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American Journal of Obstetrics and... May 2023Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard.... (Review)
Review
Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard. The condition has been attributed to the passage of fetal colonic content (meconium), intraamniotic bleeding with the presence of heme catabolic products, or both. The frequency of green-stained amniotic fluid increases as a function of gestational age, reaching approximately 27% in post-term gestation. Green-stained amniotic fluid during labor has been associated with fetal acidemia (umbilical artery pH <7.00), neonatal respiratory distress, and seizures as well as cerebral palsy. Hypoxia is widely considered a mechanism responsible for fetal defecation and meconium-stained amniotic fluid; however, most fetuses with meconium-stained amniotic fluid do not have fetal acidemia. Intraamniotic infection/inflammation has emerged as an important factor in meconium-stained amniotic fluid in term and preterm gestations, as patients with these conditions have a higher rate of clinical chorioamnionitis and neonatal sepsis. The precise mechanisms linking intraamniotic inflammation to green-stained amniotic fluid have not been determined, but the effects of oxidative stress in heme catabolism have been implicated. Two randomized clinical trials suggest that antibiotic administration decreases the rate of clinical chorioamnionitis in patients with meconium-stained amniotic fluid. A serious complication of meconium-stained amniotic fluid is meconium aspiration syndrome. This condition develops in 5% of cases presenting with meconium-stained amniotic fluid and is a severe complication typical of term newborns. Meconium aspiration syndrome is attributed to the mechanical and chemical effects of aspirated meconium coupled with local and systemic fetal inflammation. Routine naso/oropharyngeal suctioning and tracheal intubation in cases of meconium-stained amniotic fluid have not been shown to be beneficial and are no longer recommended in obstetrical practice. A systematic review of randomized controlled trials suggested that amnioinfusion may decrease the rate of meconium aspiration syndrome. Histologic examination of the fetal membranes for meconium has been invoked in medical legal litigation to time the occurrence of fetal injury. However, inferences have been largely based on the results of in vitro experiments, and extrapolation of such findings to the clinical setting warrants caution. Fetal defecation throughout gestation appears to be a physiologic phenomenon based on ultrasound as well as in observations in animals.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Meconium Aspiration Syndrome; Meconium; Amniotic Fluid; Chorioamnionitis; Pregnancy Complications; Inflammation; Heme
PubMed: 37012128
DOI: 10.1016/j.ajog.2022.11.1283 -
Obstetrics and Gynecology Jun 2021To estimate the risk of maternal and neonatal sepsis associated with chorioamnionitis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the risk of maternal and neonatal sepsis associated with chorioamnionitis.
DATA SOURCES
PubMed, BIOSIS, and ClinicalTrials.gov databases were systematically searched for full-text articles in English from inception until May 11, 2020.
METHODS OF STUDY SELECTION
We screened 1,251 studies. Randomized controlled trials, case-control, or cohort studies quantifying a relationship between chorioamnionitis and sepsis in mothers (postpartum) or neonates born at greater than 22 weeks of gestation were eligible. Studies were grouped for meta-analyses according to exposures of histologic or clinical chorioamnionitis and outcomes of maternal or neonatal sepsis.
TABULATION, INTEGRATION, AND RESULTS
One hundred three studies were included, and 55 met criteria for meta-analysis (39 studies of preterm neonates, 10 studies of general populations of preterm and term neonates, and six studies of late preterm and term neonates). Study details and quantitative data were abstracted. Random-effects models were used to generate pooled odds ratios (ORs); most studies only reported unadjusted results. Histologic chorioamnionitis was associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 4.42 [95% CI 2.68-7.29] and 5.88 [95% CI 3.68-9.41], respectively). Clinical chorioamnionitis was also associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 6.82 [95% CI 4.93-9.45] and 3.90 [95% CI 2.74-5.55], respectively). Additionally, histologic and clinical chorioamnionitis were each associated with higher odds of late-onset sepsis in preterm neonates. Confirmed sepsis incidence was 7% (early-onset) and 22% (late-onset) for histologic and 6% (early-onset) and 26% (late-onset) for clinical chorioamnionitis-exposed neonates. Three studies evaluated chorioamnionitis and maternal sepsis and were inconclusive.
CONCLUSION
Both histologic and clinical chorioamnionitis were associated with early- and late-onset sepsis in neonates. Overall, our findings support current guidelines for preventative neonatal care. There was insufficient evidence to determine the association between chorioamnionitis and maternal sepsis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42020156812.
Topics: Chorioamnionitis; Female; Gestational Age; Humans; Incidence; Infant, Newborn; Neonatal Sepsis; Postpartum Period; Pregnancy; Premature Birth; Sepsis; Term Birth; Time Factors
PubMed: 33957655
DOI: 10.1097/AOG.0000000000004377 -
International Journal of Molecular... Apr 2023Preterm premature rupture of membranes, leading to preterm birth, is associated with neonatal and maternal morbidity and mortality. The study aimed to review the... (Review)
Review
Preterm premature rupture of membranes, leading to preterm birth, is associated with neonatal and maternal morbidity and mortality. The study aimed to review the existing data on the best predictive value of pregnancy latency for known biomarkers in pregnancies after preterm premature rupture of membranes. The following databases were screened for the purposes of this systematic review: Pubmed/MEDLINE, Web of Science, EMBASE, Scopus, and the Cochrane Library. The study was conducted according to the PRISMA guidelines for systematic reviews. Only a few studies assessed biomarkers predicting pregnancy duration after PPROM. IL-6, IL-8, CRP, IL1RA, s-endoglin, βhCG, AFP, PCT, urea, creatinine, oxygen radical absorbance capacity, MDA, lipocalin-2, endotoxin activity, MMP-8, MMP-9 and S100 A8/A9 were found to have a positive predictive value for delivery timing prediction. Proinflammatory biomarkers, such as IL-6 or CRP, proved to be best correlated with delivery timing, independent of the occurrence of intrauterine infection.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Premature Birth; Interleukin-6; Fetal Membranes, Premature Rupture; Biomarkers; Gestational Age
PubMed: 37175733
DOI: 10.3390/ijms24098027 -
PLoS Medicine Dec 2019Infection is an important, preventable cause of maternal morbidity, and pregnancy-related sepsis accounts for 11% of maternal deaths. However, frequency of maternal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Infection is an important, preventable cause of maternal morbidity, and pregnancy-related sepsis accounts for 11% of maternal deaths. However, frequency of maternal infection is poorly described, and, to our knowledge, it remains the one major cause of maternal mortality without a systematic review of incidence. Our objective was to estimate the average global incidence of maternal peripartum infection.
METHODS AND FINDINGS
We searched Medline, EMBASE, Global Health, and five other databases from January 2005 to June 2016 (PROSPERO: CRD42017074591). Specific outcomes comprised chorioamnionitis in labour, puerperal endometritis, wound infection following cesarean section or perineal trauma, and sepsis occurring from onset of labour until 42 days postpartum. We assessed studies irrespective of language or study design. We excluded conference abstracts, studies of high-risk women, and data collected before 1990. Three reviewers independently selected studies, extracted data, and appraised quality. Quality criteria for incidence/prevalence studies were adapted from the Joanna Briggs Institute. We used random-effects models to obtain weighted pooled estimates of incidence risk for each outcome and metaregression to identify study-level characteristics affecting incidence. From 31,528 potentially relevant articles, we included 111 studies of infection in women in labour or postpartum from 46 countries. Four studies were randomised controlled trials, two were before-after intervention studies, and the remainder were observational cohort or cross-sectional studies. The pooled incidence in high-quality studies was 3.9% (95% Confidence Interval [CI] 1.8%-6.8%) for chorioamnionitis, 1.6% (95% CI 0.9%-2.5%) for endometritis, 1.2% (95% CI 1.0%-1.5%) for wound infection, 0.05% (95% CI 0.03%-0.07%) for sepsis, and 1.1% (95% CI 0.3%-2.4%) for maternal peripartum infection. 19% of studies met all quality criteria. There were few data from developing countries and marked heterogeneity in study designs and infection definitions, limiting the interpretation of these estimates as measures of global infection incidence. A limitation of this review is the inclusion of studies that were facility-based or restricted to low-risk groups of women.
CONCLUSIONS
In this study, we observed pooled infection estimates of almost 4% in labour and between 1%-2% of each infection outcome postpartum. This indicates maternal peripartum infection is an important complication of childbirth and that preventive efforts should be increased in light of antimicrobial resistance. Incidence risk appears lower than modelled global estimates, although differences in definitions limit comparability. Better-quality research, using standard definitions, is required to improve comparability between study settings and to demonstrate the influence of risk factors and protective interventions.
Topics: Anti-Bacterial Agents; Cesarean Section; Cross-Sectional Studies; Delivery, Obstetric; Female; Humans; Infections; Labor, Obstetric; Parturition; Peripartum Period; Postpartum Period; Pregnancy; Sepsis
PubMed: 31821329
DOI: 10.1371/journal.pmed.1002984 -
The Cochrane Database of Systematic... Feb 2020Induction of labour involves stimulating uterine contractions artificially to promote the onset of labour. There are several pharmacological, surgical and mechanical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Induction of labour involves stimulating uterine contractions artificially to promote the onset of labour. There are several pharmacological, surgical and mechanical methods used to induce labour. Membrane sweeping is a mechanical technique whereby a clinician inserts one or two fingers into the cervix and using a continuous circular sweeping motion detaches the inferior pole of the membranes from the lower uterine segment. This produces hormones that encourage effacement and dilatation potentially promoting labour. This review is an update to a review first published in 2005.
OBJECTIVES
To assess the effects and safety of membrane sweeping for induction of labour in women at or near term (≥ 36 weeks' gestation).
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (25 February 2019), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (25 February 2019), and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing membrane sweeping used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed on a predefined list of labour induction methods. Cluster-randomised trials were eligible, but none were identified.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, risk of bias and extracted data. Data were checked for accuracy. Disagreements were resolved by discussion, or by including a third review author. The certainty of the evidence was assessed using the GRADE approach.
MAIN RESULTS
We included 44 studies (20 new to this update), reporting data for 6940 women and their infants. We used random-effects throughout. Overall, the risk of bias was assessed as low or unclear risk in most domains across studies. Evidence certainty, assessed using GRADE, was found to be generally low, mainly due to study design, inconsistency and imprecision. Six studies (n = 1284) compared membrane sweeping with more than one intervention and were thus included in more than one comparison. No trials reported on the outcomes uterine hyperstimulation with/without fetal heart rate (FHR) change, uterine rupture or neonatal encephalopathy. Forty studies (6548 participants) compared membrane sweeping with no treatment/sham Women randomised to membrane sweeping may be more likely to experience: · spontaneous onset of labour (average risk ratio (aRR) 1.21, 95% confidence interval (CI) 1.08 to 1.34, 17 studies, 3170 participants, low-certainty evidence). but less likely to experience: · induction (aRR 0.73, 95% CI 0.56 to 0.94, 16 studies, 3224 participants, low-certainty evidence); There may be little to no difference between groups for: · caesareans (aRR 0.94, 95% CI 0.85 to 1.04, 32 studies, 5499 participants, moderate-certainty evidence); · spontaneous vaginal birth (aRR 1.03, 95% CI 0.99 to 1.07, 26 studies, 4538 participants, moderate-certainty evidence); · maternal death or serious morbidity (aRR 0.83, 95% CI 0.57 to 1.20, 17 studies, 2749 participants, low-certainty evidence); · neonatal perinatal death or serious morbidity (aRR 0.83, 95% CI 0.59 to 1.17, 18 studies, 3696 participants, low-certainty evidence). Four studies reported data for 480 women comparing membrane sweeping with vaginal/intracervical prostaglandins There may be little to no difference between groups for the outcomes: · spontaneous onset of labour (aRR, 1.24, 95% CI 0.98 to 1.57, 3 studies, 339 participants, low-certainty evidence); · induction (aRR 0.90, 95% CI 0.56 to 1.45, 2 studies, 157 participants, low-certainty evidence); · caesarean (aRR 0.69, 95% CI 0.44 to 1.09, 3 studies, 339 participants, low-certainty evidence); · spontaneous vaginal birth (aRR 1.12, 95% CI 0.95 to 1.32, 2 studies, 252 participants, low-certainty evidence); · maternal death or serious morbidity (aRR 0.93, 95% CI 0.27 to 3.21, 1 study, 87 participants, low-certainty evidence); · neonatal perinatal death or serious morbidity (aRR 0.40, 95% CI 0.12 to 1.33, 2 studies, 269 participants, low-certainty evidence). One study, reported data for 104 women, comparing membrane sweeping with intravenous oxytocin +/- amniotomy There may be little to no difference between groups for: · spontaneous onset of labour (aRR 1.32, 95% CI 88 to 1.96, 1 study, 69 participants, low-certainty evidence); · induction (aRR 0.51, 95% CI 0.05 to 5.42, 1 study, 69 participants, low-certainty evidence); · caesarean (aRR 0.69, 95% CI 0.12 to 3.85, 1 study, 69 participants, low-certainty evidence); · maternal death or serious morbidity was reported on, but there were no events. Two studies providing data for 160 women compared membrane sweeping with vaginal/oral misoprostol There may be little to no difference between groups for: · caesareans (RR 0.82, 95% CI 0.31 to 2.17, 1 study, 96 participants, low-certainty evidence). One study providing data for 355 women which compared once weekly membrane sweep with twice-weekly membrane sweep and a sham procedure There may be little to no difference between groups for: · induction (RR 1.19, 95% CI 0.76 to 1.85, 1 study, 234 participants, low-certainty); · caesareans (RR 0.93, 95% CI 0.60 to 1.46, 1 study, 234 participants, low-certainty evidence); · spontaneous vaginal birth (RR 1.00, 95% CI 0.86 to 1.17, 1 study, 234 participants, moderate-certainty evidence); · maternal death or serious maternal morbidity (RR 0.78, 95% CI 0.30 to 2.02, 1 study, 234 participants, low-certainty evidence); · neonatal death or serious neonatal perinatal morbidity (RR 2.00, 95% CI 0.18 to 21.76, 1 study, 234 participants, low-certainty evidence); We found no studies that compared membrane sweeping with amniotomy only or mechanical methods. Three studies, providing data for 675 women, reported that women indicated favourably on their experience of membrane sweeping with one study reporting that 88% (n = 312) of women questioned in the postnatal period would choose membrane sweeping in the next pregnancy. Two studies reporting data for 290 women reported that membrane sweeping is more cost-effective than using prostaglandins, although more research should be undertaken in this area.
AUTHORS' CONCLUSIONS
Membrane sweeping may be effective in achieving a spontaneous onset of labour, but the evidence for this was of low certainty. When compared to expectant management, it potentially reduces the incidence of formal induction of labour. Questions remain as to whether there is an optimal number of membrane sweeps and timings and gestation of these to facilitate induction of labour.
Topics: Amnion; Cervical Ripening; Female; Humans; Labor, Induced; Mechanical Phenomena; Pregnancy; Pregnancy Outcome; Randomized Controlled Trials as Topic; Risk Factors; Term Birth
PubMed: 32103497
DOI: 10.1002/14651858.CD000451.pub3 -
Clinical Rehabilitation Jun 2023To determine the effects of different therapeutic interventions that have ever been evaluated in randomized controlled trials on pain due to plantar fasciitis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the effects of different therapeutic interventions that have ever been evaluated in randomized controlled trials on pain due to plantar fasciitis.
METHODS
We searched different electronic databases until September 2022. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated. The Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the overall certainty evidence.
RESULTS
A total of 236 studies met the study criteria, including 15,401 patients. Botulinum toxin MD -2.14 (CI: -4.15, -0.14), micronized dehydrated human amnion/chorion membrane injection MD -3.31 (CI: -5.54, -1.08), dry needling MD -2.34 (CI: -4.64, -0.04), low-dye taping MD -3.60 (CI: -4.16, -3.03), low-level laser therapy MD -2.09 (CI: -2.28, -1.90), myofascial releases MD -1.79 (CI: -2.63, -0.94), platelet-rich plasma MD -2.40 (CI: -4.16, -0.63), radiofrequency MD -2.47 (CI: -4.65, -0.29), and stretching MD -1.14 (CI: -2.02, -0.26) resulted in being effective treatments for pain when compared to the control in the short term. In the medium and long term, only extracorporeal shock wave therapy MD -0.97 (CI: -1.13, -0.81)/MD -2.49 (CI: -3.17, -1.82) was effective for improving pain when compared to the control.
CONCLUSIONS
Considering the available studies, this systematic review and meta-analysis showed that different therapeutic interventions seem to be useful strategies for improving pain in patients with plantar fasciitis. In the medium and long term, only extracorporeal shock wave therapy was effective in improving pain when compared to the control.
Topics: Humans; Fasciitis, Plantar; Pain Management; Pain; Extracorporeal Shockwave Therapy; Treatment Outcome
PubMed: 36571559
DOI: 10.1177/02692155221143865 -
American Journal of Obstetrics and... May 2023This study aimed to reassess the effect of prophylactic transcervical amnioinfusion for intrapartum meconium-stained amniotic fluid on meconium aspiration syndrome and... (Meta-Analysis)
Meta-Analysis Review
Intrapartum amnioinfusion reduces meconium aspiration syndrome and improves neonatal outcomes in patients with meconium-stained fluid: a systematic review and meta-analysis.
OBJECTIVE
This study aimed to reassess the effect of prophylactic transcervical amnioinfusion for intrapartum meconium-stained amniotic fluid on meconium aspiration syndrome and other adverse neonatal and maternal outcomes.
DATA SOURCES
From inception to November 2021, a systematic search of the literature was performed in PubMed, Embase, Web of Science, and Scopus databases and gray literature sources.
STUDY ELIGIBILITY CRITERIA
We identified randomized controlled trials of patients with intrapartum moderate to thick meconium-stained amniotic fluid that evaluated the effect of amnioinfusion on adverse neonatal and maternal outcomes.
METHODS
Of note, 2 reviewers independently abstracted data and gauged study quality by assigning a modified Jadad score. Meconium aspiration syndrome constituted the primary outcome. The secondary outcomes were meconium below the cords, Apgar scores of <7 at 5 minutes, neonatal acidosis, cesarean delivery, cesarean delivery for fetal heart rate abnormalities, neonatal intensive care unit admission, and postpartum endometritis. This study calculated the odds ratios with 95% confidence intervals for categorical outcomes and weighted mean differences with 95% confidence intervals for continuous outcomes.
RESULTS
A total of 24 randomized studies with 5994 participants met the inclusion criteria. The overall odds of meconium aspiration syndrome was reduced by 67% in the amnioinfusion group (pooled odds ratio, 0.33; 95% confidence interval, 0.21-0.51). Except for postpartum endometritis, amnioinfusion was associated with a significant reduction in all secondary outcomes.
CONCLUSION
Our study found that the use of intrapartum amnioinfusion in the setting of meconium-stained amniotic fluid significantly reduces the odds of meconium aspiration syndrome and other adverse neonatal outcomes.
Topics: Pregnancy; Female; Humans; Infant, Newborn; Meconium Aspiration Syndrome; Meconium; Amnion; Endometritis; Obstetric Labor Complications; Sodium Chloride; Amniotic Fluid
PubMed: 37164492
DOI: 10.1016/j.ajog.2022.07.047 -
American Journal of Obstetrics and... Jun 2022This study aimed to estimate the effect of erythromycin vs azithromycin on the duration of latency and the rate of clinical chorioamnionitis in women with preterm... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to estimate the effect of erythromycin vs azithromycin on the duration of latency and the rate of clinical chorioamnionitis in women with preterm prelabor rupture of membranes by performing a systematic review and meta-analysis of the existing literature.
DATA SOURCES
From inception to October 2021, we explored MEDLINE, Scopus, Embase, CINAHL, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials.
STUDY ELIGIBILITY CRITERIA
Studies comparing the duration of latency and the rate of clinical chorioamnionitis between women with preterm prelabor rupture of membranes who were treated with erythromycin and those who were treated with azithromycin at the time of diagnosis were included.
METHODS
Here, 2 reviewers separately ascertained studies, obtained data, and gauged study quality. The mean length of latency and the rate of clinical chorioamnionitis were compared and mean differences and odds ratios with 95% confidence intervals were estimated.
RESULTS
A total of 5 studies with 1289 women were identified. The mean length of latency in women with preterm prelabor rupture of membranes was similar between individuals treated with erythromycin and those treated with azithromycin: 6.6 days vs 6.7 days (mean difference, 0.07 days; 95% confidence interval, -0.45 to 0.60; I, 0%). The median point prevalence rates of clinical chorioamnionitis were 25% (95% confidence interval, 12-32) in women treated with erythromycin and 14% (95% confidence interval, 9-24) in women treated with azithromycin. The overall clinical chorioamnionitis rate in women treated with azithromycin was lower than women treated with erythromycin (pooled odds ratio, 0.53; 95% confidence interval, 0.39-0.71; I, 0%).
CONCLUSION
The administration of azithromycin in women with preterm prelabor rupture of membranes was associated with a similar latency period but a lower rate of clinical chorioamnionitis than the administration of erythromycin.
Topics: Azithromycin; Chorioamnionitis; Erythromycin; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Pregnancy
PubMed: 34973176
DOI: 10.1016/j.ajog.2021.12.262 -
American Journal of Obstetrics &... Jul 2023Various prophylactic antibiotic regimens are used in the management of preterm premature rupture of membranes. We investigated the efficacy and safety of these regimens... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Various prophylactic antibiotic regimens are used in the management of preterm premature rupture of membranes. We investigated the efficacy and safety of these regimens in terms of maternal and neonatal outcomes.
DATA SOURCES
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 20, 2021.
STUDY ELIGIBILITY CRITERIA
We included randomized controlled trials involving pregnant women with preterm premature rupture of membranes before 37 weeks of gestation and a comparison of ≥2 of the following 10 antibiotic regimens: control/placebo, erythromycin, clindamycin, clindamycin plus gentamicin, penicillins, cephalosporins, co-amoxiclav, co-amoxiclav plus erythromycin, aminopenicillins plus macrolides, and cephalosporins plus macrolides.
METHODS
Two investigators independently extracted published data and assessed the risk of bias with a standard procedure following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Network meta-analysis was conducted using the random-effects model.
RESULTS
A total of 23 studies that recruited a total of 7671 pregnant women were included. Only penicillins (odds ratio, 0.46; 95% confidence interval, 0.27-0.77) had significantly superior effectiveness for maternal chorioamnionitis. Clindamycin plus gentamicin reduced the risk of clinical chorioamnionitis, with borderline significance (odds ratio, 0.16; 95% confidence interval, 0.03-1.00). By contrast, clindamycin alone increased the risk of maternal infection. For cesarean delivery, no significant differences were noted among these regimens.
CONCLUSION
Penicillins remain the recommended antibiotic regimen for reducing maternal clinical chorioamnionitis. The alternative regimen includes clindamycin plus gentamicin. Clindamycin should not be used alone.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Clindamycin; Chorioamnionitis; Amoxicillin-Potassium Clavulanate Combination; Network Meta-Analysis; Anti-Bacterial Agents; Premature Birth; Erythromycin; Macrolides; Gentamicins; Cephalosporins
PubMed: 37094635
DOI: 10.1016/j.ajogmf.2023.100978 -
Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.The Cochrane Database of Systematic... Dec 2020Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. Despite early evidence indicating a beneficial effect of antenatal corticosteroids on fetal lung maturation and widespread recommendations to use this treatment in women at risk of preterm delivery, some uncertainty remains about their effectiveness particularly with regard to their use in lower-resource settings, different gestational ages and high-risk obstetric groups such as women with hypertension or multiple pregnancies. This updated review (which supersedes an earlier review Crowley 1996) was first published in 2006 and subsequently updated in 2017.
OBJECTIVES
To assess the effects of administering a course of corticosteroids to women prior to anticipated preterm birth (before 37 weeks of pregnancy) on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and on the child in later life.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (3 September 2020), ClinicalTrials.gov, the databases that contribute to the WHO International Clinical Trials Registry Platform (ICTRP) (3 September 2020), and reference lists of the retrieved studies.
SELECTION CRITERIA
We considered all randomised controlled comparisons of antenatal corticosteroid administration with placebo, or with no treatment, given to women with a singleton or multiple pregnancy, prior to anticipated preterm delivery (elective, or following rupture of membranes or spontaneous labour), regardless of other co-morbidity, for inclusion in this review.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two review authors independently assessed trials for inclusion, assessed risk of bias, evaluated trustworthiness based on predefined criteria developed by Cochrane Pregnancy and Childbirth, extracted data and checked them for accuracy, and assessed the certainty of the evidence using the GRADE approach. Primary outcomes included perinatal death, neonatal death, RDS, intraventricular haemorrhage (IVH), birthweight, developmental delay in childhood and maternal death.
MAIN RESULTS
We included 27 studies (11,272 randomised women and 11,925 neonates) from 20 countries. Ten trials (4422 randomised women) took place in lower- or middle-resource settings. We removed six trials from the analysis that were included in the previous version of the review; this review only includes trials that meet our pre-defined trustworthiness criteria. In 19 trials the women received a single course of steroids. In the remaining eight trials repeated courses may have been prescribed. Fifteen trials were judged to be at low risk of bias, two had a high risk of bias in two or more domains and we ten trials had a high risk of bias due to lack of blinding (placebo was not used in the control arm. Overall, the certainty of evidence was moderate to high, but it was downgraded for IVH due to indirectness; for developmental delay due to risk of bias and for maternal adverse outcomes (death, chorioamnionitis and endometritis) due to imprecision. Neonatal/child outcomes Antenatal corticosteroids reduce the risk of: - perinatal death (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.77 to 0.93; 9833 infants; 14 studies; high-certainty evidence; 2.3% fewer, 95% CI 1.1% to 3.6% fewer), - neonatal death (RR 0.78, 95% CI 0.70 to 0.87; 10,609 infants; 22 studies; high-certainty evidence; 2.6% fewer, 95% CI 1.5% to 3.6% fewer), - respiratory distress syndrome (RR 0.71, 95% CI 0.65 to 0.78; 11,183 infants; studies = 26; high-certainty evidence; 4.3% fewer, 95% CI 3.2% to 5.2% fewer). Antenatal corticosteroids probably reduce the risk of IVH (RR 0.58, 95% CI 0.45 to 0.75; 8475 infants; 12 studies; moderate-certainty evidence; 1.4% fewer, 95% CI 0.8% to1.8% fewer), and probably have little to no effect on birthweight (mean difference (MD) -14.02 g, 95% CI -33.79 to 5.76; 9551 infants; 19 studies; high-certainty evidence). Antenatal corticosteroids probably lead to a reduction in developmental delay in childhood (RR 0.51, 95% CI 0.27 to 0.97; 600 children; 3 studies; moderate-certainty evidence; 3.8% fewer, 95% CI 0.2% to 5.7% fewer). Maternal outcomes Antenatal corticosteroids probably result in little to no difference in maternal death (RR 1.19, 95% CI 0.36 to 3.89; 6244 women; 6 studies; moderate-certainty evidence; 0.0% fewer, 95% CI 0.1% fewer to 0.5% more), chorioamnionitis (RR 0.86, 95% CI 0.69 to 1.08; 8374 women; 15 studies; moderate-certainty evidence; 0.5% fewer, 95% CI 1.1% fewer to 0.3% more), and endometritis (RR 1.14, 95% CI 0.82 to 1.58; 6764 women; 10 studies; moderate-certainty; 0.3% more, 95% CI 0.3% fewer to 1.1% more) The wide 95% CIs in all of these outcomes include possible benefit and possible harm.
AUTHORS' CONCLUSIONS
Evidence from this updated review supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. Treatment with antenatal corticosteroids reduces the risk of perinatal death, neonatal death and RDS and probably reduces the risk of IVH. This evidence is robust, regardless of resource setting (high, middle or low). Further research should focus on variations in the treatment regimen, effectiveness of the intervention in specific understudied subgroups such as multiple pregnancies and other high-risk obstetric groups, and the risks and benefits in the very early or very late preterm periods. Additionally, outcomes from existing trials with follow-up into childhood and adulthood are needed in order to investigate any longer-term effects of antenatal corticosteroids. We encourage authors of previous studies to provide further information which may answer any remaining questions about the use of antenatal corticosteroids without the need for further randomised controlled trials. Individual patient data meta-analyses from published trials are likely to provide answers for most of the remaining clinical uncertainties.
Topics: Adrenal Cortex Hormones; Betamethasone; Bias; Cerebral Intraventricular Hemorrhage; Developmental Disabilities; Dexamethasone; Female; Fetal Organ Maturity; Humans; Hydrocortisone; Infant, Newborn; Lung; Maternal Death; Perinatal Death; Pregnancy; Premature Birth; Prenatal Care; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 33368142
DOI: 10.1002/14651858.CD004454.pub4