Combining first and second trimester markers for Down syndrome screening: think twice.

AIMS: This study compares different screening strategies for the detection of Down syndrome and considers practical implications of using multiple screening protocols. METHODS: The performance characteristics of each screening strategy were assessed based on datasets of Down syndrome (n=11) and unaffected pregnancies (n=1006) tested in both first and second trimester, as well as data from first trimester (n=18,901) and second trimester (n=40,748) pregnancies. RESULTS: For a detection rate of 91%, the false positive rates for integrated and serum integrated screening were 2.5% and 6.3%, respectively, compared with combined first trimester (4.6%) and second trimester (12.6%) screening. Contingent and sequential screening protocols achieved detection rates of 82 to 91% with false positive rates between 2.6 and 2.9%. Contingent protocols require retesting of 15 to 20% of cases in the second trimester. Sequential and integrated protocols require retesting of 98 to 100% of cases in the second trimester. The various screening strategies did not always detect the same Down syndrome pregnancies. CONCLUSIONS: Combining first and second trimester markers for Down syndrome screening better defines the at-risk population. However, integrated protocols complicate management of screening programs and may not be suitable as primary screening strategies. It may be a better use of resources to refine current first and second trimester programs through improved access and new markers. We therefore suggest thinking twice before embracing integrated population screening programs.

3D ultrasound findings in women attending a South Australian recurrent miscarriage clinic.

BACKGROUND: Women who suffer recurrent miscarriage are a heterogeneous group. Known causes include genetic and endocrine abnormalities, anti-phospholipid syndrome and autoimmune disease. Congenital uterine abnormalities (CUAs) such as bicornuate, unicornuate, septate and arcuate uterine abnormalities are known to negatively impact on pregnancy rates, and to increase the miscarriage rates of genetically normal pregnancies. In some countries, such as Britain, 3D ultrasound of the pelvis is offered routinely to women with recurrent miscarriages. AIM: To determine the prevalence of CUAs and other pelvic pathology, in women attending a South Australian recurrent miscarriage clinic. MATERIALS AND METHODS: 3D transvaginal ultrasounds performed during the luteal phase of the menstrual cycle were offered to all patients attending the recurrent miscarriage clinic, who had not previously had a hysteroscopy, laparoscopy, HyCoSy or MRI study of their pelvis. A Philips IUI 8 MHz transvaginal probe for freehand sweep, and dedicated 3D transvaginal probe was used. 3D scans provide a coronal view of the uterus, ideal for detecting abnormalities which may be missed during routine conventional 2D scanning. RESULTS: A total of 210 women were recruited, 200 results were available, and 29% were found to have a CUA. 15% had polycystic ovaries detected, 15% were found to have fibroids, 12% adenomyosis and 1.5% Asherman's syndrome. CONCLUSIONS: 3D ultrasound evaluation of patients attending a recurrent miscarriage clinic detects CUAs, and has a high detection rate of other pelvic abnormalities that may contribute to recurrent miscarriages.

Novel TSEN54 mutation causing pontocerebellar hypoplasia type 4.

Pontocerebellar hypoplasia exhibits a diverse range of etiologies, including six known autosomal recessive, single gene disorders. We describe a molecularly confirmed case of pontocerebellar hypoplasia type 4, a rare and severe neonatal phenotype with a novel TSEN54 mutation, presenting with polyhydramnios, hypertonia, and early neonatal death. The patient manifested severe hypoplasia of the cerebellum and brainstem. The neuropathologic findings in pontocerebellar hypoplasia type 4 develop late in gestation, and therefore prenatal diagnosis with ultrasonography is of limited use. Establishing a molecular diagnosis in the proband is critical for allowing couples to plan future pregnancies.