Intracellular pH dynamics respond to microenvironment stiffening and mediate vasculogenic mimicry through ß-catenin.

Dysregulated intracellular pH (pHi) dynamics and an altered tumor microenvironment have emerged as drivers of cancer cell phenotypes. However, the molecular integration between the physical properties of the microenvironment and dynamic intracellular signaling responses remains unclear. Here, we use two metastatic cell models, one breast and one lung, to assess pHi response to varying extracellular matrix (ECM) stiffness. To experimentally model ECM stiffening, we use two tunable-stiffness hydrogel systems: Matrigel and hyaluronic acid (HA) gels, which mimic the increased protein secretion and crosslinking associated with ECM stiffening. We find that single-cell pHi decreases with increased ECM stiffness in both hydrogel systems and both metastatic cell types. We also observed that stiff ECM promotes vasculogenic mimicry (VM), a phenotype associated with metastasis and resistance. Importantly, we show that decreased pHi is both a necessary and sufficient mediator of VM, as raising pHi on stiff ECM reduces VM phenotypes and lowering pHi on soft ECM drives VM. We characterize ß-catenin as a pH-dependent molecular mediator of pH-dependent VM, where stiffness-driven changes in ß-catenin abundance can be overridden by increased pHi. We uncover a dynamic relationship between matrix stiffness and pHi, thus suggesting pHi dynamics can override mechanosensitive cell responses to the extracellular microenvironment.

SGLT2-independent effects of canagliflozin on NHE3 and mitochondrial complex I activity inhibit proximal tubule fluid transport and albumin uptake.

Beyond glycemic control, SGLT2 inhibitors (SGLT2is) have protective effects on cardiorenal function. Renoprotection has been suggested to involve inhibition of NHE3 leading to reduced ATP-dependent tubular workload and mitochondrial oxygen consumption. NHE3 activity is also important for regulation of endosomal pH, but the effects of SGLT2i on endocytosis are unknown. We used a highly differentiated cell culture model of proximal tubule (PT) cells to determine the direct effects of SGLT2i on Na+-dependent fluid transport and endocytic uptake in this nephron segment. Strikingly, canagliflozin but not empagliflozin reduced fluid transport across cell monolayers and dramatically inhibited endocytic uptake of albumin. These effects were independent of glucose and occurred at clinically relevant concentrations of drug. Canagliflozin acutely inhibited surface NHE3 activity, consistent with a direct effect, but did not affect endosomal pH or NHE3 phosphorylation. In addition, canagliflozin rapidly and selectively inhibited mitochondrial complex I activity. Inhibition of mitochondrial complex I by metformin recapitulated the effects of canagliflozin on endocytosis and fluid transport, whereas modulation of downstream effectors AMPK and mTOR did not. Mice given a single dose of canagliflozin excreted twice as much urine over 24 h compared with empagliflozin-treated mice despite similar water intake. We conclude that canagliflozin selectively suppresses Na+-dependent fluid transport and albumin uptake in PT cells via direct inhibition of NHE3 and of mitochondrial function upstream of the AMPK/mTOR axis. These additional targets of canagliflozin contribute significantly to reduced PT Na+-dependent fluid transport in vivo.NEW & NOTEWORTHY Reduced NHE3-mediated Na+ transport has been suggested to underlie the cardiorenal protection provided by SGLT2 inhibitors. We found that canagliflozin, but not empagliflozin, reduced NHE3-dependent fluid transport and endocytic uptake in cultured proximal tubule cells. These effects were independent of SGLT2 activity and resulted from inhibition of mitochondrial complex I and NHE3. Studies in mice are consistent with greater effects of canagliflozin versus empagliflozin on fluid transport. Our data suggest that these selective effects of canagliflozin contribute to reduced Na+-dependent transport in proximal tubule cells.

Intracellular pH regulates ß-catenin with low pHi increasing adhesion and signaling functions.

Intracellular pH (pHi) dynamics are linked to cell processes including proliferation, migration, and differentiation. The adherens junction (AJ) and signaling protein ß-catenin has decreased abundance at high pHi due to increased proteasomal-mediated degradation. However, the effects of low pHi on ß-catenin abundance and functions have not been characterized. Here, we show that low pHi stabilizes ß-catenin in epithelial cells using population-level and single-cell assays. ß-catenin abundance is increased at low pHi and decreased at high pHi. We also assay single-cell protein degradation rates to show that ß-catenin half-life is longer at low compared to high pHi. Importantly, we show that AJs are not disrupted by ß-catenin loss at high pHi due to rescue by plakoglobin. Finally, we show that low pHi increases ß-catenin transcriptional activity in single cells and is indistinguishable from a Wnt-on state. This work characterizes pHi as a rheostat regulating ß-catenin abundance, stability, and function and implicates ß-catenin as a molecular mediator of pHi-dependent cell processes.

"Meeting Patients Where They're at": Clinician Perspectives on Integration of Family Planning Services into Office-Based Addiction Treatment.

OBJECTIVES: To study clinician perspectives on the feasibility of incorporating family planning services within office-based addiction treatment (OBAT) clinics. We sought to understand the unique facilitators of and barriers to the integration of contraceptive services within the OBAT model with a goal to support the design and implementation of a program tailored to meet the reproductive health needs of patients with substance use disorder. METHODS: After obtaining institutional review board approval, we conducted qualitative semistructured interviews with OBAT clinicians (registered nurses, advanced practice registered nurses, and physicians) at a tertiary-care safety-net hospital. Interview transcripts were analyzed using deductive codes utilizing key components of the Promoting Action on Research Implementation in Health Services and Ottawa Decision Support Frameworks. RESULTS: We analyzed 20 interviews. Our data noted 3 major themes: (1) evidence to support integration of family planning and OBAT, (2) inherent strengths and facilitative factors of the OBAT model, and (3) barriers and challenges of the OBAT model influencing successful integration. Strengths included the destigmatizing and trust-building OBAT approach to care, common use of patient-centered counseling, and providers' nuanced understanding of substance use disorder-specific impacts on reproductive health. Barriers included time constraints, balancing urgent patient recovery needs, the desire for additional contraception provision training, and concern for potential contraceptive coercion. CONCLUSIONS: Office-based addiction treatment clinics have inherent strengths that may make it a beneficial location for integrated family planning services. Future research should elicit patient perspectives to ensure the implementation of a family planning program in OBAT that supports patients' reproductive goals while avoiding stigma or reproductive coercion.

Breastfeeding and Hormonal Contraception: A Scoping Review of Clinical Guidelines, Professional Association Recommendations, and the Literature.

Background: Postpartum contraceptive use can help prevent short-interval pregnancies, which have been associated with adverse neonatal and maternal health outcomes. Many contraceptive methods are safe for postpartum use, but patients and providers may be confused as to what impact hormonal contraception has on lactation. We performed a scoping review of the most recent U.S.-based guidelines regarding hormonal contraception on lactation to provide synthesis and recommendations to aid providers in counseling their patients. Methods: We conducted a scoping review by identifying the most recent clinical recommendations and guidelines from the Centers for Disease Control and Prevention (CDC) and three maternal and child health professional associations (American College of Obstetricians and Gynecologists [ACOG], Society for Maternal-Fetal Medicine [SMFM], and Academy of Breastfeeding Medicine [ABM]). We also reviewed the citations in these guidelines used in their development. We then conducted an updated literature review to capture studies published since the most recent systematic reviews were conducted. Results: We reviewed 1 clinical guideline from the CDC and 2 systematic reviews cited in its references, 6 professional association recommendations, and 28 publications identified through the updated literature review. Progestin-only contraceptive methods continue to demonstrate safety in breastfeeding patients, while low-quality evidence supports concerns of decreased milk supply with combined hormonal contraception. Discussion: Organizations should consider updating counseling recommendations regarding progestin-only contraceptives and lactation. Further research is needed to examine new contraceptive methods as well as the effect of hormonal contraception on lactation in the setting of preterm birth.

Preconception Periodontitis and Risk of Spontaneous Abortion in a Prospective Cohort Study.

Few studies have evaluated the association between periodontitis and spontaneous abortion (SAB), and all had limitations. We used data from the Pregnancy Study Online (PRESTO), a prospective preconception cohort study of 3,444 pregnancy planners in the United States and Canada (2019-2022), to address this question. Participants provided self-reported data on periodontitis diagnosis, treatment, and symptoms of severity (i.e., loose teeth) via the enrollment questionnaire. SAB (pregnancy loss at <20 weeks' gestation) was assessed via bimonthly follow-up questionnaires. Participants contributed person-time from the date of a positive pregnancy test to the gestational week of SAB, loss to follow-up, or 20 weeks' gestation, whichever came first. We fitted Cox regression models with weeks of gestation as the time scale to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs), and we used inverse probability of treatment weighting to account for differential loss to follow-up. We used probabilistic quantitative bias analysis to estimate the magnitude and direction of the effect of exposure misclassification bias on results. In weighted multivariable models, we saw no appreciable association between preconception periodontitis diagnosis (HR = 0.97, 95% CI: 0.76, 1.23) or treatment (HR = 1.01, 95% CI: 0.79, 1.27) and SAB. A history of loose teeth was positively associated with SAB (HR = 1.38, 95% CI: 0.88, 2.14). Quantitative bias analysis indicated that our findings were biased towards the null but with considerable uncertainty in the bias-adjusted results.

Emergency department staff perspectives on caring for patients experiencing early pregnancy loss (Boston, Massachusetts 2021).

OBJECTIVES: A preimplementation study to examine the context of, and barriers and facilitators to, providing early pregnancy loss care in one emergency department (ED), to inform implementation strategies to improve ED-based early pregnancy loss care. STUDY DESIGN: We recruited a purposive sample of participants and conducted semistructured individual qualitative interviews focused on caring for patients experiencing pregnancy loss in the ED until saturation was reached. For analysis, we used framework coding and directed content analysis. RESULTS: Participant roles in the ED included administrators (N = 5), attending physicians (N = 5), resident physicians (N = 5), and registered nurses (N = 5). Most (70%, N = 14) participants identified as female. Primary themes included (1) caring for early pregnancy loss patients is challenging and uncomfortable, (2) inability to provide compassionate early pregnancy loss care causes moral injury, and (3) stigma influences early pregnancy loss care. Participants explained that early pregnancy loss is challenging due to added pressure, patient expectations, and gaps in knowledge. They reported barriers to providing compassionate care that are out of their control, such as systematic workflows, limited physical space, and insufficient time and expressed that these barriers lead to moral injury. Participants also reflected on how early pregnancy loss and abortion stigma affect patient care. CONCLUSIONS: Caring for patients experiencing early pregnancy loss in the ED requires unique considerations. ED staff recognize this and desire more early pregnancy loss education, clearer early pregnancy loss tools and protocols, and early pregnancy loss-specific workflows. With concrete needs identified, an implementation plan to improve ED-based early pregnancy loss care can be created, which is important now more than ever, due to the impending influx in the ED for early pregnancy loss care after the Dobbs decision. IMPLICATIONS: Since the Dobbs decision, patients are self-managing abortions and/or seeking out-of-state abortion care. Without access to follow-up, more patients are presenting to the ED with early pregnancy loss. By demonstrating the unique challenges emergency medicine clinicians face, this study can support initiatives to improve ED-based early pregnancy loss care.

Single-cell intracellular pH dynamics regulate the cell cycle by timing the G1 exit and G2 transition.

Transient changes in intracellular pH (pHi) regulate normal cell behaviors, but roles for spatiotemporal pHi dynamics in single-cell behaviors remain unclear. Here, we mapped single-cell spatiotemporal pHi dynamics during mammalian cell cycle progression both with and without cell cycle synchronization. We found that single-cell pHi is dynamic throughout the cell cycle: pHi decreases at G1/S, increases in mid-S, decreases at late S, increases at G2/M and rapidly decreases during mitosis. Importantly, although pHi is highly dynamic in dividing cells, non-dividing cells have attenuated pHi dynamics. Using two independent pHi manipulation methods, we found that low pHi inhibits completion of S phase whereas high pHi promotes both S/G2 and G2/M transitions. Our data also suggest that low pHi cues G1 exit, with decreased pHi shortening G1 and increased pHi elongating G1. Furthermore, dynamic pHi is required for S phase timing, as high pHi elongates S phase and low pHi inhibits S/G2 transition. This work reveals that spatiotemporal pHi dynamics are necessary for cell cycle progression at multiple phase transitions in single human cells.

Sexual dysfunction, distress, and care-seeking among females during the preconception period.

BACKGROUND: Despite the high prevalence of female sexual dysfunction in population-based studies and the importance of sexual functioning for mixed-sex couples attempting conception, little is known about female sexual function in the preconception period. OBJECTIVE: This descriptive study aimed to assess the prevalence of female sexual dysfunction, distress, and pain with intercourse in a preconception population of pregnancy planners. The study also explored the extent to which participants discussed their sex lives with a healthcare provider during a preconception visit. STUDY DESIGN: We used data from Pregnancy Study Online, a web-based preconception cohort study (August 2020-October 2022). Eligible participants identified as female and were aged 21 to 45 years, residents of the United States or Canada, attempting pregnancy, and not using fertility treatments at cohort entry. At enrollment, participants completed a detailed baseline questionnaire. Thirty days after enrollment, participants were invited to complete an optional questionnaire about sexual function. Our study included 1120 participants who responded to the sexual function questionnaire within 1 year of completing their baseline questionnaire. We assessed sexual dysfunction using the 6-item Female Sexual Function Index, and sexual distress using the Female Sexual Distress Scale, which assess sexual function and distress in the previous 4 weeks, respectively. We also asked participants whether they had discussed their plans to conceive with a healthcare provider, and if so, whether they discussed their sex lives. If not, we collected information on perceived barriers. RESULTS: Twenty-five percent of the sample met criteria for female sexual dysfunction, whereas 12.2% met the criteria for sexual distress; 8% of our sample reported both sexual dysfunction and sexual distress. Thirty percent reported at least some pain with intercourse in the past 4 weeks. Although over 80% of the sample reported discussing their conception plans with a healthcare provider, 70% of these participants did not discuss their sex lives. The most commonly reported reasons for not discussing their sex life with a provider was not experiencing a sexual health issue, the provider not asking, feeling nervous/uncomfortable/ashamed, and feeling it was not relevant to becoming pregnant or inappropriate to discuss. The percentage of participants who reported discussing their sex lives varied across provider type, with those seeing midwives having the highest percentage (39%), followed by nurse practitioners (36%) and obstetrician-gynecologists (34%). CONCLUSION: Sexual dysfunction, distress, and painful intercourse are prevalent in the preconception period, but participants frequently did not discuss their sex lives when discussing plans to conceive. The provider not asking was a commonly reported barrier. Providers may consider raising the issue of sexual functioning at the time of a preconception visit to better support patients who may be dealing with a sexual function issue while attempting pregnancy. These findings may not generalize beyond a primarily non-Hispanic White, highly educated, and high-income population.

First-trimester surgical abortion practice in Canada in 2012.

OBJECTIVE: To evaluate practices among first-trimester surgical abortion facilities and providers in Canada in 2012 and examine the characteristics of the surgical abortion work force. DESIGN: Self-administered paper or electronic survey adapted from a survey previously fielded in the United States. SETTING: Canada. PARTICIPANTS: Facility administrators and physicians. MAIN OUTCOMES MEASURES: Descriptive statistics on reported first-trimester surgical abortion practice and provider demographic characteristics. RESULTS: Eighty-three percent of identified facilities (78 of 94) and 178 physicians responded. Of the respondents, 99% of facilities and 96% of physicians provided first-trimester surgical abortions. Responding facilities provided 68,154 first-trimester surgical abortions in 2012. This represented 96% of their reported total (combined medical and surgical) first-trimester abortions. More than half (55%) of responding facilities were community based, while 45% were hospital affiliated. Most physician providers were female (68%) and were family doctors (59%). Preoperatively, 96% of physicians routinely used ultrasound and 89% gave perioperative antibiotics. Almost half (48%) used manual vacuum aspiration, but less than 35% did so beyond 9 weeks after the last menstrual period. At most facilities, most procedures were performed under combined local anesthesia and intravenous sedation (73%); only 7% indicated deep sedation or general anesthesia were used exclusively. Postoperatively, 81% of physicians performed immediate tissue examination and 96% offered postabortion contraception on the same day as the abortion. Other assessed outcomes included medication regimens and cervical preparation, with a high degree of consistency among facilities and physicians. CONCLUSION: First-trimester surgical abortion providers are mostly family physicians and most are female. Practices across Canada were mostly uniform and followed evidence-based guidelines. Uptake of the most recent Canadian practice guidelines may help further standardize patient care and improve routine perioperative antibiotic use and immediate tissue examination.

Obesity downregulates lipid metabolism genes in first trimester placenta.

Placentas of obese women have low mitochondrial ß-oxidation of fatty acids (FA) and accumulate lipids in late pregnancy. This creates a lipotoxic environment, impairing placental efficiency. We hypothesized that placental FA metabolism is impaired in women with obesity from early pregnancy. We assessed expression of key regulators of FA metabolism in first trimester placentas of lean and obese women. Maternal fasting triglyceride and insulin levels were measured in plasma collected at the time of procedure. Expression of genes associated with FA oxidation (FAO; ACOX1, CPT2, AMPKα), FA uptake (LPL, LIPG, MFSD2A), FA synthesis (ACACA) and storage (PLIN2) were significantly reduced in placentas of obese compared to lean women. This effect was exacerbated in placentas of male fetuses. Placental ACOX1 protein was higher in women with obesity and correlated with maternal circulating triglycerides. The PPARα pathway was enriched for placental genes impacted by obesity, and PPARα antagonism significantly reduced 3H-palmitate oxidation in 1st trimester placental explants. These results demonstrate that obesity and hyperlipidemia impact placental FA metabolism as early as 7 weeks of pregnancy.

Predictors of Non-Response to a Sexual Health Survey in a North American Preconception Cohort Study.

BACKGROUND: Refusal to participate in studies related to sexual health can compromise the internal and external validity of findings. Research examining non-response to sexual health studies has primarily focused on predictors such as specific sexual attitudes and behaviors. AIM: Evaluate predictors of non-response to a supplemental sexual health survey added to a web-based cohort study, focusing on predictors that may be important in epidemiologic studies of sexual health. METHODS: In March 2021, we added the "Sexual Health and Wellbeing Questionnaire" (SQ), an optional supplemental sexual health survey, to the protocol for Pregnancy Study Online , a web-based North American prospective cohort study. Eligible participants identified as female and were aged 21-45 years, actively trying to conceive, and in a relationship with a male partner. Participants completed a baseline questionnaire at enrollment and follow-up questionnaires every 8 weeks. Participants were invited to complete the SQ 30 days after baseline questionnaire completion. The analytic sample included all Pregnancy Study Online participants who enrolled between March 2021 and December 2021 and was divided into 3 mutually-exclusive groups: (i) those who completed the baseline questionnaire only (ie, did not complete a follow-up questionnaire or the SQ), (ii) those who completed at least 1 follow-up questionnaire but not the SQ, and (iii) participants who completed the SQ (with or without a follow-up questionnaire). We compared sociodemographic, medical, lifestyle, and reproductive factors across these groups. RESULTS: Of the 1,491 enrolled participants, 302 (20.3%) completed the baseline questionnaire only, 259 (17.4%) completed a follow-up questionnaire but not the SQ, and 930 (62.4%) completed the SQ. Strong predictors of non-response (absolute difference in response >10% comparing SQ responders to baseline-only responders) included longer pregnancy attempt time at study entry, a history of infertility, and lower income and education. Compared with response to the follow-up questionnaire only, SQ response was lower among Hispanic/Latina participants and participants aged <25 years. CLINICAL TRANSLATION: The addition of sexual health surveys to established cohort studies may be an effective way to expand epidemiologic sex research efforts. STRENGTHS & LIMITATIONS: Study strengths include the prospective design, geographic heterogeneity of the cohort, and use of online methods. Our findings may not generalize to clinic-based sex research. CONCLUSION: We report that in an established North American cohort study, response to the SQ exceeded 60%. We observed few strong predictors for SQ non-response among engaged participants. Bond JC, Abrams J, Wesselink AK, et al. Predictors of Non-Response to a Sexual Health Survey in a North American Preconception Cohort Study. J Sex Med 2022;19:1707-1715.

Trusted contraception information sources for individuals with opioid use disorder.

OBJECTIVE (STUDY QUESTION): To identify trusted sources of contraception information among pregnancy-capable individuals with opioid use disorder (OUD). DATA SOURCES/STUDY SETTING: We conducted interviews between October 2018 and January 2019 at Boston Medical Center, a university-based tertiary care center. STUDY DESIGN: Data were drawn from semi-structured qualitative interviews with a convenience sample of 20 pregnant or recently pregnant individuals with OUD. We used the Ottawa Decision Support Framework, a health decision making conceptual model, to structure our interviews. We analyzed the data using inductive and deductive coding. DATA COLLECTION/ EXTRACTION METHODS: Not applicable. PRINCIPAL FINDINGS: Pregnancy-capable individuals who use opioids value friends who are not actively using opioids, including peers in recovery homes, as trusted sources of contraception information. They also value internet resources, including websites recommended by clinicians and social media posts, and established clinical providers as reliable sources of contraception information in ways that emulate individuals with other chronic medical conditions.  CONCLUSION: These sources of contraception information may explain some trends in contraceptive use among individuals with OUD, inform nonstigmatizing contraceptive counseling, and serve as a foundation for improved decision support.

Continuation rates of two different-sized copper intrauterine devices among nulliparous women: Interim 12-month results of a single-blind, randomised, multicentre trial.

Background: The most widely used copper intrauterine device (IUD) in the world (the TCu380A), and the only product available in many countries, causes side effects and early removals for many users. These problems are exacerbated in nulliparous women, who have smaller uterine cavities compared to parous women. We compared first-year continuation rates and reasons/probabilities for early removal of the TCu380A versus a smaller Belgian copper IUD among nulliparous users. Methods: This 12-month interim report is derived from a pre-planned interim analysis of a sub population and focused on key secondary comparative endpoints. In this participant-blinded trial at 16 centres in the USA, we randomised participants aged 17-40 in a 4:1 ratio to the NT380-Mini or the TCu380A. In the first year, participants had follow-up visits at 6-weeks and 3, 6, and 12-months, and a phone contact at 9 months; we documented continued use, expulsions, and reasons for removal. Among participants with successful IUD placement, we compared probabilities of IUD continuation and specific reasons for discontinuation using log-rank tests. This trial is registered with ClinicalTrials.gov number NCT03124160 and is closed to recruitment. Findings: Between June 1, 2017, and February 25, 2019, we assigned 927 nulliparous women to either the NT380-Mini (n = 744) or the TCu380A (n = 183); the analysis population was 732 (NT380-Mini) and 176 (TCu380A). Participants using the NT380-Mini, compared to the TCu380A, had higher 12-month continuation rates (78·7% [95% CI: 72·9-84·5%] vs. 70·2% [95% CI: 59·7-80·7], p = 0·014), lower rates of removal for bleeding and/or pain (8·1% vs. 16·2%, p = 0·003) and lower IUD expulsion rates (4·8% vs. 8·9%, p = 0·023), respectively. Interpretation: The NT380-Mini offers important benefits for a nulliparous population compared to the TCu380A in the first twelve months, when pivotal experiences typically occur. Higher continuation rates with the NT380-Mini may avert disruptions in contraceptive use and help users avoid unintended pregnancy. Funding: Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Mona Lisa, N.V. (Belgium).

Society of family planning clinical recommendations: Contraception and abortion care for persons who use substances.

Substance use and substance use disorder remain significant public health crises. Substance use disorder, or addiction, is a stigmatized and misunderstood disease. Accessing contraception and abortion care is particularly challenging, as people who use substances or are diagnosed with substance use disorder often experience internalized stigma and overt discrimination within the healthcare system. There are limited recommendations for the clinical care of persons with substance use disorder who seek abortion or contraception care, and limited data to support these recommendations. This Society of Family Planning clinical recommendation addresses counseling and provision of contraception and abortion for persons who use substances or have substance use disorder. As there are almost no safety or efficacy data on contraception, abortion and substance use, the recommendations utilize extrapolations of substance use disorder-adjacent medical conditions when necessary.

The association of hourly second-stage documentation with cesarean delivery and maternal blood loss.

PURPOSE OF THE ARTICLE: Cesarean rates and maternal morbidity increase with the duration of the second stage of labor. We studied the effect of hourly evaluation and documentation during the second stage of labor on maternal and fetal outcomes. MATERIALS AND METHODS: We performed a retrospective cohort study of all women who delivered at our urban, tertiary care hospital and underwent a second stage of greater than 60 min between 1 June 2016 and 31 May 2019. There were 1498 patients with complete data. Four hundred forty patients had hourly evaluation and documentation throughout the second stage and 1058 did not. We performed t-tests, Chi-squared, and regression analyses to compare cesarean delivery rate, second-stage duration, quantitative blood loss, hemorrhage and blood transfusion rates, and fetal outcomes. We performed regression analyses to evaluate for independent effect of this intervention on each outcome. RESULTS: Patients with hourly evaluation and documentation had a decreased likelihood of cesarean delivery (8.2% vs. 20.3%, p < .001), shorter second-stage of labor (98.1 min vs. 177.5 min, p < .001), decreased quantitative blood loss (514.4 mL vs. 667.7 mL, p < .001), and hemorrhage rate (12.5% vs. 19.9%, p < .001). Hourly evaluation was associated with decreased transfusion rates (3.2% vs. 5.6%, p = .05) but was not related to the number of units transfused. Regression analyses confirmed the impact of hourly documentation when potential confounders were included. These differences in outcomes were also noted when evaluation was performed and documented within every 75 min. Hourly second-stage evaluation and documentation did not affect other maternal or infant morbidities. CONCLUSION: Hourly evaluation and documentation in the second stage was associated with decreased cesarean delivery rate, second-stage duration, quantitative blood loss, hemorrhage, and transfusion.