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First trimester risk of preeclampsia and rate of spontaneous birth in patients without preeclampsia - 10/02/24

Doi : 10.1016/j.ajog.2024.01.008 
Paolo I. Cavoretto, MD a, b, Antonio Farina, MD c, d, , Noemi Salmeri, MD a, b, Argyro Syngelaki, PhD e, Min Yi Tan, MD e, Kypros H. Nicolaides, MD e
a Department of Obstetrics and Gynaecology, IRCCS San Raffaele Scientific Institute, Milan, Italy 
b Vita-Salute San Raffaele University, Milan, Italy 
c Obstetric Unit, IRCCS Azienda Ospedaliero–Universitaria di Bologna, Bologna, Italy 
d Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy 
e Fetal Medicine Research Institute, King’s College Hospital, London, United Kingdom 

Corresponding author: Antonio Farina, MD.
Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 10 February 2024

Abstract

Background

First-trimester screening for preeclampsia using a combination of maternal risk factors and mean arterial pressure, uterine artery pulsatility index, and placental growth factor, as proposed by the Fetal Medicine Foundation, provides effective prediction of preterm preeclampsia. Placental dysfunction is a potential precursor of spontaneous birth.

Objective

The objective of this study was to examine if the estimated risk of preeclampsia is associated with the gestational age at onset of spontaneous delivery in the absence of preeclampsia.

Study Design

This was a secondary analysis of the data from the Screening programme for pre-eclampsia trial in which there was a comparison of the performance of first-trimester screening for preterm preeclampsia using the Fetal Medicine Foundation model vs a traditional history-based risk scoring system. A subgroup of women from the trial with spontaneous onset of delivery (labor with intact membranes or preterm prelabor rupture of membranes) was included in this study and was arbitrarily divided into 3 groups according to the risk for preterm preeclampsia as determined by the Fetal Medicine Foundation model at 11 to 13 weeks’ gestation as follows: group 1 low risk (˂1/100); group 2 intermediate risk (1/50 to 1/100); and group 3 high risk (˃1/50). A survival analysis was carried out using a Kaplan-Meier estimator and a Cox regression analysis with stratification by the 3 preeclampsia risk groups. Occurrence of spontaneous birth in the study groups was compared using log-rank tests and hazard ratios.

Results

The study population comprised 10,820 cases with delivery after spontaneous onset of labor among the 16,451 cases who participated in the Screening programme for pre-eclampsia trial. There were 9795 cases in group 1, 583 in group 2, and 442 in group 3. The gestational age at delivery was <28, <32, <35, <37, and <40 weeks in 0.29%, 0.64%, 1.68%, 4.52%, and 44.97% of cases, respectively, in group 1; 0.69%, 1.71%, 3.26%, 7.72%, and 55.23% of cases, respectively, in group 2; and 0.45%, 1.81%, 5.66%, 13.80%, and 63.12% of cases, respectively, in group 3. The curve profile of gestational age at spontaneous birth in the 3 study groups was significantly different overall and in pairwise comparisons (P values <.001). The Cox regression analysis showed that risks increased for spontaneous birth by 18% when the intermediate-risk group was compared with the low-risk group (P˂.001) and by 41% when the high-risk group was compared with the low-risk group (P˂.001).

Conclusion

In this study that investigated birth after spontaneous onset of labor in women without preeclampsia, there were 2 major findings. First, the duration of pregnancy decreased with increasing first-trimester risk for preeclampsia. Second, in the high-risk group, when compared with the low-risk group, the risk for spontaneous birth was 4 times higher at a gestational age of 24 to 26 weeks, 3 times higher at 28 to 32 weeks, and 2 times higher at 34 to 39 weeks. These differences present major clinical implications for antepartum counselling, monitoring, and interventions in these pregnancies.

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Key words : competing risks model, first-trimester screening, labor, mean arterial pressure, placental growth factor, preeclampsia, preterm birth, SPREE study, survival analysis, uterine artery Doppler


Plan


 The authors report no conflict of interest.
 The research was financially supported through grants from various sources, including the Fetal Medicine Foundation and the National Institute for Health Research Efficacy and Mechanism Evaluation (NIHR EME) Programme under grant number 14/01/02, which is a collaboration between the Medical Research Council (MRC) and the National Institute for Health Research (NIHR). The reagents and equipment necessary for measuring the serum placental growth factor concentration were generously supplied without cost by Revvity, formerly affiliated with PerkinElmer Inc., and ThermoFisher Scientific. These organizations did not play a role in the design of the study, the collection, analyses, or interpretation of the data, writing of the research report, or decision to submit the article for publication.
 This study was conducted in accordance with the ethical standards for human research established by the Declaration of Helsinki. The Screening programme for pre-eclampsia (SPREE) trial received approval from the London-Surrey Borders Research Ethics Committee.
 Informed consent was not deemed necessary for the patients recruited retrospectively because anonymous data collection was respected. The patients of the primary study (SPREE study) provided a signed consent form for publishing the anonymized data of the clinical case including all additional analyses on the stored data set.
 Cite this article as: Cavoretto PI, Farina A, Salmeri N, et al. First trimester risk of preeclampsia and rate of spontaneous birth in patients without preeclampsia. Am J Obstet Gynecol 2024;XX:x.ex–x.ex.


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