V Kolovetsiou-Kreiner

Phase Synchronization of Hemodynamic Variables at Rest and after Deep Breathing Measured during the Course of Pregnancy

Background The autonomic nervous system plays a central role in the functioning of systems critical for the homeostasis maintenance. However, its role in the cardiovascular adaptation to pregnancy-related demands is poorly understood. We explored the maternal cardiovascular systems throughout pregnancy to quantify pregnancy-related autonomic nervous system adaptations. Methodology Continuous monitoring of heart rate (R-R interval; derived from the 3-lead electrocardiography), blood pressure, and thoracic impedance was carried out in thirty-six women at six time-points throughout pregnancy. In order to quantify in addition to the longitudinal effects on baseline levels throughout gestation the immediate adaptive heart rate and blood pressure changes at each time point, a simple reflex test, deep breathing, was applied. Consequently, heart rate variability and blood pressure variability in the low (LF) and high (HF) frequency range, respiration and baroreceptor sensitivity were analyzed in resting conditions and after deep breathing. The adjustment of the rhythms of the R-R interval, blood pressure and respiration partitioned for the sympathetic and the parasympathetic branch of the autonomic nervous system were quantified by the phase synchronization index γ, which has been adopted from the analysis of weakly coupled chaotic oscillators. Results Heart rate and LF/HF ratio increased throughout pregnancy and these effects were accompanied by a continuous loss of baroreceptor sensitivity. The increases in heart rate and LF/HF ratio levels were associated with an increasing decline in the ability to flexibly respond to additional demands (i.e., diminished adaptive responses to deep breathing). The phase synchronization index γ showed that the observed effects could be explained by a decreased coupling of respiration and the cardiovascular system (HF components of heart rate and blood pressure). Conclusions/Significance The findings suggest that during the course of pregnancy the individual systems become increasingly independent to meet the increasing demands placed on the maternal cardiovascular and respiratory system.

Heart rate variability and baroreceptor reflex sensitivity in early- versus late-onset preeclampsia

Objective To determine whether there are differences in autonomic nervous system function in early- versus late-onset preeclampsia. Methods Matched case-control study. Cases were defined as singleton pregnancies with preeclampsia at < 34+0 weeks of gestation (early-onset preeclampsia) and ≥ 34+0 weeks of gestation (late-onset preeclampsia). For each case in each of the preeclampsia subgroups, three „control”uncomplicated singleton pregnancies were matched by maternal age, height, and week of gestation. Blood pressure and heart rate were measured continuously for 30 minutes in each participant. Baroreceptor reflex sensitivity (assessed using sequence technique), time and frequency domain heart rate variability measures, as SDNN, RMSSD, LFRRI, HFRRI and LF/HFRRI of R-R intervals, were compared between groups (p<0.05 significant). Results 24 women with preeclampsia (10 with early-onset and 14 with late-onset preeclampsia) and 72 controls were included in the study. SDNN, RMSSD and HFRRI were significantly higher in the late-onset preeclampsia group compared to gestational age matched controls (p = 0.033, p = 0.002 and p = 0.018, respectively). No significant differences in SDNN RMSSD and HFRRI between early-onset preeclampsia group and gestational age matched controls were observed (p = 0.304, p = 0.325 and p = 0.824, respectively). Similarly, baroreceptor reflex sensitivity was higher in late-onset preeclampsia compared to controls at ≥ 34 weeks (p = 0.037), but not different between early-onset preeclampsia compared to controls at < 34 weeks (p = 0.50). Conclusions Heart rate variability and baroreceptor reflex sensitivity are increased in late- but not early-onset preeclampsia compared to healthy pregnancies. This indicates a better autonomic nervous system mediated adaptation to preeclampsia related cardiovascular changes in late-onset disease.

Metastasis of an undifferentiated fetal soft tissue sarcoma to the maternal compartment of the placenta: maternal aspects, pathology findings and review of the literature on fetal malignancies with placenta metastases

Sir: Cancers in pregnancy affect approximately 0.1% of all pregnant women, and the large majority are of maternal origin. While more than 50 cases of maternal cancers with metastases to the placenta and 14 cases of transplacental transmission to the fetus have been reported, primary fetal malignancies with placental involvement are extremely rare. We report the first case of an undifferentiated fetal soft tissue sarcoma involving the maternal compartment of the placenta with metastases to the chorionic villi and the intervillous space, and review all documented cases of fetal malignancies with metastases to the placenta or to the mother.

Maternal cardiovascular and endothelial function from first trimester to postpartum

Objective To explore noninvasively the complex interactions of the maternal hemodynamic system throughout pregnancy and the resulting after-effect six weeks postpartum. Methods Eighteen women were tested beginning at the 12th week of gestation at six time-points throughout pregnancy and six weeks postpartum. Heart rate, heart rate variability, blood pressure, pulse transit time (PTT), respiration, and baroreceptor sensitivity were analyzed in resting conditions. Additionally, hemoglobin, asymmetric and symmetric dimethylarginine and Endothelin (ET-1) were obtained. Results Heart rate and sympathovagal balance favoring sympathetic drive increased, the vagal tone and the baroreflex sensitivity decreased during pregnancy. Relative sympathetic drive (sympathovagal balance) reached a maximum at 6 weeks postpartum whereas the other variables did not differ compared to first trimester levels. Postpartum diastolic blood pressure was higher compared to first and second trimester. Pulse transit time and endothelial markers showed no difference throughout gestation. However, opposing variables PTT and asymmetric dimethylarginine (ADMA) were both higher six weeks postpartum. Conclusions The sympathetic up regulation throughout pregnancy goes hand in hand with a decreased baroreflex sensitivity. In the postpartum period, the autonomic nervous system, biochemical endothelial reactions and PTT show significant and opposing changes compared to pregnancy findings, indicating the complex aftermath of the increase of blood volume, the changes in perfusion strategies and blood pressure regulation that occur in pregnancy.

Comparison of two-risk assessment algorithms for preeclampsia in first trimester with consecutive intake of low-dose aspirin in the high-risk group – an observational study

Abstract We analyzed outcome of women screened for preeclampsia with two different multifactorial risk algorithms (Predictor®Software by PerkinElmer, PerkinElmer, Waltham, MA; PERK-group: n = 214 and Viewpoint® by GE Healthcare, Dornstadt, Germany; VIEW-group: n = 209) in first trimester. Women at high risk for developing preeclampsia were advised to take low-dose acetylsalicylic acid (LDA). Screening positive rates for early onset preeclampsia differed significantly between the two groups (7.9% versus 26.3%; p = 0.000). According the clinical use of screening test criteria, LDA was prescribed in 63 (29.4%) women in the PE-group and 55 (26.3%) in the VP-group (p = 0.516). There were no differences in onset of preeclampsia [4 (1.9%) versus 6 (2.9%); p = 0.540]. No early or severe preeclampsia occurred in the whole population.

History of Preeclampsia Adds to the Deleterious Effect of Chronic Stress on the Cardiac Ability to Flexibly Adapt to Challenge

Preeclampsia, a pregnancy-specific disorder, presents a major health problem during gestation, but is also associated with increased risk for cardiovascular complications in later life. We aimed to investigate whether chronic stress experience and preeclampsia may have additive adverse effects on the cardiac ability to flexibly adapt to challenge, that is, to mount an appropriately vigorous heart rate response to an acute psychological challenge, or whether they may perhaps have synergistic effects (e.g., mutual augmentation of effects). Blunted cardiac responding to challenge has been linked to poor health outcomes in the longer term. Women previously affected by preeclampsia and women after uncomplicated pregnancies were tested 15–17 weeks post-partum in a standardized stress-reactivity protocol, while cardiovascular variables were simultaneously recorded. Changes in heart rate and blood pressure in response to the stressor were analyzed with regard to the effects of history of preeclampsia and chronic stress experience. Findings indicated blunted cardiac responses in women with higher chronic stress experience (p = 0.020) and, independently from that, in women with a history of preeclampsia (p = 0.018), pointing to an additive nature of the effects of preeclampsia and chronic stress on impaired cardiovascular functioning. Consequently, if both are present, a history of preeclampsia may add to the already deleterious effects of the experience of chronic stress. The additive nature of the effects suggests that stress-reducing interventions, albeit they will not eliminate the heightened cardiovascular risk in patients with a history of preeclampsia, may improve their overall prognosis by avoiding further accumulation of risk.

Anwendbarkeit der Biomarker p16/Ki-67 bei Patientinnen mit auffälliger Zervix-Zytologie in der Schwangerschaft

Fragestellung: Zervikale Dysplasien in der Schwangerschaft sind eine Herausforderung fur Gynakologen und Geburtshelfer. Schwangerschaftsspezifische Veranderungen konnen die Spezifitat und Sensitivitat der Zytologie und Kolposkopie reduzieren. Diagnostische Eingriffe an der graviden Cervix sind mit Komplikationen assoziiert und sollten vermieden werden. Der CINtec® PLUS Kit (Roche) beinhaltet die Biomarker p16INK4a und Ki-67, welche eine Aussage uber die Deregulation der Zellzyklen, in denen der onkogene Transformationsprozess durch hrHPV begonnen hat, erlauben. Ziel der Studie war die Evaluierung der Anwendbarkeit und der Vorhersagekraft von CINtec® PLUS bei Patientinnen mit abnormen Pap-Smear in der Schwangerschaft. Methode: Im Rahmen dieser retrospektiven Studie wurden 27 abnorme Zervix-Abstriche welche in der Fruhschwangerschaft gewonnen wurden entfarbt und anschliesend mit CINtec® PLUS gefarbt. Postpartal wurden Biopsien gewonnen und die histologischen Ergebnisse dem CINtec® PLUS Ergebnis gegenubergestellt. Ergebnisse: 7 Abstriche mussten wegen technischen Problemen aus der Studie ausgeschlossen werden. Bei 14 der verbliebenen 20 auffalligen Smears zeigte sich eine positive p16/Ki-67 Farbung, 6 Smears waren negativ. Bei allen 14 Patientinnen, die positiv auf p16/Ki67 getestet wurden, zeigte die postpartale histologische Abklarung eine CIN; 5 von 6 Patientinnen mit negativer p16/Ki-67 Farbung wiesen nach der Schwangerschaft und bei weiteren Follow-up Untersuchungen eine negative Histologie auf; eine Patientin hatte eine CIN1 (p = 0,0004). Schlussfolgerung: P16/Ki-67 scheint ein nutzlicher Biomarker zur Identifizierung Schwangerer mit persistierender oder progressiver CIN zu werden.

p16/Ki-67 Dual-Stained Cytology Testing May Predict Postpartum Outcome in Patients with Abnormal Papanicolaou Cytology during Pregnancy

Objective: To evaluate the use of a new immunocytochemical dual-staining protocol, which allows for the detection of coexpression of the p16INK4a (p16) and Ki-67 biomarkers in prenatal care. It was hypothesized that dual-staining cytology may predict postpartum outcome in patients with abnormal cervical Papanicolaou (Pap) smears during pregnancy. Study Design: In this retrospective pilot study, 27 abnormal Pap smears collected from women during early pregnancy were destained and subsequently stained for p16/Ki-67. Results were correlated with histologic outcome collected during postpartum follow-up. Results: Fourteen of 20 abnormal Pap smears during pregnancy showed a positive p16/Ki-67 dual-stained cytology result, whereas 6 specimens tested negative. Seven cases were excluded due to technical reasons. All 14 patients who were positive for p16/Ki-67 dual stain had cervical intraepithelial neoplasia (CIN) on postpartum histology. In contrast, 5 out of 6 patients negative for p16/Ki-67 dual-staining had a negative histology postpartum and during follow-up, and the remaining patient showed a CIN1 (p < 0.001). Conclusion: p16/Ki-67 dual-stained cytology may provide a valuable novel approach to identify pregnant women with persistent or progressing CIN disease and may help improve the management of abnormal Pap cytology results during pregnancy.