The role of ultrasound in first-trimester screening after the introduction of NIPT as a service of public health insurance - a consensus statement of the Fetal Medicine Foundation (FMF) Germany.

Combined first-trimester screening (FTS) and noninvasive prenatal testing (NIPT) have been proven to be reliable noninvasive procedures to detect the most common chromosomal abnormalities (trisomies 21, 18, 13) in the first trimester. The aim of this paper is to demonstrate the strengths and limitations of these two procedures and to give a consensus statement of the Fetal Medicine Foundation (FMF) Germany on how to use the two techniques in the first trimester after the introduction of NIPT as a service of the statutory health insurance companies in Germany.

DEGUM Recommendations on Diagnostic Puncture in Prenatal Medicine. / Empfehlungen der DEGUM zu diagnostischen Punktionen in der Pränatalmedizin.

Diagnostic puncture (amniocentesis, chorionic villus sampling, and fetal blood sampling) is an essential part of prenatal diagnostics and the only established and sufficiently scientifically evaluated possibility of diagnosing genetic diseases from pregnancy-specific cells. The number of diagnostic punctures in Germany, as in other countries, has fallen significantly. This is largely due to the introduction of first-trimester screening with further detailed ultrasound examination of the fetus and the analysis of cf-DNA (cell-free DNA) from maternal blood (noninvasive prenatal test - NIPT). On the other hand, knowledge about the incidence and appearance of genetic diseases has increased. The development of modern molecular genetic techniques (microarray and exome analysis) makes a differentiated investigation of these diseases increasingly possible. The requirements for education and counseling regarding these complex correlations have thus increased. The studies performed in recent years make it clear that diagnostic puncture performed in expert centers is associated with a low risk of complications. In particular, the procedure-related miscarriage risk hardly differs from the background risk for spontaneous abortion. In 2013, the Section of Gynecology and Obstetrics of the German Society for Ultrasound in Medicine (DEGUM) published recommendations on diagnostic puncture in prenatal medicine 1. The developments described above and new findings in recent years make it necessary to revise and reformulate these recommendations. The aim of this review is to compile important and current facts regarding prenatal medical puncture (including technique, complications, genetic examinations). It is intended to provide basic, comprehensive, and up-to-date information on diagnostic puncture in prenatal medicine. It replaces the publication from 2013 1.

Basic Gynecologic Ultrasound Examination (Level I): DEGUM, ÖGUM, and SGUM Recommendations. / Qualitätsanforderungen an gynäkologische Ultraschall-Untersuchungen der DEGUM-Stufe I: Empfehlungen der DEGUM, ÖGUM und SGUM.

Ultrasound has become an essential diagnostic tool in gynecology, and every practicing gynecologist must be able to differentiate normal from pathologic findings, such as benign or malignant pelvic masses, adnexal torsion, pelvic inflammation disease, endometriosis, ectopic pregnancies, and congenital uterine malformations at least on a basic level. A standardized approach to the correct settings of the ultrasound system, the indications for gynecologic ultrasound investigations, and the sonographic appearance of normal anatomy and common pathologic findings in the standard planes are important prerequisites for safe and confident clinical management of gynecologic patients. Based on current publications and different national and international guidelines, updated DEGUM, ÖGUM, and SGUM recommendations for the performance of basic gynecologic ultrasound examinations were established.

Quality Requirements for gynecological ultrasound examinations of DEGUM level II - Recommendations of the Sections/Working Groups Gynecology and Obstetrics of DEGUM, ÖGUM and SGUM. / Qualitätsanforderungen an die gynäkologischen Ultraschalluntersuchungen der DEGUM Stufe II ­ Empfehlungen der Sektionen/Arbeitskreise Gynäkologie und Geburtshilfe der DEGUM, ÖGUM und SGUM.

Gynecological sonography is the central and most frequently used technical examination method used by gynecologists. Its focus is on the clarification of masses of the uterus and the adnexa, fertility diagnosis, clarification of bleeding disorders and chronic and acute pelvic problems, pelvic floor and incontinence diagnosis as well as the differential diagnosis of disturbed early pregnancy. The indication for diagnostic and therapeutic interventions, preoperative planning and postoperative controls are largely based on the findings of gynecological sonography. These examinations are particularly dependent on the experience of the examiner.Based on the proven multi-stage concept of obstetric diagnostics, gynecological sonography should primarily be performed by an experienced and specialized examiner in patients for whom the initial gynecological examinations have not yet led to a sufficient assessment of the findings. So that the expert status required for this has an objective basis, the Gynecology and Obstetrics Section of DEGUM in cooperation with ÖGUM and SGUM implemented the option of acquiring DEGUM Level II for gynecological sonography. The effectiveness of the care in the multi-level concept depends on the quality of the ultrasound examination at level I. Quality requirements for the basic examination and the differentiation between the basic and further examination have therefore already been defined by DEGUM/ÖGUM. The present work is intended to set out quality requirements for gynecological sonography of DEGUM level II and for the correspondingly certified gynecologists.Common pathologies from gynecological sonography and requirements for imaging and documentation are described.

Prenatal and Obstetric Parameters of Late Terminations: A Retrospective Analysis.

Background In Germany, the highly sensitive issue of late terminations of pregnancy and feticide is regulated in Sec. 218a para. 2 of the German Penal Code (medical indication). This study aimed to investigate the prenatal obstetric approach after feticide and the rate of maternal complications. Material and Methods All feticides of singleton pregnancies carried out at Leipzig University Hospital (n = 164) in the period between 01/2016 and 12/2019 were retrospectively analyzed. Selective feticides of multiple pregnancies were excluded from the study. Target indicators for the prenatal obstetric approach were sonographic accuracy of estimation, method used to induce feticide, time between feticide and delivery, and whether curettage was required. The rate of maternal complications was defined as blood loss of ≥ 500 ml. Results The number of feticides as a percentage of the total number of births during the investigation period was 1.6%. None of the terminations were performed primarily because of a serious risk to the mother's physical health; all of the indications to terminate the pregnancy were based on the psychosocial burden and the risk to the mother's mental health as outlined in Sec. 218a StGB (German Penal Code). The most common fetal diagnoses in the context of a maternal psychosocial emergency were central nervous system abnormalities (29.3%), numerical chromosomal aberrations (29.3%) and structural chromosomal aberrations/syndromes (21.3%). Sonographic measurements were used to estimate fetal weight and the weight of around half of the fetuses was underestimated (- 121.8 ± 155.8 g). The margin of estimation error increased with increasing gestational age (p < 0.001). Misoprostol was the most common drug administered to induce labor. No significant association was found between the method chosen for induction, parity, fetal birth position, fetal anomaly, fetal gender, birth mode or the number of previous cesarean sections and Δdelivery . However, a significantly higher loss of blood was observed with longer Δdelivery (p = 0.02). The likelihood of requiring curettage increased with increasing loss of blood. The number of maternal complications as a percentage of the total patient population was 10.4%. Only 11% of patients agreed to a postmortem examination. Conclusion Late terminations of pregnancy carried out in accordance with Sec. 218a para. 2 StGB are a reality and must be understood and accepted as a possible consequence of modern prenatal medicine. The complication rate after feticide and the subsequent obstetric procedure was 10% for the above-defined maternal complication. Late terminations and their obstetric management should be carried out in specialized perinatal centers which offer interprofessional expertise.

Doppler ultrasound in pregnancy - quality requirements of DEGUM and clinical application (part 2). / Dopplersonografie in der Schwangerschaft ­ Qualitätsanforderungen der DEGUM und klinischer Einsatz (Teil 2).

This second part on Doppler sonography in prenatal medicine and obstetrics reviews its clinical applications. While this has not become the initially anticipated screening tool, it is used for the diagnosis and surveillance of a variety of fetal pathologies. For example, the sonography-based determination of uterine artery blood flow indices is an important parameter for the first trimester multimodal preeclampsia risk assessment, increasing accuracy and providing indication for the prophylactic treatment with aspirin. It also has significant implications for the diagnosis and surveillance of growth-restricted fetuses in the second and third trimesters through Doppler-sonographic analysis of umbilical artery, middle cerebral artery and ductus venosus. Here, especially the hemodynamics of the ductus venosus provides a critical criterium for birth management of severe, early-onset FGR before 34 + 0 weeks of gestation. Further, determination of maximum blood flow velocity of the middle cerebral artery is a central parameter in fetal diagnosis of anemia which has been significantly improved by this analysis. However, it is important to note that the mentioned improvements can only be achieved through highest methodological quality. Importantly, all these analyses are also applied to twins and higher order multiples. Here, for the differential diagnosis of specific complications such as TTTS, TAPS and TRAP, the application of Doppler sonography has become indispensable. To conclude, the successful application of Doppler sonography requires both exact methodology and precise pathophysiological interpretation of the data.

Telomere attrition and dysfunction: a potential trigger of the progeroid phenotype in nijmegen breakage syndrome.

BACKGROUND: Nibrin, as part of the NBN/MRE11/RAD50 complex, is mutated in Nijmegen breakage syndrome (NBS), which leads to impaired DNA damage response and lymphoid malignancy. RESULTS: Telomere length (TL) was markedly reduced in homozygous patients (and comparably so in all chromosomes) by ~40% (qPCR) and was slightly reduced in NBS heterozygotes older than 30 years (~25% in qPCR), in accordance with the respective cancer rates. Humanized cancer-free NBS mice had normal TL. Telomere elongation was inducible by telomerase and/or alternative telomere lengthening but was associated with abnormal expression of telomeric genes involved in aging and/or cell growth. Lymphoblastoid cells from NBS patients with long survival times (>12 years) displayed the shortest telomeres and low caspase 7 activity. CONCLUSIONS: NBS is a secondary telomeropathy. The two-edged sword of telomere attrition enhances the cancer-prone situation in NBS but can also lead to a relatively stable cellular phenotype in tumor survivors. Results suggest a modular model for progeroid syndromes with abnormal expression of telomeric genes as a molecular basis. METHODS: We studied TL and function in 38 homozygous individuals, 27 heterozygotes, one homozygous fetus, six NBS lymphoblastoid cell lines, and humanized NBS mice, all with the same founder NBN mutation: c.657_661del5.

Cardiovascular variability before and after delivery: recovery from arterial stiffness in women with preeclampsia 4 days post partum.

OBJECTIVE: We studied the short-term response of autonomic control to delivery in normal pregnancies and pregnancies with preeclampsia (PE). METHODS: Fourteen healthy pregnant women and 13 women with PE were monitored within four days before and four days after delivery and compared to values of 14 non-pregnant women as controls using high-resolution electrocardiogram and noninvasive continuous blood pressure monitoring. RESULTS: In PE, blood pressure remained elevated four days postpartum, but markers for arterial stiffness normalized. In contrast, none of heart rate variability and baroreflex sensitivity parameters, altered due to either pregnancy or disease, were normalized 96 h after delivery. CONCLUSION: Four days after delivery, the maternal cardiovascular system is still strongly affected by pregnancy independent of the health status.

Multiscale entropy and detrended fluctuation analysis of QT interval and heart rate variability during normal pregnancy.

Pregnancy leads to physiological changes in various parameters of the cardiovascular system. The aim of this study was to investigate longitudinal changes in the structure and complexity of heart rate variability (HRV) and QT interval variability during the second half of normal gestation. We analysed 30-min high-resolution ECGs recorded monthly in 32 pregnant women, starting from the 20th week of gestation. Heart rate and QT variability were quantified using multiscale entropy (MSE) and detrended fluctuation analyses (DFA). DFA of HRV showed significantly higher scaling exponents towards the end of gestation (p<0.0001). MSE analysis showed a significant decrease in sample entropy of HRV with progressing gestation on scales 1-4 (p<0.05). MSE analysis and DFA of QT interval time series revealed structures significantly different from those of HRV with no significant alteration during the second half of gestation. In conclusion, pregnancy is associated with increases in long-term correlations and regularity of HRV, but it does not affect QT variability. The structure of QT time series is significantly different from that of RR time series, despite its close physiological dependence.

Relation between maternal angiogenic factors and utero-placental resistance in normal first- and second-trimester pregnancies.

OBJECTIVE: Soluble endoglin (sEng) is a novel antiangiogenic protein and elevated sEng concentrations in maternal circulation are closely related to preeclampsia and HELLP syndrome. As the perfusion of the uterine arteries as well as the dynamics of angiogenic factors between first and second trimester have prognostic value regarding pregnancy outcome, it was the aim of this study to investigate the relation between maternal angiogenic factors and uterine Doppler parameters. STUDY DESIGN: The longitudinal study includes 50 normal pregnancies. Pulsatility index (PI) of the uterine arteries was detected by Doppler ultrasound in first and second trimester. In parallel, maternal sEng and soluble fms-like tyrosine kinase 1 (sFlt1) concentration was measured using ELISA. RESULTS: In the first trimester, the sEng concentrations were 4.92 ± 1.36 ng/mL and the uterine PI was 1.14 ± 0.28. In the second trimester, the maternal sEng concentration decreased significantly to 3.99 ± 0.63 ng/mL (p < 0.05) which was associated by a decrease of the uterine PI to 0.78 ± 0.15 (p < 0.001). Soluble fms-like tyrosine kinase 1 concentrations did not differ significantly between first and second trimester (423 ± 333 vs. 444 ± 291 pg/mL). There was a significant negative correlation between sEng and uterine resistance in the second trimester (r = -0.416; p < 0.001). CONCLUSIONS: In normal pregnancy, parallel to the fall of utero-placental resistance, there is a physiological decline of the maternal sEng concentration between first and second trimester. In second trimester, there is a negative correlation between sEng and uterine Doppler parameters.

Prevalence of hepatitis B among pregnant women and its impact on pregnancy and newborn complications at a tertiary hospital in the eastern part of Germany.

BACKGROUND AND AIMS: Prevalence data of hepatitis B virus (HBV) in pregnant women in the Eastern part of Germany are missing. More importantly, no data on HBV's impact on pregnancy is known in patients living in the Western hemisphere. Our aim was to assess the prevalence of hepatitis B surface antigen (HBsAg) and its impact on pregnancy in women admitted to the department of gynecology at a German university hospital. PATIENTS AND METHODS: 8,193 women who delivered at the university hospital between 2001 and 2006 were retrospectively screened for HBsAg and if positive investigated for pregnancy and newborn complications in comparison to women without hepatitis B infection. RESULTS: 39 (0.48%) women were found to be HBsAg carriers, which is in line with other data showing lower rates in Eastern parts of Germany in relation to the Western part. Furthermore, prevalence was much lower in German-born women (0.2%) in comparison to Asian-born women (9.1%). Secondly, women with HBsAg had no significantly increased prevalence of adverse pregnancy outcomes. CONCLUSION: There is a low prevalence of HBV infection, especially among German-born women. There is no significant evidence to support increased complications in relation to HBV infection in our study.

Longitudinal changes in QT interval variability and rate adaptation in pregnancies with normal and abnormal uterine perfusion.

The maternal heart significantly adapts to the circulatory needs of pregnancy, but the effect of pregnancy on ventricular repolarization is poorly understood. The aim of this study was to quantify longitudinal changes in ventricular repolarization during pregnancy. Monthly electrocardiographs (ECGs) were recorded in 32 pregnant women with normal uterine perfusion and 32 pregnant women with abnormal perfusion, starting from the 20th week of gestation until 3 days postpartum. Ventricular repolarization was assessed through various QT interval variability and heart rate adaptation measures. The pregnancy outcomes of all women with normal perfusion were normal. Among pregnancies with abnormal uterine perfusion, 15 pregnancy outcomes were normal, but 17 pregnancies developed preeclampsia and/or small-for-gestational-age infants. In pregnancies with normal perfusion, the QT(c) interval was unaltered, but the QT interval-heart rate hysteresis lag was shorter and the QT interval-heart rate regression residual was higher compared with those of a control group of 10 healthy non-pregnant women. Pregnancies with abnormal uterine perfusion that developed pathological outcomes showed significantly smaller QT interval-heart rate regression residuals and a trend towards shorter QT(c) intervals compared with pregnant women with normal perfusion. In conclusion, pregnancy has a significant effect on ventricular repolarization. Pregnancies with abnormal uterine perfusion and subsequent pathological outcomes are paralleled by changes in ventricular repolarization that precede clinical symptoms.

Giant umbilical cord edema caused by retrograde micturition through an open patent urachus.

A giant umbilical cord is a rare finding in mature newborns and originates from different developmental etiologies. We report on a case of a mature female newborn presenting a 50 × 8-cm giant umbilical cord without further malformations. Antenatal sonographic findings of a diffuse giant umbilical cord, elevated creatinine levels of 1.3 mg/dL in umbilical cord edema, gross and histopathological findings of allantoic remnants, and umbilical urinary discharge lead to the diagnosis of a patent urachus with retrograde micturition into the umbilical cord. Postnatal surgical repair was required. In antenatal sonography, cystic and diffuse changes should be considered in the differential diagnosis of a giant umbilical cord. In cases of diffuse enlargement, elevated umbilical creatinine can support the diagnosis of a patent urachus with open leakage into the Wharton's jelly. Appropriate surgical management is required.

Preliminary report: Serum levels of retinol-binding protein 4 in preeclampsia.

The objective of the study was to investigate serum levels of the adipokine retinol-binding protein 4 (RBP4) in patients with preeclampsia (PE) as compared with healthy controls of similar gestational age. Retinol-binding protein 4 serum levels were quantified by enzyme-linked immunosorbent assay in control (n = 20) and PE (n = 16) patients. Mean maternal RBP4 concentrations were not significantly different in PE (24.5 mg/L) as compared with controls (22.3 mg/L). Furthermore, RBP4 did not correlate to clinical and biochemical measures of pregnancy outcome, renal function, glucose, and lipid metabolism, as well as inflammation. Our results do not support a role of RBP4 in the pathogenesis of PE.

Secretory products from human adipocytes stimulate proinflammatory cytokine secretion from human endothelial cells.

Hyperplasia and hypertrophy of fat cells can be found in obesity and increased adiposity is associated with endothelial dysfunction as an early event of atherosclerosis. However, it is unclear whether human adipocytes directly influence endothelial protein secretion. To study the crosstalk between fat and endothelial cells, human umbilical venous endothelial cells (HUVECs) were cultured in infranatants (Adipo) of primary differentiated human adipocytes. Interestingly, significantly increased secretion of 23 cytokines and chemokines from HUVECs was detected in four independent experiments after Adipo stimulation by protein array analysis detecting a total of 174 different proteins. Among those, time-dependent Adipo-induced upregulation of cytokine secretion in HUVECs was confirmed by ELISA for interleukin (IL)-8, monokine induced by gamma interferon, macrophage inflammatory protein (MIP)-1beta, MIP-3alpha, monocyte chemoattractant protein-1, and IL-6. Factors besides adiponectin, leptin, resistin, and tumor necrosis factor alpha appear to mediate these stimulatory effects. Our findings suggest that endothelial cell secretion is significantly influenced towards a proinflammatory pattern by adipocyte-secreted factors.

Serum levels of angiopoietin-related growth factor are increased in preeclampsia.

BACKGROUND: Preeclampsia is a serious complication in pregnancy with an increased future cardiovascular and metabolic risk for both mother and newborn. Recently, angiopoietin-related growth factor (AGF) was introduced as a novel liver-derived protein with proangiogenic and insulin-sensitizing effects. In the current study, we hypothesized that serum levels of AGF would be lower in preeclamptic patients as compared to healthy controls. METHODS: AGF was quantified by enzyme-linked immunosorbent assay (ELISA) in control and preeclamptic patients during pregnancy ( CONTROL: n =22, Preeclampsia: n =22) and 6 months after delivery ( CONTROL: n =20, Preeclampsia: n =20). Furthermore, circulating AGF was correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. RESULTS: During pregnancy, median maternal AGF concentrations were significantly higher in preeclampsia (191.6 microg/l) as compared to control subjects (136.3 microg/l) (P = 0.004). Furthermore, preeclampsia and systolic blood pressure (SBP) were associated with AGF levels in multivariate analyses independent of maternal age. However, higher circulating AGF concentrations in preeclampsia did not persist 6 months after delivery. CONCLUSIONS: Maternal AGF serum levels are significantly and paradoxically higher in preeclampsia during pregnancy. However, median postpartum circulating AGF levels are similar in preeclampsia and normal pregnancies.

Endogenous soluble receptor for advanced glycation endproducts is increased in preeclampsia.

OBJECTIVE: Preeclampsia is a serious complication in pregnancy with an increased future cardiovascular risk for both mother and newborn. Recently, low levels of endogenous soluble receptor for advanced glycation endproducts (esRAGE) have been associated with increased cardiovascular risk. In the current study, we investigated esRAGE serum levels in patients with preeclampsia as compared to healthy gestational age-matched controls. METHODS: esRAGE was quantified by enzyme-linked immunosorbent assay in controls and patients with preeclampsia during pregnancy (control: n = 20, preeclampsia: n = 16) and 6 months after delivery (control: n = 19, preeclampsia: n = 15). Furthermore, esRAGE was correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation. RESULTS: During pregnancy, median maternal serum esRAGE concentrations were more than three-fold higher in patients with preeclampsia (200 ng/l) than in controls (63 ng/l) (P < 0.01). Furthermore, esRAGE levels positively correlated with age, blood pressure, creatinine, adiponectin, and C-reactive protein, whereas a negative correlation existed with fasting insulin and the homeostasis model assessment of insulin resistance index. In multivariate analyses, homeostasis model assessment of insulin resistance and C-reactive protein independently predicted esRAGE serum levels and explained 44% of the variation in esRAGE concentrations. Surprisingly, median esRAGE concentrations 6 months after delivery were significantly lower in former patients with preeclampsia (270 ng/l) than in controls (342 ng/l) in contrast to the results obtained during pregnancy. CONCLUSION: We showed that maternal esRAGE concentrations are significantly increased in patients with preeclampsia during pregnancy. Here, insulin sensitivity and inflammatory status independently predict serum esRAGE levels.

Serum levels of the adipokine adipocyte fatty acid-binding protein are increased in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious complication of pregnancy which is associated with an increased future metabolic and cardiovascular risk for both mother and newborn. Recently, adipocyte fatty acid-binding protein (AFABP) was introduced as a novel adipokine, serum levels of which independently correlate with the development of the metabolic syndrome and cardiovascular disease in humans. In this study, we investigated serum concentrations of the adipokine AFABP in patients with PE as compared to healthy controls of similar gestational age. METHODS: AFABP serum levels were quantified by enzyme-linked immunosorbent assay (ELISA) in control (n = 20) and PE (n = 16) patients. Furthermore, AFABP was correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. RESULTS: Mean maternal AFABP concentrations were significantly elevated in PE (24.5 +/- 9.7 microg/l) as compared to controls (14.8 +/- 7.1 microg/l). Furthermore, AFABP serum levels correlated positively with age, body mass index (BMI), blood pressure, serum creatinine, free fatty acids (FFAs), leptin, and C-reactive protein (CRP). In multivariate analyses, BMI and serum creatinine remained independently associated with AFABP concentrations and explained 58% of the variation in AFABP levels. CONCLUSION: We demonstrate that maternal AFABP serum concentrations are significantly increased in PE. Furthermore, BMI and serum creatinine are independent predictors of circulating AFABP.

Bladder outlet obstruction causes fetal enterolithiasis in anorectal malformation with rectourinary fistula.

Extraluminal calcified meconium is found frequently by prenatal ultrasound in cases with bowel perforation and meconium peritonitis. Intraluminal intestinal meconium calcifications are rarely seen in prenatal sonography. Meconium calcifications result from a mixture of meconium and urine that indicates a connection between intestinal and urinary tract. We report a case of a male newborn prenatally diagnosed with intraluminal echogenic calcifications at 23 weeks of gestation, suggesting an anorectal malformation (ARM) with rectourinary fistula. At birth, the child presented with a complex ARM including high anal atresia with both perineal and rectourethral fistula. Furthermore, a bladder outlet obstruction due to a urethral stenosis was diagnosed. Vesicostomy was performed as an emergency procedure followed by colostomy during neonatal period. Posterior sagittal anorectoplasty was performed at the age of 4 months. Prenatal echogenic calcifications within bowel should raise the suspicion of ARM with rectourinary fistula and bladder outlet obstruction.

Circulating high-molecular-weight adiponectin is upregulated in preeclampsia and is related to insulin sensitivity and renal function.

OBJECTIVE: Preeclampsia (PE) is a serious cardiovascular complication in pregnancy which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, a paradoxical upregulation of the insulin-sensitizing and anti-atherogenic adipokine adiponectin has been shown in PE. Furthermore, high-molecular-weight (HMW) adiponectin has been suggested as the biologically active form of this adipokine. DESIGN AND METHODS: HMW adiponectin and total adiponectin serum concentrations were quantified by ELISA in PE (n=16) patients and pregnant control women without PE (n=20). Furthermore, HMW adiponectin and total adiponectin were correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. RESULTS: Median maternal HMW adiponectin and total adiponectin levels were significantly and independently upregulated almost twofold in PE when compared with controls. HMW adiponectin and total adiponectin correlated positively with creatinine and negatively with fasting insulin in univariate and multivariate analyses. CONCLUSIONS: We show that maternal HMW adiponectin and total adiponectin serum concentrations are significantly increased in PE and are positively associated with markers of insulin sensitivity and renal dysfunction. Adiponectin might be part of a physiological feedback mechanism improving insulin sensitivity and cardiovascular health in PE.