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Fertility and Sterility Feb 2017To investigate whether treatment with progestogens in the first trimester of pregnancy would decrease the incidence of miscarriage in women with a history of unexplained... (Meta-Analysis)
Meta-Analysis Review
Supplementation with progestogens in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials.
OBJECTIVE
To investigate whether treatment with progestogens in the first trimester of pregnancy would decrease the incidence of miscarriage in women with a history of unexplained recurrent miscarriage.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Women with a history of unexplained recurrent miscarriage.
INTERVENTION(S)
Randomized, controlled trials were identified by searching electronic databases. We included randomized, controlled trials comparing supplementation with progestogens (i.e., intervention group) in the first trimester of pregnancy with control (either placebo or no treatment) in women with a history of recurrent miscarriage. All types of progestogens, including natural P and synthetic progestins, were analyzed.
MAIN OUTCOME MEASURE(S)
The primary outcome was the incidence of miscarriage. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI).
RESULT(S)
Ten trials including 1,586 women with recurrent miscarriage were analyzed. Eight studies used placebo as control and were double-blind. Regarding the intervention, two RCTs used natural P, whereas the other eight studies used progestins: medroxyprogesterone, cyclopentylenol ether of progesterone, dydrogesterone, or 17-hydroxyprogesterone caproate. Pooled data from the 10 trials showed that women with a history of unexplained recurrent miscarriage who were randomized to the progestogens group in the first trimester and before 16 weeks had a lower risk of recurrent miscarriage (RR 0.72, 95% CI 0.53-0.97) and higher live birth rate (RR 1.07, 95% CI 1.02-1.15) compared with those who did not. No statistically significant differences were found in the other secondary outcomes, including preterm birth (RR 1.09, 95% CI 0.71-1.66), neonatal mortality (RR 1.80, 95% CI 0.44-7.34), and fetal genital abnormalities (RR 1.68, 95% CI 0.22-12.62).
CONCLUSION(S)
Our findings provide evidence that supplementation with progestogens may reduce the incidence of recurrent miscarriages and seem to be safe for the fetuses. Synthetic progestogens, including weekly IM 17-hydroxyprogesterone caproate, but not natural P, were associated with a lower risk of recurrent miscarriage. Given the limitations of the studies included in our meta-analysis, it is difficult to recommend route and dose of progestogen therapy. Further head-to-head trials of P types, dosing, and route of administration are required.
Topics: Abortion, Habitual; Chi-Square Distribution; Drug Administration Schedule; Female; Humans; Odds Ratio; Pregnancy; Pregnancy Trimester, First; Progestins; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 27887710
DOI: 10.1016/j.fertnstert.2016.10.031 -
Contraception Nov 2023This study aimed to update our 2019 systematic review of data on the effectiveness and safety of misoprostol-only for first-trimester abortion. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aimed to update our 2019 systematic review of data on the effectiveness and safety of misoprostol-only for first-trimester abortion.
STUDY DESIGN
We searched PubMed on December 18, 2022, to find published articles describing the outcomes of treatment with misoprostol-only for abortion of viable intrauterine pregnancy at ≤91 days of gestation. From each article identified, two authors independently abstracted relevant data about each group of patients treated with a distinct regimen. We assessed the risk of bias using four defined indicators. We estimated the proportion of patients with treatment failure using meta-analytic methods as well as the proportion hospitalized or transfused after treatment. We examined associations between treatment failure and selected characteristics of the groups.
RESULTS
We identified 49 papers with 66 groups that collectively included 16,354 evaluable patients, of whom 2960 (meta-analytic estimate 15%, 95% CI 12%, 19%) had treatment failures. Of 9228 patients assessed for ongoing pregnancy after treatment, 521 (meta-analytic estimate 6%, 95% CI 5%, 8%) had that condition. Failure risk was significantly associated with misoprostol dose, the total allowed number of doses, the maximum duration of dosing, and certain indicators of risk of bias. Among 11,007 patients allowed to take at least three misoprostol doses, the first consisting of misoprostol 800 mcg administered vaginally, sublingually, or buccally, the meta-analytic estimate of the failure risk was 11% (95% CI 8%, 14%). At most, 0.2% of 15,679 evaluable patients were hospitalized or received transfusions.
CONCLUSIONS
Although some studies in this updated review were adjudicated to have a high risk of bias, the results continue to support the key conclusion of our 2019 analysis: misoprostol-only is effective and safe for the termination of first-trimester intrauterine pregnancy.
IMPLICATIONS
Misoprostol-only is a safe and effective option for medication abortion in the first trimester if mifepristone is unavailable or inaccessible.
Topics: Pregnancy; Female; Humans; Misoprostol; Abortifacient Agents; Pregnancy Trimester, First; Mifepristone; Abortion, Induced; Abortifacient Agents, Nonsteroidal
PubMed: 37517447
DOI: 10.1016/j.contraception.2023.110132 -
Drug Safety Feb 2017H1 antihistamines are used for the treatment of nausea and vomiting during pregnancy as well as the symptomatic relief of asthma, urticaria, allergy, and the common... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
H1 antihistamines are used for the treatment of nausea and vomiting during pregnancy as well as the symptomatic relief of asthma, urticaria, allergy, and the common cold. Although they are overall felt to be safe during pregnancy, recently several studies have challenged this assumption, as millions of women are exposed to them in the first trimester.
METHODS
Following the guidelines of PRISMA, a systematic review was performed to retrieve all published articles involving H1-antihistamine exposure during pregnancy. Electronic databases including PubMed and EMBASE were searched for possibly relevant articles published in any language up to December 2015.
RESULTS
After removing duplicate publications, and excluding animal studies and studies on drug effectiveness, 342 articles were reviewed in detail and 37 studies fulfilled the inclusion criteria for the meta-analysis. In cohort studies, the risk of major malformation in the offspring of women exposed to H1 antihistamines was not higher than that of the control population (OR 1.07; 95% CI 0.98-1.16). The Q-statistic for heterogeneity of effects was not significant (p > 0.05, I < 25%) and there was no evidence of publication bias. Similar results were achieved with case-control studies (OR 1.05; 95% CI 0.90-1.23). Similarly, H1 antihistamines were not associated with more spontaneous abortions (OR 1.00; 95% CI 0.83-1.20), prematurity (OR 0.96; 95% CI 0.76-1.20), stillbirth (OR 1.23; 95% CI 0.48-3.18) or low birth weight (OR 1.20; 95% CI 0.63-2.29).
CONCLUSIONS
Based on our meta-analyses, which included a large number of studies, H1 antihistamines are not associated with an increased risk of major malformation or other adverse fetal outcomes. This study provides important information to both pregnant women and their healthcare providers regarding the safety and risk of H1 antihistamine use during this sensitive time.
Topics: Abnormalities, Drug-Induced; Female; Histamine H1 Antagonists; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, First; Risk
PubMed: 27878468
DOI: 10.1007/s40264-016-0479-9 -
British Journal of Clinical Pharmacology Apr 2016The aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into... (Meta-Analysis)
Meta-Analysis Review
AIMS
The aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into account indication, study design and reference category.
METHOD
A systematic review of studies published between 1966 and November 2015 was conducted using embase and MEDLINE. Studies reporting major malformations with first trimester exposure to paroxetine were included. Potentially relevant articles were assessed and relevant data extracted to calculate risk estimates. Outcomes included any major malformations and major cardiac malformations. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models.
RESULTS
Twenty-three studies were included. Compared with non-exposure to paroxetine, first trimester use of paroxetine was associated with an increased risk of any major congenital malformations combined (pooled OR 1.23, 95% CI 1.10, 1.38; n = 15 studies), major cardiac malformations (pooled OR 1.28, 95% CI 1.11, 1.47; n = 18 studies), specifically bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07, 1.89; n = 8 studies), atrial septal defects (pooled OR 2.38, 95% CI 1.14, 4.97; n = 4 studies) and right ventricular outflow track defect (pooled OR 2.29, 95% CI 1.06, 4.93; n = 4 studies). Although the estimates varied depending on the comparator group, study design and malformation detection period, a trend towards increased risk was observed.
CONCLUSIONS
Paroxetine use during the first trimester of pregnancy is associated with an increased risk of any major congenital malformations and cardiac malformations. The increase in risk is not dependent on the study method or population.
Topics: Abnormalities, Drug-Induced; Female; Heart Defects, Congenital; Humans; Maternal Exposure; Paroxetine; Pregnancy; Pregnancy Trimester, First; Risk Assessment; Selective Serotonin Reuptake Inhibitors
PubMed: 26613360
DOI: 10.1111/bcp.12849 -
Pregnancy Hypertension Dec 2023Human chorionic gonadotropin (hCG), a glycoprotein produced in the placenta, is crucial for a healthy pregnancy. We investigated the relationship between hCG levels and... (Meta-Analysis)
Meta-Analysis Review
Human chorionic gonadotropin (hCG), a glycoprotein produced in the placenta, is crucial for a healthy pregnancy. We investigated the relationship between hCG levels and adverse pregnancy outcomes. We conducted a systematic review including studies measuring hCG blood levels in the first or second trimester, reporting on any of the 12 predefined adverse pregnancy outcomes with logistic regression-adjusted association estimates. The primary outcomes were placenta-associated complications, such as miscarriage, preeclampsia, intrauterine growth restriction, and preterm delivery. We searched PubMed, Embase and CINAHL Complete. The hCG levels were analysed as multiple of the median (MoM). Odds ratio (OR) and 95% confidence interval (CI) were used. Risk of bias and the certainty of evidence were assessed using ROBINS-I and GRADE, respectively. Meta-analysis also showed that hCG levels, reported as MoM ≥2/2.31/2.5, might be associated with an increased risk of preeclampsia (OR 2.08, 95% CI 1.26 to 3.44) and preterm delivery (OR 1.29, 95% CI 1.12 to 1.47), but the evidence is very uncertain. High second trimester hCG levels may be associated with preeclampsia and preterm delivery but confidence in evidence is low.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Premature Birth; Pre-Eclampsia; Pregnancy Outcome; Chorionic Gonadotropin; Abortion, Spontaneous; Pregnancy Trimester, Second
PubMed: 37951184
DOI: 10.1016/j.preghy.2023.11.003 -
International Journal of Gynaecology... Jun 2024Evidence is inconsistent regarding the impact of late gestational diabetes mellitus (GDM) on perinatal outcomes. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence is inconsistent regarding the impact of late gestational diabetes mellitus (GDM) on perinatal outcomes.
OBJECTIVES
To evaluate associations of GDM diagnosed in the third trimester (late GDM) with adverse obstetric and neonatal outcomes.
SEARCH STRATEGY
We searched Embase, Medline, and Web of Science from January 1, 1990 to June 16, 2022, for observational studies.
SELECTION CRITERIA
Late GDM was defined as a de novo diagnosis, i.e. after a negative screening for diabetes in the second trimester, and at later than 28 weeks of pregnancy.
DATA COLLECTION AND ANALYSIS
Each abstract and full-text article was independently reviewed by the same two authors. Quality was assessed with the use of the Newcastle-Ottawa Scale. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model.
MAIN RESULTS
Twelve studies were identified as meeting the inclusion criteria, including 3103 patients (571 with late GDM and 3103 controls). Incidences of shoulder dystocia (OR 1.57, 95% CI 1.02-2.42, P = 0.040), 5-minute Apgar score <7 (OR 1.80, 95% CI 1.14-2.86, P = 0.024), cesarean delivery (OR 1.98, 95% CI 1.51-2.60, P < 0.001), and emergent cesarean delivery (OR 1.57, 95% CI 1.02-2.40, P = 0.040) were significantly higher among women with late GDM than among the controls. The groups showed similarity in the rates of fetal macrosomia, large-for-gestational-age fetuses, neonatal hypoglycemia, and hypertensive disorders of pregnancy.
CONCLUSIONS
This meta-analysis showed associations of late GDM with increased adverse perinatal outcomes. Prospective studies should evaluate the impact on perinatal outcomes of repeated third-trimester screening for late GDM.
Topics: Humans; Pregnancy; Female; Diabetes, Gestational; Pregnancy Trimester, Third; Pregnancy Outcome; Infant, Newborn; Shoulder Dystocia; Cesarean Section; Fetal Macrosomia; Apgar Score
PubMed: 37987501
DOI: 10.1002/ijgo.15254 -
Biomarkers : Biochemical Indicators of... Sep 2021The relationship between hepatokine levels during the first or early second trimester of pregnancy and the subsequent risk of gestational diabetes mellitus (GDM) have... (Meta-Analysis)
Meta-Analysis
PURPOSE
The relationship between hepatokine levels during the first or early second trimester of pregnancy and the subsequent risk of gestational diabetes mellitus (GDM) have been studied extensively. However, conclusions remain debateable whether hepatokines are potential markers of GDM. We conducted a meta-analysis of published articles to understand the association between circulating levels of selected hepatokines (including FGF21, fetuin-A, afamin, adropin, ficolin-3, selenoprotein P, ANGPTL4 and AGF) and the risk of GDM.
MATERIALS AND METHODS
We searched the PubMed, Embase, Cochrane Library and Web of Science databases for studies published before January 2021 that examined the association between hepatokines and GDM (Prospero Registration# CRD42020191408). The quality was assessed by the Newcastle-Ottawa Scale (NOS). Pooled standard mean differences (SMDs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were used to compare the levels of hepatokines in different groups using fixed effects or random effects models. Meta-regression analysis and publication bias were conducted in accordance with standard methods. The trim-fill adjustment method was used to further assess the possible effect of publication bias. Sensitivity analysis was performed by omitting each study one at a time.
RESULTS
The meta-analysis included 31 observational studies relating hepatokine levels to GDM in 4729 participants (1908 GDM, 2821 non-GDM). Serum FGF21 levels in patients with GDM were higher than those in healthy pregnant women during the second trimester and after delivery (SMD 0.89, [95% CI] 0.01-1.78 for the second trimester; SMD 1.42, [95% CI] 0.86-1.98 for after delivery). The serum levels of afamin in patients with GDM were significantly higher than those in healthy pregnant women during the first trimester and before pregnancy (SMD 0.51, [95% CI] 0.15-0.86 for first trimester; SMD 0.97, [95% CI] 0.45-1.50 for before pregnancy). Serum adropin levels in patients with GDM were higher than those in healthy pregnant women during the first and third trimesters of pregnancy (SMD 4.26, [95% CI] 3.30-5.23 for the first trimester; SMD 4.02, [95% CI] 3.09-4.94 for the third trimester). The serum levels of ficolin-3 in GDM patients were higher than those in healthy pregnant women during the second and third trimesters of pregnancy (WMD 1.43, [95% CI] 0.91-1.96 for the second trimester; SMD 1.28, [95% CI] 0.72-1.84 for the third trimester). The serum AGF level of patients with GDM was higher than that of healthy pregnant women in the control group in the third trimester (WMD 61 [95% CI] 37.04-81.96). The serum levels of selenoprotein P in patients with GDM were higher than those in healthy pregnant women in the control group during the first trimester (WMD 7.09 [95% CI] 4.6-9.57).
CONCLUSIONS
Measurement of circulating hepatokines in the first or second trimester of pregnancy may improve the identification of women at risk of developing GDM later. Prospective evaluation of the combination of hepatokines and maternal characteristics for early identification of those who do and do not require OGTT is warranted. Additional well-designed prospective studies with longitudinal assessment of hepatokines during pregnancy are needed to understand the trajectories and dynamic associations of hepatokines with GDM risk.
Topics: Adult; Biomarkers; Case-Control Studies; Diabetes, Gestational; Female; Humans; Intercellular Signaling Peptides and Proteins; Liver; Pregnancy; Pregnancy Trimesters; Risk Factors
PubMed: 34082623
DOI: 10.1080/1354750X.2021.1928754 -
Reproductive Biology and Endocrinology... Jun 2011Angiogenic factors are involved in formation of new blood vessels required for placental development and function; and critical for fetal growth and development. Soluble... (Review)
Review
Angiogenic factors are involved in formation of new blood vessels required for placental development and function; and critical for fetal growth and development. Soluble fms-like tyrosine kinase 1(sFlt-1) is an anti-angiogenic protein that inhibits formation of new blood vessels resulting in potential pregnancy complications. The objective of this study was to undertake a systematic review to assess levels of sFlt-1 in early pregnancy and association with adverse pregnancy outcomes. PubMed and Medline databases and reference lists were searched up to July 2010. Inclusion criteria were pregnant women, blood sample taken during first trimester and assessment/reporting of sFlt-1 concentrations and subsequent pregnancy complications. Twelve relevant studies were identified of 71 to 668 women. No pooling of results was undertaken due to variation in sFlt-1 concentrations (range, 166-6,349 pg/ml amongst controls), samples used (serum, plasma), different summary statistics (mean, median, odds ratio) and outcome definitions applied. Levels of sFlt-1 were generally higher among women who developed preeclampsia (11 studies) or gestational hypertension (two studies), but not significantly different to normotensive women in most studies. There was no consistent pattern in association between sFlt-1 concentrations and fetal growth restriction (4 studies); and levels were non-significantly higher for women with postpartum bleeding (1 study) and significantly lower for stillbirths (1 study).This review found no clear evidence of an association between sFlt-1 levels in first trimester and adverse pregnancy outcomes. However, findings were affected by methodological, biological and testing variations between studies; highlighting the need for consistent testing of new biomarkers and reporting of outcome measures.
Topics: Adult; Female; Humans; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Risk Factors; Vascular Endothelial Growth Factor Receptor-1
PubMed: 21649938
DOI: 10.1186/1477-7827-9-77 -
Journal of Cardiac Surgery Jul 2021Patients with aortic dissection during pregnancy and postpartum period exhibit a high mortality. At present, a complete overview of aortic dissection during pregnancy... (Review)
Review
Patients with aortic dissection during pregnancy and postpartum period exhibit a high mortality. At present, a complete overview of aortic dissection during pregnancy and postpartum period is lacking. Methods: This systematic review included 80 reports published from 2000 to 2020, comprising a total study population of 103 patients with aortic dissection. Results: We found that Stanford Type A aortic dissection was more common in prepartum cases, especially in the third trimester, while postpartum cases of aortic dissection were more common in Stanford Type B. The most common risk factor was connective tissue disease, with no other known risk factors. The mode of delivery had no significant effect on the type of postpartum aortic dissection. Reduced maternal and fetal mortality was observed when patients with Stanford Type A aortic dissection occurring after 28 gestational weeks underwent cesarean section followed by aortic replacement. Patients with Stanford Type B aortic dissection were treated mainly with medication and/or endovascular repair. Conclusion: Contemporary management of patients during pregnancy and within 12 weeks postpartum requires multidisciplinary cooperation and includes serial, noninvasive imaging, biomarker testing, and genetic risk profiling for aortopathy. Early diagnosis and accurate treatment are essential to reduce maternal and fetal mortality.
Topics: Aortic Dissection; Cesarean Section; Female; Humans; Postpartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Third
PubMed: 33928681
DOI: 10.1111/jocs.15575 -
Ultrasound in Obstetrics & Gynecology :... Dec 2017To establish reference values for flow-mediated dilatation (FMD) and brachial artery diameter (BAD) in pregnancy and to provide insight into the physiological and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To establish reference values for flow-mediated dilatation (FMD) and brachial artery diameter (BAD) in pregnancy and to provide insight into the physiological and pathological course of endothelial adaptation throughout human singleton pregnancy.
METHODS
A meta-analysis was performed following a systematic review of current literature on FMD, as a derivative for endothelial function, and BAD, throughout uncomplicated and complicated pregnancy. PubMed (NCBI) and EMBASE (Ovid) electronic databases were used for the literature search, which was performed from inception to 9 June 2016. To allow judgment of changes in comparison with the non-pregnant state, studies were required to report both non-pregnant mean reference of FMD (matched control group, prepregnancy or postpartum measurement) and mean FMD at a predetermined and reported gestational age. Pooled mean differences between the reference and pregnant FMD values were calculated for predefined intervals of gestational age.
RESULTS
Fourteen studies that enrolled 1231 participants met the inclusion criteria. Publication dates ranged from 1999 to 2014. In uncomplicated pregnancy, FMD was increased in the second and third trimesters. Between 15 and 21 weeks of gestation, absolute FMD increased the most, by a mean (95% CI) of 1.89% (0.25-3.53%). This was a relative increase of 22.5% (3.0-42.0%) compared with the non-pregnant reference. BAD increased progressively, in a steady manner, by the second trimester but not significantly in the first half of the second trimester. We could not discern differences in FMD and BAD between complicated and uncomplicated pregnancies at 29-35 weeks' gestation, reported in the three studies that met our inclusion criteria. Despite the increase in FMD and BAD throughout gestation, both reference curves were characterized by wide 95% CIs.
CONCLUSION
During healthy pregnancy, endothelium-dependent vasodilatation and BAD increase. Women with a complicated pregnancy had FMD values within the lower range when compared with those with uncomplicated pregnancy but, as a group, did not differ from each other. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adaptation, Physiological; Brachial Artery; Endothelium, Vascular; Female; Humans; Hypertension, Pregnancy-Induced; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Regional Blood Flow; Vasodilation
PubMed: 28170124
DOI: 10.1002/uog.17431