Katherine Bianco, MD


Obstetrics & Gynecology

Work and Education

Professional Education

Central University of Venezuela, Caracas, Venezuela, 6/13/1997


Yale School Of Medicine, New Haven, CT, 6/30/2004


Yale School Of Medicine, New Haven, CT, 6/30/2004


University of California San Francisco, San Francisco, CA, 8/31/2008

Board Certifications

Clinical Genetics, American Board of Medical Genetics and Genomics

Clinical Genetics and Genomics, American Board of Medical Genetics and Genomics

Maternal & Fetal Medicine, American Board of Obstetrics and Gynecology

Obstetrics & Gynecology, American Board of Obstetrics and Gynecology

All Publications

Maternal cardiac disease and perinatal outcomes in a single tertiary care center. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Gonzalez, J. M., Harris, I., Jimenez Ramirez, N., Myers, D., Killion, M., Thiet, M. P., Bianco, K. 2023; 36 (2): 2223336


Maternal mortality in the U.S. has increased, with a substantial contribution from maternal cardiac disease. As a result of improved childhood survival, more women with congenital heart disease are reaching reproductive age leading to a growing high-risk obstetric population. We sought to determine the obstetrical and neonatal outcomes of women with maternal cardiac disease, including acquired cardiovascular disease and congenital heart disease.We studied a retrospective cohort study of women that delivered from 2008 to 2013 (N=9026). Singleton pregnancies without preexisting conditions were established as the unexposed group for this study. Maternal and neonatal outcomes were compared between the unexposed group (N=7277) and women exposed to maternal (acquired or congenital) cardiac disease (N=139) as well as only congenital heart disease (N=85). Statistical comparisons used univariate/multivariable logistic and linear regression analysis controlling for confounders with p<.05 and 95% confidence intervals indicating statistical significance.Pregnancies complicated by maternal cardiac disease were associated with increased odds of preterm birth (<34weeks, <37weeks), intrauterine growth restriction (IUGR), need for assisted vaginal delivery, maternal ICU admission, and prolonged maternal hospitalization (>7d). Neonatal outcomes including small for gestational age and Apgar score <7 at 5min were increased in the pregnancies complicated by maternal cardiac disease. When pregnancies complicated by congenital heart disease were analyzed as a sub-group of the cohort, the results were similar. There were increased odds of preterm birth (<37weeks), early-term delivery, need for assisted vaginal delivery, and prolonged hospitalization. Neonatal outcomes were only significant for small for gestational age.We observed that in a select cohort of pregnancies complicated by maternal cardiac diseases (acquired or congenital), there were significant increases of adverse perinatal outcomes. Therefore, a multidisciplinary approach including maternal-fetal medicine specialists, cardiologists, obstetric anesthesia, and dedicated ancillary support is imperative for optimal care of this high-risk obstetrics population.

View details for DOI 10.1080/14767058.2023.2223336

View details for PubMedID 37369374

Clinical and Physician Factors Associated With Failed Operative Vaginal Delivery. Obstetrics and gynecology Panelli, D. M., Leonard, S. A., Joudi, N., Judy, A. E., Bianco, K., Gilbert, W. M., Main, E. K., El-Sayed, Y. Y., Lyell, D. J. 2023


To examine clinical and physician factors associated with failed operative vaginal delivery among individuals with nulliparous, term, singleton, vertex (NTSV) births.This was a retrospective cohort study of individuals with NTSV live births with an attempted operative vaginal delivery by a physician between 2016 and 2020 in California. The primary outcome was cesarean birth after failed operative vaginal delivery, identified using linked diagnosis codes, birth certificates, and physician licensing board data stratified by device type (vacuum or forceps). Clinical and physician-level exposures were selected a priori, defined using validated indices, and compared between successful and failed operative vaginal delivery attempts. Physician experience with operative vaginal delivery was estimated by calculating the number of operative vaginal delivery attempts made per physician during the study period. Multivariable mixed effects Poisson regression models with robust standard errors were used to estimate risk ratios of failed operative vaginal delivery for each exposure, adjusted for potential confounders.Of 47,973 eligible operative vaginal delivery attempts, 93.2% used vacuum and 6.8% used forceps. Of all operative vaginal delivery attempts, 1,820 (3.8%) failed; the success rate was 97.3% for vacuum attempts and 82.4% for forceps attempts. Failed operative vaginal deliveries were more likely with older patient age, higher body mass index, obstructed labor, and neonatal birth weight more than 4,000 g. Between 2016 and 2020, physicians who attempted more operative vaginal deliveries were less likely to fail. When vacuum attempts were successful, physicians who conducted them had a median of 45 vacuum attempts during the study period, compared with 27 attempts when vacuum attempts were unsuccessful (adjusted risk ratio [aRR] 0.95, 95% CI 0.93-0.96). When forceps attempts were successful, physicians who conducted them had a median of 19 forceps attempts, compared with 11 attempts when forceps attempts were unsuccessful (aRR 0.76, 95% CI 0.64-0.91).In this large, contemporary cohort with NTSV births, several clinical factors were associated with operative vaginal delivery failure. Physician experience was associated with operative vaginal delivery success, more notably for forceps attempts. These results may provide guidance for physician training in maintenance of operative vaginal delivery skills.

View details for DOI 10.1097/AOG.0000000000005181

View details for PubMedID 37141591

Shorter maternal leukocyte telomere length following cesarean birth: Implications for future research Panelli, D. M., Mayo, J. A., Wong, R. J., Becker, M., Maric, I., Wu, E., Gotlib, I. H., Aghaeepour, N., Druzin, M. L., Stevenson, D. K., Shaw, G. M., Bianco, K. MOSBY-ELSEVIER. 2023: S456-S457
Maternal congenital heart disease and effects on neonatal outcomes: the other side of the dyad Ramirez, N., Panelli, D. M., Padron, E., Dominguez, L., Miller, S. E., Beshar, I., Lee, C. J., Bianco, K. MOSBY-ELSEVIER. 2023: S554-S555
Severe maternal morbidity among people with cardiac disease: getting to the heart of the problem Darmawan, K. F., Panelli, D. M., Mayo, J. A., Leonard, S. A., Girsen, A., Carmichael, S. L., Bianco, K. MOSBY-ELSEVIER. 2023: S163-S164
A novel virtual simulation training improves providers' knowledge and confidence to manage obstetric emergencies Minor, K. C., Mayo, J. A., Bianco, K., Judy, A., Abir, G., Lee, H. C., Leonard, S. A., Sie, L., Ayotte, S., Daniels, K. I. MOSBY-ELSEVIER. 2023: S160
Addressing postpartum contraception practices utilizing a multidisciplinary Pregnancy Heart Team approach. AJOG global reports Miller, H. E., Do, S. C., Cruz, G., Panelli, D. M., Leonard, S. A., Girsen, A., Lee, C. J., Khandelwal, A., Shaw, K. A., Bianco, K. 2022; 2 (4): 100100


BACKGROUND: Cardiovascular disease has emerged as the leading cause of maternal morbidity and mortality, making planned pregnancy, and thereby reliable contraception among people with cardiovascular disease, vital.OBJECTIVE: This study aimed to compare postpartum contraceptive practices among people with cardiovascular disease (cardiac cohort) cared for by a Pregnancy Heart Team to people with other chronic comorbidities (high-risk cohort), and people without comorbidities (low-risk cohort). We hypothesized that the Pregnancy Heart Team influenced baseline contraception counseling and practices among those with cardiovascular disease.STUDY DESIGN: This was a retrospective cohort study comparing postpartum contraceptive practices between a cardiac cohort who received care by a multidisciplinary team between 2012 and 2020 and high-risk and low-risk cohorts delivering at a single academic center between 2016 and 2019. We investigated presence of a contraceptive plan (at birthing admission, discharge, and postpartum visit) and uptake of reliable contraception by 8 weeks postpartum.RESULTS: We included 1464 people: 189 with cardiovascular disease, 197 with other chronic comorbidities, and 1078 low-risk people. At birth hospitalization admission, reliable contraception was planned among 42% of the cardiac cohort, 40% of the high-risk cohort, and 31% of the low-risk cohort, with similar distributions at the time of discharge and at 8 weeks postpartum.Compared with the cardiac cohort, by 8 weeks postpartum,the high-risk cohort had similar odds of using highly reliable forms of contraception (39% vs 36%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.21) and similar odds of having a plan to use the most reliable forms of contraception (intrauterine device, implant, bilateral tubal ligation) at the time of birthing admission (42% vs 40%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.22), discharge (47% vs 45%; adjusted odds ratio, 0.95; 95% confidence interval, 0.61-1.48), and postpartum visit (35% vs 29%; adjusted odds ratio, 0.76; 95% confidence interval, 0.49-1.17).The low-risk cohort had lower odds of using a reliable form of contraception (39% vs 27%; adjusted odds ratio, 0.53; 95% confidence interval, 0.37-0.75) and was less likely to have a plan for reliable contraception at the time of birthing admission (42% vs 31%; adjusted odds ratio, 0.54; 95% confidence interval, 0.38-0.76), discharge (47% vs 33%; adjusted odds ratio, 0.58; 95% confidence interval, 0.4-0.82), and postpartum visit (35% vs 21%; adjusted odds ratio, 0.50; 95% confidence interval, 0.35-0.71).CONCLUSION: People with cardiovascular disease cared for by a Pregnancy Heart Team had higher odds of reliable postpartum contraception planning and uptake compared with a low-risk cohort and similar odds compared with a high-risk cohort. Pregnancy could serve as a critical period for contraception counseling and family planning among people with cardiovascular disease. A multidisciplinary team should be used to address postpartum contraception as a modifiable risk factor to reduce maternal morbidity and mortality among those with cardiovascular disease.

View details for DOI 10.1016/j.xagr.2022.100100

View details for PubMedID 36536840

An exploratory analysis of leukocyte telomere length among pregnant and non-pregnant people. Brain, behavior, & immunity - health Panelli, D. M., Diwan, M., Cruz, G. I., Leonard, S. A., Chueh, J., Gotlib, I. H., Bianco, K. 2022; 25: 100506


Background: Leukocyte telomere length (LTL) is a biomarker that is affected by older age, psychosocial stress, and medical comorbidities. Despite the relevance of these factors to obstetric practice, little is known about LTL in pregnancy. Our study explored longitudinal LTL dynamics in pregnant and non-pregnant people.Objective: This pilot study compares changes in LTL between pregnant and non-pregnant people over time, explores potential correlations between LTL and mental health measures, and investigates associations between short first-trimester LTL and adverse pregnancy outcomes.Study design: This was a prospective pilot cohort study of nulliparous pregnant and non-pregnant people between ages 18 and 50 who presented for care at a single institution from January to November 2020. Pregnant people were enrolled between 10 and 14 weeks gestation. Participants had two blood samples drawn for LTL; the first on the day of enrollment and the second on postpartum day 1 (pregnant cohort) or 7 months later (non-pregnant cohort). LTL was measured using quantitative PCR. The primary outcome was the difference between pregnant and non-pregnant people in LTL change between the two timepoints (basepair difference per 30-day period). Secondary outcomes included differences in responses to the Patient Health Questionnaire-9 (PHQ-9) and a survey about stress related to COVID-19. Differences in LTL were tested using t-tests and linear regression models, both crude and adjusted for age. A subgroup analysis was conducted within the pregnant cohort to examine whether shorter first-trimester LTL was associated with adverse pregnancy outcomes. We conducted t-tests to compare LTL between people with and without each categorical outcome and computed Pearson correlation coefficients between LTL and continuous outcomes such as gestational age at delivery.Results: 46 pregnant and 30 non-pregnant people were enrolled; 44 pregnant and 18 non-pregnant people completed all LTL assessments. There were no between-group differences in LTL change (-4.222.2 bp per 30 days pregnant versus -6.411.2 bp per 30 days non-pregnant, adjusted beta 2.1, 95% CI -9.0-13.2, p=0.60). The prevalence of depression and pandemic-related stress were both low overall. The two groups did not differ in PHQ-9 scores, and no correlations were significant between LTL and PHQ-9 scores. Among the 44 pregnant people, shorter first-trimester LTL was significantly correlated with earlier gestational age at delivery (r=0.35, p=0.02).Conclusion: In this exploratory pilot cohort of reproductive-aged people with low levels of psychological stress, we described baseline changes in LTL over time in pregnant and non-pregnant participants. We found a correlation between shorter first-trimester LTL and earlier gestational age at delivery, which warrants further investigation in a larger cohort.

View details for DOI 10.1016/j.bbih.2022.100506

View details for PubMedID 36110146

Severity of small-for-gestational-age and morbidity and mortality among very preterm neonates. Journal of perinatology : official journal of the California Perinatal Association Minor, K. C., Bianco, K., Sie, L., Druzin, M. L., Lee, H. C., Leonard, S. A. 2022


Evaluate the association between small for gestational age (SGA) severity and morbidity and mortality in a contemporary, population of very preterm infants.This secondary analysis of a California statewide database evaluated singleton infants born during 2008-2018 at 24-32 weeks' gestation, with a birthweight <15th percentile. We analyzed neonatal outcomes in relation to weight for gestational age (WGA) and symmetry of growth restriction.An increase in WGA by one z-score was associated with decreased major morbidity or mortality risk (aRR 0.73, 95% CI 0.68-0.77) and other adverse outcomes. The association was maintained across gestational ages and did not differ by fetal growth restriction diagnosis. Symmetric growth restriction was not associated with neonatal outcomes after standardizing for gestational age at birth.Increasing SGA severity had a significant impact on neonatal outcomes among very preterm infants.

View details for DOI 10.1038/s41372-022-01544-w

View details for PubMedID 36302849

Mixed methods evaluation of simulation-based training for postpartum hemorrhage management in Guatemala. BMC pregnancy and childbirth Parameshwar, P. S., Bianco, K., Sherwin, E. B., Meza, P. K., Tolani, A., Bates, P., Sie, L., Lopez Enriquez, A. S., Sanchez, D. E., Herrarte, E. R., Daniels, K. 2022; 22 (1): 513


BACKGROUND: To assess if simulation-based training (SBT) of B-Lynch suture and uterine balloon tamponade (UBT) for the management of postpartum hemorrhage (PPH) impacted provider attitudes, practice patterns, and patient management in Guatemala, using a mixed-methods approach.METHODS: We conducted an in-country SBT course on the management of PPH in a governmental teaching hospital in Guatemala City, Guatemala. Participants were OB/GYN providers (n=39) who had or had not received SBT before. Surveys and qualitative interviews evaluated provider knowledge and experiences with B-Lynch and UBT to treat PPH.RESULTS: Multiple-choice surveys indicated that providers who received SBT were more comfortable performing and teaching B-Lynch compared to those who did not (p=0.003 and 0.005). Qualitative interviews revealed increased provider comfort with B-Lynch compared to UBT and identified multiple barriers to uterine balloon tamponade implementation.CONCLUSIONS: Simulation-based training had a stronger impact on provider comfort with B-Lynch compared to uterine balloon tamponade. Qualitative interviews provided insight into the challenges that hinder uptake of uterine balloon tamponade, namely resource limitations and decision-making hierarchies. Capturing data through a mixed-methods approach allowed for more comprehensive program evaluation.

View details for DOI 10.1186/s12884-022-04845-2

View details for PubMedID 35751071

Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and associations with stress. BMC pregnancy and childbirth Panelli, D. M., Leonard, S. A., Wong, R. J., Becker, M., Mayo, J. A., Wu, E., Girsen, A. I., Gotlib, I. H., Aghaeepour, N., Druzin, M. L., Shaw, G. M., Stevenson, D. K., Bianco, K. 2022; 22 (1): 381


Short leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress.In this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: <200/7 weeks (Timepoint 1); 201/7 to 366/7 weeks (Timepoint 2); and 370/7 to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time of enrollment in the first trimester. LTL was measured using quantitative polymerase chain reaction (PCR). Wilcoxon signed-rank tests were used to compare LTL differences within participants across all timepoint intervals. To determine whether mode of delivery affected LTL, we compared postpartum Timepoint 3 LTLs between participants who had vaginal versus cesarean birth. Secondarily, we evaluated the association of the assessed multivariate stress profile and LTL using machine learning analysis.A total of 115 samples from 46 patients were analyzed. LTL (meanSD), expressed as telomere to single copy gene (T/S) ratios, were: 1.150.26, 1.130.23, and 1.070.21 for Timepoints 1, 2, and 3, respectively. There were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S change -0.030.26, p=0.39); 2 and 3 (-0.070.29, p=0.38) or Timepoints 1 and 3 (-0.070.21, p=0.06). Participants who underwent cesareans had significantly shorter postpartum LTLs than those who delivered vaginally (T/S ratio: 0.940.12 cesarean versus 1.120.21 vaginal, p=0.01). In secondary analysis, poor sleep quality was the main stress construct associated with shorter Timepoint 1 LTLs (p=0.02) and shorter mean LTLs (p=0.03).In this cohort of healthy pregnancies, maternal LTLs did not significantly change across gestation and postpartum LTLs were shorter after cesarean than after vaginal birth. Significant associations between sleep quality and short LTLs warrant further investigation.

View details for DOI 10.1186/s12884-022-04693-0

View details for PubMedID 35501726

Gender-based salary differences in academic medicine: a retrospective review of data from six public medical centers in the Western USA. BMJ open Miller, H., Seckel, E., White, C. L., Sanchez, D., Rubesova, E., Mueller, C., Bianco, K. 2022; 12 (4): e059216


OBJECTIVES: We assessed the effect of gender, rank and research productivity on compensation for faculty at academic medical centres.DESIGN: A web-based retrospective review of salary for professors in 2016.SETTING: Faculty from six state-run, publicly funded academic medical centres in the Western USA.PARTICIPANTS: 799 faculty members, 225 assistant (51%women), 200 associate (40%women) and 374 full professors (32%women) from general surgery (26%women), obstetrics and gynaecology (70%women) and radiology (34%women).METHODS: Archived online faculty profiles were reviewed for gender, rank and compensation (total, baseline and supplemental). Total compensation was defined as baseline compensation plus supplemental income. Baseline compensation was defined as base salary minus reductions due to participation in the voluntary Employee Reduction in Time and phased retirement programmes. Supplemental income was defined as additional salary for clinical care and research (eg, grants). Elsevier's Scopus was used to collect data on h-index, a measure of research productivity. Linear regression models were estimated to determine the relationship between these factors and salary.RESULTS: Total compensation was significantly higher for men across all professorial ranks in both general surgery [Formula: see text] and obstetrics and gynaecology [Formula: see text]. Women faculty members within these departments earned almost US$75000 less than their men colleagues. The disparity in salary originates from gaps in supplemental income, as baseline compensation was not significantly different between men and women. No significant gender difference in total compensation for radiology was found [Formula: see text]. Higher h-index was associated with higher baseline compensation across all departments as well as with supplemental income for general surgery. Higher h-index was related to lower supplemental income for radiology and was not related to supplemental income for obstetrics and gynaecology.CONCLUSIONS: Further investigations should focus on discrepancies in supplemental income, which may preferentially benefit men.

View details for DOI 10.1136/bmjopen-2021-059216

View details for PubMedID 35393330

Leukocyte Telomere Length in the First Trimester of Pregnancy and its Association with Perinatal Outcomes Panelli, D., Diwan, M., Cruz, G. I., Leonard, S. A., Chueh, J., Gotlib, I. H., Bianco, K. SPRINGER HEIDELBERG. 2022: 155
Cellular Aging and Stress in Pregnant and Non-Pregnant People During the COVID-19 Pandemic Panelli, D., Diwan, M., Cruz, G. I., Leonard, S. A., Chueh, J., Gotlib, I. H., Bianco, K. SPRINGER HEIDELBERG. 2022: 191
Metabolic profiling of placental tissue and maternal plasma to identify biomarkers of placenta accreta spectrum Miller, S. E., Contrepois, K., Michael, B., Cruz, G., Simms, I., Datoc, I., Sylvester, K., Silver, R. M., Einerson, B. D., Bianco, K., Lyell, D. J. MOSBY-ELSEVIER. 2022: S14-S15
Preterm twin gestation: The association between severity of small for gestational age and neonatal outcomes Miller, H. E., Sie, L., Minor, K. C., Bianco, K., Druzin, M. L., Lee, H. C., Leonard, S. A. MOSBY-ELSEVIER. 2022: S391-S392
Association of Neighborhood Income with Clinical Outcomes Among Pregnant Patients with Cardiac Disease Reproductive Sciences Carland, C., Panelli, D. M., Leonard, S. A., Bryant, E., Sherwin , E. B., Lee, C. J., Levin, E., Jimenez , S., Tremmel, J. A., Tsai , S., Heidenreich , P. A., Bianco , K., Khandelwal , A. 2022
Clinical factors associated with a positive postpartum depression screen in people with cardiac disease during pregnancy. Current research in psychiatry Panelli, D. M., Sherwin, E. B., Lee, C. J., Leonard, S. A., Miller, S. E., Miller, H. E., Tolani, A. T., Hoover, V., Ansari, J. R., Khandelwal, A., Bianco, K. 2022; 2 (2): 25-29


Background: While people with cardiac disease are known to be at increased lifetime risk of depression, little is known about postpartum depression rates in this population. Describing rates of positive postpartum depression screens and identifying risk factors that are unique to cardiac patients may help inform risk reduction strategies.Methods: This retrospective cohort study included pregnant patients with congenital and/or acquired cardiac disease who delivered at a single institution between 2014 and 2020. The primary outcome was a positive postpartum depression screen, defined as Edinburgh Postpartum Depression Score (EPDS) 10. Potential exposures were selected a priori and compared between patients with and without a positive postpartum depression screen using Wilcoxon rank-sum and Fisher's exact tests. Secondary outcomes were responses to a longitudinal follow-up survey sent to English-speaking patients evaluating cardiac status, mental health, and infant development.Results: Of 126 eligible cardiac patients, 23 (18.3%) had a positive postpartum depression screen. Patients with a positive postpartum depression screen were more likely to have had antepartum anticoagulation with heparin or enoxaparin (56.5% versus 26.2%, p=0.007), blood transfusion during delivery (8.7% versus 0%, p=0.032), and maternal-infant separation postpartum (52.2% versus 28.2%, p=0.047) compared to patients with a negative screen. Among 29 patients with a positive screen who responded to the follow up survey, 50% reported being formally diagnosed with anxiety or depression and 33.3% reported child development problems.Conclusions: Our results highlight the importance of screening for postpartum depression in patients with cardiac disease, especially those requiring antepartum anticoagulation or maternal-infant separation postpartum.

View details for DOI 10.46439/Psychiatry.2.027

View details for PubMedID 36570491

Cellular aging and pregnancy complications: Examining maternal leukocyte telomere length in two diverse cohorts. Panelli, D. M., Wang, X., Wong, R. J., Cruz, G., Hong, X., Aghaeepour, N., Druzin, M. L., Shaw, G. M., Zuckerman, B. S., Stevenson, D. K., Bianco, K. MOSBY-ELSEVIER. 2022: S646
Cellular aging and telomere dynamics in pregnancy. Current opinion in obstetrics & gynecology Panelli, D. M., Bianco, K. 2021


PURPOSE OF REVIEW: Telomere biology is an emerging area of scientific interest. Telomeres are deoxynucleic acid caps at the ends of chromosomes that naturally shorten over one's lifespan; because of this, short telomeres have been studied as a marker of cellular aging. Given the association between short telomeres and genetic and environmental factors, their role in pregnancy has become an intriguing area of research.RECENT FINDINGS: This review describes recent data on telomeres in pregnancy. Specifically, we discuss the association between short maternal leukocyte telomeres and poor nutritional status, between short neonatal telomeres and greater maternal psychosocial stress, and between shorter fetal amniotic membrane telomeres and the spontaneous onset of parturition. We also review recent studies suggesting that events during pregnancy can impact telomeres in the offspring years into the future.SUMMARY: Telomere length varies in maternal, placental, and neonatal cells, but within each of these compartments telomeres may play their own distinct role during pregnancy. Whether telomeres are reflective of the cumulative impact of stressors, or part of an as-yet unknown fetal programming mechanism is an area of interest. With future research, we may work toward a better understanding of gestational biology which could have far reaching intergenerational impacts.

View details for DOI 10.1097/GCO.0000000000000765

View details for PubMedID 34845136

Newborn screen metabolic panels reflect the impact of common disorders of pregnancy. Pediatric research Reiss, J. D., Chang, A. L., Mayo, J. A., Bianco, K., Lee, H. C., Stevenson, D. K., Shaw, G. M., Aghaeepour, N., Sylvester, K. G. 2021


BACKGROUND: Hypertensive disorders of pregnancy and maternal diabetes profoundly affect fetal and newborn growth, yet disturbances in intermediate metabolism and relevant mediators of fetal growth alterations remain poorly defined. We sought to determine whether there are distinct newborn screen metabolic patterns among newborns affected by maternal hypertensive disorders or diabetes in utero.METHODS: A retrospective observational study investigating distinct newborn screen metabolites in conjunction with data linked to birth and hospitalization records in the state of California between 2005 and 2010.RESULTS: A total of 41,333 maternal-infant dyads were included. Infants of diabetic mothers demonstrated associations with short-chain acylcarnitines and free carnitine. Infants born to mothers with preeclampsia with severe features and chronic hypertension with superimposed preeclampsia had alterations in acetylcarnitine, free carnitine, and ornithine levels. These results were further accentuated by size for gestational age designations.CONCLUSIONS: Infants of diabetic mothers demonstrate metabolic signs of incomplete beta oxidation and altered lipid metabolism. Infants of mothers with hypertensive disorders of pregnancy carry analyte signals that may reflect oxidative stress via altered nitric oxide signaling. The newborn screen analyte composition is influenced by the presence of these maternal conditions and is further associated with the newborn size designation at birth.IMPACT: Substantial differences in newborn screen analyte profiles were present based on the presence or absence of maternal diabetes or hypertensive disorder of pregnancy and this finding was further influenced by the newborn size designation at birth. The metabolic health of the newborn can be examined using the newborn screen and is heavily impacted by the condition of the mother during pregnancy. Utilizing the newborn screen to identify newborns affected by common conditions of pregnancy may help relate an infant's underlying biological disposition with their clinical phenotype allowing for greater risk stratification and intervention.

View details for DOI 10.1038/s41390-021-01753-7

View details for PubMedID 34671094

The impact of the COVID-19 pandemic on postpartum contraception planning AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM Miller, H. E., Henkel, A., Leonard, S. A., Miller, S. E., Tran, L., Bianco, K., Shaw, K. A. 2021; 3 (5)
Myocardial Bridge in Pregnancy: Beyond a 'Normal Anatomic Variant'. Joudi, N., Datoc, I., Leonard, S., Lee, C., Schnittger, I., Khandelwal, A., Bianco, K. SPRINGER HEIDELBERG. 2021: 267A
Long Term Patient Follow-Up of Cardiac Disease in Pregnancy: Multidisciplinary Teams Tether At-Risk Patients to the System. Miller, S. E., Panelli, D., Sherwin, E., Lee, C., Miller, H., Tolani, A., O'Mara, A., Khandelwal, A., Bianco, Y. SPRINGER HEIDELBERG. 2021: 268A-269A
Novel Approaches to Develop Critical Reference Materials for Noninvasive Prenatal Testing: A Pilot Study. The journal of applied laboratory medicine Bianco, K., Sherwin, E. B., Konigshofer, Y., Girsen, A. I., Sylvester, K. G., Garlick, R. K. 2021


BACKGROUND: Highly characterized reference materials are required to expand noninvasive prenatal testing (NIPT) for low incidence aneuploidies and microdeletions. The goal of this study was to develop reference materials for the development of next generation circulating cell-free DNA (ccfDNA) assays.METHODS: This was a prospective study of pregnancies complicated by positive prenatal genetic screening. ccfDNA was isolated from maternal plasma and amplified. Lymphoblastoid cell lines were prepared from maternal peripheral blood mononuclear cells and fetal cord blood cells. Cells were Epstein-Barr virus immortalized and expanded. Amplified DNA and to a limited extent formulated lymphoblastoid-derived ccfDNA was tested in SNP-based and chromosome counting (CC) based massively parallel sequencing assays.RESULTS: Enrolled cases included fetuses with: T21 (2), T18 (1), T18-XXX (1), XYY (1), microdeletions (1), and euploid (2). Three lymphoblastoid cells lines were prepared. Genomic DNA was extracted from cell lines and fragmented to simulate ccfDNA. ccfDNA isolation yielded about 2000 usable genome equivalents of DNA for each case for amplification. Although the sonicated genomic DNA derived from lymphoblastoid cell lines did not yield results compatible with NIPT assays, when blinded, NIPT platforms correctly identified the amplified ccfDNA isolated from blood in the majority of cases.CONCLUSIONS: This study showed that maternal blood samples from pregnancies complicated by common chromosomal abnormalities can be used to generate materials for the development and evaluation of NIPT assays.

View details for DOI 10.1093/jalm/jfab037

View details for PubMedID 34080621

Outcomes in pregnancies complicated by IUGR before 32 weeks: does the degree of SGA matter? Minor, K., Bianco, K., Sie, L., Druzin, M. L., Lee, H. C., Leonard, S. A. MOSBY-ELSEVIER. 2021: S519
To pull or not to pull: clinical factors associated with failed operative vaginal delivery Panelli, D. M., Leonard, S. A., Joudi, N., Girsen, A., Judy, A., Bianco, K., El-Sayed, Y. Y., Gilbert, W., Lyell, D. J. MOSBY-ELSEVIER. 2021: S101
The impact of the COVID-19 pandemic on postpartum contraception planning. American journal of obstetrics & gynecology MFM Miller, H. E., Henkel, A., Leonard, S. A., Miller, S. E., Tran, L., Bianco, K., Shaw, K. A. 2021: 100412

View details for DOI 10.1016/j.ajogmf.2021.100412

View details for PubMedID 34058421

Changing the Landscape of Obstetric Resident Education in LMIC Using Simulation-Based Training. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics Meza, P. K., Bianco, K., Herrarte, E., Daniels, K. 2020


OBJECTIVE: Evaluate simulation-based training (SBT) in low-and-middle-income countries (LMIC) and the long-term retention of knowledge and self-efficacy.METHODS: We conducted a SBT course on the management of post-partum hemorrhage (PPH), shoulder dystocia (SD), and maternal cardiac arrest (MCA) in three governmental teaching hospitals in Guatemala. We evaluated changes in knowledge and self-efficacy using a multiple-choice questionnaire (MCQ) for 46 OB/GYN residents. A paired Student t-test was used to analyze changes at one week and six months after the SBT.RESULTS: There was an increase in scores in clinical knowledge of MCA, P <0. 001, 95% CI [0.81, 1.49], and SD, P<0.001, 95% CI [0.41, 1.02] one week following SBT and a statistically insignificant increase in PPH scores, P= 0.617, 95% CI [-0.96, 0.60]. This increase in scores was maintained after six months, for MCA, P< 0.001, 95% CI [0.69, 1.53], SD, P= 0.02 95% CI [0.07-0.85] and PPH, P=0.04 95% CI [0.01, 1.26]. For MCA and SD levels of self-efficacy were increased one-week following training, P<0.001 95% CI [0.83, 2.30] and P= 0.008 95% CI [0.60, 3.92], respectively, and at six-months P<0.001 95% CI [0.79, 2.42] and P= 0.006 95% CI [0.66, 3.81], respectively. There was a slight increase in PPH self-efficacy scores one-week after SBT, P=0.73, 95% CI [-6.05, 4.41], maintained after six-months P= 0.38 95% CI [-6.85, 2.85].CONCLUSION: SBT was found to be an effective and feasible method to increase short and long-term clinical knowledge and self-efficacy of obstetric emergencies in LMIC.

View details for DOI 10.1002/ijgo.13526

View details for PubMedID 33314149

Measurement of Marginal Placental Cord Insertion by Prenatal Ultrasound Was Found Not to Be Predictive of Adverse Perinatal Outcomes. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine Lutz, A. B., Young-Lin, N., Leon-Martinez, D., Bianco, I. C., Seckel, E., Mrazek-Pugh, B., Bianco, K. 2020


The clinical importance of marginal cord insertion (MCI) is currently controversial. In this study, we examined the association between MCI and adverse perinatal outcomes. We also evaluated the ultrasound-measured distance from the site of placental cord insertion (PCI) to the placental margin (PCI distance) and perinatal outcomes.This was a retrospective cohort study of MCI and control pregnancies presenting to a single institution between September 2014 and August 2016. Marginal cord insertion was diagnosed on routine anatomy ultrasound scans at 20weeks' gestation. The primary outcome was fetal intolerance to labor. Secondary outcomes of interest included mode of delivery, gestational age at delivery, Apgar scores at 1 and 5 minutes, birth weight, delivery complications, and neonatal intensive care unit admission. The PCI distance was determined by an ultrasound review. Statistical significance was evaluated by a 2 analysis, descriptive statistics, Wilcoxon tests, and regression models with log-transformed outcomes, the PCI distance, or both as needed.Of 675 abnormal cord insertion cases, we identified 183 that met inclusion criteria. We found no statistically significant association between MCI and fetal intolerance to labor (odds ratio, 1.24 [95% confidence interval, 0.55-2.80]; P = .71) or secondary outcomes. Furthermore, we found no significant correlation between perinatal outcomes and the PCI distance.Our study suggests that MCI pregnancies, regardless of the specific PCI distance, might not be at increased risk of adverse perinatal outcomes. This finding questions the need for heightened antepartum surveillance of this patient population.

View details for DOI 10.1002/jum.15586

View details for PubMedID 33277931

Use of Remdesivir for Pregnant Patients with Severe Novel 2019 Coronavirus Disease. American journal of obstetrics and gynecology Igbinosa, I., Miller, S., Bianco, K., Nelson, J., Kappagoda, S., Blackburn, B. G., Grant, P., Subramanian, A., Lyell, D., El-Sayed, Y., Aziz, N. 2020

View details for DOI 10.1016/j.ajog.2020.08.001

View details for PubMedID 32771381

Changing the Landscape of Obstetric Resident Education in LMIC Using Simulation Based Training Meza, P. K., Bianco, K., Herrarte, E., Daniels, K. LIPPINCOTT WILLIAMS & WILKINS. 2020: 80S
Perinatal Outcomes in Women With Cardiac Arrhythmia. Lee, J., Sie, L., Sherwin, E. B., Girsen, A. I., Tolani, A. T., Miller, H. E., Panelli, D. M., Do, S. C., Khandelwal, A., Bianco, K. SPRINGER HEIDELBERG. 2020: 161A
Cellular Aging in Pregnancy: Telomere Dynamics Across Gestation. Panelli, D. M., Leonard, S. A., Wong, R. J., Girsen, A. I., Baskovic, M., Stevenson, D. K., Bianco, K. SPRINGER HEIDELBERG. 2020: 127A128A
Postpartum Depression Among Women with Cardiac Disease: Considerations During the Delivery Admission Panelli, D., Sherwin, E. B., Lee, C. J., Suharwardy, S., Miller, H. E., Tolani, A. T., Girsen, A. I., Leonard, S. A., Warshawsky, S., Judy, A., Khandel-Wal, A., Bianco, Y. K. SPRINGER HEIDELBERG. 2020: 246A Measurement of Marginal Placental Cord Insertion by Prenatal Ultrasound Was Found Not to Be Predictive of Adverse Perinatal Outcomes Lutz, A. B., Young-Lin, N., Leon-Martinez, D., Bianco, I. C., Seckel, E., Mrazek-Pugh, B., Bianco, K. 2020

View details for DOI 10.1002/jum.15586

Bicuspid Aortic Valve and Ascending Aortic Aneurysm in a Twin Pregnancy. JACC. Case reports Bryant, E., Tsai, S., Levin, E., Fleischman, D., Ansari, J., Fischbein, M., Bianco, K., Khandelwal, A. 2020; 2 (1): 96-100


Bicuspid aortic valve with ascending aortic aneurysm is a common condition encountered in pregnancy. There are limited data on how to manage these patients. To our knowledge, we report the only case of a bicuspid aortic valve and aortic aneurysm with twin gestations. (Level of Difficulty: Intermediate.).

View details for DOI 10.1016/j.jaccas.2019.12.012

View details for PubMedID 34316973

Trisomy 21 is Associated with Caspase-2 Upregulation in Cytotrophoblasts at the Maternal-Fetal Interface REPRODUCTIVE SCIENCES Leon-Martinez, D., Robinson, J. F., Zdravkovic, T., Genbacev, O., Gormley, M., Mcmaster, M., Fisher, S. J., Bianco, K. 2020; 27 (1): 100109


Impaired placentation is implicated in poor perinatal outcomes associated with Trisomy 21. Earlier studies revealed abnormal cytotrophoblast differentiation along the invasive pathway as a contributing mechanism. To further elucidate the causes, we evaluated Caspase-2 expression at the protein level (immunolocalization and immunoblot) in samples from Trisomy 21 (n = 9) and euploid (n = 4) age-matched placentas. Apoptosis was investigated via the TUNEL assay. An immunolocalization approach was used to characterize Caspase-3, Fas (CD95), and Fas ligand in the same samples. Caspase-2 was significantly overexpressed in Trisomy 21 placentas, with the highest expression in villous cores and invasive cytotrophoblasts. Immunolocalization showed that Caspase-3 had a similar expression pattern as Caspase-2. Using the TUNEL approach, we observed high variability in the number of apoptotic cells in biopsies from different regions of the same placenta and among different placentas. However, Trisomy 21 placentas had more apoptotic cells, specifically in cell columns and basal plates. Furthermore, Caspase-2 co-immunolocalized with Fas (CD95) and FasL in TUNEL-positive extravillous cytotrophoblasts, but not in villous cores. These results help explain the higher levels of apoptosis among placental cells of Trisomy 21 pregnancies in molecular terms. Specifically, the co-expression of Caspase-2 and Caspase-3 with other regulators of the apoptotic process in TUNEL-positive cells suggests these molecules may cooperate in launching the observed apoptosis. Among trophoblasts, only the invasive subpopulation showed this pattern, which could help explain the higher rates of adverse outcomes in these pregnancies. In future experiments, this relationship will be further examined at a functional level in cultured human trophoblasts.

View details for DOI 10.1007/s43032-019-00002-x

View details for Web of Science ID 000525433300011

View details for PubMedID 32046398

Contraception uptake among women with cardiovascular disease: The impact of a multidisciplinary team care approach Miller, H. E., Sie, L., Lee, C. J., Panelli, D. M., Sherwin, E. B., Noon, B., Girsen, A., Bianco, K. MOSBY-ELSEVIER. 2020: S707S708
Impact of gender, rank and research productivity on salary in obstetrics and gynecology Miller, H. E., Seckel, E., Sanchez, D., White, C., Mueller, C., Bianco, K. MOSBY-ELSEVIER. 2020: S356
Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia. PloS one Hao, S. n., You, J. n., Chen, L. n., Zhao, H. n., Huang, Y. n., Zheng, L. n., Tian, L. n., Maric, I. n., Liu, X. n., Li, T. n., Bianco, Y. K., Winn, V. D., Aghaeepour, N. n., Gaudilliere, B. n., Angst, M. S., Zhou, X. n., Li, Y. M., Mo, L. n., Wong, R. J., Shaw, G. M., Stevenson, D. K., Cohen, H. J., Mcelhinney, D. B., Sylvester, K. G., Ling, X. B. 2020; 15 (3): e0230000


Placental protein expression plays a crucial role during pregnancy. We hypothesized that: (1) circulating levels of pregnancy-associated, placenta-related proteins throughout gestation reflect the temporal progression of the uncomplicated, full-term pregnancy, and can effectively estimate gestational ages (GAs); and (2) preeclampsia (PE) is associated with disruptions in these protein levels early in gestation; and can identify impending PE. We also compared gestational profiles of proteins in the human and mouse, using pregnant heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like symptoms.Serum levels of placenta-related proteins-leptin (LEP), chorionic somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)-were quantified by ELISA in blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 20 subjects who developed PE with 61 samples). Multivariate analysis was performed to estimate the GA in normal pregnancy. Mean-squared errors of GA estimations were used to identify impending PE. The human protein profiles were then compared with those in the pregnant HO-1 Het mice.An elastic net-based gestational dating model was developed (R2 = 0.76) and validated (R2 = 0.61) using serum levels of the 6 proteins measured at various GAs from women with normal uncomplicated pregnancies. In women who developed PE, the model was not (R2 = -0.17) associated with GA. Deviations from the model estimations were observed in women who developed PE (P = 0.01). The model developed with 5 proteins (ELA excluded) performed similarly from sera from normal human (R2 = 0.68) and WT mouse (R2 = 0.85) pregnancies. Disruptions of this model were observed in both human PE-associated (R2 = 0.27) and mouse HO-1 Het (R2 = 0.30) pregnancies. LEP outperformed sFlt-1 and PlGF in differentiating impending PE at early human and late mouse GAs.Serum placenta-related protein profiles are temporally regulated throughout normal pregnancies and significantly disrupted in women who develop PE. LEP changes earlier than the well-established biomarkers (sFlt-1 and PlGF). There may be evidence of a causative action of HO-1 deficiency in LEP upregulation in a PE-like murine model.

View details for DOI 10.1371/journal.pone.0230000

View details for PubMedID 32126118

A Multidisciplinary Approach to Care of Pregnant Patients with History of Open Heart Surgery. Do, S. C., Lee, C. J., Sie, L., Tolani, A. T., Sherwin, E., Girsen, A. I., El-Sayed, Y. Y., Khandelwal, A., Bianco, K., Blumenfeld, Y. J. SAGE PUBLICATIONS INC. 2019: 323A324A
Maternal Outcomes in Planned and Unplanned Pregnancies in Women with Cardiac Disease. Do, S. C., Tolani, A. T., Sie, L., Girsen, A. I., Lee, C. J., Sherwin, E., Panelli, D. M., El-Sayed, Y. Y., Khandelwal, A., Blumenfeld, Y. J., Bianco, K. SAGE PUBLICATIONS INC. 2019: 323A
Care of the pregnant cardiac patient e the importance of a multidisciplinary approach Tolani, A. T., Do, S. C., Blumenfeld, Y. J., Sie, L., Girsen, A. I., Lee, C. J., Sherwin, E. B., Tsur, A., El-Sayed, Y. Y., Khandelwal, A., Bianco, K. MOSBY-ELSEVIER. 2019: S536
Outcomes of women with primary and secondary pulmonary hypertension during pregnancy Blumenfeld, Y. J., Girsen, A. I., Druzin, M. L., Lyell, D. J., Bianco, K. Y., Herrero, T., Bentley, J., Seckel, E., Zamanian, R. T., El-Sayed, Y. Y. MOSBY-ELSEVIER. 2019: S405
Donor-derived circulating cell-free DNA (ccfDNA) reference materials for concordance studies Konigshofer, Y., Butler, M. G., Dickens, J., Bianco, K., Sylvester, K. G., Anekella, B., Garlick, R. K. AMER ASSOC CANCER RESEARCH. 2018
Hospital variations in the use of forceps assisted delivery - results from a state-wide analysis Bentley, J., Lee, H., Lyell, D., El-Sayed, Y., Ness, A., Bianco, K., Spiegel, A., Blumenfeld, Y. MOSBY-ELSEVIER. 2018: S344
Maternal morbidity after forceps vs vacuum assisted delivery - Outcomes from a large state-wide cohort Bentley, J., Lyell, D., El-Sayed, Y., Ness, A., Foeller, M., Bianco, K., Spiegel, A., Martin, B., Do, S., Blumenfeld, Y. MOSBY-ELSEVIER. 2018: S345
Fetal intolerance to labor in pregnancies complicated by marginal and eccentric cord insertion Young-Lin, N., Lutz, A., Leon-Martinez, D., Ye, C., Torosis, M., Jazayeri, Y., Pugh, B., Bianco, K. MOSBY-ELSEVIER. 2018: S285
Gene expression network analysis in aneuploid human trophoblast progenitor cells (TBPC) reveals modular structures Leon-Martinez, D., Ling, X., Hao, S., Sylvester, K., Bianco, K. MOSBY-ELSEVIER. 2018: S163S164
Neonatal outcomes after operative vaginal delivery - are forceps or vacuum safer? Bentley, J. P., Lee, H., Lyell, D., El-Sayed, Y., Ness, A., Bianco, K., Yeaton-Massey, A., Blumenfeld, Y. MOSBY-ELSEVIER. 2018: S343S344
Placental transcriptomes in the common aneuploidies reveal critical regions on the trisomic chromosomes and genome-wide effects PRENATAL DIAGNOSIS Bianco, K., Gormley, M., Farrell, J., Zhou, Y., Oliverio, O., Tilden, H., McMaster, M., Fisher, S. J. 2016; 36 (9): 812-822


Chromosomal aberrations are frequently associated with birth defects and pregnancy losses. Trisomy 13, Trisomy 18 and Trisomy 21 are the most common, clinically relevant fetal aneusomies. This study used a transcriptomics approach to identify the molecular signatures at the maternal-fetal interface in each aneuploidy.We profiled placental gene expression (13-22weeks) in T13 (n=4), T18 (n=4) and T21 (n=8), and in euploid pregnancies (n=4).We found differentially expressed transcripts (2-fold) in T21 (n=160), T18 (n=80) and T13 (n=125). The majority were upregulated and most of the misexpressed genes were not located on the relevant trisomic chromosome, suggesting genome-wide dysregulation. A smaller number of the differentially expressed transcripts were encoded on the trisomic chromosome, suggesting gene dosage. In T21, <10% of the genes were transcribed from the Down syndrome critical region (21q21-22), which contributes to the clinical phenotype. In T13, 15% of the upregulated genes were on the affected chromosome (13q11-14), and in T18, the percentage increased to 24% (18q11-22 region).The trisomic placental (and possibly fetal) phenotypes are driven by the combined effects of genome-wide phenomena and increased gene dosage from the trisomic chromosome. 2016 John Wiley & Sons, Ltd.

View details for DOI 10.1002/pd.4862

View details for Web of Science ID 000384096800002

View details for PubMedID 27328057

View details for PubMedCentralID PMC5104283

Human trophoblast progenitor cell (TBPC) lines derived from aneuploid placentas: studying fundamental aspects of trophoblast biology Bianco, K., Leon-Martinez, D., Farrell, J., Gormley, M., McMaster, M., Fisher, S. J. MOSBY-ELSEVIER. 2016: S331
Integrative analysis of 111 reference human epigenomes. Nature Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., Ziller, M. J., Amin, V., Whitaker, J. W., Schultz, M. D., Ward, L. D., Sarkar, A., Quon, G., Sandstrom, R. S., Eaton, M. L., Wu, Y., Pfenning, A. R., Wang, X., Claussnitzer, M., Liu, Y., Coarfa, C., Harris, R. A., Shoresh, N., Epstein, C. B., Gjoneska, E., Leung, D., Xie, W., Hawkins, R. D., Lister, R., Hong, C., Gascard, P., Mungall, A. J., Moore, R., Chuah, E., Tam, A., Canfield, T. K., Hansen, R. S., Kaul, R., Sabo, P. J., Bansal, M. S., Carles, A., Dixon, J. R., Farh, K., Feizi, S., Karlic, R., Kim, A., Kulkarni, A., Li, D., Lowdon, R., Elliott, G., Mercer, T. R., Neph, S. J., Onuchic, V., Polak, P., Rajagopal, N., Ray, P., Sallari, R. C., Siebenthall, K. T., Sinnott-Armstrong, N. A., Stevens, M., Thurman, R. E., Wu, J., Zhang, B., Zhou, X., Beaudet, A. E., Boyer, L. A., De Jager, P. L., Farnham, P. J., Fisher, S. J., Haussler, D., Jones, S. J., Li, W., Marra, M. A., McManus, M. T., Sunyaev, S., Thomson, J. A., Tlsty, T. D., Tsai, L., Wang, W., Waterland, R. A., Zhang, M. Q., Chadwick, L. H., Bernstein, B. E., Costello, J. F., Ecker, J. R., Hirst, M., Meissner, A., Milosavljevic, A., Ren, B., Stamatoyannopoulos, J. A., Wang, T., Kellis, M. 2015; 518 (7539): 317-330


The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

View details for DOI 10.1038/nature14248

View details for PubMedID 25693563

View details for PubMedCentralID PMC4530010

Pregnancy complications are increased among women with cardiomyopathy compared to those with other cardiac diseases Bianco, K., Harris, I., Henry, D., Killion, M., Bosco, V., Thiet, M., Gonzalez, J. MOSBY-ELSEVIER. 2015: S68S69
Congenital Heart Disease and Perinatal Outcomes. Henry, D., Clay, J., Gonzalez, J. M., Harris, I. S., Tilden, H., Bianco, K. SAGE PUBLICATIONS INC. 2014: 148A
Reversal of gene dysregulation in cultured cytotrophoblasts reveals possible causes of preeclampsia JOURNAL OF CLINICAL INVESTIGATION Zhou, Y., Gormley, M. J., Hunkapiller, N. M., Kapidzic, M., Stolyarov, Y., Feng, V., Nishida, M., Drake, P. M., Bianco, K., Wang, F., McMaster, M. T., Fisher, S. J. 2013; 123 (7): 286272


During human pregnancy, a subset of placental cytotrophoblasts (CTBs) differentiates into cells that aggressively invade the uterus and its vasculature, anchoring the progeny and rerouting maternal blood to the placenta. In preeclampsia (PE), CTB invasion is limited, reducing placental perfusion and/or creating intermittent flow. This syndrome, affecting 4%-8% of pregnancies, entails maternal vascular alterations (e.g., high blood pressure, proteinuria, and edema) and, in some patients, fetal growth restriction. The only cure is removal of the faulty placenta, i.e., delivery. Previously, we showed that defective CTB differentiation contributes to the placental component of PE, but the causes were unknown. Here, we cultured CTBs isolated from PE and control placentas for 48 hours, enabling differentiation and invasion. In various severe forms of PE, transcriptomics revealed common aberrations in CTB gene expression immediately after isolation, including upregulation of SEMA3B, which resolved in culture. The addition of SEMA3B to normal CTBs inhibited invasion and recreated aspects of the PE phenotype. Additionally, SEMA3B downregulated VEGF signaling through the PI3K/AKT and GSK3 pathways, effects that were observed in PE CTBs. We propose that, in severe PE, the in vivo environment dysregulates CTB gene expression; the autocrine actions of the upregulated molecules (including SEMA3B) impair CTB differentiation, invasion and signaling; and patient-specific factors determine the signs.

View details for DOI 10.1172/JCI66966

View details for Web of Science ID 000321316700016

View details for PubMedID 23934129

View details for PubMedCentralID PMC3999620

Decidua-Placental Interface Show Abnormal Epigenetic Profiles in Common Aneuploidies Houshdaran, S., Tilden, H., Bianco, K. SAGE PUBLICATIONS INC. 2013: 254A
Genomic profiles in common aneuploidies: a combination of dose effects and whole genome misregulation Bianco, K., Gormley, M., Tilden, H., McMaster, M., Fisher, S. MOSBY-ELSEVIER. 2013: S30
Human Placenta Undergoes Global DNA Methylation Modification during Normal Gestation Houshdaran, S., Goldfien, G. A., Bianco, K. SAGE PUBLICATIONS INC. 2012: 383A384A
Genomic imprinting in offspring conceived with assisted reproductive technology 31st Annual Scientific Meeting of the Society-of-Maternal-Fetal-Medicine (SMFM) Norton, M., Haston, K., Reijo-Pera, R., Chueh, J., Blumenfeld, Y., Bianco, K., Zlatnik, M. MOSBY-ELSEVIER. 2011: S284S285
Stem Cells in Hepatic Regeneration After Injury ADVANCES IN WOUND CARE, VOL 1 Kuscuoglu, U., Bianco, K., Sylvester, K. G., Sen, C. K. 2010; 1: 52631
Effect of estradiol on oocyte development INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS Bianco, K., Mahutte, N. G., Arici, A., Sakkas, D., Taylor, H. S. 2009; 104 (3): 23032


To determine whether elevated serum estradiol (E(2)) concentrations in oocyte donors affect assisted reproduction outcome.In a retrospective cohort study of 58 consecutive oocyte donation cycles, donors were stratified into 2 groups according to E(2) concentration, group 1 (n=32; E(2)2000 pg/mL [range, 2062-6957 pg/mL]). Data were analyzed using the t test and chi(2) test.Donors in group 1 produced significantly less oocytes than donors in group 2 (19.3+/-1.7 vs 12.0+/-1.4; P<0.001), and recipients of oocytes from group 1 had significantly fewer numbers of embryos available for transfer (10.4+/-1.1 vs 6.4+/-0.8; P=0.003). However, the mean number (3.3) of embryos transferred and the pregnancy rate were the same in both groups.Elevated estradiol concentration in oocyte donors did not affect pregnancy outcome, suggesting that estradiol levels in donors do not affect oocyte development.

View details for DOI 10.1016/j.ijgo.2008.10.015

View details for Web of Science ID 000264255600015

View details for PubMedID 19056082

View details for PubMedCentralID PMC3107851

Operative vaginal delivery: Now or later? Cheng, Y. W., Bianco, K., Shaffer, B. L., Lyell, D., Caughey, A. B. MOSBY-ELSEVIER. 2007: S97
Fetal cerebellar hemorrhage in parvovirus-associated non-immune hydrops fetalis JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Glenn, O. A., Bianco, K., Barkovich, A., Callen, P. W., Parer, J. T. 2007; 20 (10): 76972


We report two cases of fetal cerebellar hemorrhage in the setting of parvovirus-associated hydrops fetalis and fetal blood transfusion. In both cases, the cerebellar hemorrhage was diagnosed by fetal magnetic resonance imaging after intrauterine blood transfusion. To our knowledge, this is the first report of fetal cerebellar hemorrhage in the setting of parvovirus-associated hydrops fetalis, and may be the result of cerebrovascular changes both during and after the transfusion.

View details for DOI 10.1080/14767050701580960

View details for Web of Science ID 000250402500011

View details for PubMedID 17763280

Second-trimester ductus venosus measurement and adverse perinatal outcome in fetuses with congenital heart disease JOURNAL OF ULTRASOUND IN MEDICINE Bianco, K., Small, M., Julien, S., Kershaw, T., Michon, M., Copel, J. 2006; 25 (8): 97982


The purpose of this study was to determine whether Doppler velocimetry of the ductus venosus (DV) predicts adverse perinatal outcome in congenital heart disease (CHD).We conducted a retrospective cohort study of all pregnant women undergoing fetal echocardiography for CHD in a single perinatal center during a 2-year period. We compared outcomes for fetuses having a diagnosis of CHD in the second trimester and abnormal DV Doppler velocimetric findings with those having CHD and normal DV Doppler findings. Karyotype, gestational age at delivery, fetal loss rate, and rate of termination were assessed. The referral value for an abnormal DV pulsatility index was above the 95th percentile for gestational age. Statistical analysis included the t test, Fisher exact test, and chi(2) test.The incidence of CHD in our population was 7%. There were 98 patients with CHD; of those, 31 had DV measurement. A total of 9 patients had an abnormal DV. Three of this group (33%) had intrauterine fetal death or perinatal death. In patients with CHD and normal DV measurements, 83% had living children versus 33% in the group with an abnormal DV (P < .05). There was no statistically significant difference in the rate of aneuploidy between the normal DV (15%) and abnormal DV (20%) groups (P = .65). The mean gestational age at delivery was similar between the normal (37.63 weeks) and abnormal (38.33 weeks) DV groups (P = .71). There was no difference in the rate of pregnancy termination.Abnormal second-trimester DV measurements are predictive of adverse perinatal outcome in patients with CHD, independent of karyotype or gestational age at delivery. This information may have a role in the counseling of parents with CHD.

View details for DOI 10.7863/jum.2006.25.8.979

View details for Web of Science ID 000239445000005

View details for PubMedID 16870891

History of miscarriage and increased incidence of fetal aneuploidy in subsequent pregnancy OBSTETRICS AND GYNECOLOGY Bianco, K., Caughey, A. B., Shaffer, B. L., Davis, R., Norton, M. E. 2006; 107 (5): 10981102


The purpose of this study was to examine the association between history of spontaneous abortion and aneuploidy in a subsequent pregnancy.This was a retrospective cohort study of women who underwent fetal karyotype analysis with amniocentesis or chorionic villus sampling at a single prenatal diagnosis center. Information on spontaneous abortions, parity, maternal age, ethnicity, type of prenatal diagnosis, and karyotype was assessed. Univariable and multivariable analyses were conducted.A total of 46,939 women were included in our analysis. Women with no prior spontaneous abortions had a 1.39% risk for any aneuploidy. In women with one prior spontaneous abortion, this risk increased to 1.67%; for women with 2 previous spontaneous abortions, the risk increased to 1.84%; and for those women who had had 3 or more prior spontaneous abortions, the risk increased further to 2.18% (P < .007). When controlling for maternal age, parity, ethnicity, and mode of prenatal diagnosis and compared with women with no prior spontaneous abortions, women with one prior spontaneous abortion (adjusted odds ratio [AOR] 1.21, 95% confidence interval [CI] 1.01-1.47) or 3 or more prior spontaneous abortions (AOR 1.51, 95% CI 1.02-2.25) had a statistically significant increase in aneuploidy in a subsequent pregnancy. Women with 2 prior spontaneous abortions had an AOR of 1.26 for aneuploidy, but the 95% CI contained unity.An increased risk of karyotypic abnormality identified at the time of prenatal diagnosis is demonstrated in patients with an increasing number of spontaneous abortions. This study provides information regarding this risk among women presenting for prenatal diagnosis. According to our data, for a woman with an a priori risk of 1 in 300 for Down syndrome, 3 prior spontaneous abortions would increase that risk by 47% to 1 in 204. These results should be confirmed in low-risk populations.

View details for DOI 10.1097/01.AOG.0000215560.86673.22

View details for Web of Science ID 000241296500019

View details for PubMedID 16648416

Second trimester ductus venosus measurements as a predictor of adverse perinatal outcome in congenital heart disease Bianco, K., Small, M., Browne, N., Julien, S., Kershaw, T., Michon, M., Copel, J. MOSBY, INC. 2004: S173
Elevated estradiol levels in oocyte donation cycles do not impair ART outcomes for the recipients. Bianco, K., Mahutte, N. G., Arici, A., Duleba, A. J., Taylor, H. S., Sakkas, D. ELSEVIER SCIENCE INC. 2003: S165
Chronic antepartum maternal hyperoxygenation in a case of severe fetal Ebstein's anomaly with circular shunt physiology. Annals of pediatric cardiology Arunamata, A. n., Axelrod, D. M., Bianco, K. n., Balasubramanian, S. n., Quirin, A. n., Tacy, T. A. ; 10 (3): 28487


Perinatal mortality remains high among fetuses diagnosed with Ebstein's anomaly of the tricuspid valve. The subgroup of patients with pulmonary valve regurgitation is at particularly high risk. In the setting of pulmonary valve regurgitation, early constriction of the ductus arteriosus may be a novel perinatal management strategy to reduce systemic steal resulting from circular shunt physiology. We report the use of chronic antepartum maternal oxygen therapy for constriction of the fetal ductus arteriosus and modulation of fetal pulmonary vascular resistance in a late presentation of Ebstein's anomaly with severe tricuspid valve regurgitation, reversal of flow in the ductus arteriosus, and continuous pulmonary valve regurgitation.

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