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Biomedical subjects

J A Copel

Publications and source records attributed to J A Copel.

At least 55 records · Page 3Linked to original sources
PubMed1997

Does a prenatal diagnosis of congenital heart disease alter short-term outcome?

Congenital heart disease (CHD) is the most common fatal congenital anomaly in the first year after birth. Fetal echocardiography has become accepted as a method of diagnosing CHD in utero, but the benefits of prenatal diagnosis have not been evaluated. We performed a cohort analysis of neonates with CHD in the absence of other life-threatening conditions. One group (I) consisted of neonates who had been diagnosed as fetuses to have CHD and who were delivered at Yale-New Haven Hospital. The other group (II) consisted of neonates who were not diagnosed to have CHD until after birth, and were either delivered at, or transferred to, the same hospital. Costs of initial hospitalization, length of hospitalization, and survival to discharge home with the parents were primary outcome measures. Our primary hypothesis was that all outcome measures would be improved by prenatal diagnosis. We also examined secondary hypotheses that these same measures would be improved among selected subgroups, including those requiring univentricular management, those amenable to biventricular repair, those with ductal dependent lesions, and those requiring any surgery during the primary admission. From January 1, 1991 to June 30, 1996 we identified 45 antenatal cases and 54 postnatal cases of CHD that met the study entry criteria. The median length (+/- SE) of initial hospitalization was 16 +/- 3.8 days in group I, and 11 +/- 3.8 days in group II (p < 0.08). The median cost of initial hospitalization was $57,678 +/- 12,340 vs. $53,604 +/- 7249 (not significant). Eighty percent of group I survived to hospital discharge compared with 67% of group II (p = 0.14). There was no difference in survival among those requiring univentricular management (64 vs. 44%), but costs and length of hospitalization were greater in group I, regardless of whether or not surgery was performed postnatally. Surgery was undertaken more often among the prenatal diagnosis group with univentricular hearts (86 vs. 56%, p < 0.05). Among those fetuses amenable to biventricular repair, survival was better (96 vs. 76%, p < 0.05) and the cost of hospitalization was lower ($30,277 +/- 16,869 vs. $64,616 +/- 9441, p = 0.06) in the prenatal diagnosis group. Prenatal diagnosis of CHD does not result in the expected savings in cost, length of hospitalization or survival in the overall group of patients. The prenatal diagnosis group showed a skew towards single ventricle physiology. Within that group a high rate of pregnancy termination results in a group of parents who are likely to choose postnatal surgery despite high short- and long-term mortality risks.

Adult↗
PubMed1997

The effect of intravascular blood transfusion on the flow velocity waveform of the portal venous system of the anemic fetus.

Our objective was to assess flow velocity waveforms of the portal venous system of the anemic fetus prior to and immediately following intravascular transfusion. Color-guided pulsed Doppler was used to obtain flow velocity waveforms from the fetal portal vein in 14 anemic fetuses that were transfused in utero for rhesus alloimmunization The portal vein velocity pattern was defined as continuous when no change in velocity during the cardiac cycle was noted. It was defined as pulsatile when a deflection of the wave was present. The flow velocity waveforms were quantified by using the ratio between the peak (highest, H) and the nadir (lowest, L) velocities (H/L ratio). Fourteen intravascular transfusions were performed. Gestational age ranged from 19.5 to 35 weeks (mean +/- SD, 26.7 +/- 5.3 weeks). The hematocrit ranged from 5.9 to 31.2% (mean +/- SD, 20.3 +/- 9%) prior to transfusion; after transfusion it was between 24.8 and 56.7% (mean +/- SD, 42 +/- 10.4%). In six cases (43%) the waveforms were pulsatile prior to transfusion; in the other eight (57%) they were continuous. The pulsatile pattern was present following transfusion in 13 cases (93%, p < 0.05). The mean of the H/L ratio was 1.3 +/- 0.38 prior to transfusion and 2.0 +/- 0.86 after transfusion (p < 0.05). Because the portal vein has continuous non-pulsatile flow in the normal fetus, the presence of pulsatility in the waves of six anemic fetuses (43%) may suggest portal hypertension. Compared to normal fetuses, there was an increased number of cases with pulsation, and even more so after transfusion. The pattern corresponds to findings in children with portal hypertension.

Anemia↗
PubMed1997

Circulating thrombomodulin levels and clinical correlates in pregnant diabetics.

The object of this study was to investigate the relationship of thrombomodulin (TM) and glycosylated hemoglobin (HbA1C) in pregnant diabetics and to determine clinical correlates. We performed a prospective cohort study of 53 patients: 25 women with insulin-dependent diabetes (group 1) and 28 with gestational diabetes (group 2). Group 1 underwent monthly determinations of HbA1C and TM. Group 2 underwent determination at 36 weeks of gestation. There was a significant difference in HbA1C between groups 1 and 2 (p=0.0005), but there was no difference in TM. There was no correlation between TM and HbA1C. TM levels correlated positively with serum creatinine (r=0.46, p=0.002), proteinuria (r=0.48, p=0.007), and duration of diabetes (r=0.41, p=0.042). TM was significantly higher in diabetics of advanced White Classification (p=0.008). With good control, TM does not appear to be elevated in a diabetic pregnancy. TM may be a marker of endothelial damage that correlates more with duration of diabetes and renal disease than with HbA1C, which reflects short-term control.

Adult↗
PubMed1997

Maternal serum uric acid levels in preeclamptic women with multiple gestations.

Our study was designed to determine serum uric acid levels and establish clinically useful cutoff values for the diagnosis of preeclampsia in twin and triplet gestations. We reviewed the medical records of 129 multiple gestations with serum uric acid levels available. Fifty-five twin gestations were complicated by preeclampsia, 51 were not. Fifteen triplet gestations were complicated by preeclampsia, and 8 were not. Preeclampsia was defined as a persistent blood pressure > or =140/90 mmHg, and proteinuria, or elevated liver enzymes, thrombocytopenia, or eclamptic seizure. Receiver operating characteristic curves were generated for twin and triplet gestations. Serum uric acid levels at different stages of gestation in twin gestations were determined. Maternal serum uric acid levels in preeclamptic twin and triplet gestations were significantly higher than those in nonpreeclamptics. Serum uric acid levels at varying gestational ages were significantly higher in preeclamptic twin gestations than in nonpreeclamptics. Maternal serum uric acid levels of 6.3 mg/dL and 6.8 mg/dL were found to be the most useful cutoff values for the diagnosis of preeclampsia in twin and triplet gestations, respectively. We conclude that compared to nonpreeclamptics, preeclamptic women with multiple gestations had significantly higher serum uric acid levels. Mean serum uric acid levels based on gestational age should be justified for the diagnosis of preeclampsia in multiple gestations.

Adult↗
PubMed1996

Prenatal detection of two different monosomic cell lines by chorionic villus sampling.

We present a prenatal case of mosaicism with at least two monosomy cell lines: one with monosomy 21 (45,XY,-21) and one missing the Y (45,X) and a possible third 46,XY in chorionic villus cell culture. Cytogenetic studies were initiated following the ultrasound detection at 11 weeks of a large cystic hygroma and in utero growth retardation. Spontaneous fetal demise occurred at 12 weeks and the pregnancy was terminated. To our knowledge, this is the first report of two different monosomic cell lines found in chorionic villus cells.

Adult↗
PubMed1996

Ultrasonographically adjusted midtrimester risk of trisomy 21 and significant chromosomal defects in advanced maternal age.

OBJECTIVE: Our purpose was to determine whether normal midtrimester ultrasonography results reduces the risk of fetal Down syndrome and any clinically significant chromosomal defects in pregnancies with advanced maternal age and to develop risk tables on the basis of age and ultrasonographic results. STUDY DESIGN: Biometry data were obtained in 4079 women between 15 and 24 weeks undergoing amniocentesis for maternal age. Expected values of humerus, femur, both combined, and abdominal circumference based on biparietal diameter were generated from a normal group. Observed/expected values of each parameter and nuchal thickness > or = 6 mm was used to screen for Down syndrome and any clinically significant chromosome defects. Receiver-operator characteristic curves were used to determine threshold screening values for each parameter. By use of stepwise logistic regression the optimal measurements for detection of chromosome anomalies were established. An abnormal ultrasonography result was defined as either abnormal biometry choroid plexus cysts or a structural defect. RESULTS: The finding of shortened humerus (observed/expected < 0.90), abnormal nuchal thickness, or an anatomic defect had the highest sensitivity for Down syndrome detection, 70.6%, p < 0.0001, whereas a short humerus, small abdominal circumference, (observed/expected < 0.92), or an anatomic defect had a sensitivity of 46.7%, p < 0.0001, for any significant chromosome defect. With a normal ultrasonography the risk of Down syndrome in a 39-year-old woman falls from 1:100 to < 1:292. CONCLUSION: A normal ultrasonography substantially reduces the risk of Down syndrome and any chromosome abnormality. This information is useful in counseling women who decline amniocentesis on the basis of maternal age.

Biometry↗
PubMed1996

Nicked free beta-subunit of human chorionic gonadotropin: a potential new marker for Down syndrome screening.

OBJECTIVE: Our purpose was to investigate maternal serum levels of nicked free beta-subunit in normal and Down syndrome pregnancies. STUDY DESIGN: Serum specimens were obtained from 64 karyotypically normal and 6 Down syndrome pregnancies before amniocentesis. Two immunoenzymometric assays for the beta- subunit of human chorionic gonadotropin were used to determine the level of free beta-subunits with peptide linkage breaks ("nicks") between residues 43 to 48. RESULTS: The mean level of nicked free beta-subunit in Down syndrome was 4.76 multiples of the median, which was significantly elevated compared with normal controls (1.07 multiples of the median, p<0.05). In 5 of 6 cases levels were > or = 2 multiples of the median, with a range of 1.96 to 15.43 multiples of the median, which was 2- to 3-fold higher than the regular free beta-subunit assay (mean level 1.53 multiples of the median, range 0.70 to 3.10 multiples of the median). In one case no nicked free-beta subunits were detectable. CONCLUSION: Our preliminary data indicate that nicked free beta-subunit of human chorionic gonadotropin might be a sensitive marker for Down syndrome screening.

Biomarkers↗
PubMed1996

Adrenal artery velocity waveforms in the appropriate and small-for-gestational-age fetus.

The purpose of this study was to compare adrenal artery flow velocity waveforms in the appropriately grown and the small-for-gestational-age fetus. Adrenal artery flow velocity waveforms were prospectively obtained from 131 appropriate- and 21 small-for-gestational-age fetuses with pulsed Doppler ultrasonography. The success rate in recording the adrenal artery was 84% (131/155) and 100% in the appropriate- and small-for-gestational-age fetuses, respectively. The pulsatility index (PI) was used to quantify the waveforms. The PI in the appropriate-for-gestational-age fetuses decreased linearly with gestational age (PI = 1.7-0.016 x gestational age). In ten small-for-gestational-age fetuses the adrenal artery PI was below the 95% confidence interval. Small-for-gestational-age fetuses with abnormal adrenal artery PI had a significantly higher incidence of fetal heart rate decelerations, preterm delivery and Cesarean sections when compared to small-for-gestational-age fetuses with normal adrenal artery PI. Our data indicate that the PI of the adrenal artery in the normal fetus decreases with advancing gestation, and they suggest that in the small-for-gestational-age fetus there is an increased blood flow to the adrenal gland. We postulate that management of the small-for-gestational-age fetus may be aided by the study of the adrenal artery flow velocity waveforms.

Adrenal Glands↗
PubMed1996

Is the fetal brain-sparing effect a risk factor for the development of intraventricular hemorrhage in the preterm infant?

The intrauterine identification of fetuses at risk of developing intraventricular hemorrhage would be helpful to the perinatologist, in light of the recent results which suggest that indomethacin given to the infant reduces the risk of developing intraventricular hemorrhage. We hypothesized that fetuses undergoing brain sparing, as identified by a lowered pulsatility index (PI) in the middle cerebral artery, and delivered prior to 34 weeks may differ in terms of being at risk for intraventricular hemorrhage from those fetuses without the brain-sparing effect. The middle cerebral artery PI was studied in 43 fetuses between 25 and 33.6 weeks' gestation. The pregnancies were complicated by pre-eclampsia, intrauterine growth restriction (IUGR) and preterm labor. A cranial sonogram was performed during the first postnatal week in all the neonates. Intraventricular hemorrhage was present in 6/22 infants with a normal middle cerebral artery PI (group A) and 0/21 with an abnormal middle cerebral artery PI (group B) (p < 0.05). The mothers of the six fetuses who developed intraventricular hemorrhage underwent preterm labor. IUGR fetuses and pre-eclampsia were more common in group B. No difference was found between the two groups when the following variables were compared: (1) gestational age at the time of the Doppler study; (2) gestational age at delivery; (3) antenatal exposure to steroids; (4) antenatal exposure to magnesium; (5) Apgar score greater than 6 at 5 min; (6) respiratory distress syndrome in the newborn; (7) necrotizing enterocolitis; (8) Cesarean section; and (9) sepsis in the infant. Although the mean birth weight was significantly lower in group B than group A, no fetus in this group developed intraventricular hemorrhage. The fetal brain-sparing effect, pre-eclampsia and IUGR were associated with a lower risk of neonatal intraventricular hemorrhage than was preterm labor. Preterm labor appears to be a key factor in the development of intraventricular hemorrhage and must be included when testing associations with intraventricular hemorrhage.

Cerebral Arteries↗
PubMed1996

Strategies for reducing the frequency of preeclampsia in pregnancies with insulin-dependent diabetes mellitus.

The object of this study was whether improving glycemic control and maintaining normal glycosylated hemoglobin (HbA1c) through pregnancy can reduce the frequency of preeclampsia. One hundred and twenty-three complete medical records of pregnant insulin-dependent diabetics (IDDM) managed at Yale-New Haven Hospital from 1983 to 1993 were reviewed. Serial HbA1c measurements and the occurrence of preeclampsia were recorded. Based on the change of HbA1c values through the pregnancy, glycemic control was categorized into four groups: group 1, high to normal; group 2, high to high; group 3, normal to normal; group 4, normal to high. The association between HbA1c change and the incidence of preeclampsia was analyzed by chi-square test and Fisher's exact test. Among 123 IDDM pregnancies, 40 (32.5%) developed preeclampsia. High HbA1c levels at any time in IDDM pregnancies were associated with an increased incidence of preeclampsia (group 1 or 2 or 4 versus group 3). Reducing HbA1c by improving glycemic control both before and during pregnancy resulted in a significantly lower incidence of pre-eclampsia (group 3 versus groups 1+2+4, p < 0.05). The best strategy for reducing the frequency of preeclampsia in IDDM pregnancies is by improving glycemic control before pregnancy.

Blood Glucose↗
PubMed1996

[Hemoglobin A1c in diabetes related to pregnancy induced hypertension].

OBJECTIVE: To test the hypothesis that the poor control of diabetes during pregnancy is correlated with a high rate of pregnancy induced hypertension (PIH). METHODS: A retrospective analysis on 146 pregnant women with diabetes mellitus of White's class B to RF (gestational diabetes was excluded) diagnosed before pregnancy was carried out in Yale-New Haven hospital, U.S.A. RESULTS: 36.3% of the diabetic women developed PIH. Hemoglobin A1c (HbA1c) levels were higher than normal in 63.7% (93 cases) of the patients during their initial prenatal visits. In the group with HbA1c score > or = 6 and White's Class D-RF, more cases developed PIH than that in groups with HbA1c score < 6 and White's Class B and C (P < 0.01, P < 0.05). CONCLUSION: Diabetic women with high HbA1c score or advanced White's Class during pregnancy were at increased risk for PIH. Good control of blood glucose level throughout pregnancy may reduce the risk of PIH in diabetic women.

Female↗
PubMed1995

Single umbilical artery: does it matter which artery is missing?

OBJECTIVE: Our purpose was to determine whether the presence of congenital anomalies in fetuses with a single umbilical artery is related to the side of the missing artery. STUDY DESIGN: During an 18-month prospective study, the side of the missing artery was identified in all pregnancies with a single umbilical artery (n = 77). Targeted sonograms and perinatal follow-up were obtained. RESULTS: The left umbilical artery was absent in 56 of 77 (73%) fetuses, compared with 21 of 77 (27%) for the right artery, p < 0.0001. Congenital anomalies occurred in 20 of 77 (26%) fetuses, with 16 of 56 (29%) in those with absence of the left artery and 4 of 21 (19%) in those with absence of the right artery, p = 0.561. Complex congenital anomalies occurred in 9 of 20 (45%) fetuses. All complex anomalies had absence of the left artery, p = 0.103. Cytogenetic abnormalities were noted in 6 fetuses, all with absence of the left artery, p = 0.181. In fetuses with a single umbilical artery as an isolated finding, small-for-gestational-age fetuses occurred in 4 of 50 (8%) pregnancies. CONCLUSION: In fetuses with a single umbilical artery the left artery is more commonly absent than the right artery. In our series cytogenetic and complex fetal anomalies occurred exclusively in fetuses with absence of the left artery. In contrast to previous reports, the incidence of small-for-gestational-age fetuses does not appear to be increased in cases of an isolated single umbilical artery.

Adolescent↗
PubMed1995

Successful in utero therapy of fetal heart block.

OBJECTIVE: Congenital complete heart block is associated with maternal autoantibodies to Ro and La proteins, which injure the fetal cardiac conduction system. We administered dexamethasone to the mothers of five fetuses with heart block caused by maternal antibodies. STUDY DESIGN: We diagnosed five cases of fetal heart block at 20 to 23 weeks and treated all mothers with dexamethasone 4 mg orally each day for the remainder of the pregnancy. All patients were positive for anti-SS-A (anti-Ro) and/or anti-SS-B (anti-La) antibodies. RESULTS: Four patients had complete heart block, and one had second-degree block. In two patients (one with complete heart block, one with second-degree heart block) the degree of block lessened with treatment. Hydrops in three complete heart block patients resolved after treatment. Maternal antibody levels did not change. Matched maternal and cord samples at delivery showed similar antibody levels. CONCLUSIONS: Complete heart block can respond to transplacental glucocorticoid therapy with improved cardiac conduction. Because there may be a concurrent myocarditis, treatment in utero may also improve cardiac contractility, leading to the observed rapid resolution of hydrops. Treatment with steroids that cross the placenta should be considered for newly diagnosed cases of complete heart block with positive antibody screens.

Adolescent↗
PubMed1995

Normal nuchal thickness in the midtrimester indicates reduced risk of Down syndrome in pregnancies with abnormal triple-screen results.

OBJECTIVE: Our purpose was to determine whether nuchal thickness measurement can identify the euploid fetuses in midtrimester pregnancies at increased risk for Down syndrome on the basis of maternal age and serum screening. STUDY DESIGN: Nuchal thickness was obtained prospectively in 651 consecutive fetuses at 14 to 21 weeks' gestation and at > or = 1:270 risk for Down syndrome on the basis of unconjugated estriol, alpha-fetoprotein, and human chorionic gonadotropin levels. The risk of Down syndrome with a normal nuchal thickness was determined. A receiver-operator characteristic curve was used to determine a serum-based risk threshold below which the risk for Down syndrome was low. The prevalence of Down syndrome in fetuses with both a normal nuchal thickness and a below-serum-risk threshold was compared with prevalence in either those above threshold risk or with an abnormal nuchal thickness. RESULTS: There were eight cases of trisomy 21 and one case each of 46,XX/47,XXX, 46,XY/47,XY, +7, and 46,XX, 11q-. The sensitivity of an abnormal nuchal thickness (> or = 6 mm) for detecting Down syndrome was four in eight (50%) (95%) confidence interval 15.3% to 84.6%). The risk of Down syndrome was significantly increased with an abnormal compared with a normal nuchal thickness, four in 13 (30.8%) versus four in 638 (0.6%), p < 0.0001. A risk threshold was defined at > or = 1:100 on the basis of the receiver-operator characteristic plot. Of 390 cases with a normal nuchal thickness and a serum risk estimate < 1:100, there were no cases of Down syndrome (0/390 vs 8/253, p = 0.002). CONCLUSION: Normal nuchal thickness significantly reduces the risk of Down syndrome and may help reduce the number of amniocenteses done for abnormal triple screen results.

Adult↗
PubMed1995

First-trimester endocervical irrigation: feasibility of obtaining trophoblast cells for prenatal diagnosis.

We sought to determine the feasibility of obtaining trophoblast cells for first-trimester prenatal diagnosis using endocervical irrigation. We studied 20 pregnant patients between 7-10.5 weeks' gestation who presented for elective pregnancy termination. Under ultrasound guidance, a specially designed plastic catheter was advanced to the level of the internal cervical os. Gentle flushing and aspiration was performed with 3 mL of normal saline. The material obtained was fixed and stained. A placental pathologist identified trophoblast cells using light microscopy. In another five cases, we attempted to culture the endocervical washings. Trophoblast cells were identified by microscopy after staining the cultured material with an anti-alpha-hCG-antibody bound stain. In ten of 20 cases (50%), trophoblast material was retrieved on irrigation. Of the five additional cases on which culture was attempted, trophoblast was successfully cultured in one, the results were equivocal in two, and culture was unsuccessful in the other two. Trophoblast cells for prenatal diagnosis can be obtained in a significant percentage of cases by first-trimester endocervical irrigation. The advantages of irrigation include technical simplicity, brief duration (less than 3 minutes), and suitability to first-trimester diagnosis. Further testing is necessary to determine the risks.

Cells, Cultured↗
PubMed1995

Umbilical artery flow velocity waveforms in monoamniotic twins with cord entanglement.

BACKGROUND: Monoamniotic twins with ultrasonographic evidence of umbilical cord entanglement present a management challenge in the antepartum period. CASES: We report two pregnancies with monoamniotic twins and ultrasonographic evidence of cord entanglement in which longitudinal Doppler flow velocity waveforms of the umbilical and middle cerebral arteries were obtained. A notch in the umbilical artery velocity waveform was noted in one twin member at 33 weeks' gestation and in both twin members of the other pregnancy at 31 weeks' gestation. Worsening of the umbilical artery velocity waveform notch with advancing gestation was noted in one fetus. CONCLUSION: The presence of a notch in the umbilical artery velocity waveform may reflect hemodynamic alterations in the fetal-placental circulation secondary to narrowing of the umbilical vessels involved in cord entanglement. This Doppler finding may be useful in the antepartum management of these pregnancies.

Adult↗