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Joshua A Copel

Publications and source records attributed to Joshua A Copel.

15 recordsLinked to original sources

Serum and urine inhibin A but not free activin A are endocrine biomarkers of severe pre-eclampsia.

OBJECTIVE: Elevation of total serum inhibin A and activin A has been interpreted as evidence of placental dysfunction in women who develop pre-eclampsia. We sought to evaluate serum and urine levels of inhibin A and free activin A in normal and hypertensive pregnancies. STUDY DESIGN: Inhibin A and free activin A were measured by immunoassay in simultaneously collected serum and urine samples from 75 women: (1) severe pre-eclampsia (n = 30); (2) mild pre-eclampsia (n = 11); (3) chronic hypertension (n = 9); (4) pregnant control women (n = 16); and (5) nonpregnant control women (n = 9). Urine levels were normalized to milligrams urine creatinine, and fractional excretions were calculated. RESULTS: Serum and urine inhibin A were increased and fractional excretion was decreased in pregnancy. Serum, urine, and fractional excretion of inhibin A were increased in severe pre-eclampsia, compared with other gravidas. The only difference observed in free activin A was a decrease in serum free activin A in chronic hypertension, compared with severe pre-eclampsia and pregnant control women. Urine inhibin A showed the greatest discrimination between severe pre-eclampsia and pregnant control women: a cut-off of 45 pg/mg urine creatinine had 96.8% sensitivity, 87.5% specificity, and 93.6% accuracy. Women with urine inhibin A greater than 90 pg/mg urine creatinine had a 17-fold relative risk (95% confidence interval 9.7-459.5) of a clinically indicated delivery due to pre-eclampsia. CONCLUSION: Serum and urine levels of inhibin A are altered in severe pre-eclampsia. Urine inhibin A may have application in the diagnosis and management of pre-eclampsia. Those with chronic hypertension have lower serum but not urine free activin A levels, compared with severe pre-eclampsia and mild pre-eclampsia.

Activins↗

Prior cesarean delivery is not associated with an increased risk of stillbirth in a subsequent pregnancy: analysis of U.S. perinatal mortality data, 1995-1997.

OBJECTIVE: An association between cesarean delivery and an increased risk of stillbirth in a subsequent pregnancy has been reported in the United Kingdom. This study investigated the association between prior cesarean delivery and unexplained intrauterine fetal demise at term in the United States. STUDY DESIGN: We conducted a cross-sectional study using the U.S. perinatal mortality data (1995 to 1997). Women aged 15 to 44 years with singleton term (37 weeks or longer) pregnancies were included in the analysis. Study groups were defined as pregnant women with a prior cesarean delivery (prior cesarean delivery) and women with no prior cesarean delivery (no cesarean delivery). Adjustments were made for maternal age, race, underlying medical conditions, and fetal congenital abnormalities. The Cochran-Mantel-Haenszel method was used for relative risk estimation at the 95% confidence interval calculation. RESULTS: A total of 11,061,599 deliveries of singleton pregnancies were recorded in the United States from January 1, 1995, to December 31, 1997. The cesarean delivery rate was 19.6%. The crude term intrauterine fetal demise rate was 1.5 per 1000 births for no cesarean delivery and 1.3 per 1000 births for prior cesarean delivery. After correction for parity greater than 1, congenital anomalies, and underlying maternal medical conditions, term intrauterine fetal demise rates were 0.6 and 0.4 per 1000 births for no cesarean delivery and prior cesarean delivery, respectively. Restriction of the analysis to women with only 1 prior delivery resulted in term intrauterine fetal demise rates of 0.8 and 0.7 per 1000 births for no cesarean delivery and prior cesarean delivery, respectively (relative risk 0.90; 95% confidence interval 0.76-1.06). CONCLUSION: A prior cesarean delivery is not associated with an increased risk of stillbirth in a subsequent pregnancy.

Adult↗

A low vaginal "pool" amniotic fluid glucose measurement is a predictive but not a sensitive marker for infection in women with preterm premature rupture of membranes.

OBJECTIVE: We sought to identify the use of vaginal amniotic fluid (vAF) glucose measurements in predicting infection of the amniotic fluid retrieved by transabdominal amniocentesis (aAF) in women with preterm premature rupture of the membranes (PPROM). STUDY DESIGN: Fluid was retrieved by aAF was retreived from 35 consecutive women with PPROM on whom an amniocentesis was clinically indicated to rule out intra-amniotic infection/inflammation and successfully completed. aAF was cultured for aerobic, anaerobic bacteria, Ureaplasma and Mycoplasma species. Clinical laboratory analysis for aAF included glucose concentration, Gram stain, lactate dehydrogenase, and white and red blood cell count. vAF was analyzed only for glucose concentration. Glucose concentration for the paired abdominal-vaginal AF samples (aAF-vAF) was determined by using well-established clinical and research laboratory methods. At the end of enrollment we stratified our patients into 2 groups: (1) positive microbial cultures (+)AFC (n = 17, gestational age [GA]: 27.3 +/- 0.7 weeks) or (2) negative microbial cultures (-)AFC (n = 18, GA: 31.3 +/- 0.5 weeks). Cohen kappa measure of concordance and receiver operating characteristic (ROC) curve analysis were used to test the ability of the vaginal "pool" glucose measurements to discriminate between women with positive or negative AF cultures. RESULTS: Women with (+)AFC ruptured and delivered at an earlier GA compared with the (-)AFC group (p < .001). The latency period was similar (P = .35). There was a significant linear correlation between aAF and vAF glucose concentrations (r = 0.783, P < .001). Women with intra-amniotic infection (IAI) had significantly lower aAF [mean +/- SEM (+)AFC: 11.4 +/- 3.2 vs (-)AFC 23.0 +/- 2.8 mg/dL, P = .01] and vAF glucose levels [(+)AFC: 10.1 +/- 2.8 vs (-)AFC: 19.8 +/- 2.9 mg/dL, P = .02] compared with the noninfected group. Cohen kappa measure of concordance indicated "substantial" agreement between aAF and vAF glucose measurements (kappa = 0.719, 95% CI = 0.491-0.947). The sensitivity of the vAF glucose level to detect IAI ranged from 82% to 47%, whereas specificity ranged from 100% to 56% depending on the threshold we used. A vaginal "pool" (vAF) glucose measurement less than 5 mg/dL had 47.1% sensitivity, 100% specificity, 100% positive predictive value, 66.7% negative predictive value, and 74.2% accuracy in identifying women with (+)AFC. CONCLUSION: Vaginal glucose determination is a readily available, inexpensive, rapid AF marker that can be measured practically in any clinical laboratory. vAF glucose measurements less than 5 mg/dL have predictive value, but low sensitivity for detection of IAI.

Adult↗

Trends in fetal echocardiography and implications for clinical practice: 1985 to 2003.

OBJECTIVE: The purpose of this study was to determine whether patterns of referral for fetal echocardiography (FE) and the subsequent yield for structural congenital heart disease (CHD) have changed between 1985 and 2003. METHODS: All FE performed between 1985 and 2003 at Yale-New Haven Hospital was reviewed. The primary indication for study and the presence of structural CHD were recorded, and data were analyzed for trends. Linear regression with Pearson coefficient calculation and Mantel-Haenszel chi(2) analysis were performed (P < .05 significant). RESULTS: Between 1985 and 2003, 10,806 patients had FE at Yale-New Haven Hospital, and 774 cases of structural CHD were detected. The annual number of studies and rate of detected structural CHD remained constant through the study period. There was a significant increase in the proportion of studies for diabetes, maternal structural CHD, suspicious 4-chamber heart, and family history of cardiac disease. There was a significant decrease in the proportion of studies for a previous child with structural CHD, cardiac teratogen exposure, other fetal anomalies, aneuploidy, fetal arrhythmia, and nonimmune hydrops. The percentage of structural CHD detected by indication remained constant through the study period. Subgroup analysis of diabetes revealed an increase in class B diabetes, while classes C and D remained stable. CONCLUSIONS: This is one of the largest series of FE and suggests that the pattern of indications has changed since 1985. Specifically, referral for diabetes (mostly class B) has increased without a change in yield of structural CHD by indication for sonography. The changing referral patterns reflect a change in obstetric demographics and has implications for obstetric care.

Chi-Square Distribution↗

Sonographic myometrial thickness predicts the latency interval of women with preterm premature rupture of the membranes and oligohydramnios.

OBJECTIVE: Term labor is associated with global thinning of the myometrium. We hypothesized that a thickened myometrium at the time of preterm premature rupture of membranes (PPROM) predicts less myometrial wall stress and, consequently, a longer latency interval. STUDY DESIGN: Myometrial thickness was measured prospectively in 76 pregnant women enrolled in the following groups: PPROM (n=28, mean [range], gestational age [GA]: 29.5 weeks [w] [21.0 w-33.0 w]), preterm nonlabor control group (P-CTR), (n=21, GA: 27.5 w [23.0 w-32.0 w]) and term nonlabor control (T-CTR) (n=27, GA: 38.6 w [37.0 w-41.6 w]). All PPROM women had oligohydramnios (AFI: 1.4 cm [0.0 cm-5.1 cm]). MT was measured ultrasonographically at the midanterior, fundal, posterior, and lower uterine segment wall in cases and controls with an intraoperator variability <10%. RESULTS: Women in the PPROM group displayed uniform thickness of the uterine body (mean +/- SEM, anterior: 10.6 +/- 0.6 mm, fundal: 10.7 +/- 0.7 mm, posterior: 8.9 +/- 0.5 mm, P=.078). At midanterior site the myometrium of the PPROM group was thicker compared to both P-CTR (P < .001) and T-CTR (P=.025) groups. This difference was preserved at the fundus (PPROM vs P-CTR, P < .001; PPROM vs T-CTR, P=.015). There was a positive correlation between fundal MT and latency period (r=0.43, P=0.02) that persisted after adjusting for GA (P=.04). A fundal MT less than 12.1 mm was 93.7% sensitive and 63.6% specific for the identification of women whose latency period was less than 120 hours. CONCLUSION: Significant thickening of the anterior and fundal walls of the uterus follows PPROM. A thick myometrium in nonlaboring patients with PPROM is associated with longer latency interval. Sonographic evaluation of MT may represent an alternative clinical tool for the prediction of a short latency interval in women with PPROM.

Adult↗

Three- and 4-dimensional ultrasound in obstetrics and gynecology: proceedings of the American Institute of Ultrasound in Medicine Consensus Conference.

The American Institute of Ultrasound in Medicine convened a panel of physicians and scientists with interest and expertise in 3-dimensional (3D) ultrasound in obstetrics and gynecology to discuss the current diagnostic benefits and technical limitations in obstetrics and gynecology and consider the utility and role of this type of imaging in clinical practice now and in the future. This conference was held in Orlando, Florida, June 16 and 17, 2005. Discussions considered state-of-the-art applications of 3D ultrasound, specific clinical situations in which it has been found to be helpful, the role of 3D volume acquisition for improving diagnostic efficiency and patient throughput, and recommendations for future investigations related to the utility of volume sonography in obstetrics and gynecology.

Female↗

First trimester ultrasound screening is effective in reducing postterm labor induction rates: a randomized controlled trial.

OBJECTIVE: This study was designed to test the null hypothesis that first trimester ultrasound crown-rump length measurement for gestational age determination will result in no difference in the rate of induction of labor for postterm pregnancy, compared with second trimester biometry alone. STUDY DESIGN: Two hundred eighteen women were randomly assigned to receive either first trimester ultrasound screening or second trimester ultrasound screening to establish the expected date of confinement. Sample size was calculated by using a 2-tailed alpha=.05 and power (1-beta)=80%. Data were analyzed with chi(2) and Fisher exact tests. RESULTS: Of 104 women randomly assigned to the first trimester screening group, 41.3% had their gestational age adjusted on the basis of the crown-rump length measurement. Of 92 women randomly assigned to the second trimester screening group, 10.9% were corrected as a result of biometry (P <.001, relative risk=0.26, 95% CI=0.15-0.46). Five women in the first trimester screening group and 12 women in the second trimester screening group had labor induced for postterm pregnancy (P=0.04, relative risk=0.37, 95% CI=0.14-0.96). CONCLUSION: The application of a program of first trimester ultrasound screening to a low-risk obstetric population results in a significant reduction in the rate of labor induction for postterm pregnancy.

Adolescent↗

Fetal stroke.

Fetal stroke, or that which occurs between 14 weeks of gestation and the onset of labor resulting in delivery, has been associated with postnatal epilepsy, mental retardation, and cerebral palsy. The entity is caused by antenatal ischemic, thrombotic, or hemorrhagic injury. We present seven new cases of fetal stroke diagnosed in utero and review the 47 cases reported in the literature. Although risk factors could not be assigned to 50% of the fetuses with stroke, the most common maternal conditions associated with fetal stroke were alloimmune thrombocytopenia and trauma. Magnetic resonance imaging was optimal for identifying fetal stroke, and prenatal imaging revealed hemorrhagic lesions in over 90% of studies; porencephalies were identified in just 13%. Seventy-eight percent of cases with reported outcome resulted in either death or adverse neurodevelopmental outcome at ages 3 months to 6 years. Fetal stroke appears to have different risk factors, clinical characteristics, and outcomes than other perinatal or childhood stroke syndromes. A better understanding of those risk factors predisposing a fetus to cerebral infarction may provide a basis for future therapeutic intervention trials. Ozduman K, Pober BR, Barnes P, Copel JA, Ogle EA, Duncan CC, Ment LR. Fetal stroke.

Brain↗

Diagnosis of cardiac defects: where we've been, where we are and where we're going.

There has been tremendous development in the field of prenatal diagnosis of cardiac disease in the last 30 years. Early work centered on the technical aspects of providing an accurate assessment of cardiac structure and function. Techniques of fetal cardiac screening have been developed and utilized throughout the world. More recently, investigators have begun to explore the ramifications of fetal cardiac diagnosis by assessing measures of outcome. In this article, the field of fetal echocardiography, as a screening tool for identifying congenital heart disease, and its impact on disease outcome is reviewed.

Echocardiography↗

Hypoechogenicity of fetal long bones: a new ultrasound marker for arthrogryposis.

OBJECTIVE: To demonstrate osteopenia associated with arthrogryposis. METHODS & RESULTS: We describe 3 cases of fetal arthrogryposis seen prenatally with the sonographic feature of severe hypoechogenicity of the long bones. This manifestation of presumed osteopenia is thought to represent osteoporosis secondary with absent fetal movement. CONCLUSION: We describe hypoechogenicity of the fetal bones as a new sonographic feature of arthrogryposis.

Abnormalities, Multiple↗

Assessment of blood flow velocity waveforms of the pulmonary circulation by multigate spectral Doppler scanning and traditional pulsed Doppler ultrasonography.

OBJECTIVE: To assess (1) pulmonary artery and peripheral pulmonary blood flow by using a multigate spectral Doppler system and standard pulsed color Doppler ultrasonography and (2) the reproducibility of peripheral pulmonary artery blood flow velocity waveforms. METHODS: Thirty-three women were enrolled in the study Fetal pulmonary artery flow velocity waveforms were investigated by multigate spectral Doppler scanning and traditional pulsed Doppler ultrasonography plus color flow mapping. To establish the relationship between these 2 methods, we calculated the correlation coefficient, coefficient of variation, and limits of agreement. RESULTS: The 2 methods were not significantly correlated. The range of measurement agreement for these 2 methods suggests that there is a significant difference between the main and peripheral pulmonary artery blood flow, and the difference should be taken into account in the interpretation of Doppler flow velocity studies of the pulmonary artery. CONCLUSIONS: Multigate spectral Doppler scanning with power Doppler imaging may be a better way to assess the average flow impedance in a highly vascularized organ. This technique supplies a large number of Doppler signals in the region of interest and offers a quantified range of Doppler measurements, improving our understanding of fetal hemodynamics.

Blood Flow Velocity↗

Mild cerebral ventriculomegaly in fetuses: characteristics and outcome.

BACKGROUND: A fetal ultrasonographic (US) finding of mild ventriculomegaly (MVM) is not uncommon, but its prognostic significance is not clearly defined. OBJECTIVE: To evaluate the clinical and US characteristics and outcome of fetuses with mild dilatation of the cerebral lateral ventricles. PATIENTS AND METHODS: We reviewed the medical records of 34 consecutive fetuses with US evidence of MVM (atrial width of the lateral ventricles = 10-15 mm) at 18-35 weeks of gestation. RESULTS: Of the 34 fetuses with MVM, 7 underwent karyotype examination and were normal. In 4 of the 34 fetuses the pregnancy was terminated (at autopsy: 1 was normal, 2 had hydrocephalus and for 1 the parents refused autopsy). Eight fetuses that were delivered had congenital malformations; 3 of them died during the early neonatal period. In 6 of the 8 fetuses with malformations, karyotypes were available and 3 had chromosomal aberrations (trisomy 18, 45XO, and triploidy 69XXX). Spontaneous in utero resolution of the MVM occurred in 10/30 (33.3%) of the cases. Of the 26 infants that remained in follow-up, 16 (61.1%) were normal at 1 month and at 2 years of age. CONCLUSIONS: Our data confirm those of previous reports as to the characteristics and outcome of MVM. In the setting of mild fetal ventriculomegaly with a normal karyotype and an absence of malformations, the outcome appears to be favorable.

Adolescent↗