Placental Perfusion Research Articles

Early Preeclampsia Effect on Preterm Newborns Outcome.

Background: An early form of preeclampsia is rare. Abnormal placentation, placental perfusion disorders, and inflammatory cytokine release will have an effect on the fetus and newborn. Material and methods: The study group consisted of preterm newborns whose mothers had a history of preeclampsia and a gestational age of between 30 weeks and 34 weeks + 6 days. The control group consists of neonates matched for gestational age with the case group, whose mothers had normal blood pressure. The incidence and severity of respiratory distress syndrome (RDS), intraventricular hemorrhage, hypoglycemia, pH gas changes, and hematological parameters were analyzed in the two groups. Results: The study group of preterm neonates had a lower birth weight than the control group (p < 0.001). Most of the deliveries in the group of newborns exposed to preeclampsia were performed by cesarean section. Severe forms of RDS were two times more frequent in the group of newborns exposed to preeclampsia compared to those in the control group. Even though we expected to see a lower incidence, owing to the high number of deliveries by cesarean section, we still observed a higher rate of intraventricular hemorrhage in the preeclampsia group (16 cases in the study group vs. 7 in the control, p = 0.085). Neutropenia and thrombocytopenia were more frequent in preterm newborns exposed to preeclampsia. Conclusions: The study shows that early preeclampsia increases the risk of complications in preterm neonates. RDS was more frequent in the exposed group than in the control group. The severity of preeclampsia correlates with hematological changes.

Importance of Doppler study of Umbilical Artery and FoetalMiddle Cerebral Artery in PIH and IUGR

Background: PIH is associated with increased vascular resistance and decreased utero -placental perfusion resulting in an increased incidence of foetal hypoxia and impaired foetalgrowth.The objective of this study was to assess the diagnostic performance of S/D ratio, resistance index(RI), pulsatility index (PI) and cerebro-placental ratio (CPR) in the prediction of adverse perinatal outcome in PIH and IUGR. Objective: is to determine S/D ratio, RI, PI, CPR and asses their diagnostic values in the prediction of adverse perinatal outcome.Material&amp; Methods:50 pregnant patients with PIH and IUGR, beyond 28 weeks of gestation, were prospectively studied at P k das institute of medical college,vaniyamkulamand subjected for Doppler study of the umbilical artery and foetal middle cerebral artery. The abnormality of above parameters was correlated with the major adverse perinatal outcome.Results:Patients with abnormal Doppler parameters had a poor perinatal outcome, compared to those who had normal Doppler study. The cerebro-placental ratios(CPR) had the sensitivity and specificity, positive and negative predictive values of 95%,76%,73%,95% respectively with Kappa value of o .68(good agreement) and p value of .000 which was statistically significant, for the prediction of major adverse perinatal outcome.Conclusions:This study shows that Doppler study of umbilical and foetal middle cerebral artery can reliably predict the neonatal morbidity and helpful in determining the optimal time of delivery in complicated pregnancies. The CPR is more accurate than the independent evaluation of S/D, RI, PI, in identifying foetus with adverse perinatal outcome.

Sepsis in the Parturient.

Sepsis is a leading cause of maternal morbidity with a high case fatality rate and leads to significant perinatal loss. Early identification and appropriate time management can significantly improve maternal and perinatal outcomes. The physiological changes of pregnancy and puerperium make pregnant women more susceptible to sepsis and also pose a challenge for early diagnosis because of overlap of clinical features and laboratory values. The validation of scoring/warning systems for sepsis in parturient needs further research. Infections during puerperium are commonly polymicrobial in nature and warrant broad-spectrum antibiotics. Maternal resuscitation in antepartum period has to be tailored to ensure fetal well-being and adequate placental perfusion. For the management of sepsis in pregnancy, the guidelines from surviving sepsis campaign (SSC) for general adult population are extrapolated with modifications related to physiological alterations in pregnancy and puerperium. Timing of delivery is based on the obstetric indications unless the source of sepsis is intrauterine.How to cite this articleJain V, Arora A, Jain K. Sepsis in the Parturient. Indian J Crit Care Med 2021;25(Suppl 3):S267–S272.

Transplacental transfer of venlafaxine evaluated by ex vivo perfusion.

Depression is frequent among pregnant women and decision for treatment with antidepressants needs careful consideration of risks for the fetus. Since data regarding fetal antidepressant exposure are rare, we aimed to evaluate transplacental transfer of venlafaxine, a selective norepinephrine reuptake inhibitor. Ex vivo human placental perfusion experiments were conducted in double closed set-up. Venlafaxine (18.1±2.1μg/L) was offered in maternal circuit and maternal-to-fetal transfer was monitored over a period of 3h. Venlafaxin and O-desmethylvenlafaxine concentrations were determined by HPLC-MS in maternal and fetal perfusion medium. We observed maternal-to-fetal transfer of venlafaxine within 5min perfusion. The concentration equilibrium was approximated between maternal (7.5±0.5μg/L) and fetal (6.5±0.6μg/L) compartment at time point 180min, which corresponds to a fetal-maternal (FM) ratio of 0.89. Our results are comparable with in vivo data from an observational study which emphasizes that the ex vivo placental perfusion model is suitable for systematic evaluation of fetal antidepressant exposure.

Maternal Cardiac Function at Midgestation and Development of Preeclampsia

BackgroundPreeclampsia (PE) is an independent risk factor for adverse maternal cardiovascular outcomes. The role of maternal cardiac function in the pathophysiology of PE remains unclear. ObjectivesThis study sought to describe differences in cardiac function at midgestation between women who develop PE and those with uncomplicated pregnancy and to establish whether routine cardiac assessment at midgestation can improve performance of screening for PE achieved by established biomarkers. MethodsMean arterial pressure was measured, medical history was obtained, and left ventricular (LV) systolic and diastolic functions were assessed using standard echocardiography and speckle tracking imaging. Uterine artery pulsatility index and serum placental growth factor and soluble fms-like tyrosine kinase-1 were measured. ResultsIn 4,795 pregnancies, 126 (2.6%) developed PE. Following multivariable analysis, peripheral vascular resistance was significantly higher and LV global longitudinal systolic strain, ejection fraction, cardiac output, and left atrial area were mildly lower in women who developed PE compared to those who did not. There was a weak association between maternal cardiovascular indices and biomarkers of placental perfusion and function. Cardiac indices did not improve the performance of screening for PE on top of maternal risk factors, mean arterial pressure, and biomarkers of placental perfusion and function. ConclusionWomen who develop PE have an increase in peripheral vascular resistance and a mild reduction in LV functional cardiac indices long before PE development. However, cardiac indices do not improve the performance of screening for PE; thus, their routine clinical use is not advocated.

A study on the correlation of placental characteristics and the onset of selective intrauterine growth restriction.

To investigate the correlation between placental characteristics and the onset of selective intrauterine growth restriction (sIUGR) and to explore the influence of placental characteristics on sIUGR onset. A retrospective cohort study was conducted at our hospital from April 2013 to April 2019. The pregnancy data and placental perfusion of 114 sIUGR patients who had received conservative treatment and delivered in our hospital were included. Correlation analysis was conducted between the total diameter of placental anastomoses, placental territory discordance, umbilical cord insertion point distance ratio, and the onset time of sIUGR. The prevalence of AA anastomoses was 88.6% (101/114), with an average total diameter of 2.8 ± 1.5 mm, the prevalence of AV anastomoses was 93.9% (107/114), with an average diameter of 5.4 ± 3.6 mm, and the prevalence of VV anastomoses was 18.4% (21/114), with an average diameter of 4.0 ± 1.9 mm. There was a significant negative correlation between the time of sIUGR onset and the placental territory discordance ratio with a Spearman correlation coefficient of -0.306 (P = 0.001). The larger the placental territory discordance, the earlier onset time of sIUGR.

Testing Pharmacokinetics and Efficacy of Pravastatin Using Feto-Maternal Interface Organ-On-Chips

Pravastatin reduce pro-inflammatory mediators in feto-maternal interface (FMi) tissues and minimize PE-like symptoms in vitro and in animal models. Several questions remain regarding the drug’s pharmacokinetics (PK), metabolism, and efficacy that cannot be fully answered using traditional 2D cell culture or placental perfusion models prior to clinical trials. We used two distinct microfluidic organ-on-chip (OOC) models that are interconnected through microchannels and maintain intercellular interactions between cells to faithfully represents the human FMi to test pravastatin’s PK and cellular responses at the fetal membranes (FM) and placenta (P).

Intrapartum epidural analgesia and emergency delivery rates due to fetal compromise by birth weight percentile

Epidural analgesia (EDA) is widely used for maternal pain relief during labour. However, hemodynamic changes induced by EDA may adversely affect placental perfusion. In fetuses who already suffer from reduced placental function, manifested by fetal growth restriction, this may carry a higher risk of intrapartum compromise. This study aims to determine the emergency delivery rates due to fetal compromise after EDA compared to alternative- and no analgesia across the spectrum of birth weight centiles.

Transplacental Pharmacokinetic Model of Digoxin Based on Ex Vivo Human Placental Perfusion Study.

Digoxin is used as first-line therapy to treat fetal supraventricular tachycardia; however, because of the narrow therapeutic window, it is essential to estimate digoxin exposure in the fetus. The data from ex vivo human placental perfusion study are used to predict in vivo fetal exposure noninvasively, but the ex vivo fetal-to-maternal concentration (F:M) ratios observed in digoxin perfusion studies were much lower than those in vivo. In the present study, we developed a human transplacental pharmacokinetic model of digoxin using previously reported ex vivo human placental perfusion data. The model consists of maternal intervillous, fetal capillary, non-perfused tissue, and syncytiotrophoblast compartments, with multidrug resistance protein (MDR) 1 and influx transporter at the microvillous membrane (MVM) and influx and efflux transporters at the basal plasma membrane (BM). The model-predicted F:M ratio was 0.66, which is consistent with the mean in vivo value of 0.77 (95% confidence interval: 0.64-0.91). The time to achieve the steady state from the ex vivo perfusion study was estimated as 1,500 minutes, which is considerably longer than the reported ex vivo experimental durations, and this difference is considered to account for the inconsistency between ex vivo and in vivo F:M ratios. Reported digoxin concentrations in a drug-drug interaction study with MDR1 inhibitors quinidine and verapamil were consistent with the profiles simulated by our model incorporating inhibition of efflux transporter at the BM in addition to MVM. Our modeling and simulation approach should be a powerful tool to predict fetal exposure and DDIs in human placenta. SIGNIFICANCE STATEMENT: We developed a human transplacental pharmacokinetic model of digoxin based on ex vivo human placental perfusion studies in order to resolve inconsistencies between reported ex vivo and in vivo fetal-to-maternal concentration ratios. The model successfully predicted the in vivo fetal exposure to digoxin and the drug-drug interactions of digoxin and P-glycoprotein/multidrug resistance protein 1 inhibitors in human placenta.

Syncytiotrophoblast-derived extracellular vesicles carry apolipoprotein-E and affect lipid synthesis of liver cells in vitro.

In normal pregnancy, hepatic metabolism adaptation occurs with an increase in lipid biosynthesis. Placental shedding of syncytiotrophoblast‐derived extracellular vesicles (STBEVs) into the maternal circulation constitutes a major signalling mechanism between foetus and mother. We investigated whether STBEVs from normal pregnant women might target liver cells in vitro and induce changes in lipid synthesis. This study was performed at the Nuffield Department of Women's & Reproductive Health, Oxford, UK. STBEVs were obtained by dual‐lobe placental perfusion from 11 normal pregnancies at term. Medium/large and small STBEVs were collected by ultracentrifugation at 10,000g and 150,000g, respectively. STBEVs were analysed by Western blot analysis and flow cytometry for co‐expression of apolipoprotein‐E (apoE) and placental alkaline phosphatase (PLAP). The uptake of STBEVs by liver cells and the effect on lipid metabolism was evaluated using a hepatocarcinoma cell line (HepG2 cells). Data were analysed by one‐way ANOVA and Student's t test. We demonstrated that: (a) STBEVs carry apoE; (b) HepG2 cells take up STBEVs through an apoE‐LDL receptor interaction; (c) STBEV incorporation into HepG2 cells resulted in (i) increased cholesterol release (ELISA); (ii) increased expression of the genes SQLE and FDPS (microarray) involved in cholesterol biosynthesis; (iii) downregulation of the CLOCK gene (microarray and PCR), involved in the circadian negative control of lipid synthesis in liver cells. In conclusion, the placenta may orchestrate the metabolic adaptation of the maternal liver through release of apoE‐positive STBEVs, by increasing lipid synthesis in a circadian‐independent fashion, meeting the nutritional needs of the growing foetus.

The Better-of-Two Strategy for Active versus Passive Management: The Option Value of Active through Time

<h3>Abstract</h3> The placenta is a temporary and complex organ critical for fetal development through its subtle but convoluted harmonization of endocrine, vascular, haemodynamic and exchange adaptations. Yet, due to experimental, technological and ethical constraints, this unique organ remains poorly understood. <i>In silico</i> tools are emerging as a powerful means to overcome these challenges and have the potential to actualize novel breakthroughs. Here, we present an interdisciplinary framework combining <i>in vitro</i> experiments used to develop an elegant and scalable <i>in silico</i> model of oxygen diffusion. We then use <i>in utero</i> imaging of placental perfusion and oxygenation in both control and growth-restricted rodent placentas for validation of our <i>in silico</i> model. Our framework revealed the structure-function relationship in the feto-placental vasculature; oxygen diffusion is impaired in growth-restricted placentas, due to the diminished arborization of growth-restricted feto-placental vasculature and the lack of decelerated flow for adequate oxygen diffusion and exchange. We highlight the mechanisms of impairment in a rat model of growth restriction, underpinned by placental vascular impairment. Our framework reports and validates the prediction of blood flow deceleration impairment in growth restricted placentas with the placenta’s oxygen transfer capability being significantly impaired, both globally and locally.

Placental Insulin-Like Growth Factor-1 Receptor, Protein Kinase B and Mammalian Target of Rapamycin are Downregulated in HIV-1 Positive Women on Antiretroviral Drugs

HIV-1 and ARV drugs uptake during pregnancy may change placental phenotype during pregnancy affecting fetal growth. We investigated the influence of maternal HIV-1 and ARV drugs on expression of placental genes important for fetus growth. A total 51 HIV-1 positives and 46 HIV-1 negative pregnant women were studied. Placental gene expression changes of insulin-like growth factor receptor 1 (IGF-1) R, mammalian target of rapamycin (mTOR), protein kinase B (AKT-1), sodium-coupled neutral amino acid transporters (Slc38a1, Slca38a2, Slc38a4), inhibin A, adrenomedullin and 11 beta-Hydroxysteroid dehydrogenase type (HSD)-2 were assessed by RT-qPCR. There was a significant decrease in mRNA expression of placental IGF-1R, mTOR, and AKT-1 in HIV-1 positive placentas compared to controls (p &lt; 0.0001). There was also significant upregulation of an antiangiogenic molecule, inhibin A and downregulation of angiogenic molecule adrenomedullin in HIV-1 positive placenta (all p &lt; 0.0001). However, the mRNA expression of placental Slc38a1 and Slca38a2 was higher in both HIV-1 positive and negative women delivering LBW babies compared to controls (p &lt; 0.0001). The placental mRNA expression of 11 β-HSD-2 increased by 17 folds in HIV-1 negative and by 3.8 folds in HIV-1 positive women delivering LBW babies. IGF-1-P13-AKT-1-mTOR signaling pathway is dysregulated in placenta of HIV-1 positive women on ARV drugs. Higher mRNA expression levels of inhibin A and lower levels of adrenomedullin occur in placenta of HIV-1 positive women delivering LBW babies. ARV drugs and HIV-1 may be involved in the disruption of vascular tone of the placenta and therefore placental perfusion.&#x0D; Keywords: Pregnant women, HIV-1, ARV drugs, Placental IGF-1-AKT-1-mTOR signaling, inhibin A, adrenomedullin, amino acid transporters.

Physiological role of aldosterone in pregnancy, importance of correction in pathological conditions. What is known about pharmacological targets

Aldosterone is the main mineralocorticosteroid hormone of the human adrenal cortex. It plays a key role in the regulation of kidney and cardiovascular function. Its role especially increases in the adaptation of the woman’s body during pregnancy, and consists in maintaining the balance of electrolytes, blood pressure, ensuring sufficient trophoblast invasion and adequate placental perfusion. This article describes the mechanism of synthesis and action of aldosterone, its biological role and place in the structure of the renin-angiotensin-aldosterone system (RAAS). A special place is given to aldosterone in maintaining hemodynamics during physiological pregnancy, and to violations of the RAAS, as a key to understanding the links in the pathogenesis of preeclampsia.

Perfluorooctane sulfonic acid (PFOS) inhibits vessel formation in a human 3D co-culture angiogenesis model (NCFs/HUVECs)

Perfluorooctane sulfonic acid (PFOS) is a ubiquitous environmental pollutant. In humans, PFOS exposure has been associated with a number of adverse health outcomes, including reduced birth weight. Whether PFOS is capable of affecting angiogenesis and thus possibly fetal development is unknown. Therefore, we investigated 1) the metabolic activity of PFOS-exposed endothelial cells (human umbilical vein endothelial cells, HUVECs), fibroblasts (normal colon fibroblasts, NCFs), and epithelial cells (human colorectal carcinoma cells, HCT116), 2) PFOS-specific inhibition of vascular endothelial growth factor receptor (VEGFR)2 stimulation in KDR/NFAT-RE HEK293 cells, and 3) the antiangiogenic potential of PFOS in a 3D in vitro angiogenesis model of HUVECs and NCFs. In terms of metabolic activity, endothelial cells (HUVECs) were much more sensitive to PFOS than fibroblasts (NCFs) or epithelial cells (HCT116). VEGFR2 signaling in KDR/NFAT-RE HEK293 cells decreased with increasing PFOS concentrations. In co-culture (angiogenesis assay), PFOS treatment resulted in a dose-dependent reduction in tip and branch formation, tip length (μm), and total structural area (μm2) with stable metabolic activity of HUVECs up to high concentrations. We conclude that PFOS possesses antiangiogenic properties. Inhibition of VEGFR2 signaling indicates a possible mechanism of action that can be linked to an existing Adverse Outcome Pathway (AOP43) containing the AO reduced birth weight. Further studies are needed to confirm PFOS-specific adverse effects on angiogenesis, placental perfusion, and fetal growth.

Mortality and Postdischarge Acute Care Utilization for Cardiovascular Conditions at Safety-Net Versus Non–Safety-Net Hospitals

Preeclampsia (PE) is an independent risk factor for adverse maternal cardiovascular outcomes. The role of maternal cardiac function in the pathophysiology of PE remains unclear.This study sought to describe differences in cardiac function at midgestation between women who develop PE and those with uncomplicated pregnancy and to establish whether routine cardiac assessment at midgestation can improve performance of screening for PE achieved by established biomarkers.Mean arterial pressure was measured, medical history was obtained, and left ventricular (LV) systolic and diastolic functions were assessed using standard echocardiography and speckle tracking imaging. Uterine artery pulsatility index and serum placental growth factor and soluble fms-like tyrosine kinase-1 were measured.In 4,795 pregnancies, 126 (2.6%) developed PE. Following multivariable analysis, peripheral vascular resistance was significantly higher and LV global longitudinal systolic strain, ejection fraction, cardiac output, and left atrial area were mildly lower in women who developed PE compared to those who did not. There was a weak association between maternal cardiovascular indices and biomarkers of placental perfusion and function. Cardiac indices did not improve the performance of screening for PE on top of maternal risk factors, mean arterial pressure, and biomarkers of placental perfusion and function.Women who develop PE have an increase in peripheral vascular resistance and a mild reduction in LV functional cardiac indices long before PE development. However, cardiac indices do not improve the performance of screening for PE; thus, their routine clinical use is not advocated.

Placental transport of parabens studied using an ex-vivo human perfusion model.

Parabens are a group of chemicals widely used as preservatives in daily consumer products such as cosmetics, food items, pharmaceuticals and household commodities. They have been broadly detected in human samples indicating a general human exposure, and concerns arose from their potential endocrine disrupting effect. Especially the exposure to parabens during pregnancy is concerning, as the time of fetal development is a particularly vulnerable period. The aim of this study was to investigate the transport and metabolism of four commonly used parabens: methyl-, ethyl-, propyl- and butylparaben (MeP, EtP, PrP and BuP) and the metabolite para-hydroxybenzoic acid (PHBA) across the human placenta. An ex-vivo human placental perfusion model was used. The test compounds were added in the maternal compartment (with initial concentrations of 1mM or 0.1mM). Placental transport was evaluated by fetal-maternal concentration ratios (FM-ratio), transport index (TI) and indicative permeability (IP). Information about parabens kinetics was taken from 10 perfusions and PHBA from 7 perfusions. Paraben metabolism was not detected. The placental transport of MeP, EtP, PrP, BuP and PHBA revealed a transfer from maternal to fetal circulations with FM120 of 0.86±0.27 (MeP), 0.98±0.28 (EtP), 1.00±0.28 (PrP), 1.12±0.59 (BuP) and 0.82±0.37 (PHBA). The test substances accumulated in the perfused tissue in some degree. The average kinetic parameters FM-ratio, TI and IP were not different between chemicals. The present study shows that the placenta barrier is permeable to all four parabens and the metabolite, which implies potential fetal exposure.

VP31.20: Fetal deaths in COVID‐19 infected pregnancies

Fetal death as an ultimate consequence of COVID-19 infection in pregnancy, is a complication that must not be underestimated. Maternal infection can trigger a hyper-inflammatory response, causing endothelial vascular dysfunction and coagulation abnormalities. These lesions compromise placental perfusion which consequently affects fetal perfusion and leads, in some situations, to fetal anoxia and death. Our case series report clinical, analytical and histopathological findings of four cases of in utero fetal demise in COVID-19 infected pregnant women, without any other obvious cause, managed at a tertiary hospital, in Portugal. All pregnancies were uncomplicated until the third trimester and either had obstetric history or developed obstetric conditions related to placental vascular compromise such as hypertensive disorders of pregnancy and fetal growth restriction. Three cases were asymptomatic for COVID-19 on admission, whereas the fourth presented mild symptoms and developed disseminated intravascular coagulation. All fetus were morphologically normal and two of them tested positive for COVID-19. Placental histopathological examinations revealed multiple signs of maternal and fetal vascular malperfusion, chorioangioma and increased perivillous fibrin deposition, findings that are consistent with those observed in hypertensive disorders of pregnancy and fetal growth restriction. This observation suggests that COVID-19 can place at greater risk of in utero fetal demise pregnancies that are already complicated by obstetric conditions related with impaired placental perfusion.

OP06.07: Association of abnormal placental perfusion with the risk of male hypospadias

OP06.07: Association of abnormal placental perfusion with the risk of male hypospadias

Uterine torsion and intrauterine growth restriction: Case report and systematic literature review

Uterine torsion (UT) in pregnancy is a rare condition in obstetric practice. It is defined as a rotation of the uterus of more than 45° around its long axis. Presentations are varied and, most of the time, this condition is recognized at laparotomy or cesarean section (CS). The aim of this study is to summarize the latest evidence about UT in pregnancy. A systematic research of the literature was conducted fetching all papers published from March 2006 to June 2020. We collected data regarding clinical features, treatment, and feto-maternal outcomes. Finally, we reported data of a case of UT associated with intrauterine growth restriction (IUGR) diagnosed and treated at our institution. According to our search strategy, 38 articles were included. In 66% of the cases, acute symptomatology was present at the onset, most frequently abdominal pain was reported. In one-third of the cases, UT was diagnosed during CS without clinical suspicion. Only in two cases, including our case, IUGR was reported. Most (66%) of the cases presented a 180° torsion. In the majority of the cases, a CS was performed also with a deliberate or accidental posterior hysterotomy. One and six cases of maternal and fetal death were, respectively, reported. UT is an infrequent obstetric condition but should be considered in case of abdominal pain, vomiting, or shock presentation during pregnancy. It could lead to a reduction in uterine blood flow contributing to poor placental perfusion, even though more evidence is needed to clarify this link.

Comparison of matrix metalloproteinase-9 and E-cadherin expression in early- and late-onset preeclampsia

BACKGROUNDPreeclampsia (PE) is one of the most common pregnancy complications worldwide. Turnover of villous trophoblast is affected by impaired placental perfusion in preeclampsia. Among the various factors that influence pro and antiangiogenic factors in trophoblast invasion of PE are E-cadherin and matrix metalloproteinase-9 (MMP-9). The current classification scheme differentiates PE into two variants early-onset (EO) and late-onset (LO) PE. The aim of this study was to compare MMP-9 and E-cadherin expression between early- (EO) and late-onset (LO) PE. METHODSThis study used a cross-sectional design involving 26 women with gestational age &lt;34 weeks (EO) and 38 women with gestational age ≥34 weeks (LO) from PE patients. Placentas born to preeclamptic mothers were taken in the form of small pieces of the maternal side to measure the levels of MMP-9 and E-cadherin by the ELISA method. Statistical analysis was assessed using the Mann Whitney and independent t-test with a significant p value &lt;0.05. RESULTSSemiquantitative proteinuria levels were significantly higher in EO-PE group compared to LO-PE group (p=0.000). Mean E-cadherin levels were significant lower in the EO-PE group (125.94 ± 54.22 pg/mg) compared to LO-PE group (157.95 ± 54.12 pg/mg) (p=0.024). However, there was no significance difference in median MMP-9 levels between EO-PE group and LO-PE group (p=0.376). CONCLUSIONThis study demonstrate that E-cadherin had lower levels in preeclampsia patients who gave birth &lt;34 weeks. This study indicated that lower levels of e-cadherin can lead to early delivery in preeclampsia patients.