Longitudinal Metabolic Profiling of Maternal Obesity, Gestational Diabetes, and Hypertensive Pregnancy Disorders.

CONTEXT: Comprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden. OBJECTIVE: To assess levels, profiles, and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM), or hypertensive disorders. DESIGN, SETTING AND PARTICIPANTS: A secondary analysis of 2 study cohorts, PREDO and RADIEL, including 741 pregnant women. MAIN OUTCOME MEASURES: We assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 [interquartile range (IQR) 12.4-13.7], 20 (IQR 19.3-23.0), and 28 (27.0-35.0) weeks of gestation. RESULTS: Across all 3 time points women with obesity [body mass index (BMI) ≥ 30kg/m2] in comparison to normal weight (BMI 18.5-24.99 kg/m2) had significantly higher levels of most very-low-density lipoprotein-related measures, many fatty and most amino acids, and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia, and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered nonsignificant after adjustment for BMI and the other pregnancy disorders. CONCLUSIONS: This study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin.

Longitudinal changes in plasma hemopexin and alpha-1-microglobulin concentrations in women with and without clinical risk factors for pre-eclampsia.

Recent studies have shown increased concentration of fetal hemoglobin (HbF) in pre-eclamptic women. Plasma hemopexin (Hpx) and alpha-1-microglobulin (A1M) are hemoglobin scavenger proteins that protect against toxic effects of free heme released in the hemoglobin degradation process. We used an enzyme-linked immunosorbent assay to analyze maternal plasma Hpx and A1M concentrations at 12-14, 18-20 and 26-28 weeks of gestation in three groups: 1) 51 women with a low risk for pre-eclampsia (LRW), 2) 49 women with a high risk for pre-eclampsia (PE) who did not develop PE (HRW) and 3) 42 women with a high risk for PE who developed PE (HRPE). The study had three aims: 1) to investigate whether longitudinal differences exist between study groups, 2) to examine if Hpx and A1M concentrations develop differently in pre-eclamptic women with small for gestational age (SGA) fetuses vs. pre-eclamptic women with appropriate for gestational age fetuses, and 3) to examine if longitudinal Hpx and A1M profiles differ by PE subtype (early-onset vs. late-onset and severe vs. non-severe PE). Repeated measures analysis of variance was used to analyze differences in Hpx and A1M concentrations between the groups. We found that the differences in longitudinal plasma Hpx and A1M concentrations in HRW compared to HRPE and to LRW may be associated with reduced risk of PE regardless of clinical risk factors. In women who developed PE, a high A1M concentration from midgestation to late second trimester was associated with SGA. There were no differences in longitudinal Hpx and A1M concentrations from first to late second trimester in high-risk women who developed early-onset or. late-onset PE or in women who developed severe or. non-severe PE.

Plasma Heme Scavengers Alpha-1-Microglobulin and Hemopexin as Biomarkers in High-Risk Pregnancies.

Women with established preeclampsia (PE) have increased plasma concentration of free fetal hemoglobin. We measured two hemoglobin scavenger system proteins, hemopexin (Hpx) and alpha-1-microglobulin (A1M) in maternal plasma using enzyme-linked immunosorbent assay during the late second trimester of pregnancy in women with high and low risk of developing PE. In total 142 women were included in nested case-control study: 42 women diagnosed with PE and 100 controls (49 randomly selected high-risk and 51 low-risk controls). The concentration of plasma A1M in high-risk controls was higher compared to low-risk controls. Women with severe PE had higher plasma A1M levels compared to women with non-severe PE. In conclusion, the concentration of plasma A1M is increased in the late second trimester in high-risk controls, suggesting activation of endogenous protective system against oxidative stress.

Prediction of pre-eclampsia and its subtypes in high-risk cohort: hyperglycosylated human chorionic gonadotropin in multivariate models.

BACKGROUND: The proportion of hyperglycosylated human chorionic gonadotropin (hCG-h) to total human chorionic gonadotropin (%hCG-h) during the first trimester is a promising biomarker for prediction of early-onset pre-eclampsia. We wanted to evaluate the performance of clinical risk factors, mean arterial pressure (MAP), %hCG-h, hCGß, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF) and mean pulsatility index of the uterine artery (Uta-PI) in the first trimester in predicting pre-eclampsia (PE) and its subtypes early-onset, late-onset, severe and non-severe PE in a high-risk cohort. METHODS: We studied a subcohort of 257 high-risk women in the prospectively collected Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) cohort. Multivariate logistic regression was used to construct the prediction models. The first model included background variables and MAP. Additionally, biomarkers were included in the second model and mean Uta-PI was included in the third model. All variables that improved the model fit were included at each step. The area under the curve (AUC) was determined for all models. RESULTS: We found that lower levels of serum PlGF concentration were associated with early-onset PE, whereas lower %hCG-h was associated with the late-onset PE. Serum PlGF was lower and hCGß higher in severe PE, while %hCG-h and serum PAPP-A were lower in non-severe PE. By using multivariate regression analyses the best prediction for all PE was achieved with the third model: AUC was 0.66, and sensitivity 36% at 90% specificity. Third model also gave the highest prediction accuracy for late-onset, severe and non-severe PE: AUC 0.66 with 32% sensitivity, AUC 0.65, 24% sensitivity and AUC 0.60, 22% sensitivity at 90% specificity, respectively. The best prediction for early-onset PE was achieved using the second model: AUC 0.68 and 20% sensitivity at 90% specificity. CONCLUSIONS: Although the multivariate models did not meet the requirements to be clinically useful screening tools, our results indicate that the biomarker profile in women with risk factors for PE is different according to the subtype of PE. The heterogeneous nature of PE results in difficulty to find new, clinically useful biomarkers for prediction of PE in early pregnancy in high-risk cohorts. TRIAL REGISTRATION: International Standard Randomised Controlled Trial number ISRCTN14030412 , Date of registration 6/09/2007, retrospectively registered.

Smooth muscle tumor of the placenta - an entrapped maternal leiomyoma: a case report.

INTRODUCTION: Neoplasms of the placenta are uncommon. Tumors arising from the placental tissue include two distinct histological types: the benign vascular tumor, chorangioma, and very rarely, choriocarcinoma. Benign leiomyomas, in contrast, are very common tumors of the uterine wall and occur in 0.1% to 12.5% of all pregnant women. However, the incorporation of uterine leiomyoma into the placenta is exceptional and raises the question of its origin. This case is possibly the first report on this kind of a placental tumor which has been examined using both immunohistochemistry and chromosome analysis. CASE PRESENTATION: A 34-year-old G4P3 Caucasian woman was followed up antenatally because of a stillbirth in her previous pregnancy. At 36 weeks' gestation, a hypoechoic, 3.6 x 4.2 cm rounded mass was noted within the placenta on ultrasound examination. Histologically, the tumor was a benign leiomyoma and this finding was supported by immunohistochemistry. The newborn infant was male. Chromosomes of the neoplasm were studied by the fluorescence in situ hybridization technique and the tumor was found to carry XX chromosomes. CONCLUSION: A rare benign smooth muscle neoplasm involving the placental parenchyma is presented. The tumor was a uterine leiomyoma of maternal origin, which had become entrapped by the placenta. This case report is of interest to the clinical specialty of obstetrics and gynecology and will advance our knowledge of the etiology of placental tumors.