Showing papers in "Prenatal Diagnosis in 2010"

The making of fetal surgery.

Abstract: Fetal diagnosis prompts the question for fetal therapy in highly selected cases. Some conditions are suitable for in utero surgical intervention. This paper reviews historically important steps in the development of fetal surgery. The first invasive fetal intervention in 1963 was an intra-uterine blood transfusion. It took another 20 years to understand the pathophysiology of other candidate fetal conditions and to develop safe anaesthetic and surgical techniques before the team at the University of California at San Francisco performed its first urinary diversion through hysterotomy. This procedure would be abandoned as renal and pulmonary function could be just as effectively salvaged by ultrasound-guided insertion of a bladder shunt. Fetoscopy is another method for direct access to the feto-placental unit. It was historically used for fetal visualisation to guide biopsies or for vascular access but was also abandoned following the introduction of high-resolution ultrasound. Miniaturisation revived fetoscopy in the 1990 s, since when it has been successfully used to operate on the placenta and umbilical cord. Today, it is also used in fetuses with congenital diaphragmatic hernia (CDH), in whom lung growth is triggered by percutaneous tracheal occlusion. It can also be used to diagnose and treat urinary obstruction. Many fetal interventions remain investigational but for a number of conditions randomised trials have established the role of in utero surgery, making fetal surgery a clinical reality in a number of fetal therapy programmes. The safety of fetal surgery is such that even non-lethal conditions, such as myelomeningocoele repair, are at this moment considered a potential indication. This, as well as fetal intervention for CDH, is currently being investigated in randomised trials.

Hypertensive disorders in pregnancy: combined screening by uterine artery Doppler, blood pressure and serum PAPP-A at 11-13 weeks.

Abstract: Objective To explore if the addition of pregnancy-associated plasma protein-A (PAPP-A) to maternal factors and biophysical markers yields a significant improvement in the detection of hypertensive disorders before the clinical onset of disease. Methods Prospective screening study for early preeclampsia (PE), late PE and gestational hypertension (GH) in women attending their first hospital visit at 11+0–13+6 weeks of gestation. The performance of screening for PE and GH by combinations of maternal factors, uterine artery with the lowest pulsatility index (L-PI), mean arterial pressure (MAP) and serum PAPP-A was determined. Results There were 8061 unaffected controls, 37 of whom developed early PE, 128 with late PE and 140 with GH. Compared to the controls, in early PE and late PE MAP and uterine artery L-PI were increased and PAPP-A was decreased. In GH PAPP-A was not significantly different from controls. In screening for a combination of maternal factors, uterine artery L-PI, MAP and PAPP-A the detection rate of early PE was 83.8%, at a 5% false-positive rate. In the prediction of late PE and GH there was no significant improvement from the addition of PAPP-A to the combination of maternal factors, MAP and uterine artery L-PI. Conclusion Measurement of PAPP-A improves the performance of screening for early PE provided by a combination of maternal factors and biophysical tests at 11–13 weeks. Copyright © 2010 John Wiley & Sons, Ltd.

Influence of maternal BMI on genetic sonography in the FaSTER trial

Abstract: OBJECTIVE: We sought to evaluate the influence of maternal body mass index (BMI) on sonographic detection employing data from the FaSTER trial. METHOD: Unselected singleton pregnancies underwent detailed genetic sonogram to evaluate for structural fetal anomalies and soft markers for aneuploidy. BMI (kg/m(2)) were calculated from reported initial visit values. Sensitivity, specificity, false positive and false negative rates (FPR and FNR), likelihood ratio, detection rates, and a missed diagnosis rate (MDR: FNR + marker recorded as 'missing'/N) were calculated. RESULTS: Eight thousand five hundred and fifty-five patients with complete BMI information had detailed genetic sonography. A lower sensitivity with an elevated FNR and MDR was observed in obese women for multiple aneuploid markers (e.g. > or =2 markers 32% sensitivity with 68% FNR among BMI 30). Similarly, the detection rate for cardiac anomalies among women at BMI <25 was higher (21.6%) at a significantly lower FPR (78.4%; 95% CI 77.3-79.5%) in comparison to obese women (8.3% with FPR 91.7%; 95% CI 90.1-93.2%). In a logistic regression model, maternal obesity significantly decreased the likelihood of sonographic detection of common anomalies (adjusted OR 0.7; 95% CI 0.6-0.9; p = 0.001). CONCLUSION: The performance of second trimester genetic sonography is influenced by obesity, with a significantly higher MDR for multiple minor markers and lower likelihood for detecting common anomalies.

First-trimester assessment of placenta function and the prediction of preeclampsia and intrauterine growth restriction

Abstract: Preeclampsia and intrauterine growth restriction (IUGR) are major contributors to perinatal mortality and morbidity worldwide. Both are characterized by impaired trophoblastic invasion of the maternal spiral arteries and their conversion from narrow muscular vessels to wide non-muscular channels. Despite improvement in the understanding of the pathophysiology of these conditions, ability to accurately identify pregnant woman who will develop them is limited. This greatly impairs the development and testing of preventive interventions. While different measures of placental dysfunction have been associated with increased risk for adverse pregnancy outcomes, the ability of any single one to accurately predict these outcomes is poor. Developing predictive tests is further challenged by difficulty in the timing of the measurements, as both the structural and biochemical characteristics of the placenta change with increasing gestational age. The ideal screening test would accurately predict the development of adverse pregnancy outcomes early enough to provide a window for preventive interventions. Improvement in ultrasound technology provides potentially useful novel tools for evaluating placental structure, but measurements need to be standardized in order to be useful. Maternal serum analyte screening is a noninvasive test of placental biochemical function, but present serum marker alone is not sufficiently accurate to suggest its routine use in clinical practice. The use of first trimester biochemical markers in combination with uterine artery Doppler screening is promising as a potential screening tool. Prospective longitudinal studies using standardized methodology are necessary to further evaluate the choice of parameters and strategies of combination to achieve the best predictive models.

The maternal age-specific live birth prevalence of trisomies 13 and 18 compared to trisomy 21 (Down syndrome).

Abstract: To estimate the maternal age-specific live birth prevalence (in the absence of prenatal diagnosis and selective termination) of trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) and compare it with that of trisomy 21 (Down syndrome).

Preimplantation genetic diagnosis at 20 years

Abstract: First reported in 1990, PGD has evolved into a complementary form of prenatal diagnosis offering novel indications. DNA for PGD can be recovered with equal safety and facility from polar bodies I and II, blastomere (8 cell embryo) and trophectoderm (5-6 day blastocyst). Diagnostic accuracy is very high (>99%) for both chromosomal abnormalities and single gene disorders. Traditional application of FISH with chromosome specific probes for detecting aneuploidy and translocations may be replaced or complemented by array comparative genome hybridization (array CGH); biopsied embryos can now be cryopreserved (vitrification) while analysis proceeds in orderly fashion. PGD has been accomplished for over 200 different single gene disorders. Novel indications for PGD not readily applicable by traditional prenatal genetic diagnosis include avoiding clinical pregnancy termination, performing preconceptional diagnosis (polar body I), obtaining prenatal diagnosis without disclosure of prenatal genotype (nondisclosure), diagnosing adult-onset disorders particularly cancer, and identifying HLA compatible embryos suitable for recovering umbilical cord blood stem cells.

Increased nuchal translucency in euploid fetuses--what should we be telling the parents?

Abstract: Nuchal translucency (NT) measurement between 11 and 14 weeks' gestation is an undisputed marker for aneuploidies. When conventional karyotyping is normal, enlarged NT is a strong marker for adverse pregnancy outcome, associated with miscarriage, intrauterine death, congenital heart defects, and numerous other structural defects and genetic syndromes. The risk of adverse outcome is proportional to the degree of NT enlargement. Although the majority of structural anomalies are amenable to ultrasound detection, unspecified genetic syndromes involving developmental delay may only emerge after birth. Concern over these prenatally undetectable conditions is a heavy burden for parents. However, following detection of enlarged NT the majority of babies with normal detailed ultrasound examination and echocardiography will have an uneventful outcome with no increased risk for developmental delay when compared to the general population. Counseling should emphasize this to help parents restore hope in normal pregnancy outcome and infant development.

Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth.

Abstract: Objective Barth Syndrome (BTHS) is an X-linked multisystem disorder (OMIM 302060) usually diagnosed in infancy and characterized by cardiac problems [dilated cardiomyopathy (DCM) ± endocardial fibroelastosis (EFE) ± left ventricular non-compaction (LVNC)], proximal myopathy, feeding problems, growth retardation, neutropenia, organic aciduria and variable respiratory chain abnormalities. We wished to determine whether BTHS had a significant impact on fetal and perinatal health in a large cohort of family groups originating from a defined region. Method Case note review on 19 families originating from the UK and known to the Barth Syndrome Service of the Bristol Royal Hospital for Children. Results Details are presented on six kindreds (32%) with genetically and biochemically proven BTHS that demonstrate a wider phenotype including male fetal loss, stillbirth and severe neonatal illness or death. In these families, 9 males were stillborn and 14 died as neonates or infants but there were no losses of females. BTHS was definitively proven in five males with fetal onset of DCM ± hydrops/EFE/LVNC. Conclusion These findings stress the importance of considering BTHS in the differential diagnosis of unexplained male hydrops, DCM, EFE, LVNC or pregnancy loss, as well as in neonates with hypoglycemia, lactic acidosis and idiopathic mitochondrial disease. Copyright © 2010 John Wiley & Sons, Ltd.

Prevention of severe thalassemia in northeast Thailand: 16 years of experience at a single university center

Abstract: Objective To demonstrate the performance of thalassemia prevention in northeast Thailand during 1993-2008. Methods Retrospective data from 1422 at-risk couples who attended from January 1993 to December 2008 were studied. All couples were suspected at-risk couples based on initial screening using standard protocols. Three thalassemia carrier types including alpha(0)-thalassemia, beta-thalassemia and hemoglobin E were identified using standard methods. Data on prenatal diagnosis were collected. Results Of the 1422 positive-screened couples, 1254 (88.2%) were diagnosed as true-positive couples. After DNA analysis, 968 of 1254 (77.2%) resulted at risk for three types of severe conditions being hemoglobin E-beta-thalassemia disease (640/968, 66.1%), homozygous alpha(0)-thalassemia (304/968, 31.4%) and homozygous beta-thalassemia (11/968, 1.1%). The remaining 1.3% of the couples were at risk for more than one disease. After genetic counseling, prenatal diagnosis was performed on 756 couples (78.1%). The proportions of affected fetuses, thalassemia carriers and unaffected fetuses were 26.9, 50.0 and 23.0%, respectively. Conclusion Implementation of a prevention and control program accompanying with a referral system for prenatal diagnosis is technically feasible in northeast Thailand and a large number of severe thalassemia diseases have been prevented during the past 16 years of operation.

Severe congenital toxoplasmosis due to a Toxoplasma gondii strain with an atypical genotype: case report and review

Abstract: Laurence Delhaes1,2*, Daniel Ajzenberg2,3,4, Bérangère Sicot5, Philippe Bourgeot5, Marie-Laure Dardé2,3,4, Eduardo Dei-Cas1,2 and Véronique Houfflin-Debarge5 1Parasitology-Mycology Service (EA3609), Faculty of Medicine, University of Nord de France (UDSL), University Hospital Centre & IFR-142, Institut Pasteur de Lille, Lille, France 2Centre National de Référence (CNR) Toxoplasmose/Toxoplasma Biological Resource Center (BRC), Limoges 87025, France 3Département de Parasitologie-Mycologie, Centre Hospitalier-Universitaire Dupuytren, Limoges 87042, France 4Laboratoire de Parasitologie-Mycologie, EA 3174-NETEC, Faculté de Médecine, Université de Limoges, Limoges 87025, France 5Department of Obstetrics, Lille Hospital, Lille University, Lille, France

A new methodology to preserve the original proportion and integrity of cell‐free fetal DNA in maternal plasma during sample processing and storage

Abstract: Objective To develop a standardized blood collection device that preserves fetal cell-free DNA and minimizes the cell-free DNA background in maternal plasma. Methods Blood samples were drawn from healthy pregnant donors into K3EDTA (BD vacutainer®) and Cell-free DNA™ BCT tubes (Streck®, Inc.) and kept at ambient temperature. Plasma was separated by centrifugation and cell-free DNA was extracted. Cell-free DNA from plasma was quantified by quantitative real-time polymerase chain reaction. Results Blood drawn into Cell-free DNA™ BCT tubes showed no change in the original proportion of fetal cell-free DNA during a 14-day storage period at ambient temperature. Conversely, maternal blood drawn into K3EDTA tubes showed a steady reduction in the original proportion of fetal cell-free DNA over the same time period. Using maternal plasma stored in Cell-free DNA™ BCT tubes for 14 days, fetal cell-free DNA was amplified 80-fold using whole genome amplification (WGA). Conclusion Using Streck's Cell-free DNA™ BCT tubes, it is possible to preserve the original proportion of fetal cell-free DNA for extended times as well as minimize the post-sampling maternal cell-free DNA background. Preserved in this way, fetal cell-free DNA can be amplified by WGA technology to be used in prenatal diagnostic tests. Copyright © 2010 John Wiley & Sons, Ltd.

Predicting the risk of pre-eclampsia between 11 and 13 weeks' gestation by combining maternal characteristics and serum analytes, PAPP-A and free β-hCG.

Abstract: Objective To determine if a simplified model for predicting pre-eclampsia (PEC) can be developed by combining first-trimester serum analytes, pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotrophin (β-hCG), and maternal characteristics. Methods A retrospective cohort study of patients seen for first-trimester aneuploidy screening from 2003 to 2009. The 5th, 10th, 90th, and 95th percentiles for the analyte multiples of the medians (MoMs) for our population were determined and evaluated for association with PEC. Univariate and backward stepwise logistic regression analyses were performed and the area under the receiver operating characteristic (ROC) curves [area under curve (AUC)] used to determine the best models for predicting PEC. Results Among 4020 women meeting the inclusion criteria, outcome data was available for 3716 (93%). There were 293 cases of PEC. The final model identified a history of pre-gestational diabetes [aOR 2.6, 95% confidence interval (CI) 1.7-3.9], chronic hypertension (cHTN) (aOR 2.6, 95% CI 1.7-3.9), maternal body mass index (BMI) > 25 (aOR 2.5, 95% CI 1.9-3.4), African American race (aOR 1.8, 95% CI 1.3-2.6), and PAPP-A MoM Conclusion Low first-trimester PAPP-A levels are associated with the development of PEC; however, the model was only modestly efficient in its predictive ability.

Diagnostic utility of array-based comparative genomic hybridization (aCGH) in a prenatal setting

Abstract: Objective Array-based comparative genomic hybridization (aCGH) is a new technique for detecting submicroscopic deletions and duplications. There is limited information regarding its use in the prenatal setting. Here, we present our experience of 269 prenatal aCGHs between 2006 and 2009. Method The indications for testing were fetal anomalies on ultrasound (U/S), advanced maternal age (AMA), family history of a disorder of unknown etiology, parental concern, abnormal routine karyotype and abnormal serum biochemical screening for common fetal aneuploidies. Results Of 15 cases with a known abnormal karyotype, 11 had a normal aCGH. This enabled us to reassure the families and the pregnancies were continued. The remaining four showed an abnormal aCGH, confirming the chromosomes were unbalanced, and were terminated. Of 254 cases with a normal karyotype, 3 had an abnormal aCGH and were terminated. Overall, new clinically relevant results were detected by aCGH in 18 cases, providing additional information for prenatal genetic counseling and risk assessment. Conclusion Our results suggest that prenatal aCGH should be offered particularly in cases with abnormal U/S. We found the rate of detecting an abnormality by aCGH in low-risk pregnancies was 1:84, but larger studies will be needed to expand our knowledge and validate our conclusions. Copyright © 2010 John Wiley & Sons, Ltd.

Hematological characteristics in neonates with twin anemia-polycythemia sequence (TAPS).

Abstract: Objective To evaluate the neonatal hematological features of monochorionic twins with twin anemia–polycythemia sequence (TAPS) and to determine the additional diagnostic value of reticulocyte count measurement. Methods A cohort of consecutive monochorionic twins with TAPS (n = 19) was included in the study and each twin pair was compared with two monochorionic twin pairs (n = 38) unaffected by TAPS or twin–twin transfusion syndrome (TTTS), matched for gestational age at birth. We measured full blood counts on day 1 and determined the incidence of anemia, polycythemia, reticulocytosis and thrombocytopenia. Results Median inter-twin hemoglobin (Hb) difference in monochorionic twins with and without TAPS was 13.7 g/dL and 2.4 g/dL, respectively (p < 0.01). Median inter-twin reticulocyte count ratio in twins with and without TAPS was 3.1 and 1.0, respectively (p < 0.01). Thrombocytopenia (platelet count < 150 × 109/L) occurred more often in the TAPS group than in the control group, 45% (17/38) versus 11% (11/38), respectively (p < 0.01). In the TAPS group, mean platelet count was significantly lower in recipients than in donors, 133 × 109/L versus 218 × 109/L, respectively (p < 0.01). Conclusions TAPS twins have a large inter-twin Hb difference in combination with a large inter-twin reticulocyte count ratio. Recipients are more often thrombocytopenic than donors, probably due to polycythemia. Copyright © 2010 John Wiley & Sons, Ltd.

A retrospective study by oligonucleotide array-CGH analysis in 50 fetuses with multiple malformations.

Abstract: Objective To retrospectively define the frequency and the nature of submicroscopic chromosomal imbalances among fetuses with multiple congenital anomalies (MCA). Methods We used oligonucleotide arrays to perform comparative genomic hybridization after termination of pregnancy in 50 polymalformated fetuses with a normal karyotype. These fetuses presented with at least three significant malformations (42 cases) or a severe brain anomaly (eight cases). Results We identified a deleterious copy number variation (CNV) in five fetuses (10%). De novo genomic imbalances identified in this study consisted of a 6qter deletion in a fetus with brain and renal malformations, a mosaicism for a 8p tetrasomy in a fetus with agenesis of corpus callosum, growth retardation, mild facial dysmorphic features, and vertebral anomalies, a 17p13.3 deletion in a fetus with a complex brain malformation, and a partial 11p trisomy in a fetus with severe growth retardation and oligoamnios. In one case, we identified a partial 17q trisomy resulting from malsegregation of a cryptic-balanced translocation. Conclusions This study shows that array comparative genomic hybridization (aCGH) is particularly effective for identifying the molecular basis of the disease phenotype in fetuses with multiple anomalies. Our study should help to define clinical relevant regions that would need to be included in targeted arrays designed for prenatal testing. Copyright © 2010 John Wiley & Sons, Ltd.

The outcome and prognostic factors of twin-twin transfusion syndrome following fetoscopic laser surgery.

Abstract: Objectives To evaluate the outcome and preoperative risks of twin–twin transfusion syndrome (TTTS) following fetoscopic laser surgery (FLS) Methods A retrospective cohort study of a series of 181 consecutive cases of TTTS before 26 weeks' gestation subjected to FLS at four centers in Japan between July 2002 and December 2006 Results The chances of survival of at least one twin at 28 days of age and 6 months of age were 912% and 901%, respectively The rate of major neurological complications in survivors at 6 months of age was 47% Preoperative findings that were significant risk factors for death were as follows: (1) being donor [odds ratio (OR): 301, 95% confidence interval (CI): 124–731, P = 0015]; (2) reversed (OR: 1178, CI: 305–4555, P < 0001) and absent (OR: 395, CI: 166–943, P = 0002) end-diastolic velocity in the umbilical artery (EDV-UA) of the donor; and (3) reversed blood flow in the ductus venosus of the recipient (OR: 235, CI: 104–529, P = 0040) Conclusions FLS leads to high survival rates and low neurological morbidity for fetuses in TTTS FLS is an effective therapeutic option for TTTS before 26 weeks of gestation Preoperative Doppler findings of the umbilical artery and the ductus venosus are useful in predicting prognosis following FLS Copyright © 2010 John Wiley & Sons, Ltd

QF‐PCR as a stand‐alone test for prenatal samples: the first 2 years' experience in the London region

Abstract: Objective To analyse the results of the first 2 years of a QF-PCR stand-alone testing strategy for the prenatal diagnosis of aneuploidy in the London region and to determine the advantages and disadvantages of this policy. Methods A review of the results of 9737 prenatal samples received for exclusion of chromosome abnormalities. All samples were subjected to QF-PCR testing for common aneuploidies but only samples fulfilling specific criteria subsequently had a full karyotype analysis. Results Of the 9737 samples received, 10.3% had a chromosome abnormality detected by QF-PCR testing. Of the 7284 samples received with no indication for karyotype analysis, 25 (0.3%) received a normal QFPCR result but subsequently had an abnormal karyotype detected either prenatally as a privately funded test or postnatally. Of these samples, without subsequent abnormal ultrasound findings, five had a chromosome abnormality associated with a poor prognosis, representing 0.069% of samples referred for Down syndrome testing. Conclusion While back-up karyotyping is required for some samples, using QF-PCR as a stand-alone prenatal test for pregnancies without ultrasound abnormalities reduces costs, provides rapid delivery of results, and avoids ambiguous and uncertain karyotype results, reducing parental anxiety. Copyright  2010 John Wiley & Sons, Ltd.

Fetal cystoscopy for severe lower urinary tract obstruction—initial experience of a single center

Abstract: Objective To report the experience with fetal cystoscopy and laser fulguration of posterior urethral values (PUV) for severe lower urinary tract obstruction (LUTO). Methods Between July 2006 and December 2008, fetal cystoscopy was offered to 23 patients whose fetuses presented with severe LUTO, favorable urinary analysis and gestational age <26 weeks. Fetal urinary biochemistry was evaluated before and after cystoscopy. All infants were followed 6–12 months after birth. Abnormal renal function was defined when serum creatinine higher than 50 µmol/L (2 Standard Deviation) or the necessity of dialysis or renal transplantation. Autopsy was always performed whenever fetal or neonatal deaths occurred. Results Eleven patients decided to undergo fetal therapy and 12 elected to continue with expectant observation. There was no difference between both groups in gestation age at diagnosis and referral examinations. Urethral atresia was diagnosed in 4/11 (36.4%) fetuses by fetal cystoscopy. At 26 weeks, fetuses that were managed expectantly presented with worse urinary biochemistry results (p < 0.05). Survival rates and percentage of infants with normal renal function were significantly higher in the cystoscopic group than in the expectant group (p < 0.05). Conclusions Percutaneous fetal cystoscopy is feasible using a thinner special cannula for prenatal diagnosis and therapy of LUTO. Prenatal laser ablation of the PUV under cystoscopy may prevent renal function deterioration improving postnatal outcome. Copyright © 2009 John Wiley & Sons, Ltd.

Prediction of adverse pregnancy outcomes by combinations of first and second trimester biochemistry markers used in the routine prenatal screening of Down syndrome.

Abstract: Objective To investigate the associations between four defined adverse pregnancy outcomes and levels of first and second trimester maternal serum markers focusing in particular on how well combinations of markers predict these adverse outcomes. Methods This was a retrospective review of associations between first and second trimester serum markers and adverse pregnancy outcomes among 141 698 women who underwent prenatal screening for Down syndrome in Ontario, Canada. Detection rates (DR), false positive rates (FPR), and odds ratios were estimated using both single and combinations of markers for the adverse outcomes defined. Results Women with decreased second trimester unconjugated oestriol (uE3), deceased first trimester maternal serum pregnancy-associated plasma protein A (PAPP-A), increased second trimester serum alpha fetoprotein (AFP), or increased second trimester total human chorionic gonadotrophin (hCG) were at greater risk of developing adverse pregnancy outcomes. At a 5% FPR, combinations of these markers predicted at best 33.3% of fetal loss and 31.5% of preterm births (PTB) before 32 weeks of gestation. Conclusion There are significant associations between the levels of first and second trimester serum markers and adverse obstetric outcomes. However, even combinations of these markers can only predict adverse obstetric outcomes with modest accuracy. Copyright © 2010 John Wiley & Sons, Ltd.

Trends in prenatal screening and diagnostic testing among women referred for advanced maternal age

Abstract: Objective We evaluated the trends in uptake of amniocentesis and chorionic villi sampling (CVS) for prenatal diagnosis compared with uptake of first and second trimester prenatal serum screening for Down syndrome among patients referred for genetic counseling for advanced maternal age (AMA). Methods Patients referred for AMA genetic counseling from 2001 through 2008 were informed of both prenatal serum screening and invasive diagnostic testing options. Testing offered and testing decisions were entered in a computer database and uptake rates calculated for each year with trends compared using logistic regression analysis. Results From 2001 through 2007, we observed a decline in amniocentesis and CVS uptake (p = 0.0001). This trend reversed in 2008 for both invasive procedures (p = 0.0001). Uptake of prenatal serum screening increased over the study period with uptake of first trimester screening increasing 1.7 fold in 2008. Conclusion Improved prenatal screening tests and increased availability of screening for AMA patients has led to a steady decline in uptake of invasive testing from 2001 through 2007. This trend reversed from 2007 through 2008. Possible reasons for this reversal are discussed. Copyright © 2010 John Wiley & Sons, Ltd.

The use of combined ultrasound and magnetic resonance imaging in the detection of fetal anomalies.

Abstract: Objective To compare the referral diagnosis based on prenatal ultrasound to diagnoses made following combined ultrasound (US) and magnetic resonance imaging (MRI) evaluation at the Texas Children's Fetal Center (TCFC) and postnatal diagnosis. Methods We performed a retrospective review of patients referred to the TCFC between September 2001 and July 2007 with a fetal structural malformation. Data were abstracted to compare the referral diagnosis to TCFC imaging diagnoses and both were compared to postnatal diagnosis. Results Two hundred and twenty-four patients were referred who had a fetal US and MRI at TCFC. The most frequent indications were for abnormalities of the central nervous system (38%) and lung/thoracic cavity (34%), with congenital diaphragmatic hernia (CDH) the single most common referral diagnosis (n = 39; 17%). In 99 cases (42.7%) the referral diagnosis was concordant with the post-referral diagnosis, however, in 68 cases (29.3%) the post-referral diagnosis changed completely, and in 65 cases (28%) additional findings were discovered. Prenatal diagnoses following imaging at TCFC were concordant with postnatal diagnoses in 94.9% of cases. Conclusions Combined ultrasound and MRI provides additional diagnostic information or a corrected diagnosis in 57% of cases over the referral ultrasound diagnosis. Copyright © 2010 John Wiley & Sons, Ltd.

Fetal cardiac tumors: a single-center experience of 40 cases.

Abstract: Objective To determine the natural history and outcome of fetal cardiac tumors. Methods This was a retrospective cohort study of all prenatally detected cases of cardiac tumors at a tertiary cardiac care center. Results Forty fetuses were identified to have one or several cardiac tumors in association with fetal hydrops (18%), ventricular obstruction (30%) and/or arrhythmia (13%). Of 33 cases with rhabdomyoma, three patients elected to terminate the pregnancy, four offspring died at birth and 26 (79%) survived. On follow-up, 95% of all live-born cases with rhabdomyomas were free of cardiac symptoms but 88% had tuberous sclerosis. All three fetuses with teratoma presented with hydrops and none of them survived. In contrast, all three fetuses with cardiac fibroma are alive and have a biventricular physiology. One fetus with a large atrial hemangioendothelioma died in early infancy. Fetal or neonatal death was associated with an earlier cardiac anomaly diagnosis, earlier delivery, larger tumor size and fetal hydrops at presentation. Conclusions The outcome of fetal cardiac tumors was predicted by the etiology and size of the cardiac mass and the presence of hydrops. Although most cardiac rhabdomyomas have a relatively benign perinatal course, the long-term prognosis is determined by the neurological manifestations associated with tuberous sclerosis. Copyright © 2010 John Wiley & Sons, Ltd.

Maternal plasma soluble fms-like tyrosine kinase-1 and free vascular endothelial growth factor at 11 to 13 weeks of gestation in preeclampsia.

Abstract: Objective To investigate the maternal plasma concentration of soluble fms-like tyrosine kinase-1 (sFlt-1) and free vascular endothelial growth factor (free-VEGF) at 11 to 13 weeks of gestation in patients destined to develop preeclampsia (PE) and to examine whether any possible differences in maternal plasma levels are related to uterine artery pulsatility index (PI) and maternal serum placental growth factor (PlGF). Methods Plasma free-VEGF, plasma sFlt-1, serum PlGF and uterine artery PI were measured at 11 to 13 weeks in 90 cases that subsequently developed PE and in 180 unaffected controls. Results In the majority of cases of PE and controls the levels of free-VEGF were undetectable. In the pregnancies that developed PE, compared to unaffected controls, uterine artery PI was higher, serum PlGF was lower but there was no significant difference in levels of sFlt-1. Conclusion Measurement of free-VEGF and sFlt-1 in maternal blood at 11 to 13 weeks of gestation is not useful in the prediction of pregnancies destined to develop PE. Copyright © 2010 John Wiley & Sons, Ltd.

Twin anemia polycythemia sequence from a prenatal perspective

Abstract: Objectives To describe the prevalence, management and outcome of spontaneous twin anemia polycythemia sequence (TAPS) diagnosed in the prenatal period. Method Retrospective analysis of 142 consecutive monochorionic twin pregnancies not diagnosed with twin to twin transfusion syndrome. TAPS cases were identified based on the presence of discordant middle cerebral artery peak systolic velocity (MCA-PSV) measurements and signs suggestive of a chronic intertwin transfusion imbalance: either an elevated reticulocyte count in the anemic twin or the presence of few small unidirectional anastomoses during fetoscopy or at postnatal placental examination. Results Three cases were identified, giving an estimated prevalence of 2%. Prenatal interventions were tailored to the characteristics of each case and consisted of intrauterine transfusion and interruption of the shared circulation by cord coagulation or laser separation. Conclusion In monochorionic twin pregnancies, TAPS is an uncommon prenatal finding. Nonetheless, its incidence seems high enough to recommend screening for this disease by MCA-PSV measurements. Copyright © 2010 John Wiley & Sons, Ltd.

Termination of pregnancy following prenatal diagnosis in France: how severe are the foetal anomalies?

Abstract: Objective To determine how severe were the conditions leading to termination of pregnancy for foetal anomaly (TOPFA) in France. Methods Detailed indications for TOPFA were extracted from medical charts. Results Of 2465 completed records, indications were: chromosomal anomalies n = 963 (39.1%), malformations of a single organ without chromosomal or genetic aetiologies n = 898 (36.4%), multiple malformations without chromosomal or genetic aetiologies n = 238 (9.7%), obstetrical complications n = 161 (6.5%), non-chromosomal genetic diseases n = 158 (6.4%), foetal infections n = 21 (0.9%), unexplained severe oligohydramnios n = 20 (0.8%), foetal exposure to teratogenic agents n = 6. Overall, 33.3% of anomalies were lethal (e.g. anencephaly), 25.2% were expected to result in isolated mental retardation (e.g. Down) and 35.1% in substantial handicap (e.g. myelomeningocele). In 6.4% of cases, the anomaly was either of late onset (e.g. Huntington's disease) or with uncertain prognosis (e.g. agenesis of corpus callosum) or severity was debatable (e.g. single limb agenesis, sickle cell disease). Conclusions Although there is no indisputable definition of which anomalies are ‘severe’, 93.6% of the decisions to terminate the pregnancy were made by women and professionals in reaction to anomalies which clearly were lethal or would lead to substantial physical and/or mental disabilities. Copyright © 2010 John Wiley & Sons, Ltd.

Minimally invasive fetal postmortem examination using magnetic resonance imaging and computerised tomography: current evidence and practical issues

Abstract: For a variety of reasons, acceptance of traditional postmortem examination following foetal or neonatal death has declined significantly in recent years in the UK. Here, we review the case for the development of less invasive autopsy using combined investigations including imaging techniques, in particular, magnetic resonance imaging and computerised tomography.

The natural history of anencephaly.

Abstract: Objective Early elective termination of pregnancy is the most common outcome of a diagnosis of anencephaly in developed countries. Experience and expertise with management of ongoing pregnancies is limited. We aimed to investigate the natural history of these pregnancies from diagnosis to delivery and to determine timing of death. Method A retrospective review of cases of anencephaly diagnosed between 2003 and 2009 in tertiary-referral university teaching hospitals in Cork. Results The majority of cases (25/26; 96%) were diagnosed prenatally at a median gestation of 21+2 weeks (range 13+4–32+4). The median maternal age was 30 years (range 17–41) and 50% were primigravidae. Seven pregnancies were complicated by polyhydramnios and four deliveries were complicated by shoulder dystocia. The median gestation at delivery was 35 weeks (range 22+5–42+6); 69% of labours were induced at a median gestation of 34 weeks. Six women (6/26; 23%) had a pre-labour intrauterine fetal death and nine women (9/26; 35%) had an intrapartum fetal death. Median neonatal survival time was 55 min (range 10 min to 8 days). Six parents donated neonatal organs for transplantation. Conclusion This study provides useful information for health professionals caring for patients with a diagnosis of anencephaly. The majority of these infants die prior to delivery but short-term survival is possible. Copyright © 2010 John Wiley & Sons, Ltd.

Maternal thyroid function at 11 to 13 weeks of gestation and subsequent development of preeclampsia

Abstract: Objective To determine if maternal thyroid function in the first trimester is altered in pregnancies that subsequently develop preeclampsia (PE). Methods Mean arterial pressure (MAP), uterine artery pulsatility index (PI) maternal serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) at 11 to 13 weeks of gestation were measured in 102 singleton pregnancies that subsequently developed PE, and the values were compared to the results of 4318 normal pregnancies. Results In both the PE groups that required delivery before 34 weeks (early-PE) and the late-PE group, compared with the unaffected group, the median MAP multiple of the normal median (MoM) and uterine artery PI MoM were significantly increased. In late-PE but not in early-PE, compared with the unaffected group, the median TSH MoM was significantly increased and the median FT4 MoM was decreased. Logistic regression analysis demonstrated that TSH MoM provided a significant contribution in the prediction of late-PE. Conclusion Impaired thyroid function may predispose to the development of late-PE, and measurement of maternal serum TSH can improve the prediction of late-PE provided by a combination of factors in the maternal history and the measurements of MAP and uterine artery PI. Copyright © 2010 John Wiley & Sons, Ltd.

Assessment of regional right ventricular longitudinal functions in fetus using velocity vector imaging technology.

Abstract: Objectives The velocity vector imaging (VVI) technique is useful to assess regional myocardial mechanics. The aim of this study was to evaluate the usefulness of this technology in assessing regional right ventricular longitudinal functions in the fetus and to establish a nomogram of the right ventricle (RV). Methods We studied 170 healthy fetuses that were divided into five groups based on gestational age. Dynamic digital images of four chambers were collected and analyzed off-line. The longitudinal VVI parameters were calculated in the right free wall and ventricular septum, respectively. Results A total of 151 out of 170 fetuses (89%) were successfully analyzed using VVI, with good inter- and intra-observer agreements. Normal values for velocity, strain, and strain rate were established. The tissue velocity gradually decreased from basal to apical segment (P 0.05). Conclusion Fetal myocardial velocity, strain, and strain rate measurements are easy to obtain and are reproducible. From mid-to-late gestation, the longitudinal tissue velocity of the RV increases with gestational age, whereas strain and strain rate remain stable. These results indicate that myocardial contractility is established in mid-gestation and remains constant throughout gestation. Copyright © 2010 John Wiley & Sons, Ltd.

First trimester aneuploidy screening in the presence of a vanishing twin: implications for maternal serum markers.

Abstract: Objective To assess the impact of a vanishing twin on the levels of the biochemical markers used in the first trimester aneuploidy screening. Methods A retrospective analysis of free β-hCG and PAPP-A levels in 270 women with a normal singleton fetus with ultrasound evidence of a vanishing twin pregnancy. Marker levels (as MoM) were compared in three groups—76 women with a second empty gestational sac, 194 women with a second gestational sac containing a dead fetus with a measurable crown rump length (CRL), and 1360 matched singleton pregnancies. Results In women with a second empty gestational sac, the median free β-hCG and PAPP-A MoMs (0.968 and 1.040, respectively) were not significantly different from the 1.0 MoM in singleton pregnancies. In the group with a vanished twin with a measurable—CRL—there was a significantly increased median PAPP-A MoM (1.317) but the median free β-hCG MoM was not changed (1.024). Modelling this bias in PAPP-A MoM the detection rate for trisomy 21 would fall from 85 to 75%. Conclusion First trimester screening in the presence of a vanishing twin may lead to errors in risk estimation. In such circumstances it may be advisable to restrict screening to the use of nuchal translucency (NT) alone. Copyright © 2009 John Wiley & Sons, Ltd.