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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Article info
Publication history
Published online: July 01, 2020
Footnotes
Disclosures: This project was funded by the Jeanne-et-Jean-Louis-Lévesque perinatal research chair at Université Laval and by the Jean-Louis-Lévesque Foundation, Montréal, QC. The funding source was not involved in the conduct of the research or the preparation of the article. Prof. Bujold holds a Clinician-Scientist Award from the Fonds de recherche du Québec — Santé (FRQ-S). Dr. Gasse holds a CIHR Doctoral Research Award and an FRQ-S Doctoral Research Award. Dr. Guerby holds a postdoctoral award from the FRQS and INSERM (Institut National de la Santé et de la Recherche Médicale). ThermoFisher/BRAHMS provided unrestricted support by supplying kits, equipment, and reagents necessary for the measurement of the biomarkers.
All authors have indicated that they meet the journal's requirements for authorship.
Identification
Copyright
© 2020 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.
