Exposure to biologic therapy and associated maternal and neonatal outcomes in pregnancies complicated by inflammatory bowel disease.

BACKGROUND: There is growing evidence that biologic therapy is safe in pregnancies complicated by inflammatory bowel disease and that its use outweighs the risk of worsening disease activity, which is associated with adverse pregnancy outcomes. To our knowledge, there are limited data regarding the use of biologic therapy and the associated maternal adverse effects such as the risk of hypertensive outcomes, postoperative complications, and infectious risk. OBJECTIVE: Our objective was to evaluate a variety of obstetrical complications including maternal infectious outcomes, hypertensive outcomes, other adverse maternal outcomes including postoperative complications, venous thromboembolism, and postpartum hemorrhage; we also evaluated the neonatal outcomes associated with biologic use in pregnancies affected by inflammatory bowel disease. STUDY DESIGN: This was a retrospective cohort study including patients with inflammatory bowel disease who were pregnant and delivered at our institution. The maternal demographics and the incidence of maternal and neonatal outcomes were compared among groups on the basis of biologic exposure using the chi-square or Fisher exact test for categorical variables and the t test or Mann-Whitney test for continuous variables. Multivariable logistic regression analysis was performed on composite outcomes adjusting for age, disease activity, maternal obesity, history of cesarean delivery, and history of corticosteroid use in pregnancy. The statistical significance was defined as P<.05. RESULTS: A total of 322 patients who were pregnant, had inflammatory bowel disease, and delivered at our institution from 2012 to 2019, were included for analysis. Of these, 112 (34%) were on biologics during pregnancy. The patients in the biologic group had significantly lower body mass indices than the patients in the nonbiologic group (median body mass index, 22.4 vs 24.0, respectively; P=.04), and they were less likely to be multiparous (41% vs 59%, respectively; P=.003). In addition, more patients in the biologic group were likely to have Crohn disease with previous inflammatory bowel disease surgery (33% vs 20%, respectively; P=.01); otherwise, the 2 groups had similar baseline characteristics. Maternal infectious and hypertensive outcomes occurred significantly more frequently in the biologic group than the nonexposed group (22% vs 7%; P=.0003 and 19% vs 8%; P=.003, respectively). This remained statistically significant in multivariable logistic regression models. Specifically, maternal infectious and hypertensive outcomes occurred significantly more frequently in the patients on a single-agent antitumor necrosis factor treatment than the patients on no inflammatory bowel disease medication (24% vs 6%; P=.002; 22% vs 6%; P=.004), which remained statistically significant in multivariable logistic regression models. There was no difference in the neonatal adverse outcomes between the 2 groups. CONCLUSION: Our data suggest an association between antepartum biologic use- specifically antitumor necrosis factor alpha therapy-and an increased risk of maternal infectious and hypertensive outcomes. This increased risk may be related to underlying disease activity and the same should be incorporated into a discussion with the patient. However, the discussion must be balanced with the important benefit of optimal disease control associated with biologic use in patients being treated for IBD.

Accuracy of third trimester ultrasound in predicting neonatal birthweight in patients with inflammatory bowel disease.

OBJECTIVE: To evaluate the accuracy of third trimester ultrasound in predicting birthweight in patients with inflammatory bowel disease (IBD) using the gestation-adjusted projection (GAP) method. STUDY DESIGN: Retrospective cohort study including pregnant patients with IBD who had third trimester ultrasounds and delivered at a single institution from 2012 to 2017. Controls included pregnant patients without IBD seen during the study period with third trimester ultrasounds. Correlation plots of GAP birthweight and actual birthweight (AB) were created for IBD-positive cases, IBD-negative controls, and IBD-positive cases with and without prior abdominal surgery. GAP predicted birthweight error was calculated for cases and controls. Univariable linear regression models estimated the association between predicted birthweight and AB. Multivariable linear regression models estimated the association between GAP birthweight and AB adjusting for age, BMI, race, and IBD status. RESULTS: 320 patients were included (172 cases and 148 controls). Cases were more likely to be older (p < 0.001), white (p < 0.001), and have a lower BMI (p = 0.001). Correlation plots of GAP birthweight and AB showed linear correlations in cases (Spearman ρ = 0.81), controls (ρ = 0.74), cases with (p = 0.78) and without prior surgery (ρ = 0.83). GAP birthweight was significantly associated with AB in controls and cases in univariable linear regression models (ß = 0.85, standard error = 0.04, p < 0.001; ß = 0.90, standard error = 0.06, p < 0.001, respectively). No significant difference was found between the parameter estimates of the two models (p = 0.47). GAP birthweight remained significantly associated with AB in a multivariable linear regression model (ß = 0.86, standard error = 0.03, p < 0.001). There were no significant differences between GAP predicted birthweight error between controls and cases (APE 11% vs 10% respectively, p = 0.56) and between cases without and with prior surgery (APE 10% vs 11%, p = 0.7). CONCLUSION: The accuracy of fetal biometry in the third trimester for predicting actual birthweight was equivalent between patients with and without IBD and those with prior abdominal surgery.

Histology-specific FGFR2 alterations and FGFR2-TACC2 fusion in mixed adenoid cystic and neuroendocrine small cell carcinoma of the uterine cervix.

Neuroendocrine small cell carcinoma of the uterine cervix portends a dismal prognosis with limited treatment options. Rarely, tumors of mixed-lineage appear in gynecologic malignancies. Here, we report a 77-year-old woman who presented with complete uterine prolapse and 4-month history of vaginal bleeding. Histopathologic evaluation revealed a mixed adenoid cystic carcinoma and neuroendocrine small cell carcinoma of the uterine cervix. The tumor was PD-L1 and HPV 35 positive. The patient was treated with up-front surgery and adjuvant radiation. Independent, histology-specific alterations in FGFR2 and a FGFR2-TACC2 fusion were identified. Progression of disease occurred within 6 months for which she received chemotherapy and immunotherapy. However, the patient expired within a year. We comprehensively review how screening for and targeting of FGFR alterations in recurrent and metastatic cervical cancer might serve as a touchstone for future treatment regimens.