Natali Aziz, M.D., M.S.

All Publications

• Treatment of Fetal Cystic Fibrosis With Cystic Fibrosis Transmembrane Conductance Regulator Modulation Therapy. Annals of internal medicine Blumenfeld, Y. J., Hintz, S. R., Aziz, N., Barth, R. A., Spano, J. M., El-Sayed, Y. Y., Milla, C. 2023

  View details for DOI 10.7326/L23-0112

  View details for PubMedID 37307583

• Importance of inclusive leadership in the pandemic response: the critical role of the physician. BMJ leader Destino, L., Lin, A., Mathew, R., Lee, T., Aziz, N., Claura, R., Kim, J., Lee, G. 2023

  Abstract

  The COVID-19 pandemic has resulted in multiple logistical and communication challenges in the face of ever-changing guidance, disease prevalence and increasing evidence.At Stanford Children's Health (SCH), we felt physician input was an important element of pandemic response infrastructure, given our lens into patient care across its continuum. We formed the COVID-19 Physician Liaison Team (CPLT) consisting of representative physicians across the care continuum. The CPLT met regularly and communicated to the SCH's COVID-19 task force responsible for the ongoing organisation pandemic response. The CPLT problem-solved around various issues including testing, patient care on our COVID-19 inpatient unit and communication gaps.The CPLT contributed to conservation of rapid COVID-19 tests for critical patient care needs, decreased incident reports on our COVID-19 inpatient unit and helped enhance communication across the organisation, with a focus on physicians.In retrospect, the approach taken was in line with a distributed leadership model with physicians as integral members contributing to active lines of communication, continual problem-solving and new pathways to provide care.

  View details for DOI 10.1136/leader-2022-000605

  View details for PubMedID 37192092

• Importance of inclusive leadership in the pandemic response: the critical role of the physician BMJ LEADER Destino, L., Lin, A., Mathew, R., Lee, T., Aziz, N., Claura, R., Kim, J., Lee, G. 2023

  View details for DOI 10.1136/leader-2022-000605

  View details for Web of Science ID 000910504000001

• Lactate and Procalcitonin Levels in Peripartum Women with Intraamniotic Infection. American journal of obstetrics & gynecology MFM DO, S. C., Miller, H. n., Leonard, S. A., Datoc, I. A., Girsen, A. I., Kappagoda, S. n., Gibbs, R. S., Aziz, N. n. 2021: 100367

  Abstract

  Serum biomarkers are used to diagnose and manage severe infections, but data on their utility during labor are limited. We compared lactate and procalcitonin levels in women with and without intraamniotic infection to determine if they are useful biomarkers for infection during labor.We performed a prospective observational cohort study of term, singleton pregnancies admitted with planned vaginal delivery in 2019 at a university medical center. Lactate and procalcitonin levels were drawn in early labor, within 2 hours following delivery, and postpartum day 1. Women with intraamniotic infection additionally had lactate and procalcitonin levels drawn following intraamniotic infection diagnosis. Samples were processed immediately in the hospital clinical laboratory. Primary outcome was mean lactate level following delivery. Secondary outcomes were lactate and procalcitonin levels at other time points. Comparisons based on infection status were performed using multivariate linear regression.22 women with intraamniotic infection and 29 uninfected women were included. Early labor mean lactate level (1.47 vs 1.49 mmol/L) and mean procalcitonin level (0.048 vs 0.039 ng/mL) did not differ and were normal in uninfected and intraamniotic infection groups. Mean lactate level was highest following delivery for women in uninfected and intraamniotic infection groups (2.00 vs 2.33 mmol/L, adjusted p=0.08, 95% CI 0.98-1.53). Lactate level returned to normal by postpartum day 1 and did not significantly differ based on the infection status at any time point in adjusted models. Procalcitonin level following delivery was higher among women with intraamniotic infection versus without infection (0.142 vs 0.091 ng/mL, adjusted p=0.03). Procalcitonin level rose further in both intraamniotic infection and uninfected groups on postpartum day 1 (0.737 vs 0.408 ng/mL, adjusted p=0.05).Lactate level is not significantly elevated in intraamniotic infection above the physiologic increase at delivery observed in women without infection. Procalcitonin level is elevated at delivery in women with intraamniotic infection and warrants further investigation as a peripartum infection marker.

  View details for DOI 10.1016/j.ajogmf.2021.100367

  View details for PubMedID 33831586

• 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

• Data-Driven Queries between Medications and Spontaneous Preterm Birth among 2.5 Million Pregnancies: Association with Genital Herpes and Antiviral Drugs. Maric, I., Borisenko, E., Winn, V. D., Weber, K. A., Wong, R. J., Aziz, N., Blumenfeld, Y. J., El-Sayed, Y. Y., Stevenson, D. K., Shaw, G. M. SAGE PUBLICATIONS INC. 2019: 389A

  View details for Web of Science ID 000459610400965

• Data-driven queries between medications and spontaneous preterm birth among 2.5 million pregnancies. Birth defects research Marić, I. n., Winn, V. D., Borisenko, E. n., Weber, K. A., Wong, R. J., Aziz, N. n., Blumenfeld, Y. J., El-Sayed, Y. Y., Stevenson, D. K., Shaw, G. M. 2019

  Abstract

  Our goal was to develop an approach that can systematically identify potential associations between medication prescribed in pregnancy and spontaneous preterm birth (sPTB) by mining large administrative "claims" databases containing hundreds of medications. One such association that we illustrate emerged with antiviral medications used for herpes treatment.IBM MarketScan® databases (2007-2016) were used. A pregnancy cohort was established using International Classification of Diseases (ICD-9/10) codes. Multiple hypothesis testing and the Benjamini-Hochberg procedure that limited false discovery rate at 5% revealed, among 863 medications, five that showed odds ratios (ORs) <1. The statistically strongest was an association between antivirals and sPTB that we illustrate as a real example of our approach, specifically for treatment of genital herpes (GH). Three groups of women were identified based on diagnosis of GH and treatment during the first 36 weeks of pregnancy: (a) GH without treatment; (b) GH treated with antivirals; (c) no GH or treatment.We identified 2,538,255 deliveries. 0.98% women had a diagnosis of GH. Among them, 60.0% received antiviral treatment. Women with treated GH had OR < 1, (OR [95% CI] = 0.91 [0.85, 0.98]). In contrast, women with untreated GH had a small increased risk of sPTB (OR [95% CI] =1.22 [1.14, 1.32]).Data-driven approaches can effectively generate new hypotheses on associations between medications and sPTB. This analysis led us to examine the association with GH treatment. While unknown confounders may impact these findings, our results indicate that women with untreated GH have a modest increased risk of sPTB.

  View details for DOI 10.1002/bdr2.1580

  View details for PubMedID 31433567

• Pregnancy-Induced Alterations in NK Cell Phenotype and Function. Frontiers in immunology Le Gars, M., Seiler, C., Kay, A. W., Bayless, N. L., Starosvetsky, E., Moore, L., Shen-Orr, S. S., Aziz, N., Khatri, P., Dekker, C. L., Swan, G. E., Davis, M. M., Holmes, S., Blish, C. A. 2019; 10: 2469

  Abstract

  Pregnant women are particularly susceptible to complications of influenza A virus infection, which may result from pregnancy-induced changes in the function of immune cells, including natural killer (NK) cells. To better understand NK cell function during pregnancy, we assessed the ability of the two main subsets of NK cells, CD56dim, and CD56bright NK cells, to respond to influenza-virus infected cells and tumor cells. During pregnancy, CD56dim and CD56bright NK cells displayed enhanced functional responses to both infected and tumor cells, with increased expression of degranulation markers and elevated frequency of NK cells producing IFN-gamma. To better understand the mechanisms driving this enhanced function, we profiled CD56dim and CD56bright NK cells from pregnant and non-pregnant women using mass cytometry. NK cells from pregnant women displayed significantly increased expression of several functional and activation markers such as CD38 on both subsets and NKp46 on CD56dim NK cells. NK cells also displayed diminished expression of the chemokine receptor CXCR3 during pregnancy. Overall, these data demonstrate that functional and phenotypic shifts occur in NK cells during pregnancy that can influence the magnitude of the immune response to both infections and tumors.

  View details for DOI 10.3389/fimmu.2019.02469

  View details for PubMedID 31708922

• Evaluation of Probiotic Oral Supplementation Effects on Group B Streptococcus Rectovaginal Colonization in Pregnant Women: A Randomized Double-Blind Placebo-Controlled Trial Aziz, N., Spiegel, A., Bentley, J., Yoffe, P., Klikoff, A., Ehrlich, K., El-Sayed, Y., Benitz, W., Norton, M. E., Taslimi, M. M. MOSBY-ELSEVIER. 2018: S509–S510

  View details for Web of Science ID 000423616600353

• Adverse pregnancy outcomes among women with urinary tract infections: comparison of sensitive and resistant organisms O'Malley, K., Suharwardy, S., Sie, L., Lee, H. C., Gibbs, R. S., Aziz, N. MOSBY-ELSEVIER. 2017: 734

  View details for Web of Science ID 000416950700088

• Hepatitis B DNA level for guidance of antiviral initiation timing in pregnant women for MTCT reduction Aziz, N., Chang, C. Y., Poongkunran, M., Javaid, A., Trinh, H. N., Lau, D., Nguyen, M. H. MOSBY-ELSEVIER. 2017: 720

  View details for Web of Science ID 000416950700053

• Serum Aminotransferase Flares in Pregnant and Postpartum Women With Current or Prior Treatment for Chronic Hepatitis B. Journal of clinical gastroenterology Chang, C. Y., Aziz, N., Poongkunran, M., Javaid, A., Trinh, H. N., Lau, D. T., Nguyen, M. H. 2017

  Abstract

  Antiviral therapy is recommended for pregnant women with chronic hepatitis B (CHB) and hepatitis B virus (HBV) DNA>200,000 IU/mL, but there is less consensus on management of women who discontinue therapy in anticipation of pregnancy or who become pregnant while on therapy. The goal of this study was to describe flares in alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women with current and/or prior treatment.This was a multicenter, retrospective study of 67 pregnancies in 56 CHB women treated before and/or during pregnancy. Main outcomes were frequency, severity, and resolution of ALT flare (≥5× upper limit of normal or ≥3× baseline, whichever was higher).During pregnancy, ALT flares (95 to 1064 U/L) were observed in 16% (7/43) of women who stopped treatment before pregnancy and 31% (4/13) of women who discontinued treatment during first trimester, many of whom had high HBV DNA levels (4.9 to 8.0 log IU/mL). No flares (0/11) were observed in women who continued treatment. Postpartum ALT flares (104 to 1584 U/L) were observed in 0% (0/15) of women who were completely untreated during pregnancy, 29% (2/7) of women who discontinued treatment in first trimester, 33% (3/9) of women who stopped treatment at delivery, and 22% (4/18) of women who continued treatment postpartum.In previously treated women with CHB, ALT flares were common during pregnancy and postpartum, especially if antiviral therapy was discontinued shortly before pregnancy, during first trimester, or at delivery. Thus, these pregnant women should be monitored closely throughout pregnancy and the early postpartum period; larger studies are needed to further characterize the natural history of HBV infection during pregnancy and postpartum.

  View details for DOI 10.1097/MCG.0000000000000822

  View details for PubMedID 28323748

• Hepatitis B DNA level for guidance of antiviral initiation timing in pregnant women for MTCT reduction Aziz, N., Chang, C., Poongkunran, M., Javaid, A., Trinh, H., Lau, D., Nguyen, M. MOSBY-ELSEVIER. 2017: S242–S243

  View details for Web of Science ID 000414256402030

• The Brief Case: Confirmed Positive HIV-1 Serologic Screening but Undetectable RNA Virus Load in a Pregnant Woman. Journal of clinical microbiology Joshi, R. P., Gomez, C. A., Steiner, D. n., Aziz, N. n., Pinsky, B. A. 2017; 55 (12): 3316–20

  View details for PubMedID 29180504

• The newborn human NK cell repertoire is phenotypically formed but functionally reduced CYTOMETRY PART B-CLINICAL CYTOMETRY Strauss-Albee, D. M., Liang, E. C., Ranganath, T., Aziz, N., Blish, C. A. 2017; 92 (1): 33-41

  Abstract

  Infection is a leading cause of death worldwide in babies under 1 month of age. Better vaccines and therapeutics are desperately needed for this vulnerable population.Because newborns rely heavily on the innate immune system, we evaluated cell phenotype and function of some of the earliest cellular responders during infection, natural killer (NK) cells. We used mass cytometry to provide a comprehensive comparison of NK cells from umbilical cord blood and adult peripheral blood.In unsupervised analyses, including viSNE and principal component analysis, the structure of the cord blood and adult NK cell repertoires are highly similar, distinguishable mainly by maturity-related markers expressed on rare subpopulations of cells. However, in functional analyses, cord blood NK cells show reduced degranulation and cytokine production following target recognition, as well as antibody-dependent cell-mediated cytotoxicity and apoptosis induction in targets.These findings show that the structure of the NK cell repertoire is intact at birth, suggesting great potential for vaccine and therapeutic strategies targeting this cell population. © 2016 International Clinical Cytometry Society.

  View details for DOI 10.1002/cyto.b.21485

  View details for Web of Science ID 000394980300005

• Closing the Brief Case: Confirmed Positive HIV-1 Serological Screening but Undetectable RNA Virus Load in a Pregnant Woman. Journal of clinical microbiology Joshi, R. P., Gomez, C. A., Steiner, D. n., Aziz, N. n., Pinsky, B. A. 2017; 55 (12): 3566–67

  View details for PubMedID 29180505

• Increased Proinflammatory Responses of Monocytes and Plasmacytoid Dendritic Cells to Influenza A Virus Infection During Pregnancy JOURNAL OF INFECTIOUS DISEASES Le Gars, M., Kay, A. W., Bayless, N. L., Aziz, N., Dekker, C. L., Swan, G. E., Davis, M. M., Blish, C. A. 2016; 214 (11): 1666-1671

  Abstract

  Pregnancy-induced alterations in immunity may contribute to the increased morbidity associated with influenza A virus infection during pregnancy. We characterized the immune response of monocytes and plasmacytoid dendritic cells (pDCs) to influenza A virus infection in 21 pregnant and 21 nonpregnant women. In pregnant women, monocytes and pDCs exhibit an exaggerated proinflammatory immune response to 2 strains of influenza A virus, compared with nonpregnant women, characterized by increased expression of major histocompatibility complex class II (approximately 2.0-fold), CD69 (approximately 2.2-fold), interferon γ-induced protein 10 (approximately 2.0-fold), and macrophage inflammatory protein 1β (approximately 1.5-fold). This enhanced innate inflammatory response during pregnancy could contribute to pulmonary inflammation following influenza A virus infection.

  View details for DOI 10.1093/infdis/jiw448

  View details for Web of Science ID 000393128800008

  View details for PubMedID 27655870

  View details for PubMedCentralID PMC5144734

• The newborn human NK cell repertoire is phenotypically formed but functionally reduced. Cytometry. Part B, Clinical cytometry Strauss-Albee, D. M., Liang, E. C., Ranganath, T., Aziz, N., Blish, C. A. 2016

  Abstract

  Infection is a leading cause of death worldwide in babies under 1 month of age. Better vaccines and therapeutics are desperately needed for this vulnerable population.Because newborns rely heavily on the innate immune system, we evaluated cell phenotype and function of some of the earliest cellular responders during infection, natural killer (NK) cells. We used mass cytometry to provide a comprehensive comparison of NK cells from umbilical cord blood and adult peripheral blood.In unsupervised analyses, including viSNE and principal component analysis, the structure of the cord blood and adult NK cell repertoires are highly similar, distinguishable mainly by maturity-related markers expressed on rare subpopulations of cells. However, in functional analyses, cord blood NK cells show reduced degranulation and cytokine production following target recognition, as well as antibody-dependent cell-mediated cytotoxicity and apoptosis induction in targets.These findings show that the structure of the NK cell repertoire is intact at birth, suggesting great potential for vaccine and therapeutic strategies targeting this cell population. © 2016 International Clinical Cytometry Society.

  View details for DOI 10.1002/cyto.b.21485

  View details for PubMedID 27718327

• Serum Alanine Aminotransferase and Hepatitis B DNA Flares in Pregnant and Postpartum Women with Chronic Hepatitis B. American journal of gastroenterology Chang, C. Y., Aziz, N., Poongkunran, M., Javaid, A., Trinh, H. N., Lau, D., Nguyen, M. H. 2016; 111 (10): 1410-1415

  Abstract

  Alterations in the immune system during pregnancy have been associated with reactivation of hepatitis B virus (HBV) in chronic hepatitis B (CHB) women. However, the effects of pregnancy on CHB remain not well understood. The goal of this study was to examine flares in HBV DNA and serum alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women untreated prior to pregnancy.This was a multicenter retrospective study of 113 pregnancies in 101 CHB women who presented during pregnancy at two community gastroenterology clinics and two tertiary medical centers in the United States during 1997-2015. Outcomes analyzed included onset, severity, and resolution of flares in HBV and ALT that occurred prior to starting antiviral therapy, if antiviral therapy was subsequently initiated. Women who initiated antiviral therapy during pregnancy were not included in the analysis of postpartum flares.HBV DNA flares were observed in 9% (8/90) of women during pregnancy and 4% (2/48) of women during postpartum. Flares in ALT (99-2522 U/l) were observed in 6% (7/112) of women during pregnancy and 10% (5/51) of women within the first 3 months of delivery. Age, HBeAg positivity, baseline HBV DNA, baseline ALT, gravida, and parity were not found to be significant predictors of flare.Flares in HBV DNA and ALT can occur during late pregnancy and early postpartum in CHB women, and can be severe. Women with CHB should therefore be closely monitored during pregnancy and early postpartum.Am J Gastroenterol advance online publication, 26 July 2016; doi:10.1038/ajg.2016.296.

  View details for DOI 10.1038/ajg.2016.296

  View details for PubMedID 27456990

• Pregnancy Does Not Attenuate the Antibody or Plasmablast Response to Inactivated Influenza Vaccine. journal of infectious diseases Kay, A. W., Bayless, N. L., Fukuyama, J., Aziz, N., Dekker, C. L., Mackey, S., Swan, G. E., Davis, M. M., Blish, C. A. 2015; 212 (6): 861-870

  Abstract

  Inactivated influenza vaccine (IIV) is recommended during pregnancy to prevent influenza infection and its complications in pregnant women and their infants. However, the extent to which pregnancy modifies the antibody response to vaccination remains unclear, and prior studies have focused primarily on hemagglutinin inhibition (HI) titers. A more comprehensive understanding of how pregnancy modifies the humoral immune response to influenza vaccination will aid in maximizing vaccine efficacy.Healthy pregnant women and control women were studied prior to, 7 days after, and 28 days after vaccination with IIV. HI titers, microneutralization (MN) titers, and the frequency of circulating plasmablasts were evaluated in pregnant versus control women.Pregnant women and control women mount similarly robust serologic immune responses to IIV, with no significant differences for any influenza strain in postvaccination geometric mean HI or MN titers. HI and MN titers correlate, though MN titers demonstrate more robust changes pre- versus postvaccination. The induction of circulating plasmablasts is increased in pregnant women versus controls (median fold-change 2.60 vs 1.49 [interquartile range, 0.94-7.53 vs 0.63-2.67]; P = .03).Pregnant women do not have impaired humoral immune responses to IIV and may have increased circulating plasmablast production compared to control women.

  View details for DOI 10.1093/infdis/jiv138

  View details for PubMedID 25740957

  View details for PubMedCentralID PMC4548461

• Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Kay, A. W., Fukuyama, J., Aziz, N., Dekker, C. L., Mackey, S., Swan, G. E., Davis, M. M., Holmes, S., Blish, C. A. 2014; 111 (40): 14506-14511

  Abstract

  Pregnant women experience increased morbidity and mortality after influenza infection, for reasons that are not understood. Although some data suggest that natural killer (NK)- and T-cell responses are suppressed during pregnancy, influenza-specific responses have not been previously evaluated. Thus, we analyzed the responses of women that were pregnant (n = 21) versus those that were not (n = 29) immediately before inactivated influenza vaccination (IIV), 7 d after vaccination, and 6 wk postpartum. Expression of CD107a (a marker of cytolysis) and production of IFN-γ and macrophage inflammatory protein (MIP) 1β were assessed by flow cytometry. Pregnant women had a significantly increased percentage of NK cells producing a MIP-1β response to pH1N1 virus compared with nonpregnant women pre-IIV [median, 6.66 vs. 0.90% (P = 0.0149)] and 7 d post-IIV [median, 11.23 vs. 2.81% (P = 0.004)], indicating a heightened chemokine response in pregnant women that was further enhanced by the vaccination. Pregnant women also exhibited significantly increased T-cell production of MIP-1β and polyfunctionality in NK and T cells to pH1N1 virus pre- and post-IIV. NK- and T-cell polyfunctionality was also enhanced in pregnant women in response to the H3N2 viral strain. In contrast, pregnant women had significantly reduced NK- and T-cell responses to phorbol 12-myristate 13-acetate and ionomycin. This type of stimulation led to the conclusion that NK- and T-cell responses during pregnancy are suppressed, but clearly this conclusion is not correct relative to the more biologically relevant assays described here. Robust cellular immune responses to influenza during pregnancy could drive pulmonary inflammation, explaining increased morbidity and mortality.

  View details for DOI 10.1073/pnas.1416569111

  View details for Web of Science ID 000342633900054

• Maternal proteinuria in twin compared with singleton pregnancies. Obstetrics and gynecology Osmundson, S. S., Lafayette, R. A., Bowen, R. A., Roque, V. C., Garabedian, M. J., Aziz, N. 2014; 124 (2): 332-337

  Abstract

  To compare 24-hour urinary protein excretion in twin and singleton pregnancies not complicated by hypertension.We prospectively evaluated mean 24-hour urinary protein excretion in twin and singleton pregnancies between 24 0/7 weeks and 36 0/7 weeks of gestation. Women with urinary tract infections, chronic hypertension, pregestational diabetes, and renal or autoimmune diseases were excluded. Collection adequacy was assessed by urinary creatinine excretion adjusted for maternal weight.Adequate samples were obtained from 50 twin and 49 singleton pregnancies at a mean gestational age of 30 weeks. At collection, the two groups were similar with regard to maternal age, gestational age, body mass index, and blood pressure. Mean urinary protein excretion was higher in twin compared with singleton pregnancies (269.3±124.1 mg compared with 204.3±92.5 mg, P=.004). Proteinuria (300 mg/day protein or greater) occurred in 38.0% (n=19) of twin and 8.2% (n=4) of singleton pregnancies (P<.001). After adjusting for confounding variables, the difference in mean total protein excretion remained significant (P=.004) and twins were more likely to have proteinuria compared with singleton pregnancies (adjusted odds ratio 9.1, 95% confidence interval 2.1-38.5). Nineteen participants developed a hypertensive disorder at a mean of 7.7 weeks after the urine collection (range 2.6-14.5 weeks). After excluding these women, proteinuria was present in 43% of twin and 7% of singleton pregnancies (P<.001).Mean 24-hour urinary protein excretion in twin pregnancies is greater than in singletons. These data suggest a reevaluation of the diagnostic criteria for preeclampsia in twin pregnancies.: II.

  View details for DOI 10.1097/AOG.0000000000000383

  View details for PubMedID 25004349

• Evaluation of serial urine viral cultures for the diagnosis of cytomegalovirus infection in neonates and infants. Pediatric and developmental pathology Chisholm, K. M., Aziz, N., McDowell, M., Guo, F. P., Srinivas, N., Benitz, W. E., Norton, M. E., Gutierrez, K., Folkins, A. K., Pinsky, B. A. 2014; 17 (3): 176-180

  Abstract

  Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide. Urine viral culture is the standard for CMV diagnosis in neonates and infants. The objectives of this study were to compare the performance of serial paired rapid shell vial cultures (SVC) and routine viral cultures (RVC), and to determine the optimal number of cultures needed to detect positive cases. From 2001 to 2011, all paired CMV SVC and RVC performed on neonates and infants less than 100 days of age were recorded. Testing episodes were defined as sets of cultures performed within 7 days of one another. A total of 1264 neonates and infants underwent 1478 testing episodes; 68 (5.4%) had at least one episode with a positive CMV culture. In episodes where CMV was detected before day 21 of life, the first specimen was positive in 100% (16/16) of cases. When testing occurred after 21 days of life, the first specimen was positive in 82.7% (43/52) of cases, requiring three cultures to reach 100% detection. The SVC was more prone to assay failure than RVC. Overall, when RVC was compared to SVC, there was 86.0% positive agreement and 99.9% negative agreement. In conclusion, three serial urine samples are necessary for detection of CMV in specimens collected between day of life 22 and 99, while one sample may be sufficient on or before day of life 21. Though SVC was more sensitive than RVC, the risk of SVC failure supports the use of multimodality testing to optimize detection.

  View details for DOI 10.2350/14-01-1432-OA.1

  View details for PubMedID 24617645

• Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY Aziz, N., Sokoloff, A., Kornak, J., Leva, N. V., Mendiola, M. L., Levison, J., Feakins, C., Shannon, M., Cohan, D. 2013; 120 (12): 1534-1547

  Abstract

  To compare time to achieve viral load <400 copies/ml and <1000 copies/ml in HIV-infected antiretroviral (ARV) -naive versus ARV-experienced pregnant women on highly active antiretroviral therapy (HAART).Retrospective cohort study.Three university medical centers, USA.HIV-infected pregnant women initiated or restarted on HAART during pregnancy.We calculated time to viral load <400 copies/ml and <1000 copies/ml in HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history.Time to HIV viral load <400 copies/ml and <1000 copies/ml.We evaluated 138 HIV-infected pregnant women, comprising 76 ARV-naive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load < 400 copies/ml during pregnancy compared with 92% of ARV-experienced women (P = 0.82). The median number of days to achieve a viral load < 400 copies/ml in the ARV-naive cohort was 25.0 (range 3.5-133; interquartile range 16-34) days compared with 27.0 (range 8-162.5; interquartile range 18.5-54.3) days in the ARV-experienced cohort (P = 0.02). In a multiple predictor analysis, women with higher adherence (adjusted relative hazard [aRH] per 10% increase in adherence 1.29, 95% confidence interval [CI] 1.08-1.54, P = 0.01) and receiving a non-nucleotide reverse transcriptase inhibitor (NNRTI) -based regimen (aRH 2.48, 95% CI 1.33-4.63, P = 0.01) were more likely to achieve viral load <400 copies/ml earlier. Increased baseline HIV log10 viral load was associated with a later time of achieving viral load <400 copies/ml (aRH 0.60, 95% CI 0.39-0.92, P = 0.02). In a corresponding model of time to achieve viral load <1000 copies/ml, adherence (aRH per 10% increase in adherence 1.79, 95% CI 1.34-2.39, P < 0.001), receipt of NNRTI (aRH 2.95, 95% CI 1.23-7.06, P = 0.02), and CD4 cell count (aRH per 50 count increase in CD4 1.12, 95% CI 1.03-1.22, P = 0.01) were associated with an earlier time to achieve viral load below this threshold. Increasing baseline HIV log10 viral load was associated with a longer time of achieving viral load <1000 copies/ml (aRH 0.54, 95% CI 0.34-0.86, P = 0.01). In multiple predictor models, previous ARV exposure was not significantly associated with time to achieve viral load below thresholds of <400 copies/ml and <1000 copies/ml.Pregnant women with ≥50% adherence, whether ARV-naive or ARV-experienced, on average achieve a viral load <400 copies/ml within a median of 26 days and a viral load of <1000 copies/ml within a median of 14 days of HAART initiation. Increased adherence, receipt of NNRTI-based regimen and lower baseline HIV log10 viral load were all statistically significant predictors of earlier time to achieve viral load <400 copies/ml and <1000 copies/ml. Increased CD4 count was statistically significant as a predictor of earlier time to achieve viral load <1000 copies/ml.

  View details for DOI 10.1111/1471-0528.12226

  View details for Web of Science ID 000325627200013

  View details for PubMedID 23924192

• Diagnosis of Congenital CMV Using PCR Performed on Formalin-fixed, Paraffin-embedded Placental Tissue. American journal of surgical pathology Folkins, A. K., Chisholm, K. M., Guo, F. P., McDowell, M., Aziz, N., Pinsky, B. A. 2013; 37 (9): 1413-1420

  Abstract

  Congenital cytomegalovirus (CMV) infection may be asymptomatic until hearing loss manifests in childhood. Because diagnosis of congenital CMV requires viral detection within an infant's first 21 days of life, CMV polymerase chain reaction (PCR) on formalin-fixed, paraffin-embedded (FFPE) placental tissue provides a unique opportunity to identify congenital exposure in cases in which CMV is not initially suspected. To assess the utility of this approach, a database of all CMV cultures performed from July 2001 to March 2012 was used to identify infants in whom urine CMV cultures were obtained within 100 days of life. Corresponding placentas were then identified through the pathology database. The database was also queried to identify placentas in which CMV immunohistochemical analysis had been performed. CMV PCR was positive in FFPE placental tissue from 100% (5/5) of cases in which the first urine culture collected before the first 21 days of life was positive. Placentas from 20 infants with negative CMV urine cultures were CMV PCR negative. Interestingly, CMV was detected in 12.5% (1/8) of placentas in which the first CMV-positive urine culture was collected after the first 21 days of life. Furthermore, 4% (1/26) of placentas with chronic villitis by histology (no urine cultures available) were CMV PCR positive. In the 10 CMV PCR-positive placentas, including 3 cases of fetal demise, CMV immunohistochemistry was positive in just 6 cases. These results suggest that the confirmation of CMV exposure in utero by PCR of FFPE placental tissue provides a useful adjunct to histologic evaluation and may identify infants requiring close clinical follow-up.

  View details for DOI 10.1097/PAS.0b013e318290f171

  View details for PubMedID 23797721

• Maternal bladder cancer diagnosed at routine first-trimester obstetric ultrasound examination. Obstetrics and gynecology Yeaton-Massey, A., Brookfield, K. F., Aziz, N., Mrazek-Pugh, B., Chueh, J. 2013; 122 (2): 464-467

  Abstract

  Bladder cancer is exceedingly rare in pregnancy and most commonly presents with gross hematuria.We describe two patients with the incidental finding of maternal bladder masses identified during routine first-trimester obstetric ultrasonographic evaluation and an ultimate diagnosis of carcinoma. After referral for urology evaluation and biopsy confirmation of bladder cancer, patients underwent surgical resection during their pregnancies without the need for further treatment and had uncomplicated pregnancy courses.The distended maternal urinary bladder at the time of first-trimester ultrasonographic evaluation offers a unique opportunity for examination and early diagnosis of incidental maternal bladder carcinoma.

  View details for DOI 10.1097/AOG.0b013e31828c5a4d

  View details for PubMedID 23884261

• Nonsurgical management of heterotopic abdominal pregnancy. Obstetrics and gynecology Yeh, J., Aziz, N., Chueh, J. 2013; 121 (2): 489-495

  Abstract

  Heterotopic abdominal pregnancies with coexisting intrauterine pregnancies pose unique therapeutic challenges, and management options, particularly nonsurgical approaches, are limited.We present a case in which selective reduction of a heterotopic abdominal pregnancy during the second trimester using fetal intracardiac injection with potassium chloride enabled subsequent vaginal delivery of the intrauterine pregnancy at term. In addition, we summarize nine cases of nonsurgical management of heterotopic abdominal pregnancies, four of which involve potassium chloride selective reduction. Our case is unique in that the abdominal fetus remained as a stable lithopedion, allowing the uncomplicated conception and vaginal delivery of a second intrauterine pregnancy without need for surgical intervention.Our case report and literature review demonstrate the use of selective potassium chloride reduction in managing heterotopic abdominal pregnancy nonsurgically.

  View details for DOI http://10.1097/AOG.0b013e3182736b09

  View details for PubMedID 23344419

• A first look at chorioamnionitis management practice variation among US obstetricians. Infectious diseases in obstetrics and gynecology Greenberg, M. B., Anderson, B. L., Schulkin, J., Norton, M. E., Aziz, N. 2012; 2012: 628362-?

  Abstract

  Objective. To examine practice patterns for diagnosis and treatment of chorioamnionitis among US obstetricians. Study Design. We distributed a mail-based survey to members of the American College of Obstetricians and Gynecologists, querying demographics, practice setting, and chorioamnionitis management strategies. We performed univariable and multivariable analyses. Results. Of 500 surveys distributed, 53.8% were returned, and 212 met study criteria and were analyzed. Most respondents work in group practice (66.0%), perform >100 deliveries per year (60.0%), have been in practice >10 years (77.3%), and work in a nonuniversity setting (85.1%). Temperature plus one additional criterion (61.3%) was the most common diagnostic strategy. Over 25 different primary antibiotic regimens were reported, including use of a single agent by 30.0% of respondents. A wide range of postpartum antibiotic duration was reported from no postpartum treatment (34.5% after vaginal delivery, 11.3% after cesarean delivery) to 48 hours of postpartum treatment (24.7% after vaginal delivery, 32.1% after cesarean delivery). No practitioner characteristic was independently associated with diagnostic or therapeutic strategies in multivariable analysis. Conclusion. There is a wide variation in contemporary clinical practices for the management of chorioamnionitis. This may represent a dearth of level I evidence. Future prospective clinical trials may provide more evidence-based practice recommendations for diagnosis and treatment of chorioamnionitis.

  View details for DOI 10.1155/2012/628362

  View details for PubMedID 23319852

  View details for PubMedCentralID PMC3540735

• Interferon Gamma Release Assay Compared With the Tuberculin Skin Test for Latent Tuberculosis Detection in Pregnancy OBSTETRICS AND GYNECOLOGY Worjoloh, A., Kato-Maeda, M., Osmond, D., Freyre, R., Aziz, N., Cohan, D. 2011; 118 (6): 1363-1370

  Abstract

  To estimate agreement and correlation between the tuberculin skin test and an interferon gamma release assay for detecting latent tuberculosis (TB) infection in pregnant women.We conducted a cross-sectional study of pregnant women initiating prenatal care at a university-affiliated public hospital between January 5, 2009, and March 15, 2010. Eligible women received a questionnaire about TB history and risk factors as well as the tuberculin skin test and phlebotomy for the interferon gamma release assay. Agreement and correlation between tests were estimated, and different cutoffs for interferon gamma release assay positivity were used to assess effect on agreement. Furthermore, predictors of test positivity and test discordance were evaluated using multivariable analysis.Of the 220 enrolled women, 199 (90.5%) returned for tuberculin skin test evaluation. Over 70% were Hispanic and 65% were born in a country with high TB prevalence. Agreement between the tuberculin skin test and interferon gamma release assay was 77.39 (κ=0.26). This agreement was not significantly changed using different cutoffs for the assay. Birth bacille Calmette-Guérin vaccination was associated with tuberculin skin test positivity (odds ratio [OR] 4.33, 95% confidence interval [CI] 1.4-13.48, P=.01), but not interferon gamma release assay positivity. There were no statistically significant predictors of the tuberculin skin test and interferon gamma release assay result discordance; however, birth in a high-prevalence country was marginally associated with tuberculin skin test-positive and interferon gamma release assay-negative results (OR 2.94, 95% CI 0.86-9.97 P=.08).Comparing the tuberculin skin test and interferon gamma release assay results in pregnancy, concordance and agreement were poor. Given that much is still unknown about the performance of interferon gamma release assays in pregnancy, further research is necessary before the tuberculin skin test is abandoned for screening of latent TB infection in pregnancy.III.

  View details for DOI 10.1097/AOG.0b013e31823834a9

  View details for Web of Science ID 000297338000022

  View details for PubMedID 22105266

  View details for PubMedCentralID PMC3232049

• Group B Streptococcus Colonization by HIV Status in Pregnant Women: Prevalence and Risk Factors JOURNAL OF WOMENS HEALTH Shah, M., Aziz, N., Leva, N., Cohan, D. 2011; 20 (11): 1737-1741

  Abstract

  To examine the prevalence of and risk factors for group B Streptococcus (GBS) colonization in an HIV-infected and uninfected pregnant population.We conducted a retrospective double cohort study comparing the prevalence of GBS colonization between 90 HIV-infected and 1947 uninfected women attending prenatal care at San Francisco General Hospital, an urban public hospital affiliated with the University of California, San Francisco. We investigated risk factors for GBS colonization, including age, ethnicity, obesity, diabetes, alcohol or illicit drug use, tobacco use, degree of immunosuppression, and infectious comorbidities.In the multivariable analysis, HIV serostatus was not independently associated with GBS colonization (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.62-1.62). Obesity (OR 1.53, 95% CI 1.13-2.07), white race (OR 1.89, 95% CI 1.30-2.75), and black race (OR 1.78, 95% CI 1.32-2.41) were independently associated with increased maternal GBS colonization. Among HIV-infected women, univariate analysis showed an association between GBS colonization and detectable HIV-1 plasma viral load at the time of rectovaginal culture (p<0.05). Mean CD4 lymphocyte count, infectious comorbidities, and HIV-1 plasma viral load at delivery were not associated with GBS colonization in HIV-infected pregnant women.HIV-1 infection is not a risk factor for GBS colonization among an ethnically diverse pregnant population at San Francisco General Hospital, although our data suggest that among HIV-infected women, plasma HIV-1 viremia may be associated with GBS colonization. Interventions that diminish HIV-1 plasma viral load and, perhaps, genital tract shedding of HIV may be associated with a reduced risk of GBS colonization in future studies.

  View details for DOI 10.1089/jwh.2011.2888

  View details for Web of Science ID 000296924400019

  View details for PubMedID 22011210

• Lymphoma in Pregnancy Initially Diagnosed as Vaginal Intraepithelial Neoplasia and Lichen Planus OBSTETRICS AND GYNECOLOGY Thuong-Thuong Nguyen, T. T., Gubens, M., Arber, D. A., Advani, R., Juretzka, M., Aziz, N. 2011; 118 (2): 486-489

  Abstract

  Non-Hodgkin's lymphoma presenting as a vaginal mass in pregnancy is uncommon.A 38-year-old primigravid woman presented at 27 weeks of gestation with vaginal lesions, bleeding, and discharge. Previous vaginal biopsies had been consistent with vaginal intraepithelial neoplasia 1 and lichen planus. After admission for this enlarging vaginal mass and bleeding, she was noted to have a newly palpable breast mass. Biopsy of the breast mass and subsequent re-evaluation of original vaginal biopsies were consistent with diffuse large B-cell lymphoma. She was treated with chemoimmunotherapy during pregnancy and delivered a viable neonate at term.Although benign vaginal conditions are common, non-Hodgkin's lymphoma should be considered in the differential diagnosis of persistent or enlarging vaginal lesions in pregnancy.

  View details for DOI 10.1097/AOG.0b013e3182234d12

  View details for PubMedID 21768862

• Antibody Treatment Promotes Compensation for Human Cytomegalovirus-Induced Pathogenesis and a Hypoxia-Like Condition in Placentas with Congenital Infection AMERICAN JOURNAL OF PATHOLOGY Maidji, E., Nigro, G., Tabata, T., McDonagh, S., Nozawa, N., Shiboski, S., Muci, S., Anceschi, M. M., Aziz, N., Adler, S. P., Pereira, L. 2010; 177 (3): 1298-1310

  Abstract

  Human cytomegalovirus (HCMV) is the major viral cause of birth defects worldwide. Affected infants can have temporary symptoms that resolve soon after birth, such as growth restriction, and permanent disabilities, including neurological impairment. Passive immunization of pregnant women with primary HCMV infection is a promising treatment to prevent congenital disease. To understand the effects of sustained viral replication on the placenta and passive transfer of protective antibodies, we performed immunohistological analysis of placental specimens from women with untreated congenital infection, HCMV-specific hyperimmune globulin treatment, and uninfected controls. In untreated infection, viral replication proteins were found in trophoblasts and endothelial cells of chorionic villi and uterine arteries. Associated damage included extensive fibrinoid deposits, fibrosis, avascular villi, and edema, which could impair placental functions. Vascular endothelial growth factor and its receptor fms-like tyrosine kinase 1 (Flt1) were up-regulated, and amniotic fluid contained elevated levels of soluble Flt1 (sFlt1), an antiangiogenic protein, relative to placental growth factor. With hyperimmune globulin treatment, placentas appeared uninfected, vascular endothelial growth factor and Flt1 expression was reduced, and sFlt1 levels in amniotic fluid were lower. An increase in the number of chorionic villi and blood vessels over that in controls suggested compensatory development for a hypoxia-like condition. Taken together the results indicate that antibody treatment can suppress HCMV replication and prevent placental dysfunction, thus improving fetal outcome.

  View details for DOI 10.2353/ajpath.2010.091210

  View details for Web of Science ID 000281717700026

  View details for PubMedID 20651234

• The Effects of Respiratory Failure on Delivery in Pregnant Patients With H1N1 2009 Influenza OBSTETRICS AND GYNECOLOGY Jafari, A., Langen, E. S., Aziz, N., Blumenfeld, Y. J., Mihm, F., Druzin, M. L. 2010; 115 (5): 1033-1035

  Abstract

  The majority of hospitalizations for H1N1 complications have been in people with high-risk comorbidities, including pregnancy. Here we describe the obstetric and critical care treatment of three patients with confirmed H1N1 influenza virus infection complicated by acute respiratory failure.We describe the clinical and therapeutic courses of three patients with confirmed H1N1 2009 influenza virus infection complicating singleton, twin, and triplet gestations, each of which were complicated by respiratory failure.These three cases illustrate that a high index of suspicion, prompt treatment, timing and mode of delivery considerations, and interdisciplinary treatment are integral to the care of pregnant patients with H1N1 influenza infections complicated by acute respiratory failure.

  View details for DOI 10.1097/AOG.0b013e3181da85fc

  View details for PubMedID 20410779

• Neonatal outcomes in the setting of preterm premature rupture of membranes complicated by chorioamnionitis 32nd Annual Meeting of the Infectious-Disease-Society-for-Obstetrics-and-Gynecology Aziz, N., Cheng, Y. W., Caughey, A. B. TAYLOR & FRANCIS LTD. 2009: 780–84

  Abstract

  To examine the outcomes of neonates born to women with chorioamnionitis in the setting of preterm premature rupture of membranes (PPROM).A retrospective cohort study was conducted of deliveries with diagnosis of PPROM between 24 and 34 weeks of gestation at an academic medical center. Patients who delivered with the diagnosis of clinical chorioamnionitis were compared with patients who delivered without this diagnosis. Neonatal outcomes including Apgar scores, intracranial hemorrhage (ICH), sepsis, pneumonia, respiratory distress syndrome (RDS), and necrotizing enterocolitis (NEC) were assessed. Dichotomous outcomes were compared using chi-square test. Multivariable regression analyses were performed to control for potential confounding variables.Of the 1153 patients diagnosed with PPROM, 29.0% were diagnosed with chorioamnionitis prior to delivery. Neonates born to mothers with a diagnosis of chorioamnionitis in the setting of PPROM had higher incidences (34.8%) of low 5-min Apgar scores, RDS, NEC, ICH, and pneumonia compared with 22.9% in neonates born to mothers without chorioamnionitis (p < 0.001).Patients who develop chorioamnionitis in the setting of PPROM are at higher risk for adverse neonatal outcomes compared with patients without chorioamnionitis in the setting of PPROM.

  View details for DOI 10.1080/14767050902922581

  View details for Web of Science ID 000270226700011

  View details for PubMedID 19557664

• Factors and outcomes associated with longer latency in preterm premature rupture of membranes JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Aziz, N., Cheng, Y. W., Caughey, A. B. 2008; 21 (11): 821-825

  Abstract

  To examine factors and outcomes associated with latency in preterm premature rupture of membranes (PPROM).A retrospective cohort study was conducted of all deliveries with a diagnosis of PPROM at 24-34 weeks of gestation at an academic medical center for the period 1980-2001. Gestational age at PPROM was examined as the primary independent variable. Primary outcome was duration from rupture of membranes until delivery. The association with neonatal and maternal perinatal morbidity was examined with duration of latency. Dichotomous outcomes were compared using the Chi-square test. Multivariable regression analyses were performed to control for potential confounding variables.One thousand one hundred and sixty-eight patients were identified. Latency duration was inversely associated with gestational age at time of PPROM (p < 0.001). These findings persisted when potential confounders were controlled for in multivariable models. Neonatal sepsis and chorioamnionitis were not associated with increased duration of latency.Earlier gestational age at time of PPROM is associated with longer latency duration, which, in turn, is not associated with increased neonatal sepsis or chorioamnionitis. These data can be used to counsel patients with PPROM about expected duration of latency and outcomes.

  View details for DOI 10.1080/14767050802251255

  View details for Web of Science ID 000261172900008

  View details for PubMedID 19031278

• Comparison of rapid intrapartum screening methods for group B streptococcal vaginal colonization JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Aziz, N., Baron, E. J., D'Souza, H., Nourbakhsh, M., Druzin, M. L., Benitz, W. E. 2005; 18 (4): 225-229

  Abstract

  To compare optical immunoassay (OIA) and rapid polymerase-chain reaction (PCR) with enrichment broth culture for intrapartum detection of vaginal group B streptococcal (GBS) colonization.Paired vaginal swabs from 315 consecutive term pregnant women at the time of presentation for delivery to a university medical center were tested for GBS by OIA, PCR, and culture. Sensitivity, specificity, and positive and negative predictive values were calculated.Vaginal colonization was identified by culture in 56 subjects (17.8%). The sensitivity of OIA (7.1%, 95% confidence interval 5.1-9.5%) was significantly less than that of unenhanced rapid PCR (62.5%, 95% CI 48.5-74.8%).Neither PCR nor OIA is sufficiently sensitive for intrapartum detection of vaginal GBS colonization. Rapid PCR is more sensitive, but further improvements in technique to increase sensitivity will be necessary if PCR is to have a useful role in the management of women at time of presentation for delivery.

  View details for DOI 10.1080/14767050500278048

  View details for Web of Science ID 000234009900003

  View details for PubMedID 16318971

• Severe intrauterine growth restriction associated with the development of a submucosal leiomyoma during pregnancy - A case report JOURNAL OF REPRODUCTIVE MEDICINE Aziz, N., Lenzi, T. A., Milki, A. A. 2005; 50 (7): 553-556

  Abstract

  Small, intramural leiomyomas are not generally considered a risk factor for poor reproductive outcomes.A patient with a 6-mm intramural leiomyoma and a normal uterine cavity by hysteroscopic evaluation who conceived after in vitro fertilization developed severe early-onset intrauterine growth restriction (IUGR), leading to pregnancy termination at 23.4 weeks' gestation. At 6 weeks postpartum, a 1.7-cm, intracavitary leiomyoma was detected on ultrasound evaluation and removed by hysteroscopic resection. The patient conceived in a subsequent in vitro fertilization cycle and gave birth to monozygotic twins with appropriate weights at 34 weeks of gestation. In the absence of other identifiable etiologies of the IUGR, it is plausible that the small, intramural leiomyoma enlarged and migrated into the cavity, causing abnormal placentation and leading to fetal growth restriction in the first pregnancy.Uterine cavity reevaluation is recommended in the investigation of IUGR before a woman attempts further pregnancies.

  View details for PubMedID 16130857

• Postpartum uterine arteriovenous fistula OBSTETRICS AND GYNECOLOGY Aziz, N., Lenzi, T. A., Jeffrey, R. B., Lyell, D. J. 2004; 103 (5): 1076-1078

  Abstract

  Uterine arteriovenous communications are uncommon lesions that may be associated with life-threatening postpartum and postinstrumentation hemorrhage.A primigravida presented with infected retained products of conception. Excessive hemorrhage of unclear etiology occurred at dilation and curettage. After a second episode of bleeding, the patient received a diagnosis of uterine arteriovenous fistula.Uterine arteriovenous communications should be included in the differential diagnosis in patients with excessive postpartum or postinstrumentation bleeding. Color and spectral flow Doppler can aid diagnosis and clinical management.

  View details for DOI 10.1097/01.AOG.0000123241.44401.01

  View details for Web of Science ID 000225470300017

  View details for PubMedID 15121613