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American Journal of Obstetrics and... Dec 2021A systematic review was conducted to determine placental outcomes following prenatal alcohol exposure in women. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
A systematic review was conducted to determine placental outcomes following prenatal alcohol exposure in women.
DATA SOURCES
The search terms "maternal OR prenatal OR pregnant OR periconception" AND "placenta" AND "alcohol OR ethanol" were used across 5 databases (PubMed, Embase, Cochrane Library, Web of Science, and CINAHL) from inception until November 2020.
STUDY ELIGIBILITY CRITERIA
Articles were included if they reported placental outcomes in an alcohol exposure group compared with a control group. Studies were excluded if placentas were from elective termination before 20 weeks' gestation, animal studies, in vitro studies, case studies, or coexposure studies.
METHODS
Study quality was assessed by 2 reviewers using the Newcastle-Ottawa Quality Assessment Scale. Title and abstract screening was conducted by 2 reviewers to remove duplicates and irrelevant studies. Remaining full text articles were screened by 2 reviewers against inclusion and exclusion criteria. Placental outcome data were extracted and tabulated separately for studies of placentation, placental weight, placental morphology, and placental molecular studies. Meta-analyses were conducted for outcomes reported by >3 studies.
RESULTS
Database searching retrieved 640 unique records. Screening against inclusion and exclusion criteria resulted in 33 included studies. The quality assessment identified that 61% of studies were high quality, 30% were average quality, and 9% were low quality. Meta-analyses indicated that prenatal alcohol exposure increased the likelihood of placental abruption (odds ratio, 1.48; 95% confidence interval, 1.37-1.60) but not placenta previa (odds ratio, 1.14; 95% confidence interval, 0.84-1.34) and resulted in a reduction in placental weight of 51 g (95% confidence interval, -82.8 to -19.3). Reports of altered placental vasculature, placental DNA methylation, and gene expression following prenatal alcohol exposure were identified. A single study examined placentas from male and female infants separately and found sex-specific placental outcomes.
CONCLUSION
Prenatal alcohol exposure increases the likelihood of placental abruption and is associated with decreased placental weight, altered placental vasculature, DNA methylation, and molecular pathways. Given the critical role of the placenta in determining pregnancy outcomes, further studies investigating the molecular mechanisms underlying alcohol-induced placental dysfunction are required. Sex-specific placental adaptations to adverse conditions in utero have been well documented; thus, future studies should examine prenatal alcohol exposure-associated placental outcomes separately by sex.
Topics: Abruptio Placentae; Alcohol Drinking; Female; Humans; Placenta Previa; Pregnancy; Pregnancy Outcome; Prenatal Exposure Delayed Effects
PubMed: 34181895
DOI: 10.1016/j.ajog.2021.06.078 -
Archives of Medical Science : AMS 2022The role of low-dose aspirin combined with low-molecular-weight heparin (LMWH) in the treatment of preeclampsia (PE) remains unclear. We aimed to assess the efficacy and... (Review)
Review
INTRODUCTION
The role of low-dose aspirin combined with low-molecular-weight heparin (LMWH) in the treatment of preeclampsia (PE) remains unclear. We aimed to assess the efficacy and safety of low-dose aspirin combined with LMWH in PE treatment, to provide evidence for clinical PE management.
MATERIAL AND METHODS
We searched PubMed and other databases for randomized controlled trials (RCTs) on the effects and safety of low-dose aspirin and LMWH in the treatment of PE up to January 31, 2021. Two researchers strictly followed the inclusion and exclusion criteria to independently conduct the literature screening, data extraction and quality evaluation. We used RevMan 5.3 statistical software for synthesized analysis.
RESULTS
A total of 8 RCTs involving 861 patients were included. The synthesized outcome indicated that the differences in systolic blood pressure (MD = -10.61, 95% CI: -13.19 - -8.02), diastolic blood pressure (MD = -9.24, 95% CI: -14.49- -4.00), 24-hour urinary protein (MD = -2.24, 95% CI: -3.97- -0.50), prothrombin time (MD = 1.42, 95% CI: 0.53-2.32), activated partial thromboplastin time (MD = 2.91, 95% CI: 2.06-3.75), FIB (MD = -1.24, 95% CI: -1.32- -1.15), and adverse perinatal outcomes (MD = 0.41, 95% CI: 0.20-0.85) between the two groups were statistically significant (all < 0.05), while the difference in the adverse reactions of pregnant women (MD = 0.44, 95% CI: 0.18-1.10) between the two groups was not statistically significant ( = 0.08). No publication bias was detected in all the synthesized outcomes (all > 0.05).
CONCLUSIONS
Low-dose aspirin combined with LMWH treatment of PE may be advantageous to improve blood pressure, 24-hour proteinuria and coagulation function, and it may reduce the adverse reactions in pregnant women without increasing adverse perinatal outcomes.
PubMed: 36457979
DOI: 10.5114/aoms/136518 -
Acta Obstetricia Et Gynecologica... Sep 2017There is no accepted consensus on thromboprophylaxis in relation to in vitro fertilization (IVF). We aimed to study the frequency of thromboembolism and to assess... (Review)
Review
INTRODUCTION
There is no accepted consensus on thromboprophylaxis in relation to in vitro fertilization (IVF). We aimed to study the frequency of thromboembolism and to assess thromboprophylaxis in relation to IVF.
MATERIAL AND METHODS
We performed a systematic review. All study designs were accepted except single case reports. Language of included articles was restricted to English.
RESULTS
Of 338 articles, 21 relevant articles (nine cohort studies, six case-control studies, three case series, and three reviews of case series) were identified. The antepartum risk of venous thromboembolism (VTE) after IVF is doubled (odds ratio 2.18, 95% CI 1.63-2.92), compared with the background pregnant population. This is due to a 5- to 10-fold increased risk during the first trimester in IVF pregnancies, in turn related to a very high risk of VTE after ovarian hyperstimulation syndrome (OHSS), i.e. up to a 100-fold increase, or an absolute risk of 1.7%. The interval from embryo transfer to VTE was 3-112 days and the interval from embryo transfer to arterial thromboembolism was 3-28 days. No robust study on thromboprophylaxis was found.
CONCLUSIONS
The antepartum risk of VTE after IVF is doubled, compared with the background pregnant population, and is in turn related to a very high risk of VTE after OHSS in the first trimester. We recommend that IVF patients with OHSS be prescribed low-molecular-weight heparin during the first trimester, whereas other IVF patients should be given thromboprophylaxis based on the same risk factors as other pregnant women.
Topics: Female; Fertilization in Vitro; Humans; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Hematologic; Sweden; Venous Thromboembolism
PubMed: 28382684
DOI: 10.1111/aogs.13147 -
Orthopaedics & Traumatology, Surgery &... Apr 2023Direct oral anticoagulants (DOACs) are recommended as a possible pharmacologic venous thromboembolism (VTE) prophylaxis in patients undergoing total hip arthroplasty... (Meta-Analysis)
Meta-Analysis Review
The effectiveness and safety of direct oral anticoagulants compared to conventional pharmacologic thromboprophylaxis in hip fracture patients: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Direct oral anticoagulants (DOACs) are recommended as a possible pharmacologic venous thromboembolism (VTE) prophylaxis in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, current guidelines did not introduce recommendations for administration of DOACs as an option for pharmacologic VTE prophylaxis in patients undergoing hip fracture surgery (HFS). The purpose of this study is to compare the effectiveness and safety of DOACs administered for pharmacologic VTE prophylaxis in patients undergoing HFS to conventional pharmacologic VTE prophylaxis, as well as mortality between these thromboprophylaxis medications.
METHODS
We performed a systematic review of multiple electronic databases for randomized controlled trials (RCTs) including patients who were subjected to HFS and prescribed either DOACs as pharmacologic VTE prophylaxis or a conventional VTE prophylaxis drug. We conducted a meta-analysis comparing effectiveness, safety and mortality of these agents between the patient groups studied. Three endpoints were studied. The first one regarding the effectiveness of the agents included clinical manifestations of VTE. The second one regarding the safety of the agents included clinical presentation of bleeding. The latter endpoint studied was mortality of patient groups studied. We generated forest plots to depict the relative risk of the above clinical manifestations between the two studied patient groups and to investigate if there is statistical significance for each patient group to present any of these clinical manifestations. Additionally, we calculated the inconsistency (I) statistic and assessed the risk of bias of RCTs included in our meta-analysis by using the modified Cochrane collaboration tool.
RESULTS
We selected 2 RCTs in this review including 279 patients totally. Patients of control groups in both eligible studies were administered enoxaparin, which is a low molecular weight heparin (LMWH). The meta-analysis found no statistically significant difference between patients prescribed DOACs and patients prescribed LMWH for VTE (95% CI 0.19 to 1.13, RR=0.46, p=0.09), deep vein thrombosis (DVT) (95% CI 0.21 to 1.32, RR=0.53, p=0.17) and pulmonary embolism (PE) (95% CI 0.03 to 3.12, RR=0.33, p=0.33), major bleeding events (95% CI 0.57 to 1.78, RR=1.01, p=0.97), minor bleeding events (95% CI 0.72 to 1.64, RR=1.09, p=0.69), all bleeding events (95% CI 0.79 to 1.38, RR=1.05, p=0.74) and mortality (95% CI 0.01 to 8.0, RR=0.33, p=0.5). The major risk of bias of the selected RCTs was the fact that either the researchers or the patients could have knowledge whether the latter were administered DOACs or LMWHs.
DISCUSSION
DOACs are not inferior compared to LMWHs regarding their effectiveness, safety and mortality in patients subjected to HFS. Further studies with larger patient samples should be conducted in the future, so that safer results and conclusions could be reached.
Topics: Humans; Anticoagulants; Venous Thromboembolism; Randomized Controlled Trials as Topic; Heparin, Low-Molecular-Weight; Enoxaparin; Hemorrhage; Hip Fractures
PubMed: 35817368
DOI: 10.1016/j.otsr.2022.103364 -
Knee Surgery, Sports Traumatology,... Sep 2022Total knee arthroplasty (TKA) has experienced exponential growth over the last decade, including increasingly younger patients with high functional demands. Highly... (Meta-Analysis)
Meta-Analysis Review
Comparable results between crosslinked polyethylene and conventional ultra-high molecular weight polyethylene implanted in total knee arthroplasty: systematic review and meta-analysis of randomised clinical trials.
PURPOSE
Total knee arthroplasty (TKA) has experienced exponential growth over the last decade, including increasingly younger patients with high functional demands. Highly crosslinked polyethylene (HXLPE) has been proven effective in reducing osteolysis and loosening revisions while improving long-term survival and performance in total hip arthroplasty; nevertheless, this superiority is not demonstrated in TKA. The aim of this systematic review and meta-analysis was to examine whether HXLPE improved overall survival and postoperative functional and radiological outcomes compared to conventional polyethylene (CPE) in TKA.
METHODS
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a literature search of five databases (PubMed, Medline, Scopus, Science Direct and Embase) was made. A PICOS model was performed. The initial screening identified 2541 studies. Each eligible clinical article was analysed according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence (LoE). Only randomised clinical trials (RCTs) of LoE 1 and 2 were included. The methodological quality of the articles was assessed using the Risk of Bias 2 (RoB 2) tool.
RESULTS
Six clinical studies were included in the final study. This systematic review and meta-analysis were registered on the International Prospective Register of Systematic Reviews (PROSPERO). A total of 2285 knees were included. Eight outcomes (total reoperations, reoperations for prosthesis loosening and infections, radiolucent lines, osteolysis, mechanical failure, postoperative KSS knee score and function score) were analysed. For none of them, a statistically significant difference was found about the superiority of HXLPE over CPE (p > 0.05).
CONCLUSIONS
There were no statistically significant differences between HXLPE and CPE for TKA concerning clinical, radiological, and functional outcomes; nevertheless, HXLPE did not show higher failure rates or complications and can be safely used for TKA.
LEVEL OF EVIDENCE
II.
Topics: Arthroplasty, Replacement, Knee; Humans; Knee Prosthesis; Osteolysis; Polyethylene; Polyethylenes; Prosthesis Design; Prosthesis Failure; Randomized Controlled Trials as Topic
PubMed: 35182171
DOI: 10.1007/s00167-022-06879-7 -
Cureus Jun 2023Osteoarthritis is a chronic degenerative joint disease that affects weight-bearing joints. Low molecular weight fraction of 5% (LMWF-5A) human serum albumin is an... (Review)
Review
The Efficacy and Safety of Intra-articular Low Molecular Weight Fraction of Human Serum Albumin for the Management of Moderate to Moderately Severe Knee Osteoarthritis: A Systematic Review and Meta-Analysis.
Osteoarthritis is a chronic degenerative joint disease that affects weight-bearing joints. Low molecular weight fraction of 5% (LMWF-5A) human serum albumin is an intra-articular injection that emerged for the treatment of knee osteoarthritis. The aim of this review is to assess the efficacy and safety of LMWF-5A versus placebo through a systematic review and meta-analysis. The Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), EBSCO, and ClinicalTrials.gov registry databases were utilized to search for studies. Only randomized controlled trials (RCTs) that evaluated the efficacy of LMWF-5A versus placebo were included. Efficacy endpoints were represented by Western Ontario and McMaster Universities Arthritis Index (WOMAC) A and C scores for pain and function, respectively. Serious adverse events (SAEs), non-serious adverse events (NSAEs), and mortality rates were used to evaluate the safety of the drug. The revised Cochrane risk of bias tool was used for the risk of bias assessment. Seven RCTs (n=2939) that met the inclusion criteria were included. The meta-analysis did not find significant improvement in pain (WOMAC A) (standardized mean difference (SMD)= -0.01, 95% confidence interval (CI) -0.10 - 0.09, P=0.87, I²=30%). Additionally, no significant change in function was noted (WOMAC C) (SMD=0.01, 95% CI -0.08 - 0.10, P=0.87, I²=22%). The pooled analysis did not find a significant difference between LMWF-5A and placebo regarding the incidence of joint swelling (P=0.84), joint stiffness (P=0.53), arthralgia (P=0.53), extremity pain (P=0.45), NSAEs (P=0.21), SAEs (P=0.92), or mortality (P=1.00). However, the subgroup analysis showed a significant reduction of 42% in NSAEs upon administration of 10 mL of LMWF-5A (risk ratio (RR)=0.58, 95% CI 0.35-0.97, P=0.04). In summary, our meta-analysis did not find significant differences between LMWF-5A and placebo regarding the incidence of NSAEs, SAEs, or mortality. On the other hand, LMWF-5A did not demonstrate superiority over saline in terms of efficacy. Therefore, it is not an effective drug for managing knee osteoarthritis.
PubMed: 37529519
DOI: 10.7759/cureus.41240 -
World Journal of Surgical Oncology Feb 2024Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients.
MATERIALS AND METHODS
A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386).
RESULTS
We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC.
CONCLUSION
DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.
Topics: Humans; Heparin, Low-Molecular-Weight; Anticoagulants; Venous Thromboembolism; Hemorrhage; Neoplasms
PubMed: 38403630
DOI: 10.1186/s12957-024-03341-5 -
The Spine Journal : Official Journal of... Jun 2023Complications such as pressure sores, pulmonary infection, urinary tract infection (UTI), and venous thromboembolism (VTE) are common after spinal cord injury (SCI).... (Review)
Review
BACKGROUND CONTEXT
Complications such as pressure sores, pulmonary infection, urinary tract infection (UTI), and venous thromboembolism (VTE) are common after spinal cord injury (SCI). These have serious consequences for patients' physical, social, and vocational well-being. Several authoritative organizations have developed guidelines for managing these complications after SCI.
PURPOSE
We aim to systematically review and appraise guidelines on the management of four common complications (pressure sores, pulmonary infection, UTI, and VTE) after SCI as well as to summarize relevant recommendations and assess the quality of their supporting evidence.
DESIGN
Systematic review.
METHODS
We searched Medline, Embase, Cochrane, and Web of Science, as well as guideline-specific databases (eg, National Guideline Clearinghouse) and Google Scholar, from January 2000 to January 2022. We included the most updated guidelines developed by specific authoritative organizations. We evaluated the included guidelines using the Appraisal of Guidelines for Research and Evaluation 2nd edition instrument, which measures six domains (eg, applicability). Recommendations extracted from guidelines were categorized as for, against, or neither for nor against. An evidence assessment was adopted to classify the quality of supporting evidence as poor, fair, or good.
RESULTS
Eleven guidelines from 2005 to 2020 were included, all of which, among the six domains, scored lowest in the domain of applicability. For pressure sores, guidelines recommended for skin inspection, repositioning, and the use of pressure reduction equipment as preventive measures and dressings, debridement, and surgery as treatment measures. For pulmonary infection, guidelines recommended for physical (eg, the use of an insufflation-exsufflation device) and pharmacological measures (eg, the use of bronchodilators). For UTI, guidelines recommended for antibiotics as a treatment measure but recommended against cranberries, methenamine salts, and acidification or alkalinization agents as preventive measures. For VTE prophylaxis, five guidelines recommended for low molecular weight heparin (LMWH). Three guidelines recommended against unfractionated heparin, whereas one guideline recommended for it. Most of the supporting evidence was of poor quality (130/139), and the rest was of fair quality (9/139).
CONCLUSIONS
For pressure sores, pulmonary infection, and UTI, evidence of poor to fair quality indicated consistent recommendations for prevention and treatment measures. For VTE, LMWH was consistently recommended, whereas recommendations on the use of unfractionated heparin were controversial.
Topics: Humans; Heparin; Heparin, Low-Molecular-Weight; Venous Thromboembolism; Pressure Ulcer; Spinal Cord Injuries; Anticoagulants
PubMed: 36521679
DOI: 10.1016/j.spinee.2022.12.001 -
Critical Care Medicine Mar 2015To evaluate the efficacy and safety of heparin in patients with sepsis, septic shock, or disseminated intravascular coagulation associated with infection. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy and safety of heparin in patients with sepsis, septic shock, or disseminated intravascular coagulation associated with infection.
DESIGN
Systematic review and metaanalysis.
DATA SOURCES
Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Global Health, Scopus, Web of Science, the International Clinical Trials Registry Platform (inception to April 2014), conference proceedings, and reference lists of relevant articles.
STUDY SELECTION AND DATA EXTRACTION
Two reviewers independently identified and extracted trial-level data from randomized trials investigating unfractionated or low molecular heparin administered to patients with sepsis, severe sepsis, septic shock, or disseminated intravascular coagulation associated with infection. Internal validity was assessed in duplicate using the Risk of Bias tool. The strength of evidence was assessed in duplicate using Grading of Recommendations Assessment, Development, and Evaluation methodology. Our primary outcome was mortality. Safety outcomes included hemorrhage, transfusion, and thrombocytopenia.
MEASUREMENTS AND MAIN RESULTS
We included nine trials enrolling 2,637 patients. Eight trials were of unclear risk of bias and one was classified as having low risk of bias. In trials comparing heparin to placebo or usual care, the risk ratio for death associated with heparin was 0.88 (95% CI, 0.77-1.00; I2 = 0%; 2,477 patients; six trials; moderate strength of evidence). In trials comparing heparin to other anticoagulants, the risk ratio for death was 1.30 (95% CI, 0.78-2.18; I2 = 0%; 160 patients; three trials; low strength of evidence). In trials comparing heparin to placebo or usual care, major hemorrhage was not statistically significantly increased (risk ratio, 0.79; 95% CI, 0.53-1.17; I2 = 0%; 2,392 patients; three trials). In one small trial of heparin compared with other anticoagulants, the risk of major hemorrhage was significantly increased (2.14; 95% CI, 1.07-4.30; 48 patients). Important secondary and safety outcomes, including minor bleeding, were sparsely reported.
CONCLUSIONS
Heparin in patients with sepsis, septic shock, and disseminated intravascular coagulation associated with infection may be associated with decreased mortality; however, the overall impact remains uncertain. Safety outcomes have been underreported and require further study. Increased major bleeding with heparin administration cannot be excluded. Large rigorous randomized trials are needed to evaluate more carefully the efficacy and safety of heparin in patients with sepsis, severe sepsis, and septic shock.
Topics: Anticoagulants; Blood Transfusion; Disseminated Intravascular Coagulation; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Randomized Controlled Trials as Topic; Sepsis; Shock, Septic; Thrombocytopenia
PubMed: 25493972
DOI: 10.1097/CCM.0000000000000763 -
Taiwanese Journal of Obstetrics &... Jan 2021To assess the roles of the low molecular weight heparin (LMWH) on recurrent pregnancy loss (RPL). The relevant studies of all randomized controlled trials (RCTs) were... (Meta-Analysis)
Meta-Analysis
To assess the roles of the low molecular weight heparin (LMWH) on recurrent pregnancy loss (RPL). The relevant studies of all randomized controlled trials (RCTs) were retrieved, and the systematic evaluation was conducted. PubMed, Embase, and Cochrane library databases were searched by using keywords, including low-molecular-weight heparin or LMWH, and recurrent miscarriage or recurrent pregnancy loss in pregnant women from their earliest data to February 2020. Two investigators independently evaluated eligibility. Risk ratios (RRs) and their corresponding 95% confidence interval (CI) were determined. To pool the results, this meta-analysis was performed using random-effect model due to the high heterogeneity among these eight studies. A total of eight RCTs involving 1854 participants were included in the meta-analysis involving 963 patients with RPL who were prescribed LMWH (enoxaparin, tinzaparin, or dalteparin) alone and 891 patients who were treated with no LMWH interventions (placebo, folic acid or non-treatment) were compared. Pooled data from the remaining eight RCTs showed the differences between intervention groups and control groups. Compared with control groups, LMWH had significantly improved live births (RR,1.19; 95%CI, 1.03 to 1.38; P = 0.02), and reduced miscarriage rates (RR, 0.62; 95%CI, 0.43 to 0.91; P = 0.01). The study suggested that LMWH could improve the live births and reduce the miscarriage rates of RPL. Therefore, LMWH might be a good treatment choice for women with unexplained PRL.
Topics: Abortion, Habitual; Adult; Cardiovascular Agents; Female; Heparin, Low-Molecular-Weight; Humans; Live Birth; Pregnancy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33494980
DOI: 10.1016/j.tjog.2020.11.001