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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 (s-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.

Objective Preeclampsia is associated with a higher maternal blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and lower levels of placental growth factor (PlGF) that appear before clinical onset. We aimed to estimate the normal progression of these biomarkers in normal pregnancies and in those affected by preeclampsia. Methods We conducted a case-cohort study including low-risk nulliparous women recruited at 11–13 weeks gestation (cohort) and women with preeclampsia (cases). Maternal blood was collected at different points during pregnancy including at the time of diagnosis of preeclampsia for cases. Maternal serum PlGF and sFlt-1 concentrations and the sFlt-1/PlGF ratio were measured using B•R•A•H•M•S plus KRYPTOR automated assays and were compared between patients in both groups matched for gestational age. Cases were stratified as early- (≤34 weeks), intermediate- (35–37 weeks) and late-onset (>37 weeks) preeclampsia. Results The cohort consisted of 45 women whose results were compared with those of 31 women who developed preeclampsia, diagnosed at a median gestational age of 32 weeks (range 25–38 weeks). We observed that sFlt-1, PlGF and their ratio fluctuated during pregnancy in both groups, with a significant correlation with gestational age after 28 weeks (P Conclusion PlGF, sFlt-1, and their ratio may be useful in the prediction and diagnosis of early- and intermediate-onset preeclampsia but are not useful for late-onset preeclampsia.

To estimate the role of first-trimester uterine artery pulsatility index (UtA-PI) for the prediction of small-for-gestational age (SGA).We conducted a prospective cohort study of nulliparous women with singleton pregnancy (Great Obstetrical Syndromes study). UtA-PI was performed at 11 + 0 to 13 + 6 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.Of 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 (P 0.01). 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%.First-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.