Placental Vascular Insufficiency Research Articles

The maternal microbiome promotes placental development in mice.

The maternal microbiome is an important regulator of gestational health, but how it affects the placenta as the interface between mother and fetus remains unexplored. Here, we show that the maternal gut microbiota supports placental development in mice. Depletion of the maternal gut microbiota restricts placental growth and impairs feto-placental vascularization. The maternal gut microbiota modulates metabolites in the maternal and fetal circulation. Short-chain fatty acids (SCFAs) stimulate cultured endothelial cell tube formation and prevent abnormalities in placental vascularization in microbiota-deficient mice. Furthermore, in a model of maternal malnutrition, gestational supplementation with SCFAs prevents placental growth restriction and vascular insufficiency. These findings highlight the importance of host-microbial symbioses during pregnancy and reveal that the maternal gut microbiome promotes placental growth and vascularization in mice.

Histopathological Study of Placentas of Hypertensive Disorders

Background and Objective: Pre-eclampsia and eclampsia are common complications in pregnancy, and they lead to utero placental vascular insufficiency. More than 38% of pregnant women succumb to seizures without meeting the clinical criteria for pre-eclampsia and eclampsia. This signifies the importance of a confirmatory diagnosis of pre-eclampsia or eclampsia using the histopathological changes seen in placenta . Hence, the aim of the study was to determine the incidence of histopathological abnormalities in the placentas of singleton pregnancies with hypertensive disorders. Materials & Methods: The study was carried out at Rajendra Institute of Medical Sciences, Ranchi, India from June 2018 to July 2020. In this study spanning two years, 134 cases of pre-eclampsia/eclampsia were included. Placenta tissues were collected from the labor room and histological slides were prepared in the Histology Lab. All the steps of Tissue Processing were done and slides were observed under the light microscope after proper staining. Results: A significant association between the histopathological parameters of the placenta, including fibrin deposition, syncytial knots, hypovascular villi and clinical diagnosis of pre-eclampsia and eclampsia was found. Conclusion: This study elucidates a significant association between placental histopathological patterns, caused by preeclampsia and eclampsia. c

COLOR DOPPLER EVALUATION OF CEREBRAL-UMBILICAL PULSATILITY INDICES AND RATIO AND IT'S USEFULLNESS AT HIGH RISK PREGNANCY.

Objective: The correlation between cerebro-umbilical pulsitility indices and high risk pregnancy. Subjects: The study was included 40patients, 20 preeclampsia patients, 20 gestational diabetes patients. Methods: All patients in the study underwent ultrasound assessment that includes fetal biometry, fetal weight, a four component biophysical profile score and Doppler ultrasound studies of umbilical artery (UA) and middle cerebral artery ( MCA). Results: The study was included 40 patients with high risk pregnancy. They were classified into 2 groups according to the risk pre-eclampsia group and diabetic group whether the two groups are equal in number being 20 per each.UA-PI is significant higher in pre-eclampsia group than diabetic group as well as MCA-PI and C/U ratio is significantly lower in pre-eclampsia group than diabetic group . Conclusion: Doppler investigation of the cerebro – umbilical pulsitlity indices and ratio play an important role in monitoring high risk pregnancies complicated by placental vascular insufficiency and fetal growth restriction (FGR). In a relatively well controlled diabetic pregnancies not complicated by preeclampsia or FGR the values of color Doppler indices are similar to normal pregnancy

609 The association between toxicology-confirmed marijuana use close to delivery and neonatal outcomes and placental pathology

Marijuana use is increasing in women of reproductive age. Prior studies on marijuana's association with obstetric and neonatal outcomes were mainly based on self-reported use remote from delivery. We aim to evaluate the association between toxicology-confirmed marijuana use, within 72 hours of delivery and adverse neonatal outcomes. We also aim to examine placental pathology in women exposed to marijuana during pregnancy. This is a retrospective study of patients delivered between January 2016 and December 2019. Singleton pregnancies with urine drug screen performed within 72 hours of delivery and placenta sent to pathology at the time of delivery were included. Women who tested positive for polysubstance use and current tobacco and alcohol users were excluded. Neonatal outcomes and placental pathology (PP) findings were compared between the women that tested negative for drugs (NDS) and positive for marijuana use (MU). PP findings were categorized into vascular malperfusion and inflammatory findings. 466 patients (NDS) and 32 (MU) were identified. MU are likely to be younger (p=0.002), black and non- Hispanic (p=0.005) and have a psychiatric history (p= 0.01). There is no difference in BMI, parity and preexisting conditions among the groups. Gestational age at delivery and antepartum complications were similar among the groups except for gestational diabetes, which was higher in NDS group (p=0.01). The mean birth weight (BW) is lower in MU group. However, low BW, defined as <2500 grams, is similar among the groups (Table-1). NICU admissions and length of stay did not differ among the groups (Table 1). MU are likely to have higher composite neonatal morbidity (p=0.09). PP did not differ among the groups (Table 2). In contrast to prior studies, MU is not associated with increased risk of low BW, when smoking is excluded. This is also demonstrated in PP, as placental vascular insufficiency is similar in both the groups. Our study also showed increased risk of composite neonatal morbidity which has not been previously reported.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Doppler Indices of Uterine, Umbilical and Fetal Middle Cerebral Arteries Before and After Sildenafil Citrate and Transdermal Nitroglycerin in Cases Suffering from Intrauterine Growth Restriction

Introduction Intrauterine growth restriction (IUGR) is a major cause of perinatal morbidity and mortality. Its diagnosis and treatment constitute one of the most important challenges of present day obstetrics. A drug that could improve maternal and fetal hemodynamics in the setting of early intrauterine growth restriction has potential benefit for at least palliation of this ominous condition. In most instances the etiology of IUGR is unknown. The absence of a uniform etiology may help one understand the existence of the large number of treatments suggested for correcting the problem Patients and methods The objective of this study was to compare the effect of transdermal nitroglycerin and oral Sildenafil citrate on Doppler indices of uterine, umbilical and fetal middle cerebral arteries, and changes in fetal weigh, abdominal circumference and amniotic fluid volume in fifty pregnant women who attended inpatient and outpatient clinics in the department of Obstetrics &amp; Gynecology in Tanta University Hospitals, and suffering from asymmetrical intrauterine growth restriction. Results of the study proved a clear significance of the growing role of transdermal nitroglycerin and Sildenafil citrate for augmenting, feto-placental blood flow in the setting of placental vascular insufficiency and IUGR, as a significant reduction in umbilical artery RI, uterine artery RI in the two groups, also abdominal circumference, AFI and estimated fetal weight were significantly increased after 21 days from treatment. That gives a promising treatment for IUGR patients.

Placenta and Umbilical Cord Cause in Antepartum Deaths.

Stillbirth is a sudden and painful event for parents and obstetrical specialists as well. It is, therefore, of greatest importance to be able to give answers for the cause in order to plan a subsequent pregnancy. The aim of this retrospective study is to estimate the placental and umbilical cord cause of intrauterine death in relation to different gestational ages. The study took place on the Medical Birth Registry of Aretaieio Hospital, National and Kapodistrian University, Athens, Greece. We include a total of 19,283 pregnancies from 1998 to 2012. In this study period, 431 embryonic deaths occurred. The clinical history was documented on admission at delivery. Conditions thought to be associated with the intrauterine fetal death were recorded. Gestational age was calculated from the last menstrual period as well as with the three-trimester system. The autopsy, placenta and umbilical cord examination were performed by the same laboratory of pathology in Aretaieio University Hospital. We found that the majority of stillbirths occurred in the second trimester. We examined placenta and umbilical cord in all cases. The most frequent histologic abnormalities were those indicated placental vascular insufficiency. As far as the umbilical cord is concerned we found that the inflammatory disorder was the most common in antepartum deaths. A single umbilical artery was significantly related to gestational diabetes and congenital embryonic anomalies. Finally, our results showed steady declines in antepartum deaths during 1998-2012. As a result, we reached the conclusion that in order to reduce the fetal death rate, we have to insist on the autopsy of the placenta and umbilical cord in order to gain the appropriate information in counseling the parents.

P05.07: Three‐dimensional power Doppler of uteroplacental vascularisation in third trimester: comparison between normal and placental insufficiency pregnancies (EVUPA study)

Intrauterine growth restriction (IUGR) and pre-eclampsia (PE) are two major pathologies related to placental vascular insufficiency. Uteroplacental vascularisation was quantified with 3D power Doppler (3DPD) in the third trimester in two populations: normal and impaired pregnancies (PE and/or IUGR). 84 women with normal pregnancy and 28 women with PE and/or IUGR pregnancies were prospectively included in this study. Utero-placental 3DPD acquisitions were performed within 72 hours before delivery using standardised machine settings. Placenta and beneath myometrium volumes were manually traced separately with the VOCAL imaging analysis software. 3DPD indices - vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI) - were calculated in each volume and compared between the 2 groups. The impact of placental position and body mass index (BMI) on 3DPD indices was also evaluated. The placental and myometrial volumes were not significantly different between normal and pathological pregnancies. The traced placental volumes were significantly reduced in case of posterior placenta (n=63) (p<0.001). Placental VI, FI and VFI were significantly reduced in PE and/or IUGR pregnancies (n= 28) compared with normal pregnancies (n= 84) ((p<0.01), for myometrium, only FI was significantly reduced in PE and/or IUGR pregnancies (p=0.02). Placental 3DPD indices (VI, FI and VFI) were significantly reduced in posterior placental cases or in the patients with BMI>25 Kg/m2 (n=48) (p<0.001). There was no impact of placental position or BMI on myometrial volume. Only myometrial FI was significantly reduced in posterior placental cases (p<0.05). 3DPD assessment of placental vascular indices has the potential for PE and or IUGR pregnancy diagnosis in the third trimester, the myometrial FI might be an interesting index for PE and or IUGR identification that isn't influenced by patient's BMI.

C2. Maternal cardiac deceleration capacity: a novel insight into maternal autonomic function

Objective: To explore maternal cardiac deceleration capacity (DC), a marker of autonomic function derived from heart rate variability analysis, in pregnancies complicated by intrauterine growth restriction (IUGR) and hypertensive disorders of pregnancy (HDP) associated to IUGR (HDP-IUGR) or to appropriate for gestational age fetuses (HDP-AGAf).Methods: Single-center case-control study conducted at Buzzi Children’s Hospital, Milan. Maternal electrocardiograms were analyzed by Phase-Rectified Signal Averaging (PRSA) to obtain cardiac beat-to-beat DC in women with: HDP-IUGR; HDP-AGAf; severe-IUGR; mild- IUGR; uncomplicated pregnancies. IUGR was defined as abdominal circumference <5th centile; severe-IUGR was associated with umbilical artery Doppler pulsatility index42SD.Results: Two- hundred and sixty-nine women recruited. Women with HDP-IUGR (n = 35) showed significantly higher cardiac DC compared both to controls (n = 141) (p = 0.003) and women with HDP-AGAf (n = 18) (p = 0.01). Women with severe-IUGR (n = 14) showed significantly higher DC than controls (p = 0.01). Women with mild-IUGR (n = 61) as with HDPAGAf showed no differences in DC compared to controls (both p = 0.3).Conclusion: Elevated cardiac deceleration capacity proves autonomic alterations in mothers with severe placental failure. We present a new bedside approach to explore maternal autonomic cardiovascular regulation that might reflect the severity of placental vascular insufficiency.

Maternal cardiac deceleration capacity: a novel insight into maternal autonomic function in pregnancies complicated by hypertensive disorders and intrauterine growth restriction

ObjectiveTo explore maternal cardiac deceleration capacity (DC), a marker of autonomic function derived from electrocardiographic (ECG) signals, in pregnancies complicated by intrauterine growth restriction (IUGR) and hypertensive disorders of pregnancy (HDP) associated to IUGR (HDP-IUGR) or to appropriate for gestational age fetal growth (HDP-AGAf). MethodsProspective single center case-control study conducted at Buzzi Children's Hospital, Milan. Maternal ECGs were analyzed by Phase Rectified Signal Averaging (PRSA) method to obtain cardiac DC in women with: HDP-IUGR, HDP-AGAf, severe-IUGR, mild-IUGR and uncomplicated pregnancies. IUGR was defined as abdominal circumference <5th centile; severe-IUGR was associated with umbilical artery Doppler pulsatility index >2 standard deviations. Non-parametric tests were adopted. Results269 women were recruited. Women with HDP-IUGR (n=35) showed significantly higher cardiac DC compared both to controls (n=141) (p=0.003) and women with HDP-AGAf (n=18) (p=0.01). Women with severe-IUGR (n=14) showed significantly higher DC than controls (p=0.01). Women with mild-IUGR (n=61) as well as women with HDP-AGAf showed no differences in DC compared to controls (both p=0.3). ConclusionsWomen with pregnancy complicated by severe placental failure, such as HDP-IUGR and severe IUGR, show significant autonomic alterations, as indicated by elevated cardiac DC. On the contrary, pregnancy complications such as HDP-AGAf and mild IUGR show no impact on maternal autonomic balance. We present a new approach to explore maternal autonomic cardiovascular regulation that might reflect the severity of placental vascular insufficiency.

Role of venous Doppler evaluation of intrauterine growth retardation

Aim of the workThe aim of this work is to determine the role of venous Doppler Ultrasonography for the prediction of adverse perinatal outcome in “intrauterine growth restricted fetus”, providing the obstetrician with additional information about the time frame and significance of the IUGR to help determine the optimal time of delivery. Patients and methodsSixty pregnant females with their age ranging between 28 and 35years, gestational age between 27 and 37weeks of gestation were enrolled in the study. All patients in the study were subjected to Doppler examination of the umbilical vein (UV), Ductus venosus (DV), right hepatic vein (HV) and umbilical artery (UA). ResultsAbnormal UA Doppler was found in 40 patients. Abnormal DV Doppler was found in 40 patients. Abnormal UV Doppler was found in 10 patients. Abnormal Rt. HV Doppler was found in 20 patients. All parameters studied were strongly related to perinatal mortality, however, none had 100% sensitivity, the pulsatility index in the Rt. HV and DV were the best single indices to use in the prediction of perinatal mortality. ConclusionWe observed that venous Doppler is superior to arterial Doppler in predicting poor perinatal outcome and that the abnormal equivocal BPP scoring significantly correlated with adverse outcome. We also, concluded that multi-vessel Doppler Ultrasonography and BPP can effectively stratify IUGR fetuses with placental vascular insufficiency into risk categories. Fetal deterioration appears to be independently reflected in these two testing modalities; their combined use is likely to be complementary.

IL-10 gene promoter and intron polymorphisms and changes in IL-10 secretion in women with idiopathic recurrent miscarriage

Is recurrent pregnancy loss (RPL) associated with polymorphisms in the promoter and intron regions of the interleukin-10 (IL-10) gene? IL-10 rs1518111 was found to be associated with RPL but the commonly studied promoter variants rs1800872, rs1800871 and 1800896 were not. Reduced expression of IL-10 is implicated in RPL, due to defective maternal immune tolerance (causing early miscarriages) or placental vascular insufficiency (causing late losses). IL-10 production is in part inherited, and IL-10 gene variants associated with reduced IL-10 expression have been analyzed for their association with RPL, often with inconclusive results. A retrospective case-control study was performed between January 2011 and April 2012. The subjects comprised 296 RPL cases and 305 control women. Genotyping of the IL-10 intron (rs1878672, rs3024492, rs1554286, rs1518111, rs3024491, rs3024490) and promoter (rs1800872, rs1800871, rs1800896) variants was done by real-time PCR, with defined clusters. A higher minor allele frequency (MAF) of rs1518111 (P = 0.03) was in seen RPL cases; but the MAFs of the remaining SNPs were comparable between cases and controls. Setting the homozygous major allele genotype (1/1) as the reference, significantly higher frequencies of heterozygous rs1554286 and rs1800872, and homozygous rs1800896 genotype carriers, and a reduced frequency of homozygous rs1518111 genotype carriers, were seen in RPL cases, while the distribution of the remaining genotypes were comparable between cases and controls. Serum IL-10 levels were significantly reduced in RPL cases compared with control women (P = 0.002), and this correlated with rs1518111 and rs1800871 genotypes in both groups, and with the rs1800872 genotype among control women. A nine-locus (rs1878672, rs3024492, rs1554286, rs1518111, rs3024491, rs3024490, rs1800872, rs1800871 and rs1800896) haploview analysis demonstrated an increased frequency of haplotype 112112121 in RPL cases, thus conferring a disease susceptibility nature to this haplotype. The main limitation of this study was that it was limited to Bahraini Arabs, thereby necessitating parallel studies of other ethnic groups. Another limitation is the study design, which prompts speculation on whether it is a cause-effect relationship. While the lack of association of the various IL-10 promoter variants with RPL was in agreement with reports from varied ethnic groups, this is the first study to confirm the association between IL-10 rs151811 intronic variant and RPL. The study was funded by grants from the Arabian Gulf University Research Fund. None of the authors report any competing interests.

Recapitulation of characteristics of human placental vascular insufficiency in a novel mouse model

ObjectiveWe tested the effects of selective reduction of placental blood flow by mesenteric uterine artery branch ligation (MUAL) resulting in fetal growth restriction (FGR). MethodsTimed mated C57BL/6J Day(D) 18 dams were divided into two groups: MUAL (n = 18); and control-sham (n = 18). Pups were delivered on D20, cross-fostered to surrogate CD-1 mothers for 4 weeks, and followed for 8 weeks. Outcome data included birth and placental weight, postnatal growth, placental volume determined by stereology, quantification of placental insulin-like growth factors-1(IGF-1) and IGF-2 and IGF binding proteins(IGFBP 2 and 6) by ELISA and gene expression by qPCR and GeneChip microarray analysis. ResultsCompared with control, MUAL had an 11% reduction in mean birth weight (1.06 ± 0.13 g vs. 0.94 ± 0.13 g, p < 0.001) but no difference in placental weight. At 4 weeks of age, mean body weights of MUAL pups were significantly lower than sham. By 8 weeks, males but not females MUAL mice achieved equivalent mean body weight to control. Placental labyrinth depth, volume, and placental gene expression of IGF-1 and 2 were significantly reduced by MUAL. In contrast, placental protein level of IGFBP-2 and 6 were significantly elevated in the MUAL. Genomic expression analysis demonstrated that MUAL pups significantly up-regulated genes that were associated with apoptosis and growth pathways. ConclusionThis novel mouse animal model of FGR using selective ligation recapitulates multiple characteristics of placental vascular insufficiency (PI) in humans. This is the first non-genetic mouse model of PI which offers its application in transgenic mice to better study the underlying mechanisms in PI. CondensationA new mouse model of placental vascular insufficiency by selective ligation of mesenteric uterine artery branch recapitulates multiple findings observed in human placental vascular insufficiency.

Complement Activation and the Resulting Placental Vascular Insufficiency Drives Fetal Growth Restriction Associated with Placental Malaria

Placental malaria (PM) is a major cause of fetal growth restriction, yet the underlying mechanism is unclear. Complement C5a and C5a receptor levels are increased with PM. C5a is implicated in fetal growth restriction in non-infection-based animal models. In a case-control study of 492 pregnant Malawian women, we find that elevated C5a levels are associated with an increased risk of delivering a small-for-gestational-age infant. C5a was significantly increased in PM and was negatively correlated with the angiogenic factor angiopoietin-1 and positively correlated with angiopoietin-2, soluble endoglin, and vascular endothelial growth factor. Genetic or pharmacological blockade of C5a or its receptor in a mouse model of PM resulted in greater fetoplacental vessel development, reduced placental vascular resistance, and improved fetal growth and survival. These data suggest that C5a drives fetal growth restriction in PM through dysregulation of angiogenic factors essential for placental vascular remodeling resulting in placental vascular insufficiency.

Preeclampsia Is a Biomarker for Vascular Disease in Both Mother and Child: The Need for a Medical Alert System

This paper reviews the literature pertaining to the impact of preeclampsia not only on the mother but particularly on the children. The review points to the higher blood pressure in children born to preeclamptic mothers compared to controls, their increased tendency to suffer strokes, the reduction in their cognitive ability, and their vulnerability to depression. Mechanisms that may induce these changes are emphasized, particularly the placental vascular insufficiency and the resulting hypoxic and proinflammatory environments in which the fetus develops. The hypothesis proposed is that these changes in the fetal-placental environment result in epigenetic programming of the child towards a higher propensity for vascular disease. The review's main recommendation is that, within ethical boundaries, the medical records of individuals born to preeclamptic mothers should clearly indicate this event and should be made available to the affected individuals so that preventive measures against vascular complications and lifestyle changes that may mitigate the latter can be instituted.

Quantification of utero-placental vascularization in a rabbit model of IUGR with three-dimensional power Doppler angiography

ObjectivesOur objective was to evaluate the 3D power Doppler angiography (PDA) in terms of feasibility and ability to detect placental hypo-perfusion in an experimental rabbit model of intrauterine growth restriction (IUGR). Study design14 pregnant females were treated with NG-nitro-L-arginine methylester (L-NAME), a nitric oxide synthase inhibitor, from day 24 to day 28 of gestation, to induce an IUGR. Concomitantly, 8 pregnant rabbits were used as controls. On day 28, 3D power Doppler indices were quantified in each utero-placental unit. Morphological examination of the placentas for the control group (n = 4) and the L-NAME group (500 mg/day, n = 4) were performed with immunohistochemical staining to discriminate the fetal capillaries in the labyrinthine area. ResultsA total of 180 live fetuses were obtained, 108 from the L-NAME group and 72 from the control group. G28 fetal weight was significantly lower in the L-NAME group than in the control group (27.40 ± 0.55 g vs 33.14 ± 0.62 g, p < 0.0001). In the L-NAME group the vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were significantly lower than in the control group (2.6 [1.4; 6.0] vs 7.6 [3.5; 12.6], p < 0.05; 28.7 [26.5; 31.3] vs 32.9 [28.3; 38.1], p < 0.05; 0.8 [0.4; 1.8] vs 2.5 [1.1; 4.1], p < 0.05, for VI, FI and VFI, respectively). Morphological examinations revealed a substantial disorganization of the placental vascular architecture in the L-NAME group. ConclusionThis experimental study demonstrates that quantitative 3D PDA indices are sensitive enough to detect placental vascular insufficiency in an experimental rabbit model of IUGR.

OS047. Quantification of placental vascularization in a rabbit model ofIUGR with three-dimensional power doppler angiography

Placental dysfunction is known to be a major cause of pregnancy complications, such as perinatal loss, preeclampsia, and intrauterine growth restriction (IUGR). Inadequate remodeling of the spiral arteries resulting in decreased blood flowto the placenta has been implicated in the pathophysiology of preeclampsia and IUGR. 3D power Doppler angiography (PDA) is a noninvasive and safe way to study blood flow within an organ or region of interest. The aim of this study was to evaluate PDA as a method to quantify placental perfusion in a pharmacological rabbit model of vascular IUGR induced by inhibition of NO synthesis. Our objective was to evaluate the 3D power Doppler angiography (PDA) in terms of feasibility and ability to detect placental hypo-perfusion in an experimental rabbit model of intrauterine growth restriction (IUGR). Fourteen pregnant females were treated with NG-nitro-L-arginine methylester (L-NAME), a nitric oxide synthase inhibitor, from day 24 to day 28 of gestation, to induce an IUGR. Concomitantly, 8 pregnant rabbits were used as controls. On day 28, 3D power Doppler indices were quantified in each uteroplacental unit. A total number of 180 live fetuses were obtained, 180 from the L-NAME group and 72 from the control group. G28 fetal weight was significantly lower in the L-NAME group than in the control group (27.40±0.55g vs 33.14±0.62g,p<0.0001). In the L-Name group the vascularization index (VI) was significantly lower than in the control group (2.6 [1.4;6.0] vs 7.6 [3.5;12.6],p<0.05). Similar results were obtained for the Flow Index (FI) and the Vascularization Flow Index (VFI). The number of fetuses considered as small for gestational age (SGA;weight<10th centile) was significantly higher in the L-NAME group than in the control group (47/108 vs 7/72,p<0.0001). The VI was significantly lower in the SGA group than in the eutrophic group (3.46 [0.46;5.9] vs 7.50 [4.22;10.9] p<0.05). Similar results were obtained for FI and VFI. This experiment study demonstrates that quantitative 3D PDA indices are sensitive enough to detect placental vascular insufficiency in an experimental model of IUGR.

Correlation between uteroplacental three‐dimensional power Doppler indices and true uterine blood flow: evaluation in a pregnant sheep model

Three-dimensional (3D) Doppler quantification within the uteroplacental unit could be of great help in understanding and screening for pre-eclampsia and intrauterine growth restriction. Yet the correlation between 3D Doppler indices and true blood flow has not been confirmed in vivo. The aim of this study was to evaluate this correlation in a pregnant sheep model. A blood flow quantitative sensor and a controllable vascular occlusion system were placed around the common uterine artery in seven sheep in late pregnancy, while all the other arterial supplies were ligated. Several occlusion levels were applied, from 0 to 100%, simultaneously with 3D Doppler acquisitions of several placentomes, using standardized settings. Each placentome was analyzed using VOCAL™ (Virtual Organ Computer-aided AnaLysis) software. The correlation between true blood flow and Doppler indices (vascularization index (VI), flow index (FI) and vascularization flow index (VFI)) was evaluated, together with measurement reproducibility. Forty-eight acquisitions were analyzed. All 3D Doppler indices were significantly correlated with true blood flow. Higher correlations were observed for VI and VFI (r = 0.81 (0.74-0.87), P < 0.0001 and r = 0.75 (0.67-0.82), P < 0.0001) compared with FI (r = 0.53 (0.38-0.64) P < 0.0001). Both intra- and interobserver reproducibility were high, with intraclass correlation coefficients of at least 0.799. This is the first in-vivo experimental study confirming a significant correlation between true blood perfusion and quantitative 3D Doppler indices measured within the uteroplacental unit. These results confirm the potential usefulness of 3D Doppler ultrasound for the assessment of placental vascular insufficiency both in clinical cases and in a research setting.

A piece in the puzzle of intrauterine fetal death: Pathological findings in placentas from term and preterm intrauterine fetal death pregnancies

Objective. To compare pathological findings of placentas from term and preterm pregnancies complicated by intrauterine fetal death (IUFD).Study design. A retrospective cohort study was conducted including deliveries complicated by IUFD. A comparison was made between placentas from term and preterm (<37 weeks' gestation) pregnancies complicated by IUFD. A second analysis was undertaken comparing IUFD placentas delivered before and after 34 weeks' gestation. Uteroplacental insufficiency was defined when one or more of the following pathological features were found: placental infarct, poor vascularity of the chorionic villi, intravascular thrombi and vascular occlusion.Results. During the study period, 849 placentas of IUFD were examined. Gross and microscopic pathological finding were noted. When comparing gross and microscopic findings in term and preterm (<37 weeks) IUFD placentas, higher rates of calcifications, tissue congestion and cellular metaplasia were found in term vs. preterm placentas. Significantly increased rates of poor tissue vascularity, placental vascular occlusion and uteroplacental insufficiency were demonstrated in preterm IUFD placentas. When comparing pathological findings in IUFD placentas delivered before and after 34 weeks' gestation, higher rates of abnormal cord insertion, calcifications, tissue congestion, infarcts and intravascular thrombi as well as poor tissue vascularity and placental vascular occlusion were demonstrated in IUFD placentas delivered before 34 weeks. Regardless of gestational age at the time of IUFD in more than 90% of placentas vascular wall thickening was found. A third of both term and preterm placentas demonstrated histological chorioamionitis.Conclusions. A vast majority of IUFD placentas reveal numerous pathological findings that reflect uteroplacental insufficiency and abnormal blood supply. Different characteristics were noted in term and preterm placentas of pregnancies complicated by IUFD. Better definition of causes and associated placental pathological findings of IUFD might aid clinicians in counseling such patients regarding the reason and risk of recurrence in subsequent pregnancies.

Interleukin 10 Gene Promoter Polymorphisms in Women with Pregnancy Loss: Preferential Association with Embryonic Wastage1

Interleukin 10 (IL10) is associated with maternal immunotolerance. IL10 also down-regulates decidual cell tissue factor expression, the main molecule triggering coagulation activation: this antithrombotic effect may protect the umbilicoplacental vasculature from the 10th wk of gestation onward. IL10 down-regulation may thus dispose to early pregnancy loss (PL) due to maternal immunotolerance defect or late pregnancy failure due to placental vascular insufficiency. IL10 gene promoter polymorphisms associated with cytokine down-regulation may help to identify the actual and probable mechanisms of IL10 modulation in pregnancy outcomes. We investigated the following four IL10 promoter polymorphisms associated with IL10 down-regulation: two single-nucleotide polymorphisms rs1800871 and rs1800872 and two polymorphic CA repeat microsatellites IL10 X78437.2:g8134CA(14_29) and IL10 X78437.2:g.5325CA(11_15). Each microsatellite was analyzed as a biallelic polymorphism. Based on a review of the literature, we define a short allele and a long allele for each microsatellite. We compared their frequencies in early PL occurring before 10 wk of amenorrhea (n = 342) and in PL occurring later on (n = 123). The mutated alleles rs1800871T (odds ratio, 3.083; 95% confidence interval, 1.984-4.792) and rs1800872A (odds ratio, 3.013; 95% confidence interval, 1.924-4.719) were associated with early PL. The haplotype rs1800872A/rs1800871T/X78437.2:g.8134CA[14_25]/X78437.2:g.5325CA[11_13], which includes the two mutated alleles, was significantly associated with the risk of early PL in a dose-dependent manner. Positivity for one haplotype was significantly associated with a 5.6-fold increase in the risk of early pregnancy failure, and positivity for two haplotypes was associated with an 8-fold increase in risk. In women with PL, some polymorphisms of the IL10 gene promoter seem to be constitutional risk factors for early (embryonic) pregnancy failure.

P31 Diffuse cavernous hemangioma of the left leg, vulva and uterus in a pregnant woman: report of a rare case

Introduction: The PAI-1 is the most important inhibitor of t-PA. High levels of PAI-1 are associated with low fibrinolytic activity. The genotype 4G/4G is associated with high plasmatic levels of this inhibitor, although the association of this polymorphism and obstetric complications is usually controversial. Objective: The aim of this study is to determine whether this polymorphism increases the risk of an obstetric complication. Methods: A total of 138 women with 154 episodes of recurrent early loss (2 or more) and/or late loss (1 or more) and/or vascular placental insufficiency (preeclampsia, FGR, abruptio placentae) were studied for the PAI 4G/5G polymorphism and compared with the prevalence in Argentinian normal population. Results: the PAI 4G/4G was significantly more prevalent in women with vascular placental insufficiency: 39.4% vs 20.9%; p: 0.022, OR 2.46 (CI 1.17 5.21). We did not find any association between this polymorphism and early or late pregnancy loss. The PAI 5G/5G was significantly more prevalent in normal population compared to women with early miscarriages 36.1% vs 20.3%; p: 0.005, 0R: 0.45 (CI: 0.25 0.81), so it suggest a protective effect. The prevalence of PAI 4G/5G was similar to controls in all the subgroups. Conclusions: Our study demonstrates a significant association between PAI 4G/4G and vascular placental insufficiency.