bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Utility of Expanded Carrier Screening: Actionability and Outcomes [35J]
Authors: Taber Katie Johansen , Beauchamp Kyle , Lazarin Gabriel , Arjunan Aishwarya , Goldberg Jim 
Published: May 2019

INTRODUCTION:
Expanded carrier screening (ECS) facilitates reproductive and pregnancy management, such as in vitro fertilization (IVF) with preimplantation genetic testing (PGT) and prenatal diagnosis. Here, we describe the impact of ECS results on planned and actual pregnancy management in the largest sample of at-risk couples (ARCs) studied to date.

METHODS:
Couples who elected ECS and were found to be at high risk of having a pregnancy (ARCs) affected by at least one of 176 genetic conditions were invited to complete a survey about the impact of ECS results on planned and actual pregnancy management.

RESULTS:
391 ARCs completed the survey. 77% of ARCs who received results before they were pregnant reported that they altered or were planning to alter pregnancy management to reduce the risk of an affected pregnancy, including IVF with PGD, use of donated gametes, adoption, avoidance of pregnancy altogether, and prenatal diagnosis if/when they became pregnant. 37% of ARCs who received results while they were pregnant elected to undergo prenatal diagnosis. Approximately one-third of pregnancies were found to be affected, and 42% of affected pregnancies were terminated. Among all ARCs, 166 pregnancies occurred subsequent to receiving ECS results; 35% of these pregnancies were achieved through IVF with PGT. Prenatal diagnosis was pursued in approximately 30% of pregnancies, with 29% of these pregnancies found to be affected and 75% of affected pregnancies terminated.

CONCLUSION:
ECS results impacted couples' reproductive decision-making and led to altered pregnancy management that reduced the risk of an affected pregnancy.
Age-Based Interpretation of Anti-Mullerian Hormone (AMH) Levels in Non-infertile Women [37J]
Authors: Maslow Bat-Sheva L. , Guarnaccia Michael , Hennessy Dayna , Klein Joshua U. 
Published: May 2019

INTRODUCTION:
Data related to AMH levels in non-infertile women are scarce, making interpretation for this population difficult. We aimed to characterize age-based AMH levels in a non-infertile population to simplify interpretation of AMH results. This study represents the largest analysis to date of AMH levels in non-infertile women.

METHODS:
This retrospective cohort study includes all women undergoing fertility assessments at Extend Fertility Medical Practice, a large oocyte cryopreservation practice, from 3/1/2016 to 9/30/2018. The study was granted IRB exempt status. AMH levels were abstracted from electronic medical records. AMH levels were measure by an independent laboratory using the Gen-II ELISA platform. To simplify clinical interpretation of AMH levels, age was categorized according to the Society for Assisted Reproductive Technologies standard. Association between age and AMH was made using Kruskal-Wallis.

RESULTS:
2623 subjects were included in the study. AMH was inversely associated with age (P<.0001). Median [IQR] AMH values by age group were as follows: <30; 2.91 [1.79-4.82] ng/mL (n=107); 30-34; 2.42 [1.38-4.22] ng/mL (n=770); 35-37; 2.03 [1.14-3.54] (n=937); 38-40; 1.50 [0.77-2.69] (n=570); 41-42; 0.92 [0.32-2.19] (n=137); >42; 0.59 [0.25-1.2] (n=101).

CONCLUSION:
Accurate representation of physiologic AMH ranges in non-infertile women is a critical element of counseling women regarding their reproductive goals. Median AMH levels in our population were generally lower than prior published reports and more likely represent physiologic levels. Data from infertility cohorts may be confounded by anovulatory subjects with preferentially higher AMH levels. Additional studies are needed to assess what thresholds in each age group constitute a pathologic AMH level.
Insomniacs in Late Pregnancy are Clinically Depressed: Exploring the Role of Nocturnal Rumination [1K]
Authors: Kalmbach David A. , Castelan Andrea Cuamatzi , Atkinson Rachel , Sangha Roopina , O'Brien Louise , Drake Christopher L. 
Published: May 2019

INTRODUCTION:
Depression afflicts 13% of pregnant women. Insomnia complaints often increase across pregnancy. As insomnia often triggers depression, women with insomnia in late pregnancy may be at high depression-risk. Cognitive-emotional dysregulation is thought to underlie both insomnia and depression. We proposed nocturnal rumination (negative repetitive thinking in bed at night) to be a key form of cognitive-emotional dysregulation linking these disorders.

METHODS:
A cross-sectional analysis of women (29.6±4.7 years) in late pregnancy (gestational weeks 26-33) receiving prenatal OB care at a large Midwestern health system completed online surveys of insomnia, depression, and nocturnal rumination. This study was IRB-approved.

RESULTS:
Of 163 women, 59.5% of women endorsed clinical insomnia. Women with insomnia reported greater depression than good sleepers (t=4.93, p<.001). A higher proportion of insomniacs were depressed (24.7%) compared to 4.5% of good sleepers (chi-squared=11.59, p<.001). Insomniacs also reported higher nocturnal rumination than good sleepers (t=6.59, p<.001). Importantly, nocturnal rumination appeared to amplify the depressogenicity of insomnia such that 36.1% of insomniacs with high rumination were depressed compared to just 5.6% of insomniacs with low rumination (chi-squared=27.20, p<.001). Indeed, ruminating insomniacs were at 26.51-fold greater odds for depression than good sleepers without rumination (p<.01). Pregnant women with insomnia or nocturnal rumination alone were not at elevated depression-risk.

CONCLUSION:
Insomniacs in late pregnancy endorse high rates of depression. Nocturnal rumination may amplify depression-risk in these women. Assessing insomnia and stress in routine prenatal care may allow opportunity for prevention or early intervention of perinatal depression through the timely deployment of treatments improving sleep and stress management.
A Retrospective Look at Fetal Growth Restriction at St. Damien Hospital in Haiti: Neonatal Outcomes [3K]
Authors: Buckley Ayisha , Persad Malini D. , Milone Gina F. , Pardo Christina , Davilmar Inolson , Garretto Diana J. 
Published: May 2019

INTRODUCTION:
Haiti is impoverished and stricken by malnutrition and adverse pregnancy outcomes. Characterization of pregnancies complicated by fetal growth restriction (FGR) has not been performed in Haiti. We sought out to characterize the outcomes of pregnancies complicated by FGR in Haiti.

METHODS:
IRB-approved, retrospective cohort study from January 2017 to May 2017 of all deliveries at St. Damien Hospital. FGR was defined as <10%ile estimated fetal weight for gestational age. Charts were documented in French. A French and Creole-speaking provider translated charts and collected data. No patients were excluded. Parametric and non-parametric statistics were used to analyze the data with P-value of <0.05.

RESULTS:
423 charts were reviewed. 8 cases (1.89%) of FGR were identified. There were no differences in maternal demographics. Patients with FGR were more likely to have preeclampsia with severe features (50% vs. 14% P=.02). FGR neonates were more likely to deliver preterm (average gestational age 32.8 weeks, vs. 37.6 weeks, P<.001), and have 5-minute Apgars <7 (37.5% vs. 8.9% P=.03). Only 87.5% of FGR neonates were classified as small for gestational age (SGA) (P<.001).

CONCLUSION:
This was the first study to evaluate FGR in Haiti. FGR neonates were more likely to deliver preterm, be SGA, and have lower Apgar scores. Due to poor documentation and inability to locate charts, long-term neonatal outcomes were not tracked. In the future, standardized patient charts and linking infant and maternal charts may help to better assess these variables. This study provides novel insight into characteristics of FGR in the Haitian population.
Evaluation of Racial Differences in the Quantity of Disialyllacto-N-tetraose (DSLNT) in Human Breast Milk [2O]
Authors: Dimoff Megan Bloomeyer , Miller Richard Charles , DiSabatino Daniel Justin , Falcone Bianca Anjelica , Hassinger Denise 
Published: May 2019

INTRODUCTION:
Premature infants are at risk of developing a diverse array of diseases and health problems. Breast milk seems to be protective against neonatal diseases such as necrotizing enterocolitis (NEC), a disease characterized by damage to the infant's intestinal tract. In the US, NEC is more common in African American infants compared to every other ethnicity. One protective factor seems to be oligosaccharides, specifically disialyllacto-N-tetraose (DSLNT). Therefore, this study examined the effect of ethnicity on DSLNT levels.

METHODS:
Breast milk was collected from 130 breastfeeding mothers that delivered term infants from day of delivery out to 338 days postpartum. Mothers self-reported their race. Breast milk was processed and analyzed by LC/MS (ESI-Q-TOF) to determine DSLNT concentrations. Primary unadjusted analysis was a two-sample t-test. Adjusted analysis by ANOVA (adjusting for days of lactation) with self-reported ethnicity dichotomized to African American or Other. IRB approval was obtained for this study.

RESULTS:
Self-reported race identified 66 African Americans and 64 individuals of other races in our study population. When adjusting for day of lactation, race did not have a significant effect (p-value=0.5770) on DSLNT content in term milk.

CONCLUSION:
DSLNT may be an important human milk oligosaccharide in preventing devastating neonatal disease. Although past studies have postulated that geographical differences in the oligosaccharide may exist, our study did not identify racial differences in the oligosaccharide in the breast milk of term neonates at our center.
Exosome Profiles for Normal and Complicated Pregnancies—A Longitudinal Study [3O]
Authors: Nakahara Angela , Elfeky Omar , Garvey Cathryn , Guanzon Dominic , Longo Sherri Anne , Salmon Carlos 
Published: May 2019

INTRODUCTION:
Exosomes are small nanovesicles which play a key role in cell-to-cell communication during pregnancy by transferring bioactive molecules to other cells and modifying their biological functions. Little is known about the changes in the concentration of circulating exosomes throughout gestation in normal and complicated pregnancies.

METHODS:
A prospective cohort of patients approved by IRB was recruited during pregnancy and retrospectively stratified based on normal (n=30), gestational diabetes mellitus (GDM) (n=10) and preeclampsia (PE) pregnancy outcomes (n=15). Total exosomes and specific placental-derived exosomes (PdE) were determined by Nanoparticle Tracking Analysis using quantum dots coupled with CD63 or PLAP antibodies. Linear mixed modeling was performed on normalized total and PdE across gestation using the lme4 package in R. Using likelihood ratio tests, statistically significant differences were found in exosome concentration across gestation.

RESULTS:
Significant factors contributing to variations in total and PdE were gestational age and pregnancy outcomes (ANOVA, p<0.05). Post-hoc analyses established that PdE concentrations increased during gestation in normal, GDM and PE pregnancies. The increase was significantly greater in GDM and PE compared with normal pregnancies. Our linear mixed modeling analysis showed that PdE increased ∼2.1-fold in PE and GDM compared to normal through gestation. Interestingly, maternal BMI, glucose concentration and fetal weight significantly affect the concentration of PdE across gestation.

CONCLUSION:
This study provides evidence of the changes exosomes present in maternal circulation across gestation, suggesting that exosomes may be involved in maternal metabolic adaptation to pregnancy. Further, exosomes can be an early predictor of adverse outcomes, including GDM and PE.
Introduction of a Novel Tool in the Management of Postpartum Hemorrhage [8O]
Authors: Miller Whitney , Hanson Sarah Jean , Groen Reinou Sybrecht 
Published: May 2019

INTRODUCTION:
Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality. A standardized approach to PPH can decrease the impact of this obstetric emergency. Simulation-based team training addresses response to medical or obstetrical emergencies. Tools such as algorithms can facilitate teamwork leading to more effective communication and performance.

METHODS:
The authors WM and RSG are part of a PPH committee at the Alaska Native Medical Center. They developed an algorithm (HEART) consisting of 5 team actions in response to PPH: (H) Help, (E) Equipment, (A) Assessment, (R) Resuscitation, and (T) Treatment. The algorithm was tested in simulation scenarios. Pre and post simulation evaluations and feedback on the algorithm were obtained.

RESULTS:
A total of 18 care givers were included in the simulation training in August 2018 and 15 completed training evaluations of the HEART tool (response rate 83%). The responses indicated that there was an increased confidence to manage PPH, (1) as a team 15% increase (from 60 to 69 points), (2) being part of a team 25% increase (from 55 to 69 points) and (3) 25% increase of confidence in actual role you have in the team to manage PPH (55 to 69 points).

CONCLUSION:
The HEART algorithm for PPH management is a team-based tool that aims to improve response of this common obstetric emergency. The HEART tool was found to be helpful in simulated scenarios. More study is needed in actual PPH events to determine tool effectiveness in improving communication, teamwork and outcome.
Monosomy X and Parental Origin of the Retained X Chromosome in Pregnancy Loss [11O]
Authors: Font Guillermo , Pombar Xavier F. , Maisenbacher Melissa 
Published: May 2019

INTRODUCTION:
To evaluate the origin of the retained X chromosome using SNP microarray in patients with monosomy X presenting with pregnancy loss. Monosomy X is a one of the most common sex chromosome anomalies found in pregnancy loss, as a result of missing X chromosome in the sperm or egg of a parent. Parental origin of the X chromosome may influence future reproductive decisions for the couple. Studies using SNP microarray have not been done to evaluate the parental origin of the retained X chromosome in patients with pregnancy loss found to have Monosomy X.

METHODS:
Miscarriage specimens from 35,615 losses shipped with maternal blood samples were sent to a single reference laboratory for cytogenetic analysis. Genotyping was performed using Illumina CytoSNP-12b microarrays and informatics.

RESULTS:
Fetal results were obtained in 30,755 cases (86.4%). Abnormal findings were identified in 17,725 fetal cases (57.6%). Of those, Monosomy X was present in 1605 cases (9.1%). The parental origin of the missing X chromosome was paternal in 1251 cases (78%) and maternal in 354 cases (22%).

CONCLUSION:
In our cohort the parental origin of the missing X chromosome was paternal in 78% of cases and maternal in 22%, which is similar to previously published estimates in live born cohorts ranging from 60-80%, but different than one study in miscarriage which had a more equal ratio of parental origin. The relationship between parental origin in pregnancy losses with Monosomy X requires further study.
Sequencing-Based Carrier Screening for Cystic Fibrosis: Ready for Prime Time? [16O]
Authors: Beauchamp Kyle , Grauman Peter , Spurka Lindsay , Lim-Harashima Jeraldine , Muzzey Dale 
Published: May 2019

INTRODUCTION:
Medical-society guidelines recommend offering carrier screening for cystic fibrosis (CF) to all women who are considering pregnancy or already pregnant. Recommended screening tests for 23 common variants, but this targeted-genotyping approach may fail to detect some at-risk couples. Here we evaluate whether a sequencing-based workflow achieves sufficient sensitivity and specificity-both analytically and clinically-to improve screening for CF.

METHODS:
Informed consent and IRB exemption for anonymized research were obtained for this study. Analytical validity was assessed using orthogonal confirmation and reference cell-line samples. Clinical validity was evaluated using concordance to the CFTR2 variant database. Finally, clinical impact (e.g., incidence) was assessed using a cohort of >100,000 screened patients (>15,000 couples). Three screening strategies were compared: genotyping of 23 ACMG common variants (“CF23”), sequencing all single nucleotide variants (SNVs) and short insertions or deletions (“indels”) in CFTR exons (“NGS”), and sequencing with copy-number variant (CNV) identification (“NGS+CNV”).

RESULTS:
Analytical accuracy of NGS+CNV was 100% for SNVs, indels, and CNVs. Among variants present in both the Counsyl and CFTR2 databases, interpretive clinical specificity was 99.4%. As compared to CF23 genotyping, NGS-based screening showed increased detection rate: of the 67 at-risk couples identified with NGS+CNV, 19 would have gone undetected in a CF23 genotyping-only regimen.

CONCLUSION:
Modern NGS, coupled with standardized variant interpretation processes, now enables the accurate implementation of CF screening based entirely on a sequencing platform. Limiting screening to 23 variants will fail to detect approximately 30% of affected pregnancies in the United States, particularly among patients who are not of Ashkenazi Jewish descent.
Value of the Continued Use of the Hexosaminidase A Enzyme Assay for Reproductive Carrier Screening [21O]
Authors: Yu Chunli , Liao Jun , Gross Susan , Chen Hongjie , Edelmann Lisa , Kornreich Ruth 
Published: May 2019

INTRODUCTION:
With the trend towards next-generation screening (NGS) for reproductive carrier screening, the value of Hexosaminidase A (HexA) enzyme assays for detecting Tay-Sachs Disease (TSD) and Sandhoff Disease (SD) carriers has been debated.

METHODS:
Results were analyzed for 27,121 individuals of varied self-reported ethnicities who underwent clinical Hex A enzyme testing as well as HEXA/HEXB NGS.

RESULTS:
481 TSD enzyme carriers were identified, of which 55% could be attributed to HEXA pathogenic (P)/likely pathogenic (LP)/pseudodeficiency (PD) variants, with Ashkenazi Jews and African Americans giving the highest and lowest collective yields, respectively. Of 186 identified SD enzyme carriers, 39% could be attributed to HEXB P/LP/PD variants, with Asians and Ashkenazi Jews giving the highest and lowest yields, respectively. The rate of HEXA variants of uncertain significance (VUSes) in TSD enzyme carriers was 11%, which is 5.4X higher than the rate in individuals with normal enzyme levels. For HEXB VUSes, the rate of 34% in SD enzyme carriers was 12.3X higher than in individuals with normal enzyme levels. 30% of TSD and 22% of SD enzyme carriers did not show P/LP/PD variants or VUSes, a phenomenon that may be explained by benign variants with in vitro effects and/or other variants not uncovered by the NGS testing platform.

CONCLUSION:
Until the majority of VUSes are reclassified and additional sources of variation in the HEXA/HEXB genes are explored, there remains a role for Hex A enzyme assays in the identification of putative carriers and TSD/SD detection rates will remain higher for tests that include enzyme analysis.
Variants of INSR rs2963 is Associated With Gestational Diabetes Mellitus and Iron Storage [22O]
Authors: Liu Junxiu , Cheng Yan , Zhang Qingying , He Mulan , Li Tingting , Cheng Haidong 
Published: May 2019

INTRODUCTION:
Gestational diabetes mellitus (GDM) was found to be related with iron status, since GDM was a gene related disease, our goal was to find susceptible single nucleotide polymorphisms (SNPs) that related with GDM and iron overload.

METHODS:
We chose 99 pregnant women with GDM and 114 normal glucose tolerance women as controls. We used Haploview software to screen the SNPs that may have stronger correlation with GDM, the SNPs of SLC2A4 (GLUT4), INSR, IRS - 1, AKT1 genes, and Tag SNPs genotype of GDM group and normal glucose tolerance group were detected by MassArray technology. The differences of genotype and allele frequency between GDM and NGT group were compared, and the correlation of SNPs with iron metabolism and GDM were analyzed.

RESULTS:
The level of serum ferritin is significantly higher in GDM group than control (25.7 (25.75) ng/ml vs 18.5 (17.74) ng/m p<0.001). There was significant difference between GDM and control for INSR gene rs2963, CT model of rs2963 was risk factor of GDM (OR 11.42, 95% CI 1.42-91.89, p=0.022, while adjusted OR 9.47, 95% CI 1.13-79.04, p=0.04). The dominant model CT+TT was risk factor of GDM (OR 12.7, 95% CI 1.60-101.05, p=0.016, while adjusted OR 10.32, 95% CI 1.25-84.95, p=0.03).Serum ferritin level in dominant model CT+TT was higher than that in CC genotype, 41.89 (32.76) ng/ml vs 19.22 (20.55) ng/ml, p=0.001.

CONCLUSION:
Iron storage level is higher in GDM than control group, INSR loci rs2963 C>T was a risk factor for GDM, and for iron supplementation the dominant model CT+TT women would be more likely to develop GDM.
Changes in Length of Stay and 30-Day Readmission Rates After Starting an Advanced Surgical Recovery Program [24O]
Authors: Manahan Kelly J. , Seeley Neil , Geisler John Patrick 
Published: May 2019

INTRODUCTION:
Advanced surgical recovery programs have been initiated at many institutions to improve quality and enhance patient safety. The objective of this study was to determine if length of stay in days (LOS) and 30-day readmission rates changed after commencing the program.

METHODS:
Medical records were examined for the last 50 patients before and first 75 patients after the beginning of the program undergoing radical complete debulking for ovarian cancer. No patients using opioids before surgery were included. No patients were knowingly excluded. Demographics, length of postoperative stay in days (LOS) and 30-day readmission rates at any hospital were collected. Two-tailed statistical tests were employed. IRB approval was either obtained or waived for the study.

RESULTS:
The mean age and BMI of the pre- (50.2 years (95% CI 47.5-52.0); 29.7 kg/m2 (95% CI 28.6-30.9) and post-program start (51.5 years (95% CI 49.6-53.4); 31.1 kg/m2 (95% CI 30.2-31.9) were not significantly different. There were no differences in radical procedures required for complete cytoreduction between the groups including bowel resections, diaphragm stripping/resection, liver wedge resections or splenectomies. Mean LOS decreased from 7.1 days (95% CI 5.9-8.3) to 2.6 (95% CI 2.6-2.8). Similarly, the readmission rate at 30-days decreased from 14% to 0% (P<0.001).

CONCLUSION:
When employed in the care of patients with ovarian cancer undergoing complete cytoreductive surgery, advanced surgical recover programs can decrease LOS without increasing 30-day readmission rates.