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Human Reproduction Update Sep 2023The number of frozen embryo transfers (FET) has increased dramatically over the past decade. Based on current evidence, there is no difference in pregnancy rates when... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The number of frozen embryo transfers (FET) has increased dramatically over the past decade. Based on current evidence, there is no difference in pregnancy rates when natural cycle FET (NC-FET) is compared to artificial cycle FET (AC-FET) in subfertile women. However, NC-FET seems to be associated with lower risk of adverse obstetric and neonatal outcomes compared with AC-FET cycles. Currently, there is no consensus about whether NC-FET needs to be combined with luteal phase support (LPS) or not. The question of how to prepare the endometrium for FET has now gained even more importance and taken the dimension of safety into account as it should not simply be reduced to the basic question of effectiveness.
OBJECTIVE AND RATIONALE
The objective of this project was to determine whether NC-FET, with or without LPS, decreases the risk of adverse obstetric and neonatal outcomes compared with AC-FET.
SEARCH METHODS
A systematic review and meta-analysis was carried out. A literature search was performed using the following databases: CINAHL, EMBASE, and MEDLINE from inception to 10 October 2022. Observational studies, including cohort studies, and registries comparing obstetric and neonatal outcomes between singleton pregnancies after NC-FET and those after AC-FET were sought. Risk of bias was assessed using the ROBINS-I tool. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. We calculated pooled odds ratios (ORs), pooled risk differences (RDs), pooled adjusted ORs, and prevalence estimates with 95% CI using a random effect model, while heterogeneity was assessed by the I2.
OUTCOMES
The conducted search identified 2436 studies, 890 duplicates were removed and 1546 studies were screened. Thirty studies (NC-FET n = 56 445; AC-FET n = 57 231) were included, 19 of which used LPS in NC-FET. Birthweight was lower following NC-FET versus AC-FET (mean difference 26.35 g; 95% CI 11.61-41.08, I2 = 63%). Furthermore NC-FET compared to AC-FET resulted in a lower risk of large for gestational age (OR 0.88, 95% 0.83-0.94, I2 = 54%), macrosomia (OR 0.81; 95% CI 0.71-0.93, I2 = 68%), low birthweight (OR 0.81, 95% CI 0.77-0.85, I2 = 41%), early pregnancy loss (OR 0.73; 95% CI 0.61-0.86, I2 = 70%), preterm birth (OR 0.80; 95% CI 0.75-0.85, I2 = 20%), very preterm birth (OR 0.66, 95% CI 0.53-0.84, I2 = 0%), hypertensive disorders of pregnancy (OR 0.60, 95% CI 0.50-0.65, I2 = 61%), pre-eclampsia (OR 0.50; 95% CI 0.42-0.60, I2 = 44%), placenta previa (OR 0.84, 95% CI 0.73-0.97, I2 = 0%), and postpartum hemorrhage (OR 0.43; 95% CI 0.38-0.48, I2 = 53%). Stratified analyses on LPS use in NC-FET suggested that, compared to AC-FET, NC-FET with LPS decreased preterm birth risk, while NC-FET without LPS did not (OR 0.75, 95% CI 0.70-0.81). LPS use did not modify the other outcomes. Heterogeneity varied from low to high, while quality of the evidence was very low to moderate.
WIDER IMPLICATIONS
This study confirms that NC-FET decreases the risk of adverse obstetric and neonatal outcomes compared with AC-FET. We estimate that for each adverse outcome, use of NC-FET may prevent 4 to 22 cases per 1000 women. Consequently, NC-FET should be the preferred treatment in women with ovulatory cycles undergoing FET. Based on very low quality of evidence, the risk of preterm birth be decreased when LPS is used in NC-FET compared to AC-FET. However, because of many uncertainties-the major being the debate about efficacy of the use of LPS-future research is needed on efficacy and safety of LPS and no recommendation can be made about the use of LPS.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Birth Weight; Premature Birth; Luteal Phase; Lipopolysaccharides; Cryopreservation; Embryo Transfer; Pregnancy Rate; Retrospective Studies
PubMed: 37172270
DOI: 10.1093/humupd/dmad011 -
The Cochrane Database of Systematic... Aug 2022Despite the widespread use of antenatal corticosteroids to prevent respiratory distress syndrome (RDS) in preterm infants, there is currently no consensus as to the type... (Review)
Review
BACKGROUND
Despite the widespread use of antenatal corticosteroids to prevent respiratory distress syndrome (RDS) in preterm infants, there is currently no consensus as to the type of corticosteroid to use, dose, frequency, timing of use or the route of administration. OBJECTIVES: To assess the effects on fetal and neonatal morbidity and mortality, on maternal morbidity and mortality, and on the child and adult in later life, of administering different types of corticosteroids (dexamethasone or betamethasone), or different corticosteroid dose regimens, including timing, frequency and mode of administration.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (9 May 2022) and reference lists of retrieved studies.
SELECTION CRITERIA
We included all identified published and unpublished randomised controlled trials or quasi-randomised controlled trials comparing any two corticosteroids (dexamethasone or betamethasone or any other corticosteroid that can cross the placenta), comparing different dose regimens (including frequency and timing of administration) in women at risk of preterm birth. We planned to exclude cross-over trials and cluster-randomised trials. We planned to include studies published as abstracts only along with studies published as full-text manuscripts.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 11 trials (2494 women and 2762 infants) in this update, all of which recruited women who were at increased risk of preterm birth or had a medical indication for preterm birth. All trials were conducted in high-income countries. Dexamethasone versus betamethasone Nine trials (2096 women and 2319 infants) compared dexamethasone versus betamethasone. All trials administered both drugs intramuscularly, and the total dose in the course was consistent (22.8 mg or 24 mg), but the regimen varied. We assessed one new study to have no serious risk of bias concerns for most outcomes, but other studies were at moderate (six trials) or high (two trials) risk of bias due to selection, detection and attrition bias. Our GRADE assessments ranged between high- and low-certainty, with downgrades due to risk of bias and imprecision. Maternal outcomes The only maternal primary outcome reported was chorioamnionitis (death and puerperal sepsis were not reported). Although the rate of chorioamnionitis was lower with dexamethasone, we did not find conclusive evidence of a difference between the two drugs (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.48 to 1.06; 1 trial, 1346 women; moderate-certainty evidence). The proportion of women experiencing maternal adverse effects of therapy was lower with dexamethasone; however, there was not conclusive evidence of a difference between interventions (RR 0.63, 95% CI 0.35 to 1.13; 2 trials, 1705 women; moderate-certainty evidence). Infant outcomes We are unsure whether the choice of drug makes a difference to the risk of any known death after randomisation, because the 95% CI was compatible with both appreciable benefit and harm with dexamethasone (RR 1.03, 95% CI 0.66 to 1.63; 5 trials, 2105 infants; moderate-certainty evidence). The choice of drug may make little or no difference to the risk of RDS (RR 1.06, 95% CI 0.91 to 1.22; 5 trials, 2105 infants; high-certainty evidence). While there may be little or no difference in the risk of intraventricular haemorrhage (IVH), there was substantial unexplained statistical heterogeneity in this result (average (a) RR 0.71, 95% CI 0.28 to 1.81; 4 trials, 1902 infants; I² = 62%; low-certainty evidence). We found no evidence of a difference between the two drugs for chronic lung disease (RR 0.92, 95% CI 0.64 to 1.34; 1 trial, 1509 infants; moderate-certainty evidence), and we are unsure of the effects on necrotising enterocolitis, because there were few events in the studies reporting this outcome (RR 5.08, 95% CI 0.25 to 105.15; 2 studies, 441 infants; low-certainty evidence). Longer-term child outcomes Only one trial consistently followed up children longer term, reporting at two years' adjusted age. There is probably little or no difference between dexamethasone and betamethasone in the risk of neurodevelopmental disability at follow-up (RR 1.02, 95% CI 0.85 to 1.22; 2 trials, 1151 infants; moderate-certainty evidence). It is unclear whether the choice of drug makes a difference to the risk of visual impairment (RR 0.33, 95% CI 0.01 to 8.15; 1 trial, 1227 children; low-certainty evidence). There may be little or no difference between the drugs for hearing impairment (RR 1.16, 95% CI 0.63 to 2.16; 1 trial, 1227 children; moderate-certainty evidence), motor developmental delay (RR 0.89, 95% CI 0.66 to 1.20; 1 trial, 1166 children; moderate-certainty evidence) or intellectual impairment (RR 0.97, 95% CI 0.79 to 1.20; 1 trial, 1161 children; moderate-certainty evidence). However, the effect estimate for cerebral palsy is compatible with both an important increase in risk with dexamethasone, and no difference between interventions (RR 2.50, 95% CI 0.97 to 6.39; 1 trial, 1223 children; low-certainty evidence). No trials followed the children beyond early childhood. Comparisons of different preparations and regimens of corticosteroids We found three studies that included a comparison of a different regimen or preparation of either dexamethasone or betamethasone (oral dexamethasone 32 mg versus intramuscular dexamethasone 24 mg; betamethasone acetate plus phosphate versus betamethasone phosphate; 12-hourly betamethasone versus 24-hourly betamethasone). The certainty of the evidence for the main outcomes from all three studies was very low, due to small sample size and risk of bias. Therefore, we were limited in our ability to draw conclusions from any of these studies.
AUTHORS' CONCLUSIONS
Overall, it remains unclear whether there are important differences between dexamethasone and betamethasone, or between one regimen and another. Most trials compared dexamethasone versus betamethasone. While for most infant and early childhood outcomes there may be no difference between these drugs, for several important outcomes for the mother, infant and child the evidence was inconclusive and did not rule out significant benefits or harms. The evidence on different antenatal corticosteroid regimens was sparse, and does not support the use of one particular corticosteroid regimen over another.
Topics: Adrenal Cortex Hormones; Betamethasone; Child; Child, Preschool; Chorioamnionitis; Dexamethasone; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Lung; Pregnancy; Premature Birth; Respiratory Distress Syndrome, Newborn
PubMed: 35943347
DOI: 10.1002/14651858.CD006764.pub4 -
The Cochrane Database of Systematic... Oct 2019Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia.
OBJECTIVES
To assess the effectiveness and safety of antiplatelet agents, such as aspirin and dipyridamole, when given to women at risk of developing pre-eclampsia.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (30 March 2018), and reference lists of retrieved studies. We updated the search in September 2019 and added the results to the awaiting classification section of the review.
SELECTION CRITERIA
All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent were included. Studies only published in abstract format were eligible for inclusion if sufficient information was available. We would have included cluster-randomised trials in the analyses along with individually-randomised trials, if any had been identified in our search strategy. Quasi-random studies were excluded. Participants were pregnant women at risk of developing pre-eclampsia. Interventions were administration of an antiplatelet agent (such as low-dose aspirin or dipyridamole), comparisons were either placebo or no antiplatelet.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trials for inclusion and extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For this update we incorporated individual participant data (IPD) from trials with this available, alongside aggregate data (AD) from trials where it was not, in order to enable reliable subgroup analyses and inclusion of two key new outcomes. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
Seventy-seven trials (40,249 women, and their babies) were included, although three trials (relating to 233 women) did not contribute data to the meta-analysis. Nine of the trials contributing data were large (> 1000 women recruited), accounting for 80% of women recruited. Although the trials took place in a wide range of countries, all of the nine large trials involved only women in high-income and/or upper middle-income countries. IPD were available for 36 trials (34,514 women), including all but one of the large trials. Low-dose aspirin alone was the intervention in all the large trials, and most trials overall. Dose in the large trials was 50 mg (1 trial, 1106 women), 60 mg (5 trials, 22,322 women), 75mg (1 trial, 3697 women) 100 mg (1 trial, 3294 women) and 150 mg (1 trial, 1776 women). Most studies were either low risk of bias or unclear risk of bias; and the large trials were all low risk of bas. Antiplatelet agents versus placebo/no treatment The use of antiplatelet agents reduced the risk of proteinuric pre-eclampsia by 18% (36,716 women, 60 trials, RR 0.82, 95% CI 0.77 to 0.88; high-quality evidence), number needed to treat for one women to benefit (NNTB) 61 (95% CI 45 to 92). There was a small (9%) reduction in the RR for preterm birth <37 weeks (35,212 women, 47 trials; RR 0.91, 95% CI 0.87 to 0.95, high-quality evidence), NNTB 61 (95% CI 42 to 114), and a 14% reduction infetal deaths, neonatal deaths or death before hospital discharge (35,391 babies, 52 trials; RR 0.85, 95% CI 0.76 to 0.95; high-quality evidence), NNTB 197 (95% CI 115 to 681). Antiplatelet agents slightly reduced the risk of small-for-gestational age babies (35,761 babies, 50 trials; RR 0.84, 95% CI 0.76 to 0.92; high-quality evidence), NNTB 146 (95% CI 90 to 386), and pregnancies with serious adverse outcome (a composite outcome including maternal death, baby death, pre-eclampsia, small-for-gestational age, and preterm birth) (RR 0.90, 95% CI 0.85 to 0.96; 17,382 women; 13 trials, high-quality evidence), NNTB 54 (95% CI 34 to 132). Antiplatelet agents probably slightly increase postpartum haemorrhage > 500 mL (23,769 women, 19 trials; RR 1.06, 95% CI 1.00 to 1.12; moderate-quality evidence due to clinical heterogeneity), and they probably marginally increase the risk of placental abruption, although for this outcome the evidence was downgraded due to a wide confidence interval including the possibility of no effect (30,775 women; 29 trials; RR 1.21, 95% CI 0.95 to 1.54; moderate-quality evidence). Data from two large trials which assessed children at aged 18 months (including results from over 5000 children), did not identify clear differences in development between the two groups.
AUTHORS' CONCLUSIONS
Administering low-dose aspirin to pregnant women led to small-to-moderate benefits, including reductions in pre-eclampsia (16 fewer per 1000 women treated), preterm birth (16 fewer per 1000 treated), the baby being born small-for-gestational age (seven fewer per 1000 treated) and fetal or neonatal death (five fewer per 1000 treated). Overall, administering antiplatelet agents to 1000 women led to 20 fewer pregnancies with serious adverse outcomes. The quality of evidence for all these outcomes was high. Aspirin probably slightly increased the risk of postpartum haemorrhage of more than 500 mL, however, the quality of evidence for this outcome was downgraded to moderate, due to concerns of clinical heterogeneity in measurements of blood loss. Antiplatelet agents probably marginally increase placental abruption, but the quality of the evidence was downgraded to moderate due to low event numbers and thus wide 95% CI. Overall, antiplatelet agents improved outcomes, and at these doses appear to be safe. Identifying women who are most likely to respond to low-dose aspirin would improve targeting of treatment. As almost all the women in this review were recruited to the trials after 12 weeks' gestation, it is unclear whether starting treatment before 12 weeks' would have additional benefits without any increase in adverse effects. While there was some indication that higher doses of aspirin would be more effective, further studies would be warranted to examine this.
Topics: Aspirin; Female; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Maternal Mortality; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Premature Birth; Prenatal Care; Randomized Controlled Trials as Topic
PubMed: 31684684
DOI: 10.1002/14651858.CD004659.pub3 -
Journal of Obstetrics and Gynaecology :... Dec 2023Pregnant women are one of the endangered groups who need special attention in the COVID-19 epidemic. We conducted a systematic review and summarised the studies that... (Meta-Analysis)
Meta-Analysis
Pregnant women are one of the endangered groups who need special attention in the COVID-19 epidemic. We conducted a systematic review and summarised the studies that reported adverse pregnancy outcomes in pregnant women with COVID-19 infection. A literature search was performed in PubMed and Scopus up to 1 September 2022, for retrieving original articles published in the English language assessing the association between COVID-19 infection and adverse pregnancy outcomes. Finally, in this review study, of 1790 articles obtained in the initial search, 141 eligible studies including 1,843,278 pregnant women were reviewed. We also performed a meta-analysis of a total of 74 cohort and case-control studies. In this meta-analysis, both fixed and random effect models were used. Publication bias was also assessed by Egger's test and the trim and fill method was conducted in case of a significant result, to adjust the bias. The result of the meta-analysis showed that the pooled prevalence of preterm delivery, maternal mortality, NICU admission and neonatal death in the group with COVID-19 infection was significantly more than those without COVID-19 infection (<.01). A meta-regression was conducted using the income level of countries. COVID-19 infection during pregnancy may cause adverse pregnancy outcomes including of preterm delivery, maternal mortality, NICU admission and neonatal death. Pregnancy loss and SARS-CoV2 positive neonates in Lower middle income are higher than in High income. Vertical transmission from mother to foetus may occur, but its immediate and long-term effects on the newborn are unclear.
Topics: Female; Humans; Infant, Newborn; Pregnancy; COVID-19; Infectious Disease Transmission, Vertical; Perinatal Death; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; SARS-CoV-2; Maternal Mortality; Intensive Care Units, Neonatal; Patient Admission
PubMed: 36651606
DOI: 10.1080/01443615.2022.2162867 -
The Cochrane Database of Systematic... Jul 2019Vitamin D supplementation during pregnancy may be needed to protect against adverse pregnancy outcomes. This is an update of a review that was first published in 2012...
BACKGROUND
Vitamin D supplementation during pregnancy may be needed to protect against adverse pregnancy outcomes. This is an update of a review that was first published in 2012 and then in 2016.
OBJECTIVES
To examine whether vitamin D supplementation alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (12 July 2018), contacted relevant organisations (15 May 2018), reference lists of retrieved trials and registries at clinicaltrials.gov and WHO International Clinical Trials Registry Platform (12 July 2018). Abstracts were included if they had enough information to extract the data.
SELECTION CRITERIA
Randomised and quasi-randomised trials evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy in comparison to placebo or no intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently i) assessed the eligibility of trials against the inclusion criteria, ii) extracted data from included trials, and iii) assessed the risk of bias of the included trials. The certainty of the evidence was assessed using the GRADE approach.
MAIN RESULTS
We included 30 trials (7033 women), excluded 60 trials, identified six as ongoing/unpublished trials and two trials are awaiting assessments.Supplementation with vitamin D alone versus placebo/no interventionA total of 22 trials involving 3725 pregnant women were included in this comparison; 19 trials were assessed as having low-to-moderate risk of bias for most domains and three trials were assessed as having high risk of bias for most domains. Supplementation with vitamin D alone during pregnancy probably reduces the risk of pre-eclampsia (risk ratio (RR) 0.48, 95% confidence interval (CI) 0.30 to 0.79; 4 trials, 499 women, moderate-certainty evidence) and gestational diabetes (RR 0.51, 95% CI 0.27 to 0.97; 4 trials, 446 women, moderate-certainty evidence); and probably reduces the risk of having a baby with low birthweight (less than 2500 g) (RR 0.55, 95% CI 0.35 to 0.87; 5 trials, 697 women, moderate-certainty evidence) compared to women who received placebo or no intervention. Vitamin D supplementation may make little or no difference in the risk of having a preterm birth < 37 weeks compared to no intervention or placebo (RR 0.66, 95% CI 0.34 to 1.30; 7 trials, 1640 women, low-certainty evidence). In terms of maternal adverse events, vitamin D supplementation may reduce the risk of severe postpartum haemorrhage (RR 0.68, 95% CI 0.51 to 0.91; 1 trial, 1134 women, low-certainty evidence). There were no cases of hypercalcaemia (1 trial, 1134 women, low-certainty evidence), and we are very uncertain as to whether vitamin D increases or decreases the risk of nephritic syndrome (RR 0.17, 95% CI 0.01 to 4.06; 1 trial, 135 women, very low-certainty evidence). However, given the scarcity of data in general for maternal adverse events, no firm conclusions can be drawn.Supplementation with vitamin D and calcium versus placebo/no interventionNine trials involving 1916 pregnant women were included in this comparison; three trials were assessed as having low risk of bias for allocation and blinding, four trials were assessed as having high risk of bias and two had some components having a low risk, high risk, or unclear risk. Supplementation with vitamin D and calcium during pregnancy probably reduces the risk of pre-eclampsia (RR 0.50, 95% CI 0.32 to 0.78; 4 trials, 1174 women, moderate-certainty evidence). The effect of the intervention is uncertain on gestational diabetes (RR 0.33,% CI 0.01 to 7.84; 1 trial, 54 women, very low-certainty evidence); and low birthweight (less than 2500 g) (RR 0.68, 95% CI 0.10 to 4.55; 2 trials, 110 women, very low-certainty evidence) compared to women who received placebo or no intervention. Supplementation with vitamin D and calcium during pregnancy may increase the risk of preterm birth < 37 weeks in comparison to women who received placebo or no intervention (RR 1.52, 95% CI 1.01 to 2.28; 5 trials, 942 women, low-certainty evidence). No trial in this comparison reported on maternal adverse events.Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D)One trial in 1300 participants was included in this comparison; it was assessed as having low risk of bias. Pre-eclampsia was not assessed. Supplementation with vitamin D + other nutrients may make little or no difference in the risk of preterm birth < 37 weeks (RR 1.04, 95% CI 0.68 to 1.59; 1 trial, 1298 women, low-certainty evidence); or low birthweight (less than 2500 g) (RR 1.12, 95% CI 0.82 to 1.51; 1 trial, 1298 women, low-certainty evidence). It is unclear whether it makes any difference to the risk of gestational diabetes (RR 0.42, 95% CI 0.10 to 1.73) or maternal adverse events (hypercalcaemia no events; hypercalciuria RR 0.25, 95% CI 0.02 to 3.97; 1 trial, 1298 women,) because the certainty of the evidence for both outcomes was found to be very low.
AUTHORS' CONCLUSIONS
We included 30 trials (7033 women) across three separate comparisons. Our GRADE assessments ranged from moderate to very low, with downgrading decisions based on limitations in study design, imprecision and indirectness.Supplementing pregnant women with vitamin D alone probably reduces the risk of pre-eclampsia, gestational diabetes, low birthweight and may reduce the risk of severe postpartum haemorrhage. It may make little or no difference in the risk of having a preterm birth < 37 weeks' gestation. Supplementing pregnant women with vitamin D and calcium probably reduces the risk of pre-eclampsia but may increase the risk of preterm births < 37 weeks (these findings warrant further research). Supplementing pregnant women with vitamin D and other nutrients may make little or no difference in the risk of preterm birth < 37 weeks' gestation or low birthweight (less than 2500 g). Additional rigorous high quality and larger randomised trials are required to evaluate the effects of vitamin D supplementation in pregnancy, particularly in relation to the risk of maternal adverse events.
Topics: Calcium, Dietary; Diabetes, Gestational; Dietary Supplements; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic; Vitamin D; Vitamins
PubMed: 31348529
DOI: 10.1002/14651858.CD008873.pub4 -
Revista Brasileira de Ginecologia E... Aug 2023To perform a systematic review and meta-analysis of studies on maternal, fetal, and neonatal outcomes of women with singleton pregnancies, after spontaneous... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To perform a systematic review and meta-analysis of studies on maternal, fetal, and neonatal outcomes of women with singleton pregnancies, after spontaneous conception, and with the diagnosis of amniotic sludge before 37 weeks of gestational age.
DATA SOURCES
We conducted a search on the PubMed, Cochrane, Bireme, and Theses databases until June 2022.
SELECTION OF STUDIES
Using the keywords or or , we found 263 articles, 132 of which were duplicates, and 70 were discarded because they did not meet the inclusion criteria.
DATA COLLECTION
The articles retrieved were analyzed by 2 reviewers; 61 were selected for full-text analysis, 18 were included for a qualitative analysis, and 14, for a quantitative analysis.
DATA SYNTHESIS
Among the maternal outcomes analyzed, there was an increased risk of preterm labor (95% confidence interval [95%CI]: 1.45-2.03), premature rupture of ovular membranes (95%CI: 1.99-3.79), and clinical (95%CI: 1.41-6.19) and histological chorioamnionitis (95%CI: 1.75-3.12). Regarding the fetal outcomes, there was a significant increase in the risk of morbidity (95%CI: 1.80-3.17), mortality (95%CI: 1.14-18.57), admission to the Neonatal Intensive Care Unit (NICU; 95%CI: 1.17-1.95), and neonatal sepsis (95%CI: 2.29-7.55).
CONCLUSION
The results of the present study indicate that the presence of amniotic sludge is a risk marker for preterm delivery. Despite the heterogeneity of the studies analyzed, even in patients with other risk factors for prematurity, such as short cervix and previous preterm delivery, the presence of amniotic sludge increases the risk of premature labor. Moreover, antibiotic therapy seems to be a treatment for amniotic sludge, and it may prolong pregnancy.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Premature Birth; Sewage; Gestational Age; Risk Factors; Databases, Factual
PubMed: 37683661
DOI: 10.1055/s-0043-1772189 -
CMAJ : Canadian Medical Association... May 2021
Meta-Analysis
Topics: COVID-19; Diabetes, Gestational; Female; Humans; Incidence; Infant, Low Birth Weight; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Severity of Illness Index; Stillbirth
PubMed: 34059502
DOI: 10.1503/cmaj.202604-f -
Ultrasound in Obstetrics & Gynecology :... Dec 2022Fetal heart-rate irregularities occur in 1-2% of pregnancies and are usually caused by premature atrial contractions (PAC). Although PAC are considered benign, they may... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Fetal heart-rate irregularities occur in 1-2% of pregnancies and are usually caused by premature atrial contractions (PAC). Although PAC are considered benign, they may be associated with cardiac defects and tachyarrhythmia. We aimed to determine the incidence of congenital heart defects (CHDs) and complications in fetuses with PAC.
METHODS
This was a systematic review and meta-analysis conducted in accordance with the PRISMA statement for reporting items for systematic reviews and meta-analyses. MEDLINE and EMBASE were searched from 1990 to June 2021 to identify studies on fetuses with PAC. The primary outcome was CHD; secondary outcomes were complications using the endpoints supraventricular tachyarrhythmia (SVT), cardiac failure and intrauterine fetal demise. Meta-analysis of proportions was performed, subdivided into high-risk and low-risk populations based on reason for referral. Pooled incidences with 95% CIs were calculated.
RESULTS
Of 2443 unique articles identified, 19 cohort studies including 2260 fetuses were included. The pooled incidence of CHD in fetuses with PAC was 2.8% (95% CI, 1.5-4.1%), when 0.6% is the incidence expected in the general population. The pooled incidence of CHD was 7.2% (95% CI, 3.5-10.9%) in the high-risk population and 0.9% (95% CI, 0.0-2.0%) in the low-risk population. SVT occurred in 1.4% (95% CI, 0.6-3.4%) of fetuses diagnosed with PAC. Cardiac failure was described in 16 fetuses (1.4% (95% CI, 0.5-3.5%)), of which eight were CHD-related. Intrauterine fetal demise occurred in four fetuses (0.9% (95% CI, 0.5-1.7%)) and was related to CHD in two cases.
CONCLUSIONS
Our findings suggest that the risk of CHD in fetuses with PAC is 4-5 times higher than that in the general population. CHD was present more frequently in the high-risk population. Consequently, an advanced ultrasound examination to diagnose PAC correctly and exclude CHD is recommended. Complications of PAC are rare but can result in fetal demise, thus weekly fetal heart-rate monitoring remains advisable to enable early detection of SVT and to prevent cardiac failure. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Female; Humans; Fetal Diseases; Premature Birth; Fetal Death; Atrial Premature Complexes; Fetus; Tachycardia; Arrhythmias, Cardiac; Heart Failure
PubMed: 35763619
DOI: 10.1002/uog.26017 -
PLoS Medicine Dec 2019There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing preterm labour and birth (tocolysis) is unproven. We conducted a systematic review and meta-analysis to assess whether antenatal magnesium sulphate is associated with unintended adverse neonatal outcomes.
METHODS AND FINDINGS
CINAHL, Cochrane Library, LILACS, MEDLINE, Embase, TOXLINE, and Web of Science, were searched (inceptions to 3 September 2019). Randomised, quasi-randomised, and non-randomised trials, cohort and case-control studies, and case reports assessing antenatal magnesium sulphate for pre-eclampsia, eclampsia, fetal neuroprotection, or tocolysis, compared with placebo/no treatment or a different magnesium sulphate regimen, were included. The primary outcome was perinatal death. Secondary outcomes included pre-specified and non-pre-specified adverse neonatal outcomes. Two reviewers screened 5,890 articles, extracted data, and assessed risk of bias following Cochrane Handbook and RTI Item Bank guidance. For randomised trials, pooled risk ratios (RRs) or mean differences, with 95% confidence intervals (CIs), were calculated using fixed- or random-effects meta-analysis. Non-randomised data were tabulated and narratively summarised. We included 197 studies (40 randomised trials, 138 non-randomised studies, and 19 case reports), of mixed quality. The 40 trials (randomising 19,265 women and their babies) were conducted from 1987 to 2018 across high- (16 trials) and low/middle-income countries (23 trials) (1 mixed). Indications included pre-eclampsia/eclampsia (24 trials), fetal neuroprotection (7 trials), and tocolysis (9 trials); 18 trials compared magnesium sulphate with placebo/no treatment, and 22 compared different regimens. For perinatal death, no clear difference in randomised trials was observed between magnesium sulphate and placebo/no treatment (RR 1.01; 95% CI 0.92 to 1.10; 8 trials, 13,654 babies), nor between regimens. Eleven of 138 non-randomised studies reported on perinatal death. Only 1 cohort (127 babies; moderate to high risk of bias) observed an increased risk of perinatal death with >48 versus ≤48 grams magnesium sulphate exposure for tocolysis. No clear secondary adverse neonatal outcomes were observed in randomised trials, and a very limited number of possible adverse outcomes warranting further consideration were identified in non-randomised studies. Where non-randomised studies observed possible harms, often no or few confounders were controlled for (moderate to high risk of bias), samples were small (200 babies or fewer), and/or results were from subgroup analyses. Limitations include missing data for important outcomes across most studies, heterogeneity of included studies, and inclusion of published data only.
CONCLUSIONS
Our findings do not support clear associations between antenatal magnesium sulphate for beneficial indications and adverse neonatal outcomes. Further large, high-quality studies (prospective cohorts or individual participant data meta-analyses) assessing specific outcomes, or the impact of regimen, pregnancy, or birth characteristics on these outcomes, would further inform safety recommendations. PROSPERO: CRD42013004451.
Topics: Case-Control Studies; Eclampsia; Female; Humans; Magnesium Sulfate; Obstetric Labor, Premature; Parturition; Pre-Eclampsia; Pregnancy; Premature Birth; Prenatal Care; Prospective Studies
PubMed: 31809499
DOI: 10.1371/journal.pmed.1002988 -
BMC Infectious Diseases Nov 2023Clinical evidence suggests that pregnant women are more vulnerable to COVID-19, since they are at increased risk for disease progression and for obstetric complications,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinical evidence suggests that pregnant women are more vulnerable to COVID-19, since they are at increased risk for disease progression and for obstetric complications, such as premature labor, miscarriage, preeclampsia, cesarean delivery, fetal growth restriction and perinatal death. Despite this evidence, pregnant women are often excluded from clinical trials, resulting in limited knowledge on COVID-19 management. The aim of this systematic review and meta-analysis is to provide better evidence on the efficacy and safety of available COVID-19 treatment in pregnant women.
METHODS
Four authors searched major electronic databases from inception until 1 st November-2022 for controlled trials/observational studies, investigating outcomes after the administration of anti-SARS-CoV-2 treatments in pregnant women affected by COVID-19. The analyses investigated the cumulative incidence of delivery and maternal outcomes in pregnant women, comparing those taking active medication vs standard care. Risk ratios (RRs) with 95% confidence intervals were calculated. Statistical significance was assessed using the random effects model and inverse-variance method. This systematic review and meta-analysis was conducted in accordance with the updated 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol has been registered in Prospero (number registration: CRD42023397445).
RESULTS
From initially 937 non duplicate records, we assessed the full texts of 40 articles, finally including ten studies. In six studies, including 1627 patients, the use of casirivimab/imdevimab (CAS/IMD), remdesivir, and IFN-alpha 2b significantly decreased the need of cesarean section ((RR = 0.665; 95%CI: 0.491-0.899; p = 0.008; I 2 = 19.5%;) (Table 1, (Fig. 1). Treatments did not decrease the risk of preterm delivery, admission to neonatal ICU, or stillbirth/perinatal loss (p-values > 0.50 for all these outcomes) and did not prevent the progression of disease towards severe degrees (k = 8; 2,374 pregnant women; RR = 0.778; 95%CI: 0.550-1.099; p = 0.15; I 2 = 0%). Moreover, the use of medications during pregnancy did not modify the incidence of maternal death in two studies (Table 2).
CONCLUSIONS
To our analysis, CAS/IMD, remdesivir, and IFN alpha 2b reduced the number of cesarean sections but demonstrated no effect on disease progression and other obstetric and COVID-19 related outcomes. The inability to evaluate the influence of viral load on illness development in pregnant women was attributed to lack of data. In our systematic review, no major side effects were reported. Though, it is essential for the medical community to focus more on clinical trials and less on episodic case reports and case series, with standardization of fetal and maternal outcomes.
Topics: Infant, Newborn; Pregnancy; Humans; Female; COVID-19; Cesarean Section; COVID-19 Drug Treatment; Stillbirth; Disease Progression; Pregnancy Outcome
PubMed: 37946100
DOI: 10.1186/s12879-023-08747-2