Publications by authors named "Peter G Napolitano"

49 Publications

Institutional prevalence of class III obesity modifies risk of adverse obstetrical outcomes.

Am J Obstet Gynecol MFM 2020 Feb 25;2(1):100058. Epub 2019 Oct 25.

Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, University of Washington, Seattle WA.

Background: Women with prepregnancy class III obesity (body mass index ≥40 kg/m) are at an increased risk of perinatal complications and adverse obstetrical outcomes. Estimates of the magnitude of risk that these women face vary widely, which may reflect differences in institutional experience caring for women with obesity.

Objective: We sought to characterize the relationship between institutional prevalence of prepregnancy class III obesity and the risk of adverse perinatal outcomes among these women, hypothesizing that higher-prevalence institutions would have lower rates of adverse maternal and perinatal outcomes among this population.

Study Design: We conducted a retrospective cohort study using chart-abstracted data on births in Washington state from Jan. 1, 2012, to Dec. 31, 2017. The analysis was restricted to hospitals that delivered at least 1 patient per month with prepregnancy class III obesity. Institutional prevalence of prepregnancy class III obesity was calculated, and hospitals were classified as either high or low prevalence. We included nulliparous women with vertex-presenting singleton pregnancies at ≥37 weeks of gestation. We excluded births with missing initial body mass index. The primary outcome was the incidence of cesarean delivery. Secondary outcomes were induction of labor, postpartum complications, postpartum readmission, and neonatal intensive care unit admissions. We compared outcomes between women with prepregnancy class III and all obesity at high- and low-prevalence hospitals using the χ test or the Fishers exact test as appropriate. Binary logistic regression was performed to compare outcomes at high- and low-prevalence hospitals. A hospital-adjusted multivariable regression model that controlled for baseline institutional rates of each outcome and compared outcomes between high- and low-prevalence hospitals was developed. A final multivariable logistic regression that controlled for both baseline institutional variation as well as potential clinical confounders was performed.

Results: A total of 20,556 women at 6 hospitals were eligible for inclusion; the prevalence of prepregnancy class III obesity was 6.2% and 2.1% in high- and low-prevalence hospitals, respectively. Obese women, including those with class III obesity in a high-prevalence hospital, were more likely to be Latina and less likely to be of advanced maternal age and carry private insurance. After adjusting for the institutional cesarean delivery rate, women with prepregnancy class III obesity had significantly increased odds of cesarean delivery (odds ratio, 1.53, 95% confidence interval, 1.12-2.10); however, after adjusting for significant covariates, the association no longer achieved significance (odds ratio, 1.68, 95% confidence interval, 0.97-2.94). The hospital-adjusted odds of postpartum readmission were significantly increased for women with prepregnancy class III obesity when delivering in low-prevalence institutions (odds ratio, 6.61, 95% confidence interval, 1.93-22.56), and the association was further strengthened after controlling for significant covariates (odds ratio, 15.20, 95% confidence interval, 2.32-99.53). None of the models demonstrated significantly different odds of induction of labor, postpartum complications, or neonatal intensive care unit admission by institutional prevalence of prepregnancy class III obesity.

Conclusion: Even after controlling for underlying hospital and subject characteristics, women with prepregnancy class III obesity had significantly increased odds of postpartum readmission, and a trend toward increased odds of cesarean delivery, when delivering in institutions with less experience caring for women with obesity.
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http://dx.doi.org/10.1016/j.ajogmf.2019.100058DOI Listing
February 2020

Correction: The orphan nuclear receptor Nr4a1 mediates perinatal neuroinflammation in a murine model of preterm labor.

Cell Death Dis 2020 Jun 30;11(6):495. Epub 2020 Jun 30.

Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41419-020-2682-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327040PMC
June 2020

The orphan nuclear receptor Nr4a1 mediates perinatal neuroinflammation in a murine model of preterm labor.

Cell Death Dis 2020 01 6;11(1):11. Epub 2020 Jan 6.

Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA, USA.

Prematurity is associated with perinatal neuroinflammation and injury. Screening for genetic modulators in an LPS murine model of preterm birth revealed the upregulation of Nr4a1, an orphan nuclear transcription factor that is normally absent or limited in embryonic brains. Concurrently, Nr4a1 was downregulated with magnesium sulfate (MgSO) and betamethasone (BMTZ) treatments administered to LPS exposed dams. To understand the role of Nr4a1 in perinatal brain injury, we compared the preterm neuroinflammatory response in Nr4a1 knockout (KO) versus wild type (wt) mice. Key inflammatory factors Il1b, Il6 and Tnf, and Iba1+ microglia were significantly lower in Nr4a1 KO versus wt brains exposed to LPS in utero. Treatment with MgSO/BMTZ mitigated the neuroinflammatory process in wt but not Nr4a1 KO brains. These results correspond with a reduction in cerebral hemorrhage in wt but not mutant embryos from dams given MgSO/BMTZ. Further analysis with Nr4a1-GFP-Cre × tdTomato loxP reporter mice revealed that the upregulation of Nr4a1 with perinatal neuroinflammation occurs in the cerebral vasculature. Altogether, this study implicates Nr4a1 in the developing vasculature as a potent mediator of neuroinflammatory brain injury that occurs with preterm birth. It is also possible that MgSO/BMTZ mitigates this process by direct or indirect inhibition of Nr4a1.
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http://dx.doi.org/10.1038/s41419-019-2196-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944691PMC
January 2020

Perinatal Pyogenic Liver Abscess: A Rare Entity and First Reported Case of .

AJP Rep 2019 Jul 20;9(3):e251-e255. Epub 2019 Aug 20.

Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Madigan Army Medical Center, Tacoma, Washington.

 Pyogenic liver abscess (PLA) is a rare clinical entity, occurring in ∼2.3 per 100,000 patients. Perinatal PLA syndromes are exceedingly rare with just seven previously described cases in the literature and no prior Klebsiella-associated reports.  A 29-year-old gravida 2 para 1 woman at 11 weeks gestation reporting fever, body aches, and headache. Search for an infectious source identified a 4-cm liver abscess. Percutaneous drainage confirmed infection. The patient was treated with antibiotics until imaging verified complete resolution of the abscess.  PLA is an uncommon etiology of sepsis in pregnancy. A thorough workup until a source was identified resulted in accurate diagnosis. This allowed for directed therapy and prompt recovery, undoubtedly contributing to favorable pregnancy outcomes in this first report of Klebsiella-associated perinatal PLA.
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http://dx.doi.org/10.1055/s-0039-1692713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702024PMC
July 2019

The Role of Extremes in Interpregnancy Interval in Women at Increased Risk for Adverse Obstetric Outcomes Due to Health Disparities: 
A Literature Review.

Curr Womens Health Rev 2018 Oct;14(3):242-250

Division of Maternal Fetal Medicine, Massachusetts General Hospital, BostonMA, USA.

Background: The interpregnancy interval (IPI) defines the time between two consecutive gestations. In the general population, women with IPIs that fall outside the recommended 18-24 month range appear to be at modestly increased risk for adverse obstetric outcomes.

Objective: The aim of this review was to assess the impact of extremes in IPI in populations with an increased baseline risk for adverse obstetric outcomes due to disparities in health and health care, including racial and ethnic groups, adolescents, and those of lower socioeconomic status.

Methods: We conducted a MEDLINE/Pubmed literature search in February 2016. Identified articles were reviewed and assigned a level of evidence.

Results: The 24 studies included in our final review were mainly retrospective with considerable heterogeneity in definitions and outcomes that prevented a quantitative meta-analysis.

Conclusion: The results of our review suggest that at-risk populations may have an increased frequency of shortened IPIs though the impact appears to be moderate and inconsistent. There was insufficient evidence to draw meaningful conclusions regarding a prolonged IPI or the effect of interventions. Based on the current literature, under-served populations are more likely to have a shortened IPI which increased the incidence of prematurity and low birth weight in some groups though the effect on additional obstetric outcomes is difficult to assess.
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http://dx.doi.org/10.2174/1573404813666170323154244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198477PMC
October 2018

Evaluating maternal hyperglycemic exposure and fetal placental arterial dysfunction in a dual cotyledon, dual perfusion model.

Placenta 2018 09 1;69:109-116. Epub 2018 Aug 1.

Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA, USA. Electronic address:

Background: Gestational diabetes affects almost 1 in 10 pregnancies and is associated with adverse outcomes including fetal demise. Pregnancy complications related to diabetes are attributed to placental vascular dysfunction. With diabetes, maternal hyperglycemia is thought to promote placental vasoconstriction. However, it remains poorly understood if and how hyperglycemia leads to placental vascular dysfunction or if humoral factors related to maternal diabetes are responsible.

Methods And Results: Utilizing a human placenta dual cotyledon, dual perfusion assay we examined the arterial pressure response to the thromboxane mimetic U44619, in cotyledons exposed to normal vs. a hyperglycemic infusion into the intervillous space. Tissues were then analyzed for the activity of key signaling molecules related to vascular tone; eNOS, Akt, PKA and VEGFR2. Results indicate a significant increase in fetal vascular resistance with maternal exposure to hyperglycemia. This response corresponded with a reduction in the phosphorylation of eNOS at Ser1177 and Akt at Thr308. In contrast, VEGFR2 at Tyr1175 and PKA at Thr197 were not different with hyperglycemia.

Conclusion: Reductions of eNOS and Akt phosphorylation at key residues implicated in nitric oxide production suggest that hyperglycemia alters the vasodilatory signaling of placental vessels. In contrast, acute hyperglycemic exposure may not alter vasoconstriction via VEGF and PKA signaling. Altogether our results link hyperglycemic exposure in human placentas to nitric oxide signaling; a mechanisms that may account for the elevations in vascular resistance commonly observed in diabetic pregnancies.
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http://dx.doi.org/10.1016/j.placenta.2018.07.015DOI Listing
September 2018

Evaluation of Sildenafil and Tadalafil for Reversing Constriction of Fetal Arteries in a Human Placenta Perfusion Model.

Hypertension 2018 07 7;72(1):167-176. Epub 2018 May 7.

Department of Clinical Investigation (N.I.), Madigan Army Medical Center, Joint Base Lewis-McCord, Tacoma, WA.

Fetal growth restriction resulting from reduced placental blood perfusion is a major cause of neonatal morbidity and mortality. Aside from intense surveillance and early delivery, there is no treatment for fetal growth restriction. A potential treatment associated with placental vasoconstriction is the class of PDE5 (phosphodiesterase type 5) inhibitors such as sildenafil, which is known to cross the placenta. In contrast, tadalafil, a more potent and selective PDE5 inhibitor has not been studied in pregnancy or experimental models of fetal growth restriction. Therefore, we compared the efficacy of these 2 PDE5 inhibitors for reversing vasoconstriction in an ex vivo human placental model and evaluating molecular and physiological responses. Sildenafil and tadalafil were infused into the intervillous space in a preconstricted human placental dual cotyledon, dual perfusion assay for the comparison of arteriole pressures and molecular indicators of drug inhibition. Results indicate a decrease arterial pressure with sildenafil citrate compared with controls, whereas tadalafil showed no difference. PDE5 and endothelial nitric oxide synthase activity were altered with sildenafil but not tadalafil. Sildenafil citrate improved preconstricted placental arterial perfusion in a human placental model, whereas tadalafil showed no response. It is possible that tadalafil did not cross the human placental barrier or was degraded by trophoblasts. This study supports human clinical trials exploring sildenafil as a potential treatment for improving fetal blood flow in fetal growth restriction associated with vasoconstriction.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.10738DOI Listing
July 2018

Long-term impact of intrauterine neuroinflammation and treatment with magnesium sulphate and betamethasone: Sex-specific differences in a preterm labor murine model.

Sci Rep 2017 12 20;7(1):17883. Epub 2017 Dec 20.

Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA, USA.

Preterm infants are at significantly increased risk for lifelong neurodevelopmental disability with male offspring disproportionately affected. Corticosteroids (such as betamethasone) and magnesium sulphate (MgSO) are administered to women in preterm labor to reduce neurologic morbidity. Despite widespread use of MgSO in clinical practice, its effects on adult offspring are not well known nor have sex-specific differences in therapeutic response been explored. The objective of our study was to examine the long-term effects of perinatal neuroinflammation and the effectiveness of prenatal MgSO/betamethasone treatments between males and females in a murine model via histologic and expression analyses. Our results demonstrate that male but not female offspring exposed to intrauterine inflammation demonstrated impaired performance in neurodevelopmental testing in early life assessed via negative geotaxis, while those exposed to injury plus treatment fared better. Histologic analysis of adult male brains identified a significant reduction in hippocampal neural density in the injured group compared to controls. Evaluation of key neural markers via qRT-PCR demonstrated more profound differences in gene expression in adult males exposed to injury and treatment compared to female offspring, which largely showed resistance to injury. Prenatal treatment with MgSO/betamethasone confers long-term benefits beyond cerebral palsy prevention with sex-specific differences in response.
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http://dx.doi.org/10.1038/s41598-017-18197-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738437PMC
December 2017

High transverse skin incisions may reduce wound complications in obese women having cesarean sections: a pilot study.

J Matern Fetal Neonatal Med 2019 Mar 1;32(5):781-785. Epub 2017 Nov 1.

b Department of OB/GYN , University of Arkansas for Medical Sciences , Little Rock , AR , USA.

Objective: Women having cesarean section have a high risk of wound complications. Our objective was to determine whether high transverse skin incisions are associated with a reduced risk of cesarean wound complications in women with BMI greater than 40.

Methods: A retrospective cohort study was undertaken of parturients ages 18-45 with BMI greater than 40 having high transverse skin incisions from January 2010 to April 2015 at a tertiary maternity hospital. Temporally matched controls had low transverse skin incisions along with a BMI greater than 40. The primary outcome, wound complication, was defined as any seroma, hematoma, dehiscence, or infection requiring opening and evacuating/debriding the wound. Secondary outcomes included rates of endometritis, number of hospital days, NICU admission, Apgar scores, birth weight, and gestational age at delivery. Analysis of outcomes was performed using two-sample t-test or Wilcoxon rank-sum test for continuous variables and Fisher's exact test for categorical variables.

Results: Thirty-two women had high transverse incisions and were temporally matched with 96 controls (low transverse incisions). The mean BMI was 49 for both groups. There was a trend toward reduced wound complications in those having high transverse skin incisions, but this did not reach statistical significance (15.63% versus 27.08%, p = .2379). Those having high transverse skin incisions had lower five minute median Apgar scores (8.0 versus 9.0, p = .0021), but no difference in umbilical artery pH values. The high transverse group also had increased NICU admissions (28.13% versus 5.21%, p = .0011), and early gestational age at delivery (36.8 versus 38.0, p = .0272).

Conclusion: High transverse skin incisions may reduce the risk of wound complications in parturients with obesity. A study with more power should be considered.
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http://dx.doi.org/10.1080/14767058.2017.1391780DOI Listing
March 2019

Bacterial endotoxin exposure invokes transcriptional changes in embryonic murine neural stem cells.

Am J Obstet Gynecol 2017 10 20;217(4):488-489. Epub 2017 Jul 20.

Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2017.07.016DOI Listing
October 2017

in Pregnancy: A Review of the Literature.

Obstet Gynecol Surv 2017 Apr;72(4):242-247

Director of MFM Fellowship, Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, WA.

Importance: is commonly found in many areas of the body where it derives a benefit without harming the host. When it does infect the host during pregnancy, is that infection a threat to the obstetric patient and does that infection cause adverse pregnancy outcomes?

Objective: The aim of this study was to review what is known about infections and the impact of an infection on pregnancy outcomes.

Evidence Acquisition: A PubMed search was undertaken with the search years unlimited to April 1, 2016, and restricted to articles in English. The search terms included "actinomyces," "pregnancy," "prenatal," "maternal," "actinomyces infection," "pregnancy," "chorioamnionitis," "preterm labor," "premature birth," or "postpartum actinomyces."

Results: Eighteen of the 154 identified articles are the basis of this review. is a rod-like positive bacterium. The diagnosis of an infection can be by culture or Gram stain. is commensal and typically only infects after a mucosal break or lesion. Seventeen cases were identified in pregnancy. Ten cases were complicated by chorioamnionitis and a preterm delivery. A nidus leading to infection was identified in 12 of the cases including women with a cervical cerclage, dental abscesses, appendicitis, renal actinomycosis, and ovarian abscesses. Adverse pregnancy outcomes have been linked with periodontal disease, but treatment did not prevent preterm delivery in a randomized, blinded, controlled trial.

Conclusions: infections in pregnancy are rare but, if they occur, have been linked primarily with preterm deliveries.

Target Audience: Obstetricians and gynecologists, family physicians.

Learning Objectives: After completing this activity, the learner should be better able to identify the areas of the body where infections occur and how the infections typically occur, identify the pathophysiologic changes that occur during pregnancy that might lead to an infection and how that infection may affect pregnancy outcomes, and describe the treatment for mild and severe infections.
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http://dx.doi.org/10.1097/OGX.0000000000000423DOI Listing
April 2017

Observations of fetal brain activity via non-invasive magnetoencephalography following administration of magnesium sulfate for neuroprotection in preterm labor.

Prenat Diagn 2016 Oct 20;36(10):982-984. Epub 2016 Sep 20.

Division of Maternal Fetal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

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http://dx.doi.org/10.1002/pd.4919DOI Listing
October 2016

Chorionic Villus Sampling, Early Amniocentesis, and Termination of Pregnancy Without Diagnostic Testing: Comparison of Fetal Risk Following Positive Non-invasive Prenatal Testing.

J Obstet Gynaecol Can 2016 05 23;38(5):441-445.e2. Epub 2016 Apr 23.

Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma WA.

Background: With the increased accuracy of non-invasive prenatal testing (NIPT) based on cell-free DNA (cfDNA) techniques, the likelihood of false-positive screening results has been reduced for high-risk populations. Following a positive screening test, a diagnostic procedure to confirm the result is strongly recommended, although some patients have terminated pregnancies because of a positive NIPT alone. Chorionic villus sampling (CVS), the diagnostic procedure of choice in the first trimester, is not available in all locations. Amniocentesis before 15 weeks, referred to as early amniocentesis (EA), is associated with a 1% rate of talipes and an increased rate of early pregnancy loss compared with CVS. Our objective was to compare the level of risk for euploid pregnancies following a positive NIPT based on the invasive procedure chosen.

Method: Using data from a 2003 meta-analysis, we estimated the rates of adverse pregnancy outcome in euploid pregnancies based on the positive predictive value (PPV) of NIPT and the invasive procedure used-that is, CVS, EA, or termination of pregnancy (TOP).

Results: Following NIPT, we found that the rate of adverse fetal outcomes in euploid pregnancies was lower for CVS than for EA at all PPV levels. As the PPV of NIPT increased, the difference in risk between EA and CVS decreased. The risk to euploid pregnancies of TOP was excessive at all PPVs.

Conclusion: CVS is the recommended diagnostic test in the first trimester because it is safer than EA for the fetus. However, EA is better than no testing when early TOP is planned. Patients should be strongly counselled against TOP without confirmatory testing.
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http://dx.doi.org/10.1016/j.jogc.2016.03.006DOI Listing
May 2016

Fish Parasites: A Growing Concern During Pregnancy.

Obstet Gynecol Surv 2016 Apr;71(4):253-9

Professor, MFM Division and Fellowship Director, University of Arkansas for Medical Sciences, Little Rock, AR.

Intestinal parasitic worms affect more than 2 billion people worldwide according to the World Health Organization. Fish-borne parasitic infections are becoming more common with the increasing popularity of sushi, sashimi, Carpaccio, tartare, gefilte, and ceviche. The ingestion of these parasites can cause serve anemia, malabsorption, severe abdominal pain, nausea, vomiting, strong allergic reactions, and gastric ulcers. Knowledge about fish parasites and pregnancy is limited. A literature search on PubMed and Web of Science used the search terms "fish parasites" OR "diphyllobothrium" OR "anisakiasis" OR "pseudoterranova" OR ("food borne parasites" AND "fish") AND "pregnancy" OR "maternal" OR "fetus" OR "fetal" OR "newborn" OR "neonatal" OR "childbirth." No limit was put on the number of years searched. There were 281 publications identified. The abstracts of all of these publications were read. After exclusion of the articles that were not relevant to pregnancy, pregnancy outcome, and fish parasites, there were 24 articles that became the basis of this review. The pathophysiology, altered maternal immunity related to the infection, limited information about fish-borne parasitic infections and pregnancy, and treatments are discussed. The main impact of a fish-borne parasitic infection on pregnant women is anemia and altered immunity, which may increase the risk of a maternal infection. The primary fetal effects include intrauterine growth restriction and preterm delivery.
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http://dx.doi.org/10.1097/OGX.0000000000000303DOI Listing
April 2016

Accuracy of the Adverse Outcome Index: An Obstetrical Quality Measure.

Jt Comm J Qual Patient Saf 2015 Aug;41(8):370-7

Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, Washington, USA.

Background: In obstetrics, a nationally accepted set of quality indicators for patient safety was not available in the United States until the development of a set of 10 adverse outcome measures-the Adverse Outcome Index (AOI). The National Perinatal Information Center (NPIC) developed hospital discharge data-based algorithms combined with a small set of supplemental patient data for calculation of the AOI. A study was conducted to determine the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of the AOI by using the National Perinatal Information Center (NPIC) algorithm.

Methods: A retrospective chart review of 4,252 obstetrical and neonatal charts from 2003 through 2007 was performed. NPIC definitions were compared with the "gold standard"-chart review.

Results: A total of 229 deliveries among the 4,000 randomly selected charts had at least one adverse outcome, reflecting an AOI of 5.7%. For detection of the 10 adverse outcomes within the AOI, the overall sensitivity of the AOI was 81.7%, specificity was 98.2%, PPV was 86.3%, and NPV was 97.4%. The Kappa value for agreement between the coded charts and the chart review was 0.82 (standard deviation=0.01, 95% confidence interval [CI]=0.80-0.85), which is considered very good.

Discussion: The AOI is highly reliant on accurate coding and provider documentation and requires validation with manual chart review. Concurrent chart review improves the accuracy of the AOI. Caution is advised when using the AOI as an exclusive measure of assessing obstetric quality because it may be heavily influenced by a single outcome measure; perineal laceration rates represented twice the frequency of all other outcomes combined. The AOI should be modified to better measure preventable adverse events and include a means of accounting for preexisting conditions.
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http://dx.doi.org/10.1016/s1553-7250(15)41048-7DOI Listing
August 2015

Transforming communication and safety culture in intrapartum care: a multi-organization blueprint.

Obstet Gynecol 2015 May;125(5):1049-1055

Department of Family Health Care Nursing, University of California San Francisco School of Nursing, San Francisco, California; the American College of Nurse-Midwives, Silver Spring, Maryland; the Association of Women's Health, Obstetric and Neonatal Nurses and the American College of Obstetricians and Gynecologists, Washington, DC; the Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Madigan Army Medical Center, Tacoma, Washington; VitalSmarts, LC, Provo, Utah; and the Society for Maternal-Fetal Medicine, Scottsdale, Arizona.

Effective, patient-centered communication facilitates interception and correction of potentially harmful conditions and errors. All team members, including women, their families, physicians, midwives, nurses, and support staff, have a role in identifying the potential for harm during labor and birth. However, the results of collaborative research studies conducted by organizations that represent professionals who care for women during labor and birth indicate that health care providers may frequently witness, but may not always report, problems with safety or clinical performance. Some of these health care providers felt resigned to the continuation of such problems and fearful of retribution if they tried to address them. Speaking up to address safety and quality concerns is a dynamic social process. Every team member must feel empowered to speak up about concerns without fear of put-downs, retribution, or receiving poor-quality care. Patient safety requires mutual accountability: individuals, teams, health care facilities, and professional associations have a shared responsibility for creating and sustaining environments of mutual respect and engaging in highly reliable perinatal care. Defects in human factors, communication, and leadership have been the leading contributors to sentinel events in perinatal care for more than a decade. Organizational commitment and executive leadership are essential to creating an environment that proactively supports safety and quality. The problem is well-known; the time for action is now.
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http://dx.doi.org/10.1097/AOG.0000000000000793DOI Listing
May 2015

Vitamin D deficiency in early pregnancy.

PLoS One 2015 21;10(4):e0123763. Epub 2015 Apr 21.

Department of Clinical Investigation, Madigan Army Medical Center, Joint Base Lewis-McChord, Tacoma, Washington, United States of America.

Objective: Vitamin D deficiency is a common problem in reproductive-aged women in the United States. The effect of vitamin D deficiency in pregnancy is unknown, but has been associated with adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in the first trimester and subsequent clinical outcomes.

Study Design: This is a retrospective cohort study. Plasma was collected in the first trimester from 310 nulliparous women with singleton gestations without significant medical problems. Competitive enzymatic vitamin D assays were performed on banked plasma specimens and pregnancy outcomes were collected after delivery. Logistic regression was performed on patients stratified by plasma vitamin D concentration and the following combined clinical outcomes: preeclampsia, preterm delivery, intrauterine growth restriction, gestational diabetes, and spontaneous abortion.

Results: Vitamin D concentrations were obtained from 235 patients (mean age 24.3 years, range 18-40 years). Seventy percent of our study population was vitamin D insufficient with a serum concentration less than 30 ng/mL (mean serum concentration 27.6 ng/mL, range 13-71.6 ng/mL). Logistic regression was performed adjusting for age, race, body mass index, tobacco use, and time of year. Adverse pregnancy outcomes included preeclampsia, growth restriction, preterm delivery, gestational diabetes, and spontaneous abortion. There was no association between vitamin D deficiency and composite adverse pregnancy outcomes with an adjusted odds ratio of 1.01 (p value 0.738, 95% confidence intervals 0.961-1.057).

Conclusion: Vitamin D deficiency did not associate with adverse pregnancy outcomes in this study population. However, the high percentage of affected individuals highlights the prevalence of vitamin D deficiency in young, reproductive-aged women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123763PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405493PMC
April 2016

Transforming communication and safety culture in intrapartum care: a multi-organization blueprint.

J Midwifery Womens Health 2015 May-Jun;60(3):237-243. Epub 2015 Apr 7.

Effective, patient-centered communication facilitates interception and correction of potentially harmful conditions and errors. All team members, including women, their families, physicians, midwives, nurses, and support staff, have a role in identifying the potential for harm during labor and birth. However, the results of collaborative research studies conducted by organizations that represent professionals who care for women during labor and birth indicate that health care providers may frequently witness, but may not always report, problems with safety or clinical performance. Some of these health care providers felt resigned to the continuation of such problems and fearful of retribution if they tried to address them. Speaking up to address safety and quality concerns is a dynamic social process. Every team member must feel empowered to speak up about concerns without fear of put-downs, retribution, or receiving poor-quality care. Patient safety requires mutual accountability: individuals, teams, health care facilities, and professional associations have a shared responsibility for creating and sustaining environments of mutual respect and engaging in highly reliable perinatal care. Defects in human factors, communication, and leadership have been the leading contributors to sentinel events in perinatal care for more than a decade. Organizational commitment and executive leadership are essential to creating an environment that proactively supports safety and quality. The problem is well-known; the time for action is now.
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http://dx.doi.org/10.1111/jmwh.12235DOI Listing
December 2016

Transforming communication and safety culture in intrapartum care: a multi-organization blueprint.

J Obstet Gynecol Neonatal Nurs 2015 May-Jun;44(3):341-9. Epub 2015 Apr 7.

Effective, patient-centered communication facilitates interception and correction of potentially harmful conditions and errors. All team members, including women, their families, physicians, midwives, nurses, and support staff, have roles in identifying the potential for harm during labor and birth. However, the results of collaborative research studies conducted by organizations that represent professionals who care for women during labor and birth indicate that health care providers may frequently witness, but may not always report, problems with safety or clinical performance. Some of these health care providers felt resigned to the continuation of such problems and fearful of retribution if they tried to address them. Speaking up to address safety and quality concerns is a dynamic social process. Every team member must feel empowered to speak up about concerns without fear of put-downs, retribution, or receiving poor-quality care. Patient safety requires mutual accountability: individuals, teams, health care facilities, and professional associations have a shared responsibility for creating and sustaining environments of mutual respect and engaging in highly reliable perinatal care. Defects in human factors, communication, and leadership have been the leading contributors to sentinel events in perinatal care for more than a decade. Organizational commitment and executive leadership are essential to creating an environment that proactively supports safety and quality. The problem is well-known; the time for action is now.
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http://dx.doi.org/10.1111/1552-6909.12575DOI Listing
February 2016

Micronized progesterone reduces vasoconstriction in the placenta.

J Matern Fetal Neonatal Med 2015 Sep 29;28(13):1581-4. Epub 2014 Sep 29.

a Department of Obstetrics and Gynecology , Carl R. Darnall Army Medical Center , TX , USA and.

Objective: To investigate if micronized progesterone (P4) has the ability to attenuate thromboxane mimetic U46619-mediated fetoplacental artery vasoconstriction.

Methods: Paired cotyledons obtained from the same placenta of five-term subjects were analyzed. The fetal artery and maternal intervillous space of one cotyledon was infused with P4 while another cotyledon was infused with control perfusate. After 30 min, a bolus dose of U44619 was administered to both cotyledons.

Results: The change in the measured fetoplacental vascular pressure caused by bolus administration of U46619 was less in the cotyledons infused with P4 (p = 0.009).

Conclusion: Continuous treatment with P4 significantly attenuates the U46619-mediated fetoplacental vasoconstriction.
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http://dx.doi.org/10.3109/14767058.2014.961008DOI Listing
September 2015

Effect of taurocholic acid on fetoplacental arterial pressures in a dual perfusion placental cotyledon model: a novel approach to intrahepatic cholestasis of pregnancy.

J Reprod Med 2014 Jul-Aug;59(7-8):367-70

Objective: To determine if continuous infusion of taurocholic acid into the fetoplacental and intervillous circulation of a placental cotyledon affects the fetal arterial pressure response after injection of the thromboxane mimetic U44619. Taurine conjugated bile acid is one bile acid putatively mediating intrahepatic cholestasis of pregnancy (ICP).

Study Design: We selected 5 placentas from normal, unlabored patients. Two cotyledons from each placenta were isolated and dually perfused. Taurocholic acid was continuously infused into the fetoplacental and intervillous circulation of the test cotyledon. After 30 minutes U44619 was injected into both the test and control cotyledon vascular circuits. Pressure excursions were measured and compared to baseline pressures using a paired Student's t test.

Results: There was significant attenuation of the pressure excursion in the cotyledons perfused with taurocholic acid as compared to controls after injection of U44619. The difference from baseline in the taurocholic cotyledon compared with controls was 44.2 mmHg vs. 71.8 mmHg (p = 0.009).

Conclusion: The perfusion of taurocholic acid attenuated the pressure response to thromboxane mimetic U44619 in the fetoplacental arterial circulation of a placental cotyledon as compared to control. This finding in our ex-vivo model may represent changes that occur in the placental vasculature with intrahepatic cholestasis of pregnancy. These placentas may have dysregulated vascular tone, which could contribute to the adverse fetal effects observed in ICP.
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September 2014

Effect of dexamethasone administered with magnesium sulfate on inflammation-mediated degradation of the blood-brain barrier using an in vitro model.

Reprod Sci 2014 Apr 27;21(4):483-91. Epub 2013 Sep 27.

1Department of Obstetrics and Gynecology, Maternal Fetal Medicine, Madigan Army Medical Center, Tacoma, WA, USA.

Patients at risk for preterm delivery are frequently administered both antenatal steroids for fetal maturation and magnesium sulfate for neuroprotection. In this study, we investigate whether steroids coadministered with magnesium sulfate preserve blood-brain barrier integrity in neuroinflammation. Human umbilical vein endothelial cells were grown in astroglial conditioned media in a 2-chamber cell culture apparatus. Treatment with tumor necrosis factor-α (TNF-α) or catalytically active recombinant matrix metalloproteinase 9 (MMP-9) simulated neuroinflammation. Membrane integrity was assessed by zona occludens 1 (ZO-1) immunoreactivity, permeability to fluorescently conjugated dextran, and transendothelial electrical resistance (TEER). The TNF-α and MMP-9 treatment increased the rate of dextran transit, decreased TEER, and decreased ZO-1 immunoreactivity at junctional interfaces. Dexamethasone pretreatment alone or in combination with 0.5 mmol/L magnesium sulfate preserved monolayer integrity after inflammatory insult. Magnesium sulfate alone was not protective. This study supports a possible interaction between steroids and magnesium in neuroprotection.
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http://dx.doi.org/10.1177/1933719113503410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960840PMC
April 2014

Aberrant glycosylation of plasma proteins in severe preeclampsia promotes monocyte adhesion.

Reprod Sci 2014 Feb 11;21(2):204-14. Epub 2013 Jun 11.

1Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, WA, USA.

Glycosylation of plasma proteins increases during pregnancy. Our objectives were to investigate an anti-inflammatory role of these proteins in normal pregnancies and determine whether aberrant protein glycosylation promotes monocyte adhesion in preeclampsia. Plasma was prospectively collected from nonpregnant controls and nulliparous patients in all 3 trimesters. Patients were divided into cohorts based on the applicable postpartum diagnosis. U937 monocytes were preconditioned with enzymatically deglycosylated plasma, and monocyte adhesion to endothelial cell monolayers was quantified by spectrophotometry. Plasma from nonpregnant controls, first trimester normotensives, and first trimester patients with mild preeclampsia inhibited monocyte-endothelial cell adhesion (P < .05), but plasma from first trimester patients with severe preeclampsia and second and third trimester normotensives did not. Deglycosylating plasma proteins significantly increased adhesion in all the cohorts. These results support a role of plasma glycoprotein interaction in monocyte-endothelial cell adhesion and could suggest a novel therapeutic target for severe preeclampsia.
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http://dx.doi.org/10.1177/1933719113492210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879990PMC
February 2014

Clinical guidelines for occupational lifting in pregnancy: evidence summary and provisional recommendations.

Am J Obstet Gynecol 2013 Aug 1;209(2):80-8. Epub 2013 Mar 1.

National Institute for Occupational Safety and Health, Cincinnati, OH, USA.

Empirically based lifting criteria established by the National Institute for Occupational Safety and Health (NIOSH) to reduce the risk of overexertion injuries in the general US working population were evaluated for application to pregnant workers. This report proposes criteria to guide decisions by medical providers about permissible weights for lifting tasks performed at work over the course of an uncomplicated pregnancy. Our evaluation included an extensive review of the literature linking occupational lifting to maternal and fetal health. Although it has been 29 years since the American Medical Association's Council on Scientific Affairs published its report on the Effects of Pregnancy on Work Performance, these guidelines continue to influence clinical decisions and workplace policies. Provisional clinical guidelines derived from the NIOSH lifting criteria that account for recent evidence for maternal and fetal health are presented and aim to improve the standard of care for pregnant workers.
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http://dx.doi.org/10.1016/j.ajog.2013.02.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552317PMC
August 2013

Physical activity, maternal metabolic measures, and the incidence of gallbladder sludge or stones during pregnancy: a randomized trial.

Am J Perinatol 2014 Jan 1;31(1):39-48. Epub 2013 Mar 1.

Department of Epidemiology, University of Washington, Seattle, Washington.

Objective: To evaluate the effect of a physical activity intervention upon the incidence of gallbladder sludge or stones during pregnancy.

Study Design: Pregnant women without gallstones were randomized to an intervention to increase moderate to vigorous physical activity or control. Intervention group women received motivational materials and small-group instruction to increase physical activity. Gallbladder ultrasound and blood draws were obtained at entry, 18 weeks' gestation, and 36 weeks' gestation.

Results: In all, 591 were randomized to the intervention and 605 women to control groups. Women in the intervention group reported modestly higher levels of physical activity compared with control women, and fewer women in the intervention group reported no physical activity during pregnancy. The incidence of gallbladder sludge or stones was similar in intervention and control groups at 18 weeks (4.8% versus 5.4%; relative risk 0.89; 95% confidence interval 0.53, 1.47) and 36 weeks (4.3% versus 3.3%; relative risk 1.31; 95% confidence interval 0.70, 2.54). Fasting glucose, lipid, insulin, leptin, and adiponectin levels were similar in the two groups, as was insulin sensitivity and the incidence of gestational diabetes.

Conclusion: An intervention to increase moderate to vigorous physical activity did not decrease the incidence of gallbladder sludge or stones during pregnancy and did not result in improvement in maternal metabolic measures.
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http://dx.doi.org/10.1055/s-0033-1334455DOI Listing
January 2014

Longitudinal analysis of maternal plasma apolipoproteins in pregnancy: a targeted proteomics approach.

Mol Cell Proteomics 2013 Jan 10;12(1):55-64. Epub 2012 Oct 10.

Madigan Healthcare System, Joint Base Lewis-McChord, Tacoma, Washington 98431, USA.

Minimally invasive diagnostic tests are needed in obstetrics to identify women at risk for complications during delivery. The apolipoproteins fluctuate in complexity and abundance in maternal plasma during pregnancy and could be incorporated into a blood test to evaluate this risk. The objective of this study was to examine the relative plasma concentrations of apolipoproteins and their biochemically modified subtypes (i.e. proteolytically processed, sialylated, cysteinylated, dimerized) over gestational time using a targeted mass spectrometry approach. Relative abundance of modified and unmodified apolipoproteins A-I, A-II, C-I, C-II, and C-III was determined by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in plasma prospectively collected from 11 gravidas with uncomplicated pregnancies at 4-5 gestational time points per patient. Apolipoproteins were readily identifiable by spectral pattern. Apo C-III(2) and Apo C-III(1) (doubly and singly sialylated Apo C-III subtypes) increased with gestational age (r(2)>0.8). Unmodified Apo A-II, Apo C-I, and Apo C-III(0) showed no correlation (r(2) = 0.01-0.1). Pro-Apo C-II did not increase significantly until third trimester (140 ± 13% of first trimester), but proteolytically cleaved, mature Apo C-II increased in late pregnancy (702 ± 130% of first trimester). Mature Apo C-II represented 6.7 ± 0.9% of total Apo C-II in early gestation and increased to 33 ± 4.5% in third trimester. A label-free, semiquantitative targeted proteomics approach was developed using LTQ-Orbitrap mass spectrometry to confirm the relative quantitative differences observed by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in Apo C-III and Apo C-II isoforms between first and third trimesters. Targeted apolipoprotein screening was applied to a cohort of term and preterm patients. Modified Apo A-II isoforms were significantly elevated in plasma from mothers who delivered prematurely relative to term controls (p = 0.02). These results support a role for targeted proteomics profiling approaches in monitoring healthy pregnancies and assessing risk of adverse obstetric outcomes.
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http://dx.doi.org/10.1074/mcp.M112.018192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536909PMC
January 2013

Interaction between maternal obesity and Bishop score in predicting successful induction of labor in term, nulliparous patients.

Am J Perinatol 2013 Jan 26;30(1):75-80. Epub 2012 Jul 26.

Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, WA 98431-0001, USA.

Objective: Determine the Bishop score most predictive of induction of labor (IOL) success for different maternal weight groups.

Study Design: Retrospective cohort study. Prospectively collected database utilized to determine the optimum Bishop score within each prepregnancy body mass index (BMI) category of term, nulliparous patients undergoing IOL.

Results: For the total group (n = 696), Bishop score ≥ 5 was most predictive of success (75% versus 56%, p < 0.0001). Within each BMI category, Bishop score ≥ 5 remained most predictive: normal weight (79% versus 64%, p < 0.01); overweight (72% versus 58%, p = 0.03); and obese (73% versus 45%, p < 0.0001). Overall, nonobese patients had more success than obese patients (70% versus 59%, p < 0.01). The nonobese group had more success than the obese group when the Bishop score was < 3 (57% versus 39%, p < 0.05) but not when it was ≥ 3 (72% versus 65%, p = 0.1). Also, there was a higher fraction of patients with Bishop score < 3 in the obese group compared with the nonobese group (25% versus 14%, p < 0.001).

Conclusion: The optimum Bishop score for predicting successful IOL in nulliparous patients was 5 regardless of BMI class. The higher IOL failure rate observed in obese women was associated with lower starting Bishop scores and was compounded by higher failure rates in obese women with Bishop scores < 3.
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http://dx.doi.org/10.1055/s-0032-1322510DOI Listing
January 2013

Nausea, vomiting, and heartburn in pregnancy: a prospective look at risk, treatment, and outcome.

J Matern Fetal Neonatal Med 2012 Aug 4;25(8):1488-93. Epub 2012 Jan 4.

Department of Medicine, University of Washington, Seattle, Washington 98195, USA.

Objective: To examine risk factors, treatment, and outcomes for nausea/vomiting (N/V) and heartburn during pregnancy.

Methods: We included 2731 women from a prospective cohort study of gallbladder disease in pregnancy. Subjects completed questionnaires at enrollment, early third trimester, and 4-6 weeks postpartum. We used logistic regression to examine independent predictors of upper gastrointestinal symptoms.

Results: Ninety-five percent of pregnant women experienced either heartburn and/or N/V. Independent predictors for heartburn included prepregnancy heartburn (OR 5.28, 95% CI 3.78-7.37), multigravidity, prepregnancy body mass index, and pregnancy weight gain. Independent predictors for N/V included prepregnancy N/V (OR 2.25, 95% CI 1.52-3.31), other digestive problems prepregnancy, younger age, single gestation, and carrying a female fetus. 11% of women with N/V and 47% of women with heartburn used pharmacologic therapy. Infants born to women with heartburn had significantly higher birth weights (p = 0.03), but gestational age at delivery was not significantly different. N/V was not associated with birth weight or gestational age at delivery. 19.7% of women with heartburn during pregnancy reported postpartum heartburn.

Conclusions: Heartburn and N/V are common pregnancy symptoms, particularly among women with a history of such symptoms. Neither condition appears to adversely affect the outcome of pregnancy. Pregnancy-related heartburn predisposes to early postpartum heartburn.
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http://dx.doi.org/10.3109/14767058.2011.644363DOI Listing
August 2012

On the front lines of patient safety: implementation and evaluation of team training in Iraq.

Jt Comm J Qual Patient Saf 2011 Aug;37(8):350-6

Andersen Simulation Center, Madigan Army Medical Center, Tacoma, Washington, USA.

Background: Team training has been identified as a key strategy for reducing medical errors and building a culture of safety in health care. Communication and coordination skills can serve as barriers to potential errors, as in the modern deployed U.S. Military Healthcare System (MHS), which emphasizes rapid movement of critically injured patients to facilities capable of providing definitive care. A team training intervention--TeamSTEPPS--was implemented on a large scale during one of the most intense phases of the conflict in Iraq. This evaluation of the program constituted the first undertaken in a combat theater of operations. IMPLEMENTING TEAMSTEPPS IN IRAQ: The Baghdad combat support hospital (CSH) conducted continuous operations from a fixed facility for a 13-month deployment--between November 2007 and December 2008. The TeamSTEPPS implementation in Iraq began at this facility and spread throughout the combat theater of operations. Teamwork training was implemented in two primary training sessions, followed up with reinforcement of team behaviors on the unit by hospital leadership.

Results: A total of 153 patient safety reports were submitted during the 13 months reviewed, 94 before TeamSTEPPS implementation and 59 afterwards. After training, there were significant decreases in the rates of communication-related errors, medication and transfusion errors, and needlestick incidents. There was a significant decrease in the rate of incidents coded communication as the primary teamwork skill that could have potentially prevented the event.

Conclusions: Process improvement programs such as TeamSTEPPS implementation can be conducted under the extremely austere conditions of a CSH in a combat zone. Teamwork training decreased medical errors in the CSH while deployed in the combat theater in Iraq.
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http://dx.doi.org/10.1016/s1553-7250(11)37045-6DOI Listing
August 2011

Elevated ratio of maternal plasma ApoCIII to ApoCII in preeclampsia.

Reprod Sci 2011 May 14;18(5):493-502. Epub 2011 Feb 14.

Division of Maternal-Fetal Medicine, Madigan Healthcare System, Joint Base Lewis-McChord, WA, USA.

Preeclampsia is a hypertensive disorder unique to pregnancy. Although the pathogenesis of the disease begins with aberrant spiral artery invasion in the first trimester, clinical symptoms usually do not present until late in pregnancy. Apolipoprotein CII (ApoCII) and its negative regulator, apolipoprotein CIII (ApoCIII), have recently been described as atherogenesis biomarkers in models of cardiovascular disease. Given the similarities in pathology, etiology, and clinical presentation between cardiovascular disease and preeclampsia, we hypothesized that the ratio of ApoCIII to ApoCII in maternal first trimester plasma would predict preeclampsia later in pregnancy. To test this hypothesis, plasma was prospectively collected from 311 nulliparas at 8 to 12 weeks gestation. After delivery, patients were divided into cohorts based on preeclampsia diagnosis. Conditioning monocytes with preeclamptic plasma potentiated monocyte adhesion to endothelial cells in an in vitro model. The ratio of ApoCIII to ApoCII was significantly elevated in patients with severe preeclampsia relative to normotensive and gestational hypertensive individuals (P < .05) as determined by mass spectrometry and competitive enzyme-linked immunosorbent assay (ELISA) assays. These results support a predictive change in the ratio of ApoCIII to ApoCII in pregnancies complicated by severe preeclampsia.
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http://dx.doi.org/10.1177/1933719110390390DOI Listing
May 2011