Cédric Gasse

Body mass index and the risk of hypertensive disorders of pregnancy: the great obstetrical syndromes (GOS) study

Abstract Objective: To estimate the association between first-trimester body mass index (BMI) and the different types of hypertensive disorders of pregnancy (HDP). Methods: A prospective cohort of nulliparous women recruited at 11–13 weeks. Height and weight were measured and BMI was reported as binary (more or less than 30u2009kg/m2), categorical (World Health Organization classification), and continuous variables. Participants were followed for development of any HDP, including preeclampsia and preterm preeclampsia. Receiver operating characteristic curves and their area under the curve (AUC) were used along with multivariate logistic regressions to develop predictive models combining BMI with other maternal characteristics. Results: We recruited 4683 eligible participants including 645 (14%) affected by obesity. Obesity was associated with greater risks of HDP (22.5 versus 8.5%, pu2009<u2009.0001), preeclampsia (10.2 versus 4.3%, pu2009<u2009.0001), and preterm preeclampsia (1.6 versus 0.6%, pu2009=u2009.006). BMI categories (AUC: 0.65; 95%CI: 0.56–0.74) and BMI combined with maternal characteristics (AUC: 0.76; 95%CI: 0.69–0.83) were better predictors of preterm preeclampsia than BMI as binary variable (AUC: 0.58; 95%CI: 0.50–0.66). Conclusions: Obesity and BMI are associated with the risk of all types of HDP. Optimal prediction of preterm preeclampsia is achieved by using BMI as a continuous variable combined with other maternal characteristics.

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

OBJECTIVEnLow-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.nnnMETHODSnThe 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.nnnRESULTSnOf 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).nnnCONCLUSIONnIn 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 mean arterial blood pressure and the risk of preeclampsia: the Great Obstetrical Syndromes (GOS) study

OBJECTIVEnTo estimate the predictive value of first-trimester mean arterial pressure (MAP) for the hypertensive disorders of pregnancy (HDP).nnnSTUDY METHODSnWe performed a prospective cohort study of nulliparous women recruited at 110/7-136/7u202fweeks. MAP was calculated from blood pressure measured on both arms simultaneously using an automated device taking a series of recordings until blood pressure stability was reached. MAP was reported as multiples of the median adjusted for gestational age. Participants were followed for development of gestational hypertension (GH), preeclampsia (PE), preterm PE (<37u202fweeks) and early-onset (EO) PE (<34u202fweeks). Receiver operating characteristic curves and the area under the curve (AUC) were used to estimate the predictive values of MAP. Multivariate logistic regressions were used to develop predictive models combining MAP and maternal characteristics.nnnRESULTSnWe obtained complete follow-up in 4700 (99%) out of 4749 eligible participants. GH without PE was observed in 250 (5.3%) participants, and PE in 241 (5.1%), including 33 (0.7%) preterm PE and 10 (0.2%) EO-PE. First-trimester MAP was associated with GH (AUC: 0.77; 95%CI: 0.74-0.80); term PE (0.73; 95%CI: 0.70-0.76), preterm PE (0.80; 95%CI: 0.73-0.87) and EO-PE (0.79; 95%CI: 0.62-0.96). At a 10% false-positive rate, first-trimester MAP could have predicted 39% of GH, 34% of term PE, 48% of preterm PE and 60% of EO-PE. The addition of maternal characteristics improved the predictive values (to 40%, 37%, 55% and 70%, respectively).nnnCONCLUSIONnFirst-trimester MAP is a strong predictor of GH and PE in nulliparous women.

Intra-amniotic inflammation and child neurodevelopment: a systematic review protocol

BackgroundIntra-amniotic inflammation is associated with adverse pregnancy and neonatal outcomes. However, the impact on child neurodevelopment remains unclear. We aim to assess the effect of intra-amniotic inflammation on neurodevelopmental outcomes in children.MethodsThe databases MEDLINE, Embase, CINAHL, and Cochrane will be searched from their inception until November 2017. Randomized trials and cohort studies in which inflammatory markers were measured in amniotic fluid collected by amniocentesis and in which infant’s neurodevelopment was assessed will be eligible. Two reviewers will independently select eligible studies, assess their risk of bias, and extract data. Results will be compared and a third party will be consulted in case of disagreement. Our primary outcome of interest is child neurodevelopment, assessed with either a validated tool or by revision of medical records for specific diagnosis. Secondary outcomes will include abnormal brain imaging. Relative risks will be pooled and sensitivity analyses will be performed for the indication of amniocentesis, gestational age at amniocentesis, gestational age at delivery, and fetal sex. Risk of bias will be assessed using the Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials or an adapted version of the ROBINS-1 for the risk of bias in non-randomized studies.DiscussionThis systematic review will report the current evidence regarding the association between amniotic inflammation and child neurodevelopment, and the modifiers of this association. The review will generate new hypotheses on pathological pathways and will guide future research.Systematic review registrationPROSPERO 2017 65065

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

OBJECTIVEnTo estimate the role of first-trimester uterine artery pulsatility index (UtA-PI) for the prediction of small-for-gestational age (SGA).nnnMETHODSnWe conducted a prospective cohort study of nulliparous women with singleton pregnancy (Great Obstetrical Syndromes study). UtA-PI was performed at 11u2009+u20090 to 13u2009+u20096 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.nnnRESULTSnOf 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 (Pu2009<u20090.01). 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%.nnnCONCLUSIONSnFirst-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 Abdominal Adipose Tissue Thickness to Predict Gestational Diabetes

OBJECTIVEnTo 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.nnnMETHODSnWe 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).nnnRESULTSnSATT (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 BMIu2009≥31.6u2009kg/m2, and 31% for TATTu2009≥61u2009mm, increasing to 42% in the model comprising all three measures.nnnCONCLUSIONnFirst-trimester ultrasound measurement of adipose tissue is associated with a higher chance of developing GDM, especially insulin-requiring GDM.

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

OBJECTIVEnThis study sought to estimate the ability of first trimester maternal serum placental growth factor (PlGF) to identify fetal aneuploidies.nnnMETHODSnA 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.nnnRESULTSnThe 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, Pu2009=u20090.05), triploidy (0.78 MoM, Pu2009=u20090.11), and 47,XX,i(22)(p10) (0.18 MoM, Pu2009=u20090.08) 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%.nnnCONCLUSIONnLow 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).

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

OBJECTIVESnAntenatal 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.nnnMETHODSnA 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.nnnRESULTSnWe 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%, Pu2009=u20090.57). 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.nnnCONCLUSIONSnAdministration of ACS remains suboptimal. Threatened preterm labour and short cervix are poorly related to optimal use of ACS therapy.

Comparative Study of Abdominal Versus Transvaginal Ultrasound for Uterine Artery Doppler Velocimetry at 11 to 13 Weeks: First-Trimester Uterine Artery Doppler Velocimetry

To compare the first‐trimester uterine artery pulsatility index (PI) measured by abdominal and transvaginal ultrasound (US).

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.