The golden tickets: impact of preference signaling on obstetrics and gynecology residency applicants.

BACKGROUND: With the residency selection process becoming more competitive and programs receiving unprecedented numbers of applications, some specialties have introduced preference signaling in an attempt to help applicants target programs of interest. In the 2022-2023 application cycle, obstetrics and gynecology also introduced a 2-tiered system with a limited number of gold signals (n=3) and silver signals (n=15). OBJECTIVE: Given the novelty of preference signaling in the obstetrics and gynecology residency application process, this study aimed to (1) assess the effect of signals on interview offers and match and (2) discuss applicant attitudes toward this preference signaling system. STUDY DESIGN: This was a voluntary cross-sectional survey study conducted in April 2023 that was open to all fourth-year medical students who applied to an obstetrics and gynecology residency in the United States. Self-reported demographics, signaling, interview, and match data were collected. In addition, students were asked about attitudes toward signaling on a 5-point Likert scale. RESULTS: Of the 1507 applicants who entered an obstetrics and gynecology residency via match or Supplemental Offer and Acceptance Program process, 969 (64.3%) completed the survey. Moreover, an additional 22 applicants who did not match responded to the survey. More respondents used all 3 gold tokens (98.3%) and all 15 silver tokens (94.3%). The mean number of applications sent was 74.3±35.1, and the mean number of interviews received per applicant was 12.8±6.6. The interviews or token yields were 64.0%±31.5% for gold tokens, 43.8%±23.1% for silver tokens, and 9.8%±10.0% for no token. Of the survey respondents, 340/951 (35.8%) matched to a gold token program, 338/951 (35.5%) matched to a silver token program, and 244/951 (25.7%) matched to a nontoken program. Furthermore, 499/951 applicants (52.5%) reported feeling slightly positive or very positive about signaling. CONCLUSION: Most obstetrics and gynecology applicants in this survey participated in preference signaling. Gold and silver tokens were associated with high ratios of interview invitations compared with no token. However, the overall number of applications did not decrease in the 2022-2023 cycle, and only half of survey respondents reported feeling positive about the signaling process. These results can inform program directors and students about application number and strategy in upcoming cycles.

Taking the Express Lane: Student Attitudes Towards Tracking in Ob/Gyn Residency.

We sought to determine the subspecialty interests of fourth-year medical students (MS4s) matched to Ob/Gyn and evaluate their attitudes towards residency tracking. Matched MS4s completed a survey regarding subspecialization, confidence in that choice, and desire for tracking. A total of 922 MS4s completed the survey. Of these, 474 (51.4%) desired subspecialty training, but were less confident in their choice compared with those desiring generalist careers (60.0/100 vs. 64.9/100, P=0.003). Those seeking subspecialty training were more likely to desire tracking (15.2% vs. 39.5%, P<0.001). In conclusion, 51% of MS4s desired subspecialty training over generalist careers. Almost 40% of these students are interested in tracking.

CYP2D6 Activity Is Correlated with Changes in Plasma Concentrations of Taurocholic Acid during Pregnancy and Postpartum in CYP2D6 Extensive Metabolizers.

Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of >20% of marketed drugs. CYP2D6 expression and activity exhibit high interindividual variability and is induced during pregnancy. The farnesoid X receptor (FXR) is a transcriptional regulator of CYP2D6 that is activated by bile acids. In pregnancy, elevated plasma bile acid concentrations are associated with maternal and fetal risks. However, modest changes in bile acid concentrations may occur during healthy pregnancy, thereby altering FXR signaling. A previous study demonstrated that hepatic tissue concentrations of bile acids positively correlated with the hepatic mRNA expression of CYP2D6. This study sought to characterize the plasma bile acid metabolome in healthy women (n = 47) during midpregnancy (25-28 weeks gestation) and ≥3 months postpartum and to determine if plasma bile acids correlate with CYP2D6 activity. It is hypothesized that during pregnancy, plasma bile acids would favor less hydrophobic bile acids (cholic acid vs. chenodeoxycholic acid) and that plasma concentrations of cholic acid and its conjugates would positively correlate with the urinary ratio of dextrorphan/dextromethorphan. At 25-28 weeks gestation, taurine-conjugated bile acids comprised 23% of the quantified serum bile acids compared with 7% ≥3 months postpartum. Taurocholic acid positively associated with the urinary ratio of dextrorphan/dextromethorphan, a biomarker of CYP2D6 activity. Collectively, these results confirm that the bile acid plasma metabolome differs between pregnancy and postpartum and provide evidence that taurocholic acid may impact CYP2D6 activity during pregnancy. SIGNIFICANCE STATEMENT: Bile acid homeostasis is altered in pregnancy, and plasma concentrations of taurocholic acid positively correlate with CYP2D6 activity. Differences between plasma and/or tissue concentrations of farnesoid X receptor ligands such as bile acids may contribute to the high interindividual variability in CYP2D6 expression and activity.

Pregnancy Has No Clinically Significant Effect on the Pharmacokinetics of Bupropion or Its Metabolites.

BACKGROUND: Bupropion (BUP) is a chiral antidepressant and smoking cessation aide with benefits and side effects correlated with parent and active metabolite concentrations. BUP is metabolized by CYP2B6, CYP2C19, and CYP3A4 to hydroxy-BUP (OH-BUP) as well as by 11ß-hydroxysteroid dehydrogenase-1 and aldo-keto reductases to threohydrobupropion (Threo) and erythrohydrobupropion (Erythro), respectively. As pregnancy alters the activity of drug-metabolizing enzymes, the authors hypothesized that BUP metabolism and BUP metabolite concentrations would be altered during pregnancy, potentially affecting the efficacy and safety of BUP in pregnant women. METHODS: Pregnant women (n = 8) taking BUP chronically were enrolled, and steady-state plasma samples and dosing interval urine samples were collected during pregnancy and postpartum. Maternal and umbilical cord venous blood samples were collected at delivery from 3 subjects, and cord blood/maternal plasma concentration ratios were calculated. The concentrations of BUP stereoisomers and their metabolites were measured. Paired t tests were used to compare pharmacokinetic parameters during pregnancy and postpartum. RESULTS: No significant changes were observed in the steady-state plasma concentrations, metabolite to parent ratios, formation clearances, or renal clearance of any of the compounds during pregnancy when compared with postpartum. The umbilical cord venous plasma concentrations of BUP and its metabolites were 30%-60% lower than maternal plasma concentrations. CONCLUSIONS: This study showed that there are no clinically meaningful differences in the stereoselective disposition of BUP or its metabolites during pregnancy, indicating that dose adjustment during pregnancy may not be necessary. The results also showed that the placenta provides a partial barrier for bupropion and its metabolite distribution to the fetus, with possible placental efflux transport of bupropion and its metabolites.

Chronic Liver Disease in the Obstetric Patient.

Chronic liver disease in pregnancy is rare. Historically, many chronic liver diseases were considered contraindications to pregnancy; however, with current monitoring and treatment strategies, pregnancy may be considered in many cases. Preconception and initial antepartum consultation should focus on disease activity, medication safety, risks of pregnancy, as well as the need for additional monitoring during pregnancy. In most cases, a multidisciplinary approach is necessary to ensure optimal maternal and fetal outcomes. Despite improving outcomes, pregnancy in women with the chronic liver disease remains high risk.

An enhanced recovery after surgery pathway for cesarean delivery decreases hospital stay and cost.

BACKGROUND: Enhanced recovery after surgery pathways provide a multidisciplinary, evidence-based approach to the care of surgical patients. They have been shown to decrease postoperative length of stay and cost in several surgical subspecialties, including gynecology, but have not been well-studied in obstetric patients who undergo cesarean delivery. OBJECTIVE: We sought to determine whether the implementation of an enhanced recovery after surgery pathway for cesarean delivery would decrease postoperative length of stay and postoperative direct cost compared with historic controls. STUDY DESIGN: We conducted a retrospective cohort study that compared postoperative length of stay and postoperative direct cost among women on the enhanced recovery after surgery cesarean delivery pathway in the first year of implementation (April 1, 2017, to March 31, 2018; n=531) compared with historic controls (March 1, 2016, to February 28, 2017; n=661). Literature review informed the development of a prototype enhanced recovery after surgery pathway for cesarean delivery based on best practices from previous enhanced recovery after surgery experience in obstetrics (if available) or from other surgical disciplines if there were no available data for obstetrics. When there was not relevant published evidence from obstetrics, the taskforce used clinical experience and expert opinion to develop the pathway. The enhanced recovery after surgery cesarean delivery pathway included preadmission patient education and preoperative, intrapartum, and postoperative elements. Some components reflected standard obstetric care, and others were specific to the enhanced recovery after surgery pathway. Women with pregestational diabetes mellitus who were receiving insulin therapy before pregnancy, women with preeclampsia with severe features, women with complex pain needs, and women with surgical complications were excluded from baseline and implementation groups. Enhanced recovery after surgery cesarean delivery pathway participation was determined by order set usage. Analysis was stratified for women who underwent planned (no labor; n=530) and unplanned (labor; n=662) cesarean delivery. Demographic and clinical characteristics, postoperative length of stay, postoperative direct cost, and readmission rates for the baseline and implementation groups were compared with the use of chi-square and t-tests. RESULTS: During the first year of implementation, 531 of 640 eligible women (83%) were included in the enhanced recovery after surgery cesarean delivery pathway. Body mass index was marginally higher in the baseline group for unplanned cesarean delivery (32.5±7.1 vs 31.4±6.7 kg/m2; P=.04). Otherwise there were no significant differences in demographic or maternal clinical characteristics between baseline or implementation groups overall or for planned or unplanned cesarean delivery. Compared with baseline, implementation of the enhanced recovery after surgery cesarean delivery pathway resulted in a significant decrease in postoperative length of stay by 7.8% or 4.86 hours overall (P<.001) and for both planned (P=.001) and unplanned (P=.002) cesarean delivery. Total postoperative direct costs decreased by 8.4% or $642.85 per patient overall (P<.001) and for both planned (P<.001) and unplanned (P<.001) cesarean delivery. There were no significant differences in readmission rates. CONCLUSION: Implementation of an enhanced recovery after surgery pathway for women who had planned or unplanned cesarean delivery was associated with significantly decreased postoperative length of stay and significant direct cost-savings per patient, without an increase in hospital readmissions. Given that cesarean delivery is 1 of the most common surgical procedures performed in the United States, positively impacting postoperative length of stay and direct cost for women who undergo cesarean delivery could have significant healthcare cost-savings.

Survey of Obstetrics and Gynecology Residents Regarding Pneumococcal Vaccination in Pregnancy: Education, Knowledge, and Barriers to Vaccination.

OBJECTIVE: The 23-valent pneumococcal vaccine is recommended for adults over 65 years of age and younger adults with certain medical conditions. The Centers for Disease Control and Prevention (CDC) state insufficient evidence to recommend routine pneumococcal vaccination during pregnancy, but the vaccine is indicated for pregnant women with certain medical conditions. We designed this project to gauge obstetrics and gynecology (OB/GYN) resident knowledge of maternal pneumococcal vaccination. METHODS: We administered a 22-question survey to OB/GYN residents about maternal pneumococcal vaccination. We performed descriptive analysis for each question. RESULTS: 238 OB/GYN residents responded. Overall, 69.3% of residents reported receiving vaccination education and 86.0% reported having ready access to vaccine guidelines and safety data. Most residents knew that asplenia (78.2%), pulmonary disease (77.3%), and HIV/AIDS (69.4%) are indications for vaccination but less knew that cardiovascular disease (45.0%), diabetes (35.8%), asthma (42.8%), nephrotic syndrome (19.7%), and renal failure (33.6%) are also indications for vaccination. CONCLUSION: OB/GYN residents are taught about vaccines and have ready access to vaccine guidelines and safety data. However, knowledge of indications for pneumococcal vaccination in pregnancy is lacking. Likely, the opportunity to vaccinate at-risk pregnant patients is being missed.

Beyond the Ivory Tower: A Comparison of Grades Across Academic and Community OB/GYN Clerkship Sites.

UNLABELLED: CONSTRUCT: Decentralized clinical education is the use of community facilities and community physicians to educate medical students. The theory behind decentralized clinical education is that academic and community sites will provide educational equivalency as determined by objective and subjective performance measures, while training more medical students and exposing students to rural or underserved communities. One of the major challenges of decentralized clinical education is ensuring site comparability in both learning opportunities and evaluation of students. BACKGROUND: Previous research has examined objective measures of student performance, but less is known about subjective performance measures, particularly in the field of obstetrics and gynecology (OB/GYN). This study explores the implications of clinical site on the adequacy of subjective and objective performance measures. APPROACH: This was a retrospective cohort study of 801 students in the University of Washington School of Medicine OB/GYN clerkship from 2008 to 2012. Academic sites included those with OB/GYN residency programs (n = 2) and community sites included those without residency programs (n = 29). The association between clerkship site and National Board of Medical Examiners (NBME) grade was assessed using linear regression and clinical and final grade using multinomial regression, estimating ß coefficient and relative risks (RR), respectively, and 95% confidence intervals (CIs), adjusting for gender, academic quarter of clerkship, and year of clerkship. RESULTS: There were no differences in NBME exam grades of students at academic sites (76.4 (7.3) versus 74.6 (8.0), ß = -0.11, 95% CI [1.35, 1.12] compared to community sites. For clinical grade, students at community sites were 2.4 times more likely to receive honors relative to high pass (RR 2.45), 95% CI [1.72, 3.50], and for final grade, students at community sites were 1.9 times more likely to receive honors relative to pass (RR 1.98), 95% CI [1.27, 3.09], and 1.6 times more likely to receive honors relative to high pass (RR 1.62), 95% CI [1.05, 2.50], compared to those at academic sites. CONCLUSIONS: Students at community sites receive higher clinical and final grades in the OB/GYN clerkship. This highlights a significant challenge in decentralized clinical education-ensuring site comparability in clinical grading, Further work should examine the differences in sites, as well as improve standardization of clinical grading. This also underscores an important consideration, as the final grade can influence medical school rank, nomination into honor societies, and ranking of residency applicants.

Renal function estimating equations performance during pregnancy and postpartum.

STUDY OBJECTIVES: The objectives of this study were to evaluate the performance of renal function estimating equations compared to measured creatinine clearance (CrCl) during pregnancy and postpartum and to evaluate which body weight (pre-pregnancy weight (PPW), actual body weight (ABW), and ideal body weight (IBW)) provides the best performance. DESIGN: A retrospective study. SETTING: Collections tookplace in the University of Washington clinical research unit. PATIENTS: Women (n = 166) who completed ≥1 pharmacokinetic (PK) study with a 6-24 h measured CrCl during pregnancy and/or ≥3 months postpartum were included. INTERVENTION: CrCl was estimated utilizing estimated glomerular filtration rate (eGFR) and CrCl equations with common weight descriptors. Analyses included Bland-Altman, relative accuracies within 10% and 25%, and root mean squared error (RMSE). Overall performance was determined by summation of rank for evaluation parameters. MEASUREMENTS AND MAIN RESULTS: During pregnancy, correlations between measured CrCl and estimated CrCl were between 0.5-0.8; equations with slopes closest to one were Modification of Diet in Renal Disease (MDRD2; PPW and ABW) and Cockcroft-Gault (CG) (PPW); and y-intercept closest to zero was Preeclampsia Glomerular Filtration Rate (PGFR). The lowest bias was seen with CG (ABW), and the highest accuracy within 25% was CG (ABW). CG (PPW) had the lowest RMSE. Postpartum, the best correlation was found with MDRD2 (PPW), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI (ABW)), and CKD-EPI 2021 (PPW). For slopes closest to one, MDRD2 (ABW) was best, whereas the equation with y-intercept closest to zero was CKD-EPI (ABW). CG (PPW) had the highest accuracy within 25%, and 100/serum creatinine (SCr) had the lowest bias. Based on overall performance, CG (PPW) was the best followed by CG (ABW) and PGFR during pregnancy and 100/SCr followed by CG (PPW) and CG (ABW) postpartum. CONCLUSION: The new CKD-EPI 2021 equation did not perform well during pregnancy. When 24-h CrCls are not available during pregnancy, CG (PPW or ABW) performed the best overall, whereas at 3 months postpartum, 100/SCr performed the best overall.

Volume, Distribution, and Inequities by Race and Gender of Clinical Experiences Reported by Medical Students Entering Obstetrics and Gynecology Residencies.

OBJECTIVE: To assess for inequities by race and gender of fourth year medical students' (MS4s) self-reported clinical experience in obstetrics and gynecology (Ob/Gyn). DESIGN: This was a voluntary, cross-sectional survey. Participants provided demographic data, information regarding their preparation for residency, and self-reported numbers of hands-on clinical experiences. Responses were compared across demographic categories to assess for disparity in pre-residency experiences. SETTING: The survey was open to all MS4s matched to Ob/Gyn internships in the United States in 2021. PARTICIPANTS: The survey was distributed primarily via social media. Eligibility was verified by participants supplying the names of their medical school of origin and their matched residency program prior to completing the survey. 1057/1469 (71.9%) MS4s entering Ob/Gyn residencies participated. Respondent characteristics were not different from nationally available data. RESULTS: Median clinical experience numbers were calculated for hysterectomies (10; IQR 5-20), suturing opportunities (15; IQR 8-30), and vaginal deliveries (5.5; IQR 2-12). Non-White students had fewer hands-on experiences with hysterectomy, suturing, and cumulative clinical experiences when compared to White MS4s (p values <0.001). Female students had fewer hands-on experiences with hysterectomies (p < 0.04), vaginal delivery (p < 0.03), and cumulative experiences (p < 0.002) than male students. When assessed by quartiles, non-White students and female students were less likely to be in the top quartile for experience and more likely to be in the bottom quartile for experience than their White and male counterparts, respectively. CONCLUSIONS: A significant number of medical students entering Ob/Gyn residency have minimal hands-on clinical experience with foundational procedures. Additionally, there are racial and gender disparities in clinical experiences of MS4s matching to Ob/Gyn internships. Future work should identify how biases in medical education may affect the access to clinical experience in medical school, and potential interventions to mitigate inequities in procedures and confidence prior to residency.

Does the Degree Matter? MD and DO Students Who Match Into OB/GYN Report Different Experiences in US Undergraduate Medical Education.

Background: Although allopathic (MD) and osteopathic (DO) students have similar curricular requirements, little is known about differences in MD and DO preparedness for obstetrics and gynecology (OB/GYN) residency. Objective: To assess differences in experiences and confidence of MD vs DO students who matched to OB/GYN. Methods: This cross-sectional survey study was open to all fourth-year medical students who matched to OB/GYN in the United States in April 2021. The survey included demographic data, clinical experiences, confidence (5-point sliding scale), and a 11-item knowledge test. Survey responses were compared to assess for disparities in experiences and confidence. Results: Survey response rate was 72.0% (1057 of 1469) students matched to OB/GYN postgraduate year 1 positions. Of the 871 MD and 175 DO responding students, MDs were more likely to have clerkships ≥6 weeks (78.1% vs 15.4%; P<.001) and a home sub-internship (92.0% vs 53.4%; P<.001). DOs reported more hands-on experiences with procedures (MD median=35 [20-35] vs DO median=40 [25-65]; P=.002). There was no difference in self-reported confidence in knowledge, technical skills, or having a realistic sense of internship, and no difference in baseline knowledge test scores. DOs felt less confident about their medical school preparation (aOR 0.40; 95% CI 0.25-0.66; P<.001) and were more likely to perceive inequity of residency preparation (aOR 1.88; 95% CI 1.18-3.00; P=.002). Conclusions: MD students matched to US OB/GYN residency programs reported longer clerkship and more home sub-internships, while DO students reported more hands-on experiences. Despite reporting similar confidence in knowledge and skills, DO students felt less prepared for internship.

Plasma hydrogen sulfide, nitric oxide, and thiocyanate levels are lower during pregnancy compared to postpartum in a cohort of women from the Pacific northwest of the United States.

AIMS: Pregnancy alters multiple physiological processes including angiogenesis, vasodilation, inflammation, and cellular redox, which are partially modulated by the gasotransmitters hydrogen sulfide (H2S) and nitric oxide (NO). In this study, we sought to determine how plasma levels of H2S, NO, and the H2S-related metabolites thiocyanate (SCN-), and methanethiol (CH3SH) change during pregnancy progression. MATERIALS AND METHODS: Plasma was collected from 45 women at three points: 25-28 weeks gestation, 28-32 week gestation, and at ≥3 months postpartum. Plasma levels of H2S, SCN-, and CH3SH were measured following derivatization using monobromobimane followed by LC-MS/MS. Plasma NO was measured indirectly using the Griess reagent. KEY FINDINGS: NO and SCN- were significantly lower in women at 25-28 weeks gestation and 28-32 weeks gestation than postpartum while plasma H2S levels were significantly lower at 28-32 weeks gestation than postpartum. No significant differences were observed in CH3SH. SIGNIFICANCE: Previous reports demonstrated that the production of H2S and NO are stimulated during pregnancy, but we observed lower levels during pregnancy compared to postpartum. Previous reports on NO have been mixed, but given the related effects of H2S and NO, it is expected that their levels would be higher during pregnancy vs. postpartum. Future studies determining the mechanism for decreased H2S and NO during pregnancy will elucidate the role of these gasotransmitters during normal and pathological progression of pregnancy.

The #ObGynInternChallenge: Reach, Adoption, Implementation, and Effectiveness of a Microlearning SMS-Distributed Curriculum.

PROBLEM: While many medical schools have implemented bootcamps or specialized curricula to prepare medical students for residency, these programs are neither universal nor consistent in their content. APPROACH: The authors created an electronic, multimodal, short messaging service (SMS)-distributed curriculum, called the #ObGynInternChallenge, to improve learners' medical knowledge, based on the Council on Resident Education in Obstetrics and Gynecology educational objectives. The curriculum was open to all fourth-year medical students who matched into obstetrics and gynecology (Ob/Gyn). Daily messages were delivered to participants' mobile devices via SMS for 25 consecutive weekdays, May 3-June 4, 2021. Each day's message included an introduction with key facts, an infographic, a website link with a podcast and additional reference materials, and at least one question. The authors assessed its reach, adoption, implementation, and effectiveness. OUTCOMES: For reach and adoption, total enrollment for the curriculum was 1,057 (72.0%) of 1,469 filled Ob/Gyn residency positions in the 2021 Match. The total cost of the intervention was $2,503.20 or $2.37 per participant. For implementation, all participants who signed up for the course received the daily messages, and 858/1,057 (81.2%) completed the course. Participants felt the curriculum was an excellent resource for studying (391/426, 91.8%) and the course was enjoyable to use (395/424, 93.2%). For effectiveness, mean score improvement was 11.6% (pre-test: 62.4%, post-test: 74.0%; P < .001). In the multivariate linear regression analysis, high podcast ( P = .02) and website use ( P = .002) were associated with greater score improvement. High social media use was associated with less improvement ( P = .02). NEXT STEPS: This study suggests promise for a low-cost, largely satisfying SMS-distributed curriculum in terms of offering some benefit for short-term knowledge gain. Next steps include expanding such a curriculum to meet standard learning objectives for all fourth-year medical students entering residency.

Effects of Pregnancy on Plasma Sphingolipids Using a Metabolomic and Quantitative Analysis Approach.

Changes in the maternal metabolome, and specifically the maternal lipidome, that occur during pregnancy are relatively unknown. The objective of this investigation was to evaluate the effects of pregnancy on sphingolipid levels using metabolomics analysis followed by confirmational, targeted quantitative analysis. We focused on three subclasses of sphingolipids: ceramides, sphingomyelins, and sphingosines. Forty-seven pregnant women aged 18 to 50 years old participated in this study. Blood samples were collected on two study days for metabolomics analysis. The pregnancy samples were collected between 25 and 28 weeks of gestation and the postpartum study day samples were collected ≥3 months postpartum. Each participant served as their own control. These samples were analyzed using a Ultra-performance liquid chromatography/mass spectroscopy/mass spectroscopy (UPLC/MS/MS) assay that yielded semi-quantitative peak area values that were used to compare sphingolipid levels between pregnancy and postpartum. Following this lipidomic analysis, quantitative LC/MS/MS targeted/confirmatory analysis was performed on the same study samples. In the metabolomic analysis, 43 sphingolipid metabolites were identified and their levels were assessed using relative peak area values. These profiled sphingolipids fell into three categories: ceramides, sphingomyelins, and sphingosines. Of the 43 analytes measured, 35 were significantly different during pregnancy (p < 0.05) (including seven ceramides, 26 sphingomyelins, and two sphingosines) and 32 were significantly higher during pregnancy compared to postpartum. Following metabolomics, a separate quantitative analysis was performed and yielded quantified concentration values for 23 different sphingolipids, four of which were also detected in the metabolomics study. Quantitative analysis supported the metabolomics results with 17 of the 23 analytes measured found to be significantly different during pregnancy including 11 ceramides, four sphingomyelins, and two sphingosines. Fourteen of these were significantly higher during pregnancy. Our data suggest an overall increase in plasma sphingolipid concentrations with possible implications in endothelial function, gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy, and fetal development. This study provides evidence for alterations in maternal sphingolipid metabolism during pregnancy.

The Effects of Pregnancy on Amino Acid Levels and Nitrogen Disposition.

Limited data are available on the effects of pregnancy on the maternal metabolome. Therefore, the objective of this study was to use metabolomics analysis to determine pathways impacted by pregnancy followed by targeted confirmatory analysis to provide more powerful conclusions about metabolic alterations during pregnancy. Forty-seven pregnant women, 18-50 years of age were included in this study, with each subject serving as their own control. Plasma samples were collected between 25 and 28 weeks gestation and again ≥3 months postpartum for metabolomics analysis utilizing an HILIC/UHPLC/MS/MS assay with confirmatory targeted specific concentration analysis for 10 of the significantly altered amino acids utilizing an LC/MS assay. Principle component analysis (PCA) on metabolomics data clearly separated pregnant and postpartum groups and identified outliers in a preliminary assessment. Of the 980 metabolites recorded, 706 were determined to be significantly different between pregnancy and postpartum. Pathway analysis revealed three significantly impacted pathways, arginine biosynthesis (p = 2 × 10-5 and FDR = 1 × 10-3), valine, leucine, and isoleucine metabolism (p = 2 × 10-5 and FDR = 2 × 10-3), and xanthine metabolism (p = 4 × 10-5 and FDR = 4 × 10-3). Of these we focused analysis on arginine biosynthesis and branched-chain amino acid (BCAA) metabolism due to their clinical importance and interconnected roles in amino acid metabolism. In the confirmational analysis, 7 of 10 metabolites were confirmed as significant and all 10 confirmed the direction of change of concentrations observed in the metabolomics analysis. The data support an alteration in urea nitrogen disposition and amino acid metabolism during pregnancy. These changes could also impact endogenous nitric oxide production and contribute to diseases of pregnancy. This study provides evidence for changes in both the ammonia-urea nitrogen and the BCAA metabolism taking place during pregnancy.

Impact of Pregnancy and Vitamin A Supplementation on CYP2D6 Activity.

The mechanism of cytochrome P450 2D6 (CYP2D6) induction during pregnancy has not been evaluated in humans. This study assessed the changes in CYP2D6 and CYP3A activities during pregnancy and postpartum, and the effect of vitamin A administration on CYP2D6 activity. Forty-seven pregnant CYP2D6 extensive metabolizers (with CYP2D6 activity scores of 1 to 2) received dextromethorphan (DM) 30 mg orally as a single dose during 3 study windows (at 25 to 28 weeks of gestation, study day 1; at 28 to 32 weeks of gestation, study day 2; and at ≥3 months postpartum, study day 3). Participants were randomly assigned to groups with no supplemental vitamin A (control) or with supplemental vitamin A (10 000 IU/day orally for 3 to 4 weeks) after study day 1. Concentrations of DM and its metabolites, dextrorphan (DX) and 3-hydroxymorphinan (3HM), were determined from a 2-hour post-dose plasma sample and cumulative 4-hour urine sample using liquid chromatography-mass spectrometry. Change in CYP2D6 activity was assessed using DX/DM plasma and urine metabolic ratios. The activity change in CYP3A was also assessed using the 3HM/DM urine metabolic ratio. The DX/DM urine ratio was significantly higher (43%) in pregnancy compared with postpartum (P = .03), indicating increased CYP2D6 activity. The DX/DM plasma ratio was substantially higher in the participants, with an activity score of 1.0 during pregnancy (P = .04) compared with postpartum. The 3HM/DM urinary ratio was significantly higher (92%) during pregnancy, reflecting increased CYP3A activity (P = .02). Vitamin A supplementation did not change CYP2D6 activity during pregnancy; however, plasma all-trans retinoic acid (atRA) concentrations were positively correlated with increased CYP2D6 activity during pregnancy and postpartum. Further research is needed to elucidate the mechanisms of increased CYP2D6 activity during pregnancy.

Cesarean delivery rates and indications in pregnancies complicated by diabetes.

OBJECTIVE: Rates of pregestational (PGDM) and gestational diabetes (GDM), and their associated pregnancy complications, are rising. Pregnancies complicated by diabetes have increased cesarean delivery (CD) rates; however, there are limited data regarding the current rates of, and contributing factors to, these deliveries. The Robson Ten Group Classification System (TGCS) is a clinically relevant, standardized framework that can be used to evaluate and analyze cesarean rates. The objective of this study was to evaluate rates of, and indications for, intrapartum, unplanned CD among pregnancies complicated by diabetes, compared to normoglycemic (NG) pregnancies, in a large United States birth cohort. METHODS: This retrospective cohort study used chart-abstracted data on births between 24 and 42 weeks' gestation at 17 hospitals that contributed to the Obstetrical Care Outcome Assessment Program database between 01/2016 and 03/2019. The CD rate for NG pregnancies, and pregnancies complicated by gestational and PGDM was calculated and compared using the Robson TGCS. The indications for intrapartum CD in patients with term, singleton, vertex gestations without a prior cesarean were then analyzed. Univariate and multivariate logistic regression models were used to compare the cesarean rate and indications for CD, between the diabetic groups and the NG group. Results were adjusted for maternal age, BMI, neonatal birth weight, and insurance status, as well as clustering by hospital. RESULTS: A total of 86,381 pregnant people were included in the study cohort. Of these 76,272 (88.3%) were NG, 8591 (9.9%) had GDM, and 1518 (1.8%) had PGDM. Compared to NG patients, overall cesarean rates were higher in patients with GDM (40.3% vs. 29.7%; aOR 1.25, 95%CI 1.18-1.31) and PGDM (60.0% vs. 29.7%; aOR 2.53, 95%CI 2.04-3.13). This finding remained true when the cohort was restricted to term, singleton, vertex laboring patients without a prior cesarean; compared to NG patients, the cesarean rate was higher in patients with GDM (17.4% vs. 12.2%, aOR 1.37, 95%CI 1.29-1.45) and PGDM (26.0% vs. 12.2%, aOR 2.55, 95%CI 2.00-3.25). The cesarean rate for fetal indications was similar in the GDM (5.7%) and NG (4.4%) groups, while those patients with PGDM had a significantly higher rate (10.4%; aOR 2.01, 95%CI 1.43-2.83). Similarly, the rate of cesarean for labor dystocia in patients with PGDM was significantly higher than in NG patients (16.9% vs. 7.0%, and aOR 2.28, 95%CI 1.66-3.13) while patients with GDM had an intermediate rate (10.6% vs. 7.0%, aOR 1.49, 95%CI 1.40-1.57). CONCLUSIONS: The CD rate is significantly higher in pregnancies complicated by diabetes, particularly pregestational, compared to NG pregnancies. Despite controlling for maternal factors and birth weight, pregnancies complicated by diabetes are more likely to undergo an unplanned intrapartum cesarean secondary to labor dystocia than their NG counterparts, but only pregnancies complicated by PGDM have an increased risk of cesarean for fetal indications. More research is needed to understand whether this higher cesarean rate is due to factors intrinsic to diabetes in laboring patients or is due to a difference in the way clinicians manage diabetics in labor.

Customized GROW vs INTERGROWTH-21st birthweight standards to identify small for gestational age associated perinatal outcomes at term.

BACKGROUND: Fetal growth restriction is associated with stillbirth and other adverse pregnancy outcomes, and the use of the correct weight standard is an essential proxy indicator of growth status and perinatal risk. OBJECTIVE: This study aimed to assess the performance of two international birthweight standards for their ability to identify perinatal morbidity and mortality indicators associated with small for gestational age infants at term. STUDY DESIGN: This retrospective cohort study used data from a multicenter perinatal quality initiative, including a multiethnic dataset of 125,826 births from 2012 to 2017. Of the singleton term births, 92,622 had complete outcome data including stillbirth, neonatal death, 5-minute Apgar score <7, neonatal glucose instability and need for newborn transfer to a higher level of care or neonatal intensive care unit admission. The customized GROW and INTERGROWTH-21st birthweight standards were applied to determine small for gestational age (<10th percentile) according to their respective methods and formulae. The associations with adverse outcomes were expressed as relative risks with 95% confidence intervals and population attributable fractions. RESULTS: GROW and INTERGROWTH-21st classified 9578 (10.3%) and 4079 (4.4%) pregnancies as small for gestational age, respectively. For all of the outcomes assessed, GROW identified more small for gestational age infants with adverse outcomes than INTERGROWTH-21st, including more stillbirths, perinatal deaths, low Apgar scores, glucose instability, newborn seizure, and transfers to a higher level of care. Moreover, 13 of 27 stillbirths (48%) that were small for gestational age by either method were identified as small for gestational age by GROW but not by INTERGROWTH-21st. Similarly, additional cases of all other adverse outcome indicators were identified by GROW as small for gestational age, whereas INTERGROWTH-21st identified in only 1 category (glucose instability) 9 of 295 cases (3.1%), which were not identified as small for gestational age by GROW. CONCLUSION: Customized assessment using GROW resulted in increased identification of small for gestational age term infants that were at significantly increased risk of an array of adverse pregnancy outcomes.

Could ultrasound midwifery training increase antenatal detection of congenital anomalies in Ghana?

BACKGROUND: As part of World Health Organization (WHO) 2016 updated antenatal care (ANC) guidelines routine ultrasonography is recommended, including to detect congenital anomalies. The Ghana Health Service (GHS) developed an in-service midwifery ultrasound training course in 2017, which includes fetal anomaly detection. Training rollout has been very limited. We sought to determine proportions of anomalies among neonates presenting to Tamale Teaching Hospital (TTH) that should be prenatally detectable by course-trained midwives in order to determine training program potential utility. METHODS: We analyzed data from a registry of neonates admitted to TTH with congenital anomaly diagnoses in 2016. We classified ultrasonographic detectability of anomalies at ≤13 and 14-23 weeks gestation, based on GHS course content and literature review. Secondary analysis included 2011-2015 retrospective chart review data. RESULTS: Eighty-five neonates with congenital anomalies were admitted to TTH in 2016. Seventy-three (86%) mothers received ≥1 ANC visit; 47 (55%) had at least one prenatal ultrasound, but only three (6%) were interpreted as abnormal. Sixteen (19%) and 26 (31%) of the anomalies should be readily detectable by course-trained midwives at ≤13 and 14-23 weeks gestation, respectively. When the 161 anomalies from 2011-2015 were also analyzed, 52 (21%) and 105 (43%) should be readily detectable at ≤13 and 14-23 weeks gestation, respectively. "Optimal conditions" (state-of-the-art equipment by ultrasonography-trained physicians) should readily identify 53 (22%) and 115 (47%) of the anomalies at ≤13 and 14-23 weeks gestation, respectively. CONCLUSION: Training Ghanaian midwives could substantially increase second trimester anomaly detection, potentially at proportions nearing highly resourced settings. Our data also highlight the need for refinement of the WHO antenatal ultrasonography recommendation for a scan before 24 weeks gestation for multiple purposes. Gestational dating accuracy requires first trimester scanning while fetal anomaly detection is more accurate during second trimester. Further specification will enhance guideline utility.