Francesca Gotsch

A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate

Introduction. Accumulating evidence suggests that an imbalance between pro-angiogenic (i.e., vascular endothelial growth factor (VEGF) and placental growth factor (PlGF)) and anti-angiogenic factors (i.e., soluble VEGF receptor-1 (sVEGFR-1, also referred to as sFlt1)) is involved in the pathophysiology of preeclampsia (PE). Endoglin is a protein that regulates the pro-angiogenic effects of transforming growth factor β, and its soluble form has recently been implicated in the pathophysiology of PE. The objective of this study was to determine if changes in maternal plasma concentration of these angiogenic and anti-angiogenic factors differ prior to development of disease among patients with normal pregnancies and those destined to develop PE (preterm and term) or to deliver a small for gestational age (SGA) neonate. Methods. This longitudinal nested case–control study included 144 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered appropriate for gestational age (AGA) neonates (n = 46); (2) patients who delivered an SGA neonate but did not develop PE (n = 56); and (3) patients who developed PE (n = 42). Longitudinal samples were collected at each prenatal visit, scheduled at 4-week intervals from the first or early second trimester until delivery. Plasma concentrations of soluble endoglin (s-Eng), sVEGFR-1, and PlGF were determined by specific and sensitive ELISA. Results. (1) Patients destined to deliver an SGA neonate had higher plasma concentrations of s-Eng throughout gestation than those with normal pregnancies; (2) patients destined to develop preterm PE and term PE had significantly higher concentrations of s-Eng than those with normal pregnancies at 23 and 30 weeks, respectively (for preterm PE: p < 0.036 and for term PE: p = 0.002); (3) patients destined to develop PE (term or preterm) and those who delivered an SGA neonate had lower plasma concentrations of PlGF than those with a normal pregnancy throughout gestation, and the maternal plasma concentration of this analyte became detectable later among patients with pregnancy complications, compared to normal pregnant women; (4) there were no significant differences in the plasma concentrations of sVEGFR-1 between patients destined to deliver an SGA neonate and those with normal pregnancies; (5) patients destined to develop preterm and term PE had a significantly higher plasma concentration of sVEGFR-1 at 26 and 29 weeks of gestation than controls (p = 0.009 and p = 0.0199, respectively); and (6) there was no significant difference in the increment of sVEGFR-1 between control patients and those who delivered an SGA neonate (p = 0.147 at 25 weeks and p = 0.8285 at 40 weeks). Conclusions. (1) Changes in the maternal plasma concentration of s-Eng, sVEGFR-1, and PlGF precede the clinical presentation of PE, but only changes in s-Eng and PlGF precede the delivery of an SGA neonate; and (2) differences in the profile of angiogenic and anti-angiogenic response to intrauterine insults may determine whether a patient will deliver an SGA neonate, develop PE, or both.

Adiponectin multimers in maternal plasma

Objective. Adiponectin is an anti-diabetic, anti-atherogenic, anti-inflammatory, and angiogenic adipokine that circulates in oligomeric complexes including: low molecular weight (LMW) trimers, medium molecular weight (MMW) hexamers, and high molecular weight (HMW) isoforms. The aim of this study was to determine whether there are changes in adiponectin multimers in pregnancy and as a function of maternal weight. Study design. In this cross-sectional study, plasma concentrations of total, HMW, MMW, and LMW adiponectin were determined in women included in three groups: (1) normal pregnant women of normal body mass index (BMI) (n = 466), (2) overweight pregnant women (BMI ≥25; n = 257), and (3) non-pregnant women of normal weight (n = 40). Blood samples were collected once from each woman between 11 and 42 weeks of gestation. Plasma adiponectin multimer concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Non-parametric statistics were used for analysis. Results. (1) The median HMW adiponectin concentration and the median HMW/total adiponectin ratio were significantly higher, and the median LMW adiponectin concentration was significantly lower in pregnant women than in non-pregnant women. (2) Among pregnant women, the median plasma concentration of total, HMW, and MMW adiponectin was significantly higher in normal weight women than in overweight patients. (3) Maternal HMW was the most prevalent adiponectin multimer regardless of gestational age or BMI status. (4) There were no significant differences in the median concentration of total, MMW, and LMW adiponectin and their relative distribution with advancing gestation. Conclusion. Human pregnancy is characterized by quantitative and qualitative changes in adiponectin multimers, especially the most active isoform, HMW adiponectin.

A role for mannose-binding lectin, a component of the innate immune system in pre-eclampsia.

Problem Mannose‐binding lectin (MBL) is a pattern‐recognition receptor that activates complement and modulates inflammation. Homozygosity for the most common allele of the MBL2 gene that is associated with high MBL serum concentrations is more prevalent among patients with pre‐eclampsia. The objective of this study was to determine maternal plasma MBL concentrations in normal pregnant women and patients with pre‐eclampsia.

Plasma soluble endoglin concentration in pre‐eclampsia is associated with an increased impedance to flow in the maternal and fetal circulations

To examine the relationship between abnormalities in uterine (UtA) and/or umbilical artery (UA) Doppler velocimetry and maternal plasma concentrations of soluble endoglin (sEng) in patients with pre‐eclampsia (PE).

Amniotic fluid angiopoietin-2 in term and preterm parturition, and intra-amniotic infection/inflammation.

Abstract Objective: Recent observations have revealed an interaction between inflammation and angiogenesis, which may be mediated by angiopoietins and chemokines. Given the importance of inflammation in parturition, we sought to determine whether angiopoietin-2 (Ang-2) is present in amniotic fluid (AF) and if its concentration changes with gestational age, labor, and in intra-amniotic infection/inflammation (IAI) in patients with spontaneous preterm labor and intact membranes. Study design: This cross-sectional study included 486 patients in the following groups: 1) women in the mid-trimester of pregnancy (14–18 weeks) who underwent amniocentesis for genetic indications and delivered a normal neonate at term (n=52); 2) normal pregnant women at term with (n=48) and without (n=45) spontaneous labor; 3) patients with an episode of spontaneous preterm labor (PTL) and intact membranes who were classified into: a) PTL without IAI who delivered at term (n=152); b) PTL without IAI who delivered preterm (<37 weeks gestation; n=107); and c) PTL with IAI (n=82). Ang-2 concentration in AF was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analysis. Results: 1) Ang-2 was detected in all AF samples; 2) the median AF Ang-2 concentration at term was significantly lower than that in the mid-trimester (1877.4 pg/mL vs. 3525.2 pg/mL; P<0.001); 3) among patients with PTL, the median AF Ang-2 concentration was significantly higher in patients with IAI than in those without IAI (4031.3 pg/mL vs. 2599.4 pg/mL; P<0.001) and those with PTL without IAI who delivered at term (4031.3 pg/mL vs. 2707.3 pg/mL; P<0.001); and 4) no significant differences were observed in the median AF Ang-2 concentration between patients with spontaneous labor at term and those at term not in labor (1722.9 pg/mL vs. 1877.4 pg/mL; P=0.6). Conclusions: 1) Ang-2, a protein involved in the process of vascular remodeling, is a physiologic constituent of the amniotic fluid and its concentration decreased with advancing gestation; 2) the median Ang-2 concentration in amniotic fluid is higher in patients with IAI than in those without; and 3) spontaneous parturition at term is not associated with changes in the AF concentration of Ang-2. These findings support the view of a link between angiopoietins and inflammation.

Prenatal diagnosis of truncus arteriosus using multiplanar display in 4D ultrasonography

Abstract Prenatal diagnosis of truncus arteriosus with two-dimensional sonography requires expertise in fetal echocardiography. Indeed, truncus arteriosus shares with tetralogy of Fallot and pulmonary atresia with a ventricular septal defect (VSD) the sonographic finding of a single arterial trunk overriding a VSD. The diagnosis of truncus arteriosus can be confirmed when either the main pulmonary artery or its branches are visualized arising from the truncus itself. This requires sequential examination of multiple scanning planes and a process of mental reconstruction of their spatial relationships. The advantage of multiplanar imaging in three-dimensional and four-dimensional ultrasonography is that it allows for the simultaneous visualization of three orthogonal anatomic planes, which can be very important in diagnosing cardiac abnormalities. We report, first, a case of truncus arteriosus diagnosed in utero where the multiplanar display modality provided important insight into the differential diagnosis of this conotruncal anomaly, and then, review the diagnosis of truncus arteriosus on ultrasound.

Iliac Crest Angle: A Novel Sonographic Parameter for the Prediction of Down Syndrome Risk During the Second Trimester of Pregnancy

To validate a new sonographic technique for the display and measurement of fetal iliac crest angle (ICA), and to determine the relative contribution of standardized fetal pelvic measurements for estimating risk of Down syndrome during the second trimester of pregnancy.

OC144: Clinical significance of the presence of amniotic fluid ‘sludge’ in patients with cervical cerclage

to 30 + 0) weeks + days in the TPTL group. Mean (SD) cervical length was similar in the control (36.1 (2.9) mm) and PPROM (36.6 (16.6) mm) groups, but shorter in the TPTL group (20.4 (9.2) mm; P = 0.01). Mean (SD) FMBV was lower in controls (9.4 (6.4)%) than in the PPROM (21.2 (10.0)%) and TPTL (18.9 (6.9)%) groups (P = 0.01). The median time between the first examination and delivery was 2 (range, 1–4) weeks in the PPROM group and 4 (range, 1–14) weeks in the TPTL group. In PPROM, 7/10 cases delivered within the 2 weeks after the first examination, and 6/7 had a FMBV above 18% in spite of a cervical length within normal values. In TPTL, there was a significant association between the cervical length and the time to delivery (r = 51, P = 0.001), but in most cases FMBV was similarly increased. Conclusions: In TPTL the cervical length correlated well with the time to delivery and FMBV did not improve this information. However, in PPROM an increment in FMBV appears to be independently associated with an earlier delivery.

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.

OP04.08: Fetal gender assignment using 3DUS and MRI of internal pelvic anatomy

Objectives: The aim of this study is to asses the feasibility of 3D ultrasound for fetal evaluation at 20–22 weeks. Methods: A cross-sectional study was designed in order to evaluate the correlation between 2D standard ultrasound and 3D multiplanar mode by means of a General Electric Voluson 730 Expert. 35 women were scanned at 20–22 weeks of gestation. A standard anatomical ultrasound was performed in each pacient. Also six volumes of each fetus were obtained (axial head, coronal face, chest, abdominal, upper extremities and lower extremities). Observer A analysed off line the 18 cases obtained by observer B, using 4D view program. Reversaly, observer B analysed the volumes obtained by observer A in 17 pacients. A third observer C also analysed the volumes obteined by A and B in order to evaluate the interobserver reproducibility in a second step. A check list of landmarks (31)was used to study the complete fetal anatomy in both ultrasound methods. For measurements, the intraclass correlation coefficient was calculated between both techniques. Results: While with 2D standard ultrasound 99% of landmarks were identified, it was 94% with 3D off line examination. Grouping by view regions : head and face 97%, 94% respectively; heart : fourchamber 100%, three vassels and trachea wiew 97%, outflow tracts 74%; abdominal structures 100% unless both kidneys 89%; both arms 89%, both hands 57%, both legs 97% and both feet 80%. Spine was completly seen in 85%. One choroid plexus cyst was seen in 2D/3D, one foot with equinovarus position was not satisfactory visualized using 3D and it was two cases of sex error. Intraclass correlation coefficient was almost perfect for biparietal diameter, cephalic circunference and femoral length, and very good for abdominal circunference. Conclusions: 3D ultrasound seems to allow a good anatomical assesment and yield reliable mesurements at 20–22 weeks of gestation. Hands, cardiac outflow tracts and feet are, by now, structures poorly assesed by 3D standard multiplanar mode