Preeclampsia is a pregnancy specific hypertensive disease that confers significant maternal and f... more Preeclampsia is a pregnancy specific hypertensive disease that confers significant maternal and fetal risks. While the exact pathophysiology of preeclampsia is unknown, it is widely accepted that placental dysfunction is mechanistically involved. Recent studies reported aberrant expression of placenta-specific microRNAs (miRNAs) in preeclampsia including miR-517a/b and miR-517c. Using placental biopsies from a preeclampsia case-control study, we found increased expression of miR-517a/b in term and preterm preeclampsia vs controls, while, miR-517c was increased only in preterm preeclampsia vs controls. To determine if miR-517a/b and miR-517c are regulated by hypoxia, we treated first trimester primary extravillous trophoblast cells (EVTs) with a hypoxia mimetic and found both were induced. To test for a mechanistic role in placental function, we overexpressed miR-517a/b or miR-517c in EVTs which resulted in decreased trophoblast invasion. Additionally, we found that miR-517a/b and mi...
Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newbo... more Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newborns. We recently showed that the GBS pigment is hemolytic and increased pigment production promotes bacterial penetration of human placenta. However, mechanisms utilized by the hemolytic pigment to induce host cell lysis and the consequence on fetal injury are not known. Here, we show that the GBS pigment induces membrane permeability in artificial lipid bilayers and host cells. Membrane defects induced by the GBS pigment trigger K(+) efflux leading to osmotic lysis of red blood cells or pyroptosis in human macrophages. Macrophages lacking the NLRP3 inflammasome recovered from pigment-induced cell damage. In a murine model of in utero infection, hyperpigmented GBS strains induced fetal injury in both an NLRP3 inflammasome-dependent and NLRP3 inflammasome-independent manner. These results demonstrate that the dual mechanism of action of the bacterial pigment/lipid toxin leading to hemolys...
Reproductive sciences (Thousand Oaks, Calif.), Jan 28, 2014
Exposure to maternal obesity in utero predisposes offspring to obesity and metabolic disease. Thi... more Exposure to maternal obesity in utero predisposes offspring to obesity and metabolic disease. This study investigated whether maternal obesity is associated with alterations in expression of fetal microRNA (miRNA). A cohort study of women with body mass index (BMI) ≥35 kg/m(2) (n = 16) versus those with normal BMI 20 to 24.9 (n = 20) was performed. All participants had normal glucose tolerance (1-hour glucose challenge test <130) and normally grown neonates (2700-3500 g). Umbilical cord samples were collected immediately after delivery. Expression of miRNA was assessed using Affymetrix GeneChip miRNA 3.0 Arrays. Differential miRNA expression was determined using Student t tests with Benjamini-Hocherg correction. For 1733 human mature miRNAs, the expression levels were not statistically different in umbilical cord blood samples from pregnancies of obese women compared to controls. Expression of fetal miRNA is not altered in umbilical cord blood in response to in utero exposure to ...
American journal of obstetrics and gynecology, 2015
The effect of a cesarean delivery in different stages of labor on spontaneous preterm birth (sPTB... more The effect of a cesarean delivery in different stages of labor on spontaneous preterm birth (sPTB) in a subsequent pregnancy has not been studied extensively. The objective of the study was to evaluate the risk of subsequent sPTB after a first-stage or second-stage cesarean delivery compared with a vaginal delivery. This was a planned secondary analysis of a large retrospective cohort study of women with 2 consecutive deliveries from 2005-2010. Women with a previous sPTB were excluded. First-stage (<10 cm) and second-stage (≥10 cm) cesarean deliveries were compared with vaginal deliveries. Data were obtained through chart abstraction. The primary outcome was sPTB (<37 wk) in a subsequent pregnancy. Categoric variables were compared with the use of χ(2) analyses, and logistic regression was used to calculate odds and control for confounders. Eight hundred eighty-seven women were included (721 vaginal deliveries; 129 first-stage and 37 second-stage cesarean deliveries). The sPTB...
OBJECTIVE: Prior studies suggest that cervical, urine, and/or GBS infections or cocaine use are a... more OBJECTIVE: Prior studies suggest that cervical, urine, and/or GBS infections or cocaine use are associated with preterm birth (PTB). While screening preterm labor (PTL) patients for these infections occurs, an association between a positive screening test and PTB has not been demonstrated. The objective of this study was to evaluate the utility of these screening tests in a cohort of women with PTL.
American Journal of Obstetrics and Gynecology, 2008
OBJECTIVE: Inflammation-induced preterm birth (IIPB) is a major cause of adverse neurological out... more OBJECTIVE: Inflammation-induced preterm birth (IIPB) is a major cause of adverse neurological outcome (ANO). ANO has been linked to white matter and glial damage. Recently, we have demonstrated that IIPB results specifically in neuronal injury. The activation of TLR-4 is implicated in inflammation-induced brain injury in both neonatal and adult animal models but has not been investigated in fetal injury from preterm birth. This study investigates whether TLR-4 is essential for fetal neuronal injury in IIPB.
American Journal of Obstetrics and Gynecology, 2007
These studies were performed to elucidate the expression of Toll-like receptors (TLRs) in the ute... more These studies were performed to elucidate the expression of Toll-like receptors (TLRs) in the uterus, cervix, and placenta in pregnancy and across gestation. Message expressions of TLR-2, -3, -4, and -9 were investigated in nonpregnant mice and across gestation in CD-1 mice. Uterine, cervical, and placental tissues were harvested, and RNA was extracted. Quantitative polymerase chain reaction was performed. Messenger RNA expression of TLRs is significantly upregulated in pregnant uterine and cervical tissues. There is differential TLR messenger RNA expression between the uterus, cervix, and placenta. In the placenta, TLR 4 is significantly downregulated. These findings suggest that the innate immune system is a dynamic system during gestation. The concept of immunosuppression during pregnancy appears to be valid in the placenta only in regard to TLR expression. Research is warranted to determine whether the upregulation in the uterus and cervix during pregnancy is associated with an increased likelihood of responding to a pathogen or serve as a protective mechanism or both.
BackgroundIn the female genital tract, vaginal colposcopy, endometrial mucosal integrity and infl... more BackgroundIn the female genital tract, vaginal colposcopy, endometrial mucosal integrity and inflammatory mediators are potential in vivo biomarkers of microbicide and contraceptive safety.
American Journal of Obstetrics and Gynecology, 2010
We determined whether an environmental exposure to bacterial vaginosis (BV) modified genetic susc... more We determined whether an environmental exposure to bacterial vaginosis (BV) modified genetic susceptibilities for spontaneous preterm delivery within genes that regulate the inflammatory response.Maternal DNA samples and vaginal smears for Gram staining were collected from 743 women (68 preterm births). We used a 1536–single nucleotide polymorphism (SNP) custom chip to study associations between genotype distributions and preterm birth.For 8 SNPs in 3 genes (protein kinase C alpha, fms-like tyrosine kinase 1, and interleukin 6), the odds ratios for preterm birth ranged from 1.9–4.0 among women with susceptible genotypes who were BV positive. The odds ratios for preterm birth were 2.0-5.0 times greater among women who were BV positive than among women who were BV negative. The significance of these differences was demonstrated by logistic regression analyses for genotype/BV interaction.These results demonstrate that the risk of preterm delivery that is associated with tag SNPs in genes that regulate the inflammatory response is modified by an environmental exposure such as bacterial vaginosis.
values using an AP diameter above the 95th percentile for abnormal postnatal function using the d... more values using an AP diameter above the 95th percentile for abnormal postnatal function using the derived reference intervals were 64%, 92%, 75%, and 87%, respectively. Conclusions: There is a high correlation between the AP diameter of the renal pelvis and gestational age. The use of gestational age specific percentiles for renal AP diameter is highly predictive of abnormal postnatal renal function.
American Journal of Obstetrics and Gynecology, 2015
To examine whether variation in neighborhood context is associated with preterm birth (PTB) outco... more To examine whether variation in neighborhood context is associated with preterm birth (PTB) outcomes and gestational age (GA) at delivery in Philadelphia, and to determine whether these associations might persist when considering relevant individual-level variables. We analyzed individual-level data collected for a prospective cohort study of singleton pregnancies with preterm labor. We merged block-group level data to each individual&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s home address. Unadjusted analyses were performed to determine the association between block-group variables and individual-level outcomes. Block-group variables identified as potential risk factors were incorporated into multivariable individual-level models to determine significance. We analyzed data for 817 women. The prevalence of PTB &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;37 weeks was 41.5%. Although in unadjusted analyses several block-group variables were associated with PTB and GA at delivery, none retained significance in individual-level multivariable models. Block-group level data were not associated with PTB outcomes or GA at delivery in Philadelphia.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2011
Exposure to prenatal inflammation is a known risk factor for long term neurobehavioral disorders ... more Exposure to prenatal inflammation is a known risk factor for long term neurobehavioral disorders including cerebral palsy, schizophrenia, and autism. Models of systemic inflammation during pregnancy have demonstrated an association with an immune response an adverse neurobehavioral outcomes for the exposed fetus. Yet, the most common route for an inflammatory exposure to a fetus is from intrauterine inflammation as occurs with chorioamnionitis. The aims of this study were to assess the effect of intrauterine inflammation on fetal and neonatal brain development and to determine if the gestational age of exposure altered the maternal or fetal response to inflammation. CD-1 timed pregnant mice on embryonic day 15 (E15) and E18.5 were utilized for this study. Dams were randomized to receive intrauterine infusion of lipopolysaccharide (LPS, 50 μg/dam) or normal saline. Different experimental groups were used to assess both acute and long-term outcomes. For each gestational age and each t...
Preeclampsia (PE), a hypertensive disorder of pregnancy, is hypothesized to be associated with, i... more Preeclampsia (PE), a hypertensive disorder of pregnancy, is hypothesized to be associated with, if not mechanistically related to abnormal placental function. However, the exact mechanisms regulating the pathogenesis of PE remain unclear. While many studies have investigated changes in gene expression in the PE placenta, the role of epigenetics in PE associated placental dysfunction remains unclear. Using the genome-wide Illumina Infinium Methylation 450 BeadChip array, we analyzed gene-specific alterations in DNA methylation in placental biopsies collected from normal pregnant women delivering at term (n = 14), with term PE (≥37 weeks; n = 19) or with preterm PE (<37 weeks, n = 12). Of the 485,582 gene loci on the array, compared to controls, 229 loci were differentially methylated in PE placentas and 3411 loci were differentially methylated in preterm PE (step up p-value <0.05 and >5% methylation difference). Functional annotation of the differentially methylated genes in...
Journal of Maternal-Fetal and Neonatal Medicine, 2009
Hypothesising that metabolic syndrome may be associated with or useful in the prediction of pre-e... more Hypothesising that metabolic syndrome may be associated with or useful in the prediction of pre-eclampsia, we investigated the association between all components of metabolic syndrome and C-reactive protein (CRP) in women with and without pre-eclampsia. A case-control study was performed. Cases had gestational hypertension or pre-eclampsia and controls were term deliveries. Clinical data and maternal serum was collected. The presence of metabolic syndrome (3/5 variables present) and a metabolic score (continuous 0-5) were investigated. Significant associations were evaluated using t-tests, and Pearson chi-square tests of association. Multivariable logistic regression was used to control for confounders. One-hundred and one cases and 267 controls were evaluated. We observed a higher odds of pre-eclampsia when metabolic syndrome was present (AOR = 2.71 [1.1-6.67], p = 0.03). For every one-unit increase in metabolic score, there was a 39% increased odds of pre-eclampsia (AOR = 1.39 [1.06-1.82], p = 0.017). The odds of pre-eclampsia were nearly four times higher when hs- CRP was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;8 (AOR = 3.61 [2.14-6.12], p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Metabolic syndrome and hs-CRP are associated with pre-eclampsia. Investigation is crucial to determine if these abnormal lipid and inflammatory pathways observed in women with pre-eclampsia are present pre-pregnancy or develop as a result of the disease process of pre-eclampsia. Further investigation is also warranted to determine whether these abnormalities persist post-pregnancy and if so, their contribution to long-term cardiovascular disease.
Journal of Maternal-Fetal and Neonatal Medicine, 2008
These studies sought to determine whether a progestational agent, specifically medroxyprogesteron... more These studies sought to determine whether a progestational agent, specifically medroxyprogesterone acetate (MPA) prevents inflammation-induced preterm birth, in a mouse model, through modulation of the host immune response. Using an established mouse model of inflammation-induced preterm birth, the activation of the immune response in maternal serum, uterus, cervix and placenta was assessed. In addition, the ability of MPA to modulate this response was investigated. Message RNA and protein expression were assessed by quantitative PCR and ELISAs respectively. Intrauterine inflammation promotes a significant up-regulation of both TH1 and TH2 mediators in all tissues studies though the response is divergent by time and tissue studied. MPA significantly differentially regulates this immune response in the uterus, cervix and placenta. In the setting of inflammation-induced preterm birth, the host immune response is activated and not limited to a traditional TH1 bias. The ability of MPA to modulate the immune response may be a critical mechanism by which progestins prevent preterm birth.
Preeclampsia is a pregnancy specific hypertensive disease that confers significant maternal and f... more Preeclampsia is a pregnancy specific hypertensive disease that confers significant maternal and fetal risks. While the exact pathophysiology of preeclampsia is unknown, it is widely accepted that placental dysfunction is mechanistically involved. Recent studies reported aberrant expression of placenta-specific microRNAs (miRNAs) in preeclampsia including miR-517a/b and miR-517c. Using placental biopsies from a preeclampsia case-control study, we found increased expression of miR-517a/b in term and preterm preeclampsia vs controls, while, miR-517c was increased only in preterm preeclampsia vs controls. To determine if miR-517a/b and miR-517c are regulated by hypoxia, we treated first trimester primary extravillous trophoblast cells (EVTs) with a hypoxia mimetic and found both were induced. To test for a mechanistic role in placental function, we overexpressed miR-517a/b or miR-517c in EVTs which resulted in decreased trophoblast invasion. Additionally, we found that miR-517a/b and mi...
Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newbo... more Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newborns. We recently showed that the GBS pigment is hemolytic and increased pigment production promotes bacterial penetration of human placenta. However, mechanisms utilized by the hemolytic pigment to induce host cell lysis and the consequence on fetal injury are not known. Here, we show that the GBS pigment induces membrane permeability in artificial lipid bilayers and host cells. Membrane defects induced by the GBS pigment trigger K(+) efflux leading to osmotic lysis of red blood cells or pyroptosis in human macrophages. Macrophages lacking the NLRP3 inflammasome recovered from pigment-induced cell damage. In a murine model of in utero infection, hyperpigmented GBS strains induced fetal injury in both an NLRP3 inflammasome-dependent and NLRP3 inflammasome-independent manner. These results demonstrate that the dual mechanism of action of the bacterial pigment/lipid toxin leading to hemolys...
Reproductive sciences (Thousand Oaks, Calif.), Jan 28, 2014
Exposure to maternal obesity in utero predisposes offspring to obesity and metabolic disease. Thi... more Exposure to maternal obesity in utero predisposes offspring to obesity and metabolic disease. This study investigated whether maternal obesity is associated with alterations in expression of fetal microRNA (miRNA). A cohort study of women with body mass index (BMI) ≥35 kg/m(2) (n = 16) versus those with normal BMI 20 to 24.9 (n = 20) was performed. All participants had normal glucose tolerance (1-hour glucose challenge test <130) and normally grown neonates (2700-3500 g). Umbilical cord samples were collected immediately after delivery. Expression of miRNA was assessed using Affymetrix GeneChip miRNA 3.0 Arrays. Differential miRNA expression was determined using Student t tests with Benjamini-Hocherg correction. For 1733 human mature miRNAs, the expression levels were not statistically different in umbilical cord blood samples from pregnancies of obese women compared to controls. Expression of fetal miRNA is not altered in umbilical cord blood in response to in utero exposure to ...
American journal of obstetrics and gynecology, 2015
The effect of a cesarean delivery in different stages of labor on spontaneous preterm birth (sPTB... more The effect of a cesarean delivery in different stages of labor on spontaneous preterm birth (sPTB) in a subsequent pregnancy has not been studied extensively. The objective of the study was to evaluate the risk of subsequent sPTB after a first-stage or second-stage cesarean delivery compared with a vaginal delivery. This was a planned secondary analysis of a large retrospective cohort study of women with 2 consecutive deliveries from 2005-2010. Women with a previous sPTB were excluded. First-stage (<10 cm) and second-stage (≥10 cm) cesarean deliveries were compared with vaginal deliveries. Data were obtained through chart abstraction. The primary outcome was sPTB (<37 wk) in a subsequent pregnancy. Categoric variables were compared with the use of χ(2) analyses, and logistic regression was used to calculate odds and control for confounders. Eight hundred eighty-seven women were included (721 vaginal deliveries; 129 first-stage and 37 second-stage cesarean deliveries). The sPTB...
OBJECTIVE: Prior studies suggest that cervical, urine, and/or GBS infections or cocaine use are a... more OBJECTIVE: Prior studies suggest that cervical, urine, and/or GBS infections or cocaine use are associated with preterm birth (PTB). While screening preterm labor (PTL) patients for these infections occurs, an association between a positive screening test and PTB has not been demonstrated. The objective of this study was to evaluate the utility of these screening tests in a cohort of women with PTL.
American Journal of Obstetrics and Gynecology, 2008
OBJECTIVE: Inflammation-induced preterm birth (IIPB) is a major cause of adverse neurological out... more OBJECTIVE: Inflammation-induced preterm birth (IIPB) is a major cause of adverse neurological outcome (ANO). ANO has been linked to white matter and glial damage. Recently, we have demonstrated that IIPB results specifically in neuronal injury. The activation of TLR-4 is implicated in inflammation-induced brain injury in both neonatal and adult animal models but has not been investigated in fetal injury from preterm birth. This study investigates whether TLR-4 is essential for fetal neuronal injury in IIPB.
American Journal of Obstetrics and Gynecology, 2007
These studies were performed to elucidate the expression of Toll-like receptors (TLRs) in the ute... more These studies were performed to elucidate the expression of Toll-like receptors (TLRs) in the uterus, cervix, and placenta in pregnancy and across gestation. Message expressions of TLR-2, -3, -4, and -9 were investigated in nonpregnant mice and across gestation in CD-1 mice. Uterine, cervical, and placental tissues were harvested, and RNA was extracted. Quantitative polymerase chain reaction was performed. Messenger RNA expression of TLRs is significantly upregulated in pregnant uterine and cervical tissues. There is differential TLR messenger RNA expression between the uterus, cervix, and placenta. In the placenta, TLR 4 is significantly downregulated. These findings suggest that the innate immune system is a dynamic system during gestation. The concept of immunosuppression during pregnancy appears to be valid in the placenta only in regard to TLR expression. Research is warranted to determine whether the upregulation in the uterus and cervix during pregnancy is associated with an increased likelihood of responding to a pathogen or serve as a protective mechanism or both.
BackgroundIn the female genital tract, vaginal colposcopy, endometrial mucosal integrity and infl... more BackgroundIn the female genital tract, vaginal colposcopy, endometrial mucosal integrity and inflammatory mediators are potential in vivo biomarkers of microbicide and contraceptive safety.
American Journal of Obstetrics and Gynecology, 2010
We determined whether an environmental exposure to bacterial vaginosis (BV) modified genetic susc... more We determined whether an environmental exposure to bacterial vaginosis (BV) modified genetic susceptibilities for spontaneous preterm delivery within genes that regulate the inflammatory response.Maternal DNA samples and vaginal smears for Gram staining were collected from 743 women (68 preterm births). We used a 1536–single nucleotide polymorphism (SNP) custom chip to study associations between genotype distributions and preterm birth.For 8 SNPs in 3 genes (protein kinase C alpha, fms-like tyrosine kinase 1, and interleukin 6), the odds ratios for preterm birth ranged from 1.9–4.0 among women with susceptible genotypes who were BV positive. The odds ratios for preterm birth were 2.0-5.0 times greater among women who were BV positive than among women who were BV negative. The significance of these differences was demonstrated by logistic regression analyses for genotype/BV interaction.These results demonstrate that the risk of preterm delivery that is associated with tag SNPs in genes that regulate the inflammatory response is modified by an environmental exposure such as bacterial vaginosis.
values using an AP diameter above the 95th percentile for abnormal postnatal function using the d... more values using an AP diameter above the 95th percentile for abnormal postnatal function using the derived reference intervals were 64%, 92%, 75%, and 87%, respectively. Conclusions: There is a high correlation between the AP diameter of the renal pelvis and gestational age. The use of gestational age specific percentiles for renal AP diameter is highly predictive of abnormal postnatal renal function.
American Journal of Obstetrics and Gynecology, 2015
To examine whether variation in neighborhood context is associated with preterm birth (PTB) outco... more To examine whether variation in neighborhood context is associated with preterm birth (PTB) outcomes and gestational age (GA) at delivery in Philadelphia, and to determine whether these associations might persist when considering relevant individual-level variables. We analyzed individual-level data collected for a prospective cohort study of singleton pregnancies with preterm labor. We merged block-group level data to each individual&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s home address. Unadjusted analyses were performed to determine the association between block-group variables and individual-level outcomes. Block-group variables identified as potential risk factors were incorporated into multivariable individual-level models to determine significance. We analyzed data for 817 women. The prevalence of PTB &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;37 weeks was 41.5%. Although in unadjusted analyses several block-group variables were associated with PTB and GA at delivery, none retained significance in individual-level multivariable models. Block-group level data were not associated with PTB outcomes or GA at delivery in Philadelphia.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2011
Exposure to prenatal inflammation is a known risk factor for long term neurobehavioral disorders ... more Exposure to prenatal inflammation is a known risk factor for long term neurobehavioral disorders including cerebral palsy, schizophrenia, and autism. Models of systemic inflammation during pregnancy have demonstrated an association with an immune response an adverse neurobehavioral outcomes for the exposed fetus. Yet, the most common route for an inflammatory exposure to a fetus is from intrauterine inflammation as occurs with chorioamnionitis. The aims of this study were to assess the effect of intrauterine inflammation on fetal and neonatal brain development and to determine if the gestational age of exposure altered the maternal or fetal response to inflammation. CD-1 timed pregnant mice on embryonic day 15 (E15) and E18.5 were utilized for this study. Dams were randomized to receive intrauterine infusion of lipopolysaccharide (LPS, 50 μg/dam) or normal saline. Different experimental groups were used to assess both acute and long-term outcomes. For each gestational age and each t...
Preeclampsia (PE), a hypertensive disorder of pregnancy, is hypothesized to be associated with, i... more Preeclampsia (PE), a hypertensive disorder of pregnancy, is hypothesized to be associated with, if not mechanistically related to abnormal placental function. However, the exact mechanisms regulating the pathogenesis of PE remain unclear. While many studies have investigated changes in gene expression in the PE placenta, the role of epigenetics in PE associated placental dysfunction remains unclear. Using the genome-wide Illumina Infinium Methylation 450 BeadChip array, we analyzed gene-specific alterations in DNA methylation in placental biopsies collected from normal pregnant women delivering at term (n = 14), with term PE (≥37 weeks; n = 19) or with preterm PE (<37 weeks, n = 12). Of the 485,582 gene loci on the array, compared to controls, 229 loci were differentially methylated in PE placentas and 3411 loci were differentially methylated in preterm PE (step up p-value <0.05 and >5% methylation difference). Functional annotation of the differentially methylated genes in...
Journal of Maternal-Fetal and Neonatal Medicine, 2009
Hypothesising that metabolic syndrome may be associated with or useful in the prediction of pre-e... more Hypothesising that metabolic syndrome may be associated with or useful in the prediction of pre-eclampsia, we investigated the association between all components of metabolic syndrome and C-reactive protein (CRP) in women with and without pre-eclampsia. A case-control study was performed. Cases had gestational hypertension or pre-eclampsia and controls were term deliveries. Clinical data and maternal serum was collected. The presence of metabolic syndrome (3/5 variables present) and a metabolic score (continuous 0-5) were investigated. Significant associations were evaluated using t-tests, and Pearson chi-square tests of association. Multivariable logistic regression was used to control for confounders. One-hundred and one cases and 267 controls were evaluated. We observed a higher odds of pre-eclampsia when metabolic syndrome was present (AOR = 2.71 [1.1-6.67], p = 0.03). For every one-unit increase in metabolic score, there was a 39% increased odds of pre-eclampsia (AOR = 1.39 [1.06-1.82], p = 0.017). The odds of pre-eclampsia were nearly four times higher when hs- CRP was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;8 (AOR = 3.61 [2.14-6.12], p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Metabolic syndrome and hs-CRP are associated with pre-eclampsia. Investigation is crucial to determine if these abnormal lipid and inflammatory pathways observed in women with pre-eclampsia are present pre-pregnancy or develop as a result of the disease process of pre-eclampsia. Further investigation is also warranted to determine whether these abnormalities persist post-pregnancy and if so, their contribution to long-term cardiovascular disease.
Journal of Maternal-Fetal and Neonatal Medicine, 2008
These studies sought to determine whether a progestational agent, specifically medroxyprogesteron... more These studies sought to determine whether a progestational agent, specifically medroxyprogesterone acetate (MPA) prevents inflammation-induced preterm birth, in a mouse model, through modulation of the host immune response. Using an established mouse model of inflammation-induced preterm birth, the activation of the immune response in maternal serum, uterus, cervix and placenta was assessed. In addition, the ability of MPA to modulate this response was investigated. Message RNA and protein expression were assessed by quantitative PCR and ELISAs respectively. Intrauterine inflammation promotes a significant up-regulation of both TH1 and TH2 mediators in all tissues studies though the response is divergent by time and tissue studied. MPA significantly differentially regulates this immune response in the uterus, cervix and placenta. In the setting of inflammation-induced preterm birth, the host immune response is activated and not limited to a traditional TH1 bias. The ability of MPA to modulate the immune response may be a critical mechanism by which progestins prevent preterm birth.
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Papers by Michal Elovitz