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First-Trimester Preterm Preeclampsia Screening in Nulliparous Women: The Great Obstetrical Syndrome (GOS) Study

      Abstract

      Objectives

      To estimate the ability of a combination of first-trimester markers to predict preterm preeclampsia in nulliparous women.

      Methods

      We conducted a prospective cohort study of nulliparous women with singleton gestations, recruited between 110 and 136 weeks gestation. Data on the following were collected: maternal age; ethnicity; chronic diseases; use of fertility treatment; body mass index; mean arterial blood pressure (MAP); serum levels of pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), alpha fetoprotein (AFP), free beta human chorionic gonadotropin (ß-hCG); and mean uterine artery pulsatility index (UtA-PI). We constructed a proportional hazard model for the prediction of preterm preeclampsia selected based on the Akaike information criterion. A receiver operating characteristic curve was created with the predicted risk from the final model. Our primary outcome was preterm preeclampsia and our secondary outcome was a composite of preeclampsia, small for gestational age, intrauterine death, and preterm birth.

      Results

      Among 4659 nulliparous women with singleton gestations, our final model included 4 variables: MAP MoM, log10PlGF MoM, log10AFP MoM and log10UtA-PI MoM. We obtained an area under the curve of 0.84 (95% CI 0.75–0.93) with a detection rate of preterm preeclampsia of 55% (95% CI 37%–73%) and a false-positive rate of 10%. Using a risk cut-off with a false-positive rate of 10%, the positive predictive value for our composite outcome was 33% (95% CI 29%–37%).

      Conclusions

      The combination of MAP, maternal serum PlGF and AFP, and UtA-PI are useful to identify nulliparous women at high risk of preterm preeclampsia but also at high risk of other great obstetrical syndromes.

      Résumé

      OBJECTIFS

      Estimer la capacité d'une combinaison de marqueurs du premier trimestre à prédire la pré-éclampsie avant terme chez les femmes nullipares.

      MÉTHODOLOGIE

      Nous avons mené une étude de cohorte prospective de grossesses monofœtales chez des femmes nullipares recrutées entre 11 SA +0 j et 13 SA + 6 j. Les données suivantes ont été recueillies : âge maternel; origine ethnique; maladies chroniques; traitement de l'infertilité; indice de masse corporelle; pression artérielle moyenne; taux sériques de protéine A plasmatique associée à la grossesse (PAPP-A), facteur de croissance placentaire (PlGF), forme soluble du récepteur au VEGF de type 1 (sFlt-1), alphafœtoprotéine (AFP), bêta-hCG libre (ß-hCG); et indice de pulsatilité moyen de l'artère utérine. Nous avons conçu un modèle des risques proportionnels pour la prédiction de la pré-éclampsie avant terme sélectionné d'après le critère d'information d'Akaïke. Une courbe d'efficacité du récepteur (courbe ROC) a été dessinée à partir du risque prédit par le modèle final. Le critère de jugement principal était la pré-éclampsie avant terme et le critère de jugement secondaire était un composite des issues suivantes : pré-éclampsie, petit poids pour l'âge gestationnel, mort intra-utérine et naissance avant terme.

      RÉSULTATS

      Pour les 4 659 grossesses monofœtales chez des femmes nullipares, notre modèle final comprenait 4 variables : multiple de la médiane (MoM) de la pression artérielle moyenne, MoM du log10 PlGF, MoM du log10 AFP, MoM du log10 de l'indice de pulsatilité des artères utérines, log10 du MoM de l'AFP et log10 du MoM de l'indice de pulsatilité moyen de l'artère utérine. Nous avons obtenu une aire sous la courbe de 0,84 (IC à 95 % : 0,75–0,93) avec un taux de détection de la pré-éclampsie avant terme de 55 % (IC à 95 % : 37 %–73 %) et un taux de faux positifs de 10 %. Le seuil de taux de faux positifs de 10 % pour un risque élevé de pré-éclampsie avant terme a une valeur prédictive positive de 33 % (IC à 95 % : 29 %–37 %) pour notre résultat composite. En utilisant un seuil de risque avec un taux de faux-positifs de 10%, la valeur prédictive positive de notre composite était de 33% (IC à 95%: 29%–37%).

      CONCLUSIONS

      La pression artérielle moyenne, les taux sériques de PlGF et de l'AFP et l'indice de pulsatilité moyen de l'artère utérine sont des données utiles une fois combinées pour identifier les femmes nullipares qui présentent un risque élevé pour la pré-éclampsie avant terme, mais aussi pour d'autres grands syndromes obstétricaux.

      Keywords

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