Pregestational maternal risk factors for preterm and term preeclampsia: A population-based cohort study.

INTRODUCTION: Most studies on factors affecting the risk of preeclampsia have not separated preterm from term preeclampsia, and we still know little about whether the predisposing conditions have a differentiated effect on the risk of preterm and term preeclampsia. Our aim was to assess whether diabetes type 1 and 2, chronic kidney disease, asthma, epilepsy, rheumatoid arthritis and chronic hypertension were differentially associated with preterm and term preeclampsia. MATERIAL AND METHODS: This is a nationwide, population-based cohort study containing all births registered in the Medical Birth Registry of Norway from 1999 to 2016. Multinomial logistic regression analysis was used to estimate relative risk ratios (RRRs) with 95% confidence intervals (95% CIs), adjusting for maternal age, parity, multiple gestation and all other studied maternal risk factors. RESULTS: We registered 1 044 860 deliveries, of which 9533 (0.9%) women had preterm preeclampsia (<37 weeks) and 26 504 (2.5%) women had term preeclampsia (>37 weeks). Most of the assessed maternal risk factors were associated with increased risk for both preterm and term preeclampsia, with adjusted RRRs ranging from 1.2 to 10.5 (preterm vs no preeclampsia) and 0.9-5.7 (term vs no preeclampsia). Diabetes type 1 and 2 (RRR preterm vs term preeclampsia 2.89, 95% CI 2.46-3.39 and RRR 1.68, 95% CI 1.25-2.25, respectively), chronic kidney disease (RRR 1.55, 95% CI 1.11-2.17) and chronic hypertension (RRR 1.85, 95% CI 1.63-2.10) were more strongly associated with preterm than term preeclampsia in adjusted analyses. For asthma, epilepsy and rheumatoid arthritis, RRRs were closer to one and not significant when comparing risk of preterm and term preeclampsia. Main results were similar when using a diagnosis at <34 weeks to define preterm preeclampsia. CONCLUSIONS: Diabetes type 1 and 2, chronic kidney disease and chronic hypertension were more strongly associated with preterm than term preeclampsia.

Molecular and phenotypic characteristics influencing the degree of cytoreduction in high-grade serous ovarian carcinomas.

BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is the deadliest ovarian cancer subtype, and survival relates to initial cytoreductive surgical treatment. The existing tools for surgical outcome prediction remain inadequate for anticipating the outcomes of the complex relationship between tumour biology, clinical phenotypes, co-morbidity and surgical skills. In this genotype-phenotype association study, we combine phenotypic markers with targeted DNA sequencing to discover novel biomarkers to guide the surgical management of primary HGSOC. METHODS: Primary tumour tissue samples (n = 97) and matched blood from a phenotypically well-characterised treatment-naïve HGSOC patient cohort were analysed by targeted massive parallel DNA sequencing (next generation sequencing [NGS]) of a panel of 360 cancer-related genes. Association analyses were performed on phenotypic traits related to complete cytoreductive surgery, while logistic regression analysis was applied for the predictive model. RESULTS: The positive influence of complete cytoreductive surgery (R0) on overall survival was confirmed (p = 0.003). Before surgery, low volumes of ascitic fluid, lower CA125 levels, higher platelet counts and relatively lower clinical stage at diagnosis were all indicators, alone and combined, for complete cytoreduction (R0). Mutations in either the chromatin remodelling SWI_SNF (p = 0.036) pathway or the histone H3K4 methylation pathway (p = 0.034) correlated with R0. The R0 group also demonstrated higher tumour mutational burden levels (p = 0.028). A predictive model was developed by combining two phenotypes and the mutational status of five genes and one genetic pathway, enabling the prediction of surgical outcomes in 87.6% of the cases in this cohort. CONCLUSION: Inclusion of molecular biomarkers adds value to the pre-operative stratification of HGSOC patients. A potential preoperative risk stratification model combining phenotypic traits and single-gene mutational status is suggested, but the set-up needs to be validated in larger cohorts.

Primary Treatment Effects for High-Grade Serous Ovarian Carcinoma Evaluated by Changes in Serum Metabolites and Lipoproteins.

High-grade serous ovarian carcinoma (HGSOC) is the most common and deadliest ovarian cancer subtype. Despite advances in treatment, the overall prognosis remains poor. Regardless of efforts to develop biomarkers to predict surgical outcome and recurrence risk and resistance, reproducible indicators are scarce. Exploring the complex tumor heterogeneity, serum profiling of metabolites and lipoprotein subfractions that reflect both systemic and local biological processes were utilized. Furthermore, the overall impact on the patient from the tumor and the treatment was investigated. The aim was to characterize the systemic metabolic effects of primary treatment in patients with advanced HGSOC. In total 28 metabolites and 112 lipoproteins were analyzed by nuclear magnetic resonance (NMR) spectroscopy in longitudinal serum samples (n = 112) from patients with advanced HGSOC (n = 24) from the IMPACT trial with linear mixed effect models and repeated measures ANOVA simultaneous component analysis. The serum profiling revealed treatment-induced changes in both lipoprotein subfractions and circulating metabolites. The development of a more atherogenic lipid profile throughout the treatment, which was more evident in patients with short time to recurrence, indicates an enhanced systemic inflammation and increased risk of cardiovascular disease after treatment. The findings suggest that treatment-induced changes in the metabolome reflect mechanisms behind the diversity in disease-related outcomes.

Use of antihistamines before or during pregnancy and risk of early-onset pre-eclampsia in allergic women: a population-based cohort study.

OBJECTIVE: We have previously found that allergy is a risk factor for early-onset pre-eclampsia. The aim of this study was to assess the association between pregestational maternal use of antihistamines and early-onset pre-eclampsia. DESIGN: A population-based cohort study. SETTING AND PARTICIPANTS: All women giving birth in Norway 2004-2016, including 692 487 pregnancies. Data from the Medical Birth Registry of Norway were linked with data from the Norwegian Prescription Database. Prescriptions of antihistamines were divided into three groups: before pregnancy (<6 months), early pregnancy (<20 weeks) and late pregnancy (20-36 weeks). ORs with 95% CIs for pre-eclampsia <34 and <37 weeks by antihistamine use were estimated by logistic regression and stratified on multiple pregnancy and parity. Predicted proportions (%) with 95% CIs were estimated. INTERVENTIONS: Use of antihistamines in relation to pregnancy in allergic women. MAIN OUTCOME MEASURES: Development of early-onset pre-eclampsia. RESULTS: 2997 (0.43%) and 5769 (0.83%) women had pre-eclampsia <34 and <37 weeks, respectively. Use of antihistamines before and in early pregnancy was associated with a risk of developing early-onset pre-eclampsia that was comparable to the background population (OR 1.0, 95% CI 0.8 to 1.2 and OR 0.9, 95% CI 0.7 to 1.1, respectively). Antihistamine use only in late pregnancy was not treated as exposure, but as an indicator of allergy, and was associated with an increased risk of early-onset pre-eclampsia (OR 1.8, 95% CI 1.5 to 2.2). Predicted proportions of pre-eclampsia <34 weeks were significantly lower in women using antihistamines before (0.41%, 95% CI 0.34 to 0.49) and in early pregnancy (0.37%, 95% CI 0.31 to 0.44), compared with women using antihistamines after placentation (0.69%, 95% CI 0.57 to 0.83). Results were similar for pre-eclampsia <37 weeks. CONCLUSIONS: Antihistamine use before or during placentation was associated with reduced risk of developing early-onset pre-eclampsia in allergic women compared with women using antihistamines after placentation.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

Put your weight behind it-Effect of body mass index on the active second stage of labour: A retrospective cohort study.

OBJECTIVE: To explore the duration of the active phase of the second stage of labour in relation to maternal pre-pregnant body mass index (BMI). DESIGN: Retrospective cohort study. SETTING: Labour wards of three Norwegian university hospitals, 2012-2019. POPULATION: Nulliparous and parous women without previous caesarean section with a live singleton fetus in cephalic presentation and spontaneous onset of labour, corresponding to the Ten Group Classification System (TGCS) group 1 and 3. METHODS: Women were stratified to BMI groups according to WHO classification, and estimated median duration of the active phase of the second stage of labour was calculated using survival analyses. Caesarean sections and operative vaginal deliveries during the active phase were censored. MAIN OUTCOME MEASURES: Estimated median duration of the active phase of second stage of labour. RESULTS: In all, 47 942 women were included in the survival analyses. Increasing BMI was associated with shorter estimated median duration of the active second stage in both TGCS groups. In TGCS group 1, the estimated median durations (interquartile range) were 44 (26-75), 43 (25-71), 39 (22-70), 33 (18-63), 34 (19-54) and 29 (16-56) minutes in BMI groups 1-6, respectively. In TGCS group 3, the corresponding values were 11 (6-19), 10 (6-17), 10 (6-16), 9 (5-15), 8 (5-13) and 7 (4-11) minutes. Increasing BMI remained associated with shorter estimated median duration in analyses stratified by oxytocin augmentation and epidural analgesia. CONCLUSION: Increasing BMI was associated with shorter estimated median duration of the active second stage of labour.

The effect of Zhang's guideline vs the WHO partograph on childbirth experience measured by the Childbirth Experience Questionnaire in the Labor Progression Study (LaPS): A cluster randomized trial.

INTRODUCTION: Childbirth experience is an increasingly recognized and important measure of quality of obstetric care. Previous research has shown that it can be affected by intrapartum care and how labor is followed. A partograph is recommended to follow labor progression by recording cervical dilation over time. There are currently different guidelines in use worldwide to follow labor progression. The two main ones are the partograph recommended by the World Health Organization (WHO) based on the work of Friedman and Philpott and a guideline based on Zhang's research. In our study we assessed the effect of adhering to Zhang's guideline or the WHO partograph on childbirth experience. Zhang's guideline describes expected normal labor progression based on data from contemporary obstetric populations, resulting in an exponential progression curve, compared with the linear WHO partograph. The choice of labor curve affects the intrapartum follow-up of women and this could potentially affect childbirth experience. MATERIAL AND METHODS: The Labor Progression Study (LaPS) study was a prospective, cluster randomized controlled trial conducted at 14 birth centers in Norway. Birth centers were randomized to either follow Zhang's guideline or the WHO partograph. Nulliparous women in active labor, with one fetus in cephalic presentation at term and spontaneous labor onset were included. At 4 weeks postpartum, included women received an online login to complete the Childbirth Experience Questionnaire (CEQ). Total score on the CEQ, the four domain scores on the CEQ, and scores on the individual items on the CEQ were compared between the two groups. RESULTS: There were 1855 women in the Zhang group and 1749 women in the WHO partograph group. There was no difference in the total or domain CEQ scores between the two groups. We found statistically significant differences for two individual items; women in the Zhang group scored lower on positive memories and feeling of control. CONCLUSIONS: Based on our findings on childbirth experience there is no reason to prefer Zhang's guideline over the WHO partograph.

Safety Aspects of Perinatal Ultrasound.

Ultrasound safety is of particular importance in fetal and neonatal scanning. Fetal tissues are vulnerable and often still developing, the scanning depth may be low, and potential biological effects have been insufficiently investigated. On the other hand, the clinical benefit may be considerable. The perinatal period is probably less vulnerable than the first and second trimesters of pregnancy, and ultrasound is often a safer alternative to other diagnostic imaging modalities. Here we present step-by-step procedures for obtaining clinically relevant images while maintaining ultrasound safety. We briefly discuss the current status of the field of ultrasound safety, with special attention to the safety of novel modalities, safety considerations when ultrasound is employed for research and education, and ultrasound of particularly vulnerable tissues, such as the neonatal lung. This CME is prepared by ECMUS, the safety committee of EFSUMB, with contributions from OB/GYN clinicians with a special interest in ultrasound safety.

A pregnant woman with acute abdomen. / En gravid kvinne med akutte magesmerter.

BACKGROUND: Acute abdomen in pregnancy is challenging. The presentation of symptoms and available diagnostic tools are directed and complicated by the pregnancy. A rare cause of acute abdomen in pregnancy requiring immediate intervention is presented. CASE PRESENTATION: A primiparous woman with 34 weeks of uncomplicated pregnancy presented with acute onset of abdominal pain, no signs of labour or vaginal bleeding, blood pressure 127/100, and pulse 90. No fetal distress was indicated by cardiotocography or abdominal ultrasound, while large amounts of intra-abdominal free fluid were identified. The clinical examination revealed free intra-abdominal fluid, which combined with the intense pain prompted an emergency caesarean section on vital indication with removal of intra-abdominal blood, immediate delivery, and manual compression of the aorta. No signs of placental abruption or rupture of the uterine wall were identified. The bleeding, originating from a spontaneous rupture of the left uterine vein, was halted by vessel ligation. Although haemodynamically stable, the woman's estimated blood loss was 4700 millilitres. The child remained for ten days in the NICU owing to prematurity. INTERPRETATION: A total of 100 case reports of acute spontaneous haemoperitoneum during pregnancy have been published. The underlying pathophysiology is undetermined, but possible risk factors include nulliparity, endometriosis causing extrauterine bleeding, and varicose veins. The condition requires immediate intervention, as morbidity and mortality rates for mother and fetus are high.

EFSUMB Clinical Safety Statement for Diagnostic Ultrasound - (2019 revision).

This document is the updated 2019 revision of the EFSUMB Clinically Safety Statement. A Safety Statement has been published by EFSUMB annually since 1994 by the Safety Committee (ECMUS) of the federation. The text is deliberately brief and gives a concise overview of safety in the use of diagnostic ultrasound.

Risk for delivery complications in Robson Group 1 for non-Western women in Norway compared with ethnic Norwegian women - A population-based observational cohort study.

OBJECTIVES: To assess the pregnancy outcome of low-risk pregnancies for women originating from non-Western countries compared with ethnic Norwegian women. STUDY DESIGN: A retrospective population-based observational cohort study with prospectively registered data. Conducted at Stavanger University Hospital, Norway, with approximately 4800 deliveries annually, from 2009 to 2015. We included women with low-risk pregnancies of non-Western origin (n = 1413), born in Africa (n = 224), Asia (n = 439), Eastern Europe (n = 499), Middle East (n = 138), South America (n = 85), Western (n = 979), and ethnic Norwegian women (n = 7028). MAIN OUTCOME MEASURES: The relative risk of emergency cesarean section or postpartum hemorrhage by country of origin was estimated by odds ratios with 95% confidence intervals using logistic multiple regression. RESULTS: In total, the pregnancy outcomes of 9392 women were analyzed. Risk of emergency cesarean section was significantly higher for women originating from Asia (aOR: 1.887), followed by Africans (aOR: 1.705). Lowest risk was found in women originating from South America (aOR: 0.480). Risk of postpartum hemorrhage was significantly higher in women originating from Asia (aOR: 1.744) compared to Norwegians. CONCLUSION: Even in a low-risk population, women originating from Asia and Africa had an elevated risk of adverse pregnancy outcome compared to the Norwegian group. The elevated risk should be considered by obstetric care providers, and we suggest that women originating from Asia and Africa would benefit from a targeted care during pregnancy and childbirth.

Maternal allergy as an isolated risk factor for early-onset preeclampsia: An epidemiological study.

Immunological mechanisms underlying the development of preeclampsia are well known, but no association to allergy has yet been demonstrated. The aim of this study was to assess the correlation between maternal pre-gestational allergy, and early-onset and late-onset preeclampsia, respectively. It was a retrospective cohort study including all women giving birth in the Norwegian cities of Stavanger (1996-2014) and Bergen (2009-2014). Pre-gestational asthma, allergy, other known risk factors for preeclampsia, maternal age and parity were obtained from the electronic medical record system. The main outcome variables were early-onset and late-onset preeclampsia (before and after 34 completed weeks of gestation, respectively). We used multinomial logistic regression to estimate odds ratios (OR) with 95% confidence intervals (95% CI) for early and late-onset preeclampsia in women with pre-gestational allergy when compared to women without allergy, adjusting for covariates. Predicted probabilities for the outcomes were also calculated. Of the 110 064 included pregnancies, 2 799 developed late-onset preeclampsia (2.5%) and 348 developed early-onset preeclampsia (0.3%). Pre-gestational allergy increased the risk of early-onset preeclampsia (OR 1.7, 95% CI 1.3-2.4), and reduced the risk of late-onset preeclampsia (OR 0.8, 95% CI 0.7-0.9). These findings add valuable information on preeclampsia as an immunological complication of pregnancy and corroborate the understanding of early- and late-onset preeclampsia as two different entities.

The effects of reducing the thermal index for bone from 1.0 to 0.5 and 0.1 on common obstetric pulsed wave Doppler measurements in the second half of pregnancy.

OBJECTIVE: To test the hypothesis that clinically relevant vessels can be visualized and interrogated with Doppler recording during the second half of pregnancy at an output energy below the currently advocated limits without loss of information. DESIGN: Observational cross-sectional study. SETTING: Tertiary fetal medicine center. SAMPLE: Based on a power calculation for equivalence studies, we recruited 65 pregnant women. METHODS: Ultrasound examination was performed at 18, 24 or 36 weeks of gestation. The umbilical artery, middle cerebral artery, ductus venosus, and both uterine arteries were identified using color Doppler, and the blood velocities were measured using pulsed wave Doppler at a thermal index for bone (TIB) of 1.0. This procedure was repeated at TIB values of 0.5 and 0.1. The depth of Doppler recording was noted. MAIN OUTCOME MEASURES: Visualization of the vessels by color Doppler at all power levels and any systematic changes or increased variance of the recorded parameters with decreasing power level. RESULTS: All vessels could be visualized by color Doppler and their flow velocities measured using pulsed wave Doppler in all participants and at all power levels. There were no systematic changes or increased parameter variance when reducing the power level, despite the insonation depth being significantly greater than in early pregnancy. CONCLUSIONS: Reducing the ultrasound power from TIB 1.0 to 0.1 does not alter color Doppler visualization or pulsed wave Doppler measurements in the second half of pregnancy. The lower power level can be recommended as a starting point for clinical examinations throughout pregnancy.

The effect of ultrasound output level on obstetric biometric measurements.

We tested the effect of reducing the ultrasound output energy on obstetric measurements made from two-dimensional (2-D) grayscale images. We measured three fetal structures (femur, umbilical vein and lateral cerebral ventricle) in 113 pregnant women, commencing with an output energy that provided a thermal index for bone (TIB) of ≤1.0, and then repeated the measurements at TIB ≤ 0.5 and then TIB ≤ 0.1. There was a trend toward shorter femur measurements and larger umbilical vein diameter measurements with decreasing output energy. However, since these effects (which did not exceed 0.03 mm) were very small compared with the inter- and intraobserver variations, they were considered to be of no clinical significance. Furthermore, the residuals did not increase when the output energy decreased, indicating that the precision of the measurements was unaltered. We conclude that using a reduced output energy setting corresponding to a TIB of 0.1 does not compromise ultrasound biometry findings.