-
The Cochrane Database of Systematic... Jun 2021Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime. An estimated 15% of pregnancies end in miscarriage. Miscarriage can lead to serious morbidity, including haemorrhage, infection, and even death, particularly in settings without adequate healthcare provision. Early miscarriages occur during the first 14 weeks of pregnancy, and can be managed expectantly, medically or surgically. However, there is uncertainty about the relative effectiveness and risks of each option.
OBJECTIVES
To estimate the relative effectiveness and safety profiles for the different management methods for early miscarriage, and to provide rankings of the available methods according to their effectiveness, safety, and side-effect profile using a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register (9 February 2021), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (12 February 2021), and reference lists of retrieved studies.
SELECTION CRITERIA
We included all randomised controlled trials assessing the effectiveness or safety of methods for miscarriage management. Early miscarriage was defined as less than or equal to 14 weeks of gestation, and included missed and incomplete miscarriage. Management of late miscarriages after 14 weeks of gestation (often referred to as intrauterine fetal deaths) was not eligible for inclusion in the review. Cluster- and quasi-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded non-randomised trials.
DATA COLLECTION AND ANALYSIS
At least three review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for the primary outcomes of complete miscarriage and composite outcome of death or serious complications. The certainty of evidence was assessed using GRADE. Relative effects for the primary outcomes are reported subgrouped by the type of miscarriage (incomplete and missed miscarriage). We also performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available methods.
MAIN RESULTS
Our network meta-analysis included 78 randomised trials involving 17,795 women from 37 countries. Most trials (71/78) were conducted in hospital settings and included women with missed or incomplete miscarriage. Across 158 trial arms, the following methods were used: 51 trial arms (33%) used misoprostol; 50 (32%) used suction aspiration; 26 (16%) used expectant management or placebo; 17 (11%) used dilatation and curettage; 11 (6%) used mifepristone plus misoprostol; and three (2%) used suction aspiration plus cervical preparation. Of these 78 studies, 71 (90%) contributed data in a usable form for meta-analysis. Complete miscarriage Based on the relative effects from the network meta-analysis of 59 trials (12,591 women), we found that five methods may be more effective than expectant management or placebo for achieving a complete miscarriage: · suction aspiration after cervical preparation (risk ratio (RR) 2.12, 95% confidence interval (CI) 1.41 to 3.20, low-certainty evidence), · dilatation and curettage (RR 1.49, 95% CI 1.26 to 1.75, low-certainty evidence), · suction aspiration (RR 1.44, 95% CI 1.29 to 1.62, low-certainty evidence), · mifepristone plus misoprostol (RR 1.42, 95% CI 1.22 to 1.66, moderate-certainty evidence), · misoprostol (RR 1.30, 95% CI 1.16 to 1.46, low-certainty evidence). The highest ranked surgical method was suction aspiration after cervical preparation. The highest ranked non-surgical treatment was mifepristone plus misoprostol. All surgical methods were ranked higher than medical methods, which in turn ranked above expectant management or placebo. Composite outcome of death and serious complications Based on the relative effects from the network meta-analysis of 35 trials (8161 women), we found that four methods with available data were compatible with a wide range of treatment effects compared with expectant management or placebo: · dilatation and curettage (RR 0.43, 95% CI 0.17 to 1.06, low-certainty evidence), · suction aspiration (RR 0.55, 95% CI 0.23 to 1.32, low-certainty evidence), · misoprostol (RR 0.50, 95% CI 0.22 to 1.15, low-certainty evidence), · mifepristone plus misoprostol (RR 0.76, 95% CI 0.31 to 1.84, low-certainty evidence). Importantly, no deaths were reported in these studies, thus this composite outcome was entirely composed of serious complications, including blood transfusions, uterine perforations, hysterectomies, and intensive care unit admissions. Expectant management and placebo ranked the lowest when compared with alternative treatment interventions. Subgroup analyses by type of miscarriage (missed or incomplete) agreed with the overall analysis in that surgical methods were the most effective treatment, followed by medical methods and then expectant management or placebo, but there are possible subgroup differences in the effectiveness of the available methods. AUTHORS' CONCLUSIONS: Based on relative effects from the network meta-analysis, all surgical and medical methods for managing a miscarriage may be more effective than expectant management or placebo. Surgical methods were ranked highest for managing a miscarriage, followed by medical methods, which in turn ranked above expectant management or placebo. Expectant management or placebo had the highest chance of serious complications, including the need for unplanned or emergency surgery. A subgroup analysis showed that surgical and medical methods may be more beneficial in women with missed miscarriage compared to women with incomplete miscarriage. Since type of miscarriage (missed and incomplete) appears to be a source of inconsistency and heterogeneity within these data, we acknowledge that the main network meta-analysis may be unreliable. However, we plan to explore this further in future updates and consider the primary analysis as separate networks for missed and incomplete miscarriage.
Topics: Abortion, Incomplete; Abortion, Missed; Abortion, Spontaneous; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Network Meta-Analysis; Oxytocics; Placebos; Pregnancy; Pregnancy Trimester, First; Randomized Controlled Trials as Topic; Suction; Vacuum Curettage; Watchful Waiting
PubMed: 34061352
DOI: 10.1002/14651858.CD012602.pub2 -
The Cochrane Database of Systematic... Mar 2017Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life.Non-invasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing.Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have.
OBJECTIVES
To estimate and compare the accuracy of first trimester ultrasound markers alone, and in combination with first trimester serum tests for the detection of Down's syndrome.
SEARCH METHODS
We carried out extensive literature searches including MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), and The Database of Abstracts of Reviews of Effects (the Cochrane Library 2011, Issue 7). We checked reference lists and published review articles for additional potentially relevant studies.
SELECTION CRITERIA
Studies evaluating tests of first trimester ultrasound screening, alone or in combination with first trimester serum tests (up to 14 weeks' gestation) for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection.
DATA COLLECTION AND ANALYSIS
Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses.
MAIN RESULTS
We included 126 studies (152 publications) involving 1,604,040 fetuses (including 8454 Down's syndrome cases). Studies were generally good quality, although differential verification was common with invasive testing of only high-risk pregnancies. Sixty test combinations were evaluated formed from combinations of 11 different ultrasound markers (nuchal translucency (NT), nasal bone, ductus venosus Doppler, maxillary bone length, fetal heart rate, aberrant right subclavian artery, frontomaxillary facial angle, presence of mitral gap, tricuspid regurgitation, tricuspid blood flow and iliac angle 90 degrees); 12 serum tests (inhibin A, alpha-fetoprotein (AFP), free beta human chorionic gonadotrophin (ßhCG), total hCG, pregnancy-associated plasma protein A (PAPP-A), unconjugated oestriol (uE3), disintegrin and metalloprotease 12 (ADAM 12), placental growth factor (PlGF), placental growth hormone (PGH), invasive trophoblast antigen (ITA) (synonymous with hyperglycosylated hCG), growth hormone binding protein (GHBP) and placental protein 13 (PP13)); and maternal age. The most frequently evaluated serum markers in combination with ultrasound markers were PAPP-A and free ßhCG.Comparisons of the 10 most frequently evaluated test strategies showed that a combined NT, PAPP-A, free ßhCG and maternal age test strategy significantly outperformed ultrasound markers alone (with or without maternal age) except nasal bone, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate (FPR). In both direct and indirect comparisons, the combined NT, PAPP-A, free ßhCG and maternal age test strategy showed superior diagnostic accuracy to an NT and maternal age test strategy (P < 0.0001). Based on the indirect comparison of all available studies for the two tests, the sensitivity (95% confidence interval) estimated at a 5% FPR for the combined NT, PAPP-A, free ßhCG and maternal age test strategy (69 studies; 1,173,853 fetuses including 6010 with Down's syndrome) was 87% (86 to 89) and for the NT and maternal age test strategy (50 studies; 530,874 fetuses including 2701 Down's syndrome pregnancies) was 71% (66 to 75). Combinations of NT with other ultrasound markers, PAPP-A and free ßhCG were evaluated in one or two studies and showed sensitivities of more than 90% and specificities of more than 95%.High-risk populations (defined before screening was done, mainly due to advanced maternal age of 35 years or more, or previous pregnancies affected with Down's syndrome) showed lower detection rates compared to routine screening populations at a 5% FPR. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under-ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting test sensitivity. Conversely, for the NT, PAPP-A, free ßhCG and maternal age test strategy, detection rates and false positive rates increased with maternal age in the five studies that provided data separately for the subset of women aged 35 years or more.
AUTHORS' CONCLUSIONS
Test strategies that combine ultrasound markers with serum markers, especially PAPP-A and free ßhCG, and maternal age were significantly better than those involving only ultrasound markers (with or without maternal age) except nasal bone. They detect about nine out of 10 Down's affected pregnancies for a fixed 5% FPR. Although the absence of nasal bone appeared to have a high diagnostic accuracy, only five out of 10 affected Down's pregnancies were detected at a 1% FPR.
Topics: Biomarkers; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Down Syndrome; False Positive Reactions; Female; Humans; Maternal Age; Nasal Bone; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 28295158
DOI: 10.1002/14651858.CD012600 -
Human Reproduction Update Sep 2020Although spontaneous miscarriage is the most common complication of human pregnancy, potential contributing factors are not fully understood. Advanced maternal age has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although spontaneous miscarriage is the most common complication of human pregnancy, potential contributing factors are not fully understood. Advanced maternal age has long been recognised as a major risk factor for miscarriage, being strongly related with fetal chromosomal abnormalities. The relation between paternal age and the risk of miscarriage is less evident, yet it is biologically plausible that an increasing number of genetic and epigenetic sperm abnormalities in older males may contribute to miscarriage. Previous meta-analyses showed associations between advanced paternal age and a broad spectrum of perinatal and paediatric outcomes. This is the first systematic review and meta-analysis on paternal age and spontaneous miscarriage.
OBJECTIVE AND RATIONALE
The aim of this systematic review and meta-analysis is to evaluate the effect of paternal age on the risk of spontaneous miscarriage.
SEARCH METHODS
PubMed, Embase and Cochrane databases were searched to identify relevant studies up to August 2019. The following free text and MeSH terms were used: paternal age, father's age, male age, husband's age, spontaneous abortion, spontaneous miscarriage, abortion, miscarriage, pregnancy loss, fetal loss and fetal death. PRISMA guidelines for systematic reviews and meta-analysis were followed. Original research articles in English language addressing the relation between paternal age and spontaneous miscarriage were included. Exclusion criteria were studies that solely focused on pregnancy outcomes following artificial reproductive technology (ART) and studies that did not adjust their effect estimates for at least maternal age. Risk of bias was qualitatively described for three domains: bias due to confounding, information bias and selection bias.
OUTCOMES
The search resulted in 975 original articles. Ten studies met the inclusion criteria and were included in the qualitative synthesis. Nine of these studies were included in the quantitative synthesis (meta-analysis). Advanced paternal age was found to be associated with an increased risk of miscarriage. Pooled risk estimates for miscarriage for age categories 30-34, 35-39, 40-44 and ≥45 years of age were 1.04 (95% CI 0.90, 1.21), 1.15 (0.92, 1.43), 1.23 (1.06, 1.43) and 1.43 (1.13, 1.81) respectively (reference category 25-29 years). A second meta-analysis was performed for the subgroup of studies investigating first trimester miscarriage. This showed similar pooled risk estimates for the first three age categories and a slightly higher pooled risk estimate for age category ≥45 years (1.74; 95% CI 1.26, 2.41).
WIDER IMPLICATIONS
Over the last decades, childbearing at later ages has become more common. It is known that frequencies of adverse reproductive outcomes, including spontaneous miscarriage, are higher in women with advanced age. We show that advanced paternal age is also associated with an increased risk of spontaneous miscarriage. Although the paternal age effect is less pronounced than that observed with advanced maternal age and residual confounding by maternal age cannot be excluded, it may have implications for preconception counselling of couples comprising an older aged male.
Topics: Abortion, Spontaneous; Adult; Aged; Fathers; Female; Humans; Male; Maternal Age; Middle Aged; Paternal Age; Pregnancy; Pregnancy Outcome; Prenatal Care; Risk Factors; Young Adult
PubMed: 32358607
DOI: 10.1093/humupd/dmaa010 -
The Lancet. Diabetes & Endocrinology Jun 2020Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight.
METHODS
In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496.
FINDINGS
We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (p=0·10). Each 1 SD increase in FT concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second.
INTERPRETATION
Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy.
FUNDING
Netherlands Organization for Scientific Research (grant 401.16.020).
Topics: Birth Weight; Female; Gestational Age; Humans; Hypothyroidism; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Pregnancy Complications; Thyroid Function Tests; Thyroid Gland
PubMed: 32445737
DOI: 10.1016/S2213-8587(20)30061-9 -
Ultrasound in Obstetrics & Gynecology :... Oct 2019To estimate the procedure-related risk of miscarriage after amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and an... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To estimate the procedure-related risk of miscarriage after amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and an updated meta-analysis.
METHODS
A search of MEDLINE, EMBASE and The Cochrane Library was carried out to identify studies reporting complications following CVS or amniocentesis. Eligible for inclusion were large controlled studies reporting data for pregnancy loss prior to 24 weeks' gestation. Study authors were contacted when required to identify additional necessary data. Data for cases that had an invasive procedure and controls were inputted into contingency tables and the risk of miscarriage was estimated for each study. Summary statistics based on a random-effects model were calculated after taking into account the weighting for each study included in the systematic review. Procedure-related risk of miscarriage was estimated as a weighted risk difference from the summary statistics for cases and controls. Subgroup analyses were performed according to the similarity in risk levels for chromosomal abnormality between the invasive-testing and control groups. Heterogeneity was assessed using the I statistic. Egger's bias was estimated to assess reporting bias in published studies.
RESULTS
The electronic search yielded 2943 potential citations, from which 12 controlled studies for amniocentesis and seven for CVS were selected for inclusion in the systematic review. A total of 580 miscarriages occurred following 63 723 amniocentesis procedures, resulting in a weighted risk of pregnancy loss of 0.91% (95% CI, 0.73-1.09%). In the control group, there were 1726 miscarriages in 330 469 pregnancies with a loss rate of 0.58% (95% CI, 0.47-0.70%). The weighted procedure-related risk of miscarriage following amniocentesis was 0.30% (95% CI, 0.11-0.49%; I = 70.1%). A total of 163 miscarriages occurred following 13 011 CVS procedures, resulting in a risk of pregnancy loss of 1.39% (95% CI, 0.76-2.02%). In the control group, there were 1946 miscarriages in 232 680 pregnancies with a loss rate of 1.23% (95% CI, 0.86-1.59%). The weighted procedure-related risk of miscarriage following CVS was 0.20% (95% CI, -0.13 to 0.52%; I = 52.7%). However, when studies including only women with similar risk profiles for chromosomal abnormality in the intervention and control groups were considered, the procedure-related risk for amniocentesis was 0.12% (95% CI, -0.05 to 0.30%; I = 44.1%) and for CVS it was -0.11% (95% CI, -0.29 to 0.08%; I = 0%).
CONCLUSIONS
The procedure-related risks of miscarriage following amniocentesis and CVS are lower than currently quoted to women. The risk appears to be negligible when these interventions were compared to control groups of the same risk profile. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Abortion, Spontaneous; Adult; Amniocentesis; Chorionic Villi Sampling; Chromosome Aberrations; Embryo Loss; Female; Gestational Age; Humans; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 31124209
DOI: 10.1002/uog.20353 -
American Journal of Obstetrics and... Jul 2018An indirect comparison meta-analysis published in 2013 reported that both vaginal progesterone and cerclage are equally efficacious for preventing preterm birth and... (Meta-Analysis)
Meta-Analysis
Vaginal progesterone is as effective as cervical cerclage to prevent preterm birth in women with a singleton gestation, previous spontaneous preterm birth, and a short cervix: updated indirect comparison meta-analysis.
BACKGROUND
An indirect comparison meta-analysis published in 2013 reported that both vaginal progesterone and cerclage are equally efficacious for preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic short cervix. The efficacy of vaginal progesterone has been challenged after publication of the OPPTIMUM study. However, this has been resolved by an individual patient-data meta-analysis (Am J Obstet Gynecol. 2018;218:161-180).
OBJECTIVE
To compare the efficacy of vaginal progesterone and cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix.
DATA SOURCES
MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to March 2018); Cochrane databases, bibliographies, and conference proceedings.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials comparing vaginal progesterone to placebo/no treatment or cerclage to no cerclage in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic cervical length <25 mm.
STUDY APPRAISAL AND SYNTHESIS METHODS
Updated systematic review and adjusted indirect comparison meta-analysis of vaginal progesterone vs cerclage using placebo/no cerclage as the common comparator. The primary outcomes were preterm birth <35 weeks of gestation and perinatal mortality. Pooled relative risks (RRs) with 95% confidence intervals were calculated.
RESULTS
Five trials comparing vaginal progesterone vs placebo (265 women) and 5 comparing cerclage vs no cerclage (504 women) were included. Vaginal progesterone, compared to placebo, significantly reduced the risk of preterm birth <35 and <32 weeks of gestation, composite perinatal morbidity/mortality, neonatal sepsis, composite neonatal morbidity, and admission to the neonatal intensive care unit (RRs from 0.29 to 0.68). Cerclage, compared to no cerclage, significantly decreased the risk of preterm birth <37, <35, <32, and <28 weeks of gestation, composite perinatal morbidity/mortality, and birthweight <1500 g (RRs from 0.64 to 0.70). Adjusted indirect comparison meta-analyses did not show statistically significant differences between vaginal progesterone and cerclage in the reduction of preterm birth or adverse perinatal outcomes.
CONCLUSION
Vaginal progesterone and cerclage are equally effective for preventing preterm birth and improving perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix. The choice of treatment will depend on adverse events and cost-effectiveness of interventions and patient/physician's preferences.
Topics: Administration, Intravaginal; Cerclage, Cervical; Cervical Length Measurement; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Neonatal Sepsis; Perinatal Mortality; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Premature Birth; Progesterone; Progestins; Secondary Prevention
PubMed: 29630885
DOI: 10.1016/j.ajog.2018.03.028 -
Prenatal Diagnosis May 2022We conducted a systematic review and meta-analysis to determine the diagnostic yield of exome sequencing (ES) for prenatal diagnosis of fetal structural anomalies, where... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We conducted a systematic review and meta-analysis to determine the diagnostic yield of exome sequencing (ES) for prenatal diagnosis of fetal structural anomalies, where karyotype/chromosomal microarray (CMA) is normal.
METHODS
Following electronic searches of four databases, we included studies with ≥10 structurally abnormal fetuses undergoing ES or whole genome sequencing. The incremental diagnostic yield of ES over CMA/karyotype was calculated and pooled in a meta-analysis. Sub-group analyses investigated effects of case selection and fetal phenotype on diagnostic yield.
RESULTS
We identified 72 reports from 66 studies, representing 4350 fetuses. The pooled incremental yield of ES was 31% (95% confidence interval (CI) 26%-36%, p < 0.0001). Diagnostic yield was significantly higher for cases pre-selected for likelihood of monogenic aetiology compared to unselected cases (42% vs. 15%, p < 0.0001). Diagnostic yield differed significantly between phenotypic sub-groups, ranging from 53% (95% CI 42%-63%, p < 0.0001) for isolated skeletal abnormalities, to 2% (95% CI 0%-5%, p = 0.04) for isolated increased nuchal translucency.
CONCLUSION
Prenatal ES provides a diagnosis in an additional 31% of structurally abnormal fetuses when CMA/karyotype is non-diagnostic. The expected diagnostic yield depends on the body system(s) affected and can be optimised by pre-selection of cases following multi-disciplinary review to determine that a monogenic cause is likely.
Topics: Exome; Female; Humans; Pregnancy; Pregnancy Trimester, First; Prenatal Diagnosis; Ultrasonography, Prenatal; Exome Sequencing
PubMed: 35170059
DOI: 10.1002/pd.6115 -
Epigenetics Dec 2023Most pregnancy complications originate with early placentation. MicroRNAs (miRNAs) may play an important role in placentation and function as biomarkers of future...
Most pregnancy complications originate with early placentation. MicroRNAs (miRNAs) may play an important role in placentation and function as biomarkers of future pregnancy complications. We summarized from the literature all first trimester circulating miRNAs associated with pregnancy complications of placental origin and further identified the miRNAs which have the most evidence as potential early biomarkers for pregnancy complications. We conducted a systematic review following PRISMA reporting guidelines (PROSPERO CRD42020183421). We identified all first trimester serum or plasma miRNAs associated with a pregnancy complication of placental origin (preeclampsia, intrauterine growth restriction (IUGR), gestational hypertension, preterm delivery) and the number of times those miRNAs were identified, as a measure of replication. Twenty-one studies examined 118 unique miRNAs, and 87 were associated with at least one pregnancy complication; preeclampsia was the most common. Seven miRNAs were significantly associated with a pregnancy complication in at least two studies: miR-125b, miR-518b, miR-628-3p, miR-365a-3p, miR-520h, miR-374a-5p, miR-191-5p. Few miRNAs were associated with more than one pregnancy complication: miR-518b and miR-520h with preeclampsia and gestational hypertension, miR-374a-5p and miR-191-5p with preterm birth and preeclampsia. Our systematic review suggests seven miRNAs as potential biomarkers of pregnancy complications. These complications are thought to originate with early placental defects and these miRNAs may also be biomarkers of placental pathology. First-trimester biomarkers of pregnancy complications can facilitate early detection and interventions.
Topics: Pregnancy; Humans; Infant, Newborn; Female; Pregnancy Trimester, First; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Circulating MicroRNA; Placenta; Premature Birth; DNA Methylation; MicroRNAs; Pregnancy Complications; Placentation; Biomarkers
PubMed: 36503407
DOI: 10.1080/15592294.2022.2152615 -
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 -
Environmental Research May 2017Season and vitamin D are indirect and direct correlates of ultraviolet (UV) radiation and are associated with pregnancy outcomes. Further to producing vitamin D, UV has... (Review)
Review
BACKGROUND
Season and vitamin D are indirect and direct correlates of ultraviolet (UV) radiation and are associated with pregnancy outcomes. Further to producing vitamin D, UV has positive effects on cardiovascular and immune health that may support a role for UV directly benefitting pregnancy.
OBJECTIVES
To investigate the effects of UV exposure on pregnancy; specifically fetal growth, preterm birth and hypertensive complications.
METHODS
We conducted a systematic review of Medline, EMBASE, DoPHER, Global Health, ProQuest Public Health, AustHealth Informit, SCOPUS and Google Scholar to identify 537 citations, 8 of which are included in this review. This review was registered on PROSPERO and a. narrative synthesis is presented following PRISMA guidance.
RESULTS
All studies were observational and assessed at high risk of bias. Higher first trimester UV was associated with and improved fetal growth and increased hypertension in pregnancy. Interpretation is limited by study design and quality. Meta-analysis was precluded by the variety of outcomes and methods.
DISCUSSION
The low number of studies and risk of bias limit the validity of any conclusions. Environmental health methodological issues are discussed with consideration given to design and analytical improvements to further address this reproductive environmental health question.
CONCLUSIONS
The evidence for UV having benefits for pregnancy hypertension and fetal growth is limited by the methodological approaches utilized. Future epidemiological efforts should focus on improving the methods of modeling and linking widely available environmental data to reproductive health outcomes.
Topics: Animals; Female; Humans; Pregnancy; Pregnancy Outcome; Ultraviolet Rays
PubMed: 28264782
DOI: 10.1016/j.envres.2017.02.026