No abstract

Preeclampsia is characterized by diffuse vascular endothelial dysfunction. Tumor necrosis factor-alpha (TNF-alpha), which plays a key role in the cytokine network responsible for immunoregulation, is also known to contribute to endothelial dysfunction and other metabolic disturbances noted in preeclampsia. Results from cross-sectional studies and one longitudinal study indicate that TNF-alpha (or its soluble receptor, sTNFp55) is increased in the peripheral circulation and amniotic fluid of women with preeclampsia as compared with normotensive women. Between December 1993 and August 1994, prediagnostic sTNFp55 concentrations (a marker of excessive TNF-alpha release) were measured in 35 women with preeclampsia and 222 normotensive women to determine whether elevations precede the clinical manifestation of the disorder. Logistic regression procedures were used to calculate maximum likelihood estimates of odds ratios and 95% confidence intervals. Mean second trimester (15-22 weeks' gestation) serum sTNFp55 concentrations, measured by enzyme-linked immunosorbent assay, were 14.4% higher in preeclamptic women than in normotensive controls (716.6 pg/ml (standard deviation 193.6) vs. 626.4 pg/ml (standard deviation 158.0); p = 0.003). The relative risk of preeclampsia increased across successively higher quintiles of sTNFp55 (odds ratios were 1.0, 1.3, 2.1, and 3.7, with the lowest quintile used as the referent; p for trend = 0.007). After adjustment for maternal age, adiposity, and parity, the relative risk between extreme quintiles was 3.3 (95% confidence interval 0.8-13.4). These findings indicate that the level of TNF-alpha in maternal circulation is increased prior to the clinical manifestation of the disorder, and they are consistent with the hypothesized role of cytokines in mediating endothelial dysfunction and the pathogenesis of preeclampsia. Further work is needed to identify modifiable risk factors for the excessive synthesis and release of TNF-alpha in pregnancy, and to assess whether lowering of TNF-alpha concentrations in pregnancy alters the incidence and severity of preeclampsia.

Purpose: To assess nuchal translucency measurements that were performed as part of routine prenatal screening for Down syndrome. Methods: Collect ultrasound measurements of nuchal translucency and crown rump length provided by individual sonographers over a 6-month period to six North American prenatal screening laboratories, along with the laboratory's nuchal translucency interpretation in multiples of the median. For sonographers with 50 or more observations, compute three nuchal translucency quality measures (medians, standard deviations, and slopes), based on epidemiological monitoring. Results: Altogether, 23,462 nuchal translucency measurements were submitted by 850 sonographers. Among the 140 sonographers (16%) who submitted more than 50 observations, 76 (54%) were found to have all three quality measures in the target range. These 140 sonographers collectively accounted for 14,210 nuchal translucency measurements (61%). The most common single measure to be out of range was nuchal translucency multiples of the median, found for 29 of the 140 sonographers (21%). Nuchal translucency (NT) is defined as the collection of fluid behind the fetal neck occurring in the first trimester of pregnancy. 1-3 When measured and interpreted correctly, it is the most discriminatory marker for Down syndrome that has been reported in a routine setting. Univariately, NT measurements can identify about 60% of Down syndrome pregnancies in the first trimester at a 5% false-positive rate. 4 Detection increases to between 80% and 85%, when NT is combined with first trimester biochemical measurements of pregnancyassociated plasma protein-A (PAPP-A) and human chorionic gonadotropin (the intact, total, or free-␤ subunit forms). 4 When NT measurements are incorporated into the integrated test (NT and PAPP-A measurements in the first trimester) and the quadruple test (␣-fetoprotein, unconjugated estriol, human chorionic gonadotropin and dimeric inhibin-A in the second trimester), 85-90% detection is achievable at a false-positive rate of 2% or less. 5,6 Acquiring the skill to properly measure NT requires specialized training and oversight. 7 Recognizing this, several national and international programs have been established to train and qualify sonographers, and also to assess their ability to consistently and accurately quantify the NT thickness. 8 -11 The hands-on performance training is usually evaluated through still images submitted to one, or a panel of, expert sonographers. Several research trials using NT measurements have shown that such training, although necessary, is not sufficient to assure reproducibility of absolute measurements among sonographers. For example, both the Serum, Urine and Ultrasound Screening Study (SURUSS) 5 and First and Second Trimester Evaluation of Risk (FASTER) study 12 found that use of sonographer-specific reference data (medians) resulted in improved screening performance.In the current study, information was sought from screening laboratories regarding how they deal with NT measurements

The adipocyte hormone, leptin, is secreted in proportion to adipose mass and is implicated in the regulation of energy balance via its central actions on food intake and sympathetic nervous system activity. The placenta was also shown recently to be a possible source of leptin in pregnant women, raising the possibility that the normal relationship between leptin and adiposity may be altered in pre-eclampsia. We therefore sought to assess the extent to which maternal second trimester serum leptin concentrations differed for women who would subsequently develop pre-eclampsia and those who would remain normotensive. This nested case-control study population comprised 38 women with pregnancy-induced hypertension and proteinuria (pre-eclampsia) and 192 normotensive women. Multiple least-squares regression procedures were used to assess the independent relationship between leptin concentrations and risk of pre-eclampsia. Serum leptin concentrations, measured by radioimmunoassay, were highly correlated with maternal pre-pregnancy and second trimester body mass index (r = 0.71 and r = 0.74 respectively; P < 0.001 for both) among normotensive women, and to a lesser extent among women who developed pre-eclampsia (r = 0.29 and r = 0.42; P = 0.09 and 0.02 respectively). Among women with a pre-pregnancy body mass index of < or = 25 kg/m2, pre-eclampsia cases compared with controls had higher mean second trimester leptin concentrations after adjustment for confounding factors. In contrast, pre-eclampsia cases had lower mean leptin concentrations than controls for those women with a pre-pregnancy body mass index above 25 kg/m2. Other factors in addition to the level of adiposity may therefore influence serum leptin concentrations in pre-eclamptic pregnant women. Our results suggest the possibility that leptin, like several other placentally derived substances (e.g. steroid hormones, eicosanoids and cytokines), may be involved in the pathogenesis of pre-eclampsia. Further work is needed to confirm our findings and to assess the metabolic importance and determinants of leptin concentrations in uncomplicated and pre-eclamptic pregnancies.

Second trimester ultrasound and biochemical markers are largely independent in fetuses with trisomy 21, however significant correlations between the two were observed in the present series. These may be important in screening protocols that combine second trimester ultrasound and biochemical markers.