Fetal Thrombo-occlusive Disease Research Articles

The Impact of Gestational Weight Gain on Subclinical Atherosclerosis, Placental Circulation and Neonatal Complications

Objective: Vascular atherosclerotic changes, mediated by environmental and genetic factors, develop years before an event. Detection of vascular damage, using ultrasonographic measurement of carotid IMT, is predictive of future cardiovascular events. The present study was designed to investigate the impact of gestational weight gain (GWG) on early atherosclerotic changes during late pregnancy, using intima media thickness (IMT), as well as placental vascular circulation and inflammatory lesions and pregnancy outcome. Design and methods: 59 women who gave birth at Wolfson Medical Center during 2018 were divided into two groups according weight gain during pregnancy: Group 1 included 32 women with pregnancy weight gain within recommended range, Group 2 included 27 wonen with exessive weight gain during pregnancy. IMT was measured by High-resolution B-mode ultrasound (Sonosite Titan/Sonosite, Inc., Bothell, Washington, USA). Placental histology was performed for vascular circulation, as well as inflammatory lesions of maternal and fetal origin. Metabolic measures such as fasting glucoe, lipids, hs-CRP, HOMA-IR were determined. Maternal and neonatal outcome parameters were collected. Results: Weight gain during the pregnancy was significantly higher in Group 1, compared to Group 2 (17.5+/-6.2 vs 6.8+/-5.7, p<0.0001), whereas pre-gestational BMI did not differ significantly between groups (p=0.059). IMT levels differed between groups and was significantly higher in group 1 compared to Group 2 (0.7+/-0.1 vs 0.6+/-0/1, p=0.028). In regression analisys, pregnancy weight gain remained a significant independent predictor of IMT. Rate of macrosomia was significantly higher in Group 1 than in Group 2 (p=0.014). Maternal vascular supply (MVS) abnormalities of the placental bed did not differ significantly between groups (p=0.297). Among placental lesions related to fetal vascular malperfusion, villous changes consistent with fetal thrombo-occlusive disease (FTOD) were significantly higher in Group 1 than in group 2 (p=0.034). Conclusion: In the present study, excessive weight gain during pregnancy was significantly and independently associated with an increased IMT. Among placental vascular lesions, villous changes consistent with fetal thrombo-occlusive disease (FTOD) were significantly higher women with excessive weight gain during pregnancy.

Insulin Treatment Is Associated With Improved Fetal Placental Vascular Circulation in Obese and Non-obese Women With Gestational Diabetes Mellitus.

Objective: The present study was designed to investigate the impact of carbohydrate restriction and insulin treatment on placental maternal and fetal vascular circulation in obese and non-obese women with gestational diabetes mellitus (GDM).Design and methods: One Hundred Ninety-One women with GDM who gave birth and underwent a placental histopathological examination at Wolfson Medical Center, Israel, were included in the study: 122 women who were treated with carbohydrate/calorie restriction diet (Group 1) and 69 women who were treated with diet plus insulin (Group 2). Additionally, each group was divided into two subgroups according to pre-pregnancy BMI: non-obese and obese.Results: Maternal vascular malperfusion lesions did not differ significantly between groups. Vascular lesions related to fetal malperfusion were significantly lower in GDM women treated by insulin and diet compared to women with diet alone (p = 0.027). Among fetal malperfusion lesions, villous changes consistent with fetal thrombo-occlusive disease (FTOD) were significantly lower in women treated with diet plus insulin and lowest in GDM women with pre-pregnancy BMI < 30 kg/m2 (p = 0.009). In the logistic regression analysis, insulin treatment was significantly associated with a decreased rate of villous changes consistent with FTOD (OR 0.97, 95% CI 0.12–0.80, p = 0.03). Prevalence of gestational hypertension was higher in obese women of both treatment groups (p = 0.024).Conclusion: Combination of obesity and GDM increased rate of FTOD and prevalence of gestational hypertension. Carbohydrate restriction diet plus insulin treatment was associated with improved fetal placental vascular circulation, especially in GDM women with pre-pregnancy BMI < 30 kg/m2.

302: Placental histopathological lesions in correlation with neonatal outcome in preeclampsia with and without severe features

We aimed to compare pregnancy outcome and placental histopathology in women with preeclampsia with and without severe features. Labor, maternal characteristics, neonatal outcome, and placental histopathology reports of pregnancies complicated by preeclampsia from 2008-2016 in a single university hospital were reviewed. Results were compared between those with and without severe features according to the current ACOG guidelines. Placental lesions were classified to maternal vascular malperfusion lesions, fetal vascular lesions consistent with fetal thrombo-occlusive disease, and maternal/fetal inflammatory responses. Small for gestational age (SGA) was defined as neonatal birth-weight ≤ 10th %. Composite adverse neonatal outcome was defined as one or more of the following early complications: sepsis, blood transfusion, phototherapy, respiratory morbidity, cerebral morbidity, NEC, or death. Regression analysis was used to identify independent associations with adverse neonatal outcome. The preeclampsia with severe features group (n=284) was characterized by a lower gestational age at delivery (35.1±3.7 vs. 36.7±2.3 wks, p<0.001), and a higher rate of cesarean deliveries (p<0.001) as compared to the preeclampsia without severe features group (n=151). Placental weight <10th percentile and lesions associated with maternal malperfusion were significantly more common in the preeclampsia with severe features group as compared to the preeclampsia without severe features (p<0.001 for both). The rate of fetal vascular supply lesions or inflammatory lesions did not differ between the groups. Additionally, the preeclampsia with severe features group had higher rates of SGA (p=0.016), NICU admission (p=0.014), and composite adverse neonatal outcome (p=0.002). Using regression analysis adverse neonatal outcome was independently associated with gestational age (aOR= 0.54, 95% CI 0.49-0.68), SGA (aOR=1.75, 95% CI=1.15-3.59), severe preeclampsia (aOR=1.8, 95%CI = 1.13-3.54) and placental maternal malperfusion lesions (aOR=2.13, 95% CI=1.05-4.39). Preeclampsia with severe features is associated with a higher rate of placental lesions and adverse neonatal outcome. The adverse neonatal outcome is associated with placental malperfusion independent of background confounders.

The placental component and obstetric outcome in severe preeclampsia with and without HELLP syndrome

ObjectiveWe aimed to compare obstetric outcome and placental-histopathology in pregnancies complicated by preeclampsia with severe features with and without HELLP syndrome. MethodsLabor, maternal characteristics, neonatal outcome and placental histopathology of pregnancies complicated with severe preeclampsia during 2008–2015 were reviewed. Results were compared between those without signs of HELLP syndrome (severe preeclampsia group) and those with concomitant HELLP syndrome (HELLP group). Placental lesions were classified to maternal vascular lesions consistent with malperfusion, fetal vascular lesions consistent with fetal thrombo-occlusive disease, and inflammatory lesions. Small-for-gestational-age (SGA) was defined as birth-weight ≤10th% and ≤5th%. Composite adverse neonatal outcome was defined as one or more early neonatal complications. ResultsCompared to the severe preeclampsia group (n = 223), the HELLP group (n = 64) was characterized by earlier gestational-age, 34.1 ± 2.7 vs. 35.3 ± 3.4 weeks, p = 0.010, higher rates of multiple pregnancies (p = 0.024), and thrombophilia (p = 0.028). Placentas in the HELLP group had higher rates of vascular and villous lesions consistent with maternal malperfusion (p = 0.023, p = 0.037 respectively). By multivariate logistic regression analysis models, vascular and villous lesions of maternal malperfusion were independently associated with HELLP syndrome (aOR 1.9, aOR 1.8, respectively). SGA was also more common in the HELLP group, both below the 10th percentile (p = 0.044) and the 5th percentile (p = 0.016). Composite adverse neonatal outcome did not differ between the groups. ConclusionSevere preeclampsia and HELLP syndrome have similar placental histopathologic findings. However, HELLP syndrome is associated with higher rates of placental maternal vascular supply lesions and SGA suggesting that the two clinical presentations share a common etiopathogenesis, with higher placental dysfunction in HELLP syndrome.

Placental histopathology lesions and pregnancy outcome in pregnancies complicated with symptomatic vs. non-symptomatic placenta previa

BackgroundThe mechanisms involved in bleeding in cases of placenta previa (PP) and the effect on pregnancy outcome is unclear. ObjectivesWe aimed to compare pregnancy outcome and placental histopathology in pregnancies complicated with symptomatic (bleeding) vs. non-symptomatic PP, and to study the effects of the co-existence of histopathological retro-placental hemorrhage (RPH) in cases of symptomatic PP on neonatal and maternal outcomes. Study designLabor and maternal characteristics, neonatal outcome and placental histopathology lesions of pregnancies with PP, delivered between 24 and 42weeks, during 2009–2015, were reviewed. Results were compared between PP who had elective cesarean delivery (CD) (previa group) and PP with bleeding necessitating emergent CD (symptomatic previa group). Placental lesions were classified to lesions consistent with maternal malperfusion or fetal thrombo-occlusive disease (vascular and villous changes), and inflammatory lesions. ResultsCompared to the previa group (n=63), the symptomatic previa group (n=74) was characterized by older patients (p<0.001), higher rate of smokers (p=0.005), thrombophilia (p=0.038), and preterm deliveries (p<0.001). Placentas within the symptomatic previa group were smaller, with higher rates of weight<10th% (p=0.02), RPH (p<0.001) and villous changes related to maternal malperfusion (p=0.023). As compared to symptomatic PP without RPH, co-existence of RPH was associated with higher rate of adverse neonatal outcome (p<0.001) and maternal blood transfusion (p=0.02). On multivariate regression analysis, composite adverse neonatal outcome was found to be dependent on coexisting RPH (OR=2.8, 95%CI 1.2–11.7, p=0.03), and low gestational age (OR=3.1, 95%CI 1.6–4.9, p=0.02). ConclusionsSymptomatic placenta previa is associated with increased placental malperfusion lesions suggesting an association of maternal malperfusion with abnormal placental separation. The coexisting finding of RPH with symptomatic placenta previa can be seen as a marker for more extensive/severe placental separation, hence the association with maternal transfusion requirements and poorer fetal outcome.

Expression and function of placental uric acid transporter GLUT9

Expression and function of placental uric acid transporter GLUT9

796: Comparison of three methods for estimated fetal weight during active labor: a prospective study

795 Intraoperative findings, placental assessment and neonatal outcome in emergent cesarean deliveries for non-reassuring fetal heart rate Eran Weiner, Jacob Bar, Nataly Fainstein, Letizia Schreiber, Avi Ben-Haroush, Michal Kovo Wolfson Medical Center, Holon, Israel, Rabin Medical Center, PetachTikva, Israel OBJECTIVE: To correlate between intra-operative findings, placental histopathology and neonatal outcome in emergent cesarean deliveries (ECD) for non-reassuring fetal heart rate (NRFHR). STUDY DESIGN: Data on ECD for NRFHR were reviewed for labor, documented intraoperative findings, neonatal outcome parameters and placental histopathology reports. Results were compared between those with and without intraoperative findings. Placental lesions were classified to those related to maternal underperfusion or fetal thrombo-occlusive disease, and those related to maternal (MIR) and fetal (FIR) inflammatory responses. Neonatal outcome consisted of low Apgar score ( 7 at 5 min), cord blood pH<7.0, and evidence of respiratory distress, necrotizing enterocolitis, sepsis, transfusion, ventilation, seizure, hypoxic-ischemic encephalopathy, phototherapy, or death. RESULTS: Intraoperative findings were observed in 49.5% of 543 women and included: cord entanglements in 77%, placental abruptions in 25.5%%, true knots in 6.6%, short cord in 6.3%, uterine rupture & dehiscence in 1.5 %, and cord prolapse in 1.5% (more than one cause was possible). Placental lesions were more common in those without intraoperative findings as compared to those with intraoperative findings: placental lesions related to maternal under-perfusion, vascular lesions , 9.1% vs. 4.1%, p1⁄40.024, and villous changes, 39.2% vs. 30.7%, p1⁄40.047, lesions consistent with fetal thrombo-occlusive disease, 13.6% vs. 7.4%, p1⁄40.024, and inflammatory lesions, MIR and FIR, p1⁄40.033, p1⁄40.001, respectively. By using multivariate logistic regression analysis, adverse neonatal outcome was found to be dependent on maternal age, gestational age, preeclampsia placental weight <10 %, and MIR. CONCLUSION: NRFHR necessitating ECD may originate from different underlying mechanisms. In about half, the insult is probably acute and can be identified intraoperatively. In the remaining half, underlying placental compromise may be involved.

Intraoperative findings, placental assessment and neonatal outcome in emergent cesarean deliveries for non-reassuring fetal heart rate

ObjectiveTo correlate between intraoperative findings, placental histopathology and neonatal outcome in emergent cesarean deliveries (ECD) for non-reassuring fetal heart rate (NRFHR). Study designData on ECD for NRFHR were reviewed for labor, documented intraoperative findings, neonatal outcome parameters and placental histopathology reports. Results were compared between those with and without intraoperative findings. Placental lesions were classified to those related to maternal underperfusion or fetal thrombo-occlusive disease, and those related to maternal (MIR) and fetal (FIR) inflammatory responses. Neonatal outcome consisted of low Apgar score (≤7 at 5min), cord blood pH<7.0, and evidence of respiratory distress, necrotizing enterocolitis, sepsis, transfusion, ventilation, seizure, hypoxic–ischemic encephalopathy, phototherapy, or death. ResultsIntraoperative findings were observed in 49.5% of 543 women, mostly cord complications (77%). Placental lesions were more common in those without intraoperative findings as compared to those with intraoperative findings: placental lesions related to maternal under-perfusion, vascular lesions, 9.1% vs. 4.1%, p=0.024, and villous changes, 39.2% vs. 30.7%, p=0.047, lesions consistent with fetal thrombo-occlusive disease, 13.6% vs. 7.4%, p=0.024, and inflammatory lesions, MIR and FIR, p=0.033, p=0.001, respectively. By using multivariate logistic regression analysis, adverse neonatal outcome was found to be dependent on maternal age, gestational age, preeclampsia placental weight <10th%, and MIR. ConclusionNRFHR necessitating ECD may originate from different underlying mechanisms. In about half, the insult is probably acute and can be identified intraoperatively. In the remaining half, underlying placental compromise may be involved.

The placental factor in early- and late-onset normotensive fetal growth restriction

ObjectiveOur objective was to investigate the placental component in early- and late-onset fetal growth restriction (FGR) compared to placentas from neonates appropriate for gestational age (AGA). Study designPlacentas from normotensive women who gave birth at 24–42 weeks to neonates with a birth-weight below the 10th percentile (FGR group), or to healthy AGA neonates (AGA group), were analyzed. Placental lesions were classified to lesions related to maternal underperfusion, lesions consistent with fetal thrombo-occlusive disease and inflammatory lesions. Findings were compared between patients who delivered ≤34 weeks (early-onset FGR) or >34 weeks (late-onset FGR) and controls with AGA neonates. ResultsThe early-onset FGR group (n = 24) had a higher rate of placental vascular lesions related to maternal underperfusion than the late-FGR group (n = 334) (41.7% vs. 8.7%, P < 0.001) and more villous lesions related to maternal underperfusion than the preterm AGA group (n = 68) (70.8% vs. 5.9%, P < 0.001). The late-onset FGR group had more placental villous lesions related to maternal underperfusion (57% vs. 19% P < 0.001) and more lesions consistent with fetal thrombo-occlusive disease (26.3% vs. 8.5%, P < 0.001) than the term AGA group (n = 153). ConclusionEarly- and late-onset FGR have different placental pathology compared with AGA controls, suggesting that a combination of fetal and maternal vascular compromise is more dominant in the late-onset FGR, rather than more severe maternal vascular compromise in early-onset FGR.

The placental vascular component in early and late intrauterine fetal death

ObjectiveTo compare the placental histopathological findings between pregnancies complicated by early (<34weeks' gestation) and late (≥34weeks' gestation) intrauterine fetal death (IUFD) and pregnancies with live births. Material & MethodsPlacentas of patients with unexplained IUFD between 22–42weeks of gestation were analyzed for maternal vascular supply lesions that include those related to maternal underperfusion (villous changes and vascular lesions), fetal vascular supply lesions that include findings consistent with fetal thrombo-occlusive disease (villous changes and vascular lesions) and maternal and fetal inflammatory response lesions. The clinical characteristics and placental findings were compared with those from live birth controls adjusted for gestational age. ResultsIn the early IUFD group (n=28), compared to controls with early delivery, a higher rate of vascular lesions consistent with fetal thrombo-occlusive disease (28.6% vs. 0, p=0.002), villous changes consistent with fetal thrombo-occlusive disease (21.4 vs. 3.6%, p=0.043), and cord related lesions (46.4% vs. 0, p<0.001), respectively, were observed. A similar high rate of maternal vascular supply lesions was detected in both groups. In the late IUFD group (n=30), compared to controls, a higher rate of cord related lesions, 40% vs. 0, respectively, p<0.001, were found. In contrast, maternal and fetal inflammatory response lesions were more common in controls than in placentas from early and late IUFD. ConclusionsThe involvement of placental fetal vascular supply lesions is more extensive in early IUFD than in late IUFD, when compared with matched controls.

Placental factor in spontaneous term labor in uncomplicated pregnancy

Objectives: To investigate the placental role in uncomplicated pregnancies and spontaneous term labor. Methods: Placentas were retrieved from women with uncomplicated pregnancies and compared between those with spontaneous term labor to those with elective cesarean delivery without labor. Placentas were analyzed for lesions consistent with maternal circulation abnormalities, lesions consistent with fetal thrombo-occlusive disease and inflammatory lesions, maternal or fetal responses. Results: The study included 139 pregnancies, 76 with term spontaneous deliveries (cases) and 63 with term elective cesarean deliveries (controls). Maternal age, gravidity, parity and BMI were significantly lower in the study group, but gestational age was higher as compared with the control group. Higher rate of maternal inflammatory lesions was observed in the study group compared to the control group, 21 vs. 1.6%, respectively, p = 0.001. No differences were observed in vascular lesions or in fetal inflammatory lesions between the groups. Conclusion: Placental maternal inflammatory changes play a role in spontaneous term labor, different from the involvement of the fetal compartment and placental vascular component in preterm labor.

The placental component in early‐onset and late‐onset preeclampsia in relation to fetal growth restriction

To identify pathological placental differences between early-onset and late-onset preeclampsia, in relation to fetal growth restriction (FGR). Placentas from patients with preeclampsia were analyzed for lesions of maternal vascular supply consistent with maternal underperfusion and lesions of fetal vascular supply consistent with fetal thrombo-occlusive disease. Findings were compared between patients who gave birth before 34 weeks (early-onset preeclampsia) and after 34 weeks (late-onset preeclampsia). Compared with the late-onset group (n = 93), the early-onset group (n = 37) had higher rates of FGR (62.2% vs 25.8%, P < 0.001) and lesions of maternal vascular supply (95% vs 60%, P < 0.001). Within the early-onset group, cases with FGR (n = 23) had more lesions of fetal vascular supply (47.8% vs 7%, P = 0.01), with similar high rates of lesions of maternal vascular supply (91% vs 100%) compared with those without FGR. Within the late-onset preeclampsia group, cases with FGR (n = 24) had higher rates of maternal vascular supply lesions (88% vs 51%, P = 0.003) than those without FGR, but similar rates of fetal vascular supply lesions (25% vs 16%, P = 0.32). The placental fetal vascular supply lesions in combination with maternal vascular lesions are more dominant in early-onset preeclampsia with FGR as compared with early-onset preeclampsia without FGR.

Intrapartum fever at term: clinical characteristics and placental pathology

Objectives: To investigate the association between clinical characteristics and placental histopathology in women with intrapartum fever (IPF) at term. Methods: Maternal characteristics, intrapartum parameters, neonatal outcome and placental pathology were compared between 120 patients with IPF (≥380C) and a control group matched for mode of delivery. Placental lesions were classified as consistent with maternal circulation abnormalities or fetal thrombo-occlusive disease or inflammatory responses of maternal (MIR) or fetal (FIR) origin. Results: Compared to controls the study group was characterized by significantly higher rates of nulliparity, extra-amniotic balloon induction of labor, and epidural anesthesia, higher gestational age, higher white blood cell count, and more vaginal examinations. On multivariate logistic regression analysis, multiple vaginal examinations were independently associated with IPF. MIR was detected in 71% of the study group compared to 21% of controls (p < 0.001), and FIR, in 32.5% and 7.5%, respectively (p < 0.001). IPF was independently associated with inflammation of maternal origin (adjusted odds ratio (OR) 8.0, 95% CI 4.2–15.2, p < 0.001) and fetal origin (adjusted OR 5.2, 95% CI 2.07–13.4, p < 0.001). Neonatal outcome was similar in the two groups. Conclusions: Multiple vaginal examinations are a significant risk factor for the development of IPF. IPF at term is independently associated with placental inflammatory lesions.

Association of non-reassuring fetal heart rate and fetal acidosis with placental histopathology

Objective To investigate the association between different placental lesions and non-reassuring fetal heart rate (NRFHR) pattern and fetal acidosis in labor. Study design Placentas from 213 women who underwent cesarean section because of NRFHR with or without fetal acidosis (pH < 7.2) were classified by histopathologic findings: consistent with maternal circulation abnormalities i.e., namely, marginal or retroplacental hemorrhage (M0), maternal underperfusion, vascular (M1) or villous changes (M2), and those consistent with fetal thrombo-occlusive disease due to vascular (F1) or villous (F2) changes. Lesions were also analyzed by maternal (MIR) or fetal (FIR) origin of inflammatory responses. Results Cord blood pH was normal in 169 neonates (7.29 ± 0.04; control group) and <7.2 in 44 (7.10 ± 0.07; study group). The study group had higher rates of histologic chorioamnionitis; MIR was detected in 34.1% compared to17.8% of controls ( p = 0.018), and FIR, in 18.2% compared to 6.5% ( p = 0.016). Neonates in the study group had lower Apgar scores and longer hospitalization. Conclusions Placental MIR and FIR are associated with cord blood acidosis in neonates delivered by cesarean section for NRFHR tracings in labor.