Perinatal morbidity among women with a previous caesarean delivery (PRISMA trial): a cluster-randomised trial.

BACKGROUND: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery. METHODS: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559. FINDINGS: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups. INTERPRETATION: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture. FUNDING: Canadian Institutes of Health Research (CIHR, MOP-142448).

Comparison of the Accuracy of INTERGROWTH-21 and Hadlock Ultrasound Formulae for Fetal Weight Prediction.

OBJECTIVE: To compare the accuracy of INTERGROWTH-21 (IG-21) versus Hadlock1 formulae for birth weight prediction on third-trimester ultrasound in a North American population. METHODS: This single-centre retrospective cohort study included all pregnant patients who had a third-trimester ultrasound between 340 and 366 weeks gestation and delivered a term singleton at our maternal-fetal medicine reference centre between April 1 and July 30, 2019. Estimated ultrasound fetal weight was calculated with both Hadlock1 and IG-21 formulae for each fetus, then reported on a centile curve to adjust for gestational age at delivery, and compared with the actual birth weight. RESULTS: The cohort included 600 women. The IG-21 formula had a comparable accuracy to Hadlock1 with mean absolute percentage errors (MAPEs) of 8.64 and 8.86, respectively (P = 0.191). Success rate, defined by a <10% discrepancy range of the actual birth weight, was significantly higher for IG-21 than for Hadlock1 (67.5% vs. 64.3%; P = 0.044). CONCLUSION: Our results do not support the superiority of IG-21 to Hadlock1. There is a need for continued research to improve birth weight prediction with the ultimate objective of increasing the detection of small for gestation age and macrosomic fetuses.

Committee Opinion No. 418: The Complete 11-14 Week Prenatal Sonographic Examination.

OBJECTIVE: Sonography during the first trimester provides an opportunity to assess a pregnancy in its early stage. This document provides an opinion about the implementation and content of prenatal sonographic examinations at 11-14 weeks gestation in Canada. TARGET POPULATION: Pregnant women at 11-14 weeks gestation. BENEFITS, HARMS, AND COSTS: The 11-14 week prenatal sonographic examination can provide important information that may contribute to pregnancy management. It can be used to confirm viability, establish gestational age, determine the number of fetuses, assess the adnexa/ovaries, and, in a multiple pregnancy, assess chorionicity and amnionicity. Scanning also offers an opportunity to detect fetal abnormalities and perform aneuploidy screening by measuring the nuchal translucency thickness. It may be valuable in screening for preeclampsia and other obstetrical disorders (by combining uterine artery Doppler scanning with other bio-clinical markers) and for invasive placentation. There are no physical harms to mother or fetus from offering a routine 11-14 week prenatal sonographic examination, and there are no extra costs for patients. EVIDENCE: Articles related to routine 11-14 week prenatal sonography were identified in a search of EMBASE and MEDLINE using the search terms first trimester ultrasound, nuchal translucency, and 11-14 week ultrasound. The search included all articles published on the topic until May 2019. Abstracts were reviewed by one author, and articles deemed relevant were then reviewed in full to determine whether to include them in the study. Articles that were not in English and articles that did not pertain to 11-14 week prenatal sonography were excluded. INTENDED AUDIENCE: This document is intended for sonographers, midwives, family physicians, obstetricians, and maternal-fetal medicine specialists.

First Trimester Mean Arterial Pressure Measured Manually Versus Using an Automated Device and the Prediction of Preeclampsia: A Case-Cohort Study.

OBJECTIVE: First trimester mean arterial blood pressure (MAP) can be used to predict preeclampsia. This study aimed to compare the performance of first trimester MAP measured with an automated device using a standardized technique versus MAP taken manually in a typical clinical setting. METHODS: A case-cohort study niched into a prospective cohort of pregnant women recruited at 11-14 weeks was performed. MAP was measured with an automated device on both arms until stability was reached. These results were compared with the MAP measured with a manual device at the closest medical visit (between 10 and 15 weeks gestation) and noted in the medical charts. Receiver-operator characteristics curve analyses were used to estimate the predictive values of MAP measured by both techniques. RESULTS: Forty-one women with preeclampsia and 167 control patients were used for the comparisons. MAP measured with an automated device decreased significantly between 11 and 14 weeks gestation (P < 0.001). Moreover, MAP measured with an automated device was a better predictor of preeclampsia (area under the curve 0.70; 95% confidence interval 0.61-0.79) than MAP measured with a manual device in a clinical setting (area under the curve 0.60; 95% confidence interval 0.50-0.70). Taken alone, MAP measured with an automated device was associated with a detection rate of preeclampsia of 34%, for a false-positive rate of 10%. CONCLUSION: First trimester MAP can predict preeclampsia. This study demonstrated that MAP measured with an automated device using a standardized technique is a better predictor than MAP measured with a manual device.

Evolution of Down Syndrome Prenatal Screening Clinical Practices in Québec.

OBJECTIVE: Prenatal screening for Down syndrome (DS) has evolved greatly over the last decades with the improvement of first- and second-trimester serum screening and the introduction of cell-free fetal DNA. This study aimed to estimate the impact of such changes on practices. METHODS: This retrospective cohort study included fetuses and newborns diagnosed with DS between 2005-2007 and 2015-2017 in the single obstetrical care centre in Québec City. Data were collected on the prenatal screening method, diagnosis, and delivery. The median was compared between the study periods. RESULTS: Complete clinical data were available for only 78 (66%) of 119 cases of DS. Significant changes were observed in screening methods, including an increase in the use of first-trimester serum, ultrasound, and cell-free fetal DNA. No significant changes were noted in terms of gestational age at diagnosis (median [interquartile range; IQR]: 17.0 [16.0-20.9] weeks in 2005-2007 vs. 17.9 [16.3-22.5] weeks in 2015-2017; P = 0.49) and delivery or termination of pregnancy (median 20.9 [IQR 18.0-23.3] weeks in 2005-2007 vs. 21.3 [18.4-23.4] weeks in 2015-2017; P = 0.46). The methods of diagnosis did not change significantly over the decade, with amniocentesis used 85% and 79% of the time, respectively (P = 0.19). CONCLUSION: The increased use of first-trimester screening and cell-free fetal DNA tests was not associated with earlier diagnosis of DS or earlier delivery or termination of pregnancy. The use of chorionic villus sampling should be encouraged for DS diagnosis when indicated because it could reduce the gestational age at diagnosis and termination if requested.

Placental Growth Factor and Soluble, Fms-Like Tyrosine Kinase-1 in Preeclampsia: A Case-Cohort (PEARL) Study.

OBJECTIVE: Preeclampsia is associated with a higher maternal blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and lower levels of placental growth factor (PlGF) that appear before clinical onset. We aimed to estimate the normal progression of these biomarkers in normal pregnancies and in those affected by preeclampsia. METHODS: We conducted a case-cohort study including low-risk nulliparous women recruited at 11-13 weeks gestation (cohort) and women with preeclampsia (cases). Maternal blood was collected at different points during pregnancy including at the time of diagnosis of preeclampsia for cases. Maternal serum PlGF and sFlt-1 concentrations and the sFlt-1/PlGF ratio were measured using B•R•A•H•M•S plus KRYPTOR automated assays and were compared between patients in both groups matched for gestational age. Cases were stratified as early- (≤34 weeks), intermediate- (35-37 weeks) and late-onset (>37 weeks) preeclampsia. RESULTS: The cohort consisted of 45 women whose results were compared with those of 31 women who developed preeclampsia, diagnosed at a median gestational age of 32 weeks (range 25-38 weeks). We observed that sFlt-1, PlGF and their ratio fluctuated during pregnancy in both groups, with a significant correlation with gestational age after 28 weeks (P < 0.05). We observed a significant difference between cases and controls, with a median ratio 100 times higher in early preeclampsia (P < 0.001), 13 times higher in intermediate preeclampsia (P < 0.001), but no significant difference between groups in late-onset preeclampsia with matched controls. CONCLUSION: PlGF, sFlt-1, and their ratio may be useful in the prediction and diagnosis of early- and intermediate-onset preeclampsia but are not useful for late-onset preeclampsia.

First and Third Trimester Uterine Scar Thickness in Women With Previous Caesarean: A Prospective Comparative Study.

BACKGROUND: Lower uterine segment (LUS) thickness in the third trimester of gestation is associated with the risk of uterine scar defect at delivery. It was suggested that first trimester residual myometrial thickness (RMT) could also predict uterine scar defect at delivery. OBJECTIVE: This study sought to correlate the RMT measured at the site of uterine scar in the first trimester with the LUS thickness measured in the third trimester. METHODS: This was a prospective cohort study of women with a singleton pregnancy and a single prior low-transverse CS. All participants underwent an evaluation of uterine scar by using transvaginal ultrasound at 11 to 13 weeks, including the presence of a scar defect and measurement of RMT; and a second evaluation at 35 to 38 weeks, combining both transvaginal and transabdominal ultrasound, for the measurement of LUS thickness. Spearman's correlation test was used to compare first and third trimester measurements. RESULTS: A total of 166 eligible participants were recruited at mean GA of 12.7 ± 0.5 weeks. We observed an absence of correlation between first trimester RMT and third trimester LUS thickness (correlation coefficient 0.10; P = 0.20). First trimester RMTs below 2.0 mm and below 2.85 mm are poor predictors of third trimester LUS thickness below 2.0 mm (sensitivity, 8% and 23%; specificity, 98% and 87%; positive predictive value, 25% and 14%, respectively). CONCLUSION: There is a poor correlation between first trimester RMT and third trimester LUS thickness in women with a previous CS. First trimester RMT should not be used to inform women on their risk of uterine rupture or to guide clinical management.

Use of Antenatal Corticosteroid Therapy: A Descriptive Study of Clinical Practice Trends.

OBJECTIVES: Antenatal corticosteroids (ACS) received within 7 days of delivery reduce perinatal morbidity and mortality associated with preterm birth. We aimed to describe the trends of ACS administration over the last decade. METHODS: A cohort study of women who received ACS in 2006, 2011, and 2016 at the CHU de Québec-Université Laval was conducted. The indication, GA at ACS, and GA at birth, were collected in 150 women randomly selected in each studied year. Our main endpoints were the frequency of ACS administration within 7 days of delivery and between 48 hours and 7 days before delivery. RESULTS: We included 447 women who received ACS at a median GA of 31.4 (range 23.6-39.0) weeks. No women received ACS after 35 weeks in 2006 and 2011. The administration of ACS for indicated delivery between 35 and 39 weeks occurred only in the last study period. Among women for whom ACS was initiated before 35 weeks, 31% received ACS in the 7 days before delivery, and only 13% received ACS between 48 hours and 7 days before birth (varying from 12% to 16%, P = 0.57). Threatened preterm labour or short cervix were the indication for ACS initiation in 39% women who received ACS before 35 weeks, but less than 5% of these women delivered between 2 and 7 days and more than 90% delivered after 14 days. CONCLUSIONS: Administration of ACS remains suboptimal. Threatened preterm labour and short cervix are poorly related to optimal use of ACS therapy.

First-Trimester Uterine Artery Doppler for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndrome Study.

OBJECTIVE: This study aimed to estimate the performance of first-trimester uterine artery (UtA) pulsatility index (PI) for the prediction of preeclampsia (PE). STUDY DESIGN: We conducted a prospective cohort study of nulliparous women with singleton gestation at 11 to 13 6/7 weeks. UtA-Doppler's was performed on both UtAs and the mean UtA-PI was reported in multiple of median (MoM) adjusted for gestational age. Using receiver operating characteristic curves and their area under the curves (AUC); we calculated the performance of UtA-PI for the prediction of PE. Proportional hazard models were used to develop prediction models combining UtA-PI and maternal characteristics. RESULTS: Out of 4,676 participants with completed follow-up, 232 (4.9%) developed PE, including 202 (4.3%) term and 30 (0.6%) preterm PE. Mean UtA-PI decreased with gestational age between 11 and 13 6/7 weeks (p < 0.001). First-trimester UtA-PI was associated with preterm (AUC: 0.69; 95% CI [confidence interval]: 0.57-0.80) but not with term (AUC: 0.52; 95% CI: 0.48-0.56) PE. UtA-PI combined with maternal characteristics could predict 45% of preterm PE at a false positive rate of 10%. CONCLUSION: First-trimester UtA-PI decreases with gestational age between 11 and 13 6/7 weeks and is associated with the risk of preterm but not term PE.

First-Trimester Placental Growth Factor for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes Cohort Study.

BACKGROUND: First-trimester maternal serum markers have been associated with preeclampsia (PE). We aimed to evaluate the performance of first-trimester placental growth factor (PlGF) for the prediction of PE in nulliparous women. SUBJECTS AND METHODS: We conducted a prospective cohort study of nulliparous women with singleton pregnancy at 11-13 weeks. Maternal serum PlGF concentration was measured using B·R·A·H·M·S PlGFplus KRYPTOR automated assays and reported in multiple of the median adjusted for gestational age. We used proportional hazard models, along with receiver operating characteristic curves and areas under the curve (AUC). RESULTS: Out of 4,652 participants, we observed 232 (4.9%) cases of PE including 202 (4.3%) term and 30 (0.6%) preterm PE. PlGF was associated with the risk of term (AUC = 0.61, 95% confidence interval [CI] 0.57-0.65) and preterm PE (AUC = 0.73, 95% CI 0.64-0.83). The models were improved with the addition of maternal characteristics (AUC for term PE 0.66, 95% CI 0.62-0.71; AUC for preterm PE 0.81, 95% CI 0.72-0.91; p < 0.01). At a false-positive rate of 10%, PlGF combined with maternal characteristics could have predicted 26% of term and 55% of preterm PE. The addition of pregnancy-associated plasma protein A did not significantly improve the prediction models. CONCLUSION: First-trimester PlGF combined with maternal characteristics is useful to predict preterm PE in nulliparous women.

First-Trimester Uterine Artery Doppler for the Prediction of SGA at Birth: The Great Obstetrical Syndromes Study.

OBJECTIVE: To estimate the role of first-trimester uterine artery pulsatility index (UtA-PI) for the prediction of small-for-gestational age (SGA). METHODS: We conducted a prospective cohort study of nulliparous women with singleton pregnancy (Great Obstetrical Syndromes study). UtA-PI was performed at 11 + 0 to 13 + 6 weeks and was reported in multiple of median (MoM). SGA was defined as birth weight below the 10th percentile and stratified as term or preterm SGA. Receiver operating characteristic curves analyses with their area under the curve (AUC) were used to estimate the predictive values of UtA-PI, alone and UtA-PI combined with maternal characteristics. We computed the detection rate and false-positive rate (FPR) of the SOGC SGA screening guidelines in our population. RESULTS: Of 4610 participants, SGA was identified in 486 pregnancies (10.3%), including 15 (0.3%) associated with preterm delivery. Compared with unaffected pregnancies, the mean log UtA-PI was significantly higher in term SGA and preterm SGA. The difference between preterm SGA and unaffected pregnancies remains significant after exclusion of SGA without preeclampsia. First-trimester UtA-PI was more predictive of preterm (AUC: 0.89) than term (AUC: 0.60) SGA (P < 0.01). Combined with maternal characteristics, UtA-PI could have predicted 64% of preterm and 20% of term SGA (10% FPR). The SOGC guidelines criteria for early screening of SGA had a detection rate of 21% for a FPR of 21%. CONCLUSIONS: First-trimester UtA-PI can be used to predict SGA, but mainly preterm SGA. The current SOGC guidelines criteria for SGA screening are not efficient in nulliparous women.

First Trimester Screening for Fetal Aneuploidies Using Placental Growth Factor: The Great Obstetrical Syndrome (GOS) Study.

OBJECTIVE: This study sought to estimate the ability of first trimester maternal serum placental growth factor (PlGF) to identify fetal aneuploidies. METHODS: A prospective cohort study of singleton pregnancy at 11 to 13 weeks was conducted. Maternal serum PlGF concentration was measured using BRAHMS PlGF plus KRYPTOR automated assays (Thermo Scientific BRAHMS, Hennigsdorf, Germany). PlGF and nuchal translucency were log-transformed and reported as multiples of the median (MoM) adjusted for crown-rump length. Detection rates were calculated using receiver-operator characteristic curves. RESULTS: The study observed 21 cases of fetal aneuploidies (0.4%) out of 4765 participants. Trisomy 21 (13 cases; 0.85 MoM; interquartile range [IQR] 0.80-0.93), trisomy 18 (two cases; 0.77 MoM; IQR 0.66-0.87) and trisomy 13 (two cases; 0.68 MoM; IQR 0.61-0.75) were associated with low PlGF concentrations. The low PlGF values observed in the cases of monosomy X (two cases; 0.85 MoM; IQR 0.82-0.88, P = 0.05), triploidy (0.78 MoM, P = 0.11), and 47,XX,i(22)(p10) (0.18 MoM, P = 0.08) were not statistically different from the controls. A model including maternal age, nuchal translucency, and PlGF could have identified all (95% CI 83%-100%) cases of trisomy 21 and six of the other fetal aneuploidies (75%) at a false-positive rate of 9%. CONCLUSION: Low first trimester PlGF is associated with an increased risk of fetal aneuploidy. PlGF combined with first trimester ultrasound (nuchal translucency, uterine artery Doppler, and early fetal anatomy) could identify not only women at high risk for preeclampsia, but also fetuses at high risk of aneuploidy for optimal further testing (non-invasive testing for common aneuploidy screening or chorionic villus sampling for full screening and diagnosis).

Does Low PAPP-A Predict Adverse Placenta-Mediated Outcomes in a Low-Risk Nulliparous Population? the Great Obstetrical Syndromes (GOS) Study.

OBJECTIVE: First-trimester low concentration of pregnancy-associated plasma protein A (PAPP-A) has been associated with adverse perinatal outcomes in high-risk populations. This study aimed to estimate the ability of PAPP-A to identify adverse outcomes in a low-risk population. METHODS: The study investigators recruited nulliparous women with singleton pregnancy at their 11-13-week ultrasound scan. Serum samples were collected, and maternal PAPP-A concentration was measured using the B⋅R⋅A⋅H⋅M⋅S PAPP-A KRYPTOR (ThermoFisher Scientific, Hennigsdorf, Germany) automated assay. PAPP-A was reported in multiple of median (MoM) adjusted for GA. Participants were followed until delivery for pregnancy outcomes including preeclampsia (PE), SGA <3rd percentile, and fetal death. Receiver operating characteristic curves with the area under the curve (AUC) were used to evaluate the predictive value of PAPP-A. The investigators calculated the detection rates (DRs) and positive predictive values (PPVs) of a PAPP-A < 0.4 MoM. RESULTS: The study investigators recruited 4739 eligible participants at a mean GA of 13 ± 6 weeks. The investigators observed 232 (4.9%) cases of PE, 84 (1.8%) cases of SGA, and 14 (0.3%) fetal deaths. PAPP-A was moderately associated with PE (AUC 0.57; 95% CI 0.53-0.61) and SGA (AUC 0.62; 95% CI 0.56-0.69), but not with fetal death (AUC 0.43; 95% CI 0.23-0.63). PAPP-A < 0.4 MoM was observed in 364 (7.7%) participants and had poor predictive values for PE (DR 9.8%; PPV 6.3%), SGA (DR 18.1%; PPV 4.4%), and fetal death (DR 21.4%; PPV 0.9%). CONCLUSION: Isolated first trimester PAPP-A has a limited predictive value for adverse pregnancy outcomes (other than trisomies). Low PAPP-A (<0.4 MoM) should be used in combination with other markers for the prediction of PE, SGA, or fetal death, and it does not constitute an indication for low-dose aspirin.

Maternal Characteristics for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes (GOS) Study.

OBJECTIVE: Low-dose aspirin started in early pregnancy significantly reduces the risk of preeclampsia (PE) in high-risk women, especially preterm PE. This study aimed to evaluate the influence of maternal characteristics on the risk of PE in nulliparous women. METHODS: The Great Obstetrical Syndromes (GOS) study recruited nulliparous women with singleton pregnancies at 11 to 13 weeks. The following maternal characteristics were collected: age, BMI, ethnicity, chronic diseases, smoking, and assisted reproductive technologies. Relative weight analyses were conducted, and predictive multivariate proportional hazard models were constructed. Receiver operating characteristic curve analyses with their area under the curve (AUC) were used to evaluate the value of each factor for the prediction of PE and preterm PE. The study also evaluated the SOGC guidelines for identification of women at high risk of PE. RESULTS: Of 4739 participants, 232 (4.9%) developed PE, including 30 (0.6%) with preterm PE. In univariate analyses, only BMI was significantly associated with the risk of PE (AUC 0.60; 95% CI 0.55-0.65) and preterm PE (AUC 0.64; 95% CI 054-0.73). Adding other maternal characteristics to BMI had a non-significant and marginal impact on the discriminative ability to the models for PE (AUC 0.62; 95% CI 0.58-0.66) and preterm PE (AUC 0.65; 95% CI 0.56-0.74). At a false-positive rate of 10%, maternal characteristics could have predicted 23% of PE and 19% of preterm PE. The SOGC guidelines were not discriminant for PE (detecting 96% of PE and 93% of preterm PE with a 94% false-positive rate). CONCLUSION: In nulliparous women, BMI is the most discriminant maternal characteristic for the prediction of PE. Maternal characteristics should not be used alone to identify nulliparous women at high risk of PE.

First-Trimester Abdominal Adipose Tissue Thickness to Predict Gestational Diabetes.

OBJECTIVE: To estimate the discriminative capacity of first-trimester subcutaneous (SATT), visceral (VATT), and total (TATT) adipose tissue thickness in predicting gestational diabetes mellitus (GDM), including that requiring insulin. METHODS: We prospectively recruited a cohort of 1048 nulliparous women. Ultrasound images were used to determine abdominal SATT, VATT, and TATT at 11 to 14 weeks' gestation. Multivariate logistic regression models were used to predict GDM, as well as insulin-requiring GDM. Model discrimination was expressed as area under the curve (AUC). RESULTS: SATT (AUC 0.66, 95% CI 0.59-0.73), VATT (AUC 0.65, 95% CI 0.58-0.73), and TATT (AUC 0.68, 95% CI 0.61-0.76) were each associated with subsequent GDM. The respective AUC values for insulin-requiring GDM were 0.70 (95% CI 0.61-0.79), 0.73 (95% CI 0.65-0.82), and 0.76 (95% CI 0.67-0.84). At a false-positive rate of 10%, the detection rate for insulin-requiring GDM was 19% for maternal age ≥35 years, 31% for a BMI ≥31.6 kg/m2, and 31% for TATT ≥61 mm, increasing to 42% in the model comprising all three measures. CONCLUSION: First-trimester ultrasound measurement of adipose tissue is associated with a higher chance of developing GDM, especially insulin-requiring GDM.

Comparative Study of Abdominal Versus Transvaginal Ultrasound for Uterine Artery Doppler Velocimetry at 11 to 13 Weeks.

OBJECTIVES: To compare the first-trimester uterine artery pulsatility index (PI) measured by abdominal and transvaginal ultrasound (US). METHODS: We performed a prospective study of singleton pregnant women recruited at 11 to 13 weeks' gestation. The mean uterine artery PI was obtained by abdominal followed by transvaginal US. The mean of the left and right uterine artery PIs was used, and differences between approaches were computed. The intraclass correlation coefficient and a Bland-Altman plot were used to compare the two approaches. RESULTS: Data were available for 940 participants, including 928 (99%) with uterine artery PIs obtained on both uterine sides. The mean uterine artery PI decreased with gestational age in both approaches (P < .001). We observed a moderate correlation between abdominal and transvaginal mean uterine artery PIs (intraclass correlation coefficient, 0.72; 95% confidence interval, 0.69 to 0.75). Values obtained by abdominal US (median, 1.70, interquartile range, 1.35 to 2.09) were greater than those obtained by transvaginal US (median, 1.65; interquartile range, 1.37 to 1.99). There was a significant increase in differences as average measurements became higher (P < .01). CONCLUSIONS: The first-trimester mean uterine artery PI decreases with gestational age in both approaches. Abdominal US could be associated with greater uterine artery PI values than transvaginal US, especially at higher measurements. The first-trimester uterine artery PI for prediction of adverse perinatal outcomes should be adjusted for gestational age and possibly for the US approach.

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. Pearson's 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.

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.

Single versus double-layer uterine closure at cesarean: impact on lower uterine segment thickness at next pregnancy.

BACKGROUND: Uterine rupture is a potential life-threatening complication during a trial of labor after cesarean delivery. Single-layer closure of the uterus at cesarean delivery has been associated with an increased risk of uterine rupture compared with double-layer closure. Lower uterine segment thickness measurement by ultrasound has been used to evaluate the quality of the uterine scar after cesarean delivery and is associated with the risk of uterine rupture. OBJECTIVE: To estimate the impact of previous uterine closure on lower uterine segment thickness. STUDY DESIGN: Women with a previous single low-transverse cesarean delivery were recruited at 34-38 weeks' gestation. Transabdominal and transvaginal ultrasound evaluation of the lower uterine segment thickness was performed by a sonographer blinded to clinical data. Previous operative reports were reviewed to obtain the type of previous uterine closure. Third-trimester lower uterine segment thickness at the next pregnancy was compared according to the number of layers sutured and according to the type of thread for uterine closure, using weighted mean differences and multivariate logistic regression analyses. RESULTS: Of 1613 women recruited, with operative reports available, 495 (31%) had a single-layer and 1118 (69%) had a double-layer closure. The mean third-trimester lower uterine segment thickness was 3.3 ± 1.3 mm and the proportion with lower uterine segment thickness <2.0 mm was 10.5%. Double-layer closure of the uterus was associated with a thicker lower uterine segment than single-layer closure (weighted mean difference: 0.11 mm; 95% confidence interval [CI], 0.02 to 0.21 mm). In multivariate logistic regression analyses, a double-layer closure also was associated with a reduced risk of lower uterine segment thickness <2.0 mm (odd ratio [OR], 0.68; 95% CI, 0.51 to 0.90). Compared with synthetic thread, the use of catgut for uterine closure had no significant impact on third-trimester lower uterine segment thickness (WMD: -0.10 mm; 95% CI, -0.22 to 0.02 mm) or on the risk of lower uterine segment thickness <2.0 mm (OR, 0.95; 95% CI, 0.67 to 1.33). Finally, double-layer closure was associated with a reduced risk of uterine scar defect (RR, 0.32; 95% CI, 0.17 to 0.61) at birth. CONCLUSION: Compared with single-layer closure, a double-layer closure of the uterus at previous cesarean delivery is associated with a thicker third-trimester lower uterine segment and a reduced risk of lower uterine segment thickness <2.0 mm in the next pregnancy. The type of thread for uterine closure has no significant impact on lower uterine segment thickness.

Impact of uterine closure on residual myometrial thickness after cesarean: a randomized controlled trial.

BACKGROUND: Incomplete healing of uterine scar after cesarean has been associated with adverse gynecological and obstetrical outcomes. Several studies reported that uterine closure at cesarean influences the healing of uterine scar and the risk of uterine rupture at subsequent pregnancies: the commonly used locked single-layer suture including the decidua being associated with a 4-fold increased risk of uterine rupture. However, data from randomized trials are lacking. OBJECTIVE: We sought to evaluate the impact of 3 techniques of uterine closure after cesarean delivery on uterine scar healing. STUDY DESIGN: This was a 3-arm 1:1:1 randomized study in women with singleton pregnancies undergoing elective primary cesarean delivery at ≥38 weeks' gestation. Closure of the uterine scar was carried out by locked single layer including the decidua, double layer with locked first layer including the decidua, or double layer with unlocked first layer excluding the decidua. Primary outcome was residual myometrial thickness (RMT) at the site of the scar, measured by transvaginal ultrasound 6 months after delivery. Secondary outcome was the RMT as a percentage of the myometrial thickness above the scar (healing ratio). Intent-to-treat analyses using Student t test were performed to compare each double-layer technique to the single-layer closure, and P < .025 was considered significant. RESULTS: Complete follow-up was obtained from 73 (90%) of the 81 participants. Compared to single-layer closure, double-layer closure with unlocked first layer was associated with thicker RMT (3.8 ± 1.6 mm vs 6.1 ± 2.2 mm; P < .001) and greater healing ratio (54 ± 20% vs 73 ± 23%; P = .004). In contrast, double-layer closure with locked first layer was not significantly different than single-layer closure in either RMT (4.8 ± 1.3; P = .032) or healing ratio (60 ± 21%; P = .287). CONCLUSION: Double-layer closure with unlocked first layer is associated with better uterine scar healing than locked single layer.