S. Demers

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.

Prevention of pre‐eclampsia by low‐molecular‐weight heparin in addition to aspirin: a meta‐analysis

To estimate the impact of adding low‐molecular‐weight heparin (LMWH) or unfractionated heparin to low‐dose aspirin started ≤ 16 weeks gestation on the prevalence of pre‐eclampsia (PE) and the delivery of a small‐for‐gestational‐age (SGA) neonate.

Factors Associated with Placental Vascularization Measured by 3D Power Doppler Ultrasonographic Sphere Biopsy between 11 and 14 Weeks of Gestation

Objective Preeclampsia is associated with placental vascularization disorders. Ultrasonographic sphere biopsy (USSB) of the placenta can estimate the vascularization of the placenta and potentially the risk of preeclampsia. We aimed to explore the factors related to placental vascularization measured with USSB in the first trimester. Study Design A prospective cohort was conducted in women recruited at 11 to 14 weeks. Three‐dimensional acquisition of the placenta with power Doppler was undertaken along with crown‐rump length (CRL). Using USSB of the full placental thickness at its center, vascularization index, flow index, and vascular flow index were measured. Pearsons correlation coefficients and multivariate linear regression were used to correlate the vascularization indices with CRL and maternal characteristics. Results A total of 5,612 women were recruited at a mean gestational age of 12.8 ± 0.6 weeks. We observed that vascularization indices increase with CRL. After adjustment, we observed that maternal age, ethnicity other than Caucasian, and body mass index were associated with lower vascularization indices, while diabetes, smoking, and assisted reproduction technology were not. We observed that parous women without history of preeclampsia had greater vascularization indices compared with nulliparous women. Conclusion Placental vascularization indices assessed by USSB fluctuate with gestational age, ethnicity, maternal age, body mass index, and previous pregnancy history.

P08.03: Low-dose aspirin for prevention of fetal growth restriction and pre-eclampsia in twins: the GAP pilot randomised trial

remained significant when sub-analysed for males (p=0.036) and for females (p=0.013). In addition neonatal gender, maternal height, weight before pregnancy and weight at term were also significantly correlated with NHC (p-values 0.014, 0.004, 0.03, 0.01 respectively). In a multivariate analysis, MHC and neonatal gender were the only significant independent predictors. However the model could explain only 8.6% of the NHC variability. Conclusions: NHC is influenced by maternal body habitus and neonatal gender. The low R2 of the prediction model implies that head growth during fetal life is influenced by other factors. Paternal body habitus and head circumference did not significantly affect neonatal head circumference. This result makes sense from an evolutionary perspective. This means that big males who may be attractive by females do not influence the fetal/neonatal head circumference, and thereby do not influence on the chances of successful vaginal delivery of their offspring.

Re: Impact of aspirin on trophoblastic invasion in women with abnormal uterine artery Doppler at 11–14 weeks

We read with interest the randomized trial of Scazzocchio et al.1 who observed that starting aspirin administration in the first trimester in low-risk women with abnormal uterine artery Doppler had no effect on uterine artery pulsatility index later in pregnancy. This randomized trial is important because few studies have evaluated the effect of low-dose aspirin started in the first trimester in such a population. While their conclusion is correct, we believe that another important conclusion should have been highlighted: low-risk pregnant women with abnormal uterine artery Doppler in the first trimester remain at low risk of adverse perinatal outcome. Most participants, regardless of whether they were administered aspirin or placebo, had normal uterine artery Doppler at 28 weeks (aspirin: 78%; placebo: 73%), and the rates of pre-eclampsia (5% and 4%, respectively) and severe pre-eclampsia (1.3% in both groups) were low. We believe that an important conclusion to draw from this trial is that uterine artery Doppler alone in the first trimester, even when performed transvaginally, has a low positive predictive value for deep placentation disorders, pre-eclampsia and severe pre-eclampsia in a low-risk population. There is, therefore, no indication for the use

P01.11: Comparison between first and third trimester evaluation of uterine scar: a prospective study

Objectives: Abnormal cerebroplacental ratio (CPR) is associated with adverse neonatal outcomes. We aim to study the relationship of the CPR in patients with preterm premature ruptures of membranes (PPROM) and severe adverse neonatal outcomes. Methods: The rate of abnormal CPR and middle cerebral artery pulsatility index (MCA-PI) was compared in women with PPROM complicated with severe adverse neonatal outcomes (SANO) and those without such complications (controls). Abnormal CPR and MCA-PI was defined as ≤ 5th percentile for gestational age. SANO was defined as having one or more of grade III or IV intraventricular hemorrhage (IVH), respiratory distress syndrome (RDS), necrotising enterocolitis (NEC), neonatal sepsis (NS) or perinatal death. Data is presented as median (quartile ranges) and n (%). Parametric and non parametric statistical analysis was performed when appropriate and a p value < 0.05 was considered statistical significant. Results: 60 women had PPROM. Fifty-seven had umbilical artery (UA) and MCA Doppler studies (26 in the study group and 31 in the control group). An average of 18 and 20 waveforms were analysed in the UA and MCA respectively. The rate of abnormal MCA PI was similar between groups (23% and 13%; OR=2[CI 0.4–11]). Only one had abnormal CPR (controls). There were four perinatal deaths (6.7%), four IVH (6.7%), three NEC (5%), two NS (3.3%) and RDS was present in 25 newborns (41.7%). Conclusions: A normal CPR does not exclude severe adverse neonatal outcomes in PPROM.

OP17.02: First trimester uterine artery Doppler for the prediction of pre-eclampsia in nulliparous women: the great obstetrical syndrome (GOS) study

Methods: We retrospectively reviewed and performed 4D-HDFI in 204 normal and 33 fetuses with confirmed diagnosis of cardiac anomalies of the great arteries. Cardiac volumes were available for post-analysis to obtain 4D rendered images of the great arteries. For the normal fetuses, two other traditional modalities including colour Doppler and HDFI were used to detect aortic arch and its branches and comparisons were made between each of these traditional methods and 4D-HDFI. Results: Two cases of interrupted aortic arch (IAA) type A, 3 cases of IAA type B, 5 cases of tetralogy of Fallot, 3 cases of double outlet right ventricle, 2 cases of truncus arteriosus, 2 cases of transposition of the great arteries, 2 cases of double aortic arch, 11 cases of right aortic arch with aberrant left subclavian arteries, 1 case of right aortic arch with mirror-image branching, and 2 cases of aberrant right subclavian artery were included in the current study. The 4D rendered images vividly depicted the origination, course, and the spatial relationship of the great arteries. For the normal fetuses, HDFI modality was superior to colour Doppler in detecting more brachiocephalic arteries throughout the gestational period. 4D-HDFI was the best method during the second trimester of pregnancy in identifying the greatest number of brachiocephalic arteries. Conclusions: HDFI and the advanced 4D-HDFI technique could facilitate identification of the anatomical features of the great arteries in both normal and abnormal fetuses, 4D-HDFI therefore provides additional and more precise information than conventional sonography techniques.

OP17.03: Pregnancy outcomes in women with positive first trimester FMF algorithm screening test: the great obstetrical syndromes (GOS) study

Methods: We retrospectively reviewed and performed 4D-HDFI in 204 normal and 33 fetuses with confirmed diagnosis of cardiac anomalies of the great arteries. Cardiac volumes were available for post-analysis to obtain 4D rendered images of the great arteries. For the normal fetuses, two other traditional modalities including colour Doppler and HDFI were used to detect aortic arch and its branches and comparisons were made between each of these traditional methods and 4D-HDFI. Results: Two cases of interrupted aortic arch (IAA) type A, 3 cases of IAA type B, 5 cases of tetralogy of Fallot, 3 cases of double outlet right ventricle, 2 cases of truncus arteriosus, 2 cases of transposition of the great arteries, 2 cases of double aortic arch, 11 cases of right aortic arch with aberrant left subclavian arteries, 1 case of right aortic arch with mirror-image branching, and 2 cases of aberrant right subclavian artery were included in the current study. The 4D rendered images vividly depicted the origination, course, and the spatial relationship of the great arteries. For the normal fetuses, HDFI modality was superior to colour Doppler in detecting more brachiocephalic arteries throughout the gestational period. 4D-HDFI was the best method during the second trimester of pregnancy in identifying the greatest number of brachiocephalic arteries. Conclusions: HDFI and the advanced 4D-HDFI technique could facilitate identification of the anatomical features of the great arteries in both normal and abnormal fetuses, 4D-HDFI therefore provides additional and more precise information than conventional sonography techniques.