CX3CL1/Fractalkine as a biomarker for early pregnancy prediction of preterm premature rupture of membranes.

OBJECTIVES: The objective of our study was to evaluate serum CX3CL1/Fractalkine, a monocyte/macrophage chemoattractant expressed in cytotrophoblasts and decidual cells, as a predictive biomarker for the occurrence of preterm premature rupture of membranes (PPROM). METHODS: A case-control study of 438 pregnancies including 82 PPROM cases and 64 preterm labor with intact membranes cases with blood samples collected at first trimester, second trimester and delivery was conducted. The predictive ability of CX3CL1 and maternal risk factors for the occurrence of PPROM was assessed by receiver operating characteristic curve analysis. A second, independent cohort was prospectively constituted to confirm the case-control study results. RESULTS: First trimester CX3CL1 was significantly increased in PPROM cases when compared to matched controls. Multivariate regression analysis highlighted a significant difference for CX3CL1 measured during the first trimester (p<0.001). Alone, CX3CL1 predicts PPROM with a 90 % sensitivity and a specificity around 40 %. The area under the receiver operating characteristic curve for PPROM prediction were 0.64 (95% confidence interval: 0.57-0.71) for first trimester CX3CL1, and 0.61 (95% confidence interval: 0.54-0.68) for maternal risk factors (body mass index<18.5 kg/m2, nulliparity, tobacco use and the absence of high school diploma). The combination of CX3CL1 and maternal risk factors significantly improved the area under the curve: 0.72 (95% confidence interval: 0.66-0.79) (p<0.001). The results were confirmed on a second independent cohort. CONCLUSIONS: CX3CL1 is a promising blood biomarker in the early (first trimester) prediction of PPROM.

First-trimester screening for Down syndrome using quadruple maternal biochemical markers.

OBJECTIVES: Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and could be combined with other biochemical markers for Down syndrome screening. We aim to estimate the predictive value of the combination of pregnancy-associated plasma protein (PAPP-A), free ß-human chorionic gonadotropin (free ß-hCG), placental growth factor (PlGF) and α-fetoprotein (AFP) with and without nuchal translucency. METHODS: Singleton pregnancies recruited at 11-14 weeks and followed until delivery. The four maternal markers were measured using Kryptor (ThermoFisher-BRAHMS) and adjusted for gestational age and maternal characteristics. The risk of Down syndrome was calculated using the Fetal Medicine Foundation algorithm and multivariate linear regression analyses in all cases and in 2,200 controls. Receiver-operator characteristic (ROC) curves were used to calculate the detection and false-positive rates. RESULTS: Twenty-six (0.2%) cases of Down syndrome were diagnosed among 13,386 participants. The combination of the four biomarkers could have detected 88% (95% CI: 72-97%) of the cases at a false-positive rate of 13% (95% CI: 12-15%). The addition of nuchal translucency would have increased the detection rate to 96% (95% CI: 82-99%) at a false-positive rate of 4% (95% CI: 4-5%) using a 1:300 cut-off and to 100% (95% CI: 89-100%) at a false-positive rate of 6% (95% CI: 5-8%) using a 1:500 cut-off. CONCLUSIONS: First-trimester screening using biochemical markers allows the identification of approximately 88% of Down syndrome cases for a false-positive rate of 13%. The addition of nuchal translucency raises the detection rate above 95% with a false-positive rate below 5%.

Impact of COVID-19 and Vaccination During Pregnancy on Placenta-Mediated Complications (COVIGRO Study).

OBJECTIVES: COVID-19 has been associated with preterm birth (PTB) and placental-mediated complications, including fetal growth restriction and preeclampsia (PE). This study aimed to estimate the impact of COVID-19 and vaccination on adverse pregnancy outcomes and markers of placental function. METHODS: We performed a study on a prospective cohort of women recruited in the first trimester of pregnancy during the early COVID-19 pandemic period (December 2020 to December 2021). At each trimester of pregnancy, the assessment included a questionnaire on COVID-19 and vaccination status; serological tests for COVID-19 (for asymptomatic infection); measurement of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in maternal blood; measurement of mean uterine artery pulsatility index (UtA-PI); and pregnancy outcomes (PTB, PE, birth weight below the fifth and the tenth percentile). RESULTS: Among 788 patients with complete data, we observed 101 (13%) cases of symptomatic infection and 74 (9%) cases of asymptomatic infection with SARS-CoV-2. Most cases (73%) of infection were among women with previous vaccination or COVID-19 infection before pregnancy. COVID-19 infection was not associated with adverse pregnancy outcomes, abnormal fetal growth, sFlt-1/PlGF ratio, or mean UtA-PI. Vaccination during pregnancy did not influence these outcomes either. We observed no case of severe COVID-19 infection requiring respiratory support. CONCLUSION: Mild symptomatic or asymptomatic COVID-19 during pregnancy did not influence the risk of adverse pregnancy outcomes and the markers of placental function in predominantly vaccinated women. Fetal growth monitoring is unlikely to be mandatory in women with mild symptoms of COVID-19.

Cord blood S100B: reference ranges and interest for early identification of newborns with brain injury.

Background Neurological complications are common in the premature and full-term neonates admitted to the intensive care unit, but the diagnosis of these complications is often difficult to make. S100B protein, measured in cord blood, may represent a valuable tool to better identify patients at risk of brain injury. Methods As a first step, we established S100B cord blood serum reference intervals from 183 preterm and 200 full-term neonates. We then measured cord blood serum S100B to identify neurological complications in 272 neonates hospitalized at the neonatal intensive care unit (NICU). Diagnosis of brain injury relied on imaging examination. Results The 95th percentiles of S100B concentration in cord blood were established as 1.21 µg/L for the 383 neonates, 0.96 µg/L for full-term neonates and 1.36 µg/L for premature neonates. Among the 272 neonates hospitalized at the NICU, 11 presented neurological complications. Using 1.27 µg/L as the optimal sensitivity/specificity threshold, S100B differentiate neonates with and without neurological complications with a sensitivity of 45.5% (95% confidence intervals [CI]: 16.7-76.6) and a specificity of 88.9% (95% CI: 84.4-92.4) (p = 0.006). In combination with arterial pH (<7.25), sensitivity increased to 90.9% (95% CI: 58.7-99.8), while specificity was 51.2% (95% CI: 44.8-57.7). The sensitivity is significantly (p = 0.03) increased in comparison to S100B alone. The specificity is significantly higher with S100B only than with pH + S100B (p < 0.001). Conclusions Cord blood S100B protein, in combination with arterial cord blood pH, has the potential to help clinicians to detect at birth neurological complications in neonates hospitalized in an NCIU.

Use of antidepressants and anxiolytics in early pregnancy and the risk of preeclampsia and gestational hypertension: a prospective study.

BACKGROUND: We investigated the association between antidepressant and anxiolytic exposure during the first and early second trimester of pregnancy (< 16 weeks), and hypertensive disorders of pregnancy (including preeclampsia and gestational hypertension) in women with singleton pregnancy. METHODS: This study is based on a large prospective cohort of 7866 pregnant women. We included pregnant women aged 18 years or older without chronic hepatic or renal disease at the time of recruitment. Participants lost to the follow-up, with multiple pregnancies and pregnancy terminations, miscarriages or fetal deaths before 20 weeks of gestation were excluded from the study, as well as women with no data on the antidepressant/anxiolytic medication use during pregnancy. Information concerning antidepressant or anxiolytic medication use was extracted from hospital records after delivery. The associations between their use and the risk of gestational hypertension or preeclampsia were calculated. RESULTS: The final sample for analysis included 6761 participants including 218 (3.2%) women who were exposed to antidepressant and/or anxiolytic medication before the 16th week of gestation. Forty-one women had a non-medicated depression or anxiety during the pregnancy. Moreover, 195 (2.9%) and 122 (1.8%) women developed gestational hypertension and preeclampsia respectively. When compared to women unexposed to antidepressant/anxiolytic medication, depression and anxiety, those using antidepressant and/or anxiolytic drugs before the 16th week of gestation were at increased risk of preeclampsia (adjusted odd ratio (aOR) 3.09 [CI95% 1.56-6.12]), especially if they continued their medication after the 16th week (aOR 3.41 [CI95% 1.66-7.02]) compared to those who did not (1.60 [CI95% 0.21-12.34]). CONCLUSIONS: Women exposed to antidepressant and/or anxiolytic medication before the 16th week of pregnancy have a 3-fold increased risk for preeclampsia when compared to women unexposed to antidepressant/anxiolytic medication, depression and anxiety. Also, our results suggested that women who stopped their medication before the 16th week of pregnancy could be benefit from reduced preeclampsia risk.

Comparison of first-tier cell-free DNA screening for common aneuploidies with conventional publically funded screening.

OBJECTIVE: This study evaluates the impact of offering cell-free DNA (cfDNA) screening as a first-tier test for trisomies 21 and 18. METHODS: This is a prospective study of pregnant women undergoing conventional prenatal screening who were offered cfDNA screening in the first trimester with clinical outcomes obtained on all pregnancies. RESULTS: A total of 1198 pregnant women were recruited. The detection rate of trisomy 21 with standard screening was 83% with a false positive rate (FPR) of 5.5% compared with 100% detection and 0% FPR for cfDNA screening. The FPR of cfDNA screening for trisomies 18 and 13 was 0.09% for each. Two percent of women underwent an invasive diagnostic procedure based on screening or ultrasound findings; without the cfDNA screening, it could have been as high as 6.8%. Amongst the 640 women with negative cfDNA results and a nuchal translucency (NT) ultrasound, only 3 had an NT greater or equal to 3.5 mm: one had a normal outcome and two lost their pregnancy before 20 weeks. CONCLUSIONS: cfDNA screening has the potential to be a highly effective first-tier screening approach leading to a significant reduction of invasive diagnostic procedures. For women with a negative cfDNA screening result, NT measurement has limited clinical utility.

Vitamin D Status and Gestational Diabetes: Effect of Smoking Status during Pregnancy.

BACKGROUND: Vitamin D status, as measured by serum 25-hydroxyvitamin D (25(OH)D), has been shown in some studies to be inversely associated with gestational diabetes risk. Recently, it has been suggested that maternal smoking status may modify this relationship. We explored the association between 25(OH)D concentration and gestational diabetes and determined if there was an interaction between smoking and 25(OH)D. METHODS: A nested case-control study was conducted in Halifax, Nova Scotia and Quebec City, Quebec. Women were recruited before 20 weeks gestation and 25(OH)D was measured. Cases were women who developed gestational diabetes and controls were frequency matched to cases on study site, gestational age at blood draw, and season and year of blood draw. Logistic regression models estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI). Models were tested for multiplicative and additive interaction, which was estimated by relative excess risk due to interaction (RERI). RESULTS: The study included 395 gestational diabetes cases and 1925 controls. Women who smoked during pregnancy and had 25(OH)D concentrations <30 nmol/L had an aOR = 3.73 [95% CI 1.95, 7.14] compared to non-smokers with 25(OH)D concentrations ≥50 nmol/L. Additive interaction was detected between smoking status and 25(OH)D [RERI = 2.44, 95% CI 0.03, 4.85]. CONCLUSION: Our study supports the inverse association of vitamin D status with gestational diabetes risk, particularly among women who smoke during pregnancy. More research is needed to confirm this finding and, if confirmed, to determine the mechanism by which the combined effect of smoking and low vitamin D status increases the risk of developing gestational diabetes.

Early prediction of gestational diabetes: a practical model combining clinical and biochemical markers.

BACKGROUND: Gestational diabetes (GDM) is usually diagnosed late in pregnancy, precluding early preventive interventions. This study aims to develop a predictive model based on clinical factors and selected biochemical markers for the early risk assessment of GDM. METHODS: Based on a prospective cohort of 7929 pregnant women from the Quebec City metropolitan area, a nested case-control study was performed including 264 women who developed GDM. Each woman who developed GDM was matched with two women with normal glycemic profile. Risk prediction models for GDM and GDM requiring insulin therapy were developed using multivariable logistic regression analyses, based on clinical characteristics and the measurement of three clinically validated biomarkers: glycated hemoglobin (HbA1c), sex hormone binding globulin (SHBG) and high-sensitivity C-reactive protein (hsCRP) measured between 14 and 17 weeks of gestation. RESULTS: HbA1c and hsCRP were higher and SHBG was lower in women who developed GDM (p<0.001). The selected model for the prediction of GDM, based on HbA1c, SHBG, BMI, past history of GDM, family history of diabetes and soft drink intake before pregnancy yielded an area under the ROC curve (AUC) of 0.79 (0.75-0.83). For the prediction of GDM requiring insulin therapy, the selected model including the same six variables yielded an AUC of 0.88 (0.84-0.92) and a sensitivity of 68.9% at a false-positive rate of 10%. CONCLUSIONS: A simple model based on clinical characteristics and biomarkers available early in pregnancy could allow the identification of women at risk of developing GDM, especially GDM requiring insulin therapy.

Cord blood vitamin D status and neonatal outcomes in a birth cohort in Quebec, Canada.

PURPOSE: Some evidence suggests that low maternal vitamin D status adversely affects perinatal health but few studies have examined cord blood vitamin D status. This project aimed to determine the association between the cord blood concentration of 25-hydroxyvitamin D [25(OH)D] and neonatal outcomes. METHODS: A nested case-control study was conducted in Quebec City, Canada from 2005 to 2010. Included were 83 cases of low birthweight (LBW; <2500 g), 301 cases of small for gestational age (SGA; <10th percentile), 223 cases of preterm birth (PTB; <37 weeks' gestation), and 1027 controls. Levels of 25(OH)D were determined by chemiluminescence immunoassay. Adjusted odds ratios (OR) and 95 % confidence intervals (CI) were estimated with logistic regression. RESULTS: Cord blood [25(OH)D] <50 nmol/L was associated with a lower risk of LBW compared to [25(OH)D] ≥75 nmol/L (OR 0.47 95 % CI 0.23-0.97). For 25(OH)D levels 50-75 nmol/L, a significant association was not demonstrated (OR 0.58, 95 % CI 0.34-1.01). No significant associations were observed between [25(OH)D] and either SGA or PTB after adjustment. CONCLUSIONS: Although our findings suggest that [25(OH)D] <50 nmol/L is associated with reduced risk of having a LBW infant, prenatal vitamin D recommendations require an examination of the literature that considers the full spectrum of maternal and neonatal outcomes.

Vitamin D status in early pregnancy and risk of preeclampsia.

OBJECTIVE: We sought to examine the association between maternal serum 25-hydroxyvitamin D (25[OH]D) concentration in early pregnancy and the subsequent diagnosis of preeclampsia (PE). STUDY DESIGN: This was a nested case-control study from 2 prospective Canadian cohorts conducted in Quebec City, Quebec, and Halifax, Nova Scotia, from 2002 through 2010. Participants were pregnant women (n = 169 cases with PE and 1975 controls). Maternal serum was drawn <20 weeks of gestation, and 25(OH)D measurement was performed. Cases were ascertained from medical records. Logistic regression analysis was used to estimate adjusted odds ratios with 95% confidence intervals. RESULTS: Women who developed PE had a significantly lower 25(OH)D concentration at a mean gestational age of 14 weeks compared with women in the control group (mean ± SD 25[OH]D 47.2 ± 17.7 vs 52.3 ± 17.2 nmol/L, P < .0001). Women with 25(OH)D <30 nmol/L compared to those with at least 50 nmol/L had a greater risk of developing PE (adjusted odds ratio, 2.23; 95% confidence interval, 1.29-3.83) after adjustment for prepregnancy body mass index, maternal age, smoking, parity, season and year of blood collection, gestational week at blood collection, and cohort site. Exploratory analysis with cubic splines demonstrated a dose-response relationship between maternal 25(OH)D and risk of PE, up to levels around 50 nmol/L, where the association appeared to plateau. CONCLUSION: Maternal vitamin D deficiency early in pregnancy defined as 25(OH)D <30 nmol/L may be an independent risk factor for PE. The relevance of vitamin D supplementation for women of childbearing age should be explored as a strategy for reducing PE and for promoting a healthier pregnancy.

Mid-trimester maternal serum AFP and hCG as markers of preterm and term adverse pregnancy outcomes.

OBJECTIVE: To evaluate the predictive values of mid-trimester serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) for preterm and term placenta-mediated adverse pregnancy outcomes (PMAPOs). METHODS: We extracted data for nulliparous women with a singleton pregnancy without aneuploidy or lethal fetal anomalies from a prospective cohort study. Maternal serum AFP and hCG measured between 13 and 17 weeks of gestation and expressed as multiples of the median (MoM) for gestational age were compared between women who developed a PMAPO (preeclampsia, intrauterine growth restriction, fetal death) before term or at term and women who did not develop any of these complications. RESULTS: Among 3466 nulliparous women, maternal serum AFP and hCG levels were available in 2110 and 2125 cases, respectively. Women who developed a PMAPO before term had a higher median level of serum AFP (1.4 vs. 1.1 MoM; P < 0.01) and hCG (1.3 vs. 1.1 MoM; P < 0.01) than controls. A serum hCG > 2.0 MoM was associated with a higher risk of PMAPO before term (RR 4.6; CI 95% 2.3 to 9.1) but had no impact on the risk of PMAPO at term (RR 1.1; CI 95% 0.7 to 1.7). Maternal serum AFP > 2.0 MoM was also associated with a significant increase in the risk of preterm PMAPO (RR 3.9; CI 95% 1.6 to 9.8) but not term PMAPO (RR 1.2; CI 95% 0.6 to 2.3). CONCLUSION: Maternal serum AFP or hCG > 2.0 MoM increases the risk of preterm PMAPO but not term PMAPO in our population. We suggest that women with elevated serum AFP or hCG should receive standard pregnancy care once they have reached 37 weeks of gestation if fetal growth is in the normal range.

Objectif : Évaluer les coefficients de prévision propres aux taux sériques d'alphafœtoprotéine (AFP) et de gonadotrophine chorionique (hCG) constatés au deuxième trimestre pour ce qui est des issues de grossesse indésirables à médiation placentaire (IGIMP) obtenues avant le terme et à terme. Méthodes : Nous avons tiré, d'une étude de cohorte prospective, des données concernant des femmes nullipares ayant connu une grossesse monofœtale exempte d'aneuploïdie ou d'anomalies fœtales mortelles. Nous avons comparé les taux sériques maternels d'AFP et de hCG (mesurés entre 13 et 17 semaines de gestation et exprimés sous forme de multiples de la médiane [MoM] en fonction de l'âge gestationnel) des femmes ayant connu une IGIMP (prééclampsie, retard de croissance intra-utérin, décès fœtal) avant le terme ou à terme à ceux des femmes qui n'en sont pas venues à connaître de telles complications. Résultats : Au sein d'un groupe de 3 466 femmes nullipares, les taux sériques maternels d'AFP et de hCG étaient connus dans 2 110 cas et 2 125 cas, respectivement. Les femmes qui ont connu une IGIMP avant le terme présentaient des valeurs de MoM pour ce qui est des taux sériques d'AFP (1,4 vs 1,1 MoM; P < 0,01) et de hCG (1,3 vs 1,1 MoM; P < 0,01) plus élevées que celles des femmes du groupe témoin. Bien que la constatation d'un taux sérique de hCG > 2,0 MoM ait été associée à un risque accru d'IGIMP avant le terme (RR, 4,6; IC à 95 %, 2,3 - 9,1), elle n'exerçait aucun effet sur le risque d'IGIMP à terme (RR, 1,1; IC à 95 %, 0,7 - 1,7). La constatation d'un taux sérique maternel d'AFP > 2,0 MoM a également été associée à une hausse considérable du risque d'IGIMP avant le terme (RR, 3,9; IC à 95 %, 1,6 - 9,8); le risque d'IGIMP à terme (RR, 1,2; IC à 95 %, 0,6 - 2,3) n'en était toutefois pas affecté. Conclusion : Au sein de la population à l'étude, les taux sériques maternels d'AFP ou de hCG > 2,0 MoM ont entraîné une hausse du risque d'IGIMP avant le terme, mais n'ont pas exercé une influence sur le risque d'IGIMP à terme. Lorsque la croissance fœtale se situe dans la plage normale, les femmes qui présentent des taux sériques élevés d'AFP ou de hCG devraient recevoir des soins de grossesse standard, une fois qu'elles ont atteint 37 semaines de gestation.

First-Trimester Placental and Myometrial Blood Perfusion Measured by Three-Dimensional Power Doppler in Preeclampsia.

OBJECTIVE: The study aims to evaluate first-trimester vascularization of the placenta and subplacental myometrium in women who subsequently develop preeclampsia. STUDY DESIGN: A case-control study nested in a prospective cohort was conducted in women with singleton pregnancy between 11 and 14 weeks' gestation. Three-dimensional standardized acquisition of the placenta and subplacental myometrium volumes with and without power Doppler was undertaken, and all participants were followed up until delivery. Each woman diagnosed with preeclampsia was matched with three controls who delivered at term without pregnancy complications. First-trimester volume, vascularization index (VI), flow index (FI), and vascular flow index (VFI) of the entire placenta and subplacental myometrium were measured separately. The results were stratified for preterm and term preeclampsia, respectively. RESULTS: A total of 1,034 women were recruited, including 16 (1.5%) who developed term preeclampsia and 4 (0.4%) who developed preterm preeclampsia. Preeclampsia was associated with a significantly lower placental VI, placental VFI, subplacental VI, and subplacental VFI in the first trimester than with the controls (all p < 0.05). All cases (4/4) of preterm preeclampsia, 56% (9/16) of term preeclampsia, and 28% (17/60) of the controls had a subplacental VI below 18% (p < 0.01). CONCLUSION: First-trimester placental and subplacental myometrium vascularizations are significantly reduced in women who subsequently develop preeclampsia.

Soluble Fms-like tyrosine kinase-1 to placental growth factor ratio in mid-pregnancy as a predictor of preterm preeclampsia in asymptomatic pregnant women.

BACKGROUND: This study aims to evaluate the performance of the soluble Fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict early-onset, preterm and severe preeclampsia at mid-pregnancy in asymptomatic women. METHODS: Based on a prospective cohort of 7929 pregnant women from the Quebec City metropolitan area, a nested case-control study was performed including 111 women who developed preeclampsia and 69 women with gestational hypertension matched with 338 normotensive women. Serum sFlt-1 and PlGF were measured between 20 and 32 weeks of gestation. The performance of the sFlt-1/PlGF ratio, expressed as raw values and multiples of the median (MoM) for the prediction of early-onset, preterm and severe preeclampsia was evaluated. RESULTS: Women who developed preeclampsia had significantly higher MoM sFlt-1/PlGF ratio (p<0.001). In the early-onset preeclampsia group, the median of the MoM distribution was 24.0 and the area under the receiver operating characteristic curve (AUC) was 0.977, giving sensitivities of 77.8% and 88.9% at false-positive rates of 5% and 10%. Positive predictive values (PPV) were 2.5% and 1.5%, respectively. In a subset between 26 and 32 weeks of gestation, at a threshold of 30, the sFlt-1/PlGF ratio yielded 100% specificity and identified, respectively, 85.7% and 65.2% of women who developed early-onset and preterm preeclampsia. CONCLUSIONS: The sFlt-1/PlGF ratio has the potential to predict early-onset and preterm preeclampsia at mid-pregnancy in asymptomatic women. However, care must be paid to the prevalence of early-onset preeclampsia in the population since low prevalence reduces PPV and may hamper clinical utility.

Prospective Validation of First-Trimester Screening for Preterm Preeclampsia in Nulliparous Women (PREDICTION Study).

BACKGROUND: Fetal Medicine Foundation (FMF) studies suggest that preterm preeclampsia can be predicted in the first trimester by combining biophysical, biochemical, and ultrasound markers and prevented using aspirin. We aimed to evaluate the FMF preterm preeclampsia screening test in nulliparous women. METHODS: We conducted a prospective multicenter cohort study of nulliparous women recruited at 11 to 14 weeks. Maternal characteristics, mean arterial blood pressure, PAPP-A (pregnancy-associated plasma protein A), PlGF (placental growth factor) in maternal blood, and uterine artery pulsatility index were collected at recruitment. The risk of preterm preeclampsia was calculated by a third party blinded to pregnancy outcomes. Receiver operating characteristic curves were used to estimate the detection rate (sensitivity) and the false-positive rate (1-specificity) for preterm (<37 weeks) and for early-onset (<34 weeks) preeclampsia according to the FMF screening test and according to the American College of Obstetricians and Gynecologists criteria. RESULTS: We recruited 7554 participants including 7325 (97%) who remained eligible after 20 weeks of which 65 (0.9%) developed preterm preeclampsia, and 22 (0.3%) developed early-onset preeclampsia. Using the FMF algorithm (cutoff of ≥1 in 110 for preterm preeclampsia), the detection rate was 63.1% for preterm preeclampsia and 77.3% for early-onset preeclampsia at a false-positive rate of 15.8%. Using the American College of Obstetricians and Gynecologists criteria, the equivalent detection rates would have been 61.5% and 59.1%, respectively, for a false-positive rate of 34.3%. CONCLUSIONS: The first-trimester FMF preeclampsia screening test predicts two-thirds of preterm preeclampsia and three-quarters of early-onset preeclampsia in nulliparous women, with a false-positive rate of ≈16%. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02189148.

Association between physical activity in early pregnancy and markers of placental growth and function.

OBJECTIVES: It has been suggested that physical activity (PA) can influence the development of the placenta and the risk of placenta-mediated complications of pregnancy. We evaluated the association between PA and early markers of placental development. METHODS: Ninety-four nulliparous women were invited to participate in a prospective observational cohort study. Assessment included measurement of placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) concentrations (expressed in multiples of the median), an ultrasound at 11 to 13 weeks for measurement of placental volume and the mean uterine artery (UtA) pulsatility index, and a questionnaire on PA. The association between PA and these markers was evaluated using univariate and multivariate regression analyses. RESULTS: We found a significantly lower concentration of PlGF and a trend towards lower placenta volume and lower PAPP-A concentration with increased PA frequency. The negative association between PA frequency and PlGF concentration remained significant after adjustment for potential confounding factors. CONCLUSION: Our results suggest that PA in early pregnancy could negatively affect placental development. This finding could explain the association between PA and severe preeclampsia. This finding deserves confirmation in a larger cohort.

Objectifs : On a avancé que l'activité physique (AP) pouvait influencer le développement du placenta et le risque de complications de grossesse à médiation placentaire. Nous avons évalué l'association entre l'AP et les marqueurs précoces du développement placentaire. Méthodes : Quatre-vingt-quatorze femmes nullipares ont été invitées à participer à une étude de cohorte observationnelle prospective. L'évaluation comprenait la mesure des concentrations en (exprimées sous forme de multiples de la médiane) en facteur de croissance placentaire (PlGF) et en protéine plasmatique placentaire de type A (PAPP-A), une échographie menée à 11 - 13 semaines aux fins de la mesure du volume placentaire et de l'indice de pulsatilité moyen de l'artère utérine (AUt), et un questionnaire sur l'AP. L'association entre l'AP et ces marqueurs a été évaluée au moyen d'analyses de régression univariées et multivariées. Résultats : Nous avons constaté que la hausse de la fréquence de l'AP s'accompagnait d'une concentration en PlGF considérablement moindre et d'une tendance à la baisse en ce qui concerne le volume placentaire et la concentration en PAPP-A. L'association négative entre la fréquence de l'AP et la concentration en PlGF est demeurée significative à la suite de la neutralisation de l'effet des facteurs de confusion potentiels. Conclusion : Nos résultats semblent indiquer que l'AP aux débuts de la grossesse pourrait exercer un effet négatif sur le développement placentaire. Cette constatation pourrait expliquer l'association entre l'AP et la prééclampsie grave. La tenue d'une étude auprès d'une cohorte de plus grande envergure à des fins de confirmation s'avère justifiée.

Canadian SARS-CoV-2 serological survey using antenatal serum samples: a retrospective seroprevalence study.

BACKGROUND: Insufficient data on the rate and distribution of SARS-CoV-2 infection in Canada has presented a substantial challenge to the public health response to the COVID-19 pandemic. Our objective was to assess SARS-CoV-2 seroprevalence in a representative sample of pregnant people throughout Canada, across multiple time points over 2 years of the pandemic, to describe the seroprevalence and show the ability of this process to provide prevalence estimates. METHODS: This Canadian retrospective serological surveillance study used existing serological prenatal samples across 10 provinces over multiple time periods: Feb. 3-21, 2020; Aug. 24-Sept. 11, 2020; Nov. 16-Dec. 4, 2020; Nov. 15-Dec. 3, 2021; and results from the province of British Columbia during a period in which the SARS-CoV-2 B.1.1.529 (Omicron) variant was predominant, from Nov. 15, 2021, to June 11, 2022. Age and postal code administrative data allowed for comparison with concurrent polymerase chain reactivity (PCR)-positive results collected by Statistics Canada and the Canadian Surveillance of COVID-19 in Pregnancy (CANCOVID-Preg) project. RESULTS: Seropositivity in antenatal serum as early as February 2020 indicates SARS-CoV-2 transmission before the World Health Organization's declaration of the pandemic. Seroprevalence in our sample of pregnant people was 1.84 to 8.90 times higher than the recorded concurrent PCR-positive prevalence recorded among females aged 20-49 years in November-December 2020. Overall seropositivity in our sample of pregnant people was low at the end of 2020, increasing to 15% in 1 province by the end of 2021. Seroprevalence among pregnant people in BC during the Omicron period increased from 5.8% to 43% from November 2021 to June 2022. INTERPRETATION: These results indicate widespread vulnerability to SARS-CoV-2 infection before vaccine availability in Canada. During the time periods sampled, public health tracking systems were under-reporting infections, and seroprevalence results during the Omicron period indicate extensive community spread of SARS-CoV-2 infection.

Modulation of fatty acid transport and metabolism by maternal obesity in the human full-term placenta.

Knowledge of the consequences of maternal obesity in human placental fatty acids (FA) transport and metabolism is limited. Animal studies suggest that placental uptake of maternal FA is altered by maternal overnutrition. We hypothesized that high maternal body mass index (BMI) affects human placental FA transport by modifying expression of key transporters. Full-term placentas were obtained by vaginal delivery from normal weight (BMI, 18.5-24.9 kg/m(2)) and obese (BMI > 30 kg/m(2)) women. Blood samples were collected from the mother at each trimester and from cord blood at delivery. mRNA and protein expression levels were evaluated with real-time RT-PCR and Western blotting. Lipoprotein lipase (LPL) activity was evaluated using enzyme fluorescence. In vitro linoleic acid transport was studied with isolated trophoblasts. Our results demonstrated that maternal obesity is associated with increased placental weight, decreased gestational age, decreased maternal high-density lipoprotein (HDL) levels during the first and third trimesters, increased maternal triglyceride levels during the second and third trimesters, and increased maternal T3 levels during all trimesters, and decreased maternal cholesterol (CHOL) and low-density lipoprotein (LDL) levels during the third trimester; and increased newborn CHOL, LDL, apolipoprotein B100, and T3 levels. Increases in placental CD36 mRNA and protein expression levels, decreased SLC27A4 and FABP1 mRNA and protein and FABP3 protein expression, and increased LPL activity and decreased villus cytotrophoblast linoleic acid transport were also observed. No changes were seen in expression of PPARA, PPARD, or PPARG mRNA and protein. Overall this study demonstrated that maternal obesity impacts placental FA uptake without affecting fetal growth. These changes, however, could modify the fetus metabolism and its predisposition to develop diseases later in life.

Candidate biochemical markers for screening of pre-eclampsia in early pregnancy.

Pre-eclampsia (PE) and other hypertensive disorders of pregnancy (HDP) are a leading cause of adverse outcomes. Their pathophysiology remains elusive, hampering the development of efficient prevention. The onset of HDP and PE and the severity of their clinical manifestations are heterogeneous. The advent of preventive measures, such as low-dose aspirin that targets high-risk women, emphasizes the need of better prediction. Until recently, only environmental information and maternal risk factors were considered, with equivocal predictive value. No validated screening procedures were available to identify at-risk women despite the emergence of Doppler ultrasonography parameters for the uterine artery (e.g., pulsatility index and bilateral notching) and pathophysiological biochemical markers (e.g., angiogenesis, inflammation, and endothelial dysfunction). Owing to its heterogeneity and lack of specific, sensitive markers among those studied so far (>200), PE is unlikely to be detected early by a single predictive parameter. Systematic reviews have concluded that no single test fulfilling World Health Organization criteria for biomarker selection can diagnose/predict a disease. However, by combining antenatal risk factors, clinical parameters, as well as biophysical and biochemical markers into multivariate algorithms, the risk of PE can be estimated with performance levels that could reach clinical utility. Performance characteristics of selected algorithms will be presented and discussed with respect to transferability to different geographic and healthcare environments.

Linking preeclampsia and cardiovascular disease later in life.

Preeclampsia (PE), which is defined as new onset hypertension after 20 weeks of pregnancy accompanied by proteinuria, is characterized by inadequate placentation, oxidative stress, inflammation and widespread endothelial dysfunction. A link between PE and long-term risk of cardiovascular disease (CVD) was suggested by retrospective studies, which found that PE was associated with a 2­3-fold risk of CVD later in life, with a 5­7-fold risk in the case of severe and/or early-onset PE. Recently, meta-analyses and prospective studies have confirmed the association between PE and the emergence of an unfavorable CVD risk profile, in particular a 3­5-fold increased prevalence of the metabolic syndrome only 8 years after the index pregnancy. PE and CVD share many risk factors, including obesity, hypertension, dyslipidemia, hypercoagulability, insulin resistance and both entities are characterized by endothelial dysfunction. PE and CVD are complex traits sharing common risk factors and pathophysiological processes, but the genetic link between both remains to be elucidated. However, recent evidence suggests that genetic determinants associated with the metabolic syndrome, inflammation and subsequent endothelial dysfunction are involved. As the evidence now supports that PE represents a risk factor for the emergence of the metabolic syndrome and CVD later in life, the importance of long-term follow-up assessment of CVD risk beginning early in women with a history of PE must be considered and translated into new preventive measures.

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

OBJECTIVE: To determine whether early administration of aspirin prevents severe and mild preeclampsia. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials were performed. Studies in which women were randomized at or before 16 weeks' gestation to low-dose aspirin versus placebo or no treatment were included. The outcomes of interest were severe preeclampsia and mild preeclampsia. Pooled relative risks with their 95% confidence intervals (CIs) were calculated. RESULTS: Among 7941 citations retrieved, 352 were completely reviewed and four studies (392 women) fulfilled the inclusion criteria and were analyzed. When compared with controls, aspirin started at ≤16 weeks was associated with a significant reduction in severe (relative risk: 0.22, 95% CI: 0.08 to 0.57) but not mild (relative risk: 0.81, 95% CI: 0.33 to 1.96) preeclampsia. CONCLUSION: Low-dose aspirin initiated at or before 16 weeks reduces the risk of severe preeclampsia, but not mild preeclampsia.