Uterine conservative-resective surgery for selected placenta accreta spectrum cases: Surgical-vascular control methods.

INTRODUCTION: The incidence of placenta accreta spectrum (PAS) has increased, but the optimal management and the optimal way to achieve vascular control are still controversial. This study aims to compare maternal outcomes between different methods of vascular control in surgical PAS management. MATERIAL AND METHODS: A retrospective cohort study on consecutive cases diagnosed with PAS between 2013 and 2020 in single tertiary hospital. The final diagnosis of PAS was made following preoperative ultrasound and confirmation during surgery. Management of PAS using cesarean hysterectomy with internal iliac artery ligation (IIAL) was compared with two types of vascular control in uterine conservative-resective surgery (IIAL vs identification-ligation of the upper vesical, upper vaginal, and uterine arteries). RESULTS: Over an 8-year period, 234 pregnant women were diagnosed with PAS meeting the inclusion criteria. Uterine conservative-resective surgery (200 cases) was associated with lower mean blood loss compared with cesarean hysterectomy with IIAL (34 cases) in all PAS cases (1379 ± 769 mL vs 3168 ± 1916 mL; p < 0.001). In sub-analysis of the two uterine conservative-resective surgery subgroups, the group with identification-ligation of the upper vesical, upper vaginal, and uterine arteries had a significantly lower blood loss compared with uterine conservative-resective surgery with IIAL (1307 ± 743 mL vs 1701 ± 813 mL; p = 0.005). Women in the hysterectomy with IIAL group had more massive transfusion (35.3% vs 2.5%; p < 0.001; odds ratio [OR] 21.3, 95% confidence interval [CI] 6.9-66), major blood loss (>1500 mL) (70.6% vs 34%, p < 0.001; OR 4.7; 95% CI 2.1-10.3), catastrophic blood loss (>2500 mL) (64.7% vs 12.5%;p < 0.001; OR 12.8, 95% CI 5.7-29.1), other complications (32% vs 12.4%; p = 0.007; OR 3.4, 95% CI 1.5-7.7), and intensive care unit admission (32.4% vs 1.5%; p < 0.001; OR 31.4, 95% CI 8.2-120.7) compared with the uterine conservative-resective surgery groups. The identification-ligation of the upper vesical, upper vaginal and uterine arteries had a significant lower risk for major blood loss (30.5% vs 50%; p = 0.041; OR 0.44, 95% CI = 0.2-0.9) compared with IIAL for vascular control of uterine conservative-resective surgery. CONCLUSIONS: Cesarean hysterectomy is not the default treatment for PAS, PAS with invasion above the vesical trigone are suitable for uterine conservative-resective surgery with upper vesical, upper vaginal and uterine artery vascular control.

New three-dimensional/four-dimensional volume rendering imaging software for detecting the abnormally invasive placenta.

OBJECTIVE: This study aimed to determine the role of three-dimensional (3D)/four-dimensional (4D) volume rendering ultrasound (VRU) in the diagnosis of abnormally invasive placenta (AIP). MATERIALS AND METHODS: Twelve consecutive patients strongly suspected of having AIP on the basis of conventional ultrasound (US) and clinical history performed between September 2016 and December 2016 in the main tertiary referral hospital in Surabaya, East Java were included in this prospective observational study. A Samsung WS 80A Elite US scanner with a 3D/4D "crystal vue" and "realistic vue" volume rendering mode was used to establish the diagnosis of AIP and evaluate the site, and depth of placental invasion. The VRU images were compared with the intraoperative findings. RESULTS: Using this novel US technique, all cases of suspected AIP were subsequently confirmed during surgery. Importantly, the new US technique provided a correct diagnosis of the degree of invasion in 11 out of these 12 suspected AIP cases: 5/5 for placenta percreta, 3/3 for placenta increta, and 2/3 for placenta accreta; one patient was misdiagnosed in terms of the degree of placenta accreta, and one patient had normal implantation). CONCLUSION: This new software of 3D/4D VRU represents a promising technique for the preoperative diagnosis and staging of AIP.

Mesenchymal stem cell secretome ameliorates over-expression of soluble fms-like tyrosine kinase-1 (sFlt-1) and fetal growth restriction (FGR) in animal SLE model.

INTRODUCTION: In the near future, stem cell research may lead to several major therapeutic innovations in medical practice. Secretome, a "by-product" of stem cell line cultures, has many advantages. Its easiness of storage, usage, and fast direct effect are some of those to consider. Fetal growth restriction (FGR) remains one of the significant challenges in maternal-fetal and neonatal medicine. Placentation failure is one of the most profound causal and is often related to increasing sFlt-1 in early pregnancy. This study aimed to investigate hUC-MSC secretome in ameliorating sFlt-1 and how to improve outcomes in preventing FGR in an animal model. MATERIALS AND METHODS: Pristane-induced systemic lupus erythematosus (SLE) in a mouse model was used to represent placentation failure and its consequences. Twenty-one mice were randomized into three groups: (I) normal pregnancy, (II) SLE, and (III) SLE with secretome treatment. Pristane was administered in all Groups four weeks prior mating period. Secretome was derived from human umbilical cord mesenchymal stem cells (hUC-MSC) conditioned medium on the 3rd and 4th passage, around day-21 until day-28 from the start of culturing process. Mesenchymal stem cell was characterized using flow cytometry for CD105+, CD90+, and CD73+ surface antigen markers. Immunohistochemistry anlysis by using Remmele's Immunoreactive Score (IRS) was used to quantify the placental sFlt-1 expression in each group. Birth weight and length were analyzed as the secondary outcome. The number of fetuses obtained was also calculated for pregnancy loss comparison between Groups. RESULTS: The administration of secretome of hUC-MSC was found to lower the expression of the placental sFlt-1 significantly in the pristane SLE animal model (10.30 ± 1.40 vs. 4.98 ± 2.57; p < 0.001) to a level seen in normal mouse pregnancies in Group I (3.88 ± 0.49; p = 0.159). Secretome also had a significant effect on preventing fetal growth restriction in the pristane SLE mouse model (birth weight: 354.29 ± 80.76 mg vs. 550 ± 64.03 mg; p < 0.001 and birth length: 14.43 ± 1.27 mm vs. 19.00 ± 1.41 mm), comparable to the birth weight and length of the normal pregnancy in Group I (540.29 ± 75.47 mg and 18.14 ± 1.34 mm, p = 0.808 and = 0.719). Secretome administration also showed a potential action to prevent high number of pregnancy loss as the number of fetuses obtained could be similar to those of mice in the normal pregnant Group (7.71 ± 1.11 vs. 7.86 ± 1.06; p = 0.794). CONCLUSIONS: Administration of secretome lowers sFlt-1 expression in placenta, improves fetal growth, and prevents pregnancy loss in a mouse SLE model.

Pravastatin suppresses inflammatory cytokines and endothelial activation in patients at risk of developing preeclampsia: INOVASIA study.

INTRODUCTION: The Indonesian INOVASIA study is an ongoing multicentre randomized, open controlled trial of pravastatin for the prevention of preeclampsia in patients deemed to be high risk. Here we evaluate the effects of pravastatin on circulating inflammatory and endothelial markers, i.e. Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Endothelin-1 (ET-1), and Nitric Oxide (NO). METHODS: Pregnant women deemed to be at a high risk of developing preeclampsia women were recruited based on the Fetal Medicine Foundation preeclampsia screening test or a history of preterm preeclampsia, or clinical risk factors in combination with an abnormal uterine artery Doppler flow pattern at 11-20 week's gestation. This is a nested cohort study within the larger trial (INOVASIA); 38 patients were consecutively recruited and assigned to the pravastatin group and the control group. Participants in the pravastatin group received pravastatin (2 × 20 mg p.o) in addition to a standard regimen of aspirin (80 mg p.o) and calcium (1 g p.o), from 14 to 20 weeks until delivery. Blood samples to measure the various biomarkers were obtained in consecutive patients before starting the research medication and just before delivery (pre and post-test examination). RESULT: The number of samples on the 2 time points for the various biomarkers was: VEGF: 38, IL-6: 30, ET-1: 38, and NO: 35. IL-6 levels decreased significantly in the pravastatin group (mean ± SD): (191.87 ± 82.99 vs. 151.85 + 48.46, p = .013), while levels in the control group did not change significantly (median (interquartile range)) (144.17 (53.91) vs. 140.82 (16.18), p = .177). ET-1 levels decreased significantly in the pravastatin group (3.64 ± 0.85 vs. 3.01 ± 0.74, p = .006) while the control group had more or less stable levels (3.57 ± 1.12 vs. 3.78 ± 0.73 p = .594). NO was the only serum marker that showed significant changes in both groups. NO levels increased in pravastatin group (11.30 (17.43) vs. 41.90 (53.18), p = .044) and decreased in control group (38.70 (34.80) vs. 10.03 (26.96), p = .002). VEGF levels appeared to follow opposite trends in the 2 groups (NS) (Pravastatin: 3.22 (0.62) vs. 3.28 (0.75), p = .402. Control: 3.38 (0.83) vs. 3.06 (0.74), p = .287). CONCLUSION: Administration of 40 mg pravastatin resulted in an improvement in NO levels, and a decrease in IL-6 and endothelin (ET-1) levels. The direction of the effect of pravastatin on these biomarkers appears to underpin the potential for a beneficial effect of pravastatin in the prevention of preeclampsia.

Magnesium intoxication in women with preeclampsia with severe features treated with magnesium sulfate.

OBJECTIVE: To evaluate the maternal-neonatal outcome in magnesium (Mg)-intoxicated women with preeclampsia with severe features (PESF) treated with magnesium sulfate (MgSO4). METHODS: A total of 19 Mg intoxicated PESF women (cases) were compared with 166 PESF women without signs of intoxication (controls). RESULTS: Mg serum levels of cases was higher compared to control group (12.36 ± 3.54 mg/dl versus 2.69 ± 0.83 mg/dl). 3 women died and 3 had major maternal morbidity in cases group compared with zero in the control group (P = 0.009). Mg intoxication was also significantly associated with perinatal deaths and low Apgar scores at 1 and 5 minutes. CONCLUSION: Mg intoxication is associated with a increased risk of maternal and perinatal mortality and morbidity.

Pre-eclampsia - A disease of an individual couple.

Preeclampsia still ranks as one of obstetrics major problems. Clinicians typically encounter preeclampsia as maternal disease with variable degrees of fetal involvement. More and more the unique immunogenetic maternal-paternal relationship is appreciated, and as such also the specific 'genetic conflict' that is characteristic of haemochorial placentation. From that perspective preeclampsia can also been seen as a disease of an individual couple with primarily maternal and fetal manifestations. Factors that are unique to a specific couple would include the length and type of sexual relationship, the maternal (decidual natural killer cells) acceptation of the invading cytotrophoblast (paternal HLA-C), and seminal levels of transforming growth factor-b and probably other cytokines. The magnitude of the maternal response would be determined by factors including a maternal set of genes determining her characteristic inflammatory responsiveness, age, quality of her endothelium, obesity/insulin resistance and probably a whole series of susceptibility genes amongst which the thrombophilias received a lot of attention in recent years. The maternal and fetal genomes perform different roles during development. Inheritable paternal, rather than maternal, imprinting of the genome is necessary for normal trophoblast development. Preeclampsia may relate to a 'hefty' genetic conflict, or a mother unable to cope with a 'physiologic' genetic conflict. The paternal contribution to preeclampsia, in addition to the actual act of fertilization is demonstrated by.

Management of preeclampsia.

Most patients with a pregnancy-induced hypertensive disorder have no clinical symptoms. So it can only be reliably detected by repetitive searches (screening) for the early signs and symptoms in the 2nd half of pregnancy. Adequate and proper prenatal care is the most important part of management of preeclampsia. Maternal antenatal monitoring includes identifying women at increased risk, early detection of preeclampsia by recognizing clinical signs and symptoms, and to observe progression of the condition to the severe state. As the etiology of preeclampsia remains in question, the only effective treatment is to deliver the infant and placenta; ancillary therapy is predominantly symptomatic and not directed at underlying causes. Once the diagnosis of preeclampsia is made, subsequent therapy will depend on the results of initial maternal and fetal evaluation. The primary objective of management of preeclampsia must always be safety of the mother. Although delivery is always appropriate for the mother, it may not be optimal for the fetus that is extremely premature. The decision between delivery and expectant management depends on fetal gestational age, maternal and fetal status at time of initial evaluation, presence of labor or rupture of fetal membranes, and level of available neonatal and maternal services. It is important to emphasize that hypertension is merely one manifestation of this disease, albeit directly related to one of the most serious consequences for the mother, i.e cerebral involvement, which may manifest itself as convulsions, focal neurological events such as cortical blindness, and even cerebral hemorrhage. The benefits of acute pharmacologic control of severe hypertension prior to delivery are generally accepted. The more contentious issues are the role of pharmacologic therapy in allowing prolongation of pregnancy and the ability of such therapy to modify the course of the underlying systemic disorder and affect fetal and maternal outcome. Ali hypertensive drugs affect both the mother and the fetus; some may produce side effects in the mother and others may produce adverse effects on the fetus or the newborn. The indirect effects of antihypertensive drugs on the fetus may be by impairing uteroplacental perfusion or directly by influencing the fetal cardiovascular circulation. In general, women with mild disease developing at 37weeks' gestation or longer have a pregnancy outcome similar to that found in normotensive pregnancy. Thus, those patients should undergo induction of labor for delivery. Induction of labor and/or delivery is also recommended for those at or beyond 34 weeks' gestation in the presence of severe preeclampsia, labor or rupture of membranes, or non-reassuring tests of fetal well-being because the mother is at slightly increased risk for development of placental abruption and progression to eclampsia. In women who remain undelivered, close maternal and fetal evaluation is essential. The type of test and frequency of evaluation will depend on fetal gestational age as well as severity of maternal condition, and presence or absence of IUGR. These tests should be repeated promptly in case of worsening maternal condition (progression to severe disease) or fetal condition (reduced fetal movement or suspected IUGR). Expectant management of severe preeclampsia:The clinical course of severe preeclampsia may be characterized by progressive deterioration in both maternal and fetal conditions. Because these pregnancies have been associated with increased rates of maternal morbidity and mortality and with significant risks for the fetus, there is universal agreement that such patients be delivered if the disease develops after 34weeks' gestational, 243. Delivery is also clearly indicated when there is imminent eclampsia (persistent severe symptoms), multiorgan dysfunction, severe IUGR, suspected placental abruption, or non-reassuring fetal testing before 34 weeks' gestation. There is disagreement however, about treatment of patients with severe preeclampsia before 34 weeks' gestation where maternal condition is stable and fetal condition is reassuring. The Cochrane review on interventionist versus expectant care states that it is not possible to draw firm conclusions, as there are only two small trials (133 women) that have compared a policy of early elective delivery, with a policy of delayed delivery, and the confidence intervals for all outcomes are wide. However, the evidence is promising that short-term morbidity for the baby may be reduced by a policy of expectant care. Sibai and Barton recently reviewed the literature on maternal and perinatal of expected management of severe preeclampsia remote from term and reviewed the major studies in the literature. Based on this review, they concluded that the results of these studies suggest that expectant treatment in a select group of women with severe preeclampsia between 24 0/7 and 32 6/7weeks of gestation in a suitable hospital is safe and improves neonatal outcome. Most studies on expectant management report 7-10days of prolongation. For gestational age of 24 0/7weeks, expectant treatment was associated with high maternal morbidity with limited perinatal benefit.

Risk factors for preterm birth in an international prospective cohort of nulliparous women.

OBJECTIVES: To identify risk factors for spontaneous preterm birth (birth <37 weeks gestation) with intact membranes (SPTB-IM) and SPTB after prelabour rupture of the membranes (SPTB-PPROM) for nulliparous pregnant women. DESIGN: Prospective international multicentre cohort. PARTICIPANTS: 3234 healthy nulliparous women with a singleton pregnancy, follow up was complete in 3184 of participants (98.5%). RESULTS: Of the 3184 women, 156 (4.9%) had their pregnancy complicated by SPTB; 96 (3.0%) and 60 (1.9%) in the SPTB-IM and SPTB-PPROM categories, respectively. Independent risk factors for SPTB-IM were shorter cervical length, abnormal uterine Doppler flow, use of marijuana pre-pregnancy, lack of overall feeling of well being, being of Caucasian ethnicity, having a mother with diabetes and/or a history of preeclampsia, and a family history of low birth weight babies. Independent risk factors for SPTB-PPROM were shorter cervical length, short stature, participant's not being the first born in the family, longer time to conceive, not waking up at night, hormonal fertility treatment (excluding clomiphene), mild hypertension, family history of recurrent gestational diabetes, and maternal family history of any miscarriage (risk reduction). Low BMI (<20) nearly doubled the risk for SPTB-PPROM (odds ratio 2.64; 95% CI 1.07-6.51). The area under the receiver operating characteristics curve (AUC), after internal validation, was 0.69 for SPTB-IM and 0.79 for SPTB-PPROM. CONCLUSION: The ability to predict PTB in healthy nulliparous women using clinical characteristics is modest. The dissimilarity of risk factors for SPTB-IM compared with SPTB-PPROM indicates different pathophysiological pathways underlie these distinct phenotypes. TRIAL REGISTRATION: ACTR.org.au ACTRN12607000551493.