First-trimester or second-trimester screening, or both, for Down's syndrome

BACKGROUND: It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters.METHODS: Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency).RESULTS: First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening.CONCLUSIONS: First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down's syndrome, with low false positive rates

First-Trimester or Second-Trimester Screening, or Both, for Down's Syndrome

BACKGROUND It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters. METHODS Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement ofalpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency). RESULTS First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening. CONCLUSIONS First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection ofDown's syndrome, with low false positive rates

Mechanism of increased maternal serum total activin A and inhibin A in preeclampsia

OBJECTIVE: To determine whether increased levels of maternal serum total activin A and inhibin A in preeclampsia are related to total blood volume, urinary clearance, or placental production. STUDY DESIGN: Activin A and inhibin A levels were measured in preeclamptic subjects and matched normotensive gravidas. In a subset of preeclamptic subjects (n = 21) and controls (n = 30), we performed blood volume studies. In an overlapping subset of preeclamptic subjects (n = 56), creatinine clearance results were available. Placental tissue was obtained from six preeclamptics and matched normotensive gravida for analysis of activin A and inhibin A mRNA expression. RESULTS: Maternal serum levels of inhibin A but not activin A were significantly negatively correlated with blood volume in preeclampsia (r(2) =.26, P =.017, and r(2) =.02, P =.44, respectively). Levels of both proteins were negatively correlated to creatinine clearance (r(2) =.29, P <.0001, and r(2) =.15, P =.003, respectively). Placental mRNA expression for both the alpha and betaA subunits was increased in preeclampsia (P =.038 and.049, respectively). CONCLUSION: Although placental mRNA expression of the subunits for both analytes is increased in preeclampsia, the increased levels of activin A appear to be more specifically a reflection of increased placental production than do the increased levels of inhibin A

Stacking Machine Learning Algorithms for Biomarker-Based Preoperative Diagnosis of a Pelvic Mass

Objective: To identify the most predictive parameters of ovarian malignancy and develop a machine learning (ML) based algorithm to preoperatively distinguish between a benign and malignant pelvic mass. Methods: Retrospective study of 70 predictive parameters collected from 140 women with a pelvic mass. The women were split into a 3:1 &ldquo;training&rdquo; to &ldquo;testing&rdquo; dataset. Feature selection was performed using Gini impurity through an embedded random forest model and principal component analysis. Nine unique ML classifiers were assessed across a variety of model-specific hyperparameters using 25 bootstrap resamples of the training data. Model predictions were then combined into an ensemble stack by LASSO regression. The final ensemble stack and individual classifiers were then applied to the testing dataset to assess model performance. Results: Feature selection identified HE4, CA125, and transferrin as three predictive parameters of malignancy. Assessment of the ensemble stack on the testing dataset outperformed all individual ML classifiers in predicting malignancy. The ensemble stack demonstrated an accuracy of 97.1%, a receiver operating characteristic (ROC) area under the curve (AUC) of 0.951, and a sensitivity of 93.3% with a specificity of 100%. Conclusions: Combining the measurement of three distinct biomarkers with the stacking of multiple ML classifiers into an ensemble can provide valuable preoperative diagnostic predictions for patients with a pelvic mass

Thyroperoxidase and thyroglobulin antibodies in early pregnancy and placental abruption

OBJECTIVE: To estimate the relationship between thyroid antibodies and placental abruption. METHODS: This cohort study assesses thyroperoxidase and thyroglobulin antibodies in relation to placental abruption among 10,062 women with singleton viable pregnancies (from the First and Second Trimester Risk of Aneuploidy [FaSTER] trial). A thyroperoxidaseantibody cutoff of 50 international units/mL is used for comparison with published data from another cohort. RESULTS: Women with elevated thyroperoxidase antibody levels in the first and second trimesters have a higher rate of placental abruption than antibody-negative women. This relationship is less strong in the first trimester (1.51% compared with 0.83%; odds ratio [OR], 1.83; 95% confidence interval [CI], 0.99–3.37) than in the second trimester (1.78% compared with 0.82%; OR, 2.20; 95% CI, 1.21–3.99). A similar, but weaker, relationship is present forthyroglobulin antibodies. Sixty-four of 782 thyroperoxidase antibody-positive pregnancies without abruption become negative by the second trimester; one pregnancy with abruptionbecomes antibody-positive. Odds ratios for pregnancies with both thyroperoxidase andthyroglobulin antibody elevations are also higher (first trimester: OR, 2.10; 95% CI, 0.91–4.86; second trimester: OR, 2.73; 95% CI, 1.17–6.33). CONCLUSION: The present data confirm an association between thyroid antibody elevations and placental abruption described in a recent report. These findings, however, do not provide support for recommending routine testing for thyroid antibodies during pregnancy. LEVEL OF EVIDENCE: I