Publications by authors named "Amanda A Allshouse"

71 Publications

Maternal serum fructosamine levels and stillbirth: A case-control study of The Stillbirth Collaborative Research Network.

BJOG 2021 Sep 16. Epub 2021 Sep 16.

Division of Maternal-Fetal Medicine, University of Utah Health Sciences, Salt Lake City.

Objective: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth.

Design: Secondary analysis of a case-control study.

Settings: Multicenter study of five geographic catchment areas in the United States (U.S).

Population Or Sample: All singleton stillbirths with known diabetes status and fructosamine measurement and representative live birth controls.

Main Outcome Measures: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounders including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth.

Results: 529 women with a stillbirth and 1499 with a live birth were included the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than a live birth after adjustment (177 ± 3.05 vs. 165 ± 2.89 μmol/L, p<0.001). The difference in fructosamine levels between stillbirths and live births was greater among diabetic women (194 ± 8.54 vs. 162 ± 3.21 μmol/L) compared to those without diabetes (171 ± 2.50 vs. 162 ± 2.56 μmol/L). The AUC for fructosamine level and stillbirth was 0.634 (0.605 - 0.663) overall, 0.713 (0.624 - 0.802) with diabetes and 0.625 (0.595 - 0.656) with no diabetes.

Conclusion: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared to live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes likely do not justify routine screening in all cases of stillbirth.
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http://dx.doi.org/10.1111/1471-0528.16922DOI Listing
September 2021

Marijuana use, fetal growth, and uterine artery Dopplers.

J Matern Fetal Neonatal Med 2021 Sep 1:1-8. Epub 2021 Sep 1.

Department of Obstetrics & Gynecology, University of Utah Health, Salt Lake City, UT, USA.

Objective: Marijuana (MJ) use is associated with adverse effects on fetal growth. We aimed to investigate the timing of suboptimal fetal growth onset in MJ-exposed pregnancies. In addition, we aimed to explore the relationship between MJ-exposure and both abnormal uterine artery (UtA) Doppler parameters and small for gestational age (SGA).

Study Design: This was a secondary analysis of a prospective multicenter cohort that enrolled nulliparous individuals delivering non-anomalous fetuses beyond 20 weeks' gestation. Marijuana exposure was ascertained by self-report or clinical urine toxicology testing. Ultrasound estimated fetal weights (EFWs) were assessed in participants at both 16w0d-21w6d and 22w0d-29w6d. EFWs and birth weight (BW) were converted to weight percentiles (wPCT). EFW and BW wPCTs were calculated using population-based standards. Additionally, a customized standard designed to be applicable to both EFWs and BWs within the same model was also used to allow for EFW to BW percentile trajectories. The primary outcome, longitudinal wPCT, was compared between individuals with and without MJ use in a linear mixed-effects regression model adjusting for tobacco. For modeling, wPCT was smoothed across gestational age; MJ was estimated as an intercept and linear difference in the slope of gestational age. UtA Doppler notching, resistance index (RI), and pulsatility index (PI) at 16w0d-21w6d were compared using -test and . SGA at delivery was also compared.

Results: Nine thousand one hundred and sixty-three individuals met inclusion criteria; 136 (1.5%) used MJ during pregnancy. Individuals who used MJ were more likely to be younger, identify as non-Hispanic Black, and have had less education. Fetuses exposed to MJ had lower wPCT beginning at 28 weeks using population-based and customized standards, when compared to those without exposure. UtA notching, PI, and RI were similar between groups. SGA was more frequent in neonates exposed to MJ using both population-based (22 vs. 9%, <.001) and customized (25 vs. 14%, <.001) curves.

Conclusions: MJ-exposed fetuses were estimated to be smaller than unexposed fetuses starting at 28 weeks' gestation across both growth standards without a difference in UtA Doppler parameters.
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http://dx.doi.org/10.1080/14767058.2021.1960973DOI Listing
September 2021

Association between pregnancy and long-term cardiac outcomes in individuals with congenital heart disease.

Am J Obstet Gynecol 2021 Jul 28. Epub 2021 Jul 28.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, UT; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Intermountain Healthcare, Salt Lake City, UT.

Background: As early life interventions for congenital heart disease improve, more patients are living to adulthood and are considering pregnancy. Scoring and classification systems predict the maternal cardiovascular risk of pregnancy in the context of congenital heart disease, but these scoring systems do not assess the potential subsequent risks following pregnancy. Data on the long-term cardiac outcomes after pregnancy are unknown for most lesion types. This limits the ability of healthcare practitioners to thoroughly counsel patients who are considering pregnancy in the setting of congenital heart disease.

Objective: We aimed to evaluate the association between pregnancy and the subsequent long-term cardiovascular health of individuals with congenital heart disease.

Study Design: This was a retrospective longitudinal cohort study of individuals identifying as female who were receiving care in two adult congenital heart disease centers from 2014 to 2019. Patient data were abstracted longitudinally from a patient age of 15 years (or from the time of entry into the healthcare system) to the conclusion of the study, death, or exit from the healthcare system. The primary endpoint, a composite adverse cardiac outcome (death, stroke, heart failure, unanticipated cardiac surgery, or a requirement for a catheterized procedure), was compared between parous (at least one pregnancy >20 weeks' gestation) and nulliparous individuals. By accounting for differences in the follow-up, the effect of pregnancy was estimated based on the time to the composite adverse outcome in a proportional hazards regression model adjusted for the World Health Organization class, baseline cardiac medications, and number of previous sternotomies. Participants were also categorized according to their lesion type, including septal defects (ventricular septal defects, atrial septal defects, atrioventricular septal defects, or atrioventricular canal defects), right-sided valvular lesions, left-sided valvular lesions, complex cardiac anomalies, and aortopathies, to evaluate if there is a differential effect of pregnancy on the primary outcome when adjusting for lesion type in a sensitivity analysis.

Results: Overall, 711 individuals were eligible for inclusion; 209 were parous and 502 nulliparous. People were classified according to the World Health Organization classification system with 86 (12.3%) being classified as class I, 76 (10.9%) being classified as class II, 272 (38.9%) being classified as class II to III, 155 (22.1%) being classified as class III, and 26 (3.7%) being classified as class IV. Aortic stenosis, bicuspid aortic valve, dilated ascending aorta or aortic root, aortic regurgitation, and pulmonary insufficiency were more common in parous individuals, whereas dextro-transposition of the great arteries, Turner syndrome, hypoplastic right heart, left superior vena cava, and other cardiac diagnoses were more common in nulliparous individuals. In multivariable modeling, pregnancy was associated with the composite adverse cardiac outcome (36.4%% vs 26.1%%; hazard ratio, 1.83; 95% confidence interval, 1.25-2.66). Parous individuals were more likely to have unanticipated cardiac surgery (28.2% vs 18.1%; P=.003). No other individual components of the primary outcome were statistically different between parous and nulliparous individuals in cross-sectional comparisons. The association between pregnancy and the primary outcome was similar in a sensitivity analysis that adjusted for cardiac lesion type (hazard ratio, 1.61; 95% confidence interval, 1.10-2.36).

Conclusion: Among individuals with congenital heart disease, pregnancy was associated with an increase in subsequent long-term adverse cardiac outcomes. These data may inform counseling of individuals with congenital heart disease who are considering pregnancy.
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http://dx.doi.org/10.1016/j.ajog.2021.07.015DOI Listing
July 2021

Rigor, reproducibility, and transparency of randomized controlled trials in obstetrics and gynecology.

Am J Obstet Gynecol MFM 2021 Jul 26;3(6):100450. Epub 2021 Jul 26.

Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, UT (Drs Bruno, Einerson, and Metz, Ms Allshouse, and Drs Scott and Blue); Department of Obstetrics and Gynecology, Intermountain Healthcare, Murray, UT (Drs Bruno, Einerson, Metz, and Blue).

Background: Randomized controlled trials are considered the highest level of evidence but fewer than half are reproducible. A rigorous methodology improves trial quality, but reproducibility may be limited by a lack of transparency in reporting. The Consolidated Standards of Reporting Trials guidelines define reporting standards, and pretrial registration requires a predefined methodology and predefined outcomes.

Objective: We evaluated obstetrics and gynecology trials published in 6 journals in terms of their adherence to the Consolidated Standards of Reporting Trials guidelines. Second, we evaluated pretrial registration compliance and concordance between the registry and publication. Furthermore, we evaluated the differences in trial characteristics among randomized controlled trials with the highest level of compliance and those with lower levels of compliance and adherence to guidelines by journal type.

Study Design: This was a cross-sectional study of obstetrics and gynecology trials published between 2017 and 2019 in 6 journals (American Journal of Obstetrics & Gynecology, BJOG: An International Journal of Obstetrics and Gynaecology, Obstetrics & Gynecology, The Journal of the American Medical Association, The Lancet, and The New England Journal of Medicine). Randomized controlled trials were identified via PubMed and manual journal archive searches. The primary outcome was adequate compliance with the Consolidated Standards of Reporting Trials guidelines defined as ≥80% of the checklist items present. Secondary outcomes included completion of pretrial registration and concordance between the pretrial registration and publication in terms of the outcomes and sample size. We compared the characteristics between trials with adequate compliance and those with inadequate compliance. Secondary analyses included comparisons of characteristics of the trials in the top quartile for compliance with the Consolidated Standards of Reporting Trials guidelines with those of the trials in lower quartiles and compliance with guidelines in obstetrics-gynecology vs non-obstetrics-gynecology journals. In an exploratory analysis, trends in compliance with the Consolidated Standards of Reporting Trials guidelines across the study period were assessed. A post hoc sensitivity analysis evaluated the outcomes after the exclusion of 2 retracted trials.

Results: Of the 170 trials included, 80% (95% confidence interval, 74%-86%) were adequately compliant with the Consolidated Standards of Reporting Trials manuscript guidelines and 66% (95% confidence interval, 59%-73%) were compliant with the abstract guidelines. Nearly all trials (98%) reported pretrial registration. Concordance between pretrial registration and publication in terms of the primary outcomes was identified for 77% of the trials, concordance in terms of the secondary outcomes was observed in 32% of the trials, and concordance in terms of sample size was observed in 60% of the trials. Trials with adequate compliance were more likely to be preregistered, include an a priori power calculation, and use an intent to treat analysis. Trials in the top quartile for compliance with the Consolidated Standards of Reporting Trials guidelines were more likely to be multicenter, international, and government funded. More trials from non-obstetrics-gynecology journals were in the top quartile for compliance with the Consolidated Standards of Reporting Trials guidelines than trials from obstetrics-gynecology journals (64.9% vs 25.7%; P<.001). No significant trends in adequate compliance were identified across the study period. Results did not differ significantly in the sensitivity analysis.

Conclusion: Of all the trials included, 20% of obstetrics-gynecology trials published in 6 high-impact journals were not compliant with the Consolidated Standards of Reporting Trials guidelines, and there were major discrepancies between pretrial registration and publication. Transparency, reproducibility, and scientific rigor in obstetrics and gynecology trial reporting needs to be improved.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100450DOI Listing
July 2021

Impact of the p-Value Threshold on Interpretation of Trial Outcomes in Obstetrics and Gynecology.

Am J Perinatol 2021 Oct 24;38(12):1223-1230. Epub 2021 Jun 24.

Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah.

Objective:  Randomized controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. However, the reproducibility crisis has raised concerns about the scientific rigor of published RCT findings. Some advocate for a lower -value threshold. We aimed to review published OB/Gyn topical RCTs in three representative OB/Gyn journals and three high impact non-OB/Gyn journals to determine if their interpretations would change with adoption of a -value threshold for significance of 0.005. Secondarily, we evaluated if there were differences in methodologic characteristics between those that did and did not lose significance.

Study Design:  A manual search was performed to identify all OB/Gyn RCTs published in the selected journals between July 2017 and June 2019. Data were collected on primary outcome(s), methodology, and -values. We determined the proportion of primary outcomes that would remain statistically significant with adoption of a -value significance threshold of 0.005 versus be reinterpreted as "suggestive" (defined as -value between 0.005 and 0.05). Chi-square or Fisher's exact test were used to compare study characteristics.

Results:  Overall, 202 RCTs met inclusion criteria; 52% in obstetrics and 48% in gynecology. Of 90 studies considered significant with <0.05 at the time of publication, 54.4% ( = 49) would maintain significant ( < 0.005), while 45.6% ( = 41) would become suggestive using the lower threshold. Most RCTs utilized a single (90.1%) versus composite (8.9%) primary outcome type, used an intent-to-treat analysis (73.3%), and studied a drug intervention (46.5%). Methodologically, 23.7% did not prespecify analysis type, 28.2% did not meet the pre-determined sample size, and 9.4% did not report an a priori sample size calculation. Studies maintaining significance were more likely to be international and report a funding source.

Conclusion:  Adopting a -value significance threshold of 0.005 would require reinterpretation of almost half of RCT results in the OB/Gyn literature. Highly variable methodological quality was identified.

Key Points: · New p-value threshold results in reinterpretation of nearly half of RCT results in OB/Gyn literature.. · Highly variable methodological quality was identified.. · Reduced use of binary interpretations of significance is necessary..
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http://dx.doi.org/10.1055/s-0041-1731345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460605PMC
October 2021

Quantification of prenatal marijuana use: evaluation of the correlation between self-report, serum, urine and umbilical cord assays among women delivering at two urban Colorado hospitals.

Addiction 2021 Jun 17. Epub 2021 Jun 17.

University of Colorado School of Medicine, Aurora, CO, USA.

Background And Aims: To estimate during pregnancy correlations between frequency of self-reported use of marijuana and quantified marijuana metabolite in biospecimens including urine, sera and umbilical cord homogenate.

Design: Prospective cohort.

Setting: Two urban hospitals in Colorado with legal recreational and medicinal marijuana.

Participants: Pregnant women (<16 weeks gestation) self-reporting marijuana use.

Measurements: Participants completed a written self-report survey and provided biospecimens at <16 weeks gestation (n = 46), 18 to 22 weeks gestation (n = 43), 32 to 36 weeks gestation (n = 39), and delivery (n = 37). Self-reported marijuana use frequency was calculated based on past-month days of use multiplied by number of daily uses. Maternal urine and sera were tested for presence (>5 ng/mL) of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH). Liquid chromatography tandem mass spectrometry quantified THC-COOH in umbilical cord homogenate (ng/g). Last marijuana use by any measure was recorded to evaluate the time frame over which THC-COOH remains detectable (>0.10 ng/g) in cord.

Findings: From December 2017 through May 2019, 51 pregnant women enrolled, and 46 were included in analyses (2 withdrew and 3 had a spontaneous abortion). The majority were normal weight, White or Black race, and insured by Medicaid. At the time of enrollment between 7 to 15 weeks' gestation, 87% had ongoing use by self-report, or positive urine or serum. The majority (33 [66%]) stopped using before delivery. Sera and urine results were strongly correlated with self-reported use frequency (Spearman correlation coefficient [r] range 0.70-0.87 across visits, P < 0.001), and with each other. There was only one positive cord result when use stopped before 22 weeks. Frequency of self-reported marijuana use at delivery had strong correlation with quantified cord THC-COOH (r = 0.80, 95% CI = 0.62-0.89).

Conclusions: Quantified umbilical cord THC-COOH appears to strongly correlate with frequency of maternal marijuana use in the last month of pregnancy. Earlier use can be measured by either quantitative urine or serum assay.
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http://dx.doi.org/10.1111/add.15606DOI Listing
June 2021

Is Exposure to Intrapartum Prostaglandins for Labor Induction Associated with a Lower Incidence of Neonatal Respiratory Distress Syndrome?

Am J Perinatol 2021 08 2;38(10):993-998. Epub 2021 May 2.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah.

Objective: Respiratory distress syndrome (RDS) is implicated in 30% of neonatal deaths. Since prostaglandins promote surfactant secretion and labor is associated with a lower risk of RDS in term neonates, it is plausible that synthetic prostaglandin (sPG) exposure is associated with a lower risk of RDS. Thus, we evaluated the association between sPG exposure and RDS in neonates born after the induction of labor (IOL).

Study Design: Secondary analysis of women with singleton pregnancies undergoing IOL at 34 to 42 weeks in the nuMoM2b study, a multicenter prospective cohort of nulliparous women. RDS rates and secondary neonatal outcomes in neonates with intrapartum sPG exposure were compared with those who had IOL with non-sPG methods (e.g., balloon catheter, amniotomy, oxytocin, and laminaria). Logistic regression models estimated the association of sPG with RDS and with secondary outcomes after adjustment for clinical and demographic factors (including gestational age). A sensitivity analysis was performed in which analysis was restricted to those with an admission cervical dilation ≤2 cm.

Results: Of 10,038 women in the total cohort, 3,071 met inclusion criteria; 1,444 were exposed and 1,627 were unexposed to sPGs. Antenatal corticosteroid exposure rates were low (3.0%) and similar between groups. In univariable analysis, neonates with sPG exposure had higher rates of RDS (3.2 vs. 2.0%, odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.01-2.50). This relationship was similar by gestational age at delivery (term vs. preterm, interaction  = 0.14). After adjustment, the association between sPG and RDS was no longer significant (adjusted odds ratio: 1.4, 95% CI: 0.9-2.3). When analysis was restricted to subjects with admission cervical dilation of ≤2 cm, there was also no association between sPG exposure and RDS.

Conclusion: In pregnancies between 34 and 42 weeks of gestation, exposure to sPG for cervical ripening or labor induction was not associated with newborn RDS.

Key Points: · RDS is implicated in 30% of neonatal deaths.. · sPG exposure was not associated with RDS.. · Avoiding preterm birth remains crucial in RDS prevention..
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http://dx.doi.org/10.1055/s-0041-1728820DOI Listing
August 2021

Human Mesenchymal Stem Cell Sheets Improve Uterine Incision Repair in a Rodent Hysterotomy Model.

Am J Perinatol 2020 Dec 27. Epub 2020 Dec 27.

Cell Sheet Tissue Engineering Center, Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, Salt Lake City, Utah.

Objective:  The study aimed to assess the feasibility of creating and transplanting human umbilical cord mesenchymal stem cell sheets applied to a rat model of hysterotomy, and additionally to determine benefits of human umbilical cord mesenchymal stem cell sheet transplantation in reducing uterine fibrosis and scarring.

Study Design:  Human umbilical cord mesenchymal stem cell sheets are generated by culturing human umbilical cord mesenchymal stem cells on thermo-responsive cell culture plates. The temperature-sensitive property of these culture dishes facilitates normal cell culture in a thin contiguous layer and allows for reliable recovery of intact stem cell sheets without use of destructive proteolytic enzymes.We developed a rat hysterotomy model using nude rats. The rat uterus has two distinct horns: one horn provided a control/untreated scarring site, while the second horn was the cell sheet transplantation site.On day 14 following surgery, complete uteri were harvested and subjected to histologic evaluations of all hysterotomy sites.

Results:  The stem cell sheet culture process yielded human umbilical cord mesenchymal stem cell sheets with surface area of approximately 1 cm.Mean myometrial thickness in the cell sheet-transplanted group was 274 µm compared with 191 µm in the control group ( = 0.02). Mean fibrotic surface area in the human umbilical cord mesenchymal stem cell sheet-transplanted group was 95,861 µm compared with 129,185 µm in the control group. Compared with control horn sites, cell sheet-transplanted horns exhibited significantly smaller fibrotic-to-normal myometrium ratios (0.18 vs. 0.27, respectively,  = 0.029). Mean number of fibroblasts in cell sheet-transplanted horns was significantly smaller than the control horns (483 vs. 716/mm, respectively,  = 0.001).

Conclusion:  Human umbilical cord mesenchymal stem cell sheet transplantation is feasible in a rat model of hysterotomy. Furthermore, use of stem cell sheets reduces fibroblast infiltration and uterine scar fibrotic tissue formation during hysterotomy healing, potentially mitigating risks of uterine scar formation.

Key Points: · Stem cell sheet transplanted to hysterotomy promotes myometrial regeneration and reduced fibrotic tissue formation.. · This study demonstrates the feasibility of using human umbilical cord mesenchymal stem cell sheets..
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http://dx.doi.org/10.1055/s-0040-1721718DOI Listing
December 2020

Characteristics of Stillbirths Associated With Diabetes in a Diverse U.S. Cohort.

Obstet Gynecol 2020 12;136(6):1095-1102

University of Utah Health, Salt Lake City, Utah; Intermountain Health Care, Murray, Utah; Northwestern University, Feinberg School of Medicine, Chicago, Illinois; RTI International, Research Triangle Park, North Carolina; the University of Health Sciences, Van Training and Research Hospital, Van, Turkey; University of Virginia Healthcare, Charlottesville, Virginia; the University of Texas Medical Branch at Galveston, Galveston, Texas; Columbia University, New York, New York; the University of Texas Health Science Center at Houston, Houston, Texas; the Rollins School of Public Health, Emory University, Atlanta, Georgia; the University of Texas at Austin, Austin, Texas; the University of Texas Health Science Center at San Antonio, San Antonio, Texas; Brown University, Providence, Rhode Island; and Yale School of Medicine, New Haven, Connecticut.

Objective: To characterize stillbirths associated with pregestational diabetes and gestational diabetes mellitus (GDM) in a large, prospective, U.S. case-control study.

Methods: A secondary analysis of stillbirths among patients enrolled in a prospective; multisite; geographically, racially, and ethnically diverse case-control study in the United States was performed. Singleton gestations with complete information regarding diabetes status and with a complete postmortem evaluation were included. A standard evaluation protocol for stillbirth cases included postmortem evaluation, placental pathology, clinical testing as performed at the discretion of the health care professional, and a recommended panel of tests. A potential cause of death was assigned to stillbirth cases using a standardized classification tool. Demographic and delivery characteristics among women with pregestational diabetes and GDM were compared with characteristics of women with no diabetes in pairwise comparisons using χ or two-sample t tests as appropriate. Sensitivity analysis was performed excluding pregnancies with genetic conditions or major fetal malformations.

Results: Of 455 stillbirth cases included in the primary analysis, women with stillbirth and diabetes were more likely to be older than 35 years and have a higher body mass index. They were also more likely to have a gestational hypertensive disorder than women without diabetes (28% vs 9.1%; P<.001). Women with pregestational diabetes had more large-for-gestational-age (LGA) neonates (26% vs 3.4%; P<.001). Stillbirths occurred more often at term in women with pregestational diabetes (36%) and those with GDM (52%). Maternal medical complications, including pregestational diabetes and others, were more often identified as a probable or possible cause of death among stillbirths with maternal diabetes (43% vs 4%, P<.001) as compared with stillbirths without diabetes.

Conclusion: Compared with stillbirths in women with no diabetes, stillbirths among women with pregestational diabetes and GDM occur later in pregnancy and are associated with hypertensive disorders of pregnancy, maternal medical complications, and LGA.
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http://dx.doi.org/10.1097/AOG.0000000000004117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680368PMC
December 2020

Maternal Marijuana Exposure, Feto-Placental Weight Ratio, and Placental Histology.

Am J Perinatol 2020 Sep 24. Epub 2020 Sep 24.

University of Utah Health, Salt Lake City, Utah.

Objective:  Marijuana use is associated with placenta-mediated adverse pregnancy outcomes including fetal growth restriction, but the mechanism remains uncertain. The objective was to evaluate the association between maternal marijuana use and the feto-placental weight ratio (FPR). Secondarily, we aimed to compare placental histology of women who used marijuana to those who did not.

Study Design:  This was a secondary analysis of singleton pregnancies enrolled in a multicenter and case-control stillbirth study. Prior marijuana use was detected by electronic medical record abstraction or cord homogenate positive for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Prior tobacco use was detected by self-report or presence of maternal serum cotinine. Stillbirths and live births were considered separately. The primary outcome was FPR. Association of marijuana use with FPR was estimated with multivariable linear modeling adjusted for fetal sex, preterm birth, and tobacco use. Comparisons between groups for placental histology were made using Chi-square and stratified by live birth and stillbirth, term and preterm deliveries, and fetal sex.

Results:  Of 1,027 participants, 224 were stillbirths and 803 were live births. Overall, 41 (4%) women used marijuana during the pregnancy. The FPR ratio was lower among exposed offspring but reached statistical significance only for term stillbirths (mean 6.84 with marijuana use vs. mean 7.8 without use,  < 0.001). In multivariable modeling, marijuana use was not significantly associated with FPR ( = 0.09). There were no differences in histologic placental features among those with and without marijuana use overall or in stratified analyses.

Conclusion:  Exposure to marijuana may not be associated with FPR. Similarly, there were no placental histologic features associated with marijuana exposure. Further study of the influence of maternal marijuana use on placental development and function is warranted to better understand the association between prenatal marijuana use and poor fetal growth.

Key Points: · Maternal marijuana exposure was not associated with the feto-placental weight ratio.. · Marijuana exposure was not associated with differences in placental histology.. · Concerning trend toward lower feto-placental weight ratios among marijuana-exposed stillbirths..
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http://dx.doi.org/10.1055/s-0040-1717092DOI Listing
September 2020

Umbilical Cord Abnormalities and Stillbirth.

Obstet Gynecol 2020 03;135(3):644-652

Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, University of Utah Healthcare, and Intermountain Healthcare, Salt Lake City, UT; the Department of Obstetrics and Gynecology, Columbia University School of Medicine, New York, New York; the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut; the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas; the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, Virginia; RTI International, Research Triangle Park, North Carolina; the University of Texas Health Science Center at San Antonio, San Antonio, Texas; the Division of Perinatal and Pediatric Pathology, Women and Infants Hospital, the Warren Alpert School of Medicine of Brown University, Providence, Rhode Island; and the Division of Pediatric Pathology, Department of Pathology, Primary Children's Medical Center, Intermountain Healthcare and University of Utah Health, Salt Lake City, Utah.

Objective: Umbilical cord abnormalities are commonly cited as a cause of stillbirth, but details regarding these stillbirths are rare. Our objective was to characterize stillbirths associated with umbilical cord abnormalities using rigorous criteria and to examine associated risk factors.

Methods: The Stillbirth Collaborative Research Network conducted a case-control study of stillbirth and live births from 2006 to 2008. We analyzed stillbirths that underwent complete fetal and placental evaluations and cause of death analysis using the INCODE (Initial Causes of Fetal Death) classification system. Umbilical cord abnormality was defined as cord entrapment (defined as nuchal, body, shoulder cord accompanied by evidence of cord occlusion on pathologic examination); knots, torsions, or strictures with thrombi, or other obstruction by pathologic examination; cord prolapse; vasa previa; and compromised fetal microcirculation, which is defined as a histopathologic finding that represents objective evidence of vascular obstruction and can be used to indirectly confirm umbilical cord abnormalities when suspected as a cause for stillbirth. We compared demographic and clinical factors between women with stillbirths associated with umbilical cord abnormalities and those associated with other causes, as well as with live births. Secondarily, we analyzed the subset of pregnancies with a low umbilical cord index.

Results: Of 496 stillbirths with complete cause of death analysis by INCODE, 94 (19%, 95% CI 16-23%) were associated with umbilical cord abnormality. Forty-five (48%) had compromised fetal microcirculation, 27 (29%) had cord entrapment, 26 (27%) knots, torsions, or stricture, and five (5%) had cord prolapse. No cases of vasa previa occurred. With few exceptions, maternal characteristics were similar between umbilical cord abnormality stillbirths and non-umbilical cord abnormality stillbirths and between umbilical cord abnormality stillbirths and live births, including among a subanalysis of those with hypo-coiled umbilical cords.

Conclusion: Umbilical cord abnormalities are an important risk factor for stillbirth, accounting for 19% of cases, even when using rigorous criteria. Few specific maternal and clinical characteristics were associated with risk.
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http://dx.doi.org/10.1097/AOG.0000000000003676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036034PMC
March 2020

Outcomes of trial of labor after cesarean birth by provider type in low-risk women.

Birth 2020 03 10;47(1):123-134. Epub 2019 Dec 10.

Obstetrics and Gynecology, Maternal Fetal Medicine & Reproductive Sciences, University of Colorado School of Medicine, Aurora, Colorado.

Background: One approach to decreasing the cesarean birth rate in the United States is to increase the availability of birth attendants, including certified nurse-midwives (CNMs), who offer trial of labor after cesarean (TOLAC). We examined associations between provider type and mode of birth for women attempting vaginal birth after cesarean (VBAC).

Methods: We performed a retrospective cohort study at a United States academic medical center using prospectively-collected data (2005-2012). We included healthy women with term singleton vertex pregnancies after one or two prior cesareans who were managed by obstetricians or CNMs. We assessed unplanned cesarean birth by provider type using univariate and logistic regression and examined labor interventions and predicted VBAC success.

Results: Overall VBAC success was 88% for 502 included patients. Unplanned cesarean rates were similar by provider type. Black race, no prior VBAC, recurring clinical indication for cesarean, labor augmentation/induction, and any Pitocin use were associated with increased unplanned cesarean. Higher parity and early-term gestational age at delivery were associated with decreased unplanned cesarean. Postpartum hemorrhage and composite maternal morbidity were increased with unplanned cesarean, but there was no difference in neonatal outcome by mode of delivery or provider type. Obstetricians had slightly higher composite adverse maternal outcomes. Nomogram-predicted VBAC success but not provider type was associated with unplanned cesarean.

Conclusions: Unplanned cesarean was similar for patients attempting labor after cesarean managed by midwives or obstetricians. Increasing the number of CNMs who manage TOLAC may help decrease the high rate of cesareans.
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http://dx.doi.org/10.1111/birt.12474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047558PMC
March 2020

Stillbirth Associated With Infection in a Diverse U.S. Cohort.

Obstet Gynecol 2019 12;134(6):1187-1196

University of Utah Health Sciences, Salt Lake City, and Intermountain Health Care, Murray, Utah; RTI International, Research Triangle Park, North Carolina; the University of Virginia Healthcare, Charlottesville, Virginia; the University of Texas Medical Branch at Galveston, Galveston, Texas; Columbia University, New York, New York; the University of Texas Health Science Center at Houston, Houston, Texas; Rollins School of Public Health, Emory University, Atlanta, Georgia; the University of Texas at Austin, Austin, and the University of Texas Health Science Center at San Antonio, San Antonio, Texas; and Yale School of Medicine, New Haven, Connecticut.

Objective: To better characterize infection-related stillbirth in terms of pathogenesis and microbiology.

Methods: We conducted a secondary analysis of 512 stillbirths in a prospective, multisite, geographically, racially and ethnically diverse, population-based study of stillbirth in the United States. Cases underwent evaluation that included maternal interview, chart abstraction, biospecimen collection, fetal autopsy, and placental pathology. Recommended evaluations included syphilis and parvovirus serology. Each case was assigned probable and possible causes of death using the INCODE Stillbirth Classification System. Cases where infection was assigned as a probable or possible cause of death were reviewed. For these cases, clinical scenario, autopsy, maternal serology, culture results, and placental pathology were evaluated.

Results: For 66 (12.9%) cases of stillbirth, infection was identified as a probable or possible cause of death. Of these, 36% (95% CI 35-38%) were categorized as a probable and 64% (95% CI 62-65%) as a possible cause of death. Infection-related stillbirth occurred earlier than non-infection-related stillbirth (median gestational age 22 vs 28 weeks, P=.001). Fetal bacterial culture results were available in 47 cases (71%), of which 35 (53%) grew identifiable organisms. The predominant species were Escherichia coli (19, 29%), group B streptococcus (GBS) (8, 12%), and enterococcus species (8, 12%). Placental pathology revealed chorioamnionitis in 50 (76%), funisitis in 27 (41%), villitis in 11 (17%), deciduitis in 35 (53%), necrosis in 27 (41%), and viral staining in seven (11%) cases. Placental pathology found inflammation or evidence of infection in 65 (99%) cases and fetal autopsy in 26 (39%) cases. In infection-related stillbirth cases, the likely causative nonbacterial organisms identified were parvovirus in two (3%) cases, syphilis in one (2%) case, cytomegalovirus (CMV) in five (8%) cases, and herpes in one (2%) case.

Conclusion: Of infection-related stillbirth cases in a large U.S. cohort, E coli, GBS, and enterococcus species were the most common bacterial pathogens and CMV the most common viral pathogen.
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http://dx.doi.org/10.1097/AOG.0000000000003515DOI Listing
December 2019

Antenatal Fetal Adrenal Measurements at 22 to 30 Weeks' Gestation, Fetal Growth Restriction, and Perinatal Morbidity.

Am J Perinatol 2021 06 22;38(7):676-682. Epub 2019 Nov 22.

Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah.

Objective: Our objective was to test the association of fetal adrenal size with perinatal morbidity among fetuses with fetal growth restriction (FGR; estimated fetal weight [EFW] < 10th percentile).

Study Design: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) adrenal study, which measured fetal adrenal gland size at 22 to 30 weeks' gestation. We analyzed the transverse adrenal area (TAA) and fetal zone area (absolute measurements and corrected for fetal size) and the ratio of the fetal zone area to the total transverse area using a composite perinatal outcome of stillbirth, neonatal intensive care unit admission, respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity, sepsis, mechanical ventilation, seizure, or death. Among fetuses with FGR, adrenal measurements were compared between those that did and did not experience the composite perinatal outcome.

Results: There were 1,709 eligible neonates. Seven percent ( = 120) were diagnosed with FGR at the time of adrenal measurement, and 14.7% ( = 251) experienced perinatal morbidity. EFW-corrected and absolute adrenal measurements were similar among fetuses with and without FGR as well as among those who did and did not experience morbidity. The area under the curve for corrected TAA was 0.52 (95% confidence interval 0.38-0.67).

Conclusion: In our cohort, adrenal size was not associated with risk of morbidity among fetuses with FGR.
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http://dx.doi.org/10.1055/s-0039-3400308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708295PMC
June 2021

Attitudes of Trainees in Obstetrics and Gynecology Regarding the Structure of Residency Training.

Obstet Gynecol 2019 10;134 Suppl 1:22S-28S

Department of Obstetrics and Gynecology, University of Colorado School of Medicine and Denver Health Medical Center, Denver, Colorado; the Department of Obstetrics and Gynecology, University of California, San Francisco School of Medicine, San Francisco, California; Loyola University School of Medicine, Maywood, Illinois; the Department of Obstetrics and Gynecology, Texas A&M School of Medicine, Bryan, Texas; the University of Utah School of Medicine, Salt Lake City, Utah; the Department of Obstetrics and Gynecology, Saint Joseph's Hospital, Denver, Colorado; and the Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, Washington.

Objective: To measure future and current resident perspectives on obstetrics and gynecology residency training structure and possible future models.

Methods: Medical students invited for obstetrics and gynecology residency interviews and residents (postgraduate year [PGY]-1-4) at the University of Colorado, the University of Washington, the University of California San Francisco, Loyola University, Saint Joseph's Hospital, and Texas A&M in 2017-2018 received a voluntary, electronic survey regarding possible models for restructuring residency training. Student and resident responses were compared using χ test for categorical and two-sample t-test for continuous items.

Results: Applicants (63%, 280/444) and residents (66%, 101/153) had similar response rates (overall response rate 64%). Applicants (24%) and residents (29%) reported having concerns about the current structure of residency training. The ideal residency duration was reported as 4 years by 72% of applicants and 85% of residents. Lack of gynecologic surgical volume was the most frequently reported concern among applicants (75%) and residents (72%). Fourth-year tracking (focusing on training aligned with postgraduation career path) was preferred by 90% of applicants and 77% of residents (P=.002) and 92% among respondents planning fellowship. Most applicants (68%) and residents (75%) preferred not starting fellowship training after the 3rd year of residency.

Discussion: The majority of learners surveyed support a 4-year training structure but likewise support individualizing training in PGY-4. It is imperative that obstetrics and gynecology leadership consider this and other feedback from learners when considering modifications to the current training paradigm.
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http://dx.doi.org/10.1097/AOG.0000000000003430DOI Listing
October 2019

Impact of Marijuana Legalization on Prevalence of Maternal Marijuana Use and Perinatal Outcomes.

Am J Perinatol 2020 01 6;37(1):59-65. Epub 2019 Sep 6.

Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah.

Objective: We aimed to assess whether marijuana legalization was associated with a difference in prevalence of prenatal use or an increase in incidence of adverse perinatal outcomes.

Study Design: The present study is a retrospective cohort of September and October deliveries in the years 2012 through 2015 at a tertiary center in Colorado. Primary outcome of the study was use of marijuana, defined by self-report or biodetection. Secondary outcomes of the study included growth restriction, spontaneous preterm birth, stillbirth, preeclampsia, and neonatal or maternal death. Marijuana use prevalence was compared by year, and secondary outcomes between two periods, before and after the opening of the first recreational dispensary.

Results: A total of 2,392 pregnant women were included (1,165 before legalization and 1,227 after). More women used marijuana over the period of legalization (trend  = 0.01). Odds of marijuana use were higher after legalization versus before (adjusted odds ratio [aOR] = 1.8, 95% confidence interval [CI]: 1.2-2.6). Incidence of growth restriction was higher after legalization (2.9 vs. 5.1%,  = 0.0084). This difference persisted after adjustment for ethnicity and other drugs in multivariable modeling (aOR = 1.9, 95%CI: 1.2-3.0).

Conclusion: The prevalence of prenatal marijuana use increased over the time of legalization. Further investigation into the population impact of legalization on obstetrical outcomes is warranted given the observed increase in growth restriction.
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http://dx.doi.org/10.1055/s-0039-1696719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957332PMC
January 2020

Duration of labor and maternal and neonatal morbidity.

Am J Obstet Gynecol MFM 2019 08 5;1(3):100032. Epub 2019 Aug 5.

Denver Health and Hospital Authority, Department of Obstetrics and Gynecology, Denver, CO; Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Denver, CO. Electronic address:

Background: Labor dystocia has been identified as a contributor to the rising cesarean delivery rate in the United States. Allowing more time for vaginal delivery, while being cognizant of maternal and neonatal outcomes, has been identified as a possible strategy to lower cesarean delivery rates.

Objective: This study aimed to characterize the relationship between the duration of active phase and second-stage labor and maternal and neonatal morbidity.

Study Design: We present a secondary analysis of the Consortium on Safe Labor project. From labors of 66,940 nonanomalous nulliparous term singleton vertex gestations, we excluded labors for which active phase (≥6 cm dilation) or second stage durations could not be calculated and from sites that did not report determinants of morbidity. For each duration of active phase or second stage labor (grouped in 1-hour increments), the adjusted maternal and neonatal composite morbidity was estimated by and compared with the morbidity associated with a duration <1 hour total and a duration of 1 hour shorter.

Results: After exclusions, 48,144 deliveries remained. In adjusted models, compared with labor durations <1 hour total, maternal composite morbidity was significantly higher across active phase and second stage durations (both P<.001); neonatal composite morbidity was higher across the second stage (P<.001), but not active phase (P=.07) duration. These relationships appear linear with no apparent inflection point, and morbidity increases more rapidly. When compared with labor durations 1 hour shorter, significant differences persisted in maternal and neonatal composite morbidity in second stage labor only through 4 and 3 hours, respectively.

Conclusion: Maternal and neonatal composite morbidity is greater with longer durations of active and second stage labor; however, no clear cutoff point was determined to suggest truncation of either stage of labor for reasons of morbidity. In addition, incrementally higher morbidities that were noted vs duration <1 hour total were obscured when comparison was made with labors 1 hour shorter, which suggests that focusing on short differences in duration of labor may mask important underlying trends.
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http://dx.doi.org/10.1016/j.ajogmf.2019.100032DOI Listing
August 2019

Self-Reported Alcohol, Tobacco, and Marijuana Use in Pregnant Women with Depressive Symptomatology.

Am J Perinatol 2020 10 25;37(12):1223-1227. Epub 2019 Jun 25.

Department of Obstetrics and Gynecology, University of Colorado, Denver, Colorado.

Objective: Substance use disorders often coexist with depression. The objective of this study was to establish whether pregnant women who report depressive symptomatology were more likely to report use of alcohol, tobacco, and marijuana during pregnancy.

Study Design: This was a secondary analysis of prospectively collected data from the Maternal-Fetal Medicine Units Network Preterm Prediction Study. Self-reported history of alcohol, tobacco, and marijuana use was compared between pregnant women with and without depressive symptomatology with adjustment for demographic factors.

Results: After adjustment for demographic factors, women with depressive symptomatology were more likely to report: any alcohol use (odds ratio [OR]: 1.4, 95% confidence interval [CI]: 1.1-1.8), >1 drink per week (OR: 1.3, 95% CI: 1.0-1.8), and >1 drink per day (OR: 2.2, 95% CI: 1.5-3.4). Women with depressive symptomatology were also more likely to report use of marijuana (OR: 1.8, 95% CI: 1.2-2.6) and cigarettes (OR: 1.4, 95% CI: 1.1-1.7).

Conclusion: Depressive symptomatology was associated with an increase in self-reported the use of alcohol, tobacco, and marijuana during pregnancy. These data reveal the importance of targeted screening of pregnant women with depressive symptomatology for substance use.
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http://dx.doi.org/10.1055/s-0039-1692685DOI Listing
October 2020

Universal early pregnancy glycosylated hemoglobin A1c as an adjunct to Carpenter-Coustan screening: an observational cohort study.

Am J Obstet Gynecol MFM 2019 03 6;1(1):24-32. Epub 2019 Mar 6.

University of Colorado School of Medicine, Aurora; Denver Health and Hospital Authority, Denver. Electronic address:

Background: Early pregnancy screening for preexisting and gestational diabetes mellitus is widely recommended, but the details of screening (eg, targeted vs universal screening, criteria to identify women requiring early screening, specific screening strategy) remain controversial and poorly defined.

Objective: The objective of the study was to determine the utility of universal early glycosylated hemoglobin A1c obtained at the first prenatal visit in diagnosing preexisting diabetes and high-risk gestational diabetes mellitus (early glycosylated hemoglobin A1c, 5.9-6.4%). We further sought to determine whether early glycosylated hemoglobin A1c could replace routine Carpenter-Coustan testing and to determine the correlation between early glycosylated hemoglobin A1c and maternal and neonatal morbidity and mortality.

Study Design: This was an observational cohort study of women delivering from May 2016 to July 2017 (14 months) at a single county teaching hospital. Multiple gestations and second deliveries during the study interval were excluded. Women with an early glycosylated hemoglobin A1c of ≥ 6.5% were diagnosed with preexisting diabetes. Women with early glycosylated hemoglobin A1c of 5.9-6.4% underwent immediate 3 hour glucose tolerance testing, which if abnormal diagnosed gestational diabetes mellitus and if normal was repeated at 24-28 weeks. Women with early glycosylated hemoglobin A1c <5.9% underwent routine Carpenter-Coustan screening at 24-28 weeks. Receiver-operator curve methodology was used to evaluate the diagnostic properties of early glycosylated hemoglobin A1c for gestational diabetes mellitus. The correlation between early glycosylated hemoglobin A1c and composite measures of maternal and neonatal morbidity and mortality were calculated.

Results: A total of 4144 deliveries remained after exclusions. Median gestational age at early glycosylated hemoglobin A1c draw was 9 weeks (interquartile range, 7-12). Early glycosylated hemoglobin A1c diagnosed 26 women with preexisting diabetes (0.8% of all patients, 37.7% of all preexisting diabetes). A total of 41.9% of 93 women with early glycosylated hemoglobin A1c of 5.9-6.4% had an early diagnosis of gestational diabetes mellitus, accounting for 25.8% of total gestational diabetes mellitus cases. Based on receiver-operator curve analysis, no early glycosylated hemoglobin A1c cutoff had sufficient sensitivity and positive predictive value to diagnose gestational diabetes mellitus. An early glycosylated hemoglobin A1c ≤5.0% (29.2% of patients) had a 98% negative predictive value for gestational diabetes mellitus, suggesting women with an early glycosylated hemoglobin A1c ≤5.0% in a similar-risk population could potentially forego further testing. The per-patient incremental cost for the glycosylated hemoglobin A1c was $3.72.

Conclusion: Early glycosylated hemoglobin A1c correlates with maternal and neonatal morbidity and mortality but cannot entirely replace routine Carpenter-Coustan testing because of poor sensitivity. Rather, its use as an adjunct to Carpenter-Coustan testing, with reflex to early 3 hour glucose tolerance testing for those with values 5.9-6.4%, is an inexpensive and simple method that identifies women with preexisting diabetes and high-risk gestational diabetes mellitus early in pregnancy, allowing early intervention and the prospect of improved outcomes.
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http://dx.doi.org/10.1016/j.ajogmf.2019.02.003DOI Listing
March 2019

Exposure to group B Streptococcal antibiotic prophylaxis and early childhood body mass index in a vaginal birth cohort.

J Matern Fetal Neonatal Med 2020 Oct 7;33(19):3318-3323. Epub 2019 Feb 7.

School of Medicine, University of Colorado, Aurora, CO, USA.

Perinatal antibiotic exposure may be associated with changes in both early infancy gut microbiota and later childhood obesity. Our objective was to evaluate if group B Streptococcus (GBS) antibiotic prophylaxis is associated with higher body mass index (BMI) in early childhood. This is a retrospective cohort study of mother/child dyads in a single hospital system over a 6-year period. All women with term, singleton, vertex, vaginal deliveries who received no antibiotics or received antibiotics only for GBS prophylaxis and whose children had BMIs available at 2-5 years of age were included. Children were divided into three groups for comparison: children born to GBS positive mothers that received antibiotics solely for GBS prophylaxis, children born to GBS negative women that received no antibiotics (healthy controls), and children born to GBS positive mothers who received no antibiotics. The primary outcome was the earliest available child BMI -score at 2-5 years of age. Multivariable linear regression was used to estimate differences in child BMI -scores between groups, adjusted for maternal BMI, age, race, parity, tobacco use, and child birthweight. Of 4825 women, 786 (16.3%) were GBS positive and received prophylactic antibiotics, 3916 (81.2%) were GBS negative and received no antibiotics, and 123 (2.5%) were GBS positive but received no antibiotics. Childhood BMI -scores were similar between children exposed to intrapartum GBS prophylaxis and healthy controls who were unexposed in both unadjusted (mean (SE), 0.04 (0.04) versus -0.3 (0.02),  = .11) and adjusted (0.01 (0.05) versus -0.04 (0.03),  = .3) models. Exposure to intrapartum antibiotic prophylaxis for GBS was not associated with higher early childhood BMI -scores compared to healthy controls.
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http://dx.doi.org/10.1080/14767058.2019.1571575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957762PMC
October 2020

Prenatal Marijuana Use by Self-Report and Umbilical Cord Sampling in a State With Marijuana Legalization.

Obstet Gynecol 2019 01;133(1):98-104

University of Utah Health and ARUP Laboratories, Salt Lake City, Utah; the University of Colorado Denver, the University of Colorado School of Medicine, and Children's Hospital Colorado, Aurora, and the Institute for Health Research, Kaiser Permanente Colorado, Denver, Colorado.

Objective: To compare self-reported maternal marijuana use with quantitative biological sampling for a marijuana metabolite, 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid, in umbilical cord homogenate in a state with legalized marijuana.

Methods: We conducted a cross-sectional study of women approached at the time of admission for delivery with live, singleton pregnancies at 24 weeks of gestation or greater at two urban medical centers in Colorado. Maternal marijuana use was estimated by 1) report to a health care provider on admission history and physical, 2) survey of self-reported use, and 3) liquid chromatography-tandem mass spectrometry analysis of umbilical cord homogenate for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Women were categorized by survey-reported last use (30 days ago or less, 30 days to 1 year, more than 1 year, never) and proportion of women with cord results above the limit of detection and limit of quantification for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid was reported for each group. Comparisons between groups were made using contingency tables. Correlation between survey-reported frequency of use and quantitative 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid cord homogenate results was evaluated.

Results: We included 116 women with self-report surveys linked to cord assay results. Six percent (95% CI 2.5-12.0%) of participants reported use in the past 30 days on survey and 2.6% (95% CI 0.5-7.4%) of participants reported marijuana use to health care providers. On umbilical cord assay, 22.4% (95% CI 15.2-31.1%) had detectable 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. The proportion of women with detectable 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid increased with more recent self-reported use. Survey-reported frequency of use in the past 30 days had moderate correlation with quantified umbilical cord 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (correlation coefficient 0.44, 95% CI 0.28-0.58, P<.001).

Conclusion: Umbilical cord sampling results in higher estimates of prenatal marijuana use than self-report even in the setting of legalization. Umbilical cord assays for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid demonstrate promise for quantifying use. Future studies should examine how the use of biological sampling informs the association between marijuana use and perinatal outcomes.
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http://dx.doi.org/10.1097/AOG.0000000000003028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370297PMC
January 2019

Fat-1 Transgene Is Associated With Improved Reproductive Outcomes.

Endocrinology 2018 12;159(12):3981-3992

Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, Colorado.

High intake of ω-3 polyunsaturated fatty acids (PUFAs) has been associated with a variety of health benefits. However, the role of ω-3 PUFAs in female reproductive function is unclear, with studies showing both positive and negative effects. The type of diet that ω-3 fatty acids are consumed with, for example, a balanced diet vs a high-fat diet (HFD), may influence how ω-3 fatty acids affect female reproductive function. To address the role of ω-3 PUFAs in female reproduction, we used the fat-1 mouse both with and without HFD exposure. Fat-1 mice constitutively express the fat-1 transgene, allowing the conversion of ω-6 to ω-3 fatty acids to yield an optimal tissue ratio of ω-6 to ω-3 fatty acids (∼1:1). In our study, at 15 weeks of age, fat-1 mice had elevated primordial follicles compared with wild-type controls with both standard chow and HFD feeding. Higher serum levels of the ω-3 docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA) were positively associated with primordial follicle numbers, whereas the ratio of the ω-6 arachidonic acid to EPA + DPA + DHA had the opposite effect. Furthermore, fat-1 mice had increased pregnancy rates and shorter time to pregnancy when fed an HFD compared with wild-type mice. In conclusion, our novel preclinical model suggests that high tissue levels of long-chain ω-3 PUFAs are associated with an improved ovarian reserve and improved reproductive outcomes. Further studies are needed to evaluate ω-3 PUFAs as a potential intervention strategy in women with diminished ovarian reserve.
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http://dx.doi.org/10.1210/en.2018-00723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260063PMC
December 2018

Career Expectations of Obstetrics and Gynecology Residents and Future Residents.

Obstet Gynecol 2018 10;132 Suppl 1:1S-7S

Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, and Denver Health Medical Center, Denver, Colorado; the Department of Obstetrics and Gynecology, UCSF School of Medicine, San Francisco, California; Loyola University Stritch School of Medicine, Chicago, Illinois; the Department of Obstetrics and Gynecology, Texas A&M School of Medicine, Bryan Texas; Colorado School of Public Health, University of Colorado, Aurora, and Department of Obstetrics and Gynecology, St. Joseph's Hospital, Denver, Colorado; and the Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, Washington.

Objective: To understand contemporary fourth-year medical student and resident career expectations in obstetrics and gynecology.

Methods: Students invited for obstetrics and gynecology residency interviews and residents (postgraduate years 1-4) at the University of Colorado, University of Washington, University of California San Francisco, Loyola University, St. Joseph's Hospital, and Texas A&M in 2016-2017 received a voluntary, electronic survey regarding career expectations. Questions were compared between students and residents using a χ test for category responses and for age a two-sample t test.

Results: Response rates were similar between students (68% [277/409]) and residents (63% [97/153]). Residents compared with students were more frequently planning to enter private practice (43% vs 19%) and less frequently planning an academic career (19.4% vs 30.4%) or subspecialties (38% vs 51%) (P<.001). Although most respondents planned to work full-time (96% vs 94.9%), 83% (vs 94%) of residents planned to work greater than 40 hours per week (P<.001). Respondents reported greater than $150,000 in educational debt (65%) and anticipated starting salary greater than $200,000 (89%). More residents planned to retire by age 60 years (23% vs 7%) (P<.001). Thirty-eight percent of residents reported having changed career plans during residency, citing work-life balance as the most important factor (89%).

Discussion: Trainees' career expectations appear to evolve over time moving toward a higher likelihood to pursue private practice, work fewer hours, and retire earlier despite large educational debt. It is critical that the specialty understand these trends when planning to address national workforce needs.
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http://dx.doi.org/10.1097/AOG.0000000000002817DOI Listing
October 2018

Recommendations From Cannabis Dispensaries About First-Trimester Cannabis Use.

Obstet Gynecol 2018 06;131(6):1031-1038

University of Colorado School of Medicine and the Colorado School of Public Health, Aurora, Colorado; the University of Utah Health, Salt Lake City, Utah; and Denver Health and Hospital Authority, Denver, Colorado.

Objective: To characterize recommendations given to pregnant women by Colorado cannabis dispensaries regarding use of cannabis products for nausea during the first trimester of pregnancy.

Methods: This was a statewide cross-sectional study in which advice about cannabis product use was requested using a mystery caller approach. The caller stated she was 8 weeks pregnant and experiencing morning sickness. Dispensaries were randomly selected from the Colorado Department of Revenue Enforcement Division website. The primary outcome was the proportion of marijuana dispensaries that recommended a cannabis product for use during pregnancy. We hypothesized that 50% of dispensaries would recommend use. A sample size of 400 was targeted to yield a two-sided 95% CI width of 10%. Secondary outcomes included the proportion endorsing cannabis use as safe during pregnancy, specific product recommendations, and encouraging discussion with a health care provider. Recommendations were compared by licensure type (medical, retail, or both) and location (rural vs urban).

Results: Of the 400 dispensaries contacted, 37% were licensed for medical sale (n=148), 28% for retail (n=111), and 35% for both (n=141). The majority, 69% (277/400), recommended treatment of morning sickness with cannabis products (95% CI 64-74%). Frequency of recommendations differed by license type (medical 83.1%, retail 60.4%, both 61.7%, P<.001). Recommendations for use were similar for dispensary location (urban 71% vs nonurban 63%, P=.18). The majority (65%) based their recommendation for use in pregnancy on personal opinion and 36% stated cannabis use is safe in pregnancy. Ultimately, 81.5% of dispensaries recommended discussion with a health care provider; however, only 31.8% made this recommendation without prompting.

Conclusion: Nearly 70% of Colorado cannabis dispensaries contacted recommended cannabis products to treat nausea in the first trimester. Few dispensaries encouraged discussion with a health care provider without prompting. As cannabis legalization expands, policy and education efforts should involve dispensaries.
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http://dx.doi.org/10.1097/AOG.0000000000002619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970054PMC
June 2018

Religiosity and faith in relation to time to metabolic syndrome for Hispanic women in a multiethnic cohort of women-Findings from the Study of Women's Health Across the Nation (SWAN).

Maturitas 2018 Jun 13;112:18-23. Epub 2018 Mar 13.

The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, United States; Department of Epidemiology and Population, Health Albert Einstein College of Medicine, Bronx, NY, United States.

Objectives: We investigated whether faith was associated with a difference in time to incident metabolic syndrome (MetS) among midlife Hispanic women vs women of other ethnicities.

Study Design: The Study of Women's Health Across the Nation (SWAN) is a community-based, longitudinal study of a cohort of midlife women. Social, demographic, psychosocial, anthropometric, medical, and physiological measures, and incident MetS were assessed in near-annual intervals using questionnaires and assays. Each participant answered key questions related to religion and meaning in her life. Differences in time to MetS were modeled by Hispanic ethnicity (vs. otherwise) among women reporting low and high levels of faith.

Main Outcome Measure: Incident MetS in the 7 years after the SWAN baseline assessment.

Results: Among 2371 women, average baseline age 46, Hispanic women (n = 168) were more likely to have higher perceived stress and financial strain than non-Hispanic women (n = 2203). Nevertheless, Hispanic women were far more likely than non-Hispanic women to report that faith brought them strength and comfort in times of adversity, that they prayed often, and that their faith was sustaining for them. Hispanic women had the highest incidence rate of MetS of any racial/ethnic group. However, among women with high levels of faith, the incidence rate of MetS was similar in the Hispanic and non-Hispanic groups. Conversely, among women with low levels of faith, Hispanic women had a faster progression to MetS than did non-Hispanic women.

Conclusions: Faith might be associated with a different risk of MetS among women of Hispanic vs other ethnicities. Among women who are not part of a faith community, Hispanic ethnicity might be a risk factor for MetS.
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http://dx.doi.org/10.1016/j.maturitas.2018.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933058PMC
June 2018

Evidence for disruption of normal circadian cortisol rhythm in women with obesity.

Gynecol Endocrinol 2018 Apr 25;34(4):336-340. Epub 2017 Oct 25.

a Department of Obstetrics and Gynecology , University of Colorado School of Medicine , Aurora , CO , USA.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis may play a role in the pathogenesis of comorbidities encountered in obesity, including the relative hypogonadotropic hypogonadism that we and others have observed. We sought to examine serum cortisol profiles throughout the day and evening in a sample of normal weight women and women with obesity. In this cross-sectional study, regularly cycling obese (n = 12) and normal weight (n = 10) women were recruited. Mean serum cortisol was measured by frequent blood sampling for 16 h (8am-midnight) in the luteal phase of the menstrual cycle. Women with obesity had significantly higher overall cortisol levels when compared to normal weight women (6.2 [4.3, 6.6] vs. 4.7 [3.7, 5.5] ug/dl, p = .04). Over the two-hour postprandial period, obese women displayed an almost two-fold greater (7.2 [6.5, 8.6] ug/dl) rise in cortisol than normal weight controls (4.4 [3.7, 6.2] ug/dl, p < .01). In addition, obese women demonstrated a sustained evening cortisol elevation compared to normal weight women, who displayed the typical decline in cortisol (3.2 [2.3, 4] vs. 2 [1.5, 3.2] ug/dl, p < .05). Changes in the HPA axis in the setting of obesity may be related to risks of obesity-associated metabolic comorbidities and reproductive dysfunction often seen in these women.
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http://dx.doi.org/10.1080/09513590.2017.1393511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876129PMC
April 2018

Obstetricians and Gynecologists of the Future: A Survey of Medical Students Applying to Residency.

Obstet Gynecol 2017 10;130 Suppl 1:1S-7S

Department of Obstetrics and Gynecology, University of Colorado School of Medicine and Denver Health Medical Center, Denver, Colorado; the Department of Obstetrics and Gynecology, University of California, San Francisco School of Medicine, San Francisco, California; Loyola University School of Medicine, Chicago, Illinois; the Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York; the Colorado School of Public Health, University of Colorado Denver, Denver, Colorado; and the Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, Washington.

Objective: To understand the characteristics and career goals of medical students selecting a career in obstetrics and gynecology.

Methods: In 2015-2016, medical students invited for interviews for obstetrics and gynecology residency at the University of Colorado, University of Washington, University of California San Francisco, Loyola University, and New York University received a voluntary 20-item electronic survey regarding factors influencing their choice of medical specialty.

Results: Two hundred twenty-six of 356 students responded (63%). Mean age was 27 years, and 88% (n=199) were women. General surgery was the most common alternate specialty (36%, n=81). The most commonly cited drawback to obstetrics and gynecology was "long hours" (66%, n=148). After residency, 157 (70%) applicants planned to complete fellowship training, 127 (56%) pursue international work, 156 (69%) seek an academic position, and 207 (92%) practice in an urban setting. One hundred twenty-four applicants (55%) planned to work 51-60 hours per week and 111 (49%) planned to take 2-3 nights of call per month. Two thirds (n=150) predicted they will have greater than $100,000 educational debt on graduation.

Conclusion: Contemporary residency applicants have high educational debt and disproportionately plan to pursue fellowship, international work, careers in academic medicine, and work in urban centers. Based on the projected career plans among obstetrics and gynecology applicants, the workforce needs of the population may not be met.
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http://dx.doi.org/10.1097/AOG.0000000000002192DOI Listing
October 2017

Prevalence of Complementary and Alternative Medicine and Herbal Remedy Use in Hispanic and Non-Hispanic White Women: Results from the Study of Women's Health Across the Nation.

J Altern Complement Med 2017 Oct 15;23(10):805-811. Epub 2017 Sep 15.

1 The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine , Bronx, NY.

Objectives: To investigate the prevalence of complementary and alternative medicine (CAM) use, including botanical/herbal remedies, among Hispanic and non-Hispanic white women from the Study of Women's Health Across the Nation (SWAN), New Jersey site. We also examined whether attitudes toward CAM and communication of its use to providers differed for Hispanic and non-Hispanic women.

Study Design: SWAN is a community-based, multiethnic cohort study of midlife women. At the 13th SWAN follow-up, women at the New Jersey site completed both a general CAM questionnaire and a culturally sensitive CAM questionnaire designed to capture herbal products commonly used in Hispanic/Latina communities. Prevalence of and attitudes toward CAM use were compared by race/ethnicity and demographic characteristics.

Results: Among 171 women (average age 61.8 years), the overall prevalence of herbal remedy use was high in both Hispanic and non-Hispanic white women (88.8% Hispanic and 81.3% non-Hispanic white), and prayer and herbal teas were the most common modalities used. Women reported the use of multiple herbal modalities (mean 6.6 for Hispanic and 4.0 for non-Hispanic white women; p = 0.001). Hispanic women were less likely to consider herbal treatment drugs (16% vs. 37.5%; p = 0.005) and were less likely to report sharing the use of herbal remedies with their doctors (14.4% Hispanic vs. 34% non-Hispanic white; p = 0.001). The number of modalities used was similar regardless of the number of prescription medications used.

Conclusions: High prevalence of herbal CAM use was observed for both Hispanic and non-Hispanic white women. Results highlight the need for healthcare providers to query women regarding CAM use to identify potential interactions with traditional treatments and to determine whether CAM is used in lieu of traditional medications.
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http://dx.doi.org/10.1089/acm.2017.0080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655422PMC
October 2017

Do maternal obesity or smoking explain the lack of effectiveness of 17-alpha hydroxyprogesterone caproate?

Am J Obstet Gynecol 2017 11 18;217(5):621. Epub 2017 Jul 18.

Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO.

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http://dx.doi.org/10.1016/j.ajog.2017.07.014DOI Listing
November 2017
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