Transabdominal and transvaginal ultrasound findings help to guide the clinical management of placenta accreta spectrum cases.

INTRODUCTION: The clinical management of placenta accreta spectrum (PAS) depends on placental topography and vascular involvement. Our aim was to determine whether transabdominal and transvaginal ultrasound signs can predict PAS management. MATERIAL AND METHODS: We conducted a retrospective cohort study of consecutive prenatally suspected PAS cases in a single tertiary-care PAS center between January 2021 and July 2022. When PAS was confirmed during surgery, abdominal and transvaginal ultrasound scans were analyzed in relation to PAS management. The preferred surgical approach of PAS was one-step conservative surgery (OSCS). Massive blood loss and PAS topography in the lower bladder trigone necessitated cesarean hysterectomy. Transvaginal ultrasound-diagnosed intracervical hypervascularity was split into three categories based on their quantity. Anatomically, the internal cervical os is located at the level of the bladder trigone and was used as landmark for upper and lower bladder trigone PAS. RESULTS: Ninety-one women underwent OSCS and 35 women underwent cesarean hysterectomy (total 126 women with PAS). Abdominal and transvaginal ultrasound features differed significantly between women that underwent OSCS and cesarean hysterectomy: decreased myometrial thickness (<1 mm), 82.4% vs. 100%, p = 0.006; placental bulge, 51.6% vs. 94.3%, p < 0.001; bladder wall interruption, 62.6% vs. 97.1%, p < 0.001; abnormal placental lacunae, 75.8% vs. 100%, p < 0.001; hypervascularity (large lacunae feeding vessels, 57.8% vs. 94.6%, p < 0.001; parametrial hypervascularity, 15.4% vs. 60%, p < 0.001; the rail sign, 6.6% vs. 28.6%, p = 0.003; three-dimensional Doppler intra-placental hypervascularity, 81.3% vs. 100%, p < 0.001; intracervical hypervascularity 60.4% vs. 94.3%, p < 0.001); and cervical length 2.5 ± 0.94 vs. 2.2 ± 0.73, p = 0.038. Other ultrasound signs were not significantly different. The results of multivariable logistic regression showed placental bulge (odds ratio [OR] 9.3; 95% CI 1.9-44.3; p = 0.005), parametrial hypervascularity (OR 4.1; 95% CI 1.541-11.085; p = 0.005), and intracervical hypervascularity (OR 9.2; 95% CI 1.905-44.056; p = 0.006) were weak predictors of OSCS. Intracervical hypervascularity Grade 1 (vascularity <50% of cervical tissue) was more present in OSCS than higher gradings two and three (91% vs. 27.6% vs. 14.3%; p < 0.001). CONCLUSIONS: Cesarean hysterectomy is associated with the PAS signs of placental bulge and Grade 2 and 3 intracervical hypervascularity. OSCS is associated with intracervical hypervascularity Grade 1 on transvaginal ultrasound. Prospective validation is required to formulate predictors for PAS management.

Prophylactic radiologic interventions to reduce postpartum hemorrhage in women with risk factors for placenta accreta spectrum disorder: a nationwide cohort study.

OBJECTIVE: To quantify the association between prophylactic radiologic interventions and perioperative blood loss in women with risk factors for placenta accreta spectrum disorder (PAS). METHODS: We conducted a retrospective nationwide cohort study of women with risk factors for placenta accreta spectrum disorder who underwent planned cesarean section in 69 Dutch hospitals between 2008 and 2013. All women had two risk factors for PAS: placenta previa/anterior low-lying placenta and a history of cesarean section(s). Women with and without ultrasonographic signs of PAS were studied as two separate groups. We compared the total blood loss of women with prophylactic radiologic interventions, defined as preoperative placement of balloon catheters or sheaths in the internal iliac or uterine arteries, with that of a control group consisting of women without prophylactic radiologic interventions using multivariable regression. We evaluated maternal morbidity by the number of red blood cell (RBC) units transfused within 24 h following childbirth (categories: 0, 1-3, >4), duration of hospital admission, and need for intensive care unit (ICU) admission. RESULTS: A total of 350 women with placenta previa/anterior low-lying placenta and history of cesarean section(s) were included: 289 with normal ultrasonography, of whom 21 received prophylactic radiologic intervention, and 61 had abnormal ultrasonography, of whom 22 received prophylactic intervention. Among women with normal ultrasonography without prophylactic intervention (n = 268), the median blood loss was 725 mL (interquartile range (IQR) 500-1500) vs. 1000 mL (IQR 550-1750) in women with intervention (n = 21); the adjusted difference in blood loss was 9 mL (95% confidence interval (CI) -315-513), p = .97). Among women with abnormal ultrasonography, those without prophylactic intervention (n = 39) had a median blood loss of 2500 mL (IQR 1200-5000) vs. 1750 mL (IQR 775-4000) in women with intervention (n = 22); the adjusted difference in blood loss was -1141 mL (95% CI -1694- -219, p = .02). Results of outcomes on maternal morbidity were comparable among women with and without prophylactic intervention. CONCLUSION: These findings suggest that prophylactic radiologic interventions prior to planned cesarean section may help to limit perioperative blood loss in women with clear signs of placenta accreta spectrum disorder on ultrasonography, but there was no evidence of a difference within the subgroup without such ultrasonographic signs. The use of these interventions should be discussed in a multidisciplinary shared decision-making process, including discussions of potential benefits and possible complications. TRIAL REGISTRATION: Netherlands Trial Registry, https://onderzoekmetmensen.nl/en/trial/28238, identifier NL4210 (NTR4363).

Association between socioeconomic status with pregnancy and neonatal outcomes: An international multicenter cohort.

INTRODUCTION: Previous evidence examining the association between socioeconomic status and pregnancy complications are conflicted and often limited to using area-based measures of socioeconomic status. In this study, we aimed to examine the association between individual-level socioeconomic factors and a wide range of adverse pregnancy and neonatal outcomes using data from the IMPROvED birth cohort conducted in Sweden, the Netherlands and Republic of Ireland. MATERIAL AND METHODS: The study cohort consisted of women who participated in the IMPROvED birth cohort between 2013 and 2017. Data on socioeconomic factors were self-reported and obtained at 15 weeks' gestation, and included level of education, employment status, relationship status, and income. Data on pregnancy and neonatal outcomes included gestational hypertension, pre-eclampsia, gestational diabetes mellitus, emergency cesarean section, preterm birth, post term delivery, small for gestational age and Apgar score at 1 min. These data were obtained within 72 h following delivery and confirmed using medical records. Multivariable logistic regression examined the association between each socioeconomic variable and each outcome separately adjusting for maternal age, maternal body mass index, maternal smoking, maternal alcohol consumption and cohort center. We also examined the effect of exposure to any ≥2 risk factors compared to none. RESULTS: A total of 2879 participants were included. Adjusted results suggested that those with less than third level of education had an increased odds of gestational hypertension (OR: 1.74, 95% CI: 1.23-2.46), while those on a middle level of income had a reduced odds of emergency cesarean section (OR: 0.59, 95% CI: 0.42-0.84). No significant associations were observed between socioeconomic variables and neonatal outcomes. Exposure to any ≥2 socioeconomic risk factors was associated with an increased risk of preterm birth (OR: 1.75, 95% CI: 1.06-2.89). CONCLUSIONS: We did not find strong evidence of associations between individual-level socioeconomic factors and pregnancy and neonatal outcomes in high-income settings overall, with only few significant associations observed among pregnancy outcomes.

Management of unexpected placenta accreta spectrum cases in resource-poor settings.

BACKGROUND: On a global scale, cases of placenta accreta spectrum are often just identified during cesarean delivery because they are missed during antenatal care screening. Routine operating teams not trained in the management of placenta accreta spectrum are faced with difficult surgical situations and have to make decisions that may define the clinical outcomes. Although there are general recommendations for the intraoperative management of placenta accreta spectrum, no studies have described the clinical reality of unexpected placenta accreta spectrum cases in resource-poor settings. OBJECTIVE: This study aimed to describe the maternal outcomes of previously undiagnosed placenta accreta spectrum managed in resource-poor settings in Colombia and Indonesia. STUDY DESIGN: This was a retrospective case series of women with histologically confirmed placenta accreta spectrum treated in 2 placenta accreta spectrum centers after referral from remote resource-poor hospitals. Clinical outcomes were analyzed according to the initial type of management: (1) no cesarean delivery; (2) placenta left in situ after cesarean delivery; (3) partial removal of the placenta after cesarean delivery; and (4) post-cesarean hysterectomy. In addition, we evaluated the use of telemedicine by comparing the outcomes of women in hospitals that used the support of the placenta accreta spectrum center during the initial surgery. RESULTS: A total of 29 women who were initially managed in Colombia (n=2) and Indonesia (n=27) were included. The lowest volume of blood loss and the lowest frequency of complications were in women who underwent deferred cesarean delivery (n=5; 17.2%) and in those who had a delayed placental delivery (n=5; 20.7%). Five maternal deaths (14%) occurred in the group that did not receive telehelp, and 4 women died of irreversible shock because of uncontrolled bleeding. CONCLUSION: Previously undiagnosed placenta accreta spectrum in resource-poor hospitals was associated with a high risk of maternal mortality. Open-close abdominal surgery or leaving the placenta in situ seem to be the best choices for unexpected placenta accreta spectrum management in resource-poor settings. Telemedicine with a placenta accreta spectrum center may improve prognosis.

OPtimal TIming of antenatal COrticosteroid administration in pregnancies complicated by early-onset fetal growth REstriction (OPTICORE): study protocol of a multicentre, retrospective cohort study.

INTRODUCTION: Early-onset fetal growth restriction (FGR) requires timely, often preterm, delivery to prevent fetal hypoxia causing stillbirth or neurologic impairment. Antenatal corticosteroids (CCS) administration reduces neonatal morbidity and mortality following preterm birth, most effectively when administered within 1 week preceding delivery. Optimal timing of CCS administration is challenging in early-onset FGR, as the exact onset and course of fetal hypoxia are unpredictable. International guidelines do not provide a directive on this topic. In the Netherlands, two timing strategies are commonly practiced: administration of CCS when the umbilical artery shows (A) a pulsatility index above the 95thh centile and (B) absent or reversed end-diastolic velocity (a more progressed disease state). This study aims to (1) use practice variation to compare CCS timing strategies in early-onset FGR on fetal and neonatal outcomes and (2) develop a dynamic tool to predict the time interval in days until delivery, as a novel timing strategy for antenatal CCS in early-onset FGR. METHODS AND ANALYSIS: A multicentre, retrospective cohort study will be performed including pregnancies complicated by early-onset FGR in six tertiary hospitals in the Netherlands in the period between 2012 and 2021 (estimated sample size n=1800). Main exclusion criteria are multiple pregnancies and fetal congenital or genetic abnormalities. Routinely collected data will be extracted from medical charts. Primary outcome for the comparison of the two CCS timing strategies is a composite of perinatal, neonatal and in-hospital mortality. Secondary outcomes include the COSGROVE core outcome set for FGR. A multivariable, mixed-effects model will be used to compare timing strategies on study outcomes. Primary outcome for the dynamic prediction tool is 'days until birth'. ETHICS AND DISSEMINATION: The need for ethical approval was waived by the Ethics Committee (University Medical Center Utrecht). Results will be published in open-access, peer-reviewed journals and disseminated by presentations at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05606497.

Impact of chemotherapy during pregnancy on fetal growth.

BACKGROUND: Chemotherapy crosses the placenta, however, it remains unclear to what extent it affects fetal growth. The current literature suggests up to 21% of the offspring of women receiving chemotherapy are small for gestational age (SGA, birth weight <10th percentile). Limiting research to birth weights only might misjudge fetal growth restriction (FGR) in this high-risk population with multiple risk factors for impaired fetal growth. Moreover, the role of the duration of chemotherapy and gestational age at initiation of chemotherapy in fetal growth is yet poorly understood. OBJECTIVE: This retrospective cohort study evaluates fetal growth and neonatal birthweights in pregnant women receiving chemotherapy. STUDY DESIGN: All pregnant patients, registered by the International Network of Cancer, Infertility and Pregnancy (INCIP), treated with chemotherapy with at least two ultrasounds reporting on fetal growth, were eligible for this study. Duration and gestational age at initiation of chemotherapy were our major determinants, followed by cancer type and stage, maternal characteristics (parity, BMI, ethnicity hypertension, and diabetes) and individual cytotoxic agents (anthracycline, taxanes, and platinum). Fetal growth outcomes were described using the following mutually exclusive groups (1) FGR, based on a Delphi consensus (2016); (2) "low risk SGA" (birth weight below the 10th percentile), but an estimated growth above the 10th percentile; (3) "fetal growth disturbance", which did not meet all FGR criteria; (4) "non-FGR". Obstetric and oncological characteristics were compared between the growth impaired groups and non-FGR group. We calculated estimated fetal weight (EFW) according to Hadlock's formula (1991) and birth weight percentile according to Nicolaides (2018). We used univariable and multivariable regression, and linear mixed effect models to investigate the effect of duration and gestational age at initiation of chemotherapy on birth weight, and fetal growth, respectively. RESULTS: We included 201 patients, diagnosed with cancer between March 2000 and March 2020. Most patients were diagnosed with breast cancer (n = 132, 66%). Regimens included anthracyclines (n = 121, 60%), (anthracyclines and) taxanes (n = 45, 22%) and platinum (n = 35, 17%). Fetal growth abnormalities were detected in 75 pregnancies: 43 (21%) FGR, 10 (5%) low risk SGA and 22 (8.5%) fetal growth disturbance. Chemotherapy prior to 20 weeks of gestation (47% vs. 25%, p = .04) and poor maternal gestational weight gain (median percentile 15 (range 0-97) vs. 8 (0-84), p = .03) were more frequent in the FGR group compared to the non-FGR group, whereas no difference was seen for specific chemotherapy or cancer types. Univariable regression identified gestational weight gain, hypertension, systemic disease, parity, neonatal sex and maternal BMI as confounders for birth weight percentiles. Multivariable regression revealed that each additional week of chemotherapy was associated with lower birth weight percentiles (-1.06; 95%CI -2.01; -0.04; p = .04), and that later initiation of chemotherapy was associated with an increase in birth weight percentile (1.10 per week; 95%CI 0.26; 1.95; p = .01). Each additional week of chemotherapy was associated with lower EFW and abdominal circumference (AC) percentiles (-1.77; 95%CI -2.21; -1.34, p < .001; -1.64; 95%CI -1.96; -1.32, p < .001, respectively). CONCLUSIONS: This study demonstrates that FGR is common after chemotherapy in pregnancy, and that the duration of chemotherapy has a negative impact. Sonographic follow-up of fetal growth and well-being is recommended.

Needs and preferences of women with prior severe preeclampsia regarding app-based cardiovascular health promotion.

BACKGROUND: Women with prior severe preeclampsia are at an increased risk for cardiovascular diseases later in life compared to women who had a normotensive pregnancy. The objective of this study was to assess their needs and preferences regarding app-based cardiovascular health promotion. METHODS: Patients (n = 35) of the Follow-Up PreEClampsia Outpatient Clinic (FUPEC), Erasmus MC, the Netherlands, participated in an anonymous online survey. The main outcomes under study were women's needs for health behavior promotion, and their preferences with respect to intervention delivery. Descriptive statistics were used to evaluate needs, and thematic analysis was used to analyze preferences. RESULTS: Women's primary need for health behavior promotion pertained to their fat and sugar intake and physical activity; for some, to their mental health (practices), fruit and vegetable intake, salt intake, and water intake; and for a few, to their alcohol and tobacco use. Most women preferred an app-based intervention to include, in descending order: the tracking of health-related metrics, an interactive platform, the use of behavior change strategies, the provision of information, and personalization. CONCLUSION: Cardiovascular health promotion targeting women with prior severe preeclampsia should feel relevant to its audience. App-based interventions are likely to be well received if they target fat and sugar intake and physical activity. These interventions should preferably track health-related metrics, be interactive, contain behavior change strategies, provide information, and be personalized. Adopting these findings during intervention design could potentially increase uptake, behavior change, and behavior change maintenance in this population.

Nicardipine for treating severe antepartum hypertension during pregnancy: Nine years of experience in more than 800 women.

INTRODUCTION: Women with severe hypertension during pregnancy require prompt stabilization with a combination of magnesium sulfate and rapidly acting intravenously administered antihypertensives. It remains unknown which antihypertensive is best suited for pregnancy. The present study evaluated the intravenous use of the calcium antagonist, nicardipine. MATERIAL AND METHODS: This multicenter, retrospective case series included all pregnant women beyond 20 weeks of gestation with severe antepartum hypertension that were treated with intravenous nicardipine. PRIMARY OUTCOME MEASURES: successful treatment, time to successful treatment, and maternal safety. Severe hypertension was defined as systolic blood pressure (SBP) of 160 mm Hg or more and/or diastolic blood pressure (DBP) of 110 mm Hg or more. RESULTS: This study included 830 women. After 1 h of treatment, two-thirds of the women had SBP below 160 mm Hg and DBP below 100 mm Hg. In three out of four women, the mean arterial pressure was below 120 mm Hg. Within 2 h of treatment, 77.4% of women achieved successful treatment. In all cases, nicardipine was eventually effective. Within the first 2 h, 42.7% of women experienced temporary low DBP (ie below 70 mm Hg) without clinical consequences for the mother or fetus. In all cases, the low DBP resolved after discontinuing or reducing the dosage of nicardipine. One case of fetal distress was attributable to maternal hypotension, and a cesarean section was performed at more than 2 h after initiating therapy. During treatment, headache, nausea, and vomiting decreased significantly. CONCLUSIONS: To date, this was the largest case-series study on the use of nicardipine for treating severe antepartum hypertension in pregnancy. We found that nicardipine could effectively and safely treat this condition. Based on its high success rate and acceptable safety profile, nicardipine should be considered a first-line treatment in women with severe hypertension in pregnancy.

Gravid uterine torsion after prone positioning in SARS-CoV2 (COVID-19)-related acute respiratory distress syndrome.

A multiparous pregnant patient was admitted to the intensive care unit in her third trimester of pregnancy for prone positioning mechanical ventilation after developing SARS-CoV2 (COVID-19)-related acute respiratory distress syndrome. Repositioning in left lateral tilt was followed by uterine contractions and cardiotocography alterations. Preterm caesarean section was performed based on persistent foetal tachycardia and suspected foetal distress, followed by a per-operative diagnosis of uterine levotorsion. This case report is the first to explore a potential causal link between prolonged prone positioning in late pregnancy and postural gravid uterine torsion and highlights the need for appropriate foetal monitoring during prone positioning mechanical ventilation support.

Clinical value of early assessment of hyperfibrinolysis by rotational thromboelastometry during postpartum hemorrhage for the prediction of severity of bleeding: A multicenter prospective cohort study in the Netherlands.

INTRODUCTION: Coagulopathy may be the result of hyperfibrinolysis and could exacerbate bleeding following childbirth. Timely recognition of hyperfibrinolysis during the earliest stages of postpartum hemorrhage could identify women at risk of more severe blood loss who may benefit from targeted anti-fibrinolytic therapy. Rotational thromboelastometry (ROTEM® ) is a point-of-care test that could detect hyperfibrinolysis. The aim of this study was to evaluate whether early assessment of hyperfibrinolysis by ROTEM during postpartum hemorrhage could predict progression to severe postpartum hemorrhage. MATERIAL AND METHODS: During a prospective cohort study in the Netherlands among women with postpartum hemorrhage (total blood loss at least 1000 ml within 24 h after childbirth) ROTEM measurements were performed following 800-1500 ml of blood loss. Hyperfibrinolysis was defined as an enzymatic fibrinolysis index (ROTEM EXTEM maximum clot lysis [ML] minus the ROTEM APTEM ML) above 15%. Severe postpartum hemorrhage was defined as a composite end point of total blood loss greater than 2000 ml, transfusion of four or more units of packed cells, and/or need for an invasive intervention. The predictive value of hyperfibrinolysis for progression to severe postpartum hemorrhage was assessed by area under the receiver operating curve (AUC) and positive and negative predictive values. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149472). RESULTS: Of 390 women included, 82 (21%) had severe postpartum hemorrhage. Four (1%) women had thromboelastometric evidence of hyperfibrinolysis, of whom two developed severe postpartum hemorrhage. The AUC for enzymatic fibrinolysis index more than 15% for progression to severe postpartum hemorrhage was 0.47 (95% CI 0.40-0.54). Positive and negative predictive values for this index were 50.0% (95% CI 6.8-93.2) and 79.3% (95% CI 74.9-83.2), respectively. CONCLUSIONS: Thromboelastometric evidence of hyperfibrinolysis was rare in women with postpartum hemorrhage when assessed between 800 and 1500 ml of blood loss. The clinical predictive value of viscoelastometric point-of-care testing for hyperfibrinolysis for progression to severe postpartum hemorrhage during early postpartum hemorrhage is limited.

Women of reproductive age in a tertiary intensive care unit: indications, outcome and the impact of pregnancy-a retrospective cohort study.

BACKGROUND: To evaluate the indications for admission and mortality rates of women of reproductive age admitted to a tertiary Intensive Care Unit (ICU) and to compare the outcomes of obstetric and non-obstetric admissions. METHODS: A retrospective cohort study was performed, including all women aged 17-41 years admitted to a level 3 ICU in the Netherlands, between January 1, 2000 and January 1, 2016. Primary outcome was indication for admission and mortality. Mortality, length of stay (LOS), need for mechanical ventilation and APACHE II score were compared between obstetric and non-obstetric admissions. The obstetric group was further analyzed for maternal and perinatal outcomes. RESULTS: 3461 women (median age 32 years) were included, with an overall mortality rate of 13.3%. The obstetric group consisted of 265 women (7.7%). The non-obstetric group (n = 3196) was admitted most often for cardiovascular disease (19.6%), followed by oncologic disease (15%). Mortality was the highest in women with oncologic disease (23.9%). The obstetric group had lower mortality compared to the non-obstetric group (4.9% vs. 14%, p < 0.001), despite higher APACHE II score (14 vs. 11, p < 0.001) and a higher ventilation rate (47.9% vs. 39%, p = 0.004). Major surgical or endovascular interventions, besides caesarean section, were performed in 46% of the obstetric group. Perinatal death occurred in 17.2% and of the surviving infants, 63.2% were born preterm and 45.1% required Neonatal Intensive Care Unit admission. CONCLUSIONS: Cardiovascular disease is the most important indication for admission and oncologic disease is associated with highest mortality in women of reproductive age. Obstetric patients constitute a small percentage of all ICU admissions in a tertiary ICU center. They have lower mortality rates than non-obstetric young female patients, despite a more severe initial presentation. Nevertheless lasting maternal morbidity and perinatal mortality and morbidity is frequent.

Clinical value of early viscoelastometric point-of-care testing during postpartum hemorrhage for the prediction of severity of bleeding: A multicenter prospective cohort study in the Netherlands.

INTRODUCTION: To evaluate rotational fibrin-based thromboelastometry (ROTEM® FIBTEM) with amplitude of clot firmness at 5 min (A5) as an early point-of-care parameter for predicting progression to severe postpartum hemorrhage, and compare its predictive value with that of fibrinogen. MATERIAL AND METHODS: Prospective cohort study in the Netherlands including women with 800-1500 ml of blood loss within 24 h following birth. Blood loss was quantitatively measured by weighing blood-soaked items and using a fluid collector bag in the operating room. Both FIBTEM A5 values and fibrinogen concentrations (Clauss method) were measured between 800 and 1500  ml of blood loss. Predictive accuracy of both biomarkers for the progression to severe postpartum hemorrhage was measured by area under the receiver operating curves (AUC). Severe postpartum hemorrhage was defined as a composite endpoint of (1) total blood loss >2000 ml, (2) transfusion of ≥4 packed cells, and/or (3) need for an invasive intervention to cease bleeding. RESULTS: Of the 391 women included, 72 (18%) developed severe postpartum hemorrhage. Median (IQR) volume of blood loss at blood sampling was 1100 ml (1000-1300) with a median (interquartile range [IQR]) fibrinogen concentration of 3.9 g/L (3.4-4.6) and FIBTEM A5 value of 17 mm (13-20). The AUC for progression to severe postpartum hemorrhage was 0.53 (95% confidence interval [CI] 0.46-0.61) for FIBTEM A5 and 0.58 (95% CI 0.50-0.65) for fibrinogen. Positive predictive values for progression to severe postpartum hemorrhage for FIBTEM A5 ≤12 mm was 22.5% (95% CI 14-33) and 50% (95% CI 25-75) for fibrinogen ≤2 g/L. CONCLUSIONS: The predictive value of FIBTEM A5 compared to fibrinogen concentrations measured between 800 and 1500 ml of blood loss following childbirth was poor to discriminate between women with and without progression towards severe postpartum hemorrhage.

Outcome of early-onset fetal growth restriction with or without abnormal umbilical artery Doppler flow.

INTRODUCTION: Early-onset fetal growth restriction is a pregnancy complication often coinciding with abnormal Doppler flow in the umbilical artery. Absent or reversed end-diastolic flow in the umbilical artery is associated with adverse perinatal outcome. As the optimal management of this condition is unclear, the objective of this study was to analyze the time interval from admission to delivery of pregnancies with early-onset fetal growth restriction, while pursuing a policy of postponing delivery unless active management of labor would be required because of fetal distress or maternal condition. We also assessed short- and long-term perinatal outcome. MATERIAL AND METHODS: In this historical cohort study, all pregnant women with singleton pregnancies, admitted during 2004-2015 with early-onset fetal growth restriction were included. Pregnancies with absent or reversed end-diastolic flow (AREDF) were compared with pregnancies with a positive end-diastolic Doppler flow (PEDF). Time until delivery was determined and perinatal outcome was assessed for both groups. RESULTS: In our study, 111 women were allocated to the PEDF group and 109 to the AREDF group. In the AREDF group, fetal distress was more often an indication for delivery, in comparison with the PEDF group (p = .004). Median time until delivery in patients admitted between 26 and 28 weeks' gestation was 6+5 weeks in the PEDF group and 1+4 weeks in the AREDF group (p = .001). No statistically significant difference was found between the Doppler groups in the composite adverse neonatal outcome, which includes at least one of the following outcomes: infant respiratory distress syndrome, sepsis, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage >grade 2, periventricular leukomalacia and perinatal death (p = .63). CONCLUSIONS: In this study, comprising pregnancies with early-onset fetal growth restriction, fetal distress was observed more frequently in the AREDF group with the consequence of delivery at an earlier stage of gestation, compared with the PEDF group. AREDF was not associated with increased perinatal morbidity and mortality compared with PEDF.

A multicenter observational survey of management strategies in 442 pregnancies with suspected placenta accreta spectrum.

INTRODUCTION: Management options for women with placenta accreta spectrum (PAS) comprise termination of pregnancy before the viable gestational age, leaving the placenta in situ for subsequent reabsorption of the placenta or delayed hysterectomy, manual removal of placenta after vaginal delivery or during cesarean section, focal resection of the affected uterine wall, and peripartum hysterectomy. The aim of this observational study was to describe actual clinical management and outcomes in PAS in a large international cohort. MATERIAL AND METHODS: Data from women in 15 referral centers of the International Society of PAS (IS-PAS) were analyzed and correlated with the clinical classification of the IS-PAS: From Grade 1 (no PAS) to Grade 6 (invasion into pelvic organs other than the bladder). PAS was usually diagnosed antenatally and the operators performing ultrasound rated the likelihood of PAS on a Likert scale of 1 to 10. RESULTS: In total, 442 women were registered in the database. No maternal deaths occurred. Mean blood loss was 2600 mL (range 150-20 000 mL). Placenta previa was present in 375 (84.8%) women and there was a history of a previous cesarean in 329 (74.4%) women. The PAS likelihood score was strongly correlated with the PAS grade (P < .001). The mode of delivery in the majority of women (n = 252, 57.0%) was cesarean hysterectomy, with a repeat laparotomy in 20 (7.9%) due to complications. In 48 women (10.8%), the placenta was intentionally left in situ, of those, 20 (41.7%) had a delayed hysterectomy. In 26 women (5.9%), focal resection was performed. Termination of pregnancy was performed in 9 (2.0%), of whom 5 had fetal abnormalities. The placenta could be removed in 90 women (20.4%) at cesarean, and in 17 (3.9%) after vaginal delivery indicating mild or no PAS. In 34 women (7.7%) with an antenatal diagnosis of PAS, the placenta spontaneously separated (false positives). We found lower blood loss (P < .002) in 2018-2019 compared with 2009-2017, suggesting a positive learning curve. CONCLUSIONS: In referral centers, the most common management for severe PAS was cesarean hysterectomy, followed by leaving the placenta in situ and focal resection. Prenatal diagnosis correlated with clinical PAS grade. No maternal deaths occurred.

Temporizing management vs immediate delivery in early-onset severe preeclampsia between 28 and 34 weeks of gestation (TOTEM study): An open-label randomized controlled trial.

INTRODUCTION: There is little evidence to guide the timing of delivery of women with early-onset severe preeclampsia. We hypothesize that immediate delivery is not inferior for neonatal outcome but reduces maternal complications compared with temporizing management. MATERIAL AND METHODS: This Dutch multicenter open-label randomized clinical trial investigated non-inferiority for neonatal outcome of temporizing management as compared with immediate delivery (TOTEM NTR 2986) in women between 27+5 and 33+5 weeks of gestation admitted for early-onset severe preeclampsia with or without HELLP syndrome. In participants allocated to receive immediate delivery, either induction of labor or cesarean section was initiated at least 48 hours after admission. Primary outcomes were adverse perinatal outcome, defined as a composite of severe respiratory distress syndrome, bronchopulmonary dysplasia, culture proven sepsis, intraventricular hemorrhage grade 3 or worse, periventricular leukomalacia grade 2 or worse, necrotizing enterocolitis stage 2 or worse, and perinatal death. Major maternal complications were secondary outcomes. It was estimated 1130 women needed to be enrolled. Analysis was by intention-to-treat. RESULTS: The trial was halted after 35 months because of slow recruitment. Between February 2011 and December 2013, a total of 56 women were randomized to immediate delivery (n = 26) or temporizing management (n = 30). Median gestational age at randomization was 30 weeks. Median prolongation of pregnancy was 2 days (interquartile range 1-3 days) in the temporizing management group. Mean birthweight was 1435 g after immediate delivery vs 1294 g after temporizing management (P = .14). The adverse perinatal outcome rate was 55% in the immediate delivery group vs 52% in the temporizing management group (relative risk 1.06; 95% confidence interval 0.67-1.70). In both groups there was one neonatal death and no maternal deaths. In the temporizing treatment group, one woman experienced pulmonary edema and one placental abruption. Analyses of only the singleton pregnancies did not result in other outcomes. CONCLUSIONS: Early termination of the trial precluded any conclusions for the main outcomes. We observed that temporizing management resulted in a modest prolongation of pregnancy without changes in perinatal and maternal outcome. Conducting a randomized study for this important research question did not prove feasible.

Maternal and neonatal outcomes in 80 patients diagnosed with non-Hodgkin lymphoma during pregnancy: results from the International Network of Cancer, Infertility and Pregnancy.

This cohort study of the International Network on Cancer, Infertility and Pregnancy (INCIP) reports the maternal and neonatal outcomes of 80 pregnant patients diagnosed with non-Hodgkin lymphoma (NHL) between 1986 and 2019, focussing on 57 (71%) patients with diffuse large B-cell lymphoma (DLBCL). Of all 80 patients, 54 (68%) pregnant patients received chemotherapy; mostly (89%) CHOP-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens. Four early pregnancies were terminated. Among 76 ongoing pregnancies, there was one stillbirth (1·3%). Overall, there was a high incidence of small for gestational age neonates (39%), preterm delivery (52%), obstetric (41%) and neonatal complications (12·5%), and this could not exclusively be explained by the receipt of antenatal chemotherapy. Half of preterm deliveries (46%) were planned in order to tailor oncological treatment. The 3-year progression-free and overall survival for patients with DLBCL treated with rituximab-CHOP was 83·4% and 95·7% for limited stage (n = 29) and 60·6% and 73·3% for advanced stage (n = 15). Of 36 pregnant patients who received rituximab, five (13%) cases with neonatal complications and three (8%) with maternal infections were reported. In conclusion, standard treatment for DLBCL can be offered to pregnant patients in obstetric centres that cater for high-risk patients.

Cerebrospinal Fluid of Preeclamptic and Normotensive Pregnant Women Compared to Nonpregnant Women Analyzed with Mass Spectrometry.

Preeclampsia is a pregnancy-specific multiorgan disorder in which impaired placental functioning and excessive oxidative stress play an important role. We previously showed distinct differences between cerebrospinal fluid proteins in patients with preeclampsia and normotensive pregnant women. An additional group of nonpregnant women was included to study the presence of pregnancy-related proteins in normotensive and preeclamptic pregnancies and whether pregnancy-related proteins were associated with preeclampsia. Cerebrospinal fluid samples were tryptically digested and subsequently measured with a nano-LC-tribrid Orbitrap mass spectrometry system. Proteins were identified by shotgun proteomic analysis based on a data-dependent acquisition method. Proteins identified in preeclampsia, normotensive pregnant controls, and nonpregnant groups were compared to the Progenesis method according to the criteria as previously described and with a secondary analysis using a Scaffold method including Benjamini-Hochberg correction for multiple testing. For preeclampsia, the Progenesis and the Scaffold method together identified 15 (eight proteins for both analyses with one overlap) proteins that were significantly different compared to normotensive control pregnancies. Three of these 15 proteins, which were elevated in cerebrospinal fluid of preeclamptic women, were described to be pregnancy proteins with a calcium-binding function. Using two analysis methods (Progenesis and Scaffold), four out of 15 differential proteins were associated with pregnancy, as described in the literature. Three out of the four pregnancy-related proteins were elevated in preeclampsia. Furthermore, the contribution of elevated (n = 4/15) and downregulated (n = 2/15) calcium-binding proteins in preeclampsia is remarkably high (40%) and needs to be elucidated further.