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Investigates the adequacy of the precision of available glucose meters for gestational diabetes screening. Coefficients of variation of meters; Calculated meter thresholds; Venous plasma glucose level of 140 mg/dl measured by glucose analyzer; Pro portion of required confirmatory testing.

Purpose: Severe, progressive twin-to-twin transfusion syndrome (TTTS) is associated with near-100% mortality if left untreated. Endoscopic laser ablation of placental vessels (ELA) is associated with 75% to 80% survival of at least one twin. The actuarial risk of fetal demise after ELA has not yet been described., Study Design: A retrospective cohort study from 2 centers on a consecutive series of 163 sets of monochorionic twins with severe TTTS (18 Quintero stage I, 55 stage II, 71 stage III, 19 stage IV) who underwent ELA. Actuarial survival was calculated and stratified for donor vs recipient and according to stage., Results: Median gestational age at diagnosis was 20.1 weeks; median operative time was 60 minutes. Overall survival was 63%, and survival of at least one twin was seen in 76% of pregnancies. Of fetal demises, 10% occurred within 48 hours after ELA, and 90% of all fetal demises occurred within 1 month. There was a 10% survival advantage of recipients over donors. Survival was similar for stages I, II, and IV (75%-80%), compared with 55% for stage III., Conclusions: Actuarial survival curves for TTTS confirms a greater burden on donor than on recipient but not at a previously reported 2:1 ratio. The current staging system does not accurately reflect post-ELA mortality risk. The unexpected higher mortality in stage III may reflect a more acute progression of the disorder in this group, an adverse effect of LA on an as yet unknown subgroup with stage III or, alternatively, preoperative demise of fulminant stage IV patients, leaving a stage IV subgroup with a more benign course and better outcome.

Objective: 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., Methods: 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., Results: 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)., Conclusion: 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.

Objective: Comparison of contingent, step-wise and integrated screening policies., Methods: Mid-trimester Down syndrome risks were retrospectively calculated from FaSTER trial data. For contingent screening, initial risk was calculated from ultrasound measurement of nuchal translucency (NT), maternal serum pregnancy-associated plasma protein (PAPP)-A and free beta-human chorionic gonadotrophin (hCG) at 11-13 weeks, and classified positive (>1 in 30), borderline (1 in 30-1500) or negative. Borderline risks were recalculated using alpha-fetoprotein, hCG, unconjugated estriol (uE3) and inhibin at 15-18 weeks, and reclassified as positive (>1 in 270) or negative. For step-wise screening, initial negative risks were also recalculated. For integrated screening, a single risk was calculated from NT, PAPP-A and the second trimester markers., Results: There were 86 Down syndrome and 32,269 unaffected pregancies. The detection rate for contingent screening was 91% and false-positive rate was 4.5%; initial detection rate was 60%, initial false-positive rate was 1.2% and borderline risk was 23%. Step-wise screening had 92% detection rate and 5.1% false-positive rate; integrated screening had 88% and 4.9% respectively., Conclusion: As predicted by modelling, the contingent screening detection rate for a fixed false-positive rate is comparable with step-wise and integrated screening, but substantially reduces the number needing to return for second trimester testing.

Objective: To evaluate the performance of first- and second-trimester screening methods for the detection of aneuploidies other than Down syndrome., Methods: Patients with singleton pregnancies at 10 weeks 3 days through 13 weeks 6 days of gestation were recruited at 15 U.S. centers. All patients had a first-trimester nuchal translucency scan, and those without cystic hygroma had a combined test (nuchal translucency, pregnancy-associated plasma protein A, and free beta-hCG) and returned at 15-18 weeks for a second-trimester quadruple screen (serum alpha-fetoprotein, total hCG, unconjugated estriol, and inhibin-A). Risk cutoff levels of 1:300 for Down syndrome and 1:100 for trisomy 18 were selected., Results: Thirty-six thousand one hundred seventy-one patients completed first-trimester screening, and 35,236 completed second-trimester screening. There were 77 cases of non-Down syndrome aneuploidies identified in this population; 41 were positive for a cystic hygroma in the first trimester, and a further 36 had a combined test, of whom 29 proceeded to quadruple screening. First-trimester screening, by cystic hygroma determination or combined screening had a 78% detection rate for all non-Down syndrome aneuploidies, with an overall false-positive rate of 6.0%. Sixty-nine percent of non-Down syndrome aneuploidies were identified as screen-positive by the second-trimester quadruple screen, at a false-positive rate of 8.9%. In the combined test, the use of trisomy 18 risks did not detect any additional non-Down syndrome aneuploidies compared with the Down syndrome risk alone. In second-trimester quadruple screening, a trisomy 18-specific algorithm detected an additional 41% non-Down syndrome aneuploidies not detected using the Down syndrome algorithm., Conclusion: First-trimester Down syndrome screening protocols can detect the majority of cases of non-Down aneuploidies. Addition of a trisomy 18-specific risk algorithm in the second trimester achieves high detection rates for aneuploidies other than Down syndrome., Level of Evidence: II.

Objective: To assess the impact of birth defects on preterm birth and low birth weight., Methods: 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., Results: 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)., Conclusion: 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., Level of Evidence: II.

Objective: To investigate the differences in costs and outcomes of Down syndrome screening using data from the First and Second Trimester Evaluation of Risk (FASTER) Trial., Methods: Seven possible screening options for Down syndrome were compared: 1) Triple Screen-maternal serum alpha fetoprotein, estriol, and hCG; 2) Quad-maternal serum alpha fetoprotein, estriol, hCG, and Inhibin A; 3) Combined First-nuchal translucency, pregnancy-associated plasma protein A (PAPP-A), free beta-hCG; 4) Integrated-nuchal translucency, PAPP-A, plus Quad; 5) Serum Integrated-PAPP-A, plus Quad; 6) Stepwise Sequential-Combined First plus Quad with results given after each test; and 7) Contingent Sequential-Combined First and only those with risk between 1:30 and 1:1,500 have Quad screen. The detection rates for each option were used given a 5% false-positive rate except for Contingent Sequential with a 4.3% false-positive rate. Outcomes included societal costs of each screening regimen (screening tests, amniocentesis, management of complications, and cost of care of Down syndrome live births), Down syndrome fetuses identified and born, the associated quality-adjusted life years, and the incremental cost-utility ratio., Results: Based on the screening results derived from the 38,033 women evaluated in the FASTER trial, the Contingent Sequential screen dominated (lower costs with better outcomes) all other screens. For example, the Contingent Sequential cost 32.3 million dollars whereas the other screens ranged from 32.8 to 37.5 million dollars. The Sequential strategy led to the identification of the most Down syndrome fetuses of all of the screens, but at a higher cost per Down syndrome case diagnosed ($719,675 compared with $690,427) as compared with the Contingent Sequential. Because of the lower overall false-positive rate leading to fewer procedure-related miscarriages, the Contingent Sequential resulted in the highest quality-adjusted life years as well. The Contingent Sequential remained the most cost-effective option throughout sensitivity analysis of inputs, including amniocentesis rate after positive screen, rate of therapeutic abortion after Down syndrome diagnosis, and rate of procedure-related miscarriages., Conclusion: Analysis of this actual data from the FASTER Trial demonstrates that the Contingent Sequential test is the most cost-effective. This information can help shape future policy regarding Down syndrome 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.

Background: Most congenital cystic lung lesions (CCLLs) do not require in utero or perinatal intervention. The management of asymptomatic lesions is controversial: the theoretical risk of infection and malignancy is offset by whether thoracotomy in asymptomatic children is justified. We examined our recent experience and the role of minimally invasive surgery., Methods: We analyzed the pre-, peri-, and postnatal findings of all consecutive CCLLs diagnosed between 1997 and 2005. We reviewed records for pre-, and postnatal imaging, management, and outcome., Results: Thirty-five CCLL were diagnosed prenatally. Since 2000, all asymptomatic lesions were removed endoscopically at 6 to 18 months (thoracoscopy for 6 extralobar sequestrations, 3 intralobar sequestrations/congenital cystic adenomatoid malformations, 5 bronchogenic cysts, and retroperitoneal laparoscopy for 2 intraabdominal sequestrations). Congenital cystic adenomatoid malformation elements were present in more than 70%. Two abdominal lesions have regressed, and 2 patients are awaiting intervention. One symptomatic infant underwent thoracotomy for congenital lobar emphysema., Conclusions: It has been argued that the risks associated with congenital lung lesions (infection and malignancy) justify intervention in the asymptomatic patient. In our experience, all these lesions could be safely removed using endosurgical techniques. Counseling of (future) parents should be updated to include minimally invasive surgery in the management algorithm.

Background: Premature rupture of membranes (PROM) remains a significant complication of fetal surgery. Rates of 40% to 100% have been reported after both open and endoscopic fetal surgery. We describe a technique of endoscopic port insertion and removal that minimizes trauma to the membranes., Methods: Twenty-seven consecutive patients undergoing endoscopic laser ablation for twin-to-twin transfusion syndrome were reviewed. In each case, a minilaparotomy was performed, and the amniotic cavity was entered under direct vision of the uterus using a Seldinger technique. The entry site was carefully dilated to accommodate a 4.0-mm-diameter cannula. A gelatin sponge plug was placed at port removal. Postoperative management and outcome were evaluated., Results: Median gestational age at operation was 21.3 weeks. Median operating time was 60 minutes. One patient delivered intraoperatively because of fetal distress. Seventeen (65.4%) patients required postoperative tocolysis (median duration, 12 hours). Median postoperative gestation was 6.5 weeks (range, 1-20 weeks). Only 1 (4.2%) of 24 patients with successful gelatin sponge placement developed PROM., Conclusions: Meticulous technique and atraumatic insertion and removal of ports help minimize the risk of postoperative amniotic leak after endoscopic fetal surgery. Our PROM rate of 4.2% contrasts sharply with previously reported rates after similar operations.

Abstract Endoscopic laser ablation of placental vessels is the most commonly performed fetal operation today. Herein, we review the pathophysiology of twin-to-twin transfusion syndrome and the challenges of its treatment. Pediatric surgeons, with their knowledge of fetal and congenital pathology, and their technical expertise with minimally invasive surgery, can be of great benefit to the patient and the medical team.

As laser ablation of placental vascular communications gains acceptance as treatment option for severe twin-to-twin transfusion syndrome (TTTS), pathologists are increasingly confronted with the interpretation of laser-treated placentas. We present our preliminary institutional experience with the gross and microscopic analysis of these specimens. Patients underwent selective ablation for severe TTTS (Quintero stages II to V) between 16 and 25 wk gestation and the placentas were examined between < 24 h and 19 wk postoperatively. The placental vasculature was injected with gelatin-dye mixtures. The type and number of vascular anastomoses were recorded, followed by routine histopathological analysis of the placenta. Foci of laser impact were identified in all placentas examined within 1 month after laser coagulation. Located along the recipient side of the dividing membrane, the laser-treated vessels appeared hemorrhagic and showed a characteristic abrupt interruption of dye filling after vascular injection. In placentas examined more than 1 month after intervention, the most frequent gross finding was the absence or relative paucity of intertwin anastomoses, associated with subchorionic fibrin deposition. Microscopically, laser-treated vessels showed varying degrees of necrosis, associated with focal hemorrhage, avascular villi, and fibrin deposition in the underlying parenchyma. In some cases of intrauterine fetal demise or placental disruption, no definite laser scars were identified. As expected, the number of residual anastomoses (all types) was significantly smaller in laser-treated placentas than in control monochorionic placentas (2.4 +/- 2.2 [ n = 10] vs. 6.2 +/- 3.2 [ n = 70], P < 0.01). Velamentous cord insertion was noted in 50% of cases; markedly uneven placental sharing in 60%. Detailed analysis of laser-treated placentas and clinicopathological correlation may lead to a better understanding of the pathophysiology of TTTS and continued refinement of therapeutic approaches for this often lethal condition.