Background: First-trimester maternal serum markers have been associated with preeclampsia (PE). We aimed to evaluate the performance of first-trimester placental growth factor (PlGF) for the prediction of PE in nulliparous women. Subjects and Methods: We conducted a prospective cohort study of nulliparous women with singleton pregnancy at 11–13 weeks. Maternal serum PlGF concentration was measured using B·R·A·H·M·S PlGFplus KRYPTOR automated assays and reported in multiple of the median adjusted for gestational age. We used proportional hazard models, along with receiver operating characteristic curves and areas under the curve (AUC). Results: Out of 4,652 participants, we observed 232 (4.9%) cases of PE including 202 (4.3%) term and 30 (0.6%) preterm PE. PlGF was associated with the risk of term (AUC = 0.61, 95% confidence interval [CI] 0.57–0.65) and preterm PE (AUC = 0.73, 95% CI 0.64–0.83). The models were improved with the addition of maternal characteristics (AUC for term PE 0.66, 95% CI 0.62–0.71; AUC for preterm PE 0.81, 95% CI 0.72–0.91; p < 0.01). At a false-positive rate of 10%, PlGF combined with maternal characteristics could have predicted 26% of term and 55% of preterm PE. The addition of pregnancy-associated plasma protein A did not significantly improve the prediction models. Conclusion: First-trimester PlGF combined with maternal characteristics is useful to predict preterm PE in nulliparous women.
Objective The purpose of this study was to evaluate the predictive value of vaginal fluid biomarkers for chorioamnionitis and adverse perinatal outcomes in women with preterm premature rupture of membranes (PPROM). Methods We recruited women with PPROM, without clinical chorioamnionitis, between 22 and 36 weeks' gestation. Vaginal fluid was collected on admission for the measurement of metalloproteinase-8 (MMP-8), interleukin-6 (IL-6), lactate, and glucose concentration. Placental pathology and neonatal charts were reviewed. Primary outcomes were histological chorioamnionitis and adverse neonatal neurological outcomes (intraventricular hemorrhage grade 2 or 3, periventricular leukomalacia, or hypoxic/ischemic encephalopathy). Linear regression analyses were used to adjust for gestational age at PPROM. Results Twenty-seven women were recruited at a mean gestational age of 31.6 ± 3.1 weeks, including 25 (93%) with successful collection of vaginal fluid sample. Histological chorioamnionitis and adverse neonatal neurological outcomes were observed in nine (33%) and four (15%) cases, respectively. In univariate analysis, MMP-8, IL-6, glucose, and lactate concentrations in vaginal fluid were associated with the risk of chorioamnionitis but not anymore after adjustment for gestational age at PPROM. MMP-8 concentration was the only biomarker associated with adverse neurological outcome, and it remained significant after adjustment for gestational age at PPROM (p = 0.02). Conclusion Vaginal fluid inflammatory biomarkers at admission for PPROM could predict adverse perinatal outcomes.
Background: To explore the use of maternal urine proteome for the identification of preeclampsia biomarkers. Methods: Maternal urine samples from women with and without preeclampsia were used for protein discovery followed by a validation study. The targeted proteins of interest were then measured in urine samples collected at 20–24 and 30–34 weeks among nine women who developed preeclampsia, one woman with fetal growth restriction, and 20 women with uncomplicated pregnancies from a longitudinal study. Protein identification and quantification was obtained using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Results: Among the 1108 urine proteins quantified in the discovery study, 21 were upregulated in preeclampsia and selected for validation. Nineteen (90%) proteins were confirmed as upregulated in preeclampsia cases. Among them, two proteins, ceruloplasmin and serpin A7, were upregulated at 20–24 weeks and 30–34 weeks of gestation (p < 0.05) in cases of preeclampsia, and could have served to identify 60% of women who subsequently developed preeclampsia and/or fetal growth restriction at 20–24 weeks of gestation, and 78% at 30–34 weeks, for a false-positive rate of 10%. Conclusions: Proteomic profiling of maternal urine can differentiate women with and without preeclampsia. Several proteins including ceruloplasmin and serpin A7 are upregulated in maternal urine before the diagnosis of preeclampsia and potentially fetal growth restriction.
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 β-human chorionic gonadotropin (free β-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%.
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