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American Journal of Obstetrics and... Aug 2023This study aimed to describe the characteristics of fetal demise after SARS-CoV-2 infections and clarify whether it is associated with clinical severity, placental... (Review)
Review
OBJECTIVE
This study aimed to describe the characteristics of fetal demise after SARS-CoV-2 infections and clarify whether it is associated with clinical severity, placental lesions, or malformations or due to actual fetal infections.
DATA SOURCES
PubMed and Web of Science databases were searched between December 1, 2019, and April 30, 2022.
STUDY ELIGIBILITY CRITERIA
Cohort, cross-sectional, and case-control studies and case series or case reports describing stillbirths or late miscarriages (ie, pregnancy loss occurring between 14 and 22 weeks of gestation, before and after the onset of labor) from mothers with SARS-CoV-2 infection during pregnancy (demonstrated by at least 1 positive real-time reverse transcription-polymerase chain reaction from nasopharyngeal swabs and/or SARS-CoV-2 placental infection). No language restriction was applied; cases with other causes possibly explaining the fetal demise were excluded.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology guidelines were followed. The quality of the case series and case reports was evaluated using the specific Mayo Clinic Evidence-Based Practice Center tool. Maternal and clinical fetal data and placental and fetal virology and histology findings were collected. Data were summarized with descriptive statistics using the World Health Organization criteria to classify disease severity and fetal-neonatal infections.
RESULTS
Data from 184 mothers and 190 fetuses were analyzed. No clear link to maternal clinical severity or fetal malformation was evident. Approximately 78% of fetal demise cases occurred during the second and third trimesters of pregnancy, approximately 6 to 13 days after the diagnosis of SARS-CoV-2 infection or the onset of symptoms. Most placentas (88%) were positive for SARS-CoV-2 or presented the histologic features of placentitis (massive fibrin deposition and chronic intervillositis) previously observed in transplacentally transmitted infections (85%-91%). Of note, 11 fetuses (5.8%) had a confirmed in utero transmitted SARS-CoV-2 infection, and 114 fetuses (60%) had a possible in utero transmitted SARS-CoV-2 infection.
CONCLUSION
The synthesis of available data showed that fetal demise generally occurs a few days after the infection with histologic placental inflammatory lesions associated with transplacental SARS-CoV-2 transmission and eventually causing placental insufficiency.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Abortion, Spontaneous; COVID-19; Cross-Sectional Studies; Fetal Death; Infectious Disease Transmission, Vertical; Placenta; Pregnancy Complications, Infectious; SARS-CoV-2; Stillbirth
PubMed: 36706855
DOI: 10.1016/j.ajog.2023.01.019 -
Human Reproduction (Oxford, England) May 2023What is the risk of miscarriage among pregnant women who received any of the COVID-19 vaccines? (Meta-Analysis)
Meta-Analysis
STUDY QUESTION
What is the risk of miscarriage among pregnant women who received any of the COVID-19 vaccines?
SUMMARY ANSWER
There is no evidence that COVID-19 vaccines are associated with an increased risk of miscarriage.
WHAT IS KNOWN ALREADY
In response to the COVID-19 pandemic, the mass roll-out of vaccines helped to boost herd immunity and reduced hospital admissions, morbidity, and mortality. Still, many were concerned about the safety of vaccines for pregnancy, which may have limited their uptake among pregnant women and those planning a pregnancy.
STUDY DESIGN, SIZE, DURATION
For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception until June 2022 using a combination of keywords and MeSH terms.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We included observational and interventional studies that enrolled pregnant women and evaluated any of the available COVID-19 vaccines compared to placebo or no vaccination. We primarily reported on miscarriage in addition to ongoing pregnancy and/or live birth.
MAIN RESULTS AND THE ROLE OF CHANCE
We included data from 21 studies (5 randomized trials and 16 observational studies) reporting on 149 685 women. The pooled rate of miscarriage among women who received a COVID-19 vaccine was 9% (n = 14 749/123 185, 95% CI 0.05-0.14). Compared to those who received a placebo or no vaccination, women who received a COVID-19 vaccine did not have a higher risk of miscarriage (risk ratio (RR) 1.07, 95% CI 0.89-1.28, I2 35.8%) and had comparable rates for ongoing pregnancy or live birth (RR 1.00, 95% CI 0.97-1.03, I2 10.72%).
LIMITATIONS, REASONS FOR CAUTION
Our analysis was limited to observational evidence with varied reporting, high heterogeneity and risk of bias across included studies, which may limit the generalizability and confidence in our findings.
WIDER IMPLICATIONS OF THE FINDINGS
COVID-19 vaccines are not associated with an increase in the risk of miscarriage or reduced rates of ongoing pregnancy or live birth among women of reproductive age. The current evidence remains limited and larger population studies are needed to further evaluate the effectiveness and safety of COVID-19 vaccination in pregnancy.
STUDY FUNDING/COMPETING INTEREST(S)
No direct funding was provided to support this work. M.P.R. was funded by the Medical Research Council Centre for Reproductive Health Grant No: MR/N022556/1. B.H.A.W. hold a personal development award from the National Institute of Health Research in the UK. All authors declare no conflict of interest.
REGISTRATION NUMBER
CRD42021289098.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; COVID-19 Vaccines; Pregnancy Rate; Pandemics; COVID-19; Live Birth; Observational Studies as Topic
PubMed: 36794918
DOI: 10.1093/humrep/dead036 -
Human Reproduction Update May 2019First-trimester miscarriage affects up to a quarter of women worldwide. With many competing treatment options available, there is a need for a comprehensive evidence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
First-trimester miscarriage affects up to a quarter of women worldwide. With many competing treatment options available, there is a need for a comprehensive evidence synthesis.
OBJECTIVES AND RATIONALE
We conducted a systematic review and network meta-analysis to assess the effectiveness and safety of treatment options for first-trimester miscarriage: expectant management (EXP), sharp dilation and curettage (D+C), electric vacuum aspiration (EVAC), manual vacuum aspiration (MVA), misoprostol alone (MISO), mifepristone+misoprostol (MIFE+MISO) and misoprostol plus electric vacuum aspiration (MISO+EVAC).
SEARCH METHODS
We searched MEDLINE, Embase, CINAHL, AMED and Cochrane Library from inception till June 2018. We included randomized trials of women with first-trimester miscarriage (<14 weeks gestation) and conducted a network meta-analysis generating both direct and mixed evidence on the effectiveness and side effects of available treatment options. The primary outcome was complete evacuation of products of conception. We assessed the risk of bias and the global network inconsistency. We compared the surface under the cumulative ranking curve (SUCRA) for each treatment.
OUTCOMES
A total of 46 trials (9250 women) were included. The quality of included studies was overall moderate with some studies demonstrating a high risk of bias. We detected unexplained inconsistency in evidence loops involving MIFE+MISO and adjusted for it. EXP had lower effectiveness compared to other treatment options. The effectiveness of medical treatments was similar compared to surgery. Mixed evidence of low confidence suggests increased effectiveness for MIFE+MISO compared to MISO alone (RR 1.49, 95% CI: 1.09-2.03). Side effects were similar among all options. Fewer women needed analgesia following EVAC compared to MISO (RR for MISO 0.43, 95% CI: 0.27-0.68) and in the EXP group compared to EVAC (RR 2.07, 95% CI: 1.25-3.41). MVA had higher ranking (low likelihood) for post-treatment infection and serious complications (SUCRA 87.6 and 79.2%, respectively) with the highest likelihood for post-treatment satisfaction (SUCRA 98%).
WIDER IMPLICATIONS
Medical treatments for first-trimester miscarriage have similar effectiveness and side effects compared to surgery. The addition of MIFE could increase the effectiveness of MISO and reduce side effects, although evidence is limited due to inconsistency. EXP has lower effectiveness compared to other treatment options.Systematic review registration: Prospero CRD42016048920.
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Spontaneous; Female; Gestational Age; Humans; Mifepristone; Misoprostol; Network Meta-Analysis; Pregnancy; Pregnancy Trimester, First; Vacuum Curettage
PubMed: 30753490
DOI: 10.1093/humupd/dmz002 -
BJOG : An International Journal of... Jan 2019There is a substantial body of research evaluating ways to prevent and manage miscarriage, but all studies do not report on the same outcomes.
BACKGROUND
There is a substantial body of research evaluating ways to prevent and manage miscarriage, but all studies do not report on the same outcomes.
OBJECTIVE
To review systematically, outcomes reported in existing miscarriage trials.
SEARCH STRATEGY
MEDLINE, Embase, CINAHL, and Cochrane were searched from inception until January 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) reporting prevention or management of miscarriage. Miscarriage was defined as a pregnancy loss in the first trimester.
DATA COLLECTION AND ANALYSIS
Data about the study characteristics, primary, and secondary outcomes were extracted.
MAIN RESULTS
We retrieved 1553 titles and abstracts, from which 208 RCTs were included. For prevention of miscarriage, the most commonly reported primary outcome was live birth and the top four reported outcomes were pregnancy loss/stillbirth (n = 112), gestation of birth (n = 68), birth dimensions (n = 65), and live birth (n = 49). For these four outcomes, 58 specific measures were used for evaluation. For management of miscarriage, the most commonly reported primary outcome was efficacy of treatment. The top four reported outcomes were bleeding (n = 186), efficacy of miscarriage treatment (n = 105), infection (n = 97), and quality of life (n = 90). For these outcomes, 130 specific measures were used for evaluation.
CONCLUSIONS
Our review found considerable variation in the reporting of primary and secondary outcomes along with the measures used to assess them. There is a need for standardised patient-centred clinical outcomes through the development of a core outcome set; the work from this systematic review will form the foundation of the core outcome set for miscarriage.
TWEETABLE ABSTRACT
There is disparity in the reporting of outcomes and the measures used to assess them in miscarriage trials.
Topics: Abortion, Spontaneous; Female; Humans; Live Birth; Outcome and Process Assessment, Health Care; Pregnancy; Randomized Controlled Trials as Topic; Research Design; Stillbirth
PubMed: 30461160
DOI: 10.1111/1471-0528.15528 -
Scandinavian Journal of Surgery : SJS :... Sep 2023Non-obstetric surgery is fairly common in pregnant women. We performed a systematic review to update data on non-obstetric surgery in pregnant women. The aim of this... (Review)
Review
BACKGROUND AND OBJECTIVE
Non-obstetric surgery is fairly common in pregnant women. We performed a systematic review to update data on non-obstetric surgery in pregnant women. The aim of this review was to evaluate the effects of non-obstetric surgery during pregnancy on pregnancy, fetal and maternal outcomes.
METHODS
A systematic literature search of MEDLINE and Scopus was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search span was from January 2000 to November 2022. Thirty-six studies matched the inclusion criteria, and 24 publications were identified through reference mining; 60 studies were included in this review. Outcome measures were miscarriage, stillbirth, preterm birth, low birth weight, low Apgar score, and infant and maternal morbidity and mortality rates.
RESULTS
We obtained data for 80,205 women who underwent non-obstetric surgery and data for 16,655,486 women who did not undergo surgery during pregnancy. Prevalence of non-obstetric surgery was between 0.23% and 0.74% (median 0.37%). Appendectomy was the most common procedure with median prevalence of 0.10%. Near half (43%) of the procedures were performed during the second trimester, 32% during the first trimester, and 25% during the third trimester. Half of surgeries were scheduled, and half were emergent. Laparoscopic and open techniques were used equally for abdominal cavity. Women who underwent non-obstetric surgery during pregnancy had increased rate of stillbirth (odds ratio (OR) 2.0) and preterm birth (OR 2.1) compared to women without surgery. Surgery during pregnancy did not increase rate of miscarriage (OR 1.1), low 5 min Apgar scores (OR 1.1), the fetus being small for gestational age (OR 1.1) or congenital anomalies (OR 1.0).
CONCLUSIONS
The prevalence of non-obstetric surgery has decreased during last decades, but still two out of 1000 pregnant women have scheduled surgery during pregnancy. Surgery during pregnancy increases the risk of stillbirth, and preterm birth. For abdominal cavity surgery, both laparoscopic and open approaches are feasible.
Topics: Infant; Pregnancy; Infant, Newborn; Female; Humans; Pregnancy Outcome; Premature Birth; Stillbirth; Abortion, Spontaneous; Fetus
PubMed: 37329286
DOI: 10.1177/14574969231175569 -
Canadian Journal of Dietetic Practice... Mar 2024Previous systematic reviews have reported on the relationship between eating disorders (EDs) and birth outcomes, but there are no existing meta-analyses on this topic.... (Meta-Analysis)
Meta-Analysis Review
Previous systematic reviews have reported on the relationship between eating disorders (EDs) and birth outcomes, but there are no existing meta-analyses on this topic. This systematic review and meta-analysis examines the association between lifetime maternal EDs, including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) with low birth weight (LBW), preterm birth (PTB), small for gestational age (SGA), large for gestational age (LGA), and miscarriage. Four databases were systematically searched for quantitative literature on maternal EDs that preceded birth outcomes. Eighteen studies met the inclusion criteria and were included in the review. The meta-analyses included 6 studies on miscarriage, 11 on PTB, 4 on LBW, 9 on SGA, and 4 on LGA. The Mantel-Haenszel random effects model was used to test the associations between EDs and birth outcomes. The results showed significant positive associations between AN and LBW (OR 1.74, 95% confidence interval (CI) 1.49, 2.03), AN and SGA (OR 1.39, 95% CI 1.17, 1.65), BN and PTB (OR 1.19, 95% CI 1.04, 1.36), and BED and LGA (OR 1.43 95% CI 1.18, 1.72). EDs were not significantly correlated with miscarriage. These findings reveal the importance of screening for and treating EDs in pregnant women.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Abortion, Spontaneous; Premature Birth; Feeding and Eating Disorders; Infant, Low Birth Weight; Infant, Small for Gestational Age
PubMed: 38032141
DOI: 10.3148/cjdpr-2023-019 -
Acta Obstetricia Et Gynecologica... Dec 2020Miscarriage, a spontaneous pregnancy loss at <24 weeks' gestation, is a common complication of pregnancy but the etiologies of miscarriage and recurrent miscarriage are... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Miscarriage, a spontaneous pregnancy loss at <24 weeks' gestation, is a common complication of pregnancy but the etiologies of miscarriage and recurrent miscarriage are not fully understood. Other obstetric conditions such as preeclampsia and preterm birth, which may share similar pathophysiology to miscarriage, exhibit familial patterns, suggesting inherited predisposition to these conditions. Parental genetic polymorphisms have been associated with unexplained miscarriage, suggesting there could be a genetically inherited predisposition to miscarriage. This systematic review and meta-analysis of observational studies aimed to assess the association between family history of miscarriage and the risk of miscarriage in women.
MATERIAL AND METHODS
A systematic review and meta-analysis of observational studies was carried out in accordance with Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Electronic searches using databases (MEDLINE, EMBASE and CINAHL) were carried out to identify eligible studies from 1946 until 2019. Observational studies (cohort or case-control) were included. Human studies only were included. Participants were women of reproductive age. Exposure was a family history of one or more miscarriage(s). The primary outcome was miscarriage in women. Abstracts were screened and data were extracted by two independent reviewers. Study quality was assessed using Critical Appraisal Skills Program (CASP) tools. Data were pooled from individual studies using the Mantel-Haenszel method to produce pooled odds ratios (ORs) with 95% confidence intervals (95% CI). Systematic review registration number (PROSPERO): CRD42019127950.
RESULTS
Thirteen studies were identified in the systematic review; 10 were eligible for inclusion in the meta-analysis. Twelve studies reported an association between family history of miscarriage and miscarriage in women. In all, 41 287 women were included in the meta-analysis. Women who miscarried were more likely to report a family history of miscarriage (pooled unadjusted OR 1.90, 95% CI 1.37-2.63). Overall study quality and size varied, with few adjusting for confounding factors. Results should be interpreted with caution as the associations presented are based on unadjusted analyses only.
CONCLUSIONS
Women who miscarry may be more likely to have a family history of miscarriage. Further research is required to confirm or refute the findings.
Topics: Abortion, Habitual; Causality; Female; Humans; Medical History Taking; Observational Studies as Topic; Pregnancy; Risk Assessment
PubMed: 32557529
DOI: 10.1111/aogs.13940 -
The Science of the Total Environment Jan 2024Prenatal exposure to metal mixtures is associated with adverse pregnancy and birth outcomes like low birth weight, preterm birth, and small for gestational age. However,... (Review)
Review
BACKGROUND
Prenatal exposure to metal mixtures is associated with adverse pregnancy and birth outcomes like low birth weight, preterm birth, and small for gestational age. However, prior studies have used individual metal analysis, lacking real-life exposure scenarios.
OBJECTIVES
This systematic review aims to evaluate the strength and consistency of the association between metal mixtures and pregnancy and birth outcomes, identify research gaps, and inform future studies and policies in this area.
METHODS
The review adhered to the updated Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) checklist, along with the guidelines for conducting systematic reviews and meta-analyses of observational studies of etiology (COSMOS-E). Our data collection involved searching the PubMed, MEDLINE, and SCOPUS databases. We utilized inclusion criteria to identify relevant studies. These chosen studies underwent thorough screening and data extraction procedures. Methodological quality evaluations were conducted using the NOS framework for cohort and case-control studies, and the AXIS tool for cross-sectional studies.
RESULTS
The review included 34 epidemiological studies, half of which focused on birth weight, and the others investigated neonate size, preterm birth, small for gestational age, miscarriage, and placental characteristics. The findings revealed significant associations between metal mixtures (including mercury (Hg), nickel (Ni), arsenic (As), cadmium (Cd), manganese (Mn), cobalt (Co), lead (Pb), zinc (Zn), barium (Ba), cesium (Cs), copper (Cu), selenium (Se), and chromium (Cr)) and adverse pregnancy and birth outcomes, demonstrating diverse effects and potential interactions.
CONCLUSION
In conclusion, this review consistently establishes connections between metal exposure during pregnancy and adverse consequences for birth weight, gestational age, and other vital birth-related metrics. This review further demonstrates the need to apply mixture methods with caution but also shows that they can be superior to traditional approaches. Further research is warranted to deeper understand the underlying mechanisms and to develop effective strategies for mitigating the potential risks associated with metal mixture exposure during pregnancy.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Abortion, Spontaneous; Birth Weight; Cross-Sectional Studies; Fetal Growth Retardation; Mercury; Metals; Placenta; Premature Birth
PubMed: 37963536
DOI: 10.1016/j.scitotenv.2023.168380 -
American Journal of Obstetrics &... Jan 2023The World Health Organization has recently declared a monkeypox outbreak as a public health emergency of global concern. The main aim of this systematic review was to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The World Health Organization has recently declared a monkeypox outbreak as a public health emergency of global concern. The main aim of this systematic review was to ascertain the maternal and perinatal outcomes of pregnancies complicated by monkeypox infection.
DATA SOURCES
The Medline, Embase, and Cochrane databases were searched on June 25, 2022 utilizing combinations of the relevant medical subject heading terms, key words, and word variants for "monkeypox" and "pregnancy."
STUDY ELIGIBILITY CRITERIA
The search and selection criteria were restricted to the English language.
METHODS
The outcomes observed were miscarriage; intrauterine, neonatal, and perinatal death; preterm birth, vertical transmission, and maternal symptoms. A metaanalysis of proportions was used to analyze the data.
RESULTS
Four studies were included. All the cases in the present systematic review presented with symptoms and signs of monkeypox infection. There was no case of maternal death. Miscarriage occurred in 39% of cases (95% confidence interval, 0-89.0), whereas intrauterine fetal death occurred in 23.0% (95% confidence interval, 0-74.0) of cases. The overall incidence of late fetal and perinatal loss was 77.0% (95% confidence interval, 26.0-100), whereas only 23% (95% confidence interval, 0-74.0) of the included fetuses survived to birth. The incidence of preterm birth before 37 weeks of gestation was 8.0% (95% confidence interval, 0-62.0). Vertical transmission occurred in 62.0% (95% confidence interval, 3.0-100) of cases. When stratifying the analysis according to gestational age at infection, fetal loss was found to occur in 67.0% (95% confidence interval, 9.0-99.0) of cases with first-trimester infection and in 82.0% (95% confidence interval, 17.0-100) of those with second-trimester infection.
CONCLUSION
Monkeypox infection in pregnancy is associated with a high risk of perinatal loss and vertical transmission. The preliminary results from this systematic review affected by a very small number of included cases highlight the need for thorough maternal and fetal surveillance in pregnancies complicated by monkeypox infection.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Premature Birth; Abortion, Spontaneous; Gestational Age; Stillbirth; Fetal Death
PubMed: 36096413
DOI: 10.1016/j.ajogmf.2022.100747 -
BMJ Open Jan 2024Literature surrounding the association between antidepressant use during pregnancy and miscarriage is conflicting. We aimed to conduct a systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Literature surrounding the association between antidepressant use during pregnancy and miscarriage is conflicting. We aimed to conduct a systematic review and meta-analysis of studies among pregnant women regarding the association between exposure to antidepressants during pregnancy and the risk of miscarriage, compared with pregnant women not exposed to antidepressants.
DESIGN
We conducted a systematic review and meta-analysis of non-randomised studies.
DATA SOURCES
We searched Medline, Embase and PsychINFO up to 6 August 2023.
ELIGIBILITY CRITERIA AND OUTCOMES
Case-control, cohort and cross-sectional study designs were selected if they compared individuals exposed to any antidepressant class during pregnancy to comparator groups of either no antidepressant use or an alternate antidepressant.
DATA EXTRACTION AND SYNTHESIS
Effect estimates were extracted from selected studies and pooled using a random-effects meta-analysis. Risk of bias (RoB) was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool, and heterogeneity assessed using the I statistic. Subgroup analyses were used to explore antidepressant classes and the impact of confounding by indication.
RESULTS
1800 records were identified from the search, of which 29 were included in the systematic review and meta-analysis. The total sample included 5 671 135 individuals. Antidepressant users initially appeared to have a higher risk of miscarriage compared with unexposed individuals from the general population (summary effect estimate: 1.24, 95% CI 1.18 to 1.31, I=69.2%; number of studies (n)=29). However, the summary estimate decreased when comparing against unexposed individuals with maternal depression (1.16, 1.04 to 1.31; I=58.6%; n=6), suggesting confounding by indication may be driving the association. 22 studies suffered from serious RoB, and only two of the 29 studies were deemed at moderate RoB.
CONCLUSIONS
After accounting for maternal depression, there is little evidence of any association between antidepressant use during pregnancy and miscarriage. Instead, the results indicate the biasing impact of confounding by indication.
Topics: Humans; Female; Pregnancy; Abortion, Spontaneous; Cross-Sectional Studies; Antidepressive Agents
PubMed: 38272551
DOI: 10.1136/bmjopen-2023-074600