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Clinical pharmacology studies that describe the pharmacokinetics and pharmacodynamics of drugs in pregnant women are critical for informing on the safe and effective use of drugs during pregnancy. That being said, multiple factors have hindered the ability to study drugs in pregnant patients. These include concerns for maternal and fetal safety, ethical considerations, the difficulty in designing appropriate trials to assess the study objectives, and funding limitations. This document summarizes the recommendations of a panel of experts convened by the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health. These experts were charged with reviewing the issues related to the development of preclinical and clinical drug studies in pregnant women and to develop strategies for addressing these issues. These findings may also be utilized in the development of future drug studies involving pregnant women and their fetus/neonate.

We compared polymerase chain reaction (PCR) analysis of specimens obtained from the distal vagina with wet mount microscopy and culture of specimens from the posterior vaginal fornix. One or all three techniques revealed that 61 (20.3%) of 300 women tested were positive for Trichomonas vaginalis. PCR analysis of distal vaginal specimens detected 56 (91.8%) of 61 infections, while wet mount microscopy and culture detected 49 (80.3%) of 61 infections. Results of this study may impact the approach to testing for T. vaginalis by eliminating the requirement of a vaginal speculum examination. The distal vagina is an appropriate testing site for T. vaginalis by PCR analysis. [ABSTRACT FROM PUBLISHER]

Objective  Group B Streptococcus (GBS) colonization of the lower urinary tract in pregnancy is associated with severe infections such as chorioamnionitis, endometritis, and pyelonephritis. The objective of this study was to compare rates of progression to pyelonephritis between GBS and Escherichia coli lower urinary tract infections (LUTIs), as well as compare infectious and obstetric morbidity secondary to these pathogens. Study Design  Retrospective cohort of pregnant women with LUTIs (asymptomatic bacteria or acute cystitis [AC]) from a single health system between July 2013 and May 2019. Demographic, infectious, antepartum, and intrapartum data were abstracted from medical records of women with GBS or E. coli LUTI. The primary outcome was progression to pyelonephritis. Secondary outcomes included pyelonephritis-related anemia, sepsis, pyelonephritis length of stay (LOS), median gestational age (GA) at delivery, preterm delivery, and low birth weight (LBW). Logistic regression was used to calculate the adjusted odds of the primary outcome. Results  Of 729 pregnant women with urinary colonization, 433 were culture positive for one of the aforementioned bacteria, with 189 (43.6%) having GBS and 244 (56.4%) having E. coli. Women with E. coli were more likely to be younger, use tobacco, have a history of AC, and have a history of preterm birth. Rates of progression to pyelonephritis were markedly higher with E. coli (15.6%) than with GBS (1.1%; p  < 0.001). Median LOS for pyelonephritis and pyelonephritis-related morbidities did not differ. Median GA at delivery, preterm delivery, and LBW rates also did not differ. In adjusted analysis, controlling for history of AC, insurance status, tobacco use, prior preterm birth, primary infection type, and maternal age, women with GBS LUTI had markedly decreased odds of developing pyelonephritis in pregnancy compared with those with E. coli (adjusted odds ratio: 0.04, 95% confidence interval: 0.01-0.28). Conclusion   Escherichia coli infections progress to pyelonephritis in pregnancy at markedly higher rates than GBS, although obstetric outcomes are similar., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Desensitization of the oxytocin receptor (OXTR) in the setting of prolonged oxytocin exposure may lead to dysfunctional labor, which increases the risk for cesarean delivery, and uterine atony, which may result in postpartum hemorrhage. The molecular mechanism for OXTR desensitization is through the agonist-mediated recruitment of the multifunctional protein β-arrestin. In addition to its desensitizing function, β-arrestins have recently been shown to simultaneously activate downstream signaling. We tested whether oxytocin stimulation promotes β-arrestin-mediated OXTR desensitization in vivo and activates β-arrestin-mediated mitogen-activated protein kinase (MAPK) growth signaling. Uterine muscle strips isolated from wild-type mice exhibited diminished uterine contractility following repeated exposure to oxytocin, whereas uterine muscle strips from β-arrestin-1 and β-arrestin-2 knockout mice showed no desensitization. Utilizing siRNA knockdown of β-arrestin-1 and β-arrestin-2 in HEK-293 cells expressing the OXTR, we demonstrated oxytocin-mediated MAPK signaling that was dependent on β-arrestin-1 and β-arrestin-2. Wild-type and β-arrestin-1 and β-arrestin-2 knockout mice receiving intravenous oxytocin also demonstrated oxytocin-mediated MAPK signaling that was dependent on β-arrestin-1 and β-arrestin-2. Finally, to test the significance of β-arrestin-mediated signaling from the OXTR, HEK-293 cells expressing the OXTR showed β-arrestin-dependent proliferation in a cell migration assay following oxytocin treatment. In conclusion, β-arrestin is a multifunctional scaffold protein that mediates both desensitization of the OXTR, leading to decreases in uterine contractility, and MAPK growth signaling following stimulation by oxytocin. The development of unique OXTR ligands that prevent receptor desensitization may be a novel approach in the treatment of adverse clinical events secondary to prolonged oxytocin therapy.