Sonia S Hassan

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Maryland, United States

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Publications (341)724.26 Total impact

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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.
    09/2014;
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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.
    09/2014;
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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;
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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.
    09/2014;
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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.
    09/2014;
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    ABSTRACT: Abstract Objective: To determine the frequency and clinical significance of sterile- and microbial-associated intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix. Methods: Amniotic fluid (AF) samples obtained by transabdominal amniocentesis from 231 asymptomatic women with a sonographic short cervix [cervical length (CL) <25 mm] were analyzed using cultivation techniques (for aerobic and anaerobic as well as genital mycoplasmas) and broad-range PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency and magnitude of intra-amniotic inflammation [defined as an AF interleukin (IL)-6 concentration ≥2.6 ng/mL], acute histologic placental inflammation, spontaneous preterm delivery, and the amniocentesis-to-delivery interval were examined according to the results of AF cultivation, PCR/ESI-MS and AF IL-6 concentrations. Results: Ten percent (24/231) of patients with a sonographic short cervix had sterile intra-amniotic inflammation (an elevated AF IL-6 concentration without evidence of microorganisms using cultivation or molecular methods). Sterile intra-amniotic inflammation was significantly more frequent than microbial-associated intra-amniotic inflammation [10.4% (24/231) vs. 2.2% (5/231); p<0.001]. Patients with sterile intra-amniotic inflammation had a significantly higher rate of spontaneous preterm delivery <34 weeks of gestation [70.8% (17/24) vs. 31.6% (55/174); p<0.001] and a significantly shorter amniocentesis-to-delivery interval than patients without intra-amniotic inflammation [median 35, (IQR: 10 - 70) vs. median 71, (IQR: 47 - 98) days, (p<0.0001)]. Conclusion: Sterile intra-amniotic inflammation is more common than microbial-associated intra-amniotic inflammation in asymptomatic women with a sonographic short cervix, and is associated with increased risk of spontaneous preterm delivery (<34 weeks). Further investigation is required to determine the causes of sterile intra-amniotic inflammation and the mechanisms whereby this condition is associated with a short cervix and spontaneous preterm delivery.
    08/2014;
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    ABSTRACT: Abstract Objective: Fetuin-A is a negative acute phase protein reactant and acts as a mediator for lipotoxicity, leading to insulin resistance. Intravascular inflammation and insulin resistance have been implicated in the mechanisms of disease responsible for preeclampsia (PE). Maternal plasma concentrations of fetuin-A at the time of diagnosis of preterm PE are lower than in control patients with a normal pregnancy outcome. However, it is unknown if the changes in maternal plasma fetuin-A concentrations precede the clinical diagnosis of the disease. We conducted a longitudinal study to determine whether patients who subsequently developed PE have a different profile of maternal plasma concentrations of fetuin-A as a function of gestational age (GA) than those with uncomplicated pregnancies. Methods: A longitudinal case-control study was performed and included 200 singleton pregnancies in the following groups: 1) patients with uncomplicated pregnancies who delivered appropriate for gestational age (AGA) neonates (n = 160); and 2) patients who subsequently developed PE (n = 40). Longitudinal samples were collected at each prenatal visit and scheduled at 4-week intervals from the first or early second trimester until delivery. Plasma fetuin-A concentrations were determined by ELISA. Analysis was performed using mixed-effects models. Results: The profiles of maternal plasma concentrations of fetuin-A differ between PE and uncomplicated pregnancies. Forward analysis indicated that the rate of increase of plasma fetuin-A concentration in patients who subsequently developed PE was lower at the beginning of pregnancy (p=0.001), yet increased faster in mid-pregnancy (p=0.0017) and reached the same concentration level as controls by 26 weeks. The rate of decrease was higher towards the end of pregnancy in patients with PE than in uncomplicated pregnancies (p=0.002). The mean maternal plasma fetuin-A concentration was significantly lower in patients with preterm PE at the time of clinical diagnosis than in women with uncomplicated pregnancies (p < 0.05). In contrast, there were no significant differences in maternal plasma fetuin-A concentration in patients who developed PE at term. Conclusions: 1) The profile of maternal plasma concentrations of fetuin-A over time (GA) in patients who develop PE is different from that of normal pregnant women; 2) the rate of change of maternal plasma concentrations of fetuin-A is positive (increases over time) in the midtrimester of normal pregnancy, and negative (decreases over time) in patients who subsequently developed PE; 3) at the time of diagnosis, the maternal plasma fetuin-A concentration is lower in preterm PE than in patients with a normal pregnancy outcome; however, such differences were not demonstrable in patients with term PE.
    08/2014;
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    ABSTRACT: Objective: To examine the association between an umbilical artery notch and fetal deterioration in monochorionic/monoamniotic (MC/MA) twins. Methods: Six MC/MA twin pregnancies were admitted at 24-28 weeks of gestation for close fetal surveillance until elective delivery at 32 weeks or earlier in the presence of signs of fetal deterioration. Ultrasound (US) examinations were performed twice weekly. The presence of cord entanglement, umbilical artery notch, abnormal Doppler parameters, a non-reassuring fetal heart rate pattern, or an abnormal fetal biophysical profile were evaluated. Results: Umbilical cord entanglement was observed on US in all pregnancies. The presence of an umbilical artery notch was noted in four out of six pregnancies and in two of them an umbilical artery notch was seen in both twins. The umbilical artery pulsatility index was normal in all fetuses. Doppler parameters of the middle cerebral artery and ductus venosus, fetal biophysical profile and fetal heart rate monitoring remained normal until delivery in all pregnancies. All neonates experienced morbidity related to prematurity; however, all were discharged home in good condition. Conclusion: The presence of an umbilical artery notch and cord entanglement, without other signs of fetal deterioration, are not indicative of an adverse perinatal outcome. © 2014 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 07/2014; · 1.90 Impact Factor
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    ABSTRACT: Abstract Aim: To investigate the effect of depth on cervical shear-wave elastography. Methods: Shear-wave elastography was applied to estimate the velocity of propagation of the acoustic force impulse (shear wave) in the cervix of 154 pregnant women at 11-36 weeks of gestation. Shear-wave speed (SWS) was evaluated in cross-sectional views of the internal and external cervical os in five regions of interest: anterior, posterior, lateral right, lateral left, and endocervix. Distance from the center of the ultrasound (US) transducer to the center of each region of interest was registered. Results: In all regions, SWS decreased significantly with gestational age (P=0.006). In the internal os, SWS was similar among the anterior, posterior, and lateral regions and lower in the endocervix. In the external os, the endocervix and anterior regions showed similar SWS values, lower than those from the posterior and lateral regions. In the endocervix, these differences remained significant after adjustment for depth, gestational age, and cervical length. SWS estimations in all regions of the internal os were higher than those of the external os, suggesting denser tissue. Conclusion: Depth from the US probe to different regions in the cervix did not significantly affect the SWS estimations.
    Journal of perinatal medicine. 07/2014;
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    ABSTRACT: ProblemInflammation and infection play a major role in preterm birth. The purpose of this study was to (i) determine the prevalence and clinical significance of sterile intra-amniotic inflammation and (ii) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box-1 (HMGB1) and the interval from amniocentesis to delivery in patients with sterile intra-amniotic inflammation.Method of studyAF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad-range PCR and mass spectrometry (PCR/ESI-MS). Sterile intra-amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra-amniotic inflammation (AF interleukin-6 ≥ 2.6 ng/mL).Results(i) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) versus 11% (15/135); (P = 0.005)], (ii) patients with sterile intra-amniotic inflammation delivered at comparable gestational ages had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial-associated intra-amniotic inflammation, and (iii) patients with sterile intra-amniotic inflammation and high AF concentrations of HMGB1 (≥8.55 ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (P = 0.02).Conclusion(i) Sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation, and (ii) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor.
    American Journal Of Reproductive Immunology 07/2014; · 3.32 Impact Factor
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    ABSTRACT: The lesion termed 'placental infarction hematoma' is associated with fetal death and adverse perinatal outcome. Such a lesion has been associated with a high risk of fetal death and abruption placentae. The fetal and placental hemodynamic changes associated with placental infarction hematoma have not been reported. This paper describes a case of early and severe growth restriction with preeclampsia, and progressive deterioration of the fetal and placental Doppler parameters in the presence of a placental infarction hematoma. © 2014 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 05/2014; · 1.90 Impact Factor
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    ABSTRACT: To evaluate fetal cerebral venous blood oxygenation, Yv, using principles of MR susceptometry. A cohort of 19 pregnant subjects, with a mean gestational age of 31.6 ± 4.7 weeks were imaged using a modified susceptibility-weighted imaging (SWI) sequence. Data quality was first assessed for feasibility of oxygen saturation measurement, and data from five subjects (mean ± std gestational age of 33.7 ± 3.6 weeks) were then chosen for further quantitative analysis. SWI phase in the superior sagittal sinus was used to evaluate oxygen saturation using the principles of MR susceptometry. Systematic error in the measured Y(v) values was studied through simulations. Simulations showed that the systematic error in Yv depended upon the assumed angle of the vessel, θ, relative to the main magnetic field and the error in that vessel angle δθ. For the typical vessel angle of θ = 30° encountered in the fetal data analyzed, a δθ as large as ±20° led to an absolute error, δYv, of less than 11%. The measured mean oxygen saturation across the five fetuses was 66% ± 9.4%. This average cerebral venous blood oxygenation value is in close agreement with values in the published literature. We have reported the first in vivo measurement of human fetal cerebral venous oxygen saturation using MRI.
    Journal of Magnetic Resonance Imaging 04/2014; 39(4):998-1006. · 2.57 Impact Factor
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    ABSTRACT: This study was undertaken to characterize the vaginal microbiota throughout normal human pregnancy using sequence-based techniques. We compared the vaginal microbial composition of non-pregnant patients with a group of pregnant women who delivered at term. A retrospective case-control longitudinal study was designed and included non-pregnant women (n = 32) and pregnant women who delivered at term (38 to 42 weeks) without complications (n = 22). Serial samples of vaginal fluid were collected from both non-pregnant and pregnant subjects. A 16S rRNA gene sequence-based survey was conducted using pyrosequencing to characterize the structure and stability of the vaginal microbiota. Linear mixed effects models and generalized estimating equations were used to identify the phylotypes whose relative abundance was different between the two study groups. The vaginal microbiota of normal pregnant women was different from that of non-pregnant women (higher abundance of Lactobacillus vaginalis, L. crispatus, L. gasseri and L. jensenii and lower abundance of 22 other phylotypes in pregnant women). Bacterial community state type (CST) IV-B or CST IV-A characterized by high relative abundance of species of genus Atopobium as well as the presence of Prevotella, Sneathia, Gardnerella, Ruminococcaceae, Parvimonas, Mobiluncus and other taxa previously shown to be associated with bacterial vaginosis were less frequent in normal pregnancy. The stability of the vaginal microbiota of pregnant women was higher than that of non-pregnant women; however, during normal pregnancy, bacterial communities do shift but almost exclusively from one CST dominated by Lactobacillus spp. to another CST dominated by Lactobacillus spp. We report the first longitudinal study of the vaginal microbiota in normal pregnancy. Differences in the composition and stability of the microbial community between pregnant and non-pregnant women were observed. Lactobacillus spp. were the predominant members of the microbial community in normal pregnancy. These results can serve as the basis to study the relationship between the vaginal microbiome and adverse pregnancy outcomes.
    Microbiome. 02/2014; 2(1):4.
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    ABSTRACT: The diagnosis of microbial invasion of the amniotic cavity (MIAC) has been traditionally performed using traditional cultivation techniques, which require growth of microorganisms in the laboratory. Shortcomings of culture methods include the time required (days) for identification of microorganisms, and that many microbes involved in the genesis of human diseases are difficult to culture. A novel technique combines broad-range real-time polymerase chain reaction with electrospray ionization time-of-flight mass spectrometry (PCR/ESI-MS) to identify and quantify genomic material from bacteria and viruses. AF samples obtained by transabdominal amniocentesis from 142 women with preterm labor and intact membranes (PTL) were analyzed using cultivation techniques (aerobic, anaerobic, and genital mycoplasmas) as well as PCR/ESI-MS. The prevalence and relative magnitude of intra-amniotic inflammation [AF interleukin 6 (IL-6) concentration ≥ 2.6 ng/mL], acute histologic chorioamnionitis, spontaneous preterm delivery, and perinatal mortality were examined. (i) The prevalence of MIAC in patients with PTL was 7% using standard cultivation techniques and 12% using PCR/ESI-MS; (ii) seven of ten patients with positive AF culture also had positive PCR/ESI-MS [≥17 genome equivalents per PCR reaction well (GE/well)]; (iii) patients with positive PCR/ESI-MS (≥17 GE/well) and negative AF cultures had significantly higher rates of intra-amniotic inflammation and acute histologic chorioamnionitis, a shorter interval to delivery [median (interquartile range-IQR)], and offspring at higher risk of perinatal mortality, than women with both tests negative [90% (9/10) versus 32% (39/122) OR: 5.6; 95% CI: 1.4-22; (P < 0.001); 70% (7/10) versus 35% (39/112); (P = 0.04); 1 (IQR: <1-2) days versus 25 (IQR: 5-51) days; (P = 0.002), respectively]; (iv) there were no significant differences in these outcomes between patients with positive PCR/ESI-MS (≥17 GE/well) who had negative AF cultures and those with positive AF cultures; and (v) PCR/ESI-MS detected genomic material from viruses in two patients (1.4%). (i) Rapid diagnosis of intra-amniotic infection is possible using PCR/ESI-MS; (ii) the combined use of biomarkers of inflammation and PCR/ESI-MS allows for the identification of specific bacteria and viruses in women with preterm labor and intra-amniotic infection; and (iii) this approach may allow for administration of timely and specific interventions to reduce morbidity attributed to infection-induced preterm birth.
    American Journal Of Reproductive Immunology 01/2014; · 3.32 Impact Factor
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    ABSTRACT: This study was undertaken to determine whether the vaginal microbiota of pregnant women who subsequently had a spontaneous preterm delivery is different from that of women who had a term delivery.
    Microbiome. 01/2014; 2:18.
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    ABSTRACT: Abstract Objective: Human pregnancy is characterized by activation of the innate immune response and suppression of adaptive immunity. The former is thought to provide protection against infection for the mother, and the latter, tolerance against paternal antigens expressed in fetal cells. Acute pyelonephritis is associated with an increased risk of acute respiratory distress syndrome and sepsis in pregnant (vs. nonpregnant) women. The objective of this study was to describe the gene expression profile (transcriptome) of maternal whole blood in acute pyelonephritis. Method: A case-control study was conducted to include pregnant women with acute pyelonephritis (n=15) and women with a normal pregnancy (n=34). Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA, USA) were used for gene expression profiling. A linear model was used to test the association between the presence of pyelonephritis and gene expression levels while controlling for white blood cell count and gestational age. A fold change of 1.5 was considered significant at a false discovery rate of 0.1. A subset of differentially expressed genes (n=56) was tested with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (cases, n=19; controls, n=59). Gene ontology and pathway analyses were applied. Results: A total of 983 genes were differentially expressed in acute pyelonephritis: 457 were upregulated and 526 were downregulated. Significant enrichment of 300 biological processes and 63 molecular functions was found in pyelonephritis. Significantly impacted pathways in pyelonephritis included (a) cytokine-cytokine receptor interaction, (b) T-cell receptor signaling, (c) Jak-STAT signaling, and (d) complement and coagulation cascades. Of 56 genes tested by qRT-PCR, 48 (85.7%) had confirmation of differential expression. Conclusion: This is the first study of the transcriptomic signature of whole blood in pregnant women with acute pyelonephritis. Acute infection during pregnancy is associated with the increased expression of genes involved in innate immunity and the decreased expression of genes involved in lymphocyte function.
    Journal of Perinatal Medicine 01/2014; 42(1):31-53. · 1.95 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 01/2014; · 3.12 Impact Factor
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    ABSTRACT: The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks) and older (GA≥31 weeks) fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed.
    PLoS ONE 01/2014; 9(5):e94423. · 3.73 Impact Factor
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    ABSTRACT: Abstract Objective: To determine if there is an association between cervical strain, evaluated using ultrasound elastography, and spontaneous preterm delivery (sPTD) <37 weeks of gestation. Methods: One hundred and eighty nine (189) women at 16-24 weeks of gestation were evaluated. Ultrasound elastography was used to estimate cervical strain in three anatomical planes: one mid-sagittal in the same plane used for cervical length measurement, and two cross sectional images: one at the level of the internal cervical os, and the other at the level of the external cervical os. In each plane, two regions of interest (endocervix and entire cervix) were examined; a total of six regions of interest were evaluated. Results: The prevalence of sPTD was 11% (21/189). Strain values from each of the six cervical regions correlated weakly with cervical length (from r=-0.24, P<0.001 to r=-0.03, P=0.69). Strain measurements obtained in a cross sectional view of the internal cervical os were significantly associated with sPTD. Women with strain values ≤25th centile in the endocervical canal (0.19) and in the entire cervix (0.14) were 80% less likely to have a sPTD than women with strain values >25th centile [endocervical: odds ratio (OR) 0.2; 95% confidence interval (CI), 0.03-0.96; entire cervix: OR 0.17; 95% CI, 0.03-0.9]. Additional adjustment for gestational age, race, smoking status, parity, maternal age, pre-pregnancy body mass index, and previous preterm delivery did not appreciably alter the magnitude or statistical significance of these associations. Strain values obtained from the external cervical os and from the sagittal view were not associated with sPTD. Conclusion: Low strain values in the internal cervical os were associated with a significantly lower risk of spontaneous preterm delivery <37 weeks of gestation.
    Journal of Perinatal Medicine 12/2013; · 1.95 Impact Factor

Publication Stats

5k Citations
724.26 Total Impact Points

Institutions

  • 2008–2014
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      • Division of Intramural Research (DIR)
      Maryland, United States
    • National Institutes of Health
      Maryland, United States
    • Emory University
      • Department of Anthropology
      Atlanta, GA, United States
  • 1999–2014
    • Wayne State University
      • Department of Obstetrics and Gynecology
      Detroit, Michigan, United States
  • 2003–2013
    • National Institute of Child Health and Human Development
      Maryland, United States
  • 2010
    • Washington University in St. Louis
      • Department of Obstetrics and Gynecology
      Saint Louis, MO, United States
  • 2000–2010
    • Detroit Medical Center
      • Division of Pathology
      Detroit, Michigan, United States
  • 2009
    • Beaumont Health System
      • Department of Obstetrics and Gynecology
      Detroit, Michigan, United States
    • William Beaumont Army Medical Center
      El Paso, Texas, United States