Search

Prenatal diagnosis of Down syndrome is widely available, but the determination of which patients should undergo prenatal diagnosis is changing. With the recent acceptance of first-trimester and integrated screening as a part of routine clinical practice, there are now a variety of accepted screening protocols for Down syndrome and other aneuploidies. These choices can be confusing both to both patients and providers. The following discussion is meant to outline the various options in prenatal screening, and their individual advantages and disadvantages. [ABSTRACT FROM AUTHOR]

Objective: To examine the hypothesis that early second trimester amniotic fluid (AF) insulin concentration is elevated and later fetal growth is augmented in gravidas demonstrating later oral glucose intolerance.Research Design and Methods: In this prospective observational cohort study, AF was sampled at 14-20 weeks' gestation in 247 subjects, and 1-h 50-g oral glucose challenge tests (GCTs) were performed at > or = 24 weeks. AF insulin was assayed by an automated immuno-chemiluminometric assay (8). Macrosomia was defined as birth weight above the 90th centile.Results: AF insulin concentration (range 1.4-44.5 pmol/l) correlated positively with gestational age and maternal weight. A logistic regression analysis, adjusted for maternal age and midpregnancy weight, showed increased AF insulin multiples of gestational age-specific medians to be associated with subsequently diagnosed gestational diabetes mellitus (GDM) (OR 1.9, CI 1.3-2.4, P = 0.029). Among 60 subjects with GCT values > 7.2 mmol/l, each unit increase in AF insulin multiple of median (MOM) was associated with a threefold increase in fetal macrosomia incidence (3.1, 1.3-4.9, P = 0.048).Conclusions: An elevated AF insulin concentration at 14-20 weeks' gestation is associated with subsequently documented maternal glucose intolerance. Among gravidas with GCT values > 7.2 mmol/l, elevated early AF insulin concentration is associated with fetal macrosomia. Maternal glucose intolerance may affect fetal insulin production before 20 weeks' gestation. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical validity of the new Access® pregnancy-associated plasma protein-A (PAPP-A) assay for Down's syndrome screening. Setting Academic hospital. Method Residual serum samples (n = 416) received for routine first trimester Down's syndrome screening (10--13 weeks) were retrieved from freezer storage and tested using two PAPP-A immunoassay methods. The new Access® assay was specifically compared, on a subset of these samples (n = 194), with an assay proven to give acceptable Down's syndrome screening performance, the PerkinElmer (PE) AutoDELFIA method. Access® PAPP-A levels were examined in relation to gestational age and maternal weight, and were compared with the PE method by regression and Bland-Altman analyses. Results Access® PAPP-A assay results were highly correlated with the PE AutoDELFIA method (r = 0.97). PAPP-A levels obtained using the Access® assay increased with advancing gestational age and were inversely related to maternal weight, as expected. The distribution of multiples of the median (MoM) values fit a log Gaussian distribution and the standard deviation of the log MoM (0.2331) matched published estimates. PAPP-A MoM levels in Down's syndrome pregnancies (n = 6, median 0.30) showed the expected reduction. Conclusion Using an appropriate gestational age-specific median equation, the Access® PAPP-A assay is expected to perform acceptably in first trimester Down's syndrome screening. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]