Stéphanie Roberge

Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis.

OBJECTIVE: To estimate the effect of low-dose aspirin started in early pregnancy on the incidence of preeclampsia and intrauterine growth restriction (IUGR). DATA SOURCES: A systematic review and meta-analysis were performed through electronic database searches (PubMed, Cochrane, Embase). METHODS OF STUDY SELECTION: Randomized controlled trials of pregnant women at risk of preeclampsia who were assigned to receive aspirin or placebo (or no treatment) were reviewed. Secondary outcomes included IUGR, severe preeclampsia and preterm birth. The effect of aspirin was analyzed as a function of gestational age at initiation of the intervention (16 weeks of gestation or less, 16 weeks of gestation or more). TABULATION, INTEGRATION, AND RESULTS: Thirty-four randomized controlled trials met the inclusion criteria, including 27 studies (11,348 women) with follow-up for the outcome of preeclampsia. Low-dose aspirin started at 16 weeks or earlier was associated with a significant reduction in preeclampsia (relative risk [RR] 0.47, 95% confidence interval [CI] 0.34–0.65, prevalence in 9.3% treated compared with 21.3% control) and IUGR (RR 0.44, 95% CI 0.30–0.65, 7% treated compared with 16.3% control), whereas aspirin started after 16 weeks was not (preeclampsia: RR 0.81, 95% CI 0.63–1.03, prevalence in 7.3% treated compared with 8.1% control; IUGR: RR 0.98, 95% CI 0.87–1.10, 10.3% treated compared with 10.5% control). Low-dose aspirin started at 16 weeks or earlier also was associated with a reduction in severe preeclampsia (RR 0.09, 95% CI 0.02–0.37, 0.7% treated compared with 15.0% control), gestational hypertension (RR 0.62, 95% CI 0.45–0.84, 16.7% treated compared with 29.7% control), and preterm birth (RR 0.22, 95% CI 0.10–0.49, 3.5% treated compared with 16.9% control). Of note, all studies for which aspirin had been started at 16 weeks or earlier included women identified to be at moderate or high risk for preeclampsia. CONCLUSION: Low-dose aspirin initiated in early pregnancy is an efficient method of reducing the incidence of preeclampsia and IUGR.

Early administration of low-dose aspirin for the prevention of preterm and term preeclampsia: a systematic review and meta-analysis.

Objective: To compare the effect of early administration of aspirin on the risk of preterm and term preeclampsia. Method: A systematic review and meta-analysis of randomized controlled trials were performed. Women who were randomized to low-dose aspirin or placebo/no treatment at or before 16 weeks of gestation were included. The outcomes of interest were preterm preeclampsia (delivery <37 weeks) and term preeclampsia. Pooled relative risks (RR) with their 95% confidence intervals (CI) were computed. Results: The search identified 7,941 citations but only five trials on a combined total of 556 women fulfilled the inclusion criteria. When compared to controls, aspirin initiated ≤16 weeks of gestation was associated with a major reduction of the risk of preterm preeclampsia (RR 0.11, 95% CI 0.04–0.33) but had no significant effect on term preeclampsia (RR 0.98, 95% CI 0.42–2.33). Conclusion: Low-dose aspirin administrated at or before 16 weeks of gestation reduces the risk of preterm but not term preeclampsia.

Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis

To compare early vs late administration of low‐dose aspirin on the risk of perinatal death and adverse perinatal outcome.

The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis

BACKGROUND: Preeclampsia and fetal growth restriction are major causes of perinatal death and handicap in survivors. Randomized clinical trials have reported that the risk of preeclampsia, severe preeclampsia, and fetal growth restriction can be reduced by the prophylactic use of aspirin in high‐risk women, but the appropriate dose of the drug to achieve this objective is not certain. OBJECTIVE: We sought to estimate the impact of aspirin dosage on the prevention of preeclampsia, severe preeclampsia, and fetal growth restriction. STUDY DESIGN: We performed a systematic review and meta‐analysis of randomized controlled trials comparing the effect of daily aspirin or placebo (or no treatment) during pregnancy. We searched MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials up to December 2015, and study bibliographies were reviewed. Authors were contacted to obtain additional data when needed. Relative risks for preeclampsia, severe preeclampsia, and fetal growth restriction were calculated with 95% confidence intervals using random‐effect models. Dose‐response effect was evaluated using meta‐regression and reported as adjusted R2. Analyses were stratified according to gestational age at initiation of aspirin (≤16 and >16 weeks) and repeated after exclusion of studies at high risk of biases. RESULTS: In all, 45 randomized controlled trials included a total of 20,909 pregnant women randomized to between 50‐150 mg of aspirin daily. When aspirin was initiated at ≤16 weeks, there was a significant reduction and a dose‐response effect for the prevention of preeclampsia (relative risk, 0.57; 95% confidence interval, 0.43–0.75; P < .001; R2, 44%; P = .036), severe preeclampsia (relative risk, 0.47; 95% confidence interval, 0.26–0.83; P = .009; R2, 100%; P = .008), and fetal growth restriction (relative risk, 0.56; 95% confidence interval, 0.44–0.70; P < .001; R2, 100%; P = .044) with higher dosages of aspirin being associated with greater reduction of the 3 outcomes. Similar results were observed after the exclusion of studies at high risk of biases. When aspirin was initiated at >16 weeks, there was a smaller reduction of preeclampsia (relative risk, 0.81; 95% confidence interval, 0.66–0.99; P = .04) without relationship with aspirin dosage (R2, 0%; P = .941). Aspirin initiated at >16 weeks was not associated with a risk reduction or a dose‐response effect for severe preeclampsia (relative risk, 0.85; 95% confidence interval, 0.64–1.14; P = .28; R2, 0%; P = .838) and fetal growth restriction (relative risk, 0.95; 95% confidence interval, 0.86–1.05; P = .34; R2, not available; P = .563). CONCLUSION: Prevention of preeclampsia and fetal growth restriction using aspirin in early pregnancy is associated with a dose‐response effect. Low‐dose aspirin initiated at >16 weeks’ gestation has a modest or no impact on the risk of preeclampsia, severe preeclampsia, and fetal growth restriction. Women at high risk for those outcomes should be identified in early pregnancy.

Sonographic Lower Uterine Segment Thickness and Risk of Uterine Scar Defect: A Systematic Review

OBJECTIVE To study the diagnostic accuracy of sonographic measurements of the lower uterine segment (LUS) thickness near term in predicting uterine scar defects in women with prior Caesarean section (CS). DATA SOURCES PubMed, Embase, and Cochrane Library (1965-2009). METHODS OF STUDY SELECTION Studies of populations of women with previous low transverse CS who underwent third-trimester evaluation of LUS thickness were selected. We retrieved articles in which number of patients, sensitivity, and specificity to predict a uterine scar defect were available. DATA SYNTHESIS Twelve eligible studies including 1834 women were identified. Uterine scar defect was reported in a total of 121 cases (6.6%). Seven studies examined the full LUS thickness only, four examined the myometrial layer specifically, and one examined both measurements. Weighted mean differences in LUS thickness and associated 95% confidence intervals between women with and without uterine scar defect were calculated. Summary receiver operating characteristic (SROC) analysis and summary diagnostic odds ratios (DOR) were used to evaluate and compare the area under the curve (AUC) and the association between LUS thickness and uterine scar defect. Women with a uterine scar defect had thinner full LUS and thinner myometrial layer (weighted mean difference of 0.98 mm; 95% CI 0.37 to 1.59, P = 0.002; and 1.13 mm; 95% CI 0.32 to 1.94 mm, P = 0.006, respectively). SROC analysis showed a stronger association between full LUS thickness and uterine scar defect (AUC: 0.84 +/- 0.03, P < 0.001) than between myometrial layer and scar defect (AUC: 0.75 +/- 0.05, P < 0.01). The optimal cut-off value varied from 2.0 to 3.5 mm for full LUS thickness and from 1.4 to 2.0 for myometrial layer. CONCLUSION Sonographic LUS thickness is a strong predictor for uterine scar defect in women with prior Caesarean section. However, because of the heterogeneity of the studies we analyzed, no ideal cut-off value can yet be recommended, which underlines the need for more standardized measurement techniques in future studies.

Single- versus double-layer closure of the hysterotomy incision during cesarean delivery and risk of uterine rupture

To evaluate the best available evidence regarding the association between single‐layer closure and uterine rupture.

Systematic review of cesarean scar assessment in the nonpregnant state: imaging techniques and uterine scar defect.

OBJECTIVE To review the ability of imaging techniques to predict incomplete healing of uterine cesarean scars before the next pregnancy. STUDY DESIGN A systematic literature review searched for studies on women who underwent previous low-transverse cesarean, evaluated by hysterography, sonohysterography (SHG), or transvaginal ultrasound (TVU). The median prevalence of scar defects was computed with 95% confidence intervals (95% CIs). Odds ratio (OR, 95% CI) identified risk factors of incomplete healing. RESULTS The analysis included 21 studies. The proportions of suspected scar defects detected by hysterography, SGH, and TVU were 58% (33 to 70), 59% (58 to 85), and 37% (20 to 65), respectively. Two studies found that women with a large uterine scar defect had a higher risk of uterine rupture or uterine scar dehiscence than those with no scar defect or small scar defect (OR: 26.05 [2.36 to 287.61], p <0.001). The only reported risk factor for scar defect was the occurrence of more than one previous cesarean (OR: 2.24 [1.13, 4.45], p = 0.02). CONCLUSION Hysterography, SGH, and TVU can detect uterine scar defects in ~50% of women with previous cesarean.

Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and metaanalysis

A systematic review and metaanalysis were performed through electronic database searches to estimate the effect of uterine closure at cesarean on the risk of adverse maternal outcome and on uterine scar evaluated by ultrasound. Randomized controlled trials, which compared single vs double layers and locking vs unlocking sutures for uterine closure of low transverse cesarean, were included. Outcomes were short-term complications (endometritis, wound infection, maternal infectious morbidity, blood transfusion, duration of surgical procedure, length of hospital stay, mean blood loss), uterine rupture or dehiscence at next pregnancy, and uterine scar evaluation by ultrasound. Twenty of 1278 citations were included in the analysis. We found that all types of closure were comparable for short-term maternal outcomes, except for single-layer closure, which had shorter operative time (-6.1 minutes; 95% confidence interval [CI], -8.7 to -3.4; P < .001) than double-layer closure. Single layer (-2.6 mm; 95% CI, -3.1 to -2.1; P < .001) and locked first layer (mean difference, -2.5 mm; 95% CI, -3.2 to -1.8; P < .001) were associated with lower residual myometrial thickness. Two studies reported no significant difference between single- vs double-layer closure for uterine dehiscence (relative risk, 1.86; 95% CI, 0.44-7.90; P = .40) or uterine rupture (no case). In conclusion, current evidence based on randomized trials does not support a specific type of uterine closure for optimal maternal outcomes and is insufficient to conclude about the risk of uterine rupture. Single-layer closure and locked first layer are possibly coupled with thinner residual myometrium thickness.

Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis

OBJECTIVE DATA: Metaanalyses of randomized controlled trials have reported contradictory results about the effect of aspirin in the prevention of preeclampsia, both in terms of the gestational age at the onset of treatment and the dose of the drug. The controversy may be resolved by a metaanalysis that includes several recently published trials and particularly the large Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence‐based Preeclampsia Prevention trial and by examination of whether there is a difference of the effect of aspirin on preterm vs term preeclampsia. STUDY: We performed a systematic review and metaanalysis that evaluated the prophylactic effect of aspirin during pregnancy. STUDY APPRAISAL AND SYNTHESIS METHODS: We completed a literature search through PubMed, Cinhal, Embase, Web of Science, and Cochrane library from 1985 to June 2017. Relative risks with random effect were calculated with their 95% confidence intervals. RESULTS: Sixteen trials that included 18,907 participants provided data for preterm and term preeclampsia. Eight of the included studies were evaluated as being of good quality, and the other 8 studies were deemed to be of poor or uncertain quality. There was high heterogeneity within studies (I2 >50%) for preterm and term preeclampsia, but no heterogeneity was found in the subgroup of preterm preeclampsia when the onset of treatment was ≤16 weeks of gestation and the daily dose of aspirin was ≥100 mg (I2=0%). Administration of aspirin was associated with reduction in the risk of preterm preeclampsia (relative risk, 0.62; 95% confidence interval, 0.45–0.87), but there was no significant effect on term preeclampsia (relative risk, 0.92; 95% confidence interval, 0.70–1.21). The reduction in preterm preeclampsia was confined to the subgroup in which aspirin was initiated at ≤16 weeks of gestation and at a daily dose of ≥100 mg (relative risk, 0.33; 95% confidence interval, 0.19–0.57). This effect was also observed in the high‐quality studies. The reduction in preterm preeclampsia that was observed in the largest trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence‐based Preeclampsia Prevention; n=1620; relative risk, 0.38; 95% confidence interval, 0.20–0.72) was similar to that in the 5 smaller trials in which aspirin was initiated at ≤16 weeks of gestation and at a daily dose of ≥100 mg (n=639; relative risk, 0.22; 95% confidence interval, 0.07–0.66). CONCLUSION: Aspirin reduces the risk of preterm preeclampsia, but not term preeclampsia, and only when it is initiated at ≤16 weeks of gestation and at a daily dose of ≥100 mg.

Role of fetal sex in the outcome of antenatal glucocorticoid treatment to prevent respiratory distress syndrome: systematic review and meta-analysis.

BACKGROUND Antenatal glucocorticoid (AGC) therapy has been associated with a decrease in respiratory distress syndrome (RDS). While preterm males remain at greater risk of RDS than females, the role of fetal sex in AGC response is not well known. OBJECTIVES To review the available evidence regarding the effect of fetal sex in the prevention of RDS using AGC. METHOD We conducted a systematic review and meta-analysis of RCTs to compare the effect of AGC in male and female infants with regard to the rates of RDS, intra-ventricular hemorrhage (IVH) grades III and IV, and neonatal mortality. Random effects with 95% confidence intervals were assessed in both groups and relative risks were compared using mixed regression. RESULTS From 248 potentially eligible articles, we included eight in the analysis for a total of 1109 male and 968 female infants. Both male and female infants had a significant decrease in the risks, but no difference between the sexes was observed in terms of reduction in RDS (RR 0.50; 95% CI 0.33 to 0.77 for males, and RR 0.57; 95% CI 0.43 to 0.75 for females, P = 0.99), reduction in IVH (P = 0.98), and reduction in neonatal mortality (P = 0.43). In a sub-analysis, use of betamethasone was associated with a significant decrease in the rate of RDS in males (RR 0.29; 95% CI 0.15 to 0.57) but dexamethasone was not (RR 0.78; 95% CI 0.57 to 1.07). Conversely, dexamethasone use was significantly helpful in females (RR 0.51; 95% CI 0.32 to 0.81) but betamethasone was not (RR 0.62; 95% CI 0.38 to 1.00). CONCLUSION The effect of AGC for prevention of RDS is similar in females and males. However, futures studies should investigate the type of AGC according to fetal/neonatal sex.