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Efficacy of the genetic sonogram in a stepwise sequential protocol for down syndrome screening

Shamshirsaz, Alireza A; Ravangard, Samadh F; Turner, Garry; Borgida, Adam; Janicki, Mary Beth; Campbell, Winston A; Zelop, Carolyn; Shamshirsaz, Amirhoushang A; Spiel, Melissa; Prabulos, Anne Marie; Feldman, Deborah; Rodis, John; Ingardia, Charles J; Gurram, Padmalatha; Fuller, Kisti; Fang, Yu M; Benn, Peter; Egan, James F X
OBJECTIVES: The purpose of this study was to evaluate the efficacy of the genetic sonogram in Down syndrome screening for women who have received the stepwise sequential test. METHODS: This retrospective cohort study included women with singleton pregnancies who underwent stepwise sequential (first-trimester combined and second-trimester serum) screening and then had a genetic sonogram between March 2005 and January 2010. Stepwise sequential Down syndrome risks were multiplied by either a positive or negative likelihood ratio based on the second-trimester sonographic findings to determine the final Down syndrome risk. A final Down syndrome risk of 1:270 or higher was considered screen positive. RESULTS: A total of 6286 women fulfilled our criteria, including 17 with Down syndrome-affected fetuses. After stepwise sequential testing, the Down syndrome detection rate was 88.2% (15 of 17), and after the genetic sonogram, there was a non-significant reduction in detection to 82.4% (14 of 17; P > .05). For the 6269 unaffected pregnancies, the genetic sonogram converted 58 screen-negative results (1%) to positive and 183 screen-positive results (3.1%) to negative. The net effect was a change in the false-positive rate from 6.2% (390 of 6269) after stepwise sequential screening to 4.2% (266 of 6269) after the genetic sonogram. CONCLUSIONS: The genetic sonogram should be applied cautiously for women who have received prior prenatal screening tests. Women with screen-positive results need to be counseled that a negative sonographic result can be falsely reassuring. Conversely, for women with screen-negative results who have a risk close to the cutoff, a sonographic examination could assist in the decision of whether to accept or reject amniocentesis.
PMID: 23980222
ISSN: 0278-4297
CID: 878642

ACR Appropriateness Criteria(R) growth disturbances - risk of intrauterine growth restriction [Guideline]

Zelop, Carolyn M; Javitt, Marcia C; Glanc, Phyllis; Dubinsky, Theodore; Harisinghani, Mukesh G; Harris, Robert D; Khati, Nadia J; Mitchell, Donald G; Pandharipande, Pari V; Pannu, Harpreet K; Podrasky, Ann E; Shipp, Thomas D; Siegel, Cary Lynn; Simpson, Lynn; Wall, Darci J; Wong-You-Cheong, Jade J
Fetal growth disturbances include fetuses at risk for intrauterine growth restriction. These fetuses may have an estimated fetal weight at less than the 10% or demonstrate a plateau of fetal growth with an estimated fetal growth greater than the 10%. Uteroplacental insufficiency may play a major role in the etiology of intrauterine growth restriction. Fetuses at risk for intrauterine fetal growth restriction are susceptible to the potential hostility of the intrauterine environment leading to fetal hypoxia and fetal acidosis. Fetal well-being can be assessed using biophysical profile, Doppler velocimetry, fetal heart rate monitoring, and fetal movement counting.Fetal growth disturbances include fetuses at risk for intrauterine growth restriction. These fetuses may have an estimated fetal weight at less than the 10% or demonstrate a plateau of fetal growth with an estimated fetal growth greater than the 10%. Uteroplacental insufficiency may play a major role in the etiology of intrauterine growth restriction. Fetuses at risk for intrauterine fetal growth restriction are susceptible to the potential hostility of the intrauterine environment leading to fetal hypoxia and fetal acidosis. Fetal well-being can be assessed using biophysical profile, Doppler velocimetry, fetal heart rate monitoring, and fetal movement counting.The ACR Appropriateness Criteria(R) are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
PMID: 23867573
ISSN: 0894-8771
CID: 878652

ACR appropriateness Criteria(R) first trimester bleeding [Guideline]

Lane, Barton F; Wong-You-Cheong, Jade J; Javitt, Marcia C; Glanc, Phyllis; Brown, Douglas L; Dubinsky, Theodore; Harisinghani, Mukesh G; Harris, Robert D; Khati, Nadia J; Mitchell, Donald G; Pandharipande, Pari V; Pannu, Harpreet K; Podrasky, Anne E; Shipp, Thomas D; Siegel, Cary Lynn; Simpson, Lynn; Wall, Darci J; Zelop, Carolyn M
Vaginal bleeding is not uncommon in the first trimester of pregnancy. Ultrasound is the foremost modality for evaluating normal development of the gestational sac and embryo and for discriminating the causes of bleeding. While correlation with quantitative betaHCG and clinical presentation is essential, sonographic criteria permit diagnosis of failed pregnancies, ectopic pregnancy, gestational trophoblastic disease and spontaneous abortion. The American College of Radiology Appropriateness Criteria guidelines have been updated to incorporate recent data. A failed pregnancy may be diagnosed when there is absence of cardiac activity in an embryo exceeding 7 mm in crown rump length or absence of an embryo when the mean sac diameter exceeds 25 mm. In a stable patient with no intrauterine pregnancy and normal adnexae, close monitoring is advised. The diagnosis of ectopic pregnancy should be based on positive findings rather than on the absence of an intrauterine sac above a threshold level of betaHCG. Following abortion, ultrasound can discriminate retained products of conception from clot and arteriovenous fistulae. The American College of Radiology Appropriateness Criteria(R) are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
PMID: 23665531
ISSN: 0894-8771
CID: 878662

ACR Appropriateness Criteria(R) Clinically Suspected Adnexal Mass

Javitt, Marcia C; Glanc, Phyllis; Brown, Douglas L; Dubinsky, Theodore; Harisinghani, Mukesh G; Khati, Nadia J; Kim, Young Bae; Mitchell, Donald G; Pandharipande, Pari V; Pannu, Harpreet K; Podrasky, Ann E; Royal, Henry D; Shipp, Thomas D; Siegel, Cary Lynn; Simpson, Lynn; Wall, Darci J; Wong-You-Cheong, Jade J; Zelop, Carolyn M
ABSTRACT: Adnexal masses are a common problem clinically and imaging-wise, and transvaginal US (TVUS) is the first-line imaging modality for assessing them in the vast majority of patients. The findings of US, however, should be correlated with the history and laboratory tests, as well as any patient symptoms. Simple cysts are uniformly benign, and most warrant no further interrogation or treatment. Complex cysts carry more significant implications, and usually engender serial ultrasound(s), with a minority of cases warranting a pelvic MRI.Morphological analysis of adnexal masses with gray-scale US can help narrow the differential diagnosis. Spectral Doppler analysis has not proven useful in most well-performed studies. However, the use of color Doppler sonography adds significant contributions to differentiating between benign and malignant masses and is recommended in all cases of complex masses. Malignant masses generally demonstrate neovascularity, with abnormal branching vessel morphology. Optimal sonographic evaluation is achieved by using a combination of gray-scale morphologic assessment and color or power Doppler imaging to detect flow within any solid areas.The ACR Appropriateness Criteria(R) are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
PMID: 23358212
ISSN: 0894-8771
CID: 220312

ACR Appropriateness Criteria(R) Multiple Gestations

Dejesus, Allison SO; Javitt, MC; Glanc, P; Andreotti, RF; Bennett, GL; Brown, DL; Dubinsky, T; Harisinghani, MG; Harris, RD; Mitchell, DG; Pandharipande, PV; Pannu, HK; Podrasky, AE; Shipp, TD; Siegel, CL; Simpson, L; Wong-You-Cheong, JJ; Zelop, CM
ABSTRACT: Multiple gestations are high-risk compared with singleton pregnancies. Prematurity and intrauterine growth restrictions are the major sources of morbidity and mortality common to all twin gestations. Monochorionic twins are at a higher risk for twin-twin transfusion, fetal growth restriction, congenital anomalies, vasa previa, velamentous insertion of the umbilical cord and fetal death. Therefore, determination of multiple gestation, amnionicity and chorionicity in the first trimester is important. Follow up examinations to evaluate fetal well-being include assessment of fetal growth and amniotic fluid volume, umbilical artery Doppler, nonstress test and biophysical profile. To date, there is a paucity of literature regarding imaging schedules for follow-up. At the very least, antepartum testing in multiple gestations is recommended in all situations in which surveillance would ordinarily be performed in a singleton pregnancy.The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed biennially by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging.
PMID: 22634795
ISSN: 0894-8771
CID: 169559

Intravital high-frequency ultrasonography to evaluate cardiovascular and uteroplacental blood flow in mouse pregnancy

Khankin, Eliyahu V; Hacker, Michele R; Zelop, Carolyn M; Karumanchi, S Ananth; Rana, Sarosh
OBJECTIVE: The objective of this study is to define the ultrasonographic changes in the cardiovascular and uteroplacental circulation of normal pregnant mice compared to non-pregnant mice using high-frequency, high-resolution ultrasonography. METHODS: Ten to twelve-week-old CD-1 mice (six non-pregnant and six pregnant animals) were used for all experiments. Vevo(R) 2100 (VisualSonics) was used to evaluate the cardiovascular and uteroplacental circulation physiology. Cardiac echocardiogram and uterine artery Doppler studies were performed on all animals. Pregnant animals were evaluated on embryonic day seven (E7), thirteen (E13) and eighteen (E18). Fetal heart rate and umbilical artery Doppler flows were obtained on pregnant animals. Three-dimensional ultrasonography imaging was utilized for quantification of placental volumes. All data are presented as median {10(th)-90(th) percentiles}. RESULTS: In pregnant mice on E7 compared to non-pregnant mice, there was an increase in cardiac output (p=0.008), stroke volume (p=0.002), ejection fraction, (p=0.02) and fractional shortening (p=0.02). The maternal heart rate increased throughout gestation (p= 0.009). During pregnancy, a gestational sac was clearly visible on E7. Between E13 and E18, the fetal size and fetal heart rate increased (p=0.001) and the umbilical artery peak systolic velocity increased (p <0.001). Minimal diastolic blood flow was observed in the umbilical artery on E13, which increased slightly on day E18 (p=0.01). There was also no change in the uterine artery resistance index between non-pregnant and pregnant mice. The placental volume increased between E13 and E18 (p=0.03). CONCLUSION: Several changes noted in cardiovascular and uteroplacental systems occurring during normal murine pregnancy have striking similarities to humans and can be accurately measured using newer ultrasonographic techniques. Further studies are needed to evaluate changes in these vascular beds in mouse models of diseases such as preeclampsia and intrauterine growth restriction.
PMCID:3337859
PMID: 22544045
ISSN: 2210-7789
CID: 220032

Morbidity following primary cesarean delivery in the Danish National Birth Cohort

Jackson, Sherri; Fleege, Laura; Fridman, Moshe; Gregory, Kimberly; Zelop, Carolyn; Olsen, Jorn
OBJECTIVE: Cesarean delivery rates are on the rise in many countries, including the United States. There is mounting evidence that cesarean delivery is associated with adverse reproductive outcomes in subsequent pregnancies. The purpose of this article is to review those outcomes in a well-defined cohort of pregnant women. STUDY DESIGN: In a cohort of primigravid women from the Danish National Birth Cohort with known baseline exposure characteristics, we stratified women by method of first delivery, vaginal or cesarean, and evaluated for appearance of adverse reproductive events in subsequent pregnancies. RESULTS: After adjusting for age, body mass index, alcohol, smoking, and socioeconomic status, women who underwent cesarean delivery at first birth were at increased risk in their subsequent pregnancy for anemia (odds ratio [OR], 2.8; 95% confidence interval [CI], 2.3-3.4), placental abruption (OR, 2.3; 95% CI, 1.5-3.6), uterine rupture (OR, 268; 95% CI, 65.6-999), and hysterectomy (OR, 28.8; 95% CI, 3.1-263.8). CONCLUSION: Women who deliver their first baby with a cesarean are at increased risk of adverse reproductive outcomes in subsequent pregnancies and should be counseled accordingly.
PMID: 22051815
ISSN: 0002-9378
CID: 878672

Placental origins of angiogenic dysfunction in mirror syndrome [Case Report]

Bixel, Kristin; Silasi, Michelle; Zelop, Carolyn M; Lim, Kee-Hak; Zsengeller, Zsuzsanna; Stillman, Isaac E; Rana, Sarosh
BACKGROUNDL: Mirror syndrome is characterized by preeclampsia-like syndrome in pregnancies complicated by fetal hydrops. We describe a case of mirror syndrome associated with angiogenic dysfunction in maternal plasma and the placenta. CASE: A pregnant patient with known fetal hydrops presented at 22 weeks gestation with features of severe preeclampsia. Measurements of plasma anti- and proangiogenic factors were consistent with a profound antiangiogenic state. Immunohistochemistry of the placenta for antiangiogenic proteins showed a pattern similar to that seen in patients with severe preeclampsia. CONCLUSION: Angiogenic imbalance may also be responsible for the preeclampsia-like condition seen in mirror syndrome.
PMID: 22150085
ISSN: 1064-1955
CID: 219962

ACR Appropriateness Criteria(R) Assessment of Gravid Cervix

Glanc P; Andreotti RF; Lee SI; Dejesus Allison SO; Bennett GL; Brown DL; Dubinsky T; Javitt MC; Mitchell DG; Podrasky AE; Shipp TD; Siegel CL; Wong-You-Cheong JJ; Zelop CM
ABSTRACT: It is well recognized that preterm birth is the leading cause of perinatal mortality and morbidity. There is a significant association between cervix length and preterm birth risk. Most authorities consider a cervical length <3 cm as the lower limit of normal. A cervical length >3 cm has a high negative predictive value for delivery less than 34 weeks. A cervical length of <15 mm is moderately predictive ( approximately 70%) of preterm birth within 48 hours. Cervical length is normally distributed and should remain relatively constant until the third trimester. Transabdominal US is the least reliable method of cervical length assessment. The most reliable method of documenting cervical length is transvaginal ultrasound (TVUS). Transperineal US is an alternative for imaging if TVUS is contraindicated, such as with premature rupture of membranes. However, the resolution is decreased compared to TVUS. Short cervix length is the single most important predictive finding for premature delivery. This observation should prompt consultation for high risk obstetrical care and consideration of other management options such as cerclage or activity restriction.The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed biennially by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging
PMID: 22124410
ISSN: 1536-0253
CID: 146237

Does antidepressant use attenuate the risk of a major depressive episode in pregnancy?

Yonkers, Kimberly A; Gotman, Nathan; Smith, Megan V; Forray, Ariadna; Belanger, Kathleen; Brunetto, Wendy L; Lin, Haiqun; Burkman, Ronald T; Zelop, Carolyn M; Lockwood, Charles J
BACKGROUND: Many women become pregnant while undergoing antidepressant treatment and are concerned about continuing antidepressant medication. However, antidepressant discontinuation may increase the risk of a new episode of major depressive disorder. We sought to estimate differences in the risk of developing a new major depressive episode among pregnant and postpartum women with recurrent illness who either did or did not use antidepressants. METHODS: Participants were recruited from obstetrical settings; we analyzed a subgroup of 778 women with a history of a depressive disorder. Diagnoses were determined by the Composite International Diagnostic Interview administered twice in pregnancy and once after delivery. We used Cox Regression to model onset of a major depressive episode with a time-dependent predictor of antidepressant use. RESULTS: There was no clear difference in risk of a major depressive episode between women who took antidepressants and women who did not (hazard ratio [HR] = 0.88; 95% CI = 0.51-1.50). After accounting for antidepressant use, clearly hazardous factors included 4 or more depressive episodes before pregnancy (HR = 1.97; 95% CI = 1.09-3.57), black race (HR = 3.69; 95% CI = 2.16-6.30), and Hispanic ethnicity (HR = 2.33; 95% CI = 1.47-3.69). CONCLUSIONS: Failure to use or discontinuation of antidepressants in pregnancy did not have a strong effect on the development of a major depressive episode. Women with 4 or more episodes before pregnancy were at high risk of a major depressive episode, independent of antidepressant use. Black and Hispanic women also were at high risk of a major depressive episode, but it is possible that this effect is attributable to unmeasured factors.
PMCID:3188383
PMID: 21900825
ISSN: 1044-3983
CID: 219932