Shali Mazaki-Tovi

Wayne State University, Detroit, MI, United States

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Publications (160)333.93 Total impact

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    ABSTRACT: Multifetal pregnancy reduction (MPR) of triplets to twins results in improved pregnancy outcomes compared with triplet gestations managed expectantly. Perinatal outcomes of early transvaginal MPR from triplets to twins were compared with reduction from triplets to singletons. Seventy-four trichorionic triplet pregnancies that underwent early transvaginal MPR at 6–8 weeks gestation were included. Cases were divided into two groups according to the initial procedure: reduction to twin (n = 55) or to singleton (n = 19) gestations. Infants from triplet pregnancies reduced to twins were delivered earlier (36.6 versus 37.9 weeks; P = 0.04) and had lower mean birth weights (2364 g versus 2748 g; P = 0.02) compared with those from triplets reduced to singleton gestations. The rates of pregnancy loss before 24 weeks (3.6% versus 5.3%), as well as of preterm delivery before 32 and 34 weeks of gestation (0% versus 5.3% and 7.3% versus 5.3%, respectively) were similar between the twin and singleton pregnancies. No significant difference was found in the prevalence of gestational diabetes (15.1% versus 5.6%) or gestational hypertension (24.5% versus 16.7%) between the groups. Selective reduction of triplet pregnancies to singleton rather than twin gestations is associated with improved outcomes.
    Reproductive biomedicine online 12/2014; · 2.68 Impact Factor
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    ABSTRACT: Abstract Objective: Magnesium sulfate (MgSO4) administered to women at risk for preterm delivery decreases the risk of cerebral palsy in their children. However, the neuroprotective effect of MgSO4 has not been shown in twin gestations. Thus, the aim of this study was to determine the maternal serum levels of magnesium in twin vs. singleton pregnancies following intravenous treatment of MgSO4. Methods: Case control study including two groups of pregnant women who received intravenous MgSO4: (1) twin gestations (n=83) and (2) singleton pregnancies (n=83). Maternal serum magnesium levels 6 and 24 h after initiation of treatment were determined in both groups. Results: Maternal serum levels of magnesium were significantly lower among patients with twin gestations compared to those with singleton ones 6 h after initiation of treatment (4.6 vs. 4.8 mg/dL, P=0.003). In addition, the rate of pregnant women who obtained therapeutic levels 6 h after initiation of treatment was significantly lower in twin gestations than in singleton ones (36% vs. 58%, P=0.008). Multiple regression analysis revealed that twin gestations were independently and significantly associated with low maternal serum magnesium levels. Conclusions: Maternal serum concentrations of magnesium are lower in twin pregnancies than in singleton ones following MgSO4 treatment, which might explain the decreased neuroprotective effect of MgSO4 reported in twin pregnancies.
    American Journal of Obstetrics and Gynecology 09/2014; · 3.88 Impact Factor
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    ABSTRACT: Objective To determine the prevalence of placental complications in patients conceived through donor versus autologous oocytes. Study Design A retrospective cohort study including two groups of patients who conceived through in vitro fertilization using: 1) donor oocyte (n=139) and 2) autologous oocyte (n=126). Only singleton gestations were included .The rate of placental complications including preeclampsia, gestational hypertension and intra uterine growth restriction (IUGR) was compared between these two groups. Results The women who conceived using donor oocytes were older compared to women who conceived using autologous oocytes (median maternal age 45 vs 41, p<0.01). The rate of hypertensive diseases of pregnancy including gestational hypertension and preeclampsia was significantly higher in ovum donor recipients compared with women conceived with autologous oocytes (25% vs 10%, p<0.01). Similarly, the rate of IUGR was also higher among patients conceived through oocytes donation although it did not reach statistical significance (9.3% vs 4%, p=0.08). When maternal age was restricted to ≤45 years, the rate of hypertensive diseases of pregnancy remained significantly higher among ovum donor compared to autologous oocyte recipients (22% vs 10%, p=0.02). Adjustment for maternal age, gravidity, parity and chronic hypertension revealed that oocyte donation was independently associated with higher rate of hypertensive diseases of pregnancy (P=0.01). Conclusions Patients conceived through oocytes donation have an increased risk for placental complications of pregnancy. These findings support the "immunological theory" suggesting that immunological intolerance between the mother and the fetus may play an important role in the pathogenesis of preeclampsia.
    American journal of obstetrics and gynecology 01/2014; · 3.28 Impact Factor
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    ABSTRACT: Abstract Objectives: Chemerin, a novel adipocytokine, has been implicated in major metabolic and inflammatory processes. Study aims were to determine whether circulating maternal chemerin concentration (1) differs between pregnant and non-pregnant women, (2) changes as a function of gestational age, and (3) correlates with maternal insulin resistance. In addition, we investigated which compartment, maternal, fetal or placental, is the source of chemerin in maternal circulation. Methods: The study included three groups: Non-pregnant (n=18), pregnant women in the first trimester (n=19) and pregnant women in the third trimester (n=33). Chemerin was measured in cord blood and in maternal serum samples taken before and after delivery. Chemerin mRNA expression was evaluated in fetal and human adult tissues. Results: Chemerin serum concentration was significantly higher in pregnant women in the third trimester than in non-pregnant and pregnant women in the first trimester. Chemerin concentration positively correlated with body mass index (BMI) and insulin resistance. Antenatal chemerin concentration was significantly lower than that during the postpartum period. Neonatal chemerin did not correlate with maternal one. Chemerin mRNA expression was abundant in fetal and adult liver and omental fat, but relatively low in placenta. Conclusions: Chemerin is increased during normal gestation and is associated with maternal BMI and insulin resistance. Maternal tissues, possibly liver and adipose tissue, contribute to the increased maternal chemerin concentration.
    Journal of Perinatal Medicine 12/2013; · 1.95 Impact Factor
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    ABSTRACT: To determine maternal plasma levels of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), placental growth factor (PLGF) and soluble endoglin (sEng) in monochorionic diamniotic (MC/DA) twin pregnancies complicated by twin to twin transfusion syndrome (TTTS) or selective intra-uterine growth restriction (sIUGR). A longitudinal cohort study of pregnant women with MC/DA twins who were classified into 3 groups: 1. Uncomplicated MC/DA twins (n=22) 2. TTTS (n=23) and 3. sIUGR (n=15). Maternal plasma samples were obtained between 13-20 and 21-28 weeks of gestation and cord blood samples were collected at delivery. Maternal plasma concentrations of sVEGFR-1, PLGF and sEng, as well as cord blood levels of sVEGFR-1were measured by ELISA. Maternal plasma levels of sVEGFR-1 and sEng were significantly higher in patients with TTTS at the early and late second trimester compared to normal monochorionic pregnancies (p<0.01). In contrast, in the sIUGR group, sVEGFR-1 and sEng levels were significantly higher only at the late second trimester (p<0.05). PLGF levels were significantly lower at the early and late second trimester in both TTTS and sIUGR compared to controls (p<0.01). Plasma concentrations of sVEGFR-1 were significantly higher among TTTS pregnancies compared to sIUGR at the late second trimester (p=0.027). Cord blood levels of sVEGFR-1 were significantly higher in the smaller IUGR twin compared to the normal co-twin. Monochorionic pregnancies complicated by TTTS and sIUGR are characterized by decreased angiogenic activity. The disparity in severity of the anti-angiogenic state between TTTS and sIUGR suggests that these two conditions may represent a continuum.
    American journal of obstetrics and gynecology 09/2013; · 3.28 Impact Factor
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    ABSTRACT: OBJECTIVE: To determine if increased placental vascular impedance to flow is associated with changes in fetal cardiac function using spatiotemporal image correlation (STIC) and Virtual Organ Computer-aided AnaLysis (VOCAL). STUDY DESIGN: A cross-sectional study was performed in fetuses with an umbilical artery pulsatility index > 95(th) percentile (ABN). Ventricular volume (end-systole, end-diastole), stroke volume (SV), cardiac output (CO), adjusted CO, and ejection fraction (EF) were compared to those of 184 normal fetuses (NL). RESULTS: 1) 34 fetuses were evaluated at a median gestational age of 28.3 (range 20.6 - 36.9) weeks; 2) mean ventricular volumes were lower for ABN than NL (end-systole, end-diastole) with a proportionally greater decrease for left ventricular volume (vs. right); 3) mean left and right SV, CO, and adjusted CO were lower for ABN (vs. NL); 4) right ventricular volume, SV, CO, and adjusted CO exceeded the left in ABN fetuses; 5) mean EF was greater for ABN than NL; and 6) median left EF was greater (vs. right) in ABN fetuses. CONCLUSION: Increased placental vascular impedance to flow is associated with changes in fetal cardiac function.
    American journal of obstetrics and gynecology 12/2012; · 3.28 Impact Factor
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    ABSTRACT: OBJECTIVE: Chemerin, a novel adipokine, has been implicated in adipogenesis, inflammation, and metabolism. The aims of this study were to determine the presence of chemerin in cord blood and its association with birthweight. STUDY DESIGN: This cross-sectional study included the following: (1) twins with (n = 24) or without (n = 28) birthweight discordancy; and (2) singletons subclassified into small-for-gestational-age (SGA; n = 18); appropriate for gestational age (AGA; n = 33); and large-for-gestational-age (LGA; n = 8). Cord blood chemerin was determined. Parametric and nonparametric statistics were used for analysis. RESULTS: The results of the study included the following: (1) within the discordant twins group, the median chemerin concentration was significantly lower in the SGA group than in their cotwins; (2) within singletons, the median chemerin concentration was significantly higher in the LGA than the AGA newborns; and (3) the regression model revealed that chemerin was independently associated with birthweight. CONCLUSION: Cord blood chemerin is present in cord blood and its concentrations are positively correlated with birthweight. These novel findings support a role of adipokines in fetal growth.
    American journal of obstetrics and gynecology 08/2012; · 3.28 Impact Factor
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    ABSTRACT: The purpose of this study was to determine whether corticosteroid administration after 34 weeks of gestation is associated with improved neonatal outcome in the presence of fetal lung immaturity. We conducted a retrospective cohort study of women who underwent amniocentesis to determine fetal lung maturity from 34-37 weeks of gestation. Patients with negative results (167 women) received steroids based on physician preference and were categorized into 2 groups: study group treated with betamethasone (n = 83 women) and control group in which patients did not receive betamethasone therapy (n = 84 women). The 2 groups were compared with respect to neonatal outcomes. Composite neonatal morbidity was defined as the presence of respiratory distress syndrome, transient tachypnea of the newborn infant, or the need for respiratory support. The rate of composite neonatal morbidity was significantly lower among infants who were exposed to steroids compared with the control group (8.4% vs 21%; P = .02). Multiple regression analysis revealed that corticosteroid administration was associated independently with the composite morbidity outcome. Antenatal steroid administration after 34 weeks of gestation is associated with improved neonatal outcome and should be considered when fetal lung immaturity is documented.
    American journal of obstetrics and gynecology 06/2012; 207(3):222.e1-4. · 3.28 Impact Factor
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    ABSTRACT: Preeclampsia, a severe unpredictable complication of pregnancy, occurs in 6% of pregnancies, usually in the second or third trimester. The specific etiology of preeclampsia remains unclear, although the pathophysiological hallmark of this condition appears to be an inadequate blood supply to the placenta. As a result of the impaired placental blood flow, intrauterine growth restriction (IUGR) and consequential fetal oxidative stress may occur. Consistent with this view, pregnancies complicated by preeclampsia and IUGR are characterized by up-regulation of key transcriptional regulators of the hypoxic response including, hif1α and as well as p53 and its target genes. Recently, the presence of circulating cell-free fetal RNA has been documented in maternal plasma. We speculated that pregnancies complicated by preeclampsia and IUGR, will be associated with an abnormal expression of p53 and/or hif1α related genes in the maternal plasma. Maternal plasma from 113 singleton pregnancies (72 normal and 41 complicated pregnancies) and 19 twins (9 normal and 10 complicated pregnancies) were collected and cell free RNA was extracted. The expression of 18 genes was measured by one step real-time RT-PCR and was analyzed for prevalence of positive/negative expression levels. Results indicate that, among the genes examined, cell free plasma expressions of p21 and hif1α were more prevalent in pregnancies complicated by hypoxia and/or IUGR (p<0.001). To conclude, we present in this manuscript data to support the association between two possible surrogate markers of hypoxia and common complications of pregnancy. More work is needed in order to implement these findings in clinical practice.
    PLoS ONE 01/2012; 7(5):e37273. · 3.53 Impact Factor
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    ABSTRACT: Early postpartum period is characterised by a dramatic decrease in insulin resistance and significant metabolic alterations. The aims of this study were to determine the changes in circulating maternal concentrations of total adiponectin, adiponectin multimers, leptin and resistin before and after the delivery and to explore their relationship with insulin sensitivity. Twenty-seven normal pregnant women at term were included in this longitudinal study. Blood samples were taken before and 4 days after elective caesarean section. Total adiponectin, adiponectin multimers, leptin, resistin, glucose, insulin and prolactin were measured in maternal serum. Adiponectin multimers were measured before and after the delivery in eight women. (1) The mean maternal serum total adiponectin concentration was significantly higher before than after delivery while the relative distribution of circulating maternal adiponectin multimers did not change after delivery; (2) the median maternal serum concentration of leptin was significantly higher in the antepartum than in the postpartum period; (3) the median maternal serum resistin concentration was comparable before and after delivery; (4) multiple linear regression analysis revealed that antepartum insulin sensitivity was associated with maternal low body mass index, and low glucose concentrations in glucose challenge test, as well as with maternal age and increased leptin concentrations. Postpartum insulin sensitivity was associated with decreased circulating resistin concentrations. Despite increase in insulin sensitivity, early postpartum period is characterised by a decrease in maternal circulating total adiponectin and by steady concentrations of resistin and adiponectin multimers compared to the late third trimester.
    Gynecological Endocrinology 06/2011; 27(9):725-31. · 1.30 Impact Factor
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    ABSTRACT: Congenital varicella syndrome, maternal varicella-zoster virus pneumonia and neonatal varicella infection are associated with serious fetomaternal morbidity and, not infrequently, mortality. Vaccination against varicella-zoster virus can prevent the disease, and outbreak control limits the exposure of pregnant women to the infectious agent. Maternal varicella-zoster immunoglobulin administration before rash development, with or without antiviral medication, can modify the progression of the disease.
    BJOG An International Journal of Obstetrics & Gynaecology 05/2011; 118(10):1155-62. · 3.76 Impact Factor
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    ABSTRACT: Listeria is commonly found in processed and prepared foods and listeriosis is associated with high morbidity and mortality. Preventative measures are well prescribed and monitoring and voluntary recall of contaminated products has resulted in a 44% reduction in the prevalence of perinatal listeriosis in the USA. Pregnant women are at high risk for listeriosis, but symptoms are non-specific and diagnosis is difficult. The intracellular life-cycle of Listeria protects the bacterium from host innate and adaptive immune responses. Antibiotic treatment requires agents able to penetrate, distribute, and remain stable within host cells. Prolonged use of high-dose ampicillin can significantly improve neonatal outcome.
    Journal of Perinatal Medicine 05/2011; 39(3):227-36. · 1.95 Impact Factor
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    ABSTRACT: The fetal inflammatory response syndrome (FIRS) has been described in the context of preterm labor and preterm prelabor rupture of the membranes and is often associated with intra-amniotic infection/inflammation. This syndrome is characterized by systemic fetal inflammation and operationally defined by an elevated fetal plasma interleukin (IL)-6. The objective of this study was to determine if FIRS can be found in fetuses with activation of their immune system, such as the one observed in Rh alloimmune-mediated fetal anemia. Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n=16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of >11 pg/ml. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis. (1) The prevalence of an elevated fetal plasma IL-6 was 25% (4/16); (2) there was an inverse relationship between the fetal hematocrit and IL-6 concentration -- the lower the hematocrit, the higher the fetal IL-6 (r=-0.68, p=0.004); (3) fetuses with anemia had a significantly higher plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile range (IQR) 1.18-2.63 vs. 1.46 pg/ml, IQR 1.76-14.7; p=0.02); (4) interestingly, all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence 40%, 4/10), while in the group without anemia, none had an elevated fetal plasma IL-6. An elevation in fetal plasma IL-6 can be observed in a subset of fetuses with anemia due to Rh alloimmunization. This observation suggests that the hallmark of FIRS can be caused by non-infection-related insults. Further studies are required to determine whether the prognosis of FIRS caused by intra-amniotic infection/inflammation is different from that induced by alloimmunization.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 03/2011; 24(3):391-6. · 1.36 Impact Factor
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    ABSTRACT: The purpose of this study was to determine whether there is a relationship between the frequency of meconium-stained amniotic fluid (MSAF) and the duration of labor in term singleton gestation. The clinical characteristics of women who delivered term singleton live newborns between 2001 and 2006 were examined. The cases involving neonates with major congenital anomalies were excluded. (1) The frequency of MSAF in term pregnancies was 18.4% (806/4376); (2) MSAF was found in only 2.8% (28/1008) of women who delivered by elective cesarean, but in 23.1% (778/3368) of women who delivered after the onset of labor (p < 0.001); (3) The longer the duration of labor (first stage, second stage, or total), the higher the frequency of MSAF (p < 0.001 for each); this remained significant after adjusting for other confounding variables such as parity, duration of rupture of membranes, gestational age at delivery, and mode of delivery (p < 0.001 for each). MSAF was found in only 2.8% (28/1008) of women who delivered before the onset of labor, but in 23.1% (778/3368) of women who delivered after the onset of labor. The longer the duration of labor, the higher the risk of MSAF in term singleton gestation.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 03/2011; 24(7):880-5. · 1.36 Impact Factor
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    ABSTRACT: To examine the association between maternal and fetal genetic variants and small-for-gestational-age (SGA). A case-control study was conducted in patients with SGA neonates (530 maternal and 436 fetal) and controls (599 maternal and 628 fetal); 190 candidate genes and 775 SNPs were studied. Single-locus, multi-locus and haplotype association analyses were performed on maternal and fetal data with logistic regression, multifactor dimensionality reduction (MDR) analysis, and haplotype-based association with 2 and 3 marker sliding windows, respectively. Ingenuity pathway analysis (IPA) software was used to assess pathways that associate with SGA. The most significant single-locus association in maternal data was with a SNP in tissue inhibitor of metalloproteinase 2 (TIMP2) (rs2277698 OR = 1.71, 95% CI [1.26-2.32], p = 0.0006) while in the fetus it was with a SNP in fibronectin 1 isoform 3 preproprotein (FN1) (rs3796123, OR = 1.46, 95% CI [1.20-1.78], p = 0.0001). Both SNPs were adjusted for potential confounders (maternal body mass index and fetal sex). Haplotype analyses resulted in associations in α 1 type I collagen preproprotein (COL1A1, rs1007086-rs2141279-rs17639446, global p = 0.006) in mothers and FN1 (rs2304573-rs1250204-rs1250215, global p = 0.045) in fetuses. Multi-locus analyses with MDR identified a two SNP model with maternal variants collagen type V α 2 (COL5A2) and plasminogen activator urokinase (PLAU) predicting SGA outcome correctly 59% of the time (p = 0.035). Genetic variants in extracellular matrix-related genes showed significant single-locus association with SGA. These data are consistent with other studies that have observed elevated circulating fibronectin concentrations in association with increased risk of SGA. The present study supports the hypothesis that DNA variants can partially explain the risk of SGA in a cohort of Hispanic women.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 02/2011; 24(2):362-80. · 1.36 Impact Factor
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    ABSTRACT: Among pregnant women, acquired viral infections with a concurrent bacterial infection is a detrimental factor associated to poor prognosis. We evaluate the effect of a viral infection that does not lead to pre-term labor on the response to low doses of lipopolysaccharide (LPS). Our objectives were (i) to characterize the effect of a viral infection concurrent with exposure to microbial products on pregnancy outcome and (ii) to characterize the placental and fetal immune responses to the viral sensitization to LPS. C57B/6 wild-type mice were injected with murine gammaherpesvirus 68 (MHV68) at E8.5. Either PBS or LPS was injected i.p. at E15.5. Pregnancy outcome and cytokine/chemokine profile from implantation sites were analyzed by multiplex. LPS treatment of MHV-68-infected animals induced pre-term delivery and fetal death in 100% of the mice. Pre-term labor was characterized by a upregulation of pro-inflammatory cytokines and chemokines in both placenta and decidua. Similar profiles were observed from MHV-68-infected human primary trophoblast and trophoblast cell lines in response to LPS. We describe for the first time that a sub-clinical viral infection in pregnant mice might sensitize to a bacterial infection leading to pre-term delivery. We propose the 'Double Hit Hypothesis' where the presence of a viral infection enhances the effect of bacterial products during pregnancy leading not only to pre-term labor but likely larger adverse outcomes.
    American Journal Of Reproductive Immunology 02/2011; 65(2):110-7. · 3.32 Impact Factor
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    ABSTRACT: Caesarean delivery is frequently complicated by surgical site infections, endometritis and urinary tract infection. Most surgical site infections occur after discharge from the hospital, and are increasingly being used as performance indicators. Worldwide, the rate of caesarean delivery is increasing. Evidence-based guidelines recommended the use of prophylactic antibiotics before surgical incision. An exception is made for caesarean delivery, where narrow-range antibiotics are administered after umbilical cord clamping because of putative neonatal benefit. However, recent evidence supports the use of pre-incision, broad-spectrum antibiotics, which result in a lower rate of maternal morbidity with no disadvantage to the neonate.
    BJOG An International Journal of Obstetrics & Gynaecology 01/2011; 118(2):193-201. · 3.76 Impact Factor
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    ABSTRACT: The aim of this study was to determine the association between cord blood adiponectin and leptin and early infant growth at one year in small for gestational age (SGA) and appropriate for gestational age (AGA) infants. In this prospective study adiponectin and leptin concentrations were determined in cord blood of (i) AGA newborns (n = 44) and (ii) SGA newborns (n = 24). At one year of age, height and weight were measured. Linear regression analysis was used to determine which factors were associated with anthropometric measurements at the age of one year. (i) SGA neonates had a significantly lower median cord blood adiponectin and leptin than AGA neonates; (ii) among SGA neonates, cord blood adiponectin concentrations were negatively correlated with body weight at one year, weight gain after one year and with BMI at one year; and (iii) among AGA neonates cord blood adiponectin concentrations were negatively correlated with body weight at one year, weight gain after one year and with BMI at one year. The disparity in cord blood adiponectin and leptin concentrations between SGA and AGA neonates suggests a role for adipokines in fetal growth.
    Journal of pediatric endocrinology & metabolism: JPEM 01/2011; 24(7-8):411-8. · 0.75 Impact Factor
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    ABSTRACT: Biomarkers for preterm labor (PTL) and delivery can be discovered through the analysis of the transcriptome (transcriptomics) and protein composition (proteomics). Characterization of the global changes in low-molecular weight compounds which constitute the 'metabolic network' of cells (metabolome) is now possible by using a 'metabolomics' approach. Metabolomic profiling has special advantages over transcriptomics and proteomics since the metabolic network is downstream from gene expression and protein synthesis, and thus more closely reflects cell activity at a functional level. This study was conducted to determine if metabolomic profiling of the amniotic fluid can identify women with spontaneous PTL at risk for preterm delivery, regardless of the presence or absence of intraamniotic infection/inflammation (IAI). Two retrospective cross-sectional studies were conducted, including three groups of pregnant women with spontaneous PTL and intact membranes: (1) PTL who delivered at term; (2) PTL without IAI who delivered preterm; and (3) PTL with IAI who delivered preterm. The first was an exploratory study that included 16, 19, and 20 patients in groups 1, 2, and 3, respectively. The second study included 40, 33, and 40 patients in groups 1, 2, and 3, respectively. Amniotic fluid metabolic profiling was performed by combining chemical separation (with gas and liquid chromatography) and mass spectrometry. Compounds were identified using authentic standards. The data were analyzed using discriminant analysis for the first study and Random Forest for the second. (1) In the first study, metabolomic profiling of the amniotic fluid was able to identify patients as belonging to the correct clinical group with an overall 96.3% (53/55) accuracy; 15 of 16 patients with PTL who delivered at term were correctly classified; all patients with PTL without IAI who delivered preterm neonates were correctly identified as such (19/19), while 19/20 patients with PTL and IAI were correctly classified. (2) In the second study, metabolomic profiling was able to identify patients as belonging to the correct clinical group with an accuracy of 88.5% (100/113); 39 of 40 patients with PTL who delivered at term were correctly classified; 29 of 33 patients with PTL without IAI who delivered preterm neonates were correctly classified. Among patients with PTL and IAI, 32/40 were correctly classified. The metabolites responsible for the classification of patients in different clinical groups were identified. A preliminary draft of the human amniotic fluid metabolome was generated and found to contain products of the intermediate metabolism of mammalian cells and xenobiotic compounds (e.g. bacterial products and Salicylamide). Among patients with spontaneous PTL with intact membranes, metabolic profiling of the amniotic fluid can be used to assess the risk of preterm delivery in the presence or absence of infection/inflammation.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 12/2010; 23(12):1344-59. · 1.36 Impact Factor
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    ABSTRACT: to characterize the transcriptome of human myometrium during spontaneous labor at term. myometrium was obtained from women with (n=19) and without labor (n=20). Illumina HumanHT-12 microarrays were utilized. Moderated t-tests and false discovery rate adjustment of P-values were applied. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for a select set of differentially expressed genes in a separate set of samples. Enzyme-linked immunosorbent assay and Western blot were utilized to confirm differential protein production in a third sample set. 1) Four hundred and seventy-one genes were differentially expressed; 2) gene ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using signaling pathway impact analysis indicated six significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-STAT signaling; and c) complement and coagulation cascades; d) NOD-like receptor signaling pathway; e) systemic lupus erythematosus; and f) chemokine signaling pathway; 4) qRT-PCR confirmed over-expression of prostaglandin-endoperoxide synthase-2, heparin binding epidermal growth factor (EGF)-like growth factor, chemokine C-C motif ligand 2 (CCL2/MCP1), leukocyte immunoglobulin-like receptor, subfamily A member 5, interleukin (IL)-8, IL-6, chemokine C-X-C motif ligand 6 (CXCL6/GCP2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta, suppressor of cytokine signaling 3 (SOCS3) and decreased expression of FK506 binding-protein 5 and aldehyde dehydrogenase in labor; 5) IL-6, CXCL6, CCL2 and SOCS3 protein expression was significantly higher in the term labor group compared to the term not in labor group. myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene expression identified with microarray was confirmed with qRT-PCR using an independent set of samples. This study represents an unbiased description of the biological processes involved in spontaneous labor at term based on transcriptomics.
    Journal of Perinatal Medicine 11/2010; 38(6):617-43. · 1.95 Impact Factor

Publication Stats

3k Citations
333.93 Total Impact Points

Institutions

  • 2007–2012
    • Wayne State University
      • Department of Obstetrics and Gynecology
      Detroit, MI, United States
  • 2011
    • Seoul National University Hospital
      • Department of Obstetrics and Gynecology
      Seoul, Seoul, South Korea
  • 2008–2011
    • 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
  • 2004–2011
    • Sheba Medical Center
      • • Institute of Endocrinology
      • • Department of Pathology
      Gan, Tel Aviv, Israel
  • 2010
    • Detroit Medical Center
      Detroit, Michigan, United States
    • Stanford University
      • Department of Medicine
      Stanford, CA, United States
  • 2007–2010
    • National Institute of Child Health and Human Development
      Maryland, United States
  • 2005–2009
    • Tel Aviv University
      • Department of Obstetrics and Gynecology
      Tel Aviv, Tel Aviv, Israel