-
Heliyon May 2024P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) multidrug resistance (MDR) transporters are localized at the luminal surface of the blood-brain barrier...
Hypoxia modulates P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) drug transporters in brain endothelial cells of the developing human blood-brain barrier.
P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) multidrug resistance (MDR) transporters are localized at the luminal surface of the blood-brain barrier (BBB). They confer fetal brain protection against harmful compounds that may be circulating in the peripheral blood. The fetus develops in low oxygen levels; however, some obstetric pathologies such as pre-eclampsia, placenta accreta/previa may result in even greater fetal hypoxic states. We investigated how hypoxia impacts MDR transporters in human fetal brain endothelial cells (hfBECs) derived from early and mid-stages of pregnancy. Hypoxia decreased BCRP protein and activity in hfBECs derived in early pregnancy. In contrast, in hfBECs derived in mid-pregnancy there was an increase in P-gp and BCRP activity following hypoxia. Results suggest a hypoxia-induced reduction in fetal brain protection in early pregnancy, but a potential increase in transporter-mediated protection at the BBB during mid-gestation. This would modify accumulation of various key physiological and pharmacological substrates of P-gp and BCRP in the developing fetal brain and potentially contribute to the pathogenesis of neurodevelopmental disorders commonly associated with hypoxia.
PubMed: 38737275
DOI: 10.1016/j.heliyon.2024.e30207 -
European Journal of Obstetrics &... Jun 2024The placenta accreta spectrum is a complex disorder characterized by abnormal invasion of the placenta into the uterine wall, posing a significant risk of...
Prophylactic occlusion balloons of both internal iliac arteries in caesarean hysterectomy for placenta accreta spectrum disorder reduces blood loss: A retrospective comparative study.
BACKGROUND
The placenta accreta spectrum is a complex disorder characterized by abnormal invasion of the placenta into the uterine wall, posing a significant risk of life-threatening haemorrhage for patients. Its incidence is on the rise, largely attributed to the increasing rates of caesarean sections. Management of this spectrum involves a multidisciplinary approach, although standardized protocols are not yet established. While caesarean hysterectomy remains the standard Gold, several adjunctive treatments have emerged in recent years to mitigate bleeding risk and associated morbidity. Among these, prophylactic occlusion balloons placed in the internal iliac arteries have shown promise. The aim of our study is to demonstrate the effect of prophylactic occlusion balloons in both uterine iliac arteries in the management of placental accreta spectrum disorders.
METHODS
A retrospective monocentric cohort study was conducted in the Department "C" of Gynaecology and Obstetrics at the Maternity Center of Tunis. The study spanned three years, from January 2nd, 2020, to December 31st, 2022. The study population consisted of two groups: Control Group (CG) comprised patients who underwent caesarean hysterectomy without internal-iliac prophylactic occlusion balloons, and Occlusion balloons of both internal iliac arteries Group (OBIIAG) included patients who underwent caesarean hysterectomy with internal-iliac prophylactic occlusion balloons.
RESULTS
A total of 38 patients were included in the study, all of whom exhibited similar epidemiological characteristics and comparable personal and obstetric histories. The most prevalent risk factor among the patients was a history of caesarean section (92%). On average, patients were diagnosed at 30 weeks of gestation, with third-trimester bleeding being the most common presentation (71% of cases). The median gestational age at delivery was between 36 and 37 weeks. We observed a significant difference in blood loss between the two groups (2888 ml in the control group and 1828 ml in the group with internal-iliac prophylactic occlusion balloons, p < 0.05). Implementation of this technique resulted in a reduced need for massive transfusions (p < 0.01) and shorter operating times (126 min for the control group and 92 min for the group with internal-iliac prophylactic occlusion balloons; p = 0.04). There were no significant differences in morbidity between the two groups.
CONCLUSION
The intra-iliac prophylactic occlusion balloons can help reduce the risk of hemorrhage and the morbidities that come with the placenta accreta spectrum disorder.
PubMed: 38736526
DOI: 10.1016/j.eurox.2024.100310 -
Diagnostics (Basel, Switzerland) Apr 2024Placenta accreta spectrum (PAS) disorder is one of the leading causes of peripartum maternal morbidity and mortality; its early identification during pregnancy is of...
Placenta accreta spectrum (PAS) disorder is one of the leading causes of peripartum maternal morbidity and mortality; its early identification during pregnancy is of utmost importance to ensure the optimal clinical outcome. The aim of the present study is to investigate the possible association of the presence and type/location of placenta previa on MRI with PAS and maternal peripartum outcome. One hundred eighty-nine pregnant women (mean age: 35 years; mean gestational age: 32 weeks) at high risk for PAS underwent a dedicated placental MRI. All women underwent a C-section within 6 weeks from the MRI. All MRIs were evaluated by two experienced genitourinary radiologists for presence, type (complete/partial vs. marginal/low lying), and location (anterior vs. anterior-posterior vs. posterior) of placenta previa. Statistical analysis was performed for possible association of type/location of previa with placental invasiveness and peripartum outcomes. Intraoperative information was used as a reference standard. Complete/partial previa was detected in 143/189 (75.6%) and marginal/low lying previa in 33/189 (17.5%) women; in 88/189 (46.6%) women, the placenta had anterior-posterior, in 54/189 (28.6%) anterior and in 41/189 (21.7%) posterior. Complete/partial previa had an at least 3-fold probability of invasiveness and was more frequently associated with unfavorable peripartum events, including massive intraoperative blood loss or hysterectomy, compared to low-lying/marginal placenta. Posterior placental location was significantly associated with lower rates of PAS and better clinical outcomes. In conclusion, the type and location of placenta previa shown with MRI seems to be associated with severity of complications during delivery and should be carefully studied.
PubMed: 38732341
DOI: 10.3390/diagnostics14090925 -
Clinical Case Reports May 2024Placenta previa, accompanied by placenta percreta, which involves invasion of the bladder, presents a significant risk of excessive bleeding during and after delivery....
KEY CLINICAL MESSAGE
Placenta previa, accompanied by placenta percreta, which involves invasion of the bladder, presents a significant risk of excessive bleeding during and after delivery. This case highlights that prophylactic embolization, conservative surgery, and careful monitoring offer an effective approach to avoid hysterectomy in cases of placenta percreta with adjacent organ involvement.
ABSTRACT
Placenta previa complicated by placenta percreta is associated with a high risk of massive intra and post-partum hemorrhage. We present a case of a 35-year-old woman (G2 P1) who was referred to the Akbar-Abadi hospital at 13 weeks of gestation. Color Doppler ultrasound indicated complete placenta previa-percreta with bladder invasion. After induction of fetal demise, bilateral uterine and bladder artery endovascular embolization was conducted for the patient. After 48 h, under ultrasound guidance, surgical resection of residual percreta tissue was conducted as much as possible. Eight weeks later, a follow-up sonography showed the minimum residual placenta tissue and she regained menstrual cycles after 2 months. This case indicated that the combination of prophylactic embolization, conservative surgical management with placenta left in situ, and follow-up with serial color Doppler monitoring, is an optimum method to avoid hysterectomy in placenta percreta patient with adjacent organ invasion.
PubMed: 38721560
DOI: 10.1002/ccr3.8879 -
American Journal of Obstetrics &... Jun 2024
Topics: Humans; Placenta Accreta; Pregnancy; Female; Evidence-Based Medicine; Cesarean Section
PubMed: 38719699
DOI: 10.1016/j.ajogmf.2024.101365 -
PloS One 2024Lebanon has a high caesarean section use and consequently, placenta accreta spectrum (PAS) is becoming more common.
Obstetric and haematological management and outcomes of women with placenta accreta spectrum by planned or urgent delivery: Secondary data analysis of a public referral hospital in Lebanon.
BACKGROUND
Lebanon has a high caesarean section use and consequently, placenta accreta spectrum (PAS) is becoming more common.
OBJECTIVES
To compare maternal characteristics, management, and outcomes of women with PAS by planned or urgent delivery at a major public referral hospital in Lebanon.
DESIGN
Secondary data analysis of prospectively collected data.
SETTING
Rafik Hariri University Hospital (public referral hospital), Beirut, Lebanon.
PARTICIPANTS
159 pregnant and postpartum women with confirmed PAS between 2007-2020.
MAIN OUTCOME MEASURES
Maternal characteristics, management, and maternal and neonatal outcomes.
RESULTS
Out of the 159 women with PAS included, 107 (67.3%) underwent planned caesarean delivery and 52 (32.7%) had urgent delivery. Women who underwent urgent delivery for PAS management were more likely to experience antenatal vaginal bleeding compared to those in the planned group (55.8% vs 28.0%, p<0.001). Median gestational age at delivery was significantly lower for the urgent group compared to the planned (34 vs. 36 weeks, p<0.001). There were no significant differences in terms of blood transfusion rates and major maternal morbidity between the two groups; however, median estimated blood loss was significantly higher for women with urgent delivery (1500ml vs. 1200ml, p = 0.011). Furthermore, the urgent delivery group had a significantly lower birth weight (2177.5g vs. 2560g, p<0.001) with higher rates of neonatal intensive care unit (NICU) admission (53.7% vs 23.8%, p<0.001) and perinatal mortality (18.5% vs 3.8%, p = 0.005).
CONCLUSION
Urgent delivery among women with PAS is associated with worse maternal and neonatal outcomes compared to the planned approach. Therefore, early referral of women with known or suspected PAS to specialized centres is highly desirable to maximise optimal outcomes for both women and infants.
Topics: Humans; Female; Pregnancy; Lebanon; Adult; Placenta Accreta; Cesarean Section; Infant, Newborn; Delivery, Obstetric; Referral and Consultation; Blood Transfusion; Pregnancy Outcome; Hospitals, Public; Secondary Data Analysis
PubMed: 38718031
DOI: 10.1371/journal.pone.0302366 -
Archives of Gynecology and Obstetrics May 2024To identify predictors and develop a scoring model to predict maternal near-miss (MNM) and maternal mortality.
PURPOSE
To identify predictors and develop a scoring model to predict maternal near-miss (MNM) and maternal mortality.
METHODS
A case-control study of 1,420 women delivered between 2014 and 2020 was conducted. Cases were women with MNM or maternal death, controls were women who had uneventful deliveries directly after women in the cases group. Antenatal characteristics and complications were reviewed. Multivariate logistic regression and Akaike information criterion were used to identify predictors and develop a risk score for MNM and maternal mortality.
RESULTS
Predictors for MNM and maternal mortality (aOR and score for predictive model) were advanced age (aOR 1.73, 95% CI 1.25-2.39, 1), obesity (aOR 2.03, 95% CI 1.22-3.39, 1), parity ≥ 3 (aOR 1.75, 95% CI 1.27-2.41, 1), history of uterine curettage (aOR 5.13, 95% CI 2.47-10.66, 3), history of postpartum hemorrhage (PPH) (aOR 13.55, 95% CI 1.40-130.99, 5), anemia (aOR 5.53, 95% CI 3.65-8.38, 3), pregestational diabetes (aOR 5.29, 95% CI 1.27-21.99, 3), heart disease (aOR 13.40, 95%CI 4.42-40.61, 5), multiple pregnancy (aOR 5.57, 95% CI 2.00-15.50, 3), placenta previa and/or placenta-accreta spectrum (aOR 48.19, 95% CI 22.75-102.09, 8), gestational hypertension/preeclampsia without severe features (aOR 5.95, 95% CI 2.64-13.45, 4), and with severe features (aOR 16.64, 95% CI 9.17-30.19, 6), preterm delivery <37 weeks (aOR 1.65, 95%CI 1.06-2.58, 1) and < 34 weeks (aOR 2.71, 95% CI 1.59-4.62, 2). A cut-off score of ≥4 gave the highest chance of correctly classified women into high risk group with 74.4% sensitivity and 90.4% specificity.
CONCLUSIONS
We identified predictors and proposed a scoring model to predict MNM and maternal mortality with acceptable predictive performance.
PubMed: 38713295
DOI: 10.1007/s00404-024-07539-6 -
BioRxiv : the Preprint Server For... Apr 2024A successful pregnancy relies on the proper cellular, biochemical, and mechanical functions of the uterus. A comprehensive understanding of uterine mechanical properties...
A successful pregnancy relies on the proper cellular, biochemical, and mechanical functions of the uterus. A comprehensive understanding of uterine mechanical properties during pregnancy is key to understanding different gynecological and obstetric disorders such as preterm birth, placenta accreta, leiomyoma, and endometriosis. This study sought to characterize the macro-scale equilibrium material behaviors of the human uterus in non-pregnancy and late pregnancy under both compressive and tensile loading. Fifty human uterine specimens from 16 patients (8 nonpregnant [NP] and 8 pregnant [PG]) were tested using spherical indentation and uniaxial tension coupled with digital image correlation (DIC). A three-level incremental load-hold protocol was applied to both tests. A microstructurally-inspired material model considering fiber architecture was applied to this dataset. Inverse finite element analysis (IFEA) was then performed to generate a single set of mechanical parameters to describe compressive and tensile behaviors. The freeze-thaw effect on uterine macro mechanical properties was also evaluated. PG tissue exhibits decreased overall stiffness and increased fiber network extensibility compared to NP uterine tissue. Under indentation, ground substance compressibility was similar between NP and PG uterine tissue. In tension, the fiber network of the PG uterus was found to be more extensible and dispersed than in nonpregnancy. Lastly, a single freeze-thaw cycle did not systematically alter the macro-scale material behavior of the human uterus.
PubMed: 38712283
DOI: 10.1101/2024.04.25.591208 -
Acta Obstetricia Et Gynecologica... May 2024Placenta accreta spectrum (PAS) can lead to major peripartum morbidity. Appropriate management approaches depend on the clinical severity, each individual's preference,...
INTRODUCTION
Placenta accreta spectrum (PAS) can lead to major peripartum morbidity. Appropriate management approaches depend on the clinical severity, each individual's preference, and the treating team's expertise. Peripartum hysterectomy is the most frequently used treatment option. However, it can impact psychological well-being and fertility. We investigated whether conservative treatment with focal resection or leaving the placenta in situ is associated with comparable or lower maternal morbidity than hysterectomy in centers of excellence within the International Society for placenta accreta spectrum (IS-PAS). Furthermore, a survey was conducted to explore potential barriers to conservative management in antenatal counseling and intraoperative decision-making.
MATERIAL AND METHODS
Confirmed PAS cases in the prospective IS-PAS database from 22 registered centers between January 2020 and June 2022 were included in the analysis. A separate online survey with 21 questions was answered by the IS-PAS center experts about indications, diagnostic criteria, patient counseling, surgical practice, changes from the preoperative treatment plan, and why conservative management may not be offered.
RESULTS
A total of 234 cases were included in the analysis: 186 women received hysterectomy and 38 women were treated by focal resection, and 10 by leaving the placenta in situ. Blood loss was lower in the focal resection group and in the placenta in situ group compared to the hysterectomy group (p = 0.04). 46.4% of the women initially planned for focal resection, and 35.7% of those initially planned for leaving the placenta in situ were ultimately treated by hysterectomy. Our survey showed that the IS-PAS centers preferred hysterectomy according to a woman's wishes (64%) and when they expected less blood loss and morbidity (41%). Eighteen percent of centers did not offer focal resection at all due to a lack of experience with this technique. Reasons for not offering to leave the placenta in situ were avoidance of unexpected reoperation (36%), puerperal infection (32%), or skepticism about the method (23%).
CONCLUSIONS
Uterus-preserving treatment strategies such as focal resection appear to be safe alternatives to peripartum hysterectomy. However, less than half of the IS-PAS centers perform them. Acceptance of conservative treatments could be increased by standardized criteria for their implementation and by systematic training for PAS experts.
PubMed: 38695676
DOI: 10.1111/aogs.14855 -
International Journal of Gynaecology... Apr 2024To investigate the association between adenomyosis and placenta accreta spectrum (PAS) and to evaluate the effect of assisted reproductive technology (ART) in mediating...
OBJECTIVES
To investigate the association between adenomyosis and placenta accreta spectrum (PAS) and to evaluate the effect of assisted reproductive technology (ART) in mediating this association.
METHODS
We retrieved data for singleton women from the Japanese nationwide perinatal registry between 2013 and 2019, excluding women with a history of adenomyomectomy. To investigate the association between adenomyosis and PAS among women, we used a multivariable logistic regression model with multiple imputation for missing data. We evaluated mediation effect of ART including in vitro fertilization and intracytoplasmic sperm injection on the association between adenomyosis and PAS using causal mediation analysis based on the counterfactual approach.
RESULTS
Of 1 500 173 pregnant women, 1539 (0.10%) had adenomyosis. The number receiving ART was 489/1539 (31.8%) and 117 482/1 498 634 (7.8%) in women with and without adenomyosis, respectively. The proportion of women who developed PAS was 21/1539 (1.4%) in women with adenomyosis and 7530/1 498 634 (0.5%) in women without adenomyosis. Adenomyosis was significantly associated with PAS (odds ratio [OR] 1.95; 95% confidence interval [CI] 1.26-3.00; P = 0.002). Mediation analysis showed that OR of the total effect of adenomyosis on PAS was 1.98 (95% CI 1.13-3.04), OR of natural indirect effect (effect explained by ART) was 1.15 (95% CI 1.01-1.41), and OR of natural direct effect (effect unexplained by ART) was 1.72 (95% CI 0.86-2.82). The proportion mediated (natural indirect effect/total effect) was 26.5%. Adenomyosis was also significantly associated with PAS without previa (OR 1.96; 95% CI 1.23-3.13, P = 0.005).
CONCLUSION
Adenomyosis was significantly associated with PAS. ART mediated 26.5% of the association between adenomyosis and PAS.
PubMed: 38676352
DOI: 10.1002/ijgo.15565