Cristiano Jodicke

Maternal Serum Adiponectin Multimers in Preeclampsia

Abstract Objective: Obesity, insulin resistance, and dyslipidemia are associated with preeclampsia. Recently, “adipose tissue failure”, characterized by dysregulation of adipokine production, has been implicated in the pathophysiology of these metabolic complications. Adiponectin, an insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic adipokine, circulates in oligomeric complexes including: low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms. These multimers exert differential biological effects, and HMW to total adiponectin ratio (SA) has been reported to be a specific marker of adiponectin activity. The aim of this study was to determine whether preeclampsia is associated with changes in circulating adiponectin multimers. Study design: This cross-sectional study included women with: 1) normal pregnancy (n=225); and 2) patients with mild preeclampsia (n=111). The study population was further stratified by first trimester BMI (normal weight <25 kg/m2 vs. overweight/obese ≥25 kg/m2). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results: 1) The median maternal HMW and LMW adiponectin concentrations were lower in patients with preeclampsia than in those with normal pregnancies (P<0.001 and P=0.01, respectively); 2) patients with preeclampsia had a lower HMW/total adiponectin ratio (P<0.001) and higher MMW/total adiponectin and LMW/total adiponectin ratios than those with a normal pregnancy (P<0.001 and P=0.009, respectively); 3) the presence of preeclampsia was independently associated with lower maternal serum HMW adiponectin concentrations (P=0.001) and with a low HMW/total adiponectin ratio (P<0.001) after correction for maternal age, maternal BMI, the difference in BMI between the third and the first trimester, and gestational age at sampling; and 4) overweight/obese pregnant women had a lower median total and HMW adiponectin concentration than normal weight pregnant women among women with normal pregnancies, but not among those with preeclampsia. Conclusion: 1) Preeclampsia is associated with a lower median concentration of the HMW adiponectin isoform, the most active form of this adipokine, and a low HMW/total adiponectin ratio, a specific marker of adiponectin biologic activity; 2) in contrast to normal pregnancy, preeclampsia is not associated with decreased circulating adiponectin multimers in overweight/obese individuals suggesting altered regulation of this adipokine in preeclampsia; 3) collectively, these findings suggest that preeclampsia is characterized by alterations in adiponectin multimers and their relative distribution implying a role for adiponectin multimers in the mechanism of disease in preeclampsia.

Amniotic fluid sTREM-1 in normal pregnancy, spontaneous parturition at term and preterm, and intra-amniotic infection/inflammation.

Objective. Intra-amniotic infection/inflammation (IAI) is one of the most important mechanisms of disease in preterm birth. Triggering receptor expressed on myeloid cells (TREM)- 1 is a transmembrane glycoprotein expressed by neutrophils, macrophages and mature monocytes. TREM-1 is upregulated in biological fluids and tissues infected by Gram (+) and Gram (−) bacteria and fungi, amplifies the production of pro-inflammatory cytokines and chemokines, and its soluble form (sTREM-1) is released in the presence of infection. The aim of this study was to determine the effect of gestational age, parturition (term and preterm) and IAI in the amniotic fluid (AF) concentrations of sTREM-1. Study design. This cross-sectional study included 434 patients in the following groups: (1) mid-trimester of pregnancy (14–18 weeks, n = 38); (2) normal pregnant women at term with (n = 39) and without (n = 39) labor; (3) patients with spontaneous preterm labor (PTL) and intact membranes classified into: (a) PTL who delivered at term (n = 99); (b) PTL who delivered preterm (<37 weeks gestation) without IAI (n = 80); and (c) PTL with IAI (n = 59); and (4) women with preterm prelabor rupture of membranes (PROM) with (n = 40) and without (n = 40) IAI. The AF concentration of sTREM-1 was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analyses. Results. (1) sTREM-1 was detected in all the AF samples; (2) the median AF sTREM-1 concentration at term was higher than in the mid-trimester (4277.6 pg/ml vs. 1140.4 pg/ml; p < 0.001); (3) among patients with PTL, the median AF sTREM-1 concentration was higher in patients with IAI than in those without IAI (6154.4 pg/ml vs. 3282.8 pg/ml; p < 0.001) and those with PTL who delivered at term (6154.4 pg/ml vs. 2794 pg/ml; p < 0.001); (4) patients with preterm PROM with IAI had a higher median AF sTREM-1 concentration than those without IAI (7893.1 pg/ml vs. 3386.6 pg/ml; p < 0.001); (5) no differences were observed in the median AF sTREM-1 concentration between patients with spontaneous labor at term and those at term not in labor (4712.4 pg/ml vs. 4277.6 pg/ml; respectively p = 0.4); and 6) an AF sTREM-1 concentration ≥6416 pg/ml (derived from a ROC curve) had a sensitivity of 72% and a specificity of 89% for the diagnosis of intra-amniotic infection. Conclusions. sTREM-1 is a physiologic constituent of the AF, and its concentration: (1) is significantly elevated in the presence of IAI; (2) increases with advancing gestation; and (3) does not change in the presence of spontaneous labor at term. We propose that sTREM-1 play a role in the innate immune response against intra-amniotic infection.

DYSREGULATION OF MATERNAL SERUM ADIPONECTIN IN PRETERM LABOR

Objective. Intra-amniotic and systemic infection/inflammation have been causally linked to preterm parturition and fetal injury. An emerging theme is that adipose tissue can orchestrate a metabolic response to insults, but also an inflammatory response via the production of adipocytokines, and that these two phenomenons are interrelated. Adiponectin, an insulin-sensitising, anti-inflammatory adipocytokine, circulates in multimeric complexes including low-molecular weight (LMW) trimers, medium-molecular weight (MMW) hexamers and high-molecular weight (HMW) isoforms. Each of these complexes can exert differential biological effects. The aim of this study was to determine whether spontaneous preterm labor (PTL) with intact membranes and intra-amniotic infection/inflammation (IAI) is associated with changes in maternal serum circulating adiponectin multimers. Study design. This cross-sectional study included patients in the following groups: (1) normal pregnant women (n = 158); (2) patients with an episode of preterm labor and intact membranes without IAI who delivered at term (n = 41); (3) preterm labor without IAI who delivered preterm (n = 27); and (4) preterm labor with IAI who delivered preterm (n = 36). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results. (1) Preterm labor leading to preterm delivery or an episode of preterm labor that does not lead to preterm delivery was associated with a lower median maternal serum concentration of total and HMW adiponectin, a lower median HMW/total adiponectin ratio and a higher median LMW/total adiponectin ratio than normal pregnancy; (2) among patients with preterm labor, those with IAI had the lowest median concentration of total and HMW adiponectin, as well as the lowest median HMW/total adiponectin ratio; (3) the changes in maternal adiponectin and adiponectin multimers remained significant after adjusting for confounding factors such as maternal age, BMI, gestational age at sampling and parity. Conclusion. (1) Preterm labor is characterised by a change in the profile of adiponectin multimers concentrations and their relative isoforms. These changes were observed in patients with an episode of preterm labor not leading to preterm delivery, in patients with intra-amniotic inflammation, or in those without evidence of intra-amniotic inflammation. (2) The changes in adiponectin multimer concentrations reported in preterm labor are different from those previously reported in spontaneous labor at term, suggesting that there is a fundamental difference between preterm labor and labor at term. (3) The findings reported herein provide the first evidence for the participation of adiponectin multimer in preterm parturition. We propose that adiponectins and adipokines in general provide a mechanism to organise the metabolic demands generated by the process of preterm parturition regardless of the nature of the insult (intra-amniotic inflammation or not).

Four‐chamber view and ‘swing technique’ (FAST) echo: a novel and simple algorithm to visualize standard fetal echocardiographic planes

To describe a novel and simple algorithm (four‐chamber view and ‘swing technique’ (FAST) echo) for visualization of standard diagnostic planes of fetal echocardiography from dataset volumes obtained with spatiotemporal image correlation (STIC) and applying a new display technology (OmniView).

Amniotic fluid soluble human leukocyte antigen-G in term and preterm parturition, and intra-amniotic infection/inflammation

Objective. Circulating soluble human leukocyte antigen-G (sHLA-G) has been associated with pregnancy complications, and determination of sHLA-G concentrations in amniotic fluid (AF) has been reported in normal pregnancies. Our aim was to determine if the AF concentrations of sHLA-G change with advancing gestation, spontaneous labor at term, and in patients with spontaneous preterm labor (PTL) with intact membranes, as well as in those with preterm prelabor rupture of membranes (PROM), in the presence or absence of intra-amniotic infection/inflammation (IAI). Study design. This cross-sectional study included the following groups: (1) mid-trimester (n = 55); (2) normal pregnancy at term with (n = 50) and without (n = 50) labor; (3) spontaneous PTL with intact membranes divided into: (a) PTL who delivered at term (n = 153); (b) PTL who delivered preterm without IAI (n = 108); and (c) PTL with IAI (n = 84); and (4) preterm PROM with (n = 46) and without (n = 44) IAI. sHLA-G concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results. (1) Among patients with PTL, the median AF sHLA-G concentration was higher in patients with IAI than in those without IAI or women that delivered at term (p < 0.001 for both comparisons); (2) Similarly, patients with preterm PROM and IAI had higher median AF sHLA-G concentrations than those without IAI (p = 0.004); (3) Among patients with PTL and delivery, those with histologic chorioamnionitis and/or funisitis had a higher median AF sHLA-G concentration than those without histologic inflammation (p < 0.001); and (4) The median AF sHLA-G concentration did not change with advancing gestational age. Conclusions. AF sHLA-G concentrations are elevated in preterm parturition associated to IAI as well as in histologic chorioamnionitis. We propose that sHLA-G may participate in the regulation of the host immune response against intra-amniotic infection.

Uterine artery Doppler in first-trimester pregnancy screening.

Uterine artery Doppler velocimetry has revolutionized the investigation of the developing placental vasculature. Abnormal placental vascular development is the basis of common obstetric disorders such as preeclampsia and intrauterine growth restriction. Uterine artery Doppler velocimetry by itself or in combination with other biochemical markers seems to be an effective first-trimester screening tool for preeclampsia and in particular early-onset preeclampsia. The diagnostic accuracy although statistically significant, is not as high for the prediction of intrauterine growth restriction unrelated to preeclampsia. In the future, first-trimester prophylaxis using antiplatelet agents in Doppler identified high-risk groups could suppress the development of these disorders.

Simple targeted arterial rendering (STAR) technique: a novel and simple method to visualize the fetal cardiac outflow tracts

To describe a novel and simple technique—simple targeted arterial rendering (STAR)—to visualize the fetal cardiac outflow tracts from dataset volumes obtained with spatiotemporal image correlation (STIC) and applying a new display technology (OmniView).

Complete trisomy 21 vs translocation Down syndrome: a comparison of modes of ascertainment

OBJECTIVE To compare the indications for invasive prenatal testing resulting in the detection of translocation Down syndrome and complete trisomy 21. STUDY DESIGN This case control study was based on a large amniocentesis and chorionic villi samples database (n = 534,795). All specimens with translocation Down syndrome (n = 203) comprised the translocation group and were compared with a maternal age-matched group (4 to 1, n = 812) in which complete trisomy 21 was detected. Women with a normal karyotype were randomly selected (n = 812) and served as controls. Indications for invasive testing were compared among the 3 paired groups using χ(2) analysis. RESULTS There were no differences in the incidence of abnormal first- and second-trimester screening tests between the translocation Down syndrome and the complete trisomy 21 groups. History of prior aneuploidy was significantly more frequent in the translocation Down syndrome group, as compared with either complete trisomy 21 fetuses or normal controls. CONCLUSION Fetuses with translocation Down syndrome present with the same screening abnormalities as fetuses with complete trisomy 21.

OP14.06: Late‐onset preeclampsia cannot be identified with either an anti‐angiogenic profile in maternal plasma or uterine artery Doppler velocimetry

the subsequent development of abnormal uterine artery Doppler velocimetry (UTDV) in the second trimester (2T). Study design: This study is based on a cohort study design to examine the predictive value of PlGF, sEng and sVEGFR-1 plasma concentrations in the identification of patients destined to develop PE. Only patients that had samples obtained between 8–13 weeks and subsequently had UTDV between 20–25 weeks were included (n = 1,316). Results: 1) Women destined to have abnormal UTDV in the 2T had a lower median 1T plasma PlGF concentration than those with normal UTDV; 2) 1T plasma PlGF concentration of < 26.8 pg/ml (derived by ROC analysis) was associated with abnormalities in UTDV in the 2T (odd ratio 3.2; 95% CI 1.8–5.5) after adjusting for confounders; and 3). Women with abnormal UTDV, with and without subsequent PE, had a lower median 1T plasma PLGF concentration than those with normal UTDV and no PE. Conclusion: A low 1T plasma PlGF concentration is associated with increased impedance to flow in the uterine circulation in the 2T, regardless of whether or not the patient developed PE. These findings suggest that PlGF plays an important role in early placentation.

P10.11: A systematic comparison of the volume of fluid‐filled fetal structures using 3D US: a comparison of SonoAVC™, VOCAL™, and inversion mode techniques

for trisomy 21 in the second trimester of pregnancy. Amongst all the markers, the nuchal fold thickness was the only marker which consistently been found to have independent predictive ability, when measured over 6,0mm in pregnancies between 16–20 weeks. The advent of three dimensional ultrasonography is an extraordinary advance in fetal medicine diagnosis, but we do not find any article describing the three dimensional evaluation of the nuchal fold thickness as a trisomy 21 marker. Objective: Comparative evaluation of the nuchal fold thickness measurement by 2D ultrasonography and 3DXI, Multi-Slice View in 16–20 week fetuses. Methods: This transversal study included 25 healthy fetuses, between 16–20 weeks. The nuchal fold thickness was first measured by the conventional bi-dimensional sonography technique, then by 3DXI Multi-slice view, using the Medison Sonoace X9 (Medison, Korea). The measures were paired by gestational age and t student test was used to compare the variables. The intra and inter observer measurements variations were studied. Results: The data obtained is in process of statistical analysis. Conclusion: Our preliminary results show that the three dimensional evaluation of the nuchal fold thickness seems to have a minimal but statistically significant measurement difference. As a preliminary study, we do recommend more studies involving bigger number of patients.