Luigi Raio

First-trimester serum levels of soluble endoglin and soluble fms-like tyrosine kinase-1 as first-trimester markers for late-onset preeclampsia

OBJECTIVE The aim of this investigation was to assess soluble endoglin (sEng) and soluble fms-like tyrosine kinase-1 (sFlt1) as first-trimester serum markers to predict preeclampsia. STUDY DESIGN First-trimester sera were obtained from 46 women with subsequent late-onset preeclampsia and from 92 controls. sEng and sFlt1 concentrations were determined immunoanalytically. Correlation analysis with inhibin A and placental growth factor levels was performed. RESULTS sEng and sFlt1 serum concentrations were higher in women with subsequent preeclampsia than in controls (mean +/- SD, sEng: 5.57 +/- 1.18 ng/mL vs 5.02 +/- 1.01 ng/mL, P = .009; sFlt1: 1764 +/- 757 pg/mL vs 1537 +/- 812 pg/mL, P = .036). Sensitivities and specificities for predicting preeclampsia were 63% and 57% for sEng and 64% and 56% for sFlt1, respectively. When sEng and inhibin A were combined, the sensitivity increased to 68%, whereas the specificity was 61%. CONCLUSION sEng and sFlt1 are increased in the first trimester in women with subsequent late-onset preeclampsia and might therefore prove useful to predict preeclampsia.

EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.

Objectives Develop recommendations for womens health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Methods Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. Results Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. Conclusions Recommendations for womens health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.

Pregnancy and reproduction in autoimmune rheumatic diseases

Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.

Perinatal outcome of fetuses with a birth weight greater than 4500 g: an analysis of 3356 cases

OBJECTIVE To assess the perinatal outcome in a series of macrosomic fetuses according to the intended mode of delivery, and to estimate the individual risk of shoulder dystocia and brachial plexus injury upon information available either prior the onset of labor or at delivery. STUDY DESIGN Perinatal and postnatal information of 3356 women who delivered during a 10-year period a macrosomic fetus (>4500 g) in vertex presentation were analyzed. After the exclusion of cases with extraneous factors that may have affected the health of the neonate, patient and neonatal characteristics were compared according to the intended mode of delivery. The contribution of factors known prior labor and at the time of deliver on the occurrence of shoulder dystocia and brachial plexus injury was analyzed using multiple logistic regression analysis. RESULTS During the study period, 2371 women were admitted to spontaneous labor, 778 underwent an induction of labor, and 207 had an elective cesarean section. All cases of shoulder dystocia (n=310), and brachial plexus injury (n=94) occurred among women who delivered vaginally. The rate of brachial plexus injury was higher in cases who had shoulder dystocia than in those who did not (58/310 versus 36/2329, P<0.001). The incidence of brachial plexus injury increases steadily from 0.8 in fetuses weighing 4500-4599 g to 2.86% in those weighing more than 5000 g (P<0.01) and from 2.1 in women taller than 180 cm to 12.5% in those shorter than 155 cm (P<0.05). After adjustment for confounding variables shoulder dystocia (OR 9.2, 95% C.I. 5.38; 15.59), operative vaginal delivery (OR 1.96, 95% C.I. 1.10; 3.49) and clavicular fracture (OR 2.9, 95% C.I. 1.31; 6.44) remained predictors of brachial plexus injury. CONCLUSION Since some of these risk factors are known prior to delivery, each woman whose fetus is suspected to weight more than 4500 g should be counseled on her individual risk of severe perinatal morbidity before a decision on the mode of delivery is taken.

Salt Sensitivity of Children With Low Birth Weight

Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3±2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by ≥3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r2=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal “fetal programming” awaits clarification.

Umbilical cord morphology and pregnancy outcome.

Traditionally, the prenatal assessment of the umbilical cord (UC) is limited to the assessment of the number of vessels and to the evaluation of umbilical artery blood flow parameters. Morphologic aspects of the UC have usually been studies by pathologists and retrospectively correlated with the perinatal outcome. The introduction of more sophisticated imaging techniques have offered the possibility to investigate the UC characteristics during fetal life from early to late gestation. A number of investigations have demonstrated that an altered structure of the UC can be associated with pathologic conditions (i.e. Preeclampsia, fetal growth restriction, diabetes, fetal demise). Nomograms of the various UC components have been generated and allow the identification of lean or large umbilical cords, entities frequently associated with fetal growth abnormalities and diabetes. A Whartons jelly reduction has also been invoked as a possible cause of fetal death in the presence of single umbilical artery. Prenatal morphometric UC characteristics as well as arterial and venous blood flow parameters in normal and pathologic conditions will be discussed.

Prematurity Is Related to High Placental Cortisol in Preeclampsia

Fetal growth is compromised in animal models with high cortisol availability. In healthy pregnancies, the fetus is protected from high circulating cortisol levels by the placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is reduced in preeclampsia. We hypothesized increased placental cortisol availability in preeclampsia as missing link to fetal growth restriction and prematurity. Placental tissue was obtained from 39 pregnant women dichotomized normotensive (n = 16) or preeclamptic (n = 23). Placental steroid hormone metabolites were analyzed by gas chromatography-mass spectrometry. Apparent 11β-HSD2 enzyme activity was calculated as substrate to product ratio. Estradiol and pregnandiol positively correlated with gestational age. Cortisol was virtually absent in 93.8% of controls, yet detectable in 79.3% of preeclamptic samples resulting in an odds ratio (OR) of 0.019 (95% CI 0.002–0.185) for the presence of placental cortisol. Apparent 11β-HSD2 activity directly correlated with birth weight (R2 = 0.16; p < 0.02) and gestational age (R2 = 0.11; p < 0.04) ensuing a reduced risk of premature delivery (OR 0.12; 95% CI 0.02–0.58). We conclude that normotensive pregnancies are characterized by an almost completely inactivated placental cortisol. In line with our hypothesis, reduced 11β-HSD2 activity in preeclampsia is unable to abolish placental cortisol, a finding clearly associated with prematurity and low birth weight.

Diffusion-weighted MR Imaging of the Placenta in Fetuses with Placental Insufficiency

PURPOSE To evaluate diffusion-weighted magnetic resonance (MR) imaging of the human placenta in fetuses with and fetuses without intrauterine growth restriction (IUGR) who were suspected of having placental insufficiency. MATERIALS AND METHODS The study was approved by the local ethics committee, and written informed consent was obtained. The authors retrospectively evaluated 1.5-T fetal MR images from 102 singleton pregnancies (mean gestation ± standard deviation, 29 weeks ± 5; range, 21-41 weeks). Morphologic and diffusion-weighted MR imaging were performed. A region of interest analysis of the apparent diffusion coefficient (ADC) of the placenta was independently performed by two observers who were blinded to clinical data and outcome. Placental insufficiency was diagnosed if flattening of the growth curve was detected at obstetric ultrasonography (US), if the birth weight was in the 10th percentile or less, or if fetal weight estimated with US was below the 10th percentile. Abnormal findings at Doppler US of the umbilical artery and histopathologic examination of specimens from the placenta were recorded. The ADCs in fetuses with placental insufficiency were compared with those in fetuses of the same gestational age without placental insufficiency and tested for normal distribution. The t tests and Pearson correlation coefficients were used to compare these results at 5% levels of significance. RESULTS Thirty-three of the 102 pregnancies were ultimately categorized as having an insufficient placenta. MR imaging depicted morphologic changes (eg, infarction or bleeding) in 27 fetuses. Placental dysfunction was suspected in 33 fetuses at diffusion-weighted imaging (mean ADC, 146.4 sec/mm(2) ± 10.63 for fetuses with placental insufficiency vs 177.1 sec/mm(2) ± 18.90 for fetuses without placental insufficiency; P < .01, with one false-positive case). The use of diffusion-weighted imaging in addition to US increased sensitivity for the detection of placental insufficiency from 73% to 100%, increased accuracy from 91% to 99%, and preserved specificity at 99%. CONCLUSION Placental dysfunction associated with growth restriction is associated with restricted diffusion and reduced ADC. A decreased ADC used as an early marker of placental damage might be indicative of pregnancy complications such as IUGR. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10092283/-/DC1.

Longitudinal umbilical vein blood flow changes in normal and growth-retarded fetuses

Objective.  To explore whether the umbilical vein blood flow of growth‐retarded fetuses with normal Doppler parameters changes over time differently to that of normally grown fetuses.

Effects of Female Genital Mutilation on Birth Outcomes in Switzerland

Objective  The primary aim of this study was to determine the desires and wishes of pregnant patients vis‐à‐vis their external genital anatomy after female genital mutilation (FGM) in the context of antenatal care and delivery in a teaching hospital setting in Switzerland.