To determine which prenatal ultrasound findings indicate the need to also obtain PCR studies for viral genome in women undergoing midtrimester amniocentesis.

This was a retrospective observational study on women that underwent amniotic fluid karyotyping and viral PCR testing for history or ultrasound based indication. Amniotic fluid was tested for adenovirus, cytomegalovirus, respiratory syncytial virus, enterovirus, Epstein–Barr virus, and parvovirus B19 using multiplex PCR study with multiple appropriate controls. Ultrasound findings were coded as normal or abnormal with 34 categories of ultrasound abnormality stratified into 18 subgroups. Relationships between these subgroups and karyotype/PCR results were tested by Pearson chi-square method or Fisher's exact test and overall logistic regression analysis.

Amniotic fluid samples from 1191 patients were obtained for the study. Abnormal karyotype was detected in 5.4% of cases (64/1191), and PCR was positive in 6.5% of cases (77/1191). Abnormal fetal ultrasonographic findings were observed in 28.4% of cases (338/1191). There was an association between intrauterine growth restriction, nonimmune hydrops fetalis, hand/foot anomalies or neural tube defects (NTDs), and PCR positivity. NTDs were associated with PCR positivity in fetuses with normal karyotype and nuchal thickening, cardiac or ventral wall defects were specifically associated with aneuploidy.

Amniotic fluid viral PCR testing should be considered for fetuses with intrauterine growth restriction, nonimmune hydrops fetalis, hand/foot anomalies, or NTDs. After aneuploidy is excluded, NTDs are associated with PCR positivity. © 2012 John Wiley & Sons, Ltd.

To compare the rates of fetal loss, low birth weight, and preterm birth between pregnancies undergoing cordocentesis at mid-pregnancy with placenta penetration and those without it.

Consecutive cases of cordocenteses were prospectively recorded. The inclusion criteria for analysis were: (1) singleton pregnancies, (2) no fetal abnormalities, (3) gestational age of 18–22 weeks, and (4) procedures performed by experienced operators. The primary outcome was fetal loss rate, and the secondary outcomes were rates of failed procedures, low birth weight, and preterm birth.

Of 6147 cordocenteses recorded, 2829 met the inclusion criteria with complete data for analysis. Of these, 654 procedures were further excluded because the puncture site was at cord insertion. The remaining 2175 cases, consisting of 615 procedures with placenta penetration and 1560 cases with no penetration, were analyzed. Cordocenteses with placenta penetration had a significantly higher rate of fetal loss (3.6% vs 1.3%, p = 0.01) as well as of low birth weight and preterm birth.

Cordocentesis with placenta penetration carries a higher risk for fetal loss, preterm birth, and low birth weight. This information may be helpful in prenatal diagnosis counseling, and it may encourage performers to avoid placenta penetration, if possible. © 2012 John Wiley & Sons, Ltd.

High resolution detection of genomic copy number abnormalities in a single cell is relevant to preimplantation genetic diagnosis and potentially to noninvasive prenatal diagnosis. Our objective is to develop a reliable array comparative genomic hybridization (CGH) platform to detect genomic imbalances as small as ~1 Mb in a single cell.

We empirically optimized the conditions for oligonucleotide-based array CGH using single cells from multiple lymphoblastoid cell lines with known copy number abnormalities. To improve resolution, we designed custom arrays with high density probes covering clinically relevant genomic regions.

The detection of megabase-sized copy number variations (CNVs) in a single cell was influenced by the number of probes clustered in the interrogated region. Using our custom array, we reproducibly detected multiple chromosome abnormalities including trisomy 21, a 1.2 Mb Williams syndrome deletion, and a 1.3 Mb CMT1A duplication. Replicate analyses yielded consistent results.

Aneuploidy and genomic imbalances with CNVs as small as 1.2 Mb in a single cell are detectable by array CGH using arrays with high-density coverage in the targeted regions. This approach has the potential to be applied for preimplantation genetic diagnosis to detect aneuploidy and common microdeletion/duplication syndromes and for noninvasive prenatal diagnosis if single fetal cells can be isolated. © 2012 John Wiley & Sons, Ltd.

A decision model was developed, which progresses through three sequential endpoints, and compares screening with no screening: (1) Pre-eclampsia yes/no: calculation of the incremental cost of pre-eclampsia-case averted; (2) Hospital discharge: calculation of the mean accumulated costs until discharge after delivery; and (3) Offspring death: calculation of the incremental cost per quality of life-adjusted life-year gained by screening. Data used includes: (1) Obstetrical data of 14 500 births; (2) cost data from the Israeli Ministry of Health and the literature; and (3) screening performance and outcome from the literature.

(1) The incremental cost of pre-eclampsia-case averted is $66 949 and $24 723 when the prevalence is 1.7 and 5% respectively. (2) With test cost of $112, the total cost until discharge with/without screening is equal. With pre-eclampsia prevalence of 3%, screening is cheaper. (3) The cost per quality of life-adjusted life-year with screening is $18 919 and < $10 000 with pre-eclampsia prevalence of 1.7 and 3%, respectively.

Screening for pre-eclampsia is cost-effective under various scenarios. Copyright © 2012 John Wiley & Sons, Ltd.

To develop a novel prenatal assay based on selective analysis of cell-free DNA in maternal blood for evaluation of fetal Trisomy 21 (T21) and Trisomy 18 (T18).

Two hundred ninety-eight pregnancies, including 39 T21 and seven T18 confirmed fetal aneuploidies, were analyzed using a novel, highly multiplexed assay, termed digital analysis of selected regions (DANSR™). Cell-free DNA from maternal blood samples was analyzed using DANSR assays for loci on chromosomes 21 and 18. Products from 96 separate patients were pooled and sequenced together. A standard Z-test of chromosomal proportions was used to distinguish aneuploid samples from average-risk pregnancy samples. DANSR aneuploidy discrimination was evaluated at various sequence depths.

At the lowest sequencing depth, corresponding to 204 000 sequencing counts per sample, average-risk cases where distinguished from T21 and T18 cases, with Z statistics for all cases exceeding 3.6. Increasing the sequencing depth to 410 000 counts per sample substantially improved separation of aneuploid and average-risk cases. A further increase to 620 000 counts per sample resulted in only marginal improvement. This depth of sequencing represents less than 5% of that required by massively parallel shotgun sequencing approaches.

Digital analysis of selected regions enables highly accurate, cost efficient, and scalable noninvasive fetal aneuploidy assessment. © 2012 John Wiley & Sons, Ltd.

Prenatal tracheal occlusion (TO) promotes lung growth and is applied clinically in fetuses with severe congenital diaphragmatic hernia. Limited data are available regarding the effect of duration of TO on lung development. Our objective was to evaluate the effects of long (2 and 2.5 days) versus short (1 day) TO on lung development in rats with nitrofen-induced diaphragmatic hernia.

Nitrofen was administered on embryonic day (ED) 9 and fetal TO performed either on ED18.5, 19 or 20 (term = 22 days). Sham-operated and untouched littermates served as controls. On ED21, lungs were harvested and only fetuses with a left-sided diaphragmatic defect were included in further analyses.

Lung–body-weight ratio incrementally increased with the duration of TO. Increased proliferation following long TO was confirmed by immunohistochemistry and qRT-PCR for the proliferation marker Ki-67. Irrespective of duration, TO induced more complex airway architecture. Medial wall thickness of pulmonary arteries was thinner after long rather than short TO.

In the nitrofen rat model of congenital diaphragmatic hernia, a longer period of TO leads to enhanced lung growth and less muscularized pulmonary arteries. © 2011 John Wiley & Sons, Ltd.

We reviewed the results of CFTR gene analysis over the period 2002 to 2009 in all consecutive cases referred because of NVFGB in Western France. We correlated these data with the presence of a more classical ultrasonographic finding (fetal echogenic bowel – FEB).

Cystic fibrosis was diagnosed in 5 of the 37 fetuses with NVFGB (13.5%, 95% confidence interval (CI): [2.5%; 24.5%]) and in only 9 of the 229 other cases referred because of FEB (3.9%, 95% CI: [3.2%; 14.7%]). In our series, all CF-affected fetuses with NVFGB also had FEB. The risk of CF was 11.6-fold higher in fetuses with both indications (NVFGB + FEB) than in fetuses with isolated FEB (45.5% vs 3.9%, RR = 11.6, 95% CI: [4.7%; 28.8%], p = 0.0001). We also estimated that the residual risk of CF was less than 1 in 68 (1.5%) when a single mutation was identified in the fetus by our molecular protocol.

Ultrasonographic evidence of NVFGB is an additional risk factor for CF in cases with FEB. Copyright © 2011 John Wiley & Sons, Ltd.

Plasma DNA was extracted from 10 mL of maternal blood from couples who both were alpha-thalassemia-1 carriers (SEA deletion). Real-time quantitative PCR was performed using fluorescence-labeled probes to monitor wild type (wt) and SEA alleles. The quantity of each allele was determined by the cycle threshold (Ct). ΔCt (Ct of wt – Ct of SEA) was calculated from each sample. Prenatal diagnosis was performed to determine fetal status.

There were 62 Hb Bart's, 62 alpha-trait, and 34 normal fetuses in this study. Mean ΔCt was 1.04±0.38, 0.21±0.37, and 0.14±0.55 in Hb Bart's, alpha-trait and normal fetuses, respectively. On the basis of the receiver operating characteristic curve, the best cut-off of ΔCt for predicting Hb Bart's was 0.51, giving a 98.4% sensitivity and 20.8% false-positive rate. All but one Hb Bart's (98.4%) had ΔCt above 0.51, whereas 74.2% of alpha-trait and 88.2% of normal fetuses had ΔCt below 0.51.

There is a positive trend to use cff-DNA in maternal plasma for prenatal diagnosis of homozygous alpha-thalassemia-1. With this technique, invasive prenatal testing and complications can be avoided in 79.2% of unaffected fetuses. Copyright © 2011 John Wiley & Sons, Ltd.

We searched the PUBMED database using keywords ‘amniocentesis’, ‘twin’, and ‘twins’ to identify articles evaluating genetic amniocentesis in twin gestations published from January 1970 to December 2010. Random effects models were used to pool procedure-related loss rates from included studies.

The definition of ‘loss’ varied across the 17 studies identified. The pooled procedure-related loss rate at < 24 weeks was 3.5% (95% confidence interval 2.6–4.7). Pooled loss rates at < 28 weeks and to term could not be calculated because of unacceptable heterogeneity of available data. Seven studies included a control (no amniocentesis) group and reported a pooled odds ratio for total pregnancy loss among cases of 1.8 (95% confidence interval 1.2–2.7). Only one study reported procedure-related loss rates by chorionicity (7.7% among monochorionics vs 1.4% among controls; p 0.02).

Analysis of published data demonstrated a pooled amniocentesis-related loss rate of 3.5% in twin gestations < 24 weeks. Pooled loss rates within other post-amniocentesis intervals or other gestational age windows and the impact of chorionicity on procedure-related loss rates cannot be determined from published data. Copyright © 2011 John Wiley & Sons, Ltd.

To evaluate the use of microarray analysis as a tool for the detection of submicroscopic chromosomal aberrations in prenatal diagnosis.

Twelve consecutive singleton fetuses with congenital heart defects but normal karyotype and normal fluorescence in situ hybridization results for the DiGeorge region were examined for chromosomal aberrations by genomic microarray analysis. Results were confirmed by fluorescence in situ hybridization and quantitative real time-polymerase chain reaction.

At 1 Mb resolution, potentially causal copy number variations were identified in 3 out of 12 fetuses (25%) comprising a 9 Mb q terminal deletion on chromosome 15, a 3.5 Mb duplication in the critical region for the Potocki–Lupski syndrome on chromosome 17 and a mosaic trisomy 7. At higher resolution, aberrations with uncertain significance were identified in a further three cases (25%).

In our study, the application of microarray analysis in prenatal testing proved to be a valuable tool for the identification of submicroscopic chromosomal aberrations where conventional cytogenetic methods failed. Selection of appropriate resolution was found to be critical to obtain reliable, diagnostically conclusive data. © 2011 John Wiley & Sons, Ltd.

We selected 48 cases of high-risk pregnancies (in utero growth retardation [IUGR] and/or at least two fetal malformations [polymalformation]). Bacterial artificial chromosome array CGH (BlueGnome) was performed on 38 fetal samples (frozen cff DNA and DNA from cultured cells) with previously normal karyotypes.

From the 38 specimens, we obtained an adequate amount of sufficient quality DNA with a better quality profile using cff DNA compared to cellular DNA.

Aberrations of clinical relevance were detected in three fetuses, and copy number variations considered as benign polymorphism were detected in one case using both sources of DNA. This results in an 8% detection rate of significant abnormalities in high-risk pregnancies with a normal karyotype using array CGH (two cases with IUGR, one with polymalformation).

These findings indicate the possibility of using cff DNA from amniotic fluid supernatant for array CGH with excellent results, even in late pregnancy when culture is no longer available. In this small series, pathogenic copy number variations are detected more often in the presence of IUGR than with polymalformation. Copyright © 2011 John Wiley & Sons, Ltd.

We retrospectively analyzed a cohort of fetuses prenatally diagnosed with SCT between September 2000 and December 2010. Postnatal outcomes were evaluated in relation to the need for intervention in utero by reviewing medical records.

Of the 35 fetuses diagnosed with SCT during the study period, ten were lost to follow up and three had been misdiagnosed as SCT. Among the remaining 22 cases, in utero interventions were performed in eight, including radiofrequency ablation (RFA) in four, shunt operations in two, RFA plus cyst aspiration in one, and RFA with subsequent shunt operation in one. Tumors of cases undergoing in utero intervention were larger with rapidly growing, more frequently vascular, and with associated polyhydramnios or cardiomegaly. The rate of preterm births was higher in the cases that underwent interventions compared with those that did not (7/8 vs 2/14). Only one tumor showed regression after RFA while the other seven increased in size. Median tumor size at birth was significantly larger in the intervention group than in the nonintervention group (136 mm vs 80 mm). The neonatal survival rate was 6/8 for the prenatal intervention group and 14/14 for the nonintervention group. Resection of SCT was required in all neonates. The most common complication after postnatal surgery was fecal incontinence.

Fetuses with SCT undergoing in utero intervention have worse prognostic features, yet their neonatal outcome is similar to those of fetuses not requiring intervention. Copyright © 2011 John Wiley & Sons, Ltd.

A survey instrument was used to assess components of decision-making among women who presented for first trimester aneuploidy screening. Knowledge and leading factors in the decision-making process were measured.

Participants (n = 139) demonstrated understanding of the etiology of Down syndrome, but less understanding of its cognitive (65.2%) and physical manifestations (58.7%). Few were able to determine risk from first trimester screen results (36.7%). Participants were more familiar with amniocentesis (84.2%) than chorionic villus sampling (73.4%), though less familiar with procedural risks (29.5% and 28.1%, respectively). The majority of participants ranked the following as key information in their decision: knowledge of their intentions about the outcome of the pregnancy based on the test results (92.4%), knowledge of chorionic villus sampling to evaluate an abnormal result (92.0%), and values and beliefs about termination (89.1%).

First trimester aneuploidy screening generates education and decision-making benchmarks for patients and providers. It is important to address these barriers as this new screen becomes a growing part of current prenatal genetic testing offerings. Copyright © 2011 John Wiley & Sons, Ltd.

One hundred NT images without measurements were selected from the digital database. Half had NT measurements between 2.5 and 3.5 mm, and half had NT measurements above 3.5 mm. Five operators (two experts, three general gynaecologist) measured fetal NT manually and automatically. Each operator was blinded to any pre-existing measurements. Each image was measured twice by each operator. Intraoperator repeatability was assessed by standard deviation of within sonographer repeated measurement. Interoperator repeatability was assessed as difference towards the gold standard, which was defined as the mean measurement of experts.

The overall standard deviation of the difference between the first and the second manual measurements was 0.14 and 0.10 mm for moderate and severely increased NT. It was 0.10 and 0.08 mm with the semi-automated system. Mean difference between the manual measurement of nonexpert operators and the gold standard was −0.01 mm for moderately increased NT and 0.02 mm for severely increased NT. With the semi-automated measurement, mean bias was similar.

The automated NT measurement leads to a further standardization of the NT assessment process. Especially inexperienced operators may benefit from this tool. Copyright © 2011 John Wiley & Sons, Ltd.

This is a cross-sectional study that enrolled 425 healthy pregnant women between the 20^th and 40^th weeks of gestation. The XI VOCAL was performed along the axial cross-section in ten sequential areas for the volumetric calculations, having the proximal and distal echogenic diaphysis as references. Second-degree polynomial regression models, with the determination of percentiles, were created to evaluate the relation between the fetal thigh volume and gestational age (GA). Intraoperator and interoperator reproducibility was evaluated using intraclass correlation coefficient.

The mean fetal thigh volume varied from 8.00 (3.90–11.90 cm³) to 122.14 cm³ (105.0–153.50 cm³) at 20 and 40 weeks of gestation, respectively. Fetal thigh volume was strongly correlated with gestational age, and the reference values can be obtained by the following mathematical equation: fetal thigh volume (cm³) = 68.70–7.63 × GA + 0.23 × GA² (R² = 0.946). The intraoperator and interoperator reproducibility were excellent, with an intraclass correlation coefficient = 1.000 and 0.999, respectively.

The reference range of fetal thigh volume was determined by 3D-ultrasound using the XI VOCAL method. Copyright © 2011 John Wiley & Sons, Ltd.

In this retrospective study data (n = 26 274) from a fetal medicine center on FCT (maternal age, fetal NT, free β-human chorionic gonadotrophin, pregnancy-associated plasma protein-A) were studied.

70.6% of cases was <36 years and 43% of the Down syndrome (DS) cases were detected in this age group. For women <36 years and advanced maternal age (AMA) women (≥36 years) detection rate (DR) and false positive rate (FPR) were 94.5% and 4.1%, and 95.8% and 13.0%, respectively (cut-off 1:200). Lowering the cut-off showed an improved balance in DR and FPR. With increasing maternal age FPR and DR increased and odds of being affected given a positive result (OAPR) decreased.

FCT is effective in women <36 and ≥36 years. The balance between FPR and DR is more favourable in women <36 years with comparable OAPR. Although FPR increases with increasing maternal age, performance of FCT in AMA women is more effective than screening based on maternal age alone. Lowering the cut-off to 1:100 in AMA women is suggested to improve screening performance. Routinely offering diagnostic testing to AMA women as a screening policy for the detection of DS seems not reasonable. Copyright © 2011 John Wiley & Sons, Ltd.

A prospective cohort study with 103 healthy pregnant women. Uterine artery Doppler velocimetry was performed at between 11 and 14 weeks of gestation. Abnormal blood flow was defined as average pulsatility index >1.5 and presence of unilateral or bilateral diastolic notch. Doppler scores were calculated by a modified scoring method of uterine artery flow velocity waveforms. Serum for measurement of homocysteine, vitamin B₁₂ and folate levels were collected when the ultrasonographic measurement was performed.

Pre-eclampsia developed in five, gestational hypertension in three, intrauterine growth restriction in two and preterm birth in eight patients. There was a significant difference between mean plasma homocysteine levels at different Doppler scores (p<0.001) and a weak positive correlation between Doppler scores and occurrence of pregnancy complications (r_s= 0.232, p<0.05). Mean homocysteine level increased with increasing Doppler scores. Any uterine artery abnormality had a sensitivity of 88.9% in predicting obstetric complications. Addition of hyperhomocytenemia to Doppler scores did not change the sensitivity.

Maternal serum homocysteine level is increased in 11 to 14 weeks of gestation that is complicated with pre-eclampsia, gestational hypertension, intrauterine growth restriction and preterm birth. Addition of homocysteine determination to uterine artery Doppler in the first trimester does not add any advantage in predicting adverse perinatal outcome. Copyright © 2011 John Wiley & Sons, Ltd.

We interviewed 201 English-speaking or Spanish-speaking caregivers of children aged 2 to 10 years. Primary outcomes were being disinclined to undergo prenatal testing or pregnancy termination for the child's condition in a future pregnancy.

While only 33% of the sample indicated they would not have prenatal testing, 75% were disinclined to terminate their pregnancy if their fetus was affected. In multivariable logistic regression analysis, Asians were significantly less likely than White participants to say they would forego prenatal testing (adjusted odds ratio (aOR) = 0.08, 95% confidence interval (CI) = 0.01–0.86, p = 0.037), while Latinos had lower odds of being disinclined to terminate (aOR = 0.27, 95% CI = 0.07–0.99, p = 0.048). Participants who felt that abortion for their child's condition should not be available were more likely to say they would forego prenatal testing (aOR = 5.10, 95% CI = 2.09–12.43, p < 0.001) and, not surprisingly, they were also at higher odds of being disinclined to terminate pregnancy for this condition (aOR = 13.63, 95% = CI 4.19–44.34, p < 0.001). Greater life satisfaction also was associated with being disinclined to terminate pregnancy (aOR = 3.40, 95% CI = 1.34–8.61, p = 0.010).

Although many parents of children with intellectual disabilities believe they would desire information regarding their fetus in a future pregnancy, most feel they would not opt to terminate their pregnancy. As new tests for intellectual disabilities become available, determining what would be most useful to prospective parents should become a high priority. Copyright © 2011 John Wiley & Sons, Ltd.

We assessed the prevalence of HBP in women at the time of the first pregnancy visit using both a prospective cohort (N = 703) and a retrospective series of women selected at random (N = 588). For the purpose of analysis, the population was divided into a high risk and a low risk group for HBP based on maternal ethnicity. Screening for HBP utilized standard screening tests for anemia, with additional high performance liquid chromatography (Variant II); molecular analysis was performed by Gap-polymerase chain reaction (Gap-PCR) and if necessary, direct sequencing and multiplex ligation-dependent probe amplification (MLPA). Family history was reported or collected from the medical records.

β-Globin defects were found in 3.9% of the total population (50/1291). The frequency in the high risk population was 5.6% (37/656), compared with 1.2% (6/501) in the low risk group. In the prospective study we found 30 HBP carriers, leading to testing of 16 partners and identification of two couples at risk. One affected child was born. Mean gestational age at the screening was 11.3 weeks with a standard deviation (SD) of 5.8.

We found that the prevalence of HBP carriers is high enough in our population to warrant HBP testing for the entire multiethnic population in early pregnancy at the time of anemia screening. This is feasible as most women had their booking early in their first trimester. Copyright © 2011 John Wiley & Sons, Ltd.

Using population-based data of the Paris Registry of Congenital Malformation for 935 fetuses with CHD and without chromosomal anomalies for the period 2001 to 2007, we calculated sensitivity of NT, its positive predictive value and likelihood ratio, for all CHD and for six types of CHD.

Sensitivity of NT was 7.1 and 4.2% for the 2.5 and 3.5 mm cut-off values, respectively; when isolated ventricular septal defects were excluded, sensitivity increased to 9.9 and 6.3%. Positive predictive values were 1.1 and 3.2% for 2.5 and 3.5 mm cut-offs, respectively. Of the six defects examined, sensitivity of NT was highest for heterotaxy followed by hypoplastic left heart syndrome and coarctation of aorta.

Prevalence of CHD was about fourfold higher for fetuses with NT ≥ 3.5 mm (3.2%) than in the general population. This higher risk is comparable to that of other risk factors commonly used for early referral to specialized echocardiography. Nevertheless, our results, suggest that NT is not a very effective or efficient tool for the prenatal screening of CHD. Copyright © 2011 John Wiley & Sons, Ltd.

Women undergoing amniocentesis or chorionic villus sampling were offered aCGH analysis. A total of 1037 prenatal samples were processed in parallel using both aCGH and G-banding for standard karyotyping. Specimen types included amniotic fluid (89.0%), chorionic villus sampling (9.5%) and cultured amniocytes (1.5%).

Chromosomal abnormalities were identified in 34 (3.3%) samples; in 9 out of 34 cases (26.5%) aCGH detected pathogenic copy number variations that would not have been found if only a standard karyotype had been performed. aCGH was also able to detect chromosomal mosaicism at as low as a 10% level. There was complete concordance between the conventional karyotyping and aCGH results, except for 2 cases that were only correctly diagnosed by aCGH.

This study demonstrates that aCGH represents an improved diagnostic tool for prenatal detection of chromosomal abnormalities. Although larger studies are needed, our results provide further evidence on the feasibility of introducing aCGH as a first-line diagnostic test in routine prenatal diagnosis practice. Copyright © 2011 John Wiley & Sons, Ltd.

Fetal penile length was measured by high resolution transvaginal ultrasound at 14 to 16 weeks and by transabdominal ultrasound at 17 to 35 weeks' gestation.

Fetal penile length increased significantly with gestational age (GA), from 7 mm at 14 weeks' to 50 mm at 35 weeks' gestation. Penile length measurements were strongly related to the biometric fetal measurements.

A reference range of the fetal penile length was constructed, measured from the proximal edge of the corpus cavernosum to the tip of the glans penis at 14 to 35 gestational weeks. This reference range can assist in early identification of true penile maldevelopment, which obligate further diagnostic workup, as opposed to the benign disorder of buried or concealed fetal penis. Copyright © 2011 John Wiley & Sons, Ltd.

One hundred and fifty lay persons and 120 medical practitioners were given separate questionnaires and asked their opinions regarding LTOP for prenatally detected fetal abnormalities of varying severity. The views regarding legalisation of LTOP and the acceptability of feticide by the lay persons were also ascertained.

More than two-thirds of the lay persons and majority (85.8%) of clinicians felt that LTOP should be allowed for fetal conditions with poor prognosis. At least 70% of lay persons felt that LTOP should be legalised for severe fetal abnormalities. For potentially treatable conditions, continuation of pregnancy in late gestation was the preferred option. For lethal malformations like anencephaly and disorders requiring lifelong treatment like meningomylocele and thalassemia major, majority of clinicians (86.7%, 69.2% and 55.8%, respectively) and lay persons (65%, 51% and 25%, respectively) had the opinion that termination of pregnancy can be offered at any gestational age.

Both the lay persons as well as the medical fraternity in India feel the need to look into revision of legalisation of LTOP particularly for fetal conditions with poor outcome. Copyright © 2011 John Wiley & Sons, Ltd.

Written questionnaires were administered to women in their third trimester.

One hundred fourteen women returned the questionnaire (80.9% response rate). Of these, 71.9% reported interest in NIPD, 22.7% were ambivalent, and 5.4% were uninterested. Safety of the fetus was the single most important factor in 75% of women's decisions. Factors associated with increased interest in NIPD included: older age (p = 0.036), higher education (p = 0.013), Caucasian or Asian ethnicity (p = 0.011), and higher likelihood to terminate an affected pregnancy (p = 0.002). Nearly 20% of women reported that they would do whatever their doctor recommended regarding NIPD, and 94.4% of women wished to meet with a genetic counselor at some point to discuss NIPD.

The majority of pregnant women report hypothetical interest in NIPD, primarily because of increased safety for the fetus, although a significant minority are uninterested or ambivalent. Discussions with healthcare providers regarding NIPD, and their recommendations, are likely to be an important factor in women's decisions about this testing. As such, adequate discussion of the implications of prenatal diagnostic testing will be critical. Copyright © 2011 John Wiley & Sons, Ltd.

We analyzed qualitative and quantitative data obtained in a previous study performed with real-time PCR to determine the accuracy of NIPD RhD following two different DNA extraction protocols. The number of days from phlebotomy until freezing of plasma at the study site was recorded and defined as transport time.

NIPD RhD results of 972 specimens were analyzed according to transport time, which varied from a few hours to a maximum of 8 days (median 2 days). No decrease of cell-free fetal DNA was observed in samples with less than 6 days transport time. There was a pivotal trend to higher cycle threshold values in samples with ≥ 6 days transport time compared with those with ≤ 5 days.

Because only a few laboratories offer an NIPD RhD service, we suggest a maximal transport time of 5 days from phlebotomy until freezing at the testing laboratory. Copyright © 2011 John Wiley & Sons, Ltd.

Post hoc analysis of 3D ultrasound volumes acquired at 11 to 13 weeks in 223 pregnancies was performed to identify the appropriate sections for evaluation of three screening markers and ten fetal anatomy landmarks. When possible, the fetal profile was used as the starting section for volume acquisition.

When the fetal profile was used, satisfactory images for assessment were obtained in 90% of cases for nuchal translucency and 72% for the nasal bone, whereas successful evaluation of the ten anatomical landmarks ranged from 0 to 99%. In alternative starting sections, the corresponding success rates were 65%, 48%, and 0–95%.

Although performance of post hoc analysis of 3D volumes is best when carried out from a profile starting section and quicker than two-dimensional analysis, it appears to be not ready for clinical use because nuchal translucency could not be examined in 10% of the fetuses. Copyright © 2011 John Wiley & Sons, Ltd.