Ricardo Palma-Dias

Cytomegalovirus in pregnancy: to screen or not to screen

BackgroundCytomegalovirus (CMV) infection is now the commonest congenital form of infective neurological handicap, recognized by the Institute of Medicine as the leading priority for the developed world in congenital infection. In the absence of an effective vaccine, universal screening for CMV in pregnancy has been proposed, in order that primary infection could be diagnosed and- potentially- the burden of disability due to congenital CMV prevented.DiscussionUniversal screening for CMV to identify seronegative women at the beginning of pregnancy could potentially reduce the burden of congenital CMV in one of three ways. The risk of acquiring the infection during pregnancy has been shown to be reduced by institution of simple hygiene measures (primary prevention). Among women who seroconvert during pregnancy, CMV hyperimmune globulin (CMV HIG) shows promise in reducing the risk of perinatal transmission (secondary prevention), and CMV HIG and/ or antivirals may be effective in reducing the risk of clinical sequelae among those known to be infected (tertiary prevention). The reports from these studies have re-ignited interest in universal screening for CMV, but against the potential benefit of these exciting therapies needs to be weighed the challenges associated with the implementation of any universal screening in pregnancy. These include; the optimal test, and timing of screening, to maximize detection; an approach to the management of equivocal results, and the cost effectiveness of the proposed screening program. In this article, we provide an overview of current knowledge and ongoing trials in the prevention, diagnosis and management of congenital CMV. Recognising that CMV screening is already being offered to many patients on an ad hoc basis, we also provide a management algorithm to guide clinicians and assist in counseling patients.SummaryWe suggest that- on the basis of current data- the criteria necessary to recommend universal screening for CMV are not yet met, but this position is likely to change if trials currently underway confirm that CMV HIG and/ or antivirals are effective in reducing the burden of congenital CMV disease.

Meeting the challenge of interpreting high‐resolution single nucleotide polymorphism array data in prenatal diagnosis: does increased diagnostic power outweigh the dilemma of rare variants?

Several studies have already shown the superiority of chromosomal microarray analysis (CMA) compared with conventional karyotyping for prenatal investigation of fetal ultrasound abnormality. This study used very high‐resolution single nucleotide polymorphism (SNP) arrays to determine the impact on detection rates of all clinical categories of copy number variations (CNVs), and address the issue of interpreting and communicating findings of uncertain or unknown clinical significance, which are to be expected at higher frequency when using very high‐resolution CMA.

Relation of cervical length at 22-24 weeks of gestation to demographic characteristics and obstetric history

Preterm delivery is the main cause of neonatal death and ultrasonographic cervical assessment has been shown to be more accurate than digital examination in recognizing a short cervix. This is a cross-sectional study, involving 1131 women at 22-24 weeks of pregnancy, designed to determine the distribution of cervical length and to examine which variables of demographic characteristics and obstetric history increase the risk of a short cervix (15 mm or less). The distribution of maternal demographic and obstetric history characteristics among patients with cervical length pound 15 mm was analyzed and compared to the findings for the general population. Risk ratios (RR) between subgroups were generated from this comparison. Median cervical length was 37 mm and in 1.5% of cases it was 15 mm or less. The proportion of women with a short cervix (< or =15 mm) was significantly higher among patients with a low body mass index (RR = 3.5) and in those with previous fetal losses between 16-23 weeks (RR = 33.1) or spontaneous preterm deliveries between 24-32 weeks (RR = 14.1). We suggest that transvaginal sonographic measurement of cervical length be performed as part of a routine midtrimester ultrasound evaluation. There are specific variables of demographic characteristics and obstetric history which increase the risk of detecting a short cervix at 22-24 weeks.

Clinical implementation of cell‐free DNA‐based aneuploidy screening: perspectives from a national audit

In late 2011, a prenatal screening test for fetal chromosomal abnormalities using cell-free DNA in maternal plasma was introduced commercially in the USA. This next-generation sequencing-based method, commonly referred to as non-invasive prenatal testing (NIPT), represented the most accurate form of screening for trisomy 21 to date1. While the NIPT market expanded rapidly in the USA, its clinical implementation in other developed countries varied considerably due to local factors, such as existing care models, insurance coverage and legal restrictions. In late 2012, NIPT became available clinically in Australia, through overseas laboratories, 1 year after it did in the USA. By the end of 2013, there were five providers in the Australian market offering NIPT on a self-funded basis. Australian subspecialists in maternal–fetal medicine and obstetric ultrasound quickly became the major sources of referral for NIPT due to their well-established role in first-trimester screening and prenatal diagnostic procedures. Despite being ‘early adopters’ of technology, Australian sonologists had concerns about NIPT that were common to many countries. Among these were definition of the appropriate indications for use, and the uncertain test-failure rates and turnaround times associated with offshore laboratory processing outside trial conditions. The lack of government regulation and lack of data collection were also key concerns2. At the time, international reports on clinical implementation were either single-center experiences3,4, or multicenter industry-sponsored studies of a single commercial assay5. In response to these issues, a group of Australian obstetric sonologists formed a collaboration to document the collective national experience of NIPT, across a range of practice types and using a variety of NIPT providers.

Noninvasive prenatal testing in routine clinical practice – An audit of NIPT and combined first‐trimester screening in an unselected Australian population

There are limited data regarding noninvasive prenatal testing (NIPT) in low‐risk populations, and the ideal aneuploidy screening model for a pregnant population has yet to be established.

Malformation of the fetal brain in thanatophoric dysplasia: US and MRI findings.

We present a case in which the unusual cerebral malformations of thanatophoric dysplasia (TD) were identified on a 21-week fetal US and confirmed by antenatal MRI, postmortem imaging and autopsy. TD is the most common lethal skeletal dysplasia and is characterized by short long bones, which are often bowed (type 1), a small thorax, and skull deformities. There is also a recognised constellation of abnormalities of the brain primarily affecting the temporal lobes that, although well described in the postmortem setting, are not widely recognized in fetal imaging. Familiarity with this appearance will facilitate accurate antenatal diagnosis.

Maternal adiposity and newborn vascular health.

The prevalence of overweight and obesity in women of childbearing age is up to 60% in developed nations.1 We sought to determine whether maternal adiposity is associated with aortic wall thickening in newborns, prior to prolonged postnatal exposure to potential confounders; and if so, whether this association is independent of birth weight, a known risk factor for later cardiovascular disease. Twenty-three pregnant women, age 35.6 years (SD 4.8; range 27.0–44.6), were recruited at 16.3 weeks gestation (SD 2.2; range 11.4–20.6) from The Womens Hospital, Melbourne, Australia. Women who had quit smoking in the previous 6 months were excluded; however those who continued to smoke were not. Maternal height and weight were measured at study entry. Overweight and obesity was defined as a body mass index (BMI)≥25 kg/m2, which we believe will not …

Screening for Placental Insufficiency by Transvaginal Uterine Artery Doppler at 22–24 Weeks of Gestation

Objective: To determine the value of routine transvaginal color Doppler assessment of the uterine arteries at 22–24 weeks of gestation in the prediction of placental insufficiency. Methods: Women with singleton pregnancies scheduled for routine ultrasound scans at 22–24 weeks were offered Doppler assessment of the uterine arteries by transvaginal ultrasound. The pulsatility index (PI) was obtained for each artery and the mean value was calculated. A mean PI >95th percentile was considered increased. Screening characteristics for predicting placental insufficiency, defined as preeclampsia, fetal growth restriction or intrauterine death, were calculated. Results: Doppler examination of the uterine arteries was carried out in 1,057 singleton pregnancies. The mean uterine artery PI was 1.03 and the 95th percentile was 1.55. In 54 cases (5.1%) the mean PI was >1.55 (screen-positive). In the study population there were 48 cases of preeclampsia (5.1%), 72 fetal growth restrictions (7.5%) and 7 intrauterine deaths (0.7%). The screen-positive group showed an incidence of 47.1% of combined adverse results. The relative risks after a positive screening test were 7.3 (CI 4.2–12.6) for pre-eclampsia, 3.9 (CI 2.3 – 6.6) for fetal growth restriction and 4.5 (CI 3.2–6.4) for overall placental insufficiency. Conclusions: Uterine artery Doppler at 22–24 weeks identifies women at higher risk for the development of subsequent complications of placental insufficiency. This test could be used in combination with other markers to stratify the level of care offered in the third trimester of pregnancy.

Subendometrial power Doppler quantification: a new classification proposal

Fifty-two women with regular menses were enrolled in the study. The patients were not allowed to use non-steroidal anti-inflammatory drugs within 24 h of any examination. All patients were examined during the mid-luteal phase (6-9 days after ovulation, according to previous ultrasound record). Power Doppler energy levels were classified into five categories according to the per cent area of sub-endometrial signal: I (<10%), II (10-25%), III (25-50%), IV (50-75%) and V (>75%). The colour Doppler signal was considered positive when it reached at least the endometrial basal layer. The picture of the endometrium was analysed and the regions of interest were identified and marked for further analysis. Each recorded image was then independently evaluated and classified by three blinded observers. According to the power Doppler classification, age, body mass index (BMI) and endometrial thickness were analysed, and no significant differences were observed among them. The Kappa test (0.70) demonstrated an excellent agreement among examiners (P = 0.0001). This study has validated a very simple and cost-effective classification for sub-endometrial vascularization. This method of quantification may potentially be of use, and its relevance to clinical practice should be explored.

Apert syndrome: temporal lobe abnormalities on fetal brain imaging

Apert syndrome is characterized by craniosynostosis and complex hand and foot syndactyly, and an increased risk of brain, palate, heart, and visceral malformations, and intellectual disability. This study aims to describe the structural brain abnormalities detected by dedicated neuroimaging of fetuses with Apert syndrome.