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Fergal D Malone

Publications and source records attributed to Fergal D Malone.

At least 19 recordsLinked to original sources
PubMed2006

Stability of first- and second-trimester serum markers after storage and shipment.

OBJECTIVE: The purpose of this study was to examine the levels of first- and second-trimester maternal serum markers used in Down syndrome screening in relation to the time between sample collection and arrival at the laboratory. METHODS: The FASTER trial, designed to compare first- and second-trimester screening tests for aneuploidy, has recently been completed, having recruited more than 38,000 patients. According to the trial protocol, all blood samples were drawn in serum separator tubes, centrifuged within 30 min and stored at 4 degrees C until shipment by air express. To examine the effect of delayed shipment, serum marker levels (expressed as multiple of the median--MoM) were evaluated in the first- and second-trimester samples and stratified by the number of days between serum collection and laboratory receipt. RESULTS: Under specified collection and shipment conditions, first and second-trimester screening marker mean levels and degrees of variance were stable for up to 9 days, with the exception of unconjugated estriol, which was stable for up to 6 days. CONCLUSION: The levels of first- and second-trimester Down syndrome screening markers can be measured reliably when the sample is centrifuged, refrigerated until shipment and received in the laboratory within a week of being drawn. A conservative approach would be to restrict testing to within 6 days of draw, with the intent to keep shipping delays to a minimum.

Biomarkers↗
PubMed2006

Is there a nuchal translucency millimeter measurement above which there is no added benefit from first trimester serum screening?

OBJECTIVE: The purpose of this study was to evaluate whether there is a nuchal translucency (NT) measurement, independent of gestational age, above which immediate diagnostic testing should be offered without waiting for first trimester serum markers. STUDY DESIGN: Thirty-six thousand one hundred twenty patients had successful measurement of simple NT at 10 3/7 to 13 6/7 weeks and had first trimester serum screening. No risks were reported until second trimester serum screening was completed. RESULTS: Thirty-two patients (0.09%) had NT > or = 4.0 mm; the lowest combined first trimester trisomy 21 risk assessment in euploid cases was 1 in 8 and among aneuploidy cases was 7 in 8. One hundred twenty-eight patients (0.3%) had simple NT > or = 3.0 mm: the lowest combined first trimester trisomy 21 risk assessment of any patient in this group was 1 in 1479 and the lowest risk assessment among aneuploid cases was 1 in 2. Ten patients (8%) had first trimester trisomy 21 risk assessments lowered to less that 1:200 and none of these 10 cases had an abnormal outcome. CONCLUSION: During first trimester Down syndrome screening, whenever an NT measurement of 3.0 mm or greater is obtained there is minimal benefit in waiting for serum screening results, and no benefit for NT of 4.0 mm or greater. Differentiation between cystic hygroma and enlarged simple NT (> or = 3.0 mm) is now a moot point as both are sufficiently high risk situations to warrant immediate CVS.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed2006

Screening for Down syndrome: practice patterns and knowledge of obstetricians and gynecologists.

OBJECTIVE: To assess obstetricians' practice patterns and knowledge regarding screening for Down syndrome. METHODS: A questionnaire was mailed to 1,105 American College of Obstetricians and Gynecologists Fellows and Junior Fellows in 2004. RESULTS: Sixty percent of questionnaires were returned. Statistical analyses were limited to the 532 practicing obstetricians. Greater than 80% felt their training and experience qualified them to counsel patients about genetic issues in pregnancy. However, 45% rated their residency training regarding prenatal diagnosis as barely adequate or nonexistent. American College of Obstetricians and Gynecologists publications were rated by 86% as an important source of information on genetic counseling. Seventy-eight percent of practitioners counsel all obstetric patients about risks for fetal aneuploidy, and 67% provide counseling for heritable genetic abnormalities. Although the majority (99%) offer second-trimester Down syndrome screening, only 55% also offer first-trimester screening for Down syndrome. Almost one half (49%) use the quad screen, and 6% offer integrated first- and second-trimester screening. The majority (88%) routinely offer amniocentesis to patients who are at elevated risk for genetic abnormalities, whereas 44% also offer chorionic villus sampling. Few (2%) perform chorionic villus sampling. CONCLUSION: Most obstetricians manage patients at risk for fetal genetic abnormalities according to American College of Obstetricians and Gynecologists educational materials. This survey identified deficiencies related to Down syndrome screening, including a limited number of practitioners performing chorionic villus sampling and physicians' own perception that training regarding genetic counseling should be improved. Educational strategies are needed to address these deficiencies before first-trimester screening programs are widely implemented. LEVEL OF EVIDENCE: III.

Amniocentesis↗
PubMed2006

Early access to prenatal care: implications for racial disparity in perinatal mortality.

OBJECTIVE: To investigate racial disparities in perinatal mortality in women with early access to prenatal care. METHODS: A prospectively collected database from a large, multicenter investigation of singleton pregnancies, the FASTER trial, was queried. Patients were recruited from an unselected obstetric population between 1999 and 2002. A total of 35,529 pregnancies with early access to prenatal care were reviewed for this analysis. The timing of perinatal loss was assessed. The following intervals were evaluated: fetal demise at less than 24 weeks of gestation, fetal demise at 24 or more weeks of gestation, and neonatal demise. Perinatal mortality was defined as the sum of these three intervals. RESULTS: The study population was 5% black, 22% Hispanic, 68% white, and 5% other. All minority races experienced higher rates of intrauterine growth restriction, preeclampsia, preterm premature rupture of membranes, gestational diabetes, placenta previa, preterm birth, very-preterm birth, cesarean delivery, light vaginal bleeding, and heavy vaginal bleeding compared with the white population. Overall perinatal mortality was 13 per 1,000 (471/35,529). The adjusted odds ratios (95% confidence intervals) for perinatal mortality (utilizing the white population as the referent race) were: black 3.5 (2.5-4.9), Hispanic 1.5 (1.2-2.1), and other 1.9 (1.3-2.8). CONCLUSION: Racial disparities in perinatal mortality persist in contemporary obstetric practice despite early access to prenatal care. LEVEL OF EVIDENCE: II-2.

Black or African American↗
PubMed2006

Pregnancy loss rates after midtrimester amniocentesis.

OBJECTIVE: The purpose of this study was to quantify the contemporary procedure-related loss rate after midtrimester amniocentesis using a database generated from patients who were recruited to the First And Second Trimester Evaluation of Risk for Aneuploidy trial. METHODS: A total of 35,003 unselected patients from the general population with viable singleton pregnancies were enrolled in the First And Second Trimester Evaluation of Risk for Aneuploidy trial between 10 3/7 and 13 6/7 weeks gestation and followed up prospectively for complete pregnancy outcome information. Patients who either did (study group, n=3,096) or did not (control group, n=31,907) undergo midtrimester amniocentesis were identified from the database. The rate of fetal loss less than 24 weeks of gestation was compared between the two groups, and multiple logistic regression analysis was used to adjust for potential confounders. RESULTS: The spontaneous fetal loss rate less than 24 weeks of gestation in the study group was 1.0% and was not statistically different from the background 0.94% rate seen in the control group (P=.74, 95% confidence interval -0.26%, 0.49%). The procedure-related loss rate after amniocentesis was 0.06% (1.0% minus the background rate of 0.94%). Women undergoing amniocentesis were 1.1 times more likely to have a spontaneous loss (95% confidence interval 0.7-1.5). CONCLUSION: The procedure-related fetal loss rate after midtrimester amniocentesis performed on patients in a contemporary prospective clinical trial was 0.06%. There was no significant difference in loss rates between those undergoing amniocentesis and those not undergoing amniocentesis. LEVEL OF EVIDENCE: II-2.

Abortion, Spontaneous↗
PubMed2006

Comparison of serum markers in first-trimester down syndrome screening.

OBJECTIVE: To estimate patterns of total hCG and inhibin A levels in the late first trimester of Down syndrome pregnancies, compare them with that of free beta-hCG, and assess screening performance of these markers individually and in combination with pregnancy-associated plasma protein-A (PAPP-A) and nuchal translucency. METHODS: Seventy-nine matched case-control sets of maternal serum samples (each Down syndrome case matched to 5 controls) from 11 through 13 completed weeks of gestation were taken from the sample bank of the First and Second Trimester Evaluation of Risk Consortium, a population-based study, and assayed for levels of free beta-hCG, total hCG, and inhibin A. Distribution characteristics and correlations of the multiples of the median values were estimated in cases and controls. Screening performance for each marker, alone and in combination with PAPP-A, nuchal translucency, and maternal age, was calculated. RESULTS: Median multiples of the median levels of free beta-hCG, total hCG, and inhibin A in cases were more elevated as gestation increased from 11 to 13 weeks, with univariate detection rates of 31%, 23%, and 29%, respectively, at a 5% false-positive rate. At 12 weeks, the multivariate detection rates at a 5% false-positive rate for nuchal translucency and PAPP-A (with maternal age) with either free beta-hCG, total hCG, or inhibin A were 84%, 83%, and 85%, respectively. The improvement in performance from nuchal translucency and PAPP-A to any of the three-marker tests was significant, while performance of any of the three-marker combinations was not significantly different from each other. CONCLUSION: Although levels of free beta-hCG in affected pregnancies were higher earlier than the levels of either total hCG or inhibin A, there was no significant difference in screening performance when either of the three markers was used with nuchal translucency and PAPP-A at 11-13 weeks of pregnancy. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2005

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.

Adult↗
PubMed2005

First trimester uterine artery Doppler abnormalities predict subsequent intrauterine growth restriction.

OBJECTIVE: This study was undertaken to evaluate the association between uterine artery Doppler velocimetry performed between 10 and 14 weeks gestation and intrauterine growth restriction (IUGR). STUDY DESIGN: Uterine artery Doppler velocimetry data were collected on 1067 women enrolled in the FASTER trial at the University of Colorado site. The data were analyzed by using univariate and multivariable logistic regression analysis. RESULTS: The uterine artery mean resistance index (RI) for the entire cohort was equal on the right and left sides (0.59 +/- 0.14). Of the 1067 women, 34.2% had unilateral or bilateral diastolic notches, 1 notch was observed in 23.8%, and bilateral notches in 10.4%. Women with a high uterine artery mean RI (> or = 75th percentile) were 5.5 times more likely to have IUGR (95% CI 1.6-18.7). There was no significant relationship between notching and IUGR. CONCLUSION: Elevated first trimester uterine artery mean RI is significantly associated with IUGR.

Adult↗
PubMed2005

Down syndrome screening in twins.

Available methods for screening for Down syndrome (DS) in twin gestations include maternal age, first-trimester nuchal translucency, first-trimester combined screening, second-trimester genetic sonography, second-trimester quad screening, and combinations of tests across different gestational ages. Biochemical screening is generally associated with detection rates at least 15% less than in singleton pregnancies. Nuchal translucency measurement may help close that gap, but the best available data (based on modeling) show approximately 75% to 85% detection rates for DS, with a 5% false-positive rate. Patients accepting screening should be aware of all options should a diagnosis of fetal aneuploidy be confirmed, including pregnancy continuation, termination of the entire pregnancy, and selective termination of an aneuploid fetus.

Clinical Trials as Topic↗
PubMed2005

Nuchal translucency-based Down syndrome screening: barriers to implementation.

Nuchal translucency sonography represents an important step forward in screening for Down syndrome. It is likely that a range of screening programs that rely on nuchal translucency sonography will become popular for general population screening. However, a number of practical implementation issues remain to be resolved before widespread utilization of this technique can be endorsed. This paper addresses some of these issues, including sonographer training, standardized nuchal translucency sonography protocol, ongoing nuchal translucency quality assurance programs, how to interpret Down syndrome risk, availability of first trimester diagnosis, and how to combine screening tests across different gestational ages.

Down Syndrome↗
PubMed2005

Impact of maternal age on obstetric outcome.

OBJECTIVE: To estimate the effect of maternal age on obstetric outcomes. METHODS: A prospective database from a multicenter investigation of singletons, the FASTER trial, was studied. Subjects were divided into 3 age groups: 1) less than 35 years, 2) 35-39 years, and 3) 40 years and older. Multivariable logistic regression analysis was used to assess the effect of age on outcomes after adjusting for race, parity, body mass index, education, marital status, smoking, medical history, use of assisted conception, and patient's study site. RESULTS: A total of 36,056 women with complete data were available: 28,398 (79%) less than 35 years of age; 6,294 (17%) 35-39 years; and 1,364 (4%) 40 years and older. Increasing age was significantly associated with miscarriage (adjusted odds ratio [adjOR]2.0 and 2.4 for ages 35-39 years and age 40 years and older, respectively), chromosomal abnormalities (adjOR 4.0 and 9.9), congenital anomalies (adjOR 1.4 and 1.7), gestational diabetes (adjOR 1.8 and 2.4), placenta previa (adjOR 1.8 and 2.8), and cesarean delivery (adjOR 1.6 and 2.0). Patients aged 35-39 years were at increased risk for macrosomia (adjOR 1.4). Increased risk for abruption (adjOR 2.3), preterm delivery (adjOR 1.4), low birth weight (adjOR 1.6), and perinatal mortality (adjOR 2.2) was noted in women aged 40 years and older. CONCLUSION: Increasing maternal age is independently associated with specific adverse pregnancy outcomes. Increasing age is a continuum rather than a threshold effect.

Adult↗
PubMed2005

Quad screen as a predictor of adverse pregnancy outcome.

OBJECTIVE: To estimate the effect of second-trimester levels of maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE3), and inhibin A (the quad screen) on obstetric complications by using a large, prospectively collected database (the FASTER database). METHODS: The FASTER trial was a multicenter study that evaluated first- and second-trimester screening programs for aneuploidy in women with singleton pregnancies. As part of this trial, patients had a quad screen drawn at 15-18 6/7 weeks. We analyzed the data to identify associations between the quad screen markers and preterm birth, intrauterine growth restriction, preeclampsia, and fetal loss. Our analysis was performed by evaluating the performance characteristics of quad screen markers individually and in combination. Crude and adjusted effects were estimated by multivariable logistic regression analysis. Patients with fetal anomalies were excluded from the analysis. RESULTS: We analyzed data from 33,145 pregnancies. We identified numerous associations between the markers and the adverse outcomes. There was a relatively low, but often significant, risk of having an adverse pregnancy complication if a patient had a single abnormal marker. However, the risk of having an adverse outcome increased significantly if a patient had 2 or more abnormal markers. The sensitivity and positive predictive values using combinations of markers is relatively low, although superior to using individual markers. CONCLUSION: These data suggest that components of the quad screen may prove useful in predicting adverse obstetric outcomes. We also showed that the total number and specific combinations of abnormal markers are most useful in predicting the risk of adverse perinatal outcome.

Adolescent↗
PubMed2005

First-trimester septated cystic hygroma: prevalence, natural history, and pediatric outcome.

OBJECTIVE: To estimate prevalence, natural history, and outcome of septated cystic hygroma in the first trimester in the general obstetric population, and to differentiate this finding from simple increased nuchal translucency. METHODS: Patients at 10.3-13.6 weeks of gestation underwent nuchal translucency sonography as part of a multicenter clinical trial. Septated cystic hygroma cases were offered chorionic villi sampling for karyotype, and targeted fetal anatomical and cardiac evaluations. Survivors were followed up for fetal and long-term pediatric outcome (median 25 months, range 12-50 months). Cases of septated cystic hygroma were also compared with cases of simple increased nuchal translucency. RESULTS: There were 134 cases of cystic hygroma (2 lost to follow-up) among 38,167 screened patients (1 in 285). Chromosomal abnormalities were diagnosed in 67 (51%), including 25 trisomy-21, 19 Turner syndrome, 13 trisomy-18, and 10 others. Major structural fetal malformations (primarily cardiac and skeletal) were diagnosed in 22 of the remaining 65 cases (34%). There were 5 cases (8%) of fetal death and 15 cases of elective pregnancy termination without evidence of abnormality. One of 23 (4%) normal survivors was diagnosed with cerebral palsy and developmental delay. Overall, survival with normal pediatric outcome was confirmed in 17% of cases (22 of 132). Compared with simple increased nuchal translucency, cystic hygroma has 5-fold, 12-fold, and 6-fold increased risk of aneuploidy, cardiac malformation, and perinatal death, respectively. CONCLUSION: First-trimester cystic hygroma was a frequent finding in a general obstetric screening program. It has the strongest prenatal association with aneuploidy described to date, with significantly worse outcome compared with simple increased nuchal translucency. Most pregnancies with normal evaluation at the completion of the second trimester resulted in a healthy infant with a normal pediatric outcome.

Abortion, Therapeutic↗
PubMed2005

Assisted reproductive technology and pregnancy outcome.

OBJECTIVE: To determine whether the use of assisted reproductive technology (ART) is associated with an increase in chromosomal abnormalities, fetal malformations, or adverse pregnancy outcomes. METHODS: A prospective database from a large multicenter investigation of singleton pregnancies, the First And Second Trimester Evaluation of Risk trial, was examined. Subjects were divided into 3 groups: no ART use, use of ovulation induction (with or without intrauterine insemination), and use of in vitro fertilization (IVF). Multivariate logistic regression analysis was used to assess association between ART and adverse pregnancy outcomes (significance of differences was accepted at P < .05). RESULTS: A total of 36,062 pregnancies were analyzed: 34,286 (95.1%) were spontaneously conceived, 1,222 (3.4%) used ovulation induction, and 554 (1.5%) used IVF. There was no association between ART and fetal growth restriction, aneuploidy, or fetal anomalies after adjustment for age, race, marital status, years of education, prior preterm delivery, prior fetal anomaly, body mass index, smoking history, and bleeding in the current pregnancy. Ovulation induction was associated with a statistically significant increase in placental abruption, fetal loss after 24 weeks, and gestational diabetes after adjustment. Use of IVF was associated with a statistically significant increase in preeclampsia, gestational hypertension, placental abruption, placenta previa, and risk of cesarean delivery. CONCLUSION: Patients who undergo IVF are at increased risk for several adverse pregnancy outcomes. Although many of these risks are not seen in patients undergoing ovulation induction, several adverse pregnancy outcomes are still increased in this group. There was no increased incidence of fetal chromosomal or structural abnormalities in the women who used any type of ART compared with the women who conceived spontaneously. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2004

A double-blinded, randomized controlled trial of oxytocin at the beginning versus the end of the third stage of labor for prevention of postpartum hemorrhage.

OBJECTIVE: The objective of this study was to compare the administration of oxytocin at the beginning and end of the third stage of labor for the prevention of postpartum hemorrhage. METHODS: Patients with documented singleton pregnancies were randomly assigned to two groups. The first received 10 units of oxytocin intramuscularly at delivery of the anterior shoulder of the fetus and an identical appearing placebo injection following delivery of the placenta. The second received the opposite medication sequence. The study was double blinded. Blood loss was measured by weighing all fluids collected, visual estimation, and serial blood counts. RESULTS: 27 women received oxytocin at the delivery of the fetal shoulder and 24 after the placenta. Oxytocin given after placenta delivery resulted in lower blood loss (345 vs. 400 ml, p = 0.28), lower collection bag weight (763 vs. 833 g, p = 0.55), lower change in HgB (-1.26 vs. -1.32 g, p = 0.86), lower DeltaHCT (-3.43 vs. -3.64%, p = 0.85), and a shorter third stage of labor duration (8.6 vs. 9.2 min, p = 0.75). The incidence of postpartum hemorrhage, defined as estimated blood loss >500 ml (0 vs. 14.8%) was significantly lowered with oxytocin following placental delivery (p = 0.049). CONCLUSIONS: In our study, postpartum hemorrhage was less frequent when oxytocin administration was delayed until after placenta delivery.

Adult↗
PubMed2004

Threatened abortion: A risk factor for poor pregnancy outcome, a population-based screening study.

OBJECTIVE: The purpose of this study was to determine whether patients with first-trimester threatened abortion are at increased risk for poor pregnancy outcome. STUDY DESIGN: A large prospective multicenter database was studied. Subjects were divided into three groups: (1) no bleeding, (2) light bleeding, and (3) heavy bleeding. Univariate and multivariable logistic regression analyses were used. RESULTS: The study comprised 16,506 patients: 14,160 patients without bleeding, 2094 patients with light bleeding, and 252 patients with heavy bleeding. Patients with vaginal bleeding, light or heavy, were more likely to experience a spontaneous loss before 24 weeks of gestation (odds ratio, 2.5 and 4.2, respectively) and cesarean delivery (odds ratio, 1.1 and 1.4, respectively). Light bleeding subjects were more likely to have preeclampsia (odds ratio, 1.5), preterm delivery (odds ratio, 1.3), and placental abruption (odds ratio, 1.6). Heavy vaginal bleeding subjects were more likely to have intrauterine growth restriction (odds ratio, 2.6), preterm delivery (odds ratio, 3.0), preterm premature rupture of membranes (odds ratio, 3.2), and placental abruption (odds ratio, 3.6). CONCLUSION: First-trimester vaginal bleeding is an independent risk factor for adverse obstetric outcome that is directly proportional to the amount of bleeding.

Abortion, Spontaneous↗