 deliveries (interquartile range, 30-35; median, 33 years old), 58 were C-sections and 42 VDs. Peripartum biologic exposure occurred in 72% (42 of 58) and 57% (24 of 42), respectively. Median time from last dose to delivery was 6 (interquartile range, 4-8) weeks; 21 (32%) received biologics within 72 hours following delivery. Seven infections occurred following C-section among 5 unique CD patients. Peripartum biologic exposure was not associated with infection (4 of 66 [6%] exposed vs 3 of 34 [8.8%] nonexposed; P = .68), nor was disease activity (P = 1.0). Crohn's disease (P = 0.02), internal penetrating phenotype (P < .001), prior IBD surgery (P = .03), and prior postpartum infection (P = .04) were associated with infection. CONCLUSIONS: Peripartum biologic exposure does not impair postpartum wound healing; however, patients with more complicated disease phenotypes require close monitoring.

No prior studies have explored risk of postpartum wound infection in women receiving biologics in the peripartum period. We found no significant increase in risk of postpartum wound infection; however, internal penetrating Crohn's phenotype may be an important risk factor.

Placental cord insertion distance from the placental margin and its association with adverse perinatal outcomes.

OBJECTIVE: The placental cord insertion (PCI) to the placental margin has not been well studied as a continuous variable in relation to birth outcomes. We sought to evaluate the impact of PCI distance on outcomes associated with placental function and development of fetal growth restriction (FGR). STUDY DESIGN: This was a retrospective study of singleton gestations that underwent a fetal anatomy ultrasound from 2011-2013. The PCI was recorded as the distance in centimeters from the placental margin. Patients had FGR if the overall estimated fetal weight was <10 % for gestational age or abdominal circumference <5 % in the third trimester. Delivery, obstetric, and neonatal outcomes were obtained via medical chart review. Logistic and linear regression models were used to assess the impact of PCI distance on maternal and neonatal delivery outcomes. RESULTS: Of the 1443 women who met inclusion criteria, 93.6 % delivered at term. The mean (±SD) PCI distance was 4.4 ± 1.4 cm. There was no association between PCI and cesarean delivery, peripartum hemorrhage (PPH), pre-eclampsia, 5-min Apgar, or intrauterine fetal demise. PCI distance was statistically significantly shorter in patients requiring neonatal intensive care unit (NICU) admission (4.1 ± 1.5 cm vs. 4.4 ± 1.4 cm, p = 0.02) and was associated with lower birthweight (p = 0.01), though this association was no longer seen when corrected for gestational age. There were 3.5 % of patients who developed FGR; PCI distances from the placental edge were not significantly different for patients who developed FGR compared to those who did not (4.2 ± 1.4 cm vs. 4.5 ± 1.4 cm, p = 0.18). Furthermore, a receiver operating characteristic (ROC) curve for PCI had poor sensitivity (area under the curve [AUC] 0.57, 95 % CI 0.49-0.65). CONCLUSION: PCI distance at the time of fetal anatomic survey is significantly associated with NICU admission, though does not appear to impact rates of preterm birth, pre-eclampsia, PPH or cesarean delivery. PCI distance in singleton gestations does not appear to be predictive of FGR.

Mitochondrial gene expression profiles are associated with intrahepatic cholestasis of pregnancy.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) affects 0.2-2% of pregnant women. While the maternal clinical course of ICP is usually benign, the fetal effects can be severe spanning from spontaneous preterm birth to fetal demise to long term effects on the health of the progeny. ICP is characterized by high maternal serum levels of bile acids and placental and hepatic bile acids accumulation. Intrahepatic cholestasis, in the non-pregnant state, has been also linked to alterations of the mitochondrial activity attributed to high oxidative stress rates driven by high intracellular bile acids concentrations. Here we explored the hypothesis that elevated bile acid levels of ICP modify the placental mitochondrial activity. METHODS: By using a set of 12 ICP and 12 control placenta samples, we assessed the expression of all 13 mitochondrial-encoded protein-coding genes and the mitochondrial DNA (mtDNA) relative abundance by real-time PCR. We also assessed the oxidative stress status by measuring DNA damage by ELISA. RESULTS: We determined that: 1) the expression of MT-ND4L (+53% - p < 0.01), MT-ND4 (-19%-0.05 < p ≤ 0.01), MT-ND5 (+40% - p < 0.01), MT-CYTB (+35% - p < 0.01) is associated with ICP; 2) the mtDNA relative abundance is not associated with ICP (0.098 in ICP vs 0.118 in controls - p > 0.05); 3) the oxidative stress status is associated with ICP (4403.9 pM 8-oxo-dG/µg DNA in ICP vs 3809.8 pM 8-oxo-dG/µg DNA in controls - p < 0.01). DISCUSSION: This preliminary study suggests that mitochondria in placenta respond to high oxidative stress to modify their gene expression which may play an important role in the pathophysiology of ICP.

The utility of screening for historical risk factors for preterm birth in women with known second trimester cervical length.

OBJECTIVE: To evaluate for the presence of risk factors (RFs) for preterm birth (PTB) in women without prior PTB having second trimester cervical length (CL) screening, and to estimate the utility of RF screening. METHODS: "Low-risk" singletons were prospectively screened with midtrimester transvaginal ultrasound CL. Prior PTB, intrauterine fetal demise and lethal anomalies were excluded. Women were analyzed based on second trimester CL (<25 mm versus ≥25 mm) and the presence of RFs for PTB. A p-value of < 0.05 was considered significant. RESULTS: A total of 639 women were screened; 8% had CL <25 mm. Ninety-eight percent of women with CL <25 mm and 95% of women with CL ≥25 mm had RFs for PTB. Five percent of women with a CL ≥25 mm delivered preterm as compared to 18% with CL <25 mm (p < 0.01). Treatment of cervical dysplasia, drug use during the pregnancy and unmarried status were significantly more common in women with CL <25 mm than CL ≥25 mm. When data were analyzed by CL, the presence of additional RFs did not add to the prediction of PTB <37 weeks. DISCUSSION: Over 95% of singleton gestations without prior PTB have ≥1 other RF for PTB. In women without prior PTB, assessment of other PTB RFs does not add to prediction of PTB provided by CL alone.

Prediction of preterm birth: cervical sonography.

The cervix has to open to allow vaginal birth. Ultrasound has now shown that this lower part of the uterus begins to show changes weeks before eventual birth. Only transvaginal ultrasound should be used to evaluate the cervix for prediction of preterm birth (PTB). The shortest best cervical length (CL) is the most effective measurement for clinical use. Proper technique is paramount for accurate results. The risk of PTB increases with ever shorter CL (<25 mm). Other factors that must be carefully considered when using CL for prediction of PTB are number of fetuses, risk factors for PTB, and gestational age at screening.