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Showing papers by "Roberto Romero published in 2010"


Journal ArticleDOI
TL;DR: The prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre‐labor rupture of membranes are studied.
Abstract: Problem The role played by microbial invasion of the amniotic cavity (MIAC) in preterm prelabor rupture of membranes (pPROM) is inadequately characterized, in part because of reliance on cultivation-based methods.

394 citations


Journal ArticleDOI
TL;DR: An animal model is developed to evaluate the consequences of a viral infection characterized by lack of fetal transmission and shows that viral infection of the placenta can elicit a fetal inflammatory response that can cause organ damage and potentially downstream developmental deficiencies.
Abstract: Pandemics pose a more significant threat to pregnant women than to the nonpregnant population and may have a detrimental effect on the well being of the fetus. We have developed an animal model to evaluate the consequences of a viral infection characterized by lack of fetal transmission. The experiments described in this work show that viral infection of the placenta can elicit a fetal inflammatory response that, in turn, can cause organ damage and potentially downstream developmental deficiencies. Furthermore, we demonstrate that viral infection of the placenta may sensitize the pregnant mother to bacterial products and promote preterm labor. It is critical to take into consideration the fact that during pregnancy it is not only the maternal immune system responding, but also the fetal/placental unit. Our results further support the immunological role of the placenta and the fetus affecting the global response of the mother to microbial infections. This is relevant for making decisions associated with treatment and prevention during pandemics.

205 citations


Journal ArticleDOI
TL;DR: Transvaginal sonographic CL at 20-24 weeks' gestation is a good predictor of spontaneous preterm birth in asymptomatic women with twin pregnancies.

203 citations


Journal ArticleDOI
TL;DR: It is proposed that chronic chorioamnionitis defines a common placental pathological lesion among the preterm labor and preterm prelabor rupture of membranes groups, especially in cases of late preterm birth.

181 citations


Journal ArticleDOI
TL;DR: 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.
Abstract: Objective. 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).Study Design. Two retrospective cross-sectional studies were conducted, including three groups of pregnant women with spontaneous PTL and intact membranes: (1) PTL who delivered at te...

150 citations


Journal ArticleDOI
TL;DR: Universal sonographic screening for short cervical length and treatment with vaginal progesterone appears to be cost-effective and yields the greatest reduction in preterm birth at <34 weeks' gestation.

148 citations


Journal ArticleDOI
TL;DR: High maternal serum concentrations of IL-6 and CRP, but not MMP-9, were associated with an increased risk of IVH, and neonatal sepsis was more frequent in neonates born to mothers with a high maternal serum concentration of CRP.
Abstract: Elevated concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) in fetal and neonatal compartments have been associated with an increased risk for preterm birth (PTB) and/or neonatal morbidity. The purpose of this study was to determine if the maternal serum concentration of IL-6, CRP, and MMP-9 in women at risk for PTB, who are not in labor and have intact membranes, are associated with an increased risk for PTB 90th percentile). However, there was no significant association after adjustment for GA at randomization and treatment group. Logistic regression analysis for each analyte indicated that high maternal serum concentrations of IL-6 and CRP, but not MMP-9, were associated with an increased risk of IVH (odds ratio [OR] 4.60, 95% confidence interval [CI] 1.86 to 10.68; OR 4.07, 95% CI 1.63 to 9.50) after adjusting for GA at randomization and treatment group. Most babies (25/30) had grade I IVH. When GA at delivery was included, elevated IL-6 remained significantly associated with IVH (OR 2.77, 95% CI 1.02 to 7.09). An elevated maternal serum concentration of IL-6 and CRP are risk factors for PTB <32 weeks and subsequent development of neonatal IVH. An elevated maternal serum IL-6 appears to confer additional risk for IVH even after adjusting for GA at delivery.

147 citations



Journal ArticleDOI
TL;DR: 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.
Abstract: Aims To characterize the transcriptome of human myometrium during spontaneous labor at term.

144 citations


Journal ArticleDOI
TL;DR: Cultivation techniques for ureaplasmas did not detect most cases of intra-amniotic infection caused by these microorganisms, and patients with a negative AF culture and a positive PCR assay were at risk for intra-ammiotic and fetal inflammation as well as spontaneous preterm birth.
Abstract: AIMS The purpose of this study was to determine the clinical significance of detecting microbial footprints of ureaplasmas in amniotic fluid (AF) using specific primers for the polymerase chain reaction (PCR) in patients presenting with cervical insufficiency. METHODS Amniocentesis was performed in 58 patients with acute cervical insufficiency (cervical dilatation, > or =1.5 cm) and intact membranes, and without regular contractions (gestational age, 16-29 weeks). AF was cultured for aerobic and anaerobic bacteria as well as genital mycoplasmas. Ureaplasmas (Ureaplasma urealyticum and Ureaplasma parvum) were detected by PCR using specific primers. Patients were divided into three groups according to the results of AF culture and PCR for ureaplasmas: those with a negative AF culture and a negative PCR (n=44), those with a negative AF culture and a positive PCR (n=10), and those with a positive AF culture regardless of PCR result (n=4). RESULTS 1) Ureaplasmas were detected by PCR in 19.0% (11/58) of patients, by culture in 5.2% (3/58), and by culture and/or PCR in 22.4% (13/58); 2) Among the 11 patients with a positive PCR for ureaplasmas, the AF culture was negative in 91% (10/11); 3) Patients with a negative AF culture and a positive PCR for ureaplasmas had a significantly higher median AF matrix metalloproteinase-8 (MMP-8) concentration and white blood cell (WBC) count than those with a negative AF culture and a negative PCR (P<0.001 and P<0.05, respectively); 4) Patients with a positive PCR for ureaplasmas but a negative AF culture had a higher rate of spontaneous preterm birth within two weeks of amniocentesis than those with a negative AF culture and a negative PCR (P<0.05 after adjusting for gestational age at amnio-centesis); 5) Of the patients who delivered within two weeks of amniocentesis, those with a positive PCR for ureaplasmas and a negative AF culture had higher rates of histologic amnionitis and funisitis than those with a negative AF culture and a negative PCR (P<0.05 after adjusting for gestational age at amniocentesis, for each); 6) However, no significant differences in the intensity of the intra-amniotic inflammatory response and perinatal outcome were found between patients with a positive AF culture and those with a negative AF culture and a positive PCR. CONCLUSIONS 1) Cultivation techniques for ureaplasmas did not detect most cases of intra-amniotic infection caused by these microorganisms (91% of cases with cervical insufficiency and microbial footprints for ureaplasmas in the amniotic cavity had a negative AF culture); 2) Patients with a negative AF culture and a positive PCR assay were at risk for intra-amniotic and fetal inflammation as well as spontaneous preterm birth.

137 citations


Journal ArticleDOI
TL;DR: Intraamniotic and maternal inflammatory responses are more intense in intraamniotic infection with genital mycoplasmas than in intraamiotics infection with other microorganisms in patients with preterm premature rupture of membranes.


Journal ArticleDOI
TL;DR: Cervicovaginal fetal fibronectin provides moderate to minimal prediction of pre term birth in women with multiple pregnancies and the test is most accurate in predicting spontaneous preterm birth within 7 days of testing in womenWith twin pregnancies and threatened preterm labor.
Abstract: Objective. To investigate the accuracy of cervicovaginal fetal fibronectin in predicting preterm birth in women with multiple pregnancies.Methods. Systematic review and meta-analysis of predictive test accuracy. Cohort or cross-sectional studies were identified through searches in databases, reference lists, proceedings, and reviews. Study selection, quality assessment, and data extraction were performed. We constructed summary receiver operating characteristic curves and calculated pooled sensitivities and specificities using a bivariate, random-effects meta-regression model. We also calculated summary likelihood ratios and post-test probabilities of preterm birth.Results. Fifteen studies (11 in asymptomatic women and 4 in women with symptoms of preterm labor) involving 1221 women with multiple pregnancies were included. Among asymptomatic women with multiple or twin pregnancies, the pooled sensitivities, specificities, and positive and negative likelihood ratios for predicting preterm birth before 32, 3...

Journal ArticleDOI
TL;DR: The development of biocompatible dendrimers bearing multiple orthogonal surface groups, enabling the attachment of drugs, imaging agents, and gel formation using minimal synthetic steps is demonstrated.


Journal ArticleDOI
TL;DR: The prevalence of MIAC in preeclampsia is low, suggesting that intra-amniotic infection plays only a limited role in preeClampsia, however, the unexpectedly high number of positive AF specimens for Sneathia/Leptotrichia warrants further investigation.
Abstract: Objective Infection has been implicated in the pathogenesis of preeclampsia, yet the association between microbial invasion of the amniotic cavity (MIAC) and preeclampsia has not been determined The aim of this study was to determine the prevalence, and microbial diversity associated with MIAC, as well as the nature of the host response to MIAC in patients with preeclampsia Method of study Amniotic fluid (AF) from 62 subjects with preeclampsia, not in labor, was analyzed with both cultivation and molecular methods Broad-range and group-specific PCR assays targeting small subunit ribosomal DNA, or other gene sequences, from bacteria, fungi and archaea were used Results were correlated with measurements of host inflammatory response, including AF white blood cell count and AF concentrations of glucose, interleukin-6 (IL-6) and MMP-8 Results 1) The rate of MIAC in preeclampsia was 16% (1/62) based on cultivation techniques, 8% (5/62) based on PCR, and 96% (6/62) based on the combined results of both methods; 2) among the six patients diagnosed with MIAC, three had a positive PCR for Sneathia/Leptotrichia spp; and 3) patients with MIAC were more likely to have evidence of an inflammatory response in the amniotic cavity than those without MIAC, as determined by a higher median AF IL-6 [165 ng/mL interquartile range (IQR): 035-462 vs 022 ng/mL IQR: 012-051; P=0002) Conclusion The prevalence of MIAC in preeclampsia is low, suggesting that intra-amniotic infection plays only a limited role in preeclampsia However, the unexpectedly high number of positive AF specimens for Sneathia/Leptotrichia warrants further investigation

Journal ArticleDOI
TL;DR: MIAC is detected by PCR in some patients with an SGA fetus who were not in labor at the time of AF collection, and intra-amniotic inflammation was detected in one of the three patients with a positive PCR result, as compared with two patients with both a negative culture and a negative PCR result.
Abstract: Objective Microbial invasion of the amniotic cavity (MIAC) has been detected in women with preterm labor, preterm prelabor rupture of membranes (PROM), and in patients at term with PROM or in spontaneous labor. Intrauterine infection is recognized as a potential cause of fetal growth restriction; yet, the frequency of MIAC in pregnancies with small-for-gestational-age (SGA) fetuses is unknown. The aim of this study was to determine the frequency, diversity and relative abundance of microbes in amniotic fluid of women with an SGA neonate using a combination of culture and molecular methods.

Journal ArticleDOI
TL;DR: Fetal death is characterised by higher maternal plasma concentrations of PlGF during the first trimester compared to normal pregnancy, and this profile changes into an anti-angiogenic one during the second and third trimesters.
Abstract: Objective. Women with a fetal death at the time of diagnosis have higher maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, than women with a normal pregnancy. An important question is whether these changes are the cause or consequence of fetal death. To address this issue, we conducted a longitudinal study and measured the maternal plasma concentrations of selective angiogenic and anti-angiogenic factors before the diagnosis of a fetal death. The anti-angiogenic factors studied were sVEGFR-1 and soluble endoglin (sEng), and the angiogenic factor, placental growth factor (PlGF).Methods. This retrospective longitudinal nested case–control study included 143 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered a term infant with an appropriate weight for gestational age (n = 124); and (2) patients who had a fetal death (n = 19). Blood samples were collected at each prenatal visit, s...

Journal ArticleDOI
TL;DR: The transcriptome of fetal membranes after spontaneous rupture of membranes in term labor is characterized by region- and tissue-specific differential expression of genes that are involved in signature pathways, which include extracellular matrix-receptor interactions.

Journal ArticleDOI
TL;DR: In this article, the authors conducted an evidence-based review of information about [corrected] amniotic fluid embolism (AFE) and estimated incidence of AFE is 1:15,200 and 1:53,800 deliveries in North America and Europe, respectively.
Abstract: We conducted an evidence-based review of information about [corrected] amniotic fluid embolism (AFE). The estimated incidence of AFE is 1:15,200 and 1:53,800 deliveries in North America and Europe, respectively. The case fatality rate and perinatal mortality associated with AFE are 13-30% and 9-44%, respectively. Risk factors associated with an [corrected] increased risk of AFE include advanced maternal age, placental abnormalities, operative deliveries, eclampsia, polyhydramnios, cervical lacerations, [corrected] and uterine rupture. The hemodynamic response in [corrected] AFE is biphasic, with initial pulmonary hypertension and right ventricular failure, followed by left ventricular failure. Promising therapies include selective pulmonary vasodilators and recombinant activated factor VIIa. Important topics for future research are presented.

Journal ArticleDOI
TL;DR: The synthesis, characterization, fabrication, and functional validation of the dendrimer‐based assay platform are described, which provides assays with significantly enhanced sensitivity, lower nonspecific adsorption, and a detection limit of 0.13 pg mL−1 for IL‐6 luminol detection and 1.15 PG mL−1for IL‐1β TMB detection, which are significantly better than those for the traditional ELISA.
Abstract: Dendrimers, with their well-defined globular shape and a high density of functional groups, are ideal nanoscale materials for templating sensor surfaces. This work exploits dendrimers as a versatile platform for capturing biomarkers with improved sensitivity and specificity. Synthesis, characterization, fabrication, and functional validation of the dendrimer-based assay platform are described. Bifunctional hydroxyl/thiol functionalized G4-polyamidoamine (PAMAM) dendrimer is synthesized and immobilized on to the polyethylene-glycol (PEG)-functionalized assay plate by coupling PEG-maleimide and dendrimer thiol groups. Simultaneously, part of the dendrimer thiol groups are converted to hydrazide functionalities. The resulting dendrimer-modified surface is coupled to the capture antibody in the Fc region of the oxidized antibody. This preserves the orientation flexibility of the antigen binding region (Fv) of the antibody. To validate the approach, the fabricated plates are further used as a solid phase for developing a sandwich type ELISA to detect IL-6 and IL-1β, important biomarkers for early stages of chorioamnionitis. The dendrimer-modified plate provides assays with significantly enhanced sensitivity, lower nonspecific adsorption, and a detection limit of 0.13 pg ml-1 for IL-6 luminol detection and 1.15 pg ml-1 for IL-1β TMB detection, which are significantly better than those for the traditional ELISA. The assays were validated in human serum samples from normal (non-pregnant) woman and pregnant women with pyelonephritis. The specificity and the improved sensitivity of the dendrimer-based capture strategy could have significant implications for the detection of a wide range of cytokines and biomarkers since the capture strategy could be applied to multiplex microbead assays, conductometric immunosensors and field effect biosensors.

Journal ArticleDOI
TL;DR: Preeclampsia, but not pregnancy with an SGA neonate or an FD, is associated with a higher median maternal plasma concentration of RBP4 than normal pregnancy, and preterm PE, and specifically early-onset PE, isassociated with higher median RBP 4 concentrations in maternal plasma compared to term PE.
Abstract: Objective Dysregulation of maternal circulating adipokines has been implicated in several “great obstetrical syndromes” including preeclampsia (PE), small-for-gestational age (SGA) neonate and fetal death (FD). It has been suggested that adipokines provide a molecular link between metabolic derangements and inflammatory response in complicated pregnancies. Retinol binding protein 4 (RBP4), a novel adipokine, plays a role in obesity-related disorders, as well as in the regulation of the immune response. The aim of this study was to determine whether there are changes in maternal plasma concentrations of RBP4 in patients with PE and in those with an SGA neonate or FD.

Journal ArticleDOI
TL;DR: Pregnant women with an IUD are at a very high risk for adverse pregnancy outcomes, and this finding can be attributed, at least in part, to the high prevalence of intra-amniotic infection and placental inflammatory lesions observed in pregnancies with a IUD.
Abstract: OBJECTIVE—Intrauterine devices (IUDs) are used for contraception worldwide; however, the management of pregnancies with an IUD poses a clinical challenge. The purpose of this study was to determine the outcome of pregnancy in patients with an IUD. STUDY DESIGN—A retrospective cohort study (December 1997-June 2007) was conducted. The cohort consisted of 12,297 pregnancies, of which 196 had an IUD. Only singleton pregnancies were included. Logistic regression analysis was used to adjust for potential confounders between the groups. RESULTS—1) Pregnancies with an IUD were associated with a higher rate of late miscarriage, preterm delivery, vaginal bleeding, clinical chorioamnionitis, and placental abruption than those without an IUD; 2) among patients with available histologic examination of the placenta, the rate of histologic chorioamnionitis and/or funisitis was higher in patients with an IUD than in those without an IUD (54.2% vs. 14.7%; p<.001). Similarly, among patients who underwent an amniocentesis, the prevalence of microbial invasion of the amniotic cavity (MIAC) was also higher in pregnant women with an IUD than in those without an IUD (45.9% vs. 8.8%; p<.001); and 3) intra-amniotic infection caused by Candida species was more frequently present in pregnancies with an IUD than in those without an IUD (31.1% vs. 6.3%; p<.001). CONCLUSION—Pregnant women with an IUD are at a very high risk for adverse pregnancy outcomes. This finding can be attributed, at least in part, to the high prevalence of intra-amniotic infection and placental inflammatory lesions observed in pregnancies with an IUD.

Journal ArticleDOI
TL;DR: Patients with placenta previa presenting with vaginal bleeding have intra-amniotic infection in 5.7% of the cases, and IAI in 17.9%, which is a risk factor for preterm delivery within 48 h.
Abstract: OBJECTIVE Idiopathic vaginal bleeding, a common complication of pregnancy, increases the risk of small-for-gestational age (SGA) neonate, preeclampsia and preterm delivery and can be the only clinical manifestation of intra-amniotic infection and/or inflammation (IAI). Placenta previa is thought to be protective against ascending intrauterine infection, yet an excess of histologic chorioamnionitis has been reported in this condition. The aim of this study was to determine the frequency and clinical significance of IAI in women with placenta previa and vaginal bleeding in the absence of preterm labor. STUDY DESIGN A retrospective cohort study including 35 women with placenta previa and vaginal bleeding <37 weeks of gestation who underwent amniocentesis was undertaken. Patients with multiple gestations were excluded. Intra-amniotic infection was defined as a positive culture for microorganisms, and intra-amniotic inflammation as an elevated amniotic fluid interleukin (IL)-6 concentration. IL-6 concentrations were determined by ELISA in 28 amniotic fluid samples available. Non-parametric statistics were used for analysis. RESULTS 1) The prevalence of intra-amniotic infection was 5.7% (2/35), and that of IAI was 17.9% (5/28); 2) the gestational age at delivery was lower in patients with IAI than in those without IAI [29.4 weeks, interquartile range (IQR): 23.1-34.7 vs. 35.4 weeks, IQR: 33.9-36.9; P=0.028]; and 3) patients with placenta previa and IAI had a higher rate of delivery within 48 h (80% (4/5) vs. 19% (4/21); P=0.008) than those without IAI. CONCLUSIONS Patients with placenta previa presenting with vaginal bleeding have intra-amniotic infection in 5.7% of the cases, and IAI in 17.9%. IAI in patients with placenta previa and vaginal bleeding is a risk factor for preterm delivery within 48 h.

Journal ArticleDOI
TL;DR: In this article, a mouse model was used to determine whether uterine natural killer (uNK) cell cytotoxic activation induces infection/inflammation-associated preterm labor and delivery.
Abstract: Objective The purpose of this study was to determine in a mouse model whether uterine natural killer (uNK) cell cytotoxic activation induces infection/inflammation-associated preterm labor and delivery. Study Design Wild type or interleukin (IL)-10 –/– mice were injected intraperitoneally with lipopolysaccharide on gestational day 14. Mice were either killed for collection of uteroplacental tissue, spleen, and serum or allowed to deliver. Uteroplacental tissue was used for histology and characterization of uNK cells. Results Low-dose lipopolysaccharide treatment triggered preterm labor and delivery in IL-10 –/– , but not wild type mice, in a manner independent of progesterone levels. Preterm labor and delivery in IL-10 –/– mice was associated with an increased number and placental infiltration of cytotoxic uNK cells and placental cell death. Depletion of NK cells or tumor necrosis factor (TNF)-α neutralization in these mice restored term delivery. Furthermore, TNF-α neutralization prevented uNK cell infiltration and placental cell apoptosis. Conclusion The uNK cell-TNF-α–IL-10 axis plays an important role in the genesis of infection/inflammation-induced preterm labor/delivery.

Journal ArticleDOI
TL;DR: The aim of this study was to determine whether the risk of early spontaneous preterm delivery in asymptomatic women with a sonographic cervical length of ≤ 15 mm in the mid‐trimester changes as a function of gestational age at diagnosis.
Abstract: Objective—The aim of this study was to determine whether the risk of early spontaneous preterm delivery (sPTD) in asymptomatic women with a sonographic cervical length ≤15 mm in the mid-trimester changes as a function of gestational age at diagnos Methods—This cohort study included 109 asymptomatic patients with a sonographic sonographic cervical length ≤15 mm diagnosed at 14–24 weeks of gestation. Women with a multifetal gestation, cerclage, and those with a cervical dilatation >2 cm were excluded. The study population was stratified by gestational age at diagnosis (<20 weeks vs. 20–24 weeks) and by cervical length (≤10 mm vs. 11–15 mm). The primary outcome variables were PTD <28 and <32 weeks’ gestation and the diagnosis-to-delivery interval. Results—1) The median gestational age at diagnosis of a short cervix before 20 weeks and at 20–24 weeks was 18.9 and 22.7 weeks, respectively; 2) women diagnosed before 20 weeks had a higher rate of sPTD at <28 weeks (76.9% vs. 30.9%; p<0.001) and at <32 weeks (80.8% vs. 48.1%; p=0.004), and a shorter median diagnosis-to-delivery interval (21 vs. 61.5 days, p=0.003) than those diagnosed at 20–24 weeks; 3) The rate of amniotic fluid “sludge” was higher among patients diagnosed at <20 weeks of gestation than those diagnosed between 20 and 24 weeks (92.3% vs. 48.2%;p<0.001). Conclusions—Asymptomatic women with a sonographic cervical length ≤15 mm diagnosed before 20 weeks have a dramatic and significantly higher risk of early preterm delivery than women diagnosed at 20–24 weeks. These findings can be helpful to physicians in counseling these patients, and may suggest different mechanisms of disease leading to a sonographic short cervix before or after 20 weeks of gestation.

Journal ArticleDOI
TL;DR: A sensitive and specific fluorimetric assay for the determination of pyruvate is reported here and the usefulness of the assay is demonstrated by the accurate measurement of intracellular and extracellular pyruVate concentrations.

Journal ArticleDOI
TL;DR: The conjugates showed significant increase in antioxidant activity compared to free drug as seen from the inhibition of LPS induced ROS, NO, GSH and tumor necrosis factor-alpha (TNF-alpha) release in microglial cells.

Journal ArticleDOI
TL;DR: The overall findings suggest that entry of drugs conjugated to dendrimers would be restricted across the human fetal membranes when administered topically by intravaginal route, suggesting new ways of selectively delivering therapeutics to the mother without affecting the fetus.

Journal ArticleDOI
TL;DR: Bilateral uterine artery notching between 23 and 25 weeks' gestation is an independent risk factor for the development of early‐onset preeclampsia and gestational hypertension and should be considered in the assessment of risk for theDevelopment of these pregnancy complications.
Abstract: Objective. The purpose of this study was to determine the value of bilateral uterine artery notching in the second trimester in the risk assessment for preeclampsia, gestational hypertension, and small-for-gestational-age (SGA) without preeclampsia. Methods. This prospective cohort study included 4190 singleton pregnancies that underwent ultrasound examination between 23 and 25 weeks' gestation. The 95th percentiles of the mean pulsatility index (PI) and resistive index (RI) of both uterine arteries were calculated. Multivariable logistic regression analyses were performed to determine if bilateral uterine artery notching is an independent explanatory variable for the occurrence of preeclampsia, early-onset preeclampsia (≤34 weeks), late-onset preeclampsia (>34 weeks), gestational hypertension, and delivery of an SGA neonate without preeclampsia, while controlling for confounding factors. Results. (1) The prevalence of preeclampsia, early-onset preeclampsia, late-onset preeclampsia, SGA, and gestational hypertension were 3.4%, 0.5%, 2.9%, 10%, and 7.9%, respectively; (2) 7.2% of the study population had bilateral uterine artery notching; and (3) bilateral uterine artery notching was an independent explanatory variable for the development of preeclampsia (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.28-3.36), early-onset preeclampsia (OR, 4.47; 95% CI, 1.50-13.35), and gestational hypertension (OR, 1.50; 95% CI, 1.02-2.26), but not for late-onset preeclampsia or SGA. Conclusions. Bilateral uterine notching between 23 and 25 weeks' gestation is an independent risk factor for the development of early-onset preeclampsia and gestational hypertension. Thus, bilateral uterine artery notching should be considered in the assessment of risk for the development of these pregnancy complications.