NSGC practice guideline: prenatal screening and diagnostic testing options for chromosome aneuploidy.

The BUN and FASTER studies, two prospective multicenter trials in the United States, validated the accuracy and detection rates of first and second trimester screening previously reported abroad. These studies, coupled with the 2007 release of the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin that endorsed first trimester screening as an alternative to traditional second trimester multiple marker screening, led to an explosion of screening options available to pregnant women. ACOG also recommended that invasive diagnostic testing for chromosome aneuploidy be made available to all women regardless of maternal age. More recently, another option known as Non-invasive Prenatal Testing (NIPT) became available to screen for chromosome aneuploidy. While screening and testing options may be limited due to a variety of factors, healthcare providers need to be aware of the options in their area in order to provide their patients with accurate and reliable information. If not presented clearly, patients may feel overwhelmed at the number of choices available. The following guideline includes recommendations for healthcare providers regarding which screening or diagnostic test should be offered based on availability, insurance coverage, and timing of a patient's entry into prenatal care, as well as a triage assessment so that a general process can be adapted to unique situations.

Three-dimensional ultrasound in the prenatal diagnosis of cleidocranial dysplasia associated with B-cell immunodeficiency.

A patient with a singleton pregnancy was referred for three-dimensional ultrasonography (3DUS) at 18 + 3 weeks for suspected hypomineralization of the skull bones and absence of the nasal bones. Three-dimensional rendered images of the fetal skull revealed widening of the coronal sutures, absence of the squamous portion of the temporal bone, and absence of the occipital bone, except for two areas of ossification. In addition, a fractured right clavicle was identified. The remainder of the fetal anatomy was normal and biometry was appropriate for gestational age. Genetic amniocentesis revealed a 46,XX fetal karyotype. Family history was positive for a 5-year-old sibling with an open anterior fontanelle. Cleidocranial dysplasia was suspected. A female neonate was delivered by elective repeat Cesarean section at 40 + 3 weeks of gestation without complications and discharged home 3 days after delivery. Prenatal diagnosis was confirmed by physical and radiological evaluation. The infant died at 8 weeks of age due to respiratory syncytial virus pneumonia secondary to B-cell deficiency. RUNX2 mutations were not detected by molecular analysis. There are three relevant aspects to this case: (1) clear visualization of the widened fontanelles and hypomineralized occipital bones was possible with the use of 3DUS; (2) a clavicular fracture was identified in utero with combined high-resolution two-dimensional and 3DUS; and (3) although absence of the nasal bones is most commonly observed in fetuses with chromosomal disorders (e.g. trisomy 21 and trisomy 18), a careful examination of the skeleton should be considered in fetuses with absent nasal bones and a normal karyotype.

First-trimester three-dimensional ultrasonographic findings in a fetus with frontonasal malformation.

A case of a frontonasal malformation observed during the first trimester with three-dimensional ultrasonography and fetoscopy is reported. Absence of the nasal bone and a poorly characterized nose were visualized at 11 5/7 weeks by two-dimensional ultrasonography. Rendered three-dimensional ultrasound images revealed absence of the nasal bridge, widely spaced frontal bones and hypertelorism. Fetoscopy, performed at 12 3/7 weeks, confirmed the hypertelorism and showed a broad translucent nose with a flat nasal bridge. The final diagnosis of frontonasal malformation was made at autopsy after pregnancy termination. A review of prenatally diagnosed cases as well as the various syndromes having frontonasal malformation as a common denominator is presented.

Prenatal diagnosis of membranous ventricular septal aneurysms and their association with absence of atrioventricular valve 'offsetting'.

Congenital aneurysm of the membranous portion of the ventricular septum in association with absence of atrioventricular valve 'offsetting' was diagnosed in two fetuses at 29 and 34 weeks. In the first case the fetus had a normal karyotype and no other structural heart defects, whereas in the second case there was a partial deletion of the long arm of chromosome 5 and an absent pulmonary valve syndrome. The association of absence of 'offsetting' with aneurysms of the membranous ventricular septum may represent spontaneous closure of ventricular septal defects initially extended to the inlet.