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Objectives: To identify maternal plasma protein markers for early preeclampsia (delivery <34 weeks of gestation) and to determine whether the prediction performance is affected by disease severity and presence of placental lesions consistent with maternal vascular malperfusion (MVM) among cases. Study design: This longitudinal case-control study included 90 patients with a normal pregnancy and 33 patients with early preeclampsia. Two to six maternal plasma samples were collected throughout gestation from each woman. The abundance of 1,125 proteins was measured using high-affinity aptamer-based proteomic assays, and data were modeled using linear mixed-effects models. After data transformation into multiples of the mean values for gestational age, parsimonious linear discriminant analysis risk models were fit for each gestational-age interval (8–16, 16.1–22, 22.1–28, 28.1–32 weeks). Proteomic profiles of early preeclampsia cases were also compared to those of a combined set of controls and late preeclampsia cases (n = 76) reported previously. Prediction performance was estimated via bootstrap. Results: We found that 1) multi-protein models at 16.1–22 weeks of gestation predicted early preeclampsia with a sensitivity of 71% at a false-positive rate (FPR) of 10%. High abundance of matrix metalloproteinase-7 and glycoprotein IIbIIIa complex were the most reliable predictors at this gestational age; 2) at 22.1–28 weeks of gestation, lower abundance of placental growth factor (PlGF) and vascular endothelial growth factor A, isoform 121 (VEGF-121), as well as elevated sialic acid binding immunoglobulin-like lectin 6 (siglec-6) and activin-A, were the best predictors of the subsequent development of early preeclampsia (81% sensitivity, FPR = 10%); 3) at 28.1–32 weeks of gestation, the sensitivity of multi-protein models was 85% (FPR = 10%) with the best predictors being activated leukocyte cell adhesion molecule, siglec-6, and VEGF-121; 4) the increase in siglec-6, activin-A, and VEGF-121 at 22.1–28 weeks of gestation differentiated women who subsequently developed early preeclampsia from those who had a normal pregnancy or developed late preeclampsia (sensitivity 77%, FPR = 10%); 5) the sensitivity of risk models was higher for early preeclampsia with placental MVM lesions than for the entire early preeclampsia group (90% versus 71% at 16.1–22 weeks; 87% versus 81% at 22.1–28 weeks; and 90% versus 85% at 28.1–32 weeks, all FPR = 10%); and 6) the sensitivity of prediction models was higher for severe early preeclampsia than for the entire early preeclampsia group (84% versus 71% at 16.1–22 weeks). Conclusion: We have presented herein a catalogue of proteome changes in maternal plasma proteome that precede the diagnosis of preeclampsia and can distinguish among early and late phenotypes. The sensitivity of maternal plasma protein models for early preeclampsia is higher in women with underlying vascular placental disease and in those with a severe phenotype. [ABSTRACT FROM AUTHOR]

Objectives: Preeclampsia and fetal growth restriction are obstetrical syndromes associated with abnormal placental implantation and changes in the activation status of maternal leukocytes. This study is aimed to determine by a simple, rapid fluorescent assay the changes in maternal serum total cell-free DNA (t-cfDNA) concentrations in women with preeclampsia and those with fetal growth restriction (FGR). Study design: A cross-sectional study was conducted measuring maternal serum t-cfDNA concentrations. Women were classified into the following groups: 1) patients with preeclampsia (n = 21); 2) FGR-estimated fetal weight below the 10thpercentile (n = 28); and 3) normal pregnancy (n = 39). Serum samples were directly assayed for t-cfDNA using a rapid fluorescent SYBR Gold assay. Elevated maternal serum t-cfDNA concentrations were defined as a cutoff>850ng/ml. Nonparametric statistics were used for analysis. Results: Women with preeclampsia had a higher median maternal serum concentration (802 ng/ml, 400–2272 ng/ml) than women with a normal pregnancy (499 ng/ml, 0–1892 ng/ml, p = 0.004) and those with FGR (484 ng/ml, 72–2187 ng/ml, p = 0.012). Moreover, even patients with FGR <5th percentile and abnormal Doppler had a lower median maternal serum t-cfDNA than those with preeclampsia (median 487 ng/ml, 144–1971 ng/ml, p = 0.022). The median concentration of t-cfDNA did not differ between women with a normal pregnancy and those with FGR (p = 0.54), as well as those with fetuses <5th percentile and abnormal Doppler (p = 0.7). Women with preeclampsia had a higher proportion of elevated t-cfDNA than those with a normal pregnancy (p = 0.015) and patients with FGR (p = 0.025). Conclusions: Preeclampsia is associated with higher maternal serum t-cfDNA concentration than normal pregnancy or FGR. This observation may reflect an increased systemic activation of the maternal inflammation, rather than placental; this assumption is supported by the fact that we did not observe a significant change in the maternal serum t-cfDNA in patients with placental-mediated FGR. [ABSTRACT FROM AUTHOR]

• Dichorionic triplet gestations have higher rate of early preterm delivery. • Dichorionic triplet gestations have higher rate of extreme early preterm delivery. • Past preterm delivery is a risk factor for early preterm delivery in triplets. • Rate of neonatal death is higher in the dichorionic triplet gestations. Triplet gestations are associated with increased maternal, fetal, and neonatal complications particularly early and extreme preterm delivery. Identifying and interrupting the preterm delivery cascade could prevent the fetal, neonatal, and long-term childhood complications. The shared circulation and placental vascular anastomosis are responsible for the occurrence of twin-to-twin transfusion syndrome, selective fetal growth restriction as well as the higher risk of morbidity and mortality observed in mono and dichorionic compared to trichorionic triplet gestations. Thus, the aim of this study was to determine the effect of chorionicity on maternal, fetal, and neonatal outcomes of triplet pregnancies as it has not been fully ascertained. A retrospective population-based cohort study of 125 parturient with triplets' pregnancy who delivered at a single tertiary hospital. 98 trichorionic and 27 dichorionic gestations were included. Maternal demographic and obstetric characteristics as well as pregnancy and postpartum complications were similar in the two study groups. The median gestational age at delivery was lower among dichorionic than trichorionic triplet gestations (median 31 vs 33 weeks, p < 0.046). Early (<32 weeks) and extreme preterm delivery (<28 weeks) were more prevalent in the dichorionic than the trichorionic group (early − 56 % vs 34 %, p < 0.038; extreme − 33.3 % vs 8 %, p < 0.002). We found no difference in fetal or newborns' complications and characteristics between the groups. However, the rate of neonatal death was significantly higher in the dichorionic compared to trichorionic triplet gestations (22 % vs 7 %, p < 0.038). A multivariate logistic regression model to determine the variables that contribute to early preterm delivery in triplet gestations showed that women who experienced a past preterm delivery had an independently higher risk for early preterm delivery in the triplet gestation (adj. OR 5.91, 95 % CI 1.16–30.03). Neither maternal age nor chorionicity were found to be independent risk factors for early preterm delivery. Dichorionic triplet gestations exhibit a higher rate of early (<32 weeks) and extreme (<28 weeks) preterm delivery and are more prone to neonatal death compared to trichorionic gestations. Past preterm delivery is an independent risk factor for early preterm delivery in a triplet gestation. [ABSTRACT FROM AUTHOR]

Objective: Recent studies suggest an association between Human Papilloma Virus (HPV) infection, cervical inflammation and obstetric complications (i.e. spontaneous preterm parturition and cervical insufficiency). It has been proposed that viral inflammation of the placenta causes changes in the mother's immune reaction to bacterial pathogens, which leads to enhanced inflammatory reaction and preterm delivery. Therefore, the aim of this population-based study was to determine the association between abnormal cervical cytology prior to pregnancy and obstetric outcomes.Study Design: A Retrospective population-based cohort study was designed, including all women who had a Pap smear up to two years prior to delivery or during first trimester of pregnancy (n = 15,357). Women were divided into the following groups, according to Pap smear results: group 1 - Normal PAP smear (n = 11,261); group 2 - Pap smear with evidence of an inflammatory process (n = 3895); and group 3 - Pap smear with evidence of HPV infection (n = 201). Obstetrical outcomes, gestational age at delivery, and pregnancy complications were compared among the groups.Results: The rate of HPV infection in our study population was 1.3%. The rate of preterm delivery (group 1 - 8.5%, group 2 - 8.5%, group 3 - 7%, p = 0.7), preterm PROM (group 1 - 1.7%, group 2-1.6%, group 3 - 2%, p = 0.66) and cervical insufficiency (group 1 - 0.5%, group 2 - 0.7%, group 3 - 1.5%, p = 0.11) did not differ significantly among the study groups. There was no statistical difference in the rate of premature rapture of membranes, newborn small-for-gestational-age, preeclampsia or placental abruption. Women with abnormal cervical cytology, either due to inflammation or HPV infection, had similar obstetric outcome in comparison to those with a normal cervical cytology.Conclusion: This population-based retrospective cohort study indicates no association between positive HPV testing with Pap smear and obstetric complications such as preterm delivery, cervical insufficiency, placental abruption, PROM, Preterm PROM, neonatal SGA and preeclampsia, in a population with low prevalence HPV infection. [ABSTRACT FROM AUTHOR]