Objective We sought to perform validation studies of previously published and newly derived first-trimester metabolomic algorithms for prediction of early preeclampsia (PE). Study Design Nuclear ...magnetic resonance–based metabolomic analysis was performed on first-trimester serum in 50 women who subsequently developed early PE and in 108 first-trimester controls. Random stratification and allocation was used to divide cases into a discovery group (30 early PE and 65 controls) for generation of the biomarker model(s) and a validation group (20 early PE and 43 controls) to ensure an unbiased assessment of the predictive algorithms. Cross-validation testing on the different algorithms was performed to confirm their robustness before use. Metabolites, demographic features, clinical characteristics, and uterine Doppler pulsatility index data were evaluated. Area under the receiver operator characteristic curve (AUC), 95% confidence interval (CI), sensitivity, and specificity of the biomarker models were derived. Results Validation testing found that the metabolite-only model had an AUC of 0.835 (95% CI, 0.769–0.941) with a 75% sensitivity and 74.4% specificity and for the metabolites plus uterine Doppler pulsatility index model it was 0.916 (95% CI, 0.836–0.996), 90%, and 88.4%, respectively. Predictive metabolites included arginine and 2-hydroxybutyrate, which are known to be involved in vascular dilation, and insulin resistance and impaired glucose regulation, respectively. Conclusion We found confirmatory evidence that first-trimester metabolomic biomarkers can predict future development of early PE.
First-trimester metabolomic detection of late-onset preeclampsia Bahado-Singh, Ray O., MD, MBA; Akolekar, Ranjit, MD; Mandal, Rupasri, PhD ...
American journal of obstetrics and gynecology,
2013, January 2013, 2013-Jan, 2013-01-00, 20130101, Letnik:
208, Številka:
1
Journal Article
Recenzirano
Objective We sought to identify first-trimester maternal serum biomarkers for the prediction of late-onset preeclampsia (PE) using metabolomic analysis. Study Design In a case-control study, nuclear ...magnetic resonance–based metabolomic analysis was performed on first-trimester maternal serum between 11+0 -13+6 weeks of gestation. There were 30 cases of late-onset PE, ie, requiring delivery ≥37 weeks, and 59 unaffected controls. The concentrations of 40 metabolites were compared between the 2 groups. We also compared 30 early-onset cases to the late-onset group. Results A total of 14 metabolites were significantly elevated and 3 significantly reduced in first-trimester serum of late-onset PE patients. A complex model consisting of multiple metabolites and maternal demographic characteristics had a 76.6% sensitivity at 100% specificity for PE detection. A simplified model using fewer predictors yielded 60% sensitivity at 96.6% specificity. Strong separation of late- vs early-onset PE groups was achieved. Conclusion Significant differences in the first-trimester metabolites were noted in women who went on to developed late-onset PE and between early- and late-onset PE.
Objective The objective of the study was to identify metabolomic markers in maternal first-trimester serum for the detection of fetal congenital heart defects (CHDs). Study Design Mass spectrometry ...(direct injection/liquid chromatography and tandem mass spectrometry) and nuclear magnetic resonance spectrometry–based metabolomic analyses were performed between 11 weeks' and 13 weeks 6 days' gestation on maternal serum. A total of 27 CHD cases and 59 controls were compared. There were no known or suspected chromosomal or syndromic abnormalities indicated. Results A total of 174 metabolites were identified and quantified using the 2 analytical methods. There were 14 overlapping metabolites between platforms. We identified 123 metabolites that demonstrated significant differences on a univariate analysis in maternal first-trimester serum in CHD vs normal cases. There was a significant disturbance in acylcarnitine, sphingomyelin, and other metabolite levels in CHD pregnancies. Predictive algorithms were developed for CHD detection. High sensitivity (0.929; 95% confidence interval CI, 0.92–1.00) and specificity (0.932; 95% CI, 0.78–1.00) for CHD detection were achieved (area under the curve, 0.992; 95% CI, 0.973–1.0). Conclusion In the first such report, we demonstrated the feasibility of the use of metabolomic developing biomarkers for the first-trimester prediction of CHD. Abnormal lipid metabolism appeared to be a significant feature of CHD pregnancies.
Objective We evaluated whether improvements in pregnancy outcomes after treatment of mild gestational diabetes mellitus differed in magnitude on the basis of fetal gender. Study Design This is a ...secondary analysis of a masked randomized controlled trial of treatment for mild gestational diabetes mellitus. The results included preeclampsia or gestational hypertension, birthweight, neonatal fat mass, and composite adverse outcomes for both neonate (preterm birth, small for gestational age, or neonatal intensive care unit admission) and mother (labor induction, cesarean delivery, preeclampsia, or gestational hypertension). After stratification according to fetal gender, the interaction of gender with treatment status was estimated for these outcomes. Results Of the 469 pregnancies with male fetuses, 244 pregnancies were assigned randomly to treatment, and 225 pregnancies were assigned randomly to routine care. Of the 463 pregnancies with female fetuses, 233 pregnancies were assigned randomly to treatment, and 230 pregnancies were assigned randomly to routine care. The interaction of gender with treatment status was significant for fat mass ( P = .04) and birthweight percentile ( P = .02). Among women who were assigned to the treatment group, male offspring were significantly more likely to have both a lower birthweight percentile (50.7 ± 29.2 vs 62.5 ± 30.2 percentile; P < .0001) and less neonatal fat mass (487 ± 229.6 g vs 416.6 ± 172.8 g; P = .0005,) whereas these differences were not significant among female offspring. There was no interaction between fetal gender and treatment group with regard to other outcomes. Conclusion The magnitude of the reduction of a newborn's birthweight percentile and neonatal fat mass that were related to the treatment of mild gestational diabetes mellitus appears greater for male neonates.
Abstract Fetal MRI is now a well-established imaging modality for the diagnostic evaluation of fetuses with congenital anomalies. In this article, the authors provide a brief overview of the physical ...principles involved in fetal MRI imaging, the sequences that are used in clinical practice today, current indications, and limitations. A review of current evidence supports the following indications for fetal MRI: suspected central nervous system anomalies, neck and oropharyngeal masses, diaphragmatic hernia, abdominal masses or bowel pathology not fully characterized by ultrasonography, and suspected fetal infection. Other indications should be decided on a case-by-case basis with close collaboration between the departments of maternal–fetal medicine and radiology. More research is needed to determine the role of fetal MRI in functional neuroimaging at higher magnetic field strengths (3 T).
Objective The objective of the study was to examine the effect of selective fetoscopic laser photocoagulation (SFLP) vs serial amnioreduction (AR) on perinatal mortality in severe twin-twin ...transfusion syndrome (TTTS). Study Design This was a 5 year multicenter, prospective, randomized controlled trial. The primary outcome variable was 30 day postnatal survival of donors and recipients. Results There was no statistically significant difference in 30-day postnatal survival between SFLP or AR treatment for donors at 55% (11 of 20) vs 55% (11 of 20) ( P = 1.0, odds ratio OR 1, 95% confidence interval CI 0.242 to 4.14) or recipients at 30% (6 of 20) vs 45% (9 of 20) ( P = .51, OR 1.88, 95% CI 0.44 to 8.64). There was no difference in 30 day survival of 1 or both twins on a per-pregnancy basis between AR at 75% (15 of 20) and SFLP at 65% (13 of 20) ( P = .73, OR 1.62, 95% CI 0.34 to 8.09). Overall survival (newborns divided by the number of fetuses treated) was not statistically significant for AR at 60% (24 of 40) vs SFLP 45% (18 of 40) ( P = .18, OR 2.01, 95% CI 0.76 to 5.44). There was a statistically significant increase in fetal recipient mortality in the SFLP arm at 70% (14 of 20) vs the AR arm at 35% (7 of 20) ( P = .25, OR 5.31, 95% CI 1.19 to 27.6). This was offset by increased recipient neonatal mortality of 30% (6 of 20) in the AR arm. Echocardiographic abnormality in recipient twin Cardiovascular Profile Score is the most significant predictor of recipient mortality ( P = .055, OR 3.025/point) by logistic regression analysis. Conclusion The outcome of the trial did not conclusively determine whether AR or SFLP is a superior treatment modality. TTTS cardiomyopathy appears to be an important factor in recipient survival in TTTS.
Objective The purpose of this study was to determine whether nuclear magnetic resonance–based metabolomic markers in first-trimester maternal serum can detect fetuses with trisomy 18. Study Design ...This was a study of pregnancies between 11 weeks and 13 weeks 6 days' gestation. We analyzed 30 cases of trisomy 18 and a total of 114 euploid cases. Nuclear magnetic resonance–based metabolomic analysis was performed. A further analysis was performed that compared 30 cases with trisomy 18 and 30 trisomy 21 (T21) cases. Results Metabolomic markers were sensitive for trisomy 18 detection. A combination of 2-hydroxybutyrate, glycerol and maternal age had a 73.3% sensitivity and 96.6% specificity for trisomy 18 detection, with an area under the receiver operating curve: 0.92 ( P < .001). Other metabolite markers, which include trimethylamine, were sensitive for distinguishing trisomy 18 from T21 cases. Conclusion This is the first report of prenatal trisomy 18 detection that has been based on metabolomic analysis. Preliminary results suggest that such markers are sensitive not only for the detection of fetal trisomy 18 but also for distinguishing this aneuploidy from T21.
Abstract Ischemic placental disease is a recently coined term that describes the vascular insufficiency now believed to be an important etiologic factor in preeclampsia, intrauterine fetal growth ...restriction, and placental abruption. Given the increased risk for poor maternal and fetal outcomes, early prediction and prevention of this disorder is of significant clinical interest for many. In this article, we review the second- and third-trimester serum and ultrasound markers predictive of ischemic placental disease. Limited first-trimester data is also presented. While current studies report a statistical association between marker levels and various adverse perinatal outcomes, the observed diagnostic accuracy is below the threshold required for clinical utility. An exception to this generalization is uterine artery Doppler for the prediction of early-onset preeclampsia. Metabolomics is a relatively new analytic platform that holds promise as a first-trimester marker for the prediction of both early- and late-onset preeclampsia.
Objective We sought to ascertain the risk of reduced fetal brain growth in cases of isolated congenital heart defect (CHD) based on microcephaly at birth. Study Design In a case-control study, head ...circumference was compared in 401 newborns with isolated CHD with 401 control subjects. Microcephaly was defined as head circumference below third percentile. The rates of microcephaly in multiple different categories of major CHD were ascertained along with logistic regression analyses to determine the specific types of cardiac defects that were significantly associated with microcephaly. Results Isolated CHD in the fetus was associated with an increased risk of microcephaly as were tetralogy of Fallot, coarctation/aortic arch hypoplasia, and hypoplastic left ventricle syndrome. Tetralogy of Fallot odds ratio, 2.6; 95% confidence interval, 1.1-6.3; P < .04 and coarctation/aortic arch hypoplasia, odds ratio, 2.8; 95% confidence interval, 1.5-5.1; P < .001 were significant independent predictors of microcephaly. Conclusion The finding of microcephaly at birth in nonsyndromic CHD provides strong evidence in support of intrauterine hypoxic central nervous system damage. Potential changes in prenatal management including aggressive antepartum surveillance and earlier delivery warrant urgent consideration.
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