Sonia S Hassan

Wayne State University, Detroit, Michigan, United States

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Publications (359)945.98 Total impact

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    ABSTRACT: To evaluate the association between cervical strain assessed with quasi-static elastography and spontaneous preterm delivery. Quasi-static elastography was used to estimate cervical strain in 545 pregnant women with singleton pregnancies from 11 weeks to 28 weeks of gestation. Cervical strain was evaluated in one sagittal plane and in the cross-sectional planes of the internal cervical os and external cervical os. The distribution of strain values was categorized into quartiles for each studied region and their association with spontaneous preterm delivery at ≤34 weeks and at <37 weeks of gestation was evaluated using logistic regression. The prevalence of spontaneous preterm delivery at <37 weeks of gestation was 8.2% (n=45), and that at ≤34 weeks of gestation was 3.8% (n=21). Strain in the internal cervical os was the only elastography value associated with spontaneous preterm delivery. Women with strain values in the 3rd and 4th quartiles had a significantly higher risk of spontaneous preterm delivery at ≤34 weeks and at <37 weeks of gestation when compared to women with strain values in the lowest quartile. When adjusting for a short cervix (<25 mm) and gestational age at examination, women with strain values in the 3rd quartile maintained a significant association with spontaneous preterm delivery at ≤34 weeks (OR 9.0; 95% CI, 1.1-74.0; P=0.02), whereas women with strain values in the highest quartile were marginally more likely than women with lowest quartile strain values to deliver spontaneously at ≤37 weeks of gestation (OR 95% CI: 2.8; [0.9-9.0]; P=0.08). Increased strain in the internal cervical os is associated with higher risk of spontaneous preterm delivery both at ≤34 and <37 weeks of gestation.
    Journal of Perinatal Medicine 03/2015; DOI:10.1515/jpm-2014-0382 · 1.43 Impact Factor
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    ABSTRACT: Preterm prelabor rupture of membranes (preterm PROM) accounts for 30-40% of spontaneous preterm deliveries and thus is a major contributor to perinatal morbidity and mortality. An amniotic fluid (AF) interleukin-6 (IL-6) concentration is a key cytokine for the identification of intra-amniotic inflammation, and patients at risk of impending preterm delivery, and adverse pregnancy complications. The conventional method to determine IL-6 concentrations in AF is an enzyme-linked immunosorbent assay (ELISA). However, this technique is not available in clinical settings and the results may take several days. A lateral flow-based immunoassay, or point of care (POC) test, has been developed to address this issue. The objective of this study was to compare the performance of AF IL-6 determined by the POC test to that determined by ELISA for the identification of intra-amniotic inflammation in patients with preterm PROM. This retrospective cohort study includes 56 women with singleton pregnancies who presented with preterm PROM. Amniocentesis was performed at the time of diagnosis and AF was analyzed using cultivation techniques for aerobic and anaerobic bacteria as well as genital mycoplasmas. AF Gram stain and AF white blood cell counts were determined. AF IL-6 concentrations were measured using both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation defined as AF ELISA IL-6 > 2,600 pg/ml. A previously determined cut-off of 745 pg/ml was used to define a positive POC test. 1) The POC test for AF IL-6 concentrations had 97% sensitivity and 96% specificity for the identification of intra-amniotic inflammation, as defined using ELISA among patients with preterm PROM; and 2) the diagnostic performance of the POC test for IL-6 was strongly correlated to that of an ELISA test for the identification of intra-amniotic inflammation and was equivalent for the identification of acute inflammatory placental lesions and MIAC. A point of care AF IL-6 test can identify intra-amniotic inflammation in patients with preterm PROM. Results can be available within 20 minutes - this makes it possible to implement interventions designed to treat intra-amniotic inflammation and improve pregnancy outcomes.
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    ABSTRACT: Preterm birth is associated with 5 to 18% of pregnancies and is the leading cause of neonatal morbidity and mortality. Amniotic fluid (AF) interleukin-6 (IL-6) is a key cytokine for the identification of intra-amniotic inflammation, and patients with an elevated amniotic fluid IL-6 are at risk for impending preterm delivery. However, results of the conventional method of measurement (enzyme-linked immunosorbent assay; ELISA) are usually not available in time to inform care. The objective of this study was to determine whether a point of care (POC) test or lateral-flow based immunoassay for measurement of amniotic fluid (AF) IL-6 concentrations can identify patients with intra-amniotic inflammation and/or infection, and those destined to deliver spontaneously before term among women with preterm labor and intact membranes. One hundred thirty six women with singleton pregnancies who presented with symptoms of preterm labor and underwent amniocentesis were included in this study. Amniocentesis was performed at the time of diagnosis of preterm labor. AF Gram stain and AF white blood cell counts were determined. Microbial invasion of the amniotic cavity (MIAC) was defined according to the results of AF culture (aerobic and anaerobic as well as genital mycoplasmas). AF IL-6 concentrations were determined by both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation, defined as AF ELISA IL-6 > 2,600 pg/ml . 1) AF IL-6 concentrations determined by a POC test have high sensitivity (93%), specificity (91%), and a positive likelihood ratio of 10 for the identification of intra-amniotic inflammation by using a threshold of 745 pg/ml; 2) the POC test and ELISA for IL-6 perform similarly in the identification of MIAC, acute inflammatory lesions of placenta, and patients at risk of impending spontaneous preterm delivery. A point of care AF IL-6 test can identify intra-amniotic inflammation in women who present with preterm labor and intact membranes and those who will subsequently deliver spontaneously before 34 weeks of gestation. Results can be available within 20 minutes-this has important clinical implications and opens avenues for early diagnosis as well as treatment of intra-amniotic inflammation/infection.
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    ABSTRACT: Objective: To investigate dynamic changes in myometrial thickness during the third stage of labor. Methods: Myometrial thickness was measured using ultrasound at one-minute time intervals during the third stage of labor in the mid-region of the upper and lower uterine segments in 151 patients including: women with a long third stage of labor (n = 30), postpartum hemorrhage (n = 4), preterm delivery (n = 7) and clinical chorioamnionitis (n = 4). Differences between myometrial thickness of the uterine segments and as a function of time were evaluated. Results: There was a significant linear increase in the mean myometrial thickness of the upper uterine segments, as well as a significant linear decrease in the mean myometrial thickness of the lower uterine segments until the expulsion of the placenta (p < 0.001). The ratio of the measurements of the upper to the lower uterine segments increased significantly as a function of time (p < 0.0001). In women with postpartum hemorrhage, preterm delivery, and clinical chorioamnionitis, an uncoordinated pattern among the uterine segments was observed. Conclusion: A well-coordinated activity between the upper and lower uterine segments is demonstrated in normal placental delivery. In some clinical conditions this pattern is not observed, increasing the time for placental delivery and the risk of postpartum hemorrhage. © 2015 S. Karger AG, Basel.
    Gynecologic and Obstetric Investigation 01/2015; DOI:10.1159/000370001 · 1.10 Impact Factor
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    ABSTRACT: Preterm preeclampsia is associated with the failure of trophoblast invasion, placental hypoxic/ischemic injury and the release of toxic substances, which promote the terminal pathway of preeclampsia. In term preeclampsia, factors yet unknown trigger the placenta to induce the terminal pathway. The contribution of the villous trophoblast to these pathologic events has not been fully elucidated. Here we aimed to study how stress and signaling pathways influence trophoblastic functions in various subforms of preeclampsia. Tissue microarrays (TMAs) were constructed from placentas obtained from pregnant women in the following groups: 1-2) preterm preeclampsia with (n = 8) or without (n = 7) HELLP syndrome; 3) late-onset preeclampsia (n = 8); 4-5) preterm (n = 5) and term (n = 9) controls. TMA slides were stained for phosphorylated Akt-1, ERK1/2, JNK, and p38 kinases, and trophoblastic immunostainings were semi-quantitatively evaluated. BeWo cells were kept in various stress conditions, and the expression of FLT1, GCM1, LEP, and PGF was profiled by qRT-PCR, while Akt-1, ERK1/2, JNK, and p38 kinase activities were measured with phospho-kinase immunoassays. We found that: 1) Placental LEP and FLT1 expression was up-regulated in preterm preeclampsia with or without HELLP syndrome compared to controls; 2) Mean pp38 immunoscore was higher in preterm preeclampsia, especially in cases with HELLP syndrome, than in controls. 3) Mean pERK1/2 immunoscore was higher in preterm preeclampsia with HELLP syndrome than in controls. 4) In BeWo cells, ischemia up-regulated LEP expression, and it increased JNK and decreased ERK1/2 activity. 5) Hypoxia up-regulated FLT1 and down-regulated PGF expression, and it increased ERK1/2, JNK and p38 activity. 6) IL-1β treatment down-regulated PGF expression, and it increased JNK and p38 activity. 7) The p38 signaling pathway had the most impact on LEP, FLT1 and PGF expression. In conclusion, hypoxic and ischemic stress, along with unknown factors, activates trophoblastic p38 signaling, which has a key role in villous trophoblastic functional changes in preterm preeclampsia. The activation of ERK1/2 signaling may induce additional trophoblastic functional changes in HELLP syndrome, while distinct mechanisms may promote late-onset preeclampsia.
    Pathology & Oncology Research 01/2015; DOI:10.1007/s12253-014-9872-9 · 1.81 Impact Factor
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    ABSTRACT: To identify potential biomarkers for early preeclampsia (PE) with placental lesions consistent with maternal vascular underperfusion (MVU) using a novel proteomic approach. A longitudinal study included uncomplicated singleton pregnant women whose samples were collected between 24 and 42weeks (controls: n=50, total samples=199). Cases were women with early PE (delivered <34weeks) who had placental lesions consistent with MVU (n=44) and the samples were collected at the time of diagnosis. Proteomic profiles were analyzed using aptamer-based multiplexed proteomic technology which measured 1129 proteins. Log transformed and normalized protein concentrations in uncomplicated pregnancies were modeled using locally weighted linear quantile regression to establish the 10th and 90th percentiles of their distribution as a function of gestational age. Sensitivity for each protein in the identification of early PE with MVU at fixed 90% specificity was computed. Confidence intervals (CI) for sensitivity estimates were obtained by using a bootstrap procedure. (1) Twenty-five proteins had a sensitivity of at least 80% (at 90% specificity) for the identification of early PE with MVU; (2) four proteins (soluble tyrosine-protein kinase receptor-1, PlGF, and two newly-identified biomarkers had more than 90% sensitivity to identify such disorder; (3) each of these 4 proteins had at least 91% with 95% CI between 73% and 100% when confirmed by bootstrap; and (4) the median coefficient of variation (CV) for 1129 proteins was 6.07% (IQR=4.4-8.5%). Four proteins each had at least 90% sensitivity and specificity in the identification of patients with PE. The panel included two novel markers. Protein expression profiles in maternal plasma in normal pregnancy and early PE with MVU (red dots). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) P. Chaemsaithong: None. R. Romero: None. A.L. Tarca: None. Z. Xu: None. A.I. Ahmed: None. S.S. Hassan: None. L. Yeo: None. T. Chaiworapongsa: None. Copyright © 2014.
    01/2015; 5(1):48-9. DOI:10.1016/j.preghy.2014.10.094
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    ABSTRACT: Abstract Introduction: The objectives of this study were: 1) to determine the amniotic fluid (AF) microbiology of patients with the diagnosis of clinical chorioamnionitis at term using both cultivation and molecular techniques; and 2) to examine the relationship between intra-amniotic inflammation with and without microorganisms and placental lesions consistent with acute AF infection. The AF samples obtained by transabdominal amniocentesis from 46 women with clinical signs of chorioamnionitis at term were analyzed using cultivation techniques (for aerobic and anerobic bacteria as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation [defined as an AF interleukin 6 (IL-6) concentration ≥2.6 ng/mL], and placental lesions consistent with acute AF infection (acute histologic chorioamnionitis and/or acute funisitis) were examined according to the results of AF cultivation and PCR/ESI-MS as well as AF IL-6 concentrations. 1) Culture identified bacteria in AF from 46% (21/46) of the participants, whereas PCR/ESI-MS was positive for microorganisms in 59% (27/46) - combining these two tests, microorganisms were detected in 61% (28/46) of patients with clinical chorioamnionitis at term. Eight patients had discordant test results; one had a positive culture and negative PCR/ESI-MS result, whereas seven patients had positive PCR/ESI-MS results and negative cultures. 2) Ureaplasma urealyticum (n=8) and Gardnerella vaginalis (n=10) were the microorganisms most frequently identified by cultivation and PCR/ESI-MS, respectively. 3) When combining the results of AF culture, PCR/ESI-MS and AF IL-6 concentrations, 15% (7/46) of patients did not have intra-amniotic inflammation or infection, 6.5% (3/46) had only MIAC, 54% (25/46) had microbial-associated intra-amniotic inflammation, and 24% (11/46) had intra-amniotic inflammation without detectable microorganisms. 4) Placental lesions consistent with acute AF infection were significantly more frequent in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [70.8% (17/24) vs. 28.6% (2/7); P=0.04]. Microorganisms in the AF were identified in 61% of patients with clinical chorioamnionitis at term; 54% had microbial-associated intra-amniotic inflammation, whereas 24% had intra-amniotic inflammation without detectable microorganisms.
    Journal of Perinatal Medicine 01/2015; 43(1):19-36. DOI:10.1515/jpm-2014-0249 · 1.43 Impact Factor
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    ABSTRACT: Soluble ST2 (sST2) has been implicated in the pathophysiology of preeclampsia (PE). sST2 inhibits interleukin (IL)-33, and thus, favors a shift towards a Th1 immune response. This protein is elevated in maternal plasma of women with PE at time of diagnosis and the magnitude of change is similar to that of anti-angiogenic factors (7.3-fold). The objective was to determine whether: (1) patients with PE have a different profile of plasma sST2concentrations than those with uncomplicated pregnancies; and (2) the changes in sST2 occur prior to the diagnosis of PE. A longitudinal nested case-control study included singleton pregnancies in the following groups: (1) uncomplicated pregnancies (n=160; 1101 samples); and (2) patients who subsequently developed PE (cases, n=40; 227 samples). Cases were early (delivered <34 weeks, n=9) and late PE (n=31). Maternal plasma sST2 concentrations were determined by ELISA. Analysis used mixed-effects models. (1) Patients who subsequently developed PE had a different profile (concentration changes over time) of plasma sST2 concentrations than normal pregnancies (p<0.0001); (2) Plasma sST2 concentration in early and late PE was significantly higher than uncomplicated pregnancies from 22 to 33 weeks of gestation, respectively (both p<0.05) and (3) these changes started approximately 6 weeks prior to clinical diagnosis. Maternal plasma sST2 concentrations are elevated six weeks prior to clinical diagnosis of PE. An increase in maternal plasma concentration of sST2 may contribute to exaggerated intravascular inflammatory response, and/or, the Th1/Th2 imbalance. Figure legend: Maternal plasma concentrations of sST2 in uncomplicated pregnancies (black) and PE (red). The vertical lines on the PE curve denote significant differences between the two groups. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) P. Chaemsaithong: None. R. Romero: None. A.L. Tarca: None. Z. Xu: None. A.I. Ahmed: None. S.S. Hassan: None. L. Yeo: None. T. Chaiworapongsa: None. Copyright © 2014.
    01/2015; 5(1):27-8. DOI:10.1016/j.preghy.2014.10.058
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    ABSTRACT: The traditional approach to understand health and disease has relied on the analyses of individual genes or proteins. Yet, biological functions are the expression of integrated and interdependent networks. We examined the behavior of protein networks in peripheral blood of normal pregnant women and those with preeclampsia (PE). A cross-sectional study was conducted to include: (1) normal pregnancy (n=50); (2) early PE (delivered <34 weeks; n=44); and (3) late PE (n=43). Multiplex assay systems were used to measure proteins. Log transformed and normalized protein concentrations in normal pregnancies were modeled using locally weighted linear quantile regression. Protein abundance was represented as MOM. Differentially expressed proteins were retained to conduct a network analysis. (1) Eighty-six and 24 proteins were differentially expressed in early and late PE, respectively (fold >1.5 and adjusted p 4); (2) network analysis demonstrated a more coordinated protein activity in early PE with four distinct modules (Figure). These modules represented proteins involved in cell adhesion molecules, cytokine-cytokine receptor interaction; and coagulation cascade; and (3) the cyan module which was enriched in proteins involved in cell adhesion molecules pathway was present in early, but not in normal or late PE. We report for the first time increased connectivity in protein-protein correlation networks in PE. We propose that characterizing the protein network structure and behavior provides insight into complex diseases. Figure Legend Protein correlation network in early preeclampsia. Four protein modules were identified (green, blue, gold, magenta). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) P. Chaemsaithong: None. R. Romero: None. A.L. Tarca: None. Z. Xu: None. M. Shaman: None. K. Lannaman: None. A.I. Ahmed: None. S.S. Hassan: None. L. Yeo: None. T. Chaiworapongsa: None. Copyright © 2014.
    01/2015; 5(1):42-3. DOI:10.1016/j.preghy.2014.10.084
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    ABSTRACT: Soluble fms-like tyrosine kinase (sFlt)-1-e15a, a primate-specific sFlt-1-isoform most abundant in the human placenta in preeclampsia, can induce preeclampsia in mice. This study compared the effects of full-length human (h)sFlt-1-e15a with those of truncated mouse (m)sFlt-1(1-3) used in previous preeclampsia studies on pregnancy outcome and clinical symptoms in preeclampsia.
    PLoS ONE 11/2014; 9(11):e110867. DOI:10.1371/journal.pone.0110867 · 3.53 Impact Factor
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    ABSTRACT: Abstract Objectives: Our two objectives were to evaluate the feasibility of fetal brain magnetic resonance imaging (MRI) using a fast spin echo sequence at 3.0T field strength with low radio frequency (rf) energy deposition (as measured by specific absorption rate: SAR) and to compare image quality, tissue contrast and conspicuity between 1.5T and 3.0T MRI. Methods: T2 weighted images of the fetal brain at 1.5T were compared to similar data obtained in the same fetus using a modified sequence at 3.0T. Quantitative whole-body SAR and normalized image signal to noise ratio (SNR), a nominal scoring scheme based evaluation of diagnostic image quality, and tissue contrast and conspicuity for specific anatomical structures in the brain were compared between 1.5T and 3.0T. Results: Twelve pregnant women underwent both 1.5T and 3.0T MRI examinations. The image SNR was significantly higher (P=0.03) and whole-body SAR was significantly lower (P<0.0001) for images obtained at 3.0T compared to 1.5T. All cases at both field strengths were scored as having diagnostic image quality. Images from 3.0T MRI (compared to 1.5T) were equal (57%; 21/37) or superior (35%; 13/37) for tissue contrast and equal (61%; 20/33) or superior (33%, 11/33) for conspicuity. Conclusions: It is possible to obtain fetal brain images with higher resolution and better SNR at 3.0T with simultaneous reduction in SAR compared to 1.5T. Images of the fetal brain obtained at 3.0T demonstrated superior tissue contrast and conspicuity compared to 1.5T.
    Journal of Perinatal Medicine 10/2014; DOI:10.1515/jpm-2014-0268 · 1.43 Impact Factor
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    ABSTRACT: Abstract Objective: Acute atherosis is characterized by subendothelial lipid-filled foam cells, fibrinoid necrosis and perivascular lymphocytic infiltration. This lesion is generally confined to non-transformed spiral arteries and is frequently observed in patients with preeclampsia. However, the frequency of acute atherosis in the great obstetrical syndrome is unknown. The purpose of this study was to determine the frequency and the topographic distribution of acute atherosis in the placentas and placental bed biopsy samples obtained from women with normal pregnancy and those affected by the great obstetrical syndromes. We also examined the relationship between acute atherosis and pregnancy outcome in patients with preeclampsia. Material and methods: A retrospective cohort study of pregnant women who delivered between July 1998 and July 2014 at Hutzel Women's Hospital/Detroit Medical Center was conducted examine 16,345 placentas. Patients were classified into the following groups: 1) uncomplicated pregnancy; 2) spontaneous preterm labor and preterm prelabor rupture of membranes (PPROM); 3) preeclampsia; 4) gestational hypertension; 5) small for gestational age; 6) chronic hypertension; 5) fetal death; 6) spontaneous abortion; and 7) others. A subset of patients had placenta bed biopsy. The incidence of acute atherosis was compared among the different groups. Results: 1) The prevalence of acute atherosis in uncomplicated pregnancies was 0.4% (29/6,961) based upon examination of nearly 7,000 placentas; 2) the frequency of acute atherosis was 10.2% (181/1,779) in preeclampsia, 9% (26/292) in fetal death, 2.5% (3/120) in midtrimester spontaneous abortion, 1.7% (22/1,298) in small for gestational age neonates, and 1.2% (23/1,841) in spontaneous preterm labor and PPROM; 3) among patients with preeclampsia, those with acute atherosis had significantly more severe disease, earlier onset, and a greater frequency of small for gestational age neonates (p < 0.05 all); 4) the lesion was more frequently observed in the decidua (parietalis or basalis) than in the decidual segment of the spiral arteries in patients with placental bed biopsies. Conclusions: Acute atherosis is rare in normal pregnancy, and occurs more frequently in patients with pregnancy complications, including preeclampsia, spontaneous preterm labor, preterm PROM, midtrimester spontaneous abortion, fetal death, and SGA.
    Journal of Maternal-Fetal and Neonatal Medicine 10/2014; DOI:10.3109/14767058.2014.976198 · 1.21 Impact Factor
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    ABSTRACT: Purpose: To evaluate the feasibility of performing fetal brain magnetic resonance venography using susceptibility weighted imaging (SWI). Materials and Methods: After obtaining informed consent, pregnant women in the second and third trimester were imaged using a modified SWI sequence. Fetal SWI acquisition was repeated when fetal or maternal motion was encountered. The median and maximum number of times an SWI sequence was repeated was four and six respectively. All SWI image data were systematically evaluated by a pediatric neuroradiologist for image quality using an ordinal scoring scheme: 1. diagnostic; 2. diagnostic with artifacts; and 3. nondiagnostic. The best score in an individual fetus was used for further statistical analysis. Visibility of venous vasculature was also scored using a dichotomous variable. A subset of SWI data was re-evaluated by the first and independently by a second pediatric neuroradiologist. Kappa coefficients were computed to assess intra-rater and inter-rater reliability. Results: SWI image data from a total of 22 fetuses were analyzed. Median gestational age and interquartile range of the fetuses imaged were 32 (29.9-34.9) weeks. In 68.2% of the cases (n = 15), there was no artifact; 22.7% (n = 5) had minor artifacts and 9.1% (n = 2) of the data was of nondiagnostic quality. Cerebral venous vasculature was visible in 86.4% (n = 19) of the cases. Substantial agreement (Kappa = 0.73; 95% confidence interval 0.44-1.00)) was observed for intra-rater reliability and moderate agreement (Kappa = 0.48; 95% confidence interval 0.19-0.77) was observed for inter-rater reliability. Conclusion: It is feasible to perform fetal brain venography in humans using SWI.
    Journal of Magnetic Resonance Imaging 10/2014; 40(4). DOI:10.1002/jmri.24476 · 2.57 Impact Factor
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    ABSTRACT: Formation of operational neural networks is one of the most significant accomplishments of human fetal brain growth. Recent advances in functional magnetic resonance imaging (fMRI) have made it possible to obtain information about brain function during fetal development. Specifically, resting-state fMRI and novel signal covariation approaches have opened up a new avenue for non-invasive assessment of neural functional connectivity (FC) before birth. Early studies in this area have unearthed new insights about principles of prenatal brain function. However, very little is known about the emergence and maturation of neural networks during fetal life. Here, we obtained cross-sectional rs-fMRI data from 39 fetuses between 24 and 38 weeks postconceptual age to examine patterns of connectivity across ten neural FC networks. We identified primitive forms of motor, visual, default mode, thalamic, and temporal networks in the human fetal brain. We discovered the first evidence of increased long-range, cerebral-cerebellar, cortical-subcortical, and intra-hemispheric FC with advancing fetal age. Continued aggregation of data about fundamental neural connectivity systems in utero is essential to establishing principles of connectomics at the beginning of human life. Normative data provides a vital context against which to compare instances of abnormal neurobiological development.
    Developmental Cognitive Neuroscience 09/2014; 11. DOI:10.1016/j.dcn.2014.09.001 · 3.71 Impact Factor
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    ABSTRACT: Abstract Objective: Endocan, a dermatan sulphate proteoglycan produced by endothelial cells, is considered a biomarker for endothelial cell activation/dysfunction. Preeclampsia (PE) is characterized by systemic vascular inflammation, and endothelial cell activation/ dysfunction. Therefore, the objectives of this study were to determine if: 1) plasma endocan concentrations in PE differ from that of uncomplicated pregnancy; 2) changes in plasma endocan concentration relate to the severity of preeclampsia, and whether these changes are specific or observed in other obstetrical syndromes such as small-for-gestational age (SGA), fetal death (FD), preterm labor (PTL) or preterm prelabor rupture of membranes (PROM); 3) a correlation exists between plasma concentration of endocan and angiogenic (placental growth factor or PlGF) /anti-angiogenic factors (soluble vascular endothelial growth factor receptor or sVEGFR-1, and soluble endoglin or sEng) among pregnancies complicated by PE; and 4) plasma endocan concentrations in patients with preeclampsia and acute pyelonephritis (both conditions in which there is endothelial cell activation) differ. Method: This cross-sectional study included the following groups: 1) uncomplicated pregnancy (n=130); 2) preeclampsia (n=102); 3) pregnant women without preeclampsia who delivered a SGA neonate (n= 51); 4) FD (n=49); 5) acute pyelonephritis (AP; n=35); 6) spontaneous PTL (n=75); and 7) preterm PROM (n= 64). Plasma endocan concentrations were determined in all groups, and PIGF, sEng and VEGFR-1 plasma concentrations were measured by ELISA in the preeclampsia group. Results: 1) Women with preeclampsia had a significantly higher median plasma endocan concentration than those with uncomplicated pregnancies (p= 0.004); 2) among women with preeclampsia, the median plasma endocan concentration did not differ significantly according to disease severity (p=0.1), abnormal uterine artery Doppler velocimetry (p =0.7), or whether diagnosis was made before or after 34 weeks gestational age (p=0.3); 3) plasma endocan concentration in women with preeclampsia correlated positively with plasma anti-angiogenic factor concentrations [ sVEGFR-1:Spearman rho 0.34, p=0.001 and sEng: Spearman rho 0.30, p=0.003]; 4) pregnancies complicated by acute pyelonephritis with bacteremia had a lower median plasma endocan concentration than pregnancies complicated by acute pyelonephritis without bacteremia (p=0.004), as well as uncomplicated pregnancies (p=0.001); and 5) there was no significant difference in the median plasma endocan concentration between uncomplicated pregnancies and those complicated by FD, delivery of an SGA neonate, PTL or preterm PROM (other members of the "great obstetrical syndromes"; each p>0.05). Conclusion: The median maternal plasma endocan concentrations were higher preeclampsia and lower in acute pyelonephritis with bacteremia than in uncomplicated pregnancy No significant difference was observed in the median plasma endocan concentration between other great obstetrical syndromes and uncomplicated pregnancies. The difference in the direction of change of endocan in preeclampsia and acute pyelonephritis with bacteremia may be consistent with the view that both disease entities differ in pathogenic mechanisms, despite their associations with systemic vascular inflammation and endothelial cell activation/dysfunction.
    Journal of Maternal-Fetal and Neonatal Medicine 09/2014; DOI:10.3109/14767058.2014.964676 · 1.21 Impact Factor
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    ABSTRACT: Abstract Objective: The objectives of this study were to: 1) determine the amniotic fluid (AF) microbiology of patients with preterm prelabor rupture of membranes (PROM); and 2) examine the relationship between intra-amniotic inflammation with and without microorganisms (sterile inflammation) and adverse pregnancy outcomes in patients with preterm PROM. Methods: AF samples obtained from 59 women with preterm PROM were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital mycoplasmas) and with broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). AF concentration of interleukin-6 (IL-6) was determined using ELISA. Results of both tests were correlated with AF IL-6 concentrations, and the occurrence of adverse obstetrical/perinatal outcomes. Results: 1) PCR/ESI-MS, AF culture, and the combination of these two tests, each identified microorganisms in 36% (21/59), 24% (14/59) and 41% (24/59) of women with preterm PROM, respectively; 2) the most frequent microorganisms found in the amniotic cavity were Sneathia species and Ureaplasma urealyticum; 3) the frequency of microbial-associated and sterile intra-amniotic inflammation was overall similar [29% (17/59)]: - however, the prevalence of each differed according to the gestational age when PROM occurred; 4) the earlier the gestational age at preterm PROM, the higher the frequency of both microbial-associated and sterile intra-amniotic inflammation; 5) the intensity of the intra-amniotic inflammatory response against microorganisms is stronger when preterm PROM occurs early in pregnancy; and 6) the frequency of acute placental inflammation (histologic chorioamnionitis and/or funisitis) was significantly higher in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [93.3% (14/15) vs. 38% (6/16); p=0.001]. Conclusions: 1) The frequency of microorganisms in preterm PROM is 40% using both cultivation and PCR/ESI-MS; 2) PCR/ESI-MS identified microorganisms in the AF of 50% more women with preterm PROM than did AF culture; and 3) sterile intra-amniotic inflammation was present in 29% of these patients, and it was as or more common than microbial-associated intra-amniotic inflammation among those presenting after, but not before, 24 weeks of gestation.
    Journal of Maternal-Fetal and Neonatal Medicine 09/2014; DOI:10.3109/14767058.2014.958463 · 1.21 Impact Factor
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    ABSTRACT: Abstract Objective: We sought to determine whether cumulative evidence of perinatal inflammation was associated with increased risk in a "multi-hit" model of neonatal white matter injury (WMI). Methods: This retrospective cohort study included very preterm (gestational ages at delivery <32 weeks) live-born singleton neonates delivered at Hutzel Women's Hospital, Detroit, MI, from 2006 to 2011. Four pathologists blinded to clinical diagnoses and outcomes performed histological examinations according to standardized protocols. Neurosonography was obtained per routine clinical care. The primary indicator of WMI was ventriculomegaly (VE). Neonatal inflammation-initiating illnesses included bacteremia, surgical necrotizing enterocolitis, other infections, and those requiring mechanical ventilation. Results: A total of 425 live-born singleton neonates delivered before the 32nd week of gestation were included. Newborns delivered of pregnancies affected by chronic chorioamnionitis who had histologic evidence of an acute fetal inflammatory response were at increased risk of VE, unlike those without funisitis, relative to referent newborns without either condition, adjusting for gestational age [odds ratio (OR) 4.7; 95% confidence interval (CI) 1.4-15.8 vs. OR 1.3; 95% CI 0.7-2.6]. Similarly, newborns with funisitis who developed neonatal inflammation-initiating illness were at increased risk of VE, unlike those who did not develop such illness, compared to the referent group without either condition [OR 3.6 (95% CI 1.5-8.3) vs. OR 1.7 (95% CI 0.5-5.5)]. The greater the number of these three types of inflammation documented, the higher the risk of VE (P<0.0001). Conclusion: Chronic placental inflammation, acute fetal inflammation, and neonatal inflammation-initiating illness seem to interact in contributing risk information and/or directly damaging the developing brain of newborns delivered very preterm.
    Journal of Perinatal Medicine 09/2014; 42(6). DOI:10.1515/jpm-2014-0250 · 1.43 Impact Factor
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    ABSTRACT: Abstract Objective: Acute atherosis is a lesion of the spiral arteries characterized by fibrinoid necrosis of the vessel wall, an accumulation of fat-containing macrophages, and a mononuclear perivascular infiltrate, which can be found in patients with preeclampsia, fetal death, small-for-gestational age, spontaneous preterm labor/premature prelabor rupture of membrane, and spontaneous mid-trimester abortion. This lesion is thought to decrease blood flow to the intervillous space which may lead to other vascular lesions of the placenta. The objective of this study was to test whether there is an association between acute atherosis and placental lesions that are consistent with maternal vascular underperfusion, amniotic fluid infection, fetal vascular thrombo-occlusive disease or chronic inflammation. Material and methods: A retrospective cohort study of pregnant women who delivered between July 1998 and July 2014 at Hutzel Women's Hospital/Detroit Medical Center was conducted examine 16,457 placentas. The frequency of placenta lesions (diagnosed using the criteria of the Perinatal Section of the Society for Pediatric Pathology) was compared between pregnancies with and without acute atherosis. Results: Among 16,457 women who were enrolled, 10.2% (1,671/16,457) were excluded, leaving 14,786 women who contributed data for analysis. Among them, the prevalence of acute atherosis was 2.2% (326/14,786). Women with acute atherosis were more than six times as likely as those without to have placental lesions consistent with maternal underperfusion (adjusted odds ratio- aOR: 6.7; 95% CI 5.2-8.6). To a lesser degree, acute atherosis was also associated with greater risks of having either lesions consistent with fetal vascular thrombo-occlusive disease (aOR 1.7; 95% CI 1.2-2.3) or chronic chorioamnionitis (aOR 1.9; 95% CI 1.3-3), but not with other chronic inflammatory lesions, after adjusting for gestational age at delivery. In contrast, women with acute atherosis were 60% less likely to have lesions consistent with amniotic fluid infection, adjusting for gestational age at delivery (aOR 0.4; 95% CI 0.3-0.5). Conclusions: Acute atherosis is associated with increased risks of having placental lesions consistent with maternal vascular underperfusion, and to a lesser extent, chronic chorioamnionitis and those consistent with fetal vascular thrombo-occlusive disease.
    Journal of Maternal-Fetal and Neonatal Medicine 09/2014; DOI:10.3109/14767058.2014.960835 · 1.21 Impact Factor
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    ABSTRACT: Abstract Objective: Intra-amniotic inflammation is a mechanism of disease implicated in preterm labor, preterm PROM, cervical insufficiency, a short cervix, and idiopathic vaginal bleeding. Determination of interleukin (IL)-6 with immunoassays has been proven for more than 2 decades to be an excellent method for the detection of intra-amniotic inflammation. However, assessment of IL-6 for this indication has been based on immunoassays which are not clinically available, and this has been an obstacle for the implementation of this test in clinical practice. It is now possible to obtain results within 20 minutes with a point of care test which requires minimal laboratory support. This test is based on lateral flow-based immunoassay. The objective of this study was to compare amniotic fluid (AF) IL-6 and interferon-γ -inducible protein 10 (IP-10 or CXCL-10) concentrations determined using lateral flow-based immunoassay or point of care (POC) test and standard enzyme-linked immunosorbent assay (ELISA) techniques. Material and methods: AF samples were collected from patients with singleton gestations and symptoms of preterm labor (n=20). AF IL-6 and IP-10 concentrations were determined by lateral flow-based immunoassay and ELISA. Intra-amniotic inflammation was defined as AF IL-6 > 2.6 ng/ml. AF IL-6 and IP-10 concentrations between two assays were compared. Results: 1) Lateral flow-based immunoassay point of care AF IL-6 and IP-10 test results were strongly correlated with concentrations of this cytokine/chemokine determined by ELISA (Spearman's ρ =0.92 and 0.83, respectively, both p < 0.0001); 2) AF IL-6 concentrations determined by the lateral flow-based immunoassay test were, on average, 30% lower than those determined by ELISA, and the median difference was statistically significant (p < 0.0001); and 3) in contrast, AF IP-10 concentrations determined by the lateral flow-based immunoassay test were, on average, only 7% lower than those determined by ELISA, and the median difference was not statistically significant (p =0.81). Conclusion: Amniotic fluid IL-6 and IP-10 concentrations determined using a lateral flow-based immunoassay point of care are strongly correlated with concentrations determined by conventional ELISA. This justifies further studies about the diagnostic indices and predictive values of this point of care test.
    Journal of Maternal-Fetal and Neonatal Medicine 09/2014; DOI:10.3109/14767058.2014.961417 · 1.21 Impact Factor
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    ABSTRACT: The dysregulation of maternal-fetal immune tolerance is one of the proposed mechanisms leading to preeclampsia. Galectins are key regulator proteins of the immune response in vertebrates and maternal-fetal immune tolerance in eutherian mammals. Previously we found that three genes in a Chr19 cluster encoding for human placental galectins (i.e. galectin-13 (PP13), galectin-14 and galectin-16) emerged during primate evolution and may confer immune tolerance to the semi-allogeneic fetus during the long gestation of anthropoids. Here we present evidence that the villous trophoblastic expression of these galectin genes is developmentally regulated by DNA methylation and induced by key transcription factors of villous placental development during trophoblast fusion and differentiation. This latter mechanism arose via the co-option of binding sites for these transcription factors through promoter evolution and the insertion of an anthropoid-specific L1PREC2 transposable element into the 5’ untranslated region of an ancestral gene followed by gene duplication events. Among placental Chr19 cluster galectin genes, the expression of LGALS13 and LGALS14 is down-regulated in preterm severe preeclampsia associated with SGA. We reveal that this phenomenon is partly originated from the dysregulated expression of key transcription factors controlling trophoblastic functions and galectin gene expression. In addition, the differential DNA methylation of these genes was also observed in preterm preeclampsia irrespective of SGA, suggesting their complex placental dysregulation in this multifaceted syndrome.
    Placenta 08/2014; 35(11). DOI:10.1016/j.placenta.2014.07.015 · 3.29 Impact Factor

Publication Stats

6k Citations
945.98 Total Impact Points

Institutions

  • 1999–2015
    • Wayne State University
      • Department of Obstetrics and Gynecology
      Detroit, Michigan, United States
  • 2007–2014
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      • Division of Intramural Research (DIR)
      Maryland, United States
    • University of Texas Medical Branch at Galveston
      • Department of Obstetrics and Gynecology
      Galveston, Texas, United States
  • 2003–2013
    • National Institute of Child Health and Human Development
      Maryland, United States
    • Thomas Jefferson University
      • Department of Obstetrics & Gynecology
      Filadelfia, Pennsylvania, United States
  • 2006
    • Vanderbilt University
      Нашвилл, Michigan, United States
    • University of Iowa
      • Department of Obstetrics and Gynecology
      Iowa City, Iowa, United States
    • Universitair Medisch Centrum Groningen
      Groningen, Groningen, Netherlands
    • University College Dublin
      Dublin, Leinster, Ireland
  • 2000–2006
    • Detroit Medical Center
      Detroit, Michigan, United States