The use of loop diuretics in the context of hypertensive disorders of pregnancy: a systematic review and meta-analysis.

AIMS: Addressing volume expansion may improve the management of hypertension across the pregnancy continuum. We conducted a systematic review to summarize the evidence on the use of loop diuretics in the context of hypertensive disorders during pregnancy and the postpartum period. METHODS AND RESULTS: Medline, Embase, Cochrane library, ClinicalTrials.gov, and Google Scholar were searched for original research articles published up to 29 June 2021. Of the 2801 results screened, 15 studies were included: eight randomized controlled trials, six before-after studies, and one cohort study. Based on random effects meta-analysis of before-after studies, antepartum use of loop diuretics was associated with lower DBP [mean difference -17.73 mmHg, (95% confidence intervals -34.50 to -0.96); I2 = 94%] and lower cardiac output [mean difference -0.75 l/min, (-1.11 to -0.39); I2 = 0%], with no difference in SBP, mean arterial pressure, heart rate, or total peripheral resistance. Meta-analysis of randomized controlled trials revealed that postpartum use of loop diuretics was associated with decreased need for additional antihypertensive patients [relative risk 0.69, (0.50-0.97); I2 = 14%], and an increased duration of hospitalization [mean difference 8.80 h, (4.46-13.14); I2 = 83%], with no difference in the need for antihypertensive therapy at hospital discharge, or persistent postpartum hypertension. CONCLUSION: Antepartum use of loop diuretics lowered DBP and cardiac output, while their postpartum use reduced the need for additional antihypertensive medications. There was insufficient evidence to suggest a clear benefit. Future studies focusing on women with hypertensive pregnancy disorders who may most likely benefit from loop diuretics are required.

Induction of labour in low-risk pregnancies before 40 weeks of gestation: A systematic review and meta-analysis of randomized trials.

This systematic review of 16 randomized trials, which included 8796 pregnancies, did not demonstrate a reduction in caesarean births or perinatal morbidity from induction of labour (IoL) at 39-40 weeks for non-medical indications. However, IoL at 39-40 weeks may be associated with a lower incidence of maternal hypertensive disorders, a shorter duration of the first stage of labour, fewer instances of meconium-stained amniotic fluid, lower mean birth weights, longer duration of (maternal) hospitalization, and higher epidural usage. Until regional data on clinical benefits, resource implications and long-term impact are available, a prudent approach would be to encourage shared decision-making, wherein birthing persons with low-risk pregnancies are given the opportunity to assess the risks and benefits of IoL at 39-40 weeks over expectant management and allowed to consider their decision in the light of their values and preferences and local resource availability.

Composite adverse outcomes in obstetric studies: a systematic review.

BACKGROUND: Composite outcomes are increasingly being used in obstetric trials. The aim of this systematic review is to critically appraise the use of composite outcomes in obstetric RCTs with an intention of identifying limitations and providing potential solutions for future research. METHODS: The study protocol was prospectively registered. Medline, Embase, Cochrane Databases and www.clinicaltrials.gov were searched for randomized controlled trials (RCTs) published in English between 1999 and 2019, using search terms related to pregnancy and composite outcomes. STUDY ELIGIBILITY CRITERIA: RCTs involving an obstetric condition that reported on a composite outcome. STUDY APPRAISAL AND SYNTHESIS METHODS: Screening and data extraction were performed in duplicate, and a descriptive synthesis and critical appraisal of composite obstetric outcomes, is presented. RESULTS: Of the 4170 results screened, we identified 156 RCTs, reporting on 181 composite outcomes. Of these, 158 composite outcomes related to general morbidity and mortality, either exclusively maternal (n=20), fetal-neonatal [perinatal] (n=116) or maternal and perinatal (n=22) were included in the final analysis. Obstetric composite outcomes included between two and 16 components. Components that comprised these composite outcomes were often dissimilar in terms of severity and frequency of occurrence, unlikely to have similar relative risk reductions and sometimes unrelated to the study's primary objective - important pre-requisites to consider while constructing composite outcomes. In addition, composite adverse obstetric outcomes often do not incorporate the perspectives of pregnant persons, embrace a holistic view of health or consider outcomes related to both members of the mother-fetus dyad. CONCLUSIONS: Composite outcomes are being increasingly used as primary outcomes in obstetric RCTs, based on which study conclusions are drawn and clinical recommendations made. However, there is a lack of consistency with regard to what components should be included within a composite adverse obstetric outcome and how these components should be measured. The use of novel research methods such as concept mapping may be able to address some of the limitations with the development of composite adverse obstetric outcomes, to inform future research.

Birth outcomes in women with body mass index of 40 kg/m2 or greater stratified by planned and actual mode of birth: a systematic review and meta-analysis.

INTRODUCTION: Pregnant women with a body mass index (BMI) ≥40 kg/m2 are at an increased risk of requiring planned- and unplanned cesarean deliveries (CD). The aim of this systematic review is to compare outcomes in women with BMI ≥ 40 kg/m2 based on planned and actual mode of birth. MATERIAL AND METHODS: Five databases were searched for English and French-language publications until February 2019, and all studies reporting on delivery outcomes in women with BMI ≥ 40 kg/m2 , stratified by planned and actual mode of birth, were included. Risk-of-bias was assessed using the Newcastle-Ottawa Scale. Relative risks (RR) and 95% confidence intervals were calculated using random-effects meta-analysis. RESULTS: Ten observational studies were included. Anticipated vaginal birth vs planned CD (5 studies, n = 2216) was associated with higher risk for postpartum hemorrhage (13.0% vs 4.1%, P < .001, numbers needed to harm (NNH = 11), I2  = 0%) but lower risk for wound complications (7.6% vs 14.5%, P < .001, numbers needed to treat (NNT = 15), I2  = 58.3%). Planned trial of labor vs repeat CD (3 studies, n = 4144) was associated with higher risk for uterine dehiscence (0.94% vs 0.42%, P = .04, NNH = 200, I2  = 0%), endometritis (5.1% vs 2.2%, P < .001, NNH = 35, I2  = 0%), prolonged hospitalization (one study, 30.3% vs 26.0%, P = .003, NNH = 23), low five-minute Apgar scores (4.9% vs 1.7%, RR 2.95 (2.03, 4.28), NNH = 30, I2  = 0%) and birth trauma (1.1% vs 0.2%, P < .001, NNH = 111, I2  = 0%). Successful vaginal birth vs intrapartum CD (n = 3625) was associated with lower risk of postpartum hemorrhage (15.1% vs 70%, P < .001, NNT = 2, I2  = 0%), wound complications (one study, 0% vs 4.4%, P = .007, NNT = 23), prolonged hospitalization (one study, 1.9% vs 6.7%, 0.04, NNT = 21) and low five-minute Apgar scores (one study, 1.0% vs 5.6%, P = .03, NNT = 22), but more birth trauma (5.9% vs 0.6%, P = .005, NNH = 19, I2  = 0%). Compared groups had dissimilar demographic characteristics. Although studies scored 6-7/9 on risk-of-bias assessment, they were at high-risk for confounding by indication. CONCLUSIONS: Evidence from observational studies suggests clinical equipoise regarding the optimal mode of delivery in women with BMI ≥ 40 kg/m2 and no prior CD. This question is best answered by a randomized trial. Based on an unplanned subgroup analysis, for women with BMI ≥ 40 kg/m2 and prior CD, repeat CD may be associated with better clinical outcomes.

Association of Receipt of Palliative Care Interventions With Health Care Use, Quality of Life, and Symptom Burden Among Adults With Chronic Noncancer Illness: A Systematic Review and Meta-analysis.

Importance: The evidence for palliative care exists predominantly for patients with cancer. The effect of palliative care on important end-of-life outcomes in patients with noncancer illness is unclear. Objective: To measure the association between palliative care and acute health care use, quality of life (QOL), and symptom burden in adults with chronic noncancer illnesses. Data Sources: MEDLINE, Embase, CINAHL, PsycINFO, and PubMed from inception to April 18, 2020. Study Selection: Randomized clinical trials of palliative care interventions in adults with chronic noncancer illness. Studies involving at least 50% of patients with cancer were excluded. Data Extraction and Synthesis: Two reviewers independently screened, selected, and extracted data from studies. Narrative synthesis was conducted for all trials. All outcomes were analyzed using random-effects meta-analysis. Main Outcomes and Measures: Acute health care use (hospitalizations and emergency department use), disease-generic and disease-specific quality of life (QOL), and symptoms, with estimates of QOL translated to units of the Functional Assessment of Chronic Illness Therapy-Palliative Care scale (range, 0 [worst] to 184 [best]; minimal clinically important difference, 9 points) and symptoms translated to units of the Edmonton Symptom Assessment Scale global distress score (range, 0 [best] to 90 [worst]; minimal clinically important difference, 5.7 points). Results: Twenty-eight trials provided data on 13 664 patients (mean age, 74 years; 46% were women). Ten trials were of heart failure (n = 4068 patients), 11 of mixed disease (n = 8119), 4 of dementia (n = 1036), and 3 of chronic obstructive pulmonary disease (n = 441). Palliative care, compared with usual care, was statistically significantly associated with less emergency department use (9 trials [n = 2712]; 20% vs 24%; odds ratio, 0.82 [95% CI, 0.68-1.00]; I2 = 3%), less hospitalization (14 trials [n = 3706]; 38% vs 42%; odds ratio, 0.80 [95% CI, 0.65-0.99]; I2 = 41%), and modestly lower symptom burden (11 trials [n = 2598]; pooled standardized mean difference (SMD), -0.12; [95% CI, -0.20 to -0.03]; I2 = 0%; Edmonton Symptom Assessment Scale score mean difference, -1.6 [95% CI, -2.6 to -0.4]). Palliative care was not significantly associated with disease-generic QOL (6 trials [n = 1334]; SMD, 0.18 [95% CI, -0.24 to 0.61]; I2 = 87%; Functional Assessment of Chronic Illness Therapy-Palliative Care score mean difference, 4.7 [95% CI, -6.3 to 15.9]) or disease-specific measures of QOL (11 trials [n = 2204]; SMD, 0.07 [95% CI, -0.09 to 0.23]; I2 = 68%). Conclusions and Relevance: In this systematic review and meta-analysis of randomized clinical trials of patients with primarily noncancer illness, palliative care, compared with usual care, was statistically significantly associated with less acute health care use and modestly lower symptom burden, but there was no significant difference in quality of life. Analyses for some outcomes were based predominantly on studies of patients with heart failure, which may limit generalizability to other chronic illnesses.

Development of a Core outcome set for fetal Myelomeningocele (COSMiC): study protocol.

BACKGROUND: Open spina bifida (OSB) is one of the most common congenital central nervous system defects and leads to long-term physical and cognitive disabilities. Open fetal surgery for OSB improves neurological outcomes and reduces the need for ventriculoperitoneal shunting, compared to postnatal surgery, but is associated with a significant risk of prematurity and maternal morbidity. Fetoscopic surgery comes with less maternal morbidity, yet the question remains whether the procedure is neuroprotective and reduces prematurity. Comparison of outcomes between different treatment options is challenging due to inconsistent outcome reporting. We aim to develop and disseminate a core outcome set (COS) for fetal OSB, to ensure that outcomes relevant to all stakeholders are collected and reported in a standardised fashion in future studies. METHODS: The COS will be developed using a validated Delphi methodology. A systematic literature review will be performed to identify outcomes previously reported for prenatally diagnosed OSB. We will assess maternal (primary and subsequent pregnancies), fetal, neonatal and childhood outcomes until adolescence. In a second phase, we will conduct semi-structured interviews with stakeholders, to ensure representation of additional relevant outcomes that may not have been reported in the literature. We will include patients and parents, as well as health professionals involved in the care of these pregnancies and children (fetal medicine specialists, fetal surgeons, neonatologists/paediatricians and allied health). Subsequently, an international group of key stakeholders will rate the importance of the identified outcomes using three sequential online rounds of a modified Delphi Survey. Final agreement on outcomes to be included in the COS, their definition and measurement will be achieved through a face-to-face consensus meeting with all stakeholder groups. Dissemination of the final COS will be ensured through different media and relevant societies. DISCUSSION: Development and implementation of a COS for fetal OSB will ensure consistent outcome reporting in future clinical trials, systematic reviews and clinical practice guidelines. This will lead to higher quality research, better evidence-based clinical practice and ultimately improved maternal, fetal and long-term childhood outcomes. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42018104880 . Registered on December 5, 2018. Core Outcome Measures in Effectiveness Trials (COMET): 1187.

Risk of singleton preterm birth after prior twin preterm birth: a systematic review and meta-analysis.

OBJECTIVE DATA: The purpose of this study was to conduct a systematic review and meta-analyses of literature regarding the risk of preterm birth in singleton pregnancies after a preterm twin birth. STUDY: We conducted a literature search of Embase, Ovid Medline, and Cochrane from inception until February 28, 2019. Studies that evaluated women with a previous twin birth followed by a singleton birth were included. STUDY APPRAISAL AND SYNTHESIS METHODS: Data were abstracted in duplicate, and summary odds ratios and confidence intervals were calculated with the use of random effects model. Risk of bias was assessed with the use of the Newcastle-Ottawa Scale, and quality of evidence was evaluated with the use of the Grades of Recommendation, Assessment, Development, and Evaluation approach. The primary outcome was a preterm singleton birth (<37 weeks gestational age); secondary outcomes included risk of late preterm birth (34-36+6 weeks gestation), preterm birth between 30 and 33+6 weeks gestation, and preterm birth at <30 weeks gestation. Subanalysis of risk of singleton preterm birth after spontaneous twin birth was also performed. A priori, the protocol was developed and registered with PROSPERO (2016; registration number: CRD42017053382). RESULTS: We included 8 cohort studies at low risk-of-bias met inclusion criteria for the systematic review and 6 for the meta-analysis. Compared with women with previous term twin births, women who had previous preterm (<37 weeks gestation) twin births were at increased odds of preterm singleton birth in subsequent pregnancy (odds ratio, 4.34; 95% confidence interval, 2.83-6.65). Gestational age at birth of previous twin pregnancy was an effect modifier. Compared with previous term twin births, the odd ratios of subsequent preterm singleton birth were 2.13 (95% confidence interval, 1.21-3.74) if twins were born between 34 and 36+6 weeks gestation, 5.18 (95% confidence interval, 2.78-9.64) if twins were born between 30 and 33+6 weeks gestation, and 9.78 (95% confidence interval, 4.99-18.98) if twins were born at <30 weeks gestation. A similar trend was seen for the risk of singleton preterm birth after spontaneous twin preterm birth. CONCLUSION: A history of preterm twin birth is associated with higher odds of subsequent preterm singleton birth. The odds increase with decreasing gestational age of previous twin birth.

Safety of Cabergoline for Postpartum Lactation Inhibition or Suppression: A Systematic Review.

This study sought to perform a systematic review of adverse events reported with the use of cabergoline for postpartum lactation inhibition or suppression in women aged 15 to 50. Following registration with PROSPERO (CRD42017049894), a comprehensive search of the Ovid databases Medline, Embase, and CENTRAL, along with PubMed, was conducted from January 1, 1985 to January 25, 2018. All study designs investigating cabergoline use for postpartum lactation inhibition or suppression in women aged 15 to 50 were included. A total of 695 articles were retrieved, and 25 articles were eligible for inclusion. Adverse events were then reported in terms of frequency, with percentages calculated according to the total number of women exposed to the intervention. A bias assessment of the articles was also performed. Among a total of 757 women, 108 adverse events were observed in 96 women (14.2%). The most common adverse events were dizziness (35 of 757), headache (30 of 757), and nausea or vomiting (19 of 757). These events were described as short-lived, self-resolving, and dose dependent. One pharmacovigilance study reported 29 "serious" events from a total of 175 events in 72 case reports, which included thromboembolic and neurologic events. Four case studies specifically addressed the psychiatric population, with one half reporting psychiatric symptoms following administration of cabergoline. In conclusion, this systematic review demonstrates that adverse events were generally benign and tolerable following the administration of cabergoline. However, pharmacovigilance data reveal that vigilance is still needed given the occurrence of rare but serious events.

Risk of singleton preterm birth after prior twin preterm birth: a cohort study.

Objective: To determine whether preterm birth in a twin pregnancy increases the risk of subsequent preterm birth (PTB) in a singleton pregnancy and to identify predictors for singleton PTB in women with previous twin PTB.Method: A retrospective cohort study of women with prior twin birth followed by a singleton birth in two tertiary referral centres between 2000 and 2016 was conducted. Rate of PTB in subsequent singleton pregnancy was compared between women who experienced previous preterm versus term twin birth. Analysis was further stratified by gestational age at twin and singleton birth, etiology for PTB and chorionicity in the twin pregnancy.Results: A total of 378 women met the inclusion criteria, of whom 252 (66.7%) experienced PTB in the index twin pregnancy. The overall rate of PTB in the subsequent singleton pregnancy was 11.6% (44/378). Women with prior twin PTB had a higher rate of PTB in the subsequent singleton pregnancy compared with women with prior term twin birth (17.5 versus 6.3%, p = .003, or 3.12, 95%-CI 1.42-6.85), mainly due to a higher rate of late singleton preterm birth (13.1 versus 4.0%, p = .005). Findings of higher odds of PTB in the subsequent singleton pregnancy was limited to women who gave birth before 340/7 weeks in the twin pregnancy and was related to the degree of prematurity (prior twin PTB at 300/7-336/7 weeks: OR 3.09, 95%-CI 1.12-8.51; prior twin PTB at <300/7 weeks: OR 5.8, 95%-CI 2.46-13.68). The association between previous twin PTB and subsequent singleton PTB was limited to women with prior spontaneous twin PTB (OR 3.34, 95%-CI 1.50-7.45).Conclusion: Women with a history of spontaneous PTB in a twin pregnancy are at increased odds of PTB in subsequent singleton pregnancies compared to women with prior term twin birth, and the risk is related to the severity of prematurity in the index twin pregnancy.

Comparative efficacy of opioids for older adults presenting to the emergency department with acute pain: Systematic review.

OBJECTIVE: To systematically review the literature for studies comparing the efficacy of opioid analgesics for older adults (≥ 65 years) presenting to the emergency department (ED) with acute pain. DATA SOURCES: The Cochrane Library, MEDLINE, EMBASE, Web of Science, and CINAHL were searched up to August or September 2017. Reference lists were searched for potential articles and ClinicalTrials.gov was searched for unpublished trials. STUDY SELECTION: Randomized controlled trials (RCTs) were sought that compared the efficacy of 2 or more opioid analgesics for acute pain in older patients (≥ 65 years) in the ED. Two reviewers independently screened abstracts, assessed study quality, and extracted data. SYNTHESIS: After screening titles and abstracts of 1315 citations, the full texts of 63 studies were reviewed and 1 RCT met the inclusion criteria. This study randomized older adult patients presenting to an urban academic ED with acute, severe pain to receive a single dose of either 0.0075 mg/kg intravenous hydromorphone or 0.05 mg/kg intravenous morphine. This study found no clinical or statistical difference between the 2 treatments. CONCLUSION: The lack of published research in this area demonstrates a considerable gap in knowledge of the comparative efficacy of opioid analgesics in the growing older adult patient population. Physicians are often uncertain in their choice of analgesia, potentially contributing to the undertreatment of pain. It is clear that well designed RCTs are urgently needed.