Karin Fuchs

Role of second-trimester genetic sonography after Down syndrome screening.

OBJECTIVE: To estimate the effectiveness of second-trimester genetic sonography in modifying Down syndrome screening test results. METHODS: The First and Second Trimester Evaluation of Risk (FASTER) aneuploidy screening trial participants were studied from 13 centers where a 15- to 23-week genetic sonogram was performed in the same center. Midtrimester Down syndrome risks were estimated for five screening test policies: first-trimester combined, second-trimester quadruple, and testing sequentially by integrated, stepwise, or contingent protocols. The maternal age-specific risk and the screening test risk were modified using likelihood ratios derived from the ultrasound findings. Separate likelihood ratios were obtained for the presence or absence of at least one major fetal structural malformation and for each “soft” sonographic marker statistically significant at the P<.005 level. Detection and false-positive rate were calculated for the genetic sonogram alone and for each test before and after risk modification. RESULTS: A total of 7,842 pregnancies were studied, including 59 with Down syndrome. Major malformations and 8 of the 18 soft markers evaluated were highly significant. The detection rate for a 5% false-positive rate for the genetic sonogram alone was 69%; the detection rate increased from 81% to 90% with the combined test, from 81% to 90% with the quadruple test, from 93% to 98% with the integrated test, from 97% to 98% with the stepwise test, and from 95% to 97% with the contingent test. The stepwise and contingent use of the genetic sonogram after first-trimester screening both yielded a 90% detection rate. CONCLUSION: Genetic sonography can increase detection rates substantially for combined and quadruple tests and more modestly for sequential protocols. Substituting sonography for quadruple markers in sequential screening was not useful. LEVEL OF EVIDENCE: II

Nonspontaneous late preterm birth: etiology and outcomes

OBJECTIVEnWe sought to determine the proportion of evidence-based (EB), vs non-EB (NEB) iatrogenic late preterm birth, and to compare corresponding rates of neonatal intensive care unit (NICU) admission.nnnSTUDY DESIGNnWe performed a retrospective cohort study. Cases were categorized as EB or NEB. NICU admission was compared between groups in both univariate and multivariate analysis.nnnRESULTSnOf 2693 late preterm deliveries, 32.3% (872/2693) were iatrogenic; 56.7% were delivered for NEB indications. Women with NEB deliveries were older (30.0 vs 28.6 years, P = .001), and more likely to be pregnant with twins (18.8% vs 7.9%, P < .001), have private insurance (80.3% vs 59.0%, P < .001), or have a second complicating factor (27.5% vs 10.1%, P < .001). A total of 56% of EB deliveries resulted in NICU admissions. After controlling for confounders, early gestational age (34 vs 36 weeks: odds ratio, 19.34; 95% confidence interval, 4.28-87.5) and mode of delivery (cesarean: odds ratio, 1.88; 95% confidence interval, 1.15-3.05) were most strongly associated with NICU admission.nnnCONCLUSIONnOver half of nonspontaneous late preterm births were NEB. EB guidelines are needed.

Performing a fetal anatomy scan at the time of first-trimester screening.

Over the past decade, prenatal diagnosis has shifted rapidly from the second trimester into the first trimester. Although the nuchal-translucency scan may detect a small proportion of fetal structural malformations, fetal anatomy is not routinely assessed until the fetal anatomical survey is performed in the second trimester between 18 and 22 weeks. The recent development of high-frequency transvaginal ultrasound transducers has led to vastly improved ultrasound resolution and improved visualization of fetal anatomy earlier in gestation. Several pilot studies of a first-trimester anatomic survey have reported detection rates comparable with those achieved in the routine second-trimester anatomic survey. As advanced ultrasound technology becomes more available, there is an urgent need to evaluate the diagnostic ability of a first-trimester anatomic survey and to determine the role of a first-trimester anatomic survey in the current screening paradigm.

First-Trimester Cystic Hygroma: Relationship of Nuchal Translucency Thickness and Outcomes

OBJECTIVE: To estimate the relationship between nuchal translucency thickness and abnormal karyotype, major congenital anomaly, perinatal loss, and composite abnormal outcome in fetuses with first-trimester nuchal cystic hygroma. METHODS: We performed a retrospective cohort study of first-trimester fetuses with ultrasound-diagnosed nuchal cystic hygroma collected over a 10-year period. RESULTS: There were 944 first-trimester fetuses with nuchal cystic hygroma. A karyotype abnormality occurred in 54.9% (400 of 729) of fetuses. A major congenital anomaly occurred in 28.8% (61 of 212) of fetuses with a normal karyotype. Perinatal loss occurred in 39% (115 of 295) of fetuses not electively terminated. Overall, an abnormal outcome occurred in 86.6% (543 of 627) of fetuses. After adjusting for potential confounders, every 1-mm increase in nuchal translucency thickness increased the odds of an abnormal karyotype by 44% (adjusted odds ratio [OR] 1.44, 95% confidence interval [CI] 1.29–1.60, P<.001), the odds of major congenital anomaly by 26% (adjusted OR 1.26, 95% CI, 1.08–1.47, P=.003), the odds of perinatal loss by 47% (adjusted OR 1.47, 95% CI 1.07–2.02, P=.019), and the odds of a composite abnormal outcome by 77% (adjusted OR 1.77, 95% CI 1.15–2.74, P=.01). CONCLUSION: First-trimester nuchal cystic hygroma is associated with high rates of karyotype abnormality, major congenital anomaly, perinatal loss, and abnormal outcome. As the thickness of the nuchal translucency increases, the odds of abnormal karyotype, major congenital anomaly, perinatal loss, and abnormal outcome increase. LEVEL OF EVIDENCE: II

Single versus repeat courses of antenatal steroids to improve neonatal outcomes : Risks and benefits

Recent additions to the literature provide evidence supporting the use of repeat courses of antenatal steroids. Both human and animal studies offer evidence that repeat courses of corticosteroids improve neonatal pulmonary outcomes, especially for the infants delivered at earlier gestational ages. Although there is also evidence to suggest altered neuronal maturation and intrauterine growth restriction in animals treated with repeat steroids, randomized controlled studies in humans have shown that birth weight reduction was only seen in those infants treated with 4 or more courses of corticosteroids. In addition, the reduction in neonatal birth weight and head circumference seen after multiple courses of antenatal corticosteroids normalizes by the time of hospital discharge. Studies are ongoing to investigate the 24-month postdelivery physical and neurodevelopmental outcomes in infants exposed to repeat courses of antenatal corticosteroids. Although there is evidence demonstrating the safety of a single repeat, or “rescue”, dose of antenatal corticosteroids, this must be tempered against the adverse effects seen after multiple courses of weekly repeat steroids. Randomized controlled trials are needed to determine the optimal number of courses of antenatal steroids to reduce the frequency of neonatal respiratory distress syndrome (RDS) without adversely affecting other neonatal outcomes. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to recall that although there are studies that support repeated courses of antenatal steroids, 24-month postdelivery and neurodevelopmental studies in infants exposed to repeated antenatal steroids are ongoing and also state that a “rescue”, single repeat dose, seven days after the first dose, appears prudent in only those mothers who are imminent of delivery prior to 32 weeks’ gestation.

Implementation of a national nuchal translucency education and quality monitoring program.

In 2004, leaders in first-trimester aneuploidy screening and a multidisciplinary group of experts established the Nuchal Translucency Quality Review Program, a national program to standardize education, credentialing, and quality monitoring of nuchal translucency. Since its inception, the program has credentialed more than 6,600 physician and ultrasonographer participants and collected more than 2.4 million nuchal translucency measurements. Ongoing quality monitoring is conducted through statistical analysis comparing the distribution and standard deviation of participants nuchal translucency measurements against those obtained from a standard referent curve. Results of these analyses are distributed to participants quarterly and are used to track each participants performance and to trigger performance improvement activities or mandatory remediation. This program could serve as a template for future education and credentialing programs that include partnerships with academic leaders, national professional organizations, and industry.

Estimating Gestational Age From Ultrasound Fetal Biometrics

OBJECTIVEnTo compare the accuracy of a new formula with one developed in 1984 (and still in common use) and to develop and compare racial and ethnic-specific and racial and ethnic-neutral formulas.nnnMETHODSnThe Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons was a prospective cohort study that recruited women in four self-reported racial-ethnic groups-non-Hispanic black, Hispanic, non-Hispanic white, and Asian-with singleton gestations from 12 U.S. centers (2009-2013). Women with a certain last menstrual period confirmed by first-trimester ultrasonogram had longitudinal fetal measurements by credentialed study ultrasonographers blinded to the gestational age at their five follow-up visits. Regression analyses were performed with linear mixed models to develop gestational age estimating formulas. Repeated cross-validation was used for validation. The estimation error was defined as the mean squared difference between the estimated and observed gestational age and was used to compare the formulas accuracy.nnnRESULTSnThe new formula estimated the gestational age (±2 SD) within ±7 days from 14 to 20 weeks of gestation, ±10 days from 21 to 27 weeks of gestation, and ±17 days from 28 to 40 weeks of gestation. The new formula performed significantly better than a formula developed in 1984 with an estimation error of 10.4 compared with 11.2 days from 21 to 27 weeks of gestation and 17.0 compared with 19.8 days at 28-40 weeks of gestation, respectively. Racial and ethnic-specific formulas did not outperform the racial and ethnic-neutral formula.nnnCONCLUSIONnThe NICHD gestational age estimation formula is associated with smaller errors than a well-established historical formula. Racial and ethnic-specific formulas are not superior to a racial-ethnic-neutral one.

159 – Monochorionic Monoamniotic Twin Gestations

Abstract The term monochorionic refers to a multiple gestation with one placental disk (or chorion), whereas monoamniotic describes the presence of only one amniotic cavity. By definition, monoamniotic twin pregnancies are monozygotic. In the early first trimester, monochorionic monoamniotic twin pregnancies can be identified by the presence of one gestational sac and one amniotic sac containing two fetuses. Monochorionic monoamniotic pregnancies are characterized by the presence of two fetuses of the same gender, a single placenta, and the absence of an intertwin membrane. Ultrasound (US) detection of cord entanglement is diagnostic of a monoamniotic gestation. In addition to risk of preterm delivery and growth disorders present in all twin gestations, monochorionic monoamniotic pregnancies are at risk of congenital anomalies, twin transfusion syndrome, and an increased risk of perinatal mortality related to cord entanglement. Serial prenatal US scans and heightened prenatal surveillance are essential in the management of monoamniotic twin pregnancies.

160 – Monochorionic Diamniotic Twin Gestations

Abstract The term dichorionic refers to a multiple gestation with two distinct placental disks (or two chorions); the term diamniotic describes a pregnancy with two distinct amniotic cavities. Either monozygotic or dizygotic twinning can result in a dichorionic diamniotic twin gestation. In the early first trimester, dichorionic diamniotic twin pregnancies can be identified by the presence of two distinct gestational sacs separated by a thick dividing membrane, each containing a separate fetal pole, yolk sac, and amniotic sac. Dichorionic pregnancies have a thick intertwin membrane and a characteristic thick triangular projection of placenta between the layers of the dividing membrane known as the twin peak or lambda sign. The finding of two distinct placental masses each with a cord insertion or the finding of discordant fetal gender is almost always diagnostic of a dichorionic twin gestation. Prenatal ultrasound (US) is essential in the management of dichorionic twin pregnancies to allow determination of chorionicity, evaluation of fetal anatomy, and serial US assessment of cervical length and fetal growth.

158 – Chorionicity of Multiple Gestations

Abstract Chorionicity refers to the number of placentas in a multiple gestation; amnionicity refers to the number of amniotic cavities. Prenatal determination of chorionicity and amnionicity is essential in the clinical management of multiple gestations. In the first trimester, chorionicity can be determined by counting the number of gestational sacs, and the number of yolk sacs can be used to predict amnionicity. In the late first trimester and early second trimester, systematic evaluation of placental number, fetal gender, and insertion of the intertwin membrane into the placenta allows accurate prenatal diagnosis of chorionicity. In dichorionic pregnancies, the intertwin membrane remains thick with a triangular projection of placenta known as the twin peak or lambda sign, which is visible between the layers of the dividing membrane. In monochorionic pregnancies, the intertwin membrane inserts directly into the placenta forming a characteristic “T” sign.