Efficacy and Safety Analyses of Recombinant Factor VIIa in Severe Post-Partum Hemorrhage.

Background: Despite a range of available treatments, it is still sometimes challenging to treat patients with severe post-partum hemorrhage (sPPH). Objective: This study evaluated the efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 (NCT04723979), OS-2, OS-3, and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligations, arterial embolization, or hysterectomy) and safety (incidence of thromboembolic events (TE) and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa-exposed women only. Results: A total of 446 women exposed to rFVIIa and 1717 non-exposed controls were included. In the RCT, fewer rFVIIa-exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio: 0.11; 95% confidence interval: 0.03-0.35). In OS-1, more rFVIIa-exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio: 2.46; 95% confidence interval: 1.06-5.99). In OS-2, 17% (3/18) of rFVIIa-exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio: 0.33; 95% confidence interval: 0.03-1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa-exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa on the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

Is There a Cumulative Effect for Congenital Heart Defects in Monochorionic Twins after Assisted Reproduction? - A Retrospective Analysis at a Tertiary Referral Center.

Introduction: The aim of our study was to compare maternal, chorionicity and neonatal complications in monochorionic (MC) twins between spontaneously conceived (SC) and assisted reproductive technologies (ART) pregnancies. Material and Methods: This was a retrospective cohort study between January 2010 to December 2019 at a tertiary referral University center. All consecutive pregnancies with MC twins that delivered at our University hospital were included. Maternal, chorionicity and neonatal complications were recorded and compared between SC and ART pregnancies. Results: 393 MC pregnancies were included for final analysis, including 353 (89.8%) SC and 40 (10.2%) pregnancies conceived after ART. Hypothyroidism was the only maternal condition seen significantly more often in ART pregnancies (35.0% vs 12.5%, p = 0.001). There were no significant differences in chorionicity complications, such as twin-twin transfusion syndrome, selective fetal growth restriction and twin anemia-polycythemia sequence (40.0% in ART pregnancies vs 31.6% in SC pregnancies, p = 0.291). At least one congenital anomaly in one twin was seen significantly more often in ART pregnancies (18.8% vs 8.1%, p = 0.004), especially congenital heart defects (16.3% vs 6.2%, p = 0.005). There were no other significant differences in neonatal outcomes between both groups, however, there were non-significant trends in gestational age at delivery (34 weeks in ART pregnancies vs 35 weeks, p = 0.078) and birthweight (1951 g ± 747 in ART pregnancies vs 2143 g ± 579, p = 0.066). Conclusion: This is the largest cohort study to date comparing maternal, chorionicity and neonatal complications between MC twin pregnancies after ART and after SC. Hypothyroidism was the only maternal condition occurring more frequently in pregnancies conceived after ART. There were no significant differences in chorionicity complications, in contrast to previously reported studies. While MC twins and ART pregnancies per se are known to be at risk for congenital heart defects, there seems to be a cumulative effect in MC pregnancies conceived after ART.

Hypertensive disorders of pregnancy share common cfDNA methylation profiles.

Hypertensive disorders of pregnancy (HDP) contribute substantially to perinatal morbidity and mortality. Epigenetic changes point towards cardio-metabolic dysregulation for these vascular disorders. In early pregnancy, epigenetic changes using cell free DNA (cfDNA) are largely unexplored. We aimed to investigate these in HDP between 11 and 14 weeks of gestation by analysis of cfDNA methylation profiles in patients with hypertensive disorders. We identified patients without chronic hypertension but with subsequent development of preeclampsia (PE) (n = 11), with chronic hypertension (HT) but without PE development (n = 14), and lacking both PE and HT (n = 422). We matched patients according to PE risk factors into three groups (n = 5 each group): (1) PE: no HT but PE development, (2) HT: chronic hypertension but no PE and (3) Control: no PE or HT. We successfully optimized our cfDNA isolation process prior to whole genome bisulfite sequencing. Analysis of cfDNA methylation changes indicate a common predisposition in PE and HT groups, chiefly of maternal origin. Assessment of significant differentially methylated regions and annotated genes point towards a common cardiovascular predisposition in preeclampsia and hypertension groups in the first trimester. We postulate the pivotal role of the maternal cardiovascular system in HDP, which is already evident in the first trimester.

Obstetrical and Fertility Outcomes Following Transcatheter Pelvic Arterial Embolization for Postpartum Hemorrhage: A Cohort Follow-Up Study.

Objectives: Management of severe postpartum hemorrhage (PPH) includes transcatheter pelvic arterial embolization (TAE). Data regarding subsequent fertility and obstetrical outcomes is limited, as most fertility outcomes derive from TAE in uterine fibroma. The purpose of our study was to evaluate the long-term outcomes of patients undergoing TAE, particularly concerning subsequent fertility and following pregnancies. Material and methods: We included 28 patients who underwent TAE for PPH at our institution between 2009 and 2018 in a retrospective cohort study. Data were assessed by reviewing patients' charts and by contacting the patients. Results: Ten patients had prophylactic balloon occlusion before cesarean section because of anticipated PPH, with planned hysterectomy by placenta increta/percreta. All these patients were excluded from the analysis regarding fertility. 16 (73%) patients reported having regular menstruation after TAE. In total, 11 women had no desire for subsequent pregnancy. Seven of the remaining 11 patients (63.6%) had a total of 13 spontaneous pregnancies, nine of these resulted in miscarriages. Four patients delivered a live baby (36.4%). Two of these (50%) had recurrent PPH and treatment was conservative. Of the patients with infertility (n = 4, 36.4%), two (18.1%) underwent assisted infertility treatment without success. Conclusion: Our study suggests that the fertility of patients undergoing TAE due to PPH is limited. In women who conceive, the risk for first trimester miscarriage as well as recurrent PPH seems to be increased. If this is a consequence of the underlying cause of PPH or the TAE remains unknown. Larger follow-up cohorts are needed. In the meantime, patients who desire pregnancy after TAE should be counseled accordingly.

Red blood cell transfusion in obstetrics and its implication for patient blood management: a retrospective analysis in Switzerland from 1998 to 2016.

PURPOSE: Peripartum hemorrhage (PPH) remains one of the main causes of maternal mortality worldwide. Treatment includes administration of packed red blood cells (RBC) in severe cases and patient blood management (PBM) may reduce it significantly. In our study, we wanted to retrospectively assess red blood cell administration in PPH to evaluate the impact of PBM in Switzerland. METHODS: Using data from the Swiss obstetric hospital registry (Arbeitsgemeinschaft Schweizer Frauenkliniken, ASF), we included patients with deliveries from 1998 to 2016. We examined available obstetric data as well as blood loss and RBC administration in the acute and subacute peripartal phase. We categorized data into two time intervals: 1998-2011 and 2012-2016, as new PPH guidelines in Switzerland were established in 2012. RESULTS: PPH incidence increased between 1998 and 2016 significantly. The number of vaginal instrumental deliveries and cesarean sections increased as well. Administration of three or more RBC units, as defined in the ASF registry, in the acute and subacute phase in Switzerland has decreased after 2012. Conversely, we saw an increase in the administration of one to two RBC units in the acute and subacute phase. Nevertheless, overall RBC administration has been decreasing from 1998 to 2016. CONCLUSION: The increase of patients obtaining one or two units of RBC for PPH suggests that there may be a potential for effective implication of PBM in obstetrics. Reduction of RBC transfusion in the context of PPH may not only decrease maternal morbidity, but decrease economic costs as well.

Patient blood management in obstetrics - Review.

Patient blood management (PBM) aims to reduce red blood cell transfusion, minimize preoperative anemia, reduce intraoperative blood loss as well as optimize hemostasis, and individually manage postoperative anemia. Benefits include improved clinical outcome with a reduction in patient morbidity and mortality, but also lower hospital costs and shorter hospital length of stay. To date, it has been successfully implemented in several medical specialties, such as cardiac, trauma and orthopedic surgery. In obstetrics, postpartum hemorrhage (PPH) is one of the leading causes of maternal mortality. PBM has the potential to improve outcome of mother and child. However, pregnancy and childbirth pose a special challenge to PBM, and several adaptations compared to PBM in elective surgery are necessary. To date, awareness of the clinical advantages of PBM among obstetricians and midwifes regarding PBM and its concept in PPH is limited. In the following review, we therefore aim to present the current status quo in PBM in obstetrics and its challenges in the clinical routine.

Do late preterm twins face an increased neonatal morbidity compared with singletons?

OBJECTIVE: Late preterm infants (born between 34 0/7 and 36 6/7 weeks of gestation) have been shown to have a higher morbidity and mortality than term infants. Furthermore, twins, both term and preterm, have a higher neonatal morbidity than singletons. The aim of our study was to examine if late preterm twins consequently have twice the neonatal morbidity when both risk factors prematurity and multiple pregnancy are present. STUDY DESIGN: A retrospective single-centre study was conducted to compare neonatal outcome of late preterm singletons and late preterm twins born between 34 0/7 and 36 6/7 weeks of gestation as well as term twins with a gestational age from 37 0/7 to 41 6/7 weeks. Primary outcome was length of hospitalisation. Secondary outcome was neonatal morbidity. RESULTS: A total of 845 infants were included. Late preterm twins (n = 243) were hospitalised significantly longer than term twins (n = 107) (13.5 ± 8.0 vs 6.29 ± 2.0 days, p <0.001) and late preterm singletons (n = 495) (13.5 ± 8.0 vs 12.6 ± 8.6 days, p = 0.011). Hyperbilirubinaemia occurred significantly more often in late preterm singletons than in late preterm twins (49.7 vs 29.2%; p<0.001). Otherwise, no significant differences were detected regarding neonatal morbidities or mortality of late preterm singletons and late preterm twins. Late preterm twins had a significantly higher incidence of most morbidities than term twins. CONCLUSION: Late preterm twins are hospitalised significantly longer than similar-aged singletons, but have otherwise similar neonatal morbidities. Hyperbilirubinaemia is less frequent in late preterm twins than late preterm singletons.

Impact of Fetal Weight Estimation on the Prediction of Neonatal Morbidity and Mortality at the Limit of Viability.

INTRODUCTION: To determine the accuracy of estimated fetal weight (EFW) at the limit of viability in a delivery room setting and its impact on the prediction of neonatal outcome. MATERIAL AND METHODS: In this retrospective, single-center cohort study we included patients with preterm birth between 230/7 and 260/7 weeks of gestation. Neonates were divided into 3 groups according to birth weight at delivery (accuracy index 90-110%, <90%, >110%). Neonatal outcome for each group was categorized into survival with and without impairment and death, with a follow-up period of 6 weeks. RESULTS: Eighty-seven newborns were included, with 62.1% accurately estimated. Gestational age at birth, fetal sex, maternal body mass index, and time interval between birth and ultrasound affected the accuracy of EFW. Chances of survival were significantly higher in the underestimated group for birth weight at delivery compared with estimated weight (p < 0.001), with risk of death being significantly lower (p < 0.001). The reverse was true for overestimated infants, for both risk of death and chances of survival. At 6 weeks' follow-up, there were significantly more deceased overestimated infants (p = 0.041). DISCUSSION: Our study shows that inaccuracy of EFW at the limit of viability occurs frequently in a delivery room setting with a potential impact on neonatal outcome.

Factors influencing the accuracy of fetal weight estimation with a focus on preterm birth at the limit of viability: a systematic literature review.

BACKGROUND: Fetal weight estimation (FWE) is an important factor for clinical management decisions, especially in imminent preterm birth at the limit of viability between 23(0/7) and 26(0/7) weeks of gestation. It is crucial to detect and eliminate factors that have a negative impact on the accuracy of FWE. DATA SOURCES: In this systematic literature review, we investigated 14 factors that may influence the accuracy of FWE, in particular in preterm neonates born at the limit of viability. RESULTS: We found that gestational age, maternal body mass index, amniotic fluid index and ruptured membranes, presentation of the fetus, location of the placenta and the presence of multiple fetuses do not seem to have an impact on FWE accuracy. The influence of the examiner's grade of experience and that of fetal gender were discussed controversially. Fetal weight, time interval between estimation and delivery and the use of different formulas seem to have an evident effect on FWE accuracy. No results were obtained on the impact of active labor. DISCUSSION: This review reveals that only few studies investigated factors possibly influencing the accuracy of FWE in preterm neonates at the limit of viability. Further research in this specific age group on potential confounding factors is needed.

"Broken heart" after cesarean delivery. Case report and review of literature.

OBJECTIVE: To present a rare case of a multiparous woman undergoing elective cesarean section with apparent symptoms of acute coronary syndrome and who was later diagnosed with Takotsubo cardiomyopathy (TCM; "broken heart syndrome"). To review similar case reports already reported in literature. METHODS: Literature search on the occurrence of TCM in pregnancy using MEDLINE and Cochrane databases. RESULTS: TCM might occur in women with no known pre-existing cardiomyopathy and uncomplicated pregnancies undergoing cesarean section, especially in combination with the administration of catecholamines/vasoconstrictive substances and possibly also oxytocin and prostaglandins. CONCLUSIONS: Since TCM is related to emotional and physical stress, the surroundings during cesarean section should be kept quiet and smooth. Adrenergic stimulants (adrenaline, phenylephrine, ergonovine, ephedrine) and anticholinergics (atropine) should be used with caution and adequate volume substitution prior to the onset of spinal analgesia for the prevention of hypotension should be provided. If signs of an acute coronary syndrome during cesarean section do occur, echocardiography is obligatory for diagnosis of TCM.