Evaluation of novel biomarkers for early pregnancy outcome prediction†.

OBJECTIVE: To assess performance and discriminatory capacity of commercially available enzyme-linked immunosorbent assays of biomarkers for predicting first trimester pregnancy outcome in a multi-center cohort. DESIGN: In a case-control study at three academic centers of women with pain and bleeding in early pregnancy, enzyme-linked immunosorbent assays of biomarkers were screened for assay performance. Performance was assessed via functional sensitivity, assay reportable range, recovery/linearity, and intra-assay precision (%Coefficient of Variation). Top candidates were analyzed for discriminatory capacity for viability and location among 210 women with tubal ectopic pregnancy, viable intrauterine pregnancy, or miscarriage. Assay discrimination was assessed by visual plots, area under the curve with 95% confidence intervals, and measures of central tendency with two-sample t-tests. RESULTS: Of 25 biomarkers evaluated, 22 demonstrated good or acceptable assay performance. Transgelin-2, oviductal glycoprotein, and integrin-linked kinase were rejected due to poor performance. The best biomarkers for discrimination of pregnancy location were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 1, insulin-like growth factor binding protein 1, kisspeptin (KISS1), pregnancy-specific beta-1-glycoprotein 3, and beta parvin (PARVB). The best biomarkers for discrimination of pregnancy viability were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 3, EH domain-containing protein 3, KISS1, WAP four-disulfide core domain protein 2 (HE4), quiescin sulfhydryl oxidase 2, and pregnancy-specific beta-1-glycoprotein 1. CONCLUSION: Performance of commercially available enzyme-linked immunosorbent assays was acceptable for a panel of novel biomarkers to predict early pregnancy outcome. Of these, six and seven candidates demonstrated good discriminatory capacity of pregnancy location and viability, respectively, when validated in a distinct external population. Four markers demonstrated good discrimination for both location and viability.

Cost-effectiveness analysis of expectant vs active management for treatment of persistent pregnancies of unknown location.

BACKGROUND: Persistent pregnancies of unknown location are defined by abnormally trending serum human chorionic gonadotropin with nondiagnostic ultrasound. There is no consensus on optimal management. OBJECTIVE: This study aimed to assess the cost-effectiveness of 3 primary management strategies for persistent pregnancies of unknown location: (1) expectant management, (2) empirical 2-dose methotrexate, and (3) uterine evacuation followed by methotrexate, if indicated. STUDY DESIGN: This was a prospective economic evaluation performed concurrently with the Expectant versus Active Management for Treatment of Persistent Pregnancies of Unknown Location multicenter randomized trial that was conducted from July 2014 to June 2019. Participants were randomized 1:1:1 to expectant management, 2-dose methotrexate, or uterine evacuation. The analysis was from the healthcare sector perspective with a 6-week time horizon after randomization. Costs were expressed in 2018 US dollars. Effectiveness was measured in quality-adjusted life years and the rate of salpingectomy. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were generated. Sensitivity analyses were performed to assess the robustness of the analysis. RESULTS: Methotrexate had the lowest mean cost ($875), followed by expectant management ($1085) and uterine evacuation ($1902) (P=.001). Expectant management had the highest mean quality-adjusted life years (0.1043), followed by methotrexate (0.1031) and uterine evacuation (0.0992) (P=.0001). The salpingectomy rate was higher for expectant management than for methotrexate (9.4% vs 1.2%, respectively; P=.02) and for expectant management than for uterine evacuation (9.4% vs 8.1%, respectively; P=.04). Uterine evacuation, with the highest costs and the lowest quality-adjusted life years, was dominated by both expectant management and methotrexate. In the base case analysis, expectant management was not cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year given an incremental cost-effectiveness ratio of $175,083 per quality-adjusted life year gained (95% confidence interval, -$1,666,825 to $2,676,375). Threshold analysis demonstrated that methotrexate administration would have to cost $214 (an increase of $16 or 8%) to favor expectant management. Moreover, expectant management would be favorable in lower-risk patient populations with rates of laparoscopic surgical management for ectopic pregnancy not exceeding 4% of pregnancies of unknown location. Based on the cost-effectiveness acceptability curves, the probability of expectant management being cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year gained was 50%. The results were dependent on the cost of surgical intervention and the expected rate of methotrexate failure. CONCLUSION: The management of pregnancies of unknown location with a 2-dose methotrexate protocol may be cost-effective compared with expectant management and uterine evacuation. Although uterine evacuation was dominated, expectant management vs methotrexate results were sensitive to modest changes in treatment costs of both methotrexate and surgical management.

High-Volume Surgeons and Reducing Racial Disparities in Route of Hysterectomy.

STUDY OBJECTIVE: To examine racial disparities in route of hysterectomy and perioperative outcomes before and after expansion of high-volume minimally invasive surgeons (>10 minimally invasive hysterectomies (MIH)/year) DESIGN: Retrospective cohort study SETTING: Multi-center academic teaching institution PATIENTS: All patients who underwent a scheduled hysterectomy for benign indications during 2018 (pre-intervention) and 2022 (post-intervention) INTERVENTIONS: Recruitment of Fellowship in Minimally Invasive Gynecologic Surgery (FMIGS)- trained faculty and increased surgical training for academic specialists in obstetrics and gynecology occurred in 2020. MEASUREMENTS AND MAIN RESULTS: Patients in the pre-intervention cohort (n=171) were older (median age 45 years vs. 43 years, p=0.003) while patients in the post-intervention cohort (n=234) had a higher burden of comorbidities (26% ASA class III vs. 19%, p=0.03). Uterine weight was not significantly different between cohorts (p=0.328). Between the pre-intervention and post-intervention cohorts, high-volume minimally invasive surgeons increased from 27% (n=4) to 44% (n=7) of those performing hysterectomies within the division and percentage of hysterectomies performed via minimally invasive route increased (63% vs. 82%, p<0.001). In the pre-intervention cohort, Black patients had a lower percentage of hysterectomies performed via minimally invasive route compared to White patients (Black = 56% MIH vs. White = 76% MIH, p=0.014). In the post-intervention cohort, differences by race were no longer significant (Black = 78% MIH vs. White = 87% MIH, p= 0.127). There was a significant increase (22%) in MIH for Black patients between cohorts (p<0.001). After adjusting for age, BMI, ASA class, prior surgery, and uterine weight, disparities by race were no longer present in the post-intervention cohort. Perioperative outcomes including length of stay (p<0.001), infection rates (p=0.002) and blood loss (p=0.01) improved post-intervention. CONCLUSION: Increasing FMIGs-trained gynecologic surgeons and providing more opportunities in robotic/laparoscopic training for academic specialists may improve access to MIH for Black patients and reduce disparities.

Telehealth utilization in gynecologic oncology clinical trials.

OBJECTIVE: Prior to the COVID-19 pandemic, telehealth visits and remote clinical trial operations (such as local collection of laboratory tests or imaging studies) were underutilized in gynecologic oncology clinical trials. Current literature on these operational changes provides anecdotal experience and expert opinion with few studies describing patient-level safety data. We aimed to evaluate the safety and feasibility of telehealth and remote clinical trial operations during the COVID-19 Pandemic. METHODS: Gynecologic oncology patients enrolled and actively receiving treatment on a clinical trial at a single, academic institution during the designated pre-Telehealth and Telehealth periods were identified. Patients with at least 1 provider or research coordinator telehealth visit were included. Patient demographics, health system encounters, adverse events, and protocol deviations were collected. Pairwise comparisons were performed between the pre-Telehealth and Telehealth period with each patient serving as their own control. RESULTS: Thirty-one patients met inclusion criteria. Virtual provider visits and off-site laboratory testing increased during the Telehealth period. Delays in provider visits, imaging, and laboratory testing did not differ between time periods. Total and minor protocol deviations increased in incidence during the Telehealth period and were due to documentation of telehealth and deferment of non-therapeutic testing. Major protocol deviations, emergency department visits, admissions, and severe adverse events were of low incidence and did not differ between time periods. CONCLUSIONS: Telehealth and remote clinical trial operations appeared safe and did not compromise clinical trial protocols in a small, single institutional study. Larger scale evaluations of such trial adaptations should be performed to determine continued utility following the Pandemic.

Cell-free DNA screening for trisomy 21 in twin pregnancy: a large multicenter cohort study.

BACKGROUND: Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. OBJECTIVE: This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13. STUDY DESIGN: This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. RESULTS: A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. CONCLUSION: Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.

"Every minute counts": association between operative time and post-operative complications for patients undergoing minimally invasive sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Our aim was to assess whether operative time is independently associated with post-operative complications for minimally invasive sacrocolpopexy (MISCP). METHODS: Using the National Surgical Quality Improvement Program (NSQIP) database, patients undergoing MISCP from 2015 to 2020 were identified by CPT code. The following data were extracted: demographics, concomitant procedures (hysterectomies, midurethral sling, and anterior or posterior repair), and post-operative complications. Complications were categorized into minor, major, and composite, modeled after the Clavien-Dindo classification. For analysis, covariates associated with operative time and composite complications were identified using a general linear model and Chi-squared or Fisher's exact test as appropriate. Then, adjusted spline regression was performed as a test of nonlinearity between operative time and composite complications. Adjusted relative risks of complications by 60-min increments were estimated using Poisson regression with robust error variance. RESULTS: A total of 13,239 patients who underwent MISCP were analyzed. Overall, mean operative time (SD) was 189.5 (78.3) min. Post-operative complication rates were 2.6% for minor, 4.7% for major, and 7.3% for composite complications. Age, smoking, and sling were the only covariates associated with both operative time and post-operative complications. Adjusted spline regression demonstrated linearity (p<0.0001). With each 60-min increase in operative time, adjusted relative risks (95% CI) were 1.14 for composite (1.09, 1.19), 1.16 for minor (1.10, 1.21), and 1.11 (1.03, 1.20) for major complications. CONCLUSIONS: Operative time is independently and linearly associated with post-operative complications for patients undergoing MISCP, even when adjusted for demographic variables and concomitant procedures.

Telephone-Based Intervention to Improve Family Planning Care in Pregnancies of Unknown Location: Retrospective Pre-Post Study.

BACKGROUND: Patients followed for a pregnancy of unknown location are generally followed by a team of clinicians through telephone calls, and their contraceptive needs at the time of pregnancy resolution may not be addressed. OBJECTIVE: This study aimed to assess contraceptive counseling and contraceptive uptake before and after a telephone-based intervention. METHODS: This was a retrospective pre-post study assessing pregnancy intendedness in patients with a pregnancy of unknown location and the proportion of patients who received contraceptive counseling and a contraceptive prescription before and after the initiation of a telephone-based intervention. We reviewed medical records 1 year before and 1 year after implementation of our intervention for demographic characteristics, pregnancy intendedness, pregnancy outcome, contraceptive counseling documentation, receipt of contraception, and repeat pregnancy within 6 months. We assessed the effects of an implementation strategy to address family planning needs once pregnancy was resolved by comparing the proportions of patients who were counseled and received contraception before and after our intervention was implemented. We performed logistic regression to identify associations between covariates and the outcomes of contraceptive counseling documentation and receipt of contraception. RESULTS: Of the 220 patients in the combined cohort, the majority were Black (161/220, 73%) and ultimately had a resolved pregnancy of unknown location (162/220, 74%), and the proportion of pregnancies documented as unintended was 60% (132/220). Before our intervention, 27 of 100 (27%) patients received contraceptive counseling, compared with 94 of 120 (78%) patients after the intervention (odds ratio [OR] 9.77, 95% CI 5.26-18.16). Before the intervention, 17 of 90 (19%) patients who did not desire repeat pregnancy received contraception, compared with 32 of 86 (37%) patients after the intervention (OR 2.54, 95% CI 1.28-5.05). Our postintervention cohort had an increased odds of receiving contraceptive counseling (OR 9.77, 95% CI 5.26-18.16) and of receiving a contraceptive prescription (OR 2.54, 95% CI 1.28-5.05) compared with our preintervention cohort. CONCLUSIONS: We found that over half of patients with a pregnancy of unknown location have an unintended pregnancy, and standardization of care through a telephone-based intervention improves contraceptive counseling and prescribing in patients with a resolved pregnancy of unknown location. This intervention could be used at any institution that follows patients with a pregnancy of unknown location remotely to improve care.

Outcomes of assisted reproductive technology procedures performed on weekdays versus weekends: a retrospective cohort study.

PURPOSE: To evaluate if assisted reproductive technology (ART) outcomes are different based on whether procedures - oocyte retrieval, insemination, embryo biopsy, or embryo transfer - are performed on a weekday versus weekend/holiday. METHODS: Retrospective cohort study of all patients ≥ 18 years old who underwent oocyte retrieval for in vitro fertilization or oocyte banking (n = 3,197 cycles), fresh or natural-cycle frozen embryo transfers (n = 1,739 transfers), or had embryos biopsied for pre-implantation genetic testing (n = 4,568 embryos) in a large academic practice from 2015-2020. The primary outcomes were as follows: oocyte maturity for oocyte retrievals; fertilization rate for insemination; rate of no result on pre-implantation genetic testing for embryo biopsy; and live birth rate for embryo transfers. RESULTS: The average number of procedures performed per embryologist per day was higher on weekends/holidays than weekdays. For oocyte retrievals performed on weekdays vs. weekends/holidays, there was no difference in oocyte maturity rate (88% vs 88%). There was no difference in the fertilization rate (82% vs 80%) in cycles that had intracytoplasmic sperm injection performed on weekdays vs. weekends/holidays. No difference was found in the no result rate for embryos biopsied on weekdays vs. weekends/holidays (2.5% vs 1.8%). Finally, there was no difference by weekday vs. weekend/holiday in the live birth rate per transfer among all transfers (39.6% vs 36.1%), or when stratified by fresh (35.1% vs 34.9%) or frozen embryo transfer (49.7% vs. 39.6%). CONCLUSION: We found no differences in ART outcomes among women who had their oocyte retrievals, inseminations, embryo biopsies, or embryo transfers performed on weekdays versus weekends/holidays.

Induced Abortion and the Risk of Rh Sensitization.

Importance: While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion surrounding risks and benefits of Rh testing and treatment. As abortion care in traditional clinical settings becomes harder to access, many people are choosing to self-manage and need to know if ancillary blood type testing is necessary. Objective: To determine how frequently maternal exposure to fetal red blood cells (fRBCs) exceeds the most conservative published threshold for Rh sensitization in induced first-trimester abortion. Design, Setting, and Participants: Multicenter, observational, prospective cohort study using high-throughput flow cytometry to detect circulating fRBCs in paired maternal blood samples before and after induced first-trimester abortion (medication or procedural). Individuals undergoing induced first-trimester abortion before 12 weeks 0 days' gestation were included. Paired blood samples were available from 506 participants who underwent either medical (n = 319 [63.0%]) or procedural (n = 187 [37.0%]) abortion. Exposure: Induced first-trimester abortion. Main Outcomes and Measures: The primary outcome was the proportion of participants with fRBC counts above the sensitization threshold (125 fRBCs/5 million total RBCs) after induced first-trimester abortion. Results: Among the 506 participants, the mean (SD) age was 27.4 (5.5) years, 313 (61.9%) were Black, and 123 (24.3%) were White. Three of the 506 participants had elevated fRBC counts at baseline; 1 of these patients had an elevated fRBC count following the abortion (0.2% [95% CI, 0%-0.93%]). No other participants had elevated fRBC counts above the sensitization threshold after induced first-trimester abortion. The median change from baseline was 0 fRBCs, with upper 95th and 99th percentiles of 24 and 35.6 fRBCs, respectively. Although there was a strong association between the preabortion and postabortion fRBC counts, no other baseline characteristic was significantly associated with postabortion fRBC count. Conclusions and Relevance: Induced first-trimester abortion is not a risk factor for Rh sensitization, indicating that Rh testing and treatment are unnecessary before 12 weeks' gestation. This evidence may be used to inform international guidelines for Rh immunoglobulin administration following first-trimester induced abortion.

Exploring technology-based interventions to improve oral contraceptive pill adherence: a cross-sectional survey.

PURPOSE: To assess the resources that oral contraceptive pill (OCP) users currently use and wish to use after missing pills. MATERIALS AND METHODS: People 18-44 years old with a OCP prescription were emailed a cross-sectional survey to assess how they obtain information about managing missed pills, what information they would prefer to access, and whether they would use additional information if it were available. We performed a logistic regression and a dominance analysis to compare independent predictors of desire for a technological resource at the time of missed pills. RESULTS: We received 166 completed surveys. Nearly half of participants (47%, n = 76, 95% CI 39.0-54.4%) did not seek information about managing their missed pills. When missing a pill, more patients preferred non-technology-based information (57.1%, n = 93, 95% CI 49.3-64.5%) over technology-based information (43%, n = 70, 95% CI 35.5-50.7%). Most reported they would appreciate more information at the time of missed pills (76%, n = 124, 95% CI 68.9-82.0%). The strongest predictors for desire for technology-based information were: current use of technology, lower parity, white race, and higher educational attainment. CONCLUSIONS: This study indicates that most OCP users would utilise additional information at the time of a missed pill if they had access to it and that they desire information in varying formats.

Patients desire more educational information at the time of missed oral contraceptive pills, and preferences are varied regarding the format of patient information. Implementation of high-quality counseling with oral contraceptive pills requires a broad range of educational materials as well as provider education.

Medical management of early pregnancy loss is cost-effective compared with office uterine aspiration.

BACKGROUND: Early pregnancy loss, also referred to as miscarriage, is common, affecting approximately 1 million people in the United States annually. Early pregnancy loss can be treated with expectant management, medications, or surgical procedures-strategies that differ in patient experience, effectiveness, and cost. One of the medications used for early pregnancy loss treatment, mifepristone, is uniquely regulated by the Food and Drug Administration. OBJECTIVE: This study aimed to compare the cost-effectiveness from the healthcare sector perspective of medical management of early pregnancy loss, using the standard of care medication regimen of mifepristone and misoprostol, with that of office uterine aspiration. STUDY DESIGN: We developed a decision analytical model to compare the cost-effectiveness of early pregnancy loss treatment with medical management with that of office uterine aspiration. Data on medical management came from the Pregnancy Failure Regimens randomized clinical trial, and data on uterine aspiration came from the published literature. The analysis was from the healthcare sector perspective with a 30-day time horizon. Costs were in 2018 US dollars. Effectiveness was measured in quality-adjust life-years gained and the rate of complete gestational sac expulsion with no additional interventions. Our primary outcome was the incremental cost per quality-adjust life-year gained. Sensitivity analysis was performed to identify the key uncertainties. RESULTS: Mean per-person costs were higher for uterine aspiration than for medical management ($828 [95% confidence interval, $789-$868] vs $661 [95% confidence interval, $556-$766]; P=.004). Uterine aspiration more frequently led to complete gestational sac expulsion than medical management (97.3% vs 83.8%; P=.0001); however, estimated quality-adjust life-years were higher for medical management than for uterine aspiration (0.082 [95% confidence interval, 0.8148-0.08248] vs 0.079 [95% confidence interval, 0.0789-0.0791]; P<.0001). Medical management dominated uterine aspiration, with lower costs and higher confidence interval. The probability that medical management is cost-effective relative to uterine aspiration is 97.5% for all willingness-to-pay values of ≥$5600/quality-adjust life-year. Sensitivity analysis did not identify any thresholds that would substantially change outcomes. CONCLUSION: Although office-based uterine aspiration more often results in treatment completion without further intervention, medical management with mifepristone pretreatment costs less and yields similar quality-adjust life-years, making it an attractive alternative. Our findings provided evidence that increasing access to mifepristone and eliminating unnecessary restrictions will improve early pregnancy care.

Screening Echocardiogram in High-Risk Women with Class III Obesity to Predict the Risk of Preeclampsia.

OBJECTIVE: Women with obesity and other comorbidities such as hypertension and diabetes are at an increased risk of preeclampsia and perinatal morbidity. This study evaluates whether screening echocardiogram can identify women with obesity at a higher risk of preeclampsia. METHODS: We conducted a retrospective cohort study of women with class III obesity (body mass index [BMI] ≥40 kg/m2) and one or more medical comorbidities associated with an increased risk of preeclampsia (such as diabetes, hypertension, and rheumatologic disease) undergoing screening echocardiogram. Abnormal findings were defined as the presence of one or more of the following: diastolic dysfunction, ejection fraction of ≤45%, or cardiac chamber enlargement or hypertrophy. Multivariable logistic regression was used to estimate the odds ratio (OR) of gestational hypertension/mild preeclampsia, severe preeclampsia, and any preterm delivery <37 weeks associated with abnormal echocardiographic findings when controlling for potential confounders. RESULTS: Of 267 eligible women, 174 (64%) underwent screening echocardiograms. Sixty-nine women (40%) had abnormal echocardiograms. Maternal clinical characteristics were similar between women with normal echocardiographic findings and women with abnormal findings. Women with abnormal echocardiograms were more likely to have chronic hypertension (78 vs. 62%, p = 0.04) and a history of preeclampsia (27 vs. 10%, p = 0.02). After controlling for confounders, women with abnormal echocardiogram were at an increased risk of hypertensive disorders of pregnancy, OR 6.80 (95% confidence interval [CI] 3.32-13.93, p = 0.01), and in particular severe preeclampsia, OR 8.77 (95% CI 3.90-19.74, p = 0.01). CONCLUSION: Among pregnant women with class III obesity and medical comorbidities, screening echocardiogram may help identify a subset of women at the highest risk of developing preeclampsia. KEY POINTS: · Women with obesity and comorbid conditions are at a high risk of abnormal echocardiogram.. · Women with obesity, medical comorbid conditions, and abnormal echo are at a high risk of preeclampsia.. · Screening echocardiogram can help identify obese women at the highest risk of severe preeclampsia..

Impact of past surgical history on perioperative outcomes in gynecologic surgery.

OBJECTIVE: We sought to determine if past surgical history is associated with perioperative outcomes for patients undergoing hysterectomy. METHODS: A retrospective cohort study was conducted at a single, tertiary, academic health system of women who underwent hysterectomy from May 2016 - May 2017. Past surgical history (PSH) involving any abdominal or pelvic surgery, baseline demographics and perioperative outcomes were collected. For purposes of analyses, PSH was defined using three algorithms: 1) any prior abdominopelvic surgery, 2) having had abdominopelvic surgeries likely to cause adhesive disease, 3) anatomic location of prior PSH (none; pelvic; abdominal; or abdominal+pelvic). Descriptive, bivariable and multivariable analyses were performed. RESULTS: 1256 patients underwent hysterectomy. In adjusted analyses, PSH defined by any prior abdominopelvic surgery was associated with length of stay (LOS) (2.1 days (95%CI 1.9, 2.2) vs. 1.8 (95%CI 1.6, 2.0), (p=0.02)). PSH of procedures likely to cause adhesive disease was associated with greater estimated blood loss (EBL) (243.2 mL (95%CI 208.1, 278.3) vs. 189.0 (95%CI 1734, 204.7), (p=0.01)), longer LOS (2.5 days (95%CI 2.2, 2.8) vs. 1.9 (95%CI 1.7, 2.0), (p<0.01)), and more readmissions (OR 2.4, 95%CI 1.3, 4.5) (p<0.01). PSH defined by anatomic location revealed a trend (p=0.07) towards greater EBL in those with prior pelvic or abdominal+pelvic surgery compared to none or abdominal only, whereas LOS, readmissions and operative times did not differ. Increased total number of prior open surgeries was associated with operative time (p<0.0001), EBL (p<0.0001), hospital LOS (p<0.0001) and readmission (p=0.026). CONCLUSIONS: Prior abdominopelvic surgery is associated with worse perioperative outcome measures in women undergoing hysterectomy.

Association of Fetal Fraction of Cell-Free DNA and Hypertensive Disorders of Pregnancy.

OBJECTIVE: The objective of this study is to examine the relationship between fetal fraction and hypertensive disorders of pregnancy. STUDY DESIGN: This is a retrospective cohort study of women with singleton pregnancies who had cell-free DNA (cfDNA) screening at 10 to 20 weeks of gestation. The primary outcome was the development of gestational hypertension (gHTN), preeclampsia (PEC), and PEC with severe features. Multinomial logistic regression was performed to assess the relationship between fetal fraction and pregnancy outcomes of interest while controlling for potential confounders. RESULTS: Among 2,701 women meeting inclusion criteria, 387 (14.3%) were diagnosed with hypertensive disorders of pregnancy. First-trimester fetal fraction was significantly lower in women diagnosed with hypertensive disorders of pregnancy (10.9 vs. 12.4, p < 0.0001). An increased risk of gHTN and PEC, PEC with severe features with delivery > 34 weeks, and PEC with severe features with delivery ≤ 34 weeks was seen with lower first-trimester fetal fractions (odds ratio [OR]: 0.55, 95% confidence interval [CI] [0.36-0.83], p = 0.005; OR: 0.59, 95% CI [0.35-0.99], p = 0.048; and OR: 0.27, 95% CI [0.08-0.96], p = 0.044). The relationship between fetal fraction and hypertensive disorders of pregnancy was not statistically significant after adjusting for maternal age, race, body mass index, and chronic hypertension. CONCLUSION: Fetal fraction of cfDNA at 10 to 20 weeks of gestation was not associated with the development of hypertensive disorders of pregnancy.

Adverse Maternal Outcomes Associated with Uterine Extensions at the Time of Cesarean Delivery.

OBJECTIVE: We sought to compare adverse maternal outcomes between women with and without a uterine extension at the time of cesarean. STUDY DESIGN: We conducted a retrospective cohort study of women with and without a uterine extension during a primary low transverse cesarean of a full-term singleton gestation. The primary outcomes were (1) estimated blood loss (EBL) and (2) composite maternal morbidity (defined as ≥ 1 of the following: blood transfusion, endometritis, or readmission). Pearson's chi-square or Fisher's exact test was used to compare categorical data; Student's t-test or Mann-Whitney's U-tests was used for continuous data. Linear and logistic regressions were used to adjust for confounding factors. RESULTS: There were 252 women included (126 with extension and 126 without an extension). Women with extensions had a higher EBL (1,038 vs. 832 mL, p < 0.001) and higher rate of the composite maternal morbidity (19.1 vs. 5.6%, p = 0.001). Additionally, women with extensions had an increased risk of postpartum hemorrhage ≥ 1 L (53.2 vs. 23.8%, p < 0.001) and 1.5 L (12.7 vs. 0%, p < 0.001) and were associated with prolonged length of hospital stay (29 vs. 17%, p = 0.04). CONCLUSION: Uterine extensions are associated with adverse maternal outcomes including higher EBL and increase in maternal morbidity.

Outcomes After Induction of Labor Compared With Dilation and Evacuation for the Management of Rupture of Membranes in the Second Trimester.

Previable and periviable rupture of membranes is associated with significant morbidity for the pregnant patient. For those who have a choice of options and undergo active management, it is not known how the risks of induction of labor compare with those for dilation and evacuation (D&E). We performed a retrospective cohort study of patients with rupture of membranes between 14 0/7 and 23 6/7 weeks of gestation who opted for active management. Adverse events (52.2% vs 16.9%, P <.01) and time to uterine evacuation greater than 24 hours (26.7% vs 9.6%, P =.01) were more common among patients undergoing induction of labor. In a multivariable regression, induction of labor was an independent risk factor for complications (odds ratio 5.70, 95% CI, 2.35-13.82) compared with D&E. Severe complications were rare across both groups (4.4% for patients undergoing induction vs 2.6% for D&E, P =.63). Given the differing risks by termination method, access to D&E is an important treatment option for this patient population.

Multiplexed serum biomarkers to discriminate nonviable and ectopic pregnancy.

OBJECTIVE: To evaluate combinations of candidate biomarkers to develop a multiplexed prediction model for identifying the viability and location of an early pregnancy. In this study, we assessed 24 biomarkers with multiple machine learning-based methodologies to assess if multiplexed biomarkers may improve the diagnosis of normal and abnormal early pregnancies. DESIGN: A nested case-control design evaluated the predictive ability and discrimination of biomarkers in patients at risk of early pregnancy failure in the first trimester to classify viability and location. SETTING: Three university hospitals. PATIENTS: A total of 218 individuals with pain and/or bleeding in early pregnancy: 75 had an ongoing intrauterine gestation; 68 had ectopic pregnancies (EPs); and 75 had miscarriages. INTERVENTIONS: Serum levels of 24 biomarkers were assessed in the same patients. Multiple machine learning-based methodologies to evaluate combinations of these top candidates to develop a multiplexed prediction model for the identification of a nonviable pregnancy (ongoing intrauterine pregnancy vs. miscarriage or EP) and an EP (EP vs. ongoing intrauterine pregnancy or miscarriage). MAIN OUTCOME MEASURES: The predicted classification using each model was compared with the actual diagnosis, and sensitivity, specificity, positive predictive value, negative predictive value, conclusive classification, and accuracy were calculated. RESULTS: Models using classification regression tree analysis using 3 (pregnancy-specific beta-1-glycoprotein 3 [PSG3], chorionic gonadotropin-alpha subunit, and pregnancy-associated plasma protein-A) biomarkers were able to predict a maximum sensitivity of 93.3% and a maximum specificity of 98.6%. The model with the highest accuracy was 97.4% (with 70.2% receiving classification). Models using an overlapping group of 3 (soluble fms-like tyrosine kinase-1, PSG3, and tissue factor pathway inhibitor 2) biomarkers achieved a maximum sensitivity of 98.5% and a maximum specificity of 95.3%. The model with the highest accuracy was 94.4% (with 65.6% receiving classification). When the models were used simultaneously, the conclusive classification increased to 72.7% with an accuracy of 95.9%. The predictive ability of the biomarkers in the random forest produced similar test characteristics when using 11 predictive biomarkers. CONCLUSION: We have demonstrated a pool of biomarkers from divergent biological pathways that can be used to classify individuals with potential early pregnancy loss. The biomarkers choriogonadotropin alpha, pregnancy-associated plasma protein-A, and PSG3 can be used to predict viability, and soluble fms-like tyrosine kinase-1, tissue factor pathway inhibitor 2, and PSG3 can be used to predict pregnancy location.

Reduction of racial disparities in urine drug testing after implementation of a standardized testing policy for pregnant patients.

BACKGROUND: Drug use during pregnancy can have implications for maternal and fetal morbidity and mortality and legal ramifications for patients. The American College of Obstetricians and Gynecologists guideline states that drug screening policies during pregnancy should be applied equally to all people and notes that biological screening is not necessary, stating that verbal screening is adequate. Despite this guidance, institutions do not consistently implement urine drug screening policies that reduce biased testing and mitigate legal risks to the patient. OBJECTIVE: This study aimed to evaluate the effects of a standardized urine drug testing policy in labor and delivery on the number of drug tests performed, self-reported racial makeup of those tested, provider-reported testing indications, and neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study. A urine drug screening and testing policy was introduced in December 2019. The electronic medical record was queried for the number of urine drug tests performed on patients admitted to the labor and delivery unit from January 1, 2019, to April 30, 2019. The number of urine drug tests performed between January 1, 2019, and April 30, 2019, was compared with the number of urine drug tests performed between January 1, 2020, and April 30, 2020. The primary outcome was the proportion of urine drug tests performed based on race before and after the implementation of a drug testing policy. The secondary outcomes included total number of drug tests, Finnegan scores (a proxy for the neonatal abstinence syndrome), and testing indications. To understand perceived testing indications, pre- and postintervention provider surveys were administered. Chi-square and Fisher exact tests were used to compare categorical variables. The Wilcoxon rank-sum test was used to compare nonparametric data. The Student t test and 1-way analysis of variance were used to compare means. Multivariable logistic regression was used to construct an adjusted model that included covariates. RESULTS: In 2019, Black patients were more likely to undergo urine drug testing than White patients, even after adjusting for insurance status (adjusted odds ratio, 3.4; confidence interval, 1.55-7.32). In 2020, there was no difference in testing based on race after adjusting for insurance status (adjusted odds ratio, 1.3; confidence interval, 0.55-2.95). There was a reduction in the number of drug tests performed between January 2019 and April 2019 compared with between January 2020 and April 2020 (137 vs 71; P<.001). This was not accompanied by a statistically significant change in the incidence of neonatal abstinence syndrome measured by mean Finnegan scores (P=.4). Before the implementation of a drug testing policy, 68% of providers requested patient consent for testing; after the implementation of a drug testing policy, 93% requested patient consent for testing (P=.002). CONCLUSION: The implementation of a urine drug testing policy improved consent for testing and reduced disparities in testing based on race and the overall rate of drug testing without affecting neonatal outcomes.

Evaluation of a decision aid for early pregnancy loss: A pilot randomized controlled trial in Philadelphia, Pennsylvania.

OBJECTIVES: To evaluate the effect of a decision aid on decisional conflict scale in patients choosing management for early pregnancy loss. STUDY DESIGN: We conducted a pilot randomized control trial to assess the effect of the Healthwise patient decision aid on decisional conflict scale in patients with early pregnancy loss as compared with a control website. Patients 18years and older were eligible if they had an early pregnancy loss between 5 and 12 completed weeks of gestation. Participants completed surveys at baseline, poststudy intervention, after consultation, and 1week postconsultation. Surveys assessed participant scores on the decisional conflict scale (scale 0-100), knowledge, assessment of shared decision-making, satisfaction, and decision regret. Our primary outcome was the poststudy-intervention decisional conflict scale score. RESULTS: From July 2020 through March 2021 we randomized 60 participants. After the intervention, the median decisional conflict scale score for the control group was 10 [0-30] and 0 [0-20] for the intervention group (p = 0.17). When assessing the decisional conflict scale subscales postintervention, the informed subscale for the control group was 16.7 [0-33.3] as opposed to 0 [0] for the patient decision aid group (p = 0.003). Knowledge remained significantly higher in the experimental arm from the postintervention to the 1-week follow-up. We found no differences between groups when assessing our other metrics. CONCLUSIONS: Use of a validated decision aid did not result in statistically significant differences in the total decisional conflict scale scores as compared with the control. Participants allocated to the intervention were more informed postintervention and had consistently higher knowledge scores. IMPLICATIONS: Use of a validated decision aid prior to early pregnancy loss management consultation did not affect overall decisional conflict but resulted in improved knowledge.

Predictive value of 5-Factor modified frailty index in Oncologic and benign hysterectomies.

Background: The 5-factor modified frailty index (mFI-5) has been validated against the original 11-factor modified frailty index in gynecologic surgery, however its utility has not been evaluated between benign versus gynecologic oncology patient populations. Objective: To evaluate the predictive value of the mFI-5 in identifying women at increased risk for major postoperative complications, readmission, or death within 30 days of hysterectomy for benign and oncologic indications. Methods: Patients who underwent hysterectomy between 2015 and 2017 were identified from the NSQIP database and stratified into benign or malignant indications. Demographic and mFI-5 variables were extracted. The mFI-5 was calculated by dividing the sum of all affirmative variables by the total number of input variables in the database. Logistic regression modeling was performed adjusting for confounders. C-statistic with 95% CI was obtained post-regression. Results: 80,293 hysterectomies (59,078 benign and 21,215 oncologic) were identified. The benign group was more likely to have an mFI-5 score of 0 (70 % vs 50 %, p = 0.001) and had shorter operative times (p = 0.001). In the benign group, mFI-5 was a strong predictor of mortality (c = 0.819, CI 0.704-0.933). Within the oncology group, the mFI-5 was a strong predictor of mortality (c = 0.801, CI 0.750-0.851), particularly for uterine and cervical cancers. It was moderately predictive of readmission (c = 0.671, CI 0.656-0.686) and strongly predictive of Clavien-Dindo class III and IV complications (c = 0.732, CI 0.713-0.750). Conclusion: The mFI-5 is a strong predictor of 30-day mortality and serious postoperative complications. These findings have the potential to improve identification of high-risk patients in the preoperative setting.