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Jodi D Hoffman,
Diana W Bianchi, Lisa M Sullivan,
Brenda L Mackinnon,
Jamie Collins,
Fergal D Malone,
T Flint Porter,
David A Nyberg,
Christine H Comstock,
Radek Bukowski,
Richard L Berkowitz,
Susan J Gross,
Lorraine Dugoff,
Sabrina D Craigo,
Ilan E Timor-Tritsch,
Stephen R Carr,
Honor M Wolfe,
Mary E D'Alton
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ABSTRACT: The FASTER trial compared first and second trimester screening methods for aneuploidy. We examined relationships between maternal serum markers and common congenital anomalies in the pediatric outcome data set of 36 837 subjects.
We used nested case-control studies, with cases defined by the most common anomalies in our follow-up database, and up to four controls matched by enrollment site, maternal age and race, enrollment gestational age, and infant gender. Serum markers were dichotomized to > or = 2 or < 0.5 multiples of the median (MoM). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated.
Statistically significant (p < 0.05) associations were found between inhibin A > or = 2 MoM with fetal multicystic dysplastic kidney (MCDK) (OR = 27.5, 95% CI: 2.8-267.7) and two-vessel cord (OR = 4.22, 95% CI:1.6-10.9); hCG of > or = 2 MoM with MCDK (OR = 19.56, 95% CI: 1.9-196.2) and hydrocele (OR = 2.48, 95% CI: 1.3-4.6); and PAPP-A > or = 2.0 MoM with hydrocele (OR = 1.88, 95% CI:1.1-3.3).
In this large prospective study, significant associations were found between several maternal serum markers and congenital anomalies. This suggests potential additional benefits to screening programs that are primarily designed to detect aneuploidy.
Prenatal Diagnosis 12/2008; 28(13):1204-8. · 2.11 Impact Factor
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Siobhan M Dolan,
Susan J Gross,
Irwin R Merkatz,
Vincent Faber, Lisa M Sullivan,
Fergal D Malone,
T Flint Porter,
David A Nyberg,
Christine H Comstock,
Gary D V Hankins,
Keith Eddleman,
Lorraine Dugoff,
Sabrina D Craigo,
Ilan Timor-Tritsch,
Stephen R Carr,
Honor M Wolfe,
Diana W Bianchi,
Mary E D'Alton
[show abstract]
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ABSTRACT: To assess the impact of birth defects on preterm birth and low birth weight.
Data from a large, prospective multi-center trial, the First and Second Trimester Evaluation of Risk (FASTER) Trial, were examined. All live births at more than 24 weeks of gestation with data on outcome and confounders were divided into two comparison groups: 1) those with a chromosomal or structural abnormality (birth defect) and 2) those with no abnormality detected in chromosomes or anatomy. Propensity scores were used to balance the groups, account for confounding, and reduce the bias of a large number of potential confounding factors in the assessment of the impact of a birth defect on outcome. Multiple logistic regression analysis was applied.
A singleton liveborn infant with a birth defect was 2.7 times more likely to be delivered preterm before 37 weeks of gestation (95% confidence interval [CI] 2.3-3.2), 7.0 times more likely to be delivered preterm before 34 weeks (95% CI 5.5-8.9), and 11.5 times more likely to be delivered very preterm before 32 weeks (95% CI 8.7-15.2). A singleton liveborn with a birth defect was 3.6 times more likely to have low birth weight at less than 2,500 g (95% CI 3.0-4.3) and 11.3 times more likely to be very low birth weight at less than 1,500 g (95% CI 8.5-15.1).
Birth defects are associated with preterm birth and low birth weight after controlling for multiple confounding factors, including shared risk factors and pregnancy complications, using propensity scoring adjustment in multivariable regression analysis. The independent effects of risk factors on perinatal outcomes such as preterm birth and low birth weight, usually complicated by numerous confounding factors, may benefit from the application of this methodology, which can be used to minimize bias and account for confounding. Furthermore, this suggests that clinical and public health interventions aimed at preventing birth defects may have added benefits in preventing preterm birth and low birth weight.
II.
Obstetrics and Gynecology 09/2007; 110(2 Pt 1):318-24. · 4.73 Impact Factor
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Andrew J Healy,
Fergal D Malone, Lisa M Sullivan,
T Flint Porter,
David A Luthy,
Christine H Comstock,
George Saade,
Richard Berkowitz,
Susan Klugman,
Lorraine Dugoff,
Sabrina D Craigo,
Ilan Timor-Tritsch,
Stephen R Carr,
Honor M Wolfe,
Diana W Bianchi,
Mary E D'Alton
[show abstract]
[hide abstract]
ABSTRACT: To investigate racial disparities in perinatal mortality in women with early access to prenatal care.
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.
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).
Racial disparities in perinatal mortality persist in contemporary obstetric practice despite early access to prenatal care.
II-2.
Obstetrics and Gynecology 04/2006; 107(3):625-31. · 4.73 Impact Factor
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ABSTRACT: This study was undertaken to determine whether laser thermocoagulation for twin-twin transfusion syndrome (TTTS) causes increased cell-free fetal DNA levels in maternal plasma, potentially as a result of placental injury.
We enrolled 34 patients with twin pregnancies complicated by severe TTTS who underwent fetoscopic selective laser ablation of placental vascular anastomoses. Blood samples were drawn before and sequentially after the procedure. Fetal DNA in maternal plasma was quantified by polymerase chain reaction amplification of a Y-chromosome sequence.
Compared with baseline, median elevations of fetal DNA levels were 0.8% at 30 minutes ( P = .32), 15.8% at 60 minutes ( P = .1), 179.5% at 24 hours ( P = .003), and 172.9% at 48 hours ( P = .003). Factors associated with increased fetal DNA levels at 24 hours after procedure included longer operation time, higher number of vessels ablated, and subsequent in utero fetal death ( P = .01, .04, and .04, respectively).
Persistent elevation of fetal DNA levels in maternal plasma after laser ablation suggests that circulating fetal DNA could derive from placental injury. Plasma fetal DNA analysis may be an additional prognostic marker for fetal outcome after laser therapy.
American Journal of Obstetrics and Gynecology 03/2005; 192(2):604-9. · 3.47 Impact Factor
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Clinical Chemistry 02/2005; 51(1):217-9. · 7.91 Impact Factor
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ABSTRACT: Analysis of cell-free fetal DNA (fDNA) and RNA in maternal plasma could be useful in the diagnosis and management of complications of pregnancy. In this review, we discuss our studies to investigate the potential of fetal nucleic acid measurement in maternal plasma as a marker of fetomaternal hemorrhage (FMH) after elective first-trimester termination of pregnancy (TOP). Using quantitative real-time PCR amplification of the DYS1 sequence, elevation of plasma fDNA levels after TOP was observed, especially in the late first trimester. This corresponds with the functional development of the placental vascular structure and fetal hematopoiesis. This Y sequence-based PCR amplification assay, however, limits the analysis to pregnant women carrying male fetuses. Therefore, we also developed a real-time quantitative reverse-transcriptase PCR assay of the gamma-globin transcript as a marker of fetal erythroid cells. Although plasma gamma-globin mRNA levels were decreased after TOP in many patients, an elevation was observed in some patients at greater than 9 weeks' gestation, which is consistent with the increase in plasma fDNA levels. Our data suggest that fetal hematopoietic cells contribute to the pool of fetal nucleic acids in the maternal circulation. Measurement of cell-free fetal nucleic acid levels in maternal plasma may have clinical application as a novel marker of FMH after 9 weeks of gestation.
Annals of the New York Academy of Sciences 07/2004; 1022:129-34. · 3.15 Impact Factor
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ABSTRACT: To determine if first-trimester elective termination of pregnancy affects cell-free fetal DNA (fDNA) levels in maternal plasma.
Prospective cohort study.
Clinical and academic research centers.
One hundred thirty-four women who underwent first-trimester elective termination procedures.
None.
Real-time polymerase chain reaction (PCR) amplification and measurement of DYS1, a Y-chromosome sequence, was used as a marker of fDNA.
We detected fDNA in pretermination samples from 27 out of 71 patients in the surgical arm, and 29 out of 63 patients in the medical arm. Based on confirmation of male gender in placental tissue, the sensitivity of fDNA detection is 92.6%. We detected fDNA as early as 32 days of gestation, which increased 4.2 genome equivalents/mL/week. In the surgical arm, the mean level of posttermination fDNA, adjusted for the clearance of fDNA in maternal blood, was higher than projected based on an expected increase with gestational age. In the medical arm, six patients had increased fDNA levels up to 11 days following termination.
We found that fDNA can be reliably quantified in the early first trimester; fDNA elevation that occurs shortly after surgical termination may reflect fetomaternal hemorrhage or destruction of trophoblastic villi. Continued elevation of fDNA for several days may occur following medical termination.
Fertility and Sterility 04/2004; 81(3):638-44. · 3.56 Impact Factor
