Acute and chronic optic nerve head biomechanics and intraocular pressure changes in patients receiving multiple intravitreal injections of anti-VEGF.

PURPOSE: To evaluate acute and chronic changes in optic nerve head (ONH) structures and intraocular pressure (IOP) in patients receiving intravitreal injections (IVIs) of anti-VEGF. METHODS: Twenty-nine eyes receiving IVIs for the first time were studied. IOP, retinal nerve fiber layer (RNFL) thickness, and ONH structures were evaluated by Spectralis optical coherence tomography with enhanced depth imaging technology. Structures were measured before and 5 min after each one of the three monthly injections of a loading dose treatment. In 13 eyes (44.8%) with more than six IVIs, another evaluation pre and immediately postinjection was performed after 1 year. RESULTS: A significant acute and transient IOP increase (all p ≤ 0.001), Bruch's membrane opening (BMO) enlargement (p ≤ 0.001), cup widening (p < 0.05) and deepening (p ≤ 0.001), and prelaminar tissue thinning (p ≤ 0.001) were observed 5 min after each injection. Compared with baseline values, a significant BMO expansion (p = 0.001) and RNFL thinning (p < 0.001) were observed in the third month. In eyes with more than six IVIs, similar immediate postinjection changes, including IOP increase (p = 0.001), prelaminar tissue thinning (p = 0.007), and cup deepening (p = 0.012) were observed at 1 year, while BMO expansion was not significant (p = 0.556). Compared with baseline preinjection values, a significant BMO expansion (p = 0.003), prelaminar tissue thinning (p = 0.011), and cup deepening (p = 0.006) in the inferior region of the ONH occurred. No change in IOP was observed at the end of follow-up. CONCLUSIONS: Repeated IVIs could lead to irreversible changes in ONH structures. Large-scale, prospective studies are required to determine the long-term effects of anti-VEGF treatments in ONH tissues.

Higher levels of procoagulant microparticles in women with recurrent miscarriage are not associated with antiphospholipid antibodies.

STUDY QUESTION: Are the levels of circulating cell-derived microparticles (cMPs) in patients with recurrent miscarriage (RM) associated with the antiphospholipid syndrome (APS)? SUMMARY ANSWER: cMPs in women with RM are not associated with antiphospholipid antibodies (aPLs). WHAT IS KNOWN ALREADY: Previous studies have focused on cMP levels in RM patients. Most studies have shown higher levels of cMPs in RM patients whereas others have reported lower levels. Data regarding cMPs in patients with the APS are scanty in the literature. STUDY DESIGN, SIZE, DURATION: A case-control study including three groups of patients. A total of 154 women were prospectively recruited from September 2009 to October 2013. Four patients refused to participate. The APS group consisted of 50 women that had been previously diagnosed with primary APS and had had ≥3 consecutive first trimester miscarriages. The uRM group included 52 couples with ≥3 consecutive first trimester miscarriages of unknown etiology. The fertile control (FER) group was composed of 52 healthy fertile women with no history of pregnancy losses. Miscarriage was defined as intrauterine pregnancy loss at <10 weeks' size on ultrasound. PARTICIPANTS/MATERIALS, SETTING, METHODS: Venous blood samples for coagulation studies and cMP determinations were obtained. All patients underwent a thrombophilia study. MAIN RESULTS AND THE ROLE OF CHANCE: cMP levels were significantly higher in the APS and uRM groups versus the FER group (P < 0.0001 and P = 0.009, respectively) (cMP number × 10(3)/ml plasma [mean ± SD]: APS: 18.5 ± 13.6; uRM: 16.3 ± 13.8; FER: 9.7 ± 4.6). There were no statistically significant differences in cMP levels between the APS and uRM groups. LIMITATIONS, REASONS FOR CAUTION: The sample size was arbitrarily decided according to previous studies analyzing cMPs in RM patients. Different cMP subtypes were not investigated. WIDER IMPLICATIONS OF THE FINDINGS: The present study adds further data on the subject showing that patients with RM, irrespective of testing positive for aPLs, have increased levels of cMPs compared with healthy fertile controls. The presence of elevated cMPs in RM women may reflect an ongoing systemic pathological, albeit asymptomatic, status that can become deleterious in the setting of pregnancy. STUDY FUNDING/COMPETING INTERESTS: This study was supported in part by grant from FIS-PI11/01560 within the 'Plan Nacional de I+D+I' and co-funded by the 'ISCIII-Subdirección General de Evaluación' and the 'Fondo Europeo de Desarrollo Regional (FEDER)'. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: Not applicable.

Evidence of second-trimester changes in head biometry and brain perfusion in fetuses with congenital heart disease.

OBJECTIVES: To evaluate the associations between congenital heart disease (CHD) and head biometry and cerebrovascular blood flow dynamics at the time of diagnosis of CHD in the second trimester of pregnancy. METHODS: This was a study of 95 consecutive fetuses diagnosed with CHD. At the time of diagnosis, fetal biometry was performed and brain perfusion was assessed by middle cerebral artery pulsatility index (MCA-PI), cerebroplacental ratio (CPR) and fractional moving blood volume (FMBV). The results were compared with those of 95 normal fetuses matched for gestational age. RESULTS: Median gestational age at diagnosis was 22 + 3 (range, 20 + 0 to 23 + 5) weeks. Fetuses with CHD showed significantly lower MCA-PI and CPR Z-scores (-0.23 vs 0.34 and -0.37 vs 0.30, respectively; both P < 0.001) and higher FMBV Z-scores (2.35 vs 0.15; P < 0.001). FMBV > 95(th) percentile was observed in 81.1% of cases as compared with 10.5% in controls (P < 0.001). Moreover, cases showed significantly smaller biparietal diameter (BPD) and head circumference (HC) Z-scores (-1.61 vs -0.43 and -0.89 vs 0.09, respectively; both P < 0.001), with a higher proportion of BPD and HC measurements below the 5(th) percentile compared with controls (51.6% vs 13.7% and 26.3% vs 4.2%, respectively; both P < 0.001). These findings were more pronounced in those cases with types of CHD associated with compromised oxygenated blood delivery to the brain, such as left outflow tract obstruction and transposition of the great arteries. CONCLUSIONS: A high proportion of fetuses with CHD have a smaller head and increased brain perfusion already in the second trimester, suggesting an early onset of the mechanisms leading to poorer neurodevelopment later in life.

Isolated ventricular septal defects in the era of advanced fetal echocardiography: risk of chromosomal anomalies and spontaneous closure rate from diagnosis to age of 1 year.

OBJECTIVES: To evaluate, in a cohort of 248 fetuses seen at a tertiary referral center, the frequency of isolated ventricular septal defects (VSD) among all congenital heart defects (CHD), the association with chromosomal and postnatal anomalies and the rate of spontaneous closure. METHODS: This was a 6-year study on 10,800 women referred for fetal echocardiography, with 995 confirmed cases of CHD. The prevalence and characteristics of VSDs were analyzed, including follow-up until 1 year of age. Multivariate binary logistic regression analysis was performed to test the independent contribution of the ratio of the diameter of the VSD to that of the aorta (VSD/aorta ratio) (< 0.5 or ≥ 0.5) and location of VSD (perimembranous or muscular) in the prediction of spontaneous closure before the age of 1 year. RESULTS: Two hundred and forty-eight VSDs (24.9% of all CHDs) were diagnosed, of which 216 (87.1%) were muscular and 32 (12.9%) perimembranous. Median gestational age at diagnosis was 30.4 (range, 17-41) weeks and mean size 2.6 ± 0.77 mm. Clinically relevant chromosomal anomalies were found in one (3.1%) perimembranous VSD compared with none in 216 muscular defects (P = 0.12). Postnatal malformations were diagnosed in eight of the 211 cases (3.8%) evaluated at 12 months postpartum. Spontaneous closure occurred prenatally in 13 fetuses (5.2%) and postnatally in 151 of the 198 infants (76.3%) who had an open VSD at birth. Closure was predicted by the VSD/aorta ratio (odds ratio (OR) 0.445 (95% CI, 0.216-0.914); P < 0.03) and location (OR 0.385 (95% CI, 0.160-0.926); P < 0.03). CONCLUSIONS: In our fetal cardiology unit, isolated muscular VSD is today the most prevalent CHD. In contrast to the findings of postnatal studies, muscular VSDs were more common than perimembranous VSDs. Perimembranous VSDs were associated with a higher risk of chromosomal anomalies than were muscular VSDs, which had a similar risk to those of normal pregnancies. Spontaneous closure of the VSD was frequent and occurred in most cases postnatally.

Evaluation of fetal vocal cords to select candidates for successful fetoscopic treatment of congenital high airway obstruction syndrome: preliminary case series.

OBJECTIVE: Congenital high airway obstruction syndrome (CHAOS) normally has a dire prognosis due to laryngeal atresia and association with other anomalies. However, rare cases with an isolated tracheal membrane have been described. We assessed systematically the larynx and vocal cords in fetuses with CHAOS, with the goal of identifying such cases and attempting fetoscopic deobstruction. METHODS: Between 2008 and 2012, 7 cases of CHAOS were referred to our institution. The ultrasonographic aspect of the larynx and trachea was assessed. We report the ultrasound findings, necropsy findings of 6 cases and perinatal outcome in 1 case undergoing therapy. RESULTS: In 6 cases, laryngeal atresia was presumed by ultrasound and confirmed by necropsy after termination of pregnancy. In 1 case, normal appearance of the vocal cords led to suspicion of a possible isolated tracheal web completely occluding the trachea. Fetoscopy confirmed the finding, thus the membrane was perforated. Lung size normalized and hydrops resolved. A normal fetus was delivered at term, requiring no respiratory support. At 9 months of age, the infant showed a normal laryngoscopy and was developing well. CONCLUSIONS: Systematic ultrasound assessment of the vocal cords can be performed in fetuses with CHAOS. We report the first case of long-term intact survival after fetoscopic airway deobstruction.

Cisterna magna width at 11-13 weeks in the detection of posterior fossa anomalies.

OBJECTIVE: To construct reference ranges for cisterna magna (CM) width at 11-13 weeks' gestation in healthy fetuses and determine whether open spina bifida and posterior fossa anomalies could be diagnosed in the first trimester. METHODS: This was a retrospective study. CM width reference ranges were constructed based on the measurements obtained from 80 healthy fetuses with normal postnatal outcome undergoing routine first-trimester ultrasound at 11-13 weeks, using the Lambda-Mu-Sigma method. CM was measured in the fetal mid-sagittal view, as routinely used for nuchal translucency assessment. In addition, first-trimester ultrasound images in 11 fetuses with open spina bifida or posterior fossa anomalies, most of which were diagnosed later in pregnancy, were retrospectively reviewed, and CM measurements were compared against reference ranges. RESULTS: CM width was noted to increase with gestational age in normal fetuses. The anomalies in the 11 fetuses we reviewed were: open spina bifida (n = 5), megacisterna magna (n = 3), Blake's pouch cyst (n = 2) and posterior fossa arachnoid cyst (n = 1). All fetuses with open spina bifida had a CM width below the 5(th) percentile. In the two fetuses with Blake's pouch cyst and in two with megacisterna magna, CM width was above the 95(th) percentile. In one of the fetuses with a megacisterna magna and the one with an arachnoid cyst, CM width was within normal range. CONCLUSION: We have constructed reference ranges for CM width at 11-13 weeks using the mid-sagittal view. It appears that first-trimester CM width can be used as a marker for the early detection of open spina bifida. However, our findings need to be confirmed in prospective large series.

Decompression through tracheobronchial endoscopy of bronchial atresia presenting as massive pulmonary tumor: a new indication for fetoscopic surgery.

This is the first report of fetoscopy to successfully treat a case of bilobar bronchial atresia presenting in the form of a massive right lung tumor causing severe thoracic compression with mediastinal shift, pulmonary hypoplasia and eventually fetal hydrops. The presence of an echolucent tubular structure in the pulmonary hilum was identified as the intrapulmonary continuation of the interrupted main bronchus, and led to the diagnosis of main bronchial atresia. After extensive discussion and counseling, a fetoscopic operation was designed and indicated. The procedure consisted of a fetal tracheoscopy and access to the right main bronchus, which was perforated with a diode laser until a communication with the dead end of the intrapulmonary main bronchus was achieved. After the operation a significant reduction in size was observed, hydrops and mediastinal shift disappeared and O/E LHR increased to 85%. The fetus was born at term and lobectomy of two dysplastic pulmonary lobes was performed. The infant is developing well at 14 months of age. This report demonstrates that fetoscopic airway decompression can achieve fetal survival in the rare event of main bronchus atresia.

The CUSUM test applied in prospective nuchal translucency quality review.

OBJECTIVES: To design a cumulative sum (CUSUM) test for prospective nuchal translucency (NT) measurement quality review that is as stringent as the retrospective quality review methods based on distribution parameters currently in use. METHODS: The database including all fetal NT measurements obtained during a 2-year period in a single center was reviewed, and measurements obtained by sonologists who measured fewer than 100 cases were excluded. The NT distribution parameters proposed by The Fetal Medicine Foundation (FMF) and the Women & Infants Hospital of Rhode Island (WIHRI) were assessed in the whole NT series and in sonologist-specific distributions. A previously described CUSUM model was adapted to fulfil our objective. RESULTS: Two thousand four hundred and seventy-five NT measurements were obtained by seven sonologists during the study period (January 2007-December 2008). In the assessment of sonologist-specific NT distributions, two sonologists fulfilled all the FMF and WIHRI criteria, one showed NT overestimation and four failed due to NT underestimation. Our new CUSUM test model, based on multiples of the median deviations, showed good agreement with the FMF and WIHRI methods in the assessment of sonologist-specific performance. CONCLUSIONS: Our CUSUM test model showed close agreement with the retrospective quality review methods based on distribution parameters currently in use, but with the advantage that it can be applied prospectively, allowing for earlier correction of deviations from target performance.

Cord occlusion followed by laser cord transection in monochorionic monoamniotic discordant twins.

OBJECTIVE: To compare the outcomes of a consecutive case series of monochorionic (MC) monoamniotic (MA) discordant twins treated with umbilical cord occlusion and transection, with those of a cohort of MC diamniotic (DA) twins treated with conventional cord occlusion. METHODS: This study included 17 MCMA twins (12 true MA and five iatrogenic) treated with cord occlusion and transection and a control group of 72 MCDA discordant twins treated during the same period with cord occlusion in a single center. Duration of surgery, rates of preterm delivery (PTD) or preterm premature rupture of membranes (PPROM) < 32 weeks and intrauterine fetal demise (IUFD), perinatal outcome and neonatal survival were prospectively recorded in both groups. RESULTS: Median durations of surgery were 28.5 (range, 14.0-74.0) min and 24.0 (3.0-60.0) min in the cord transection and control groups, respectively (P = 0.24). There were no significant differences between cord transection and control groups in the rates of PPROM (35.3% vs. 20.8%, P = 0.22), PTD (41.2% vs. 28.2%, P = 0.29), IUFD (0% vs. 2.8%, P = 1.0) and neonatal survival (76.5% vs. 80.6%, P = 1.0). Gestational age at delivery (median 35.0 (24.5-39.0) vs. 37.1 (26.2-41.0) weeks, P = 0.21) and fetal birth weight (2215 (800-3200) g vs. 2605 (588-3830) g, P = 0.51) were similar between study groups. CONCLUSION: Cord occlusion and transection in MCMA discordant twins resulted in similar perinatal outcomes to those of MCDA discordant twins treated with cord occlusion.

Gestational age- and estimated fetal weight-adjusted reference ranges for myocardial tissue Doppler indices at 24-41 weeks' gestation.

OBJECTIVES: To construct gestational age (GA)- and estimated fetal weight (EFW)-adjusted reference ranges for tissue Doppler cardiac function parameters from 24 to 41 weeks' gestation. METHODS: This was a prospective cross-sectional observational study involving 213 singleton pregnancies between 24 and 41 weeks' gestation. Myocardial peak velocities and myocardial performance index (MPI') were measured by tissue Doppler ultrasonography (values indicated by 'prime') in the left and right annulus and interventricular septum. Left and right atrioventricular parameters were also measured by conventional Doppler and ratios between the values found by the two methods calculated. Regression analysis was used to determine GA- and EFW-adjusted reference ranges and to construct nomograms for tissue Doppler parameters. RESULTS: All myocardial peak velocities, left and right E'/A' and left MPI' showed a progressive increase with GA. In contrast, left and right E/E' showed a progressive decline. Septal E'/A', and right and septal MPI' remained constant. Myocardial peak velocities showed a progressive increase with increasing fetal weight. CONCLUSIONS: Normal data of fetal myocardial peak velocities, their ratios and MPI' by tissue Doppler adjusted by GA and EFW are provided. The reported reference values may be useful in research or clinical studies and can be used in fetuses with intrauterine growth restriction.

Feticide followed by mifepristone-misoprostol regimen for midtrimester termination of pregnancy in two cases of complete placenta previa.

Placenta previa (PP), with a frequency of 5-7% in the second trimester, is considered one of the most important causes of obstetric hemorrhage. Surgical curettage is the classically recommended method to perform a midtrimester termination of pregnancy (TOP) in the presence of PP. Recent clinical reports suggest that induction of delivery is possible in these cases, but no information on mifepristone-misoprostol regimen is available. We present 2 cases of mifepristone-misoprostol midtrimester TOP with a diagnosis of complete PP. In both cases, a preinduction feticide was performed. Neither of the 2 cases presented a significant maternal bleeding. This report is relevant considering that this regimen is the most widely used and generally reported as the safest and most effective medical midtrimester TOP method.

Accuracy of four-dimensional spatiotemporal image correlation echocardiography in the prenatal diagnosis of congenital heart defects.

OBJECTIVE: To evaluate the accuracy of four-dimensional (4D) spatiotemporal image correlation (STIC) echocardiography for the diagnosis of fetal congenital heart disease (CHD) in a selected high-risk population. METHODS: Three hundred and sixty-three pregnant women referred for suspected CHD on screening ultrasound were evaluated by means of conventional echocardiography between 14 and 41 weeks' gestation and 4D-STIC volumes were obtained (including gray-scale and color Doppler information). Stored volumes were analyzed, at least 1 year after they had been acquired, by examiners blinded to the patients' identities and outcomes. The STIC diagnoses were compared to those made on conventional two-dimensional echocardiography and the accuracy of diagnosis was assessed with respect to postnatal examination, or autopsy in cases of termination of pregnancy or perinatal death. RESULTS: The mean gestational age at volume acquisition was 24 + 5 weeks. STIC evaluation was possible in 98% of cases. Twenty-one cases were lost to follow-up, with a total of 167 normal hearts and 175 cases of CHD diagnosed at postnatal evaluation. The overall accuracy, sensitivity, specificity and positive and negative predictive values of STIC in determining the presence or absence of CHD were 91.6, 94.9, 88.1, 89.7 and 94.0%, respectively. Absolute concordance with the final specific diagnosis among cases with confirmed CHD was 74.3% for STIC echocardiography, compared with 81.7% for real-time evaluation. CONCLUSION: 4D-STIC echocardiography performed by experienced operators can be used in fetuses at risk for cardiac anomalies in order to reliably provide reassurance of normality or to accurately diagnose major structural heart defects.

The 'question mark' sign as a new ultrasound marker of tetralogy of Fallot in the fetus.

OBJECTIVE: To describe a new ultrasonographic marker, the 'question-mark' sign, to assist in the diagnosis of tetralogy of Fallot (TOF) in the fetus, and to evaluate its prevalence in TOF as compared with other cardiac defects. METHODS: A prospective evaluation over a 5-year period of a consecutive series of 3998 pregnant women undergoing fetal echocardiography from 12 to 40 weeks' gestation due to high risk for congenital heart disease (CHD). Standard echocardiographic planes with color Doppler assessment and evaluation of the whole aortic arch, from the left ventricular outflow tract to the descending aorta in the axial upper mediastinum views, were performed. The question-mark sign corresponded with an enlarged and dilated ascending aorta and aortic arch in the three-vessel view of the upper fetal mediastinum. The frequency of this sign was evaluated in cases with TOF and in other cases of cardiac defects, as well as in fetuses with normal cardiac scans in this series. RESULTS: CHD was diagnosed in a total of 447 (11.2%) fetuses at a median gestational age of 24 (range, 12-40) weeks. Forty-two of the 447 (9.4%) had TOF, of which 29 cases (69.0%) had classical TOF (pulmonary stenosis), nine (21.4%) pulmonary atresia and four (9.5%) absent pulmonary valve syndrome. A question-mark sign was observed in 16/29 (55.2%) cases of classical TOF and in 8/9 (88.9%) cases of TOF with pulmonary atresia. The sign was never observed in any of the cases of TOF with a right-sided aortic arch. Likewise, the sign was observed in 1/405 (0.2%) cases with other cardiac anomalies (a fetus with a complex cardiac defect) and in none of the fetuses with normal hearts. CONCLUSIONS: The finding of an enlarged aorta with a question-mark shape should raise a strong suspicion of tetralogy of Fallot, in particular the variant with pulmonary atresia. This sign may be useful in screening considering that prenatal diagnosis of TOF by routine ultrasonography remains a challenge.

Intra- and interobserver repeatability of fetal cardiac examination using four-dimensional spatiotemporal image correlation in each trimester of pregnancy.

OBJECTIVE: To assess the intra- and interobserver repeatability of the evaluation of fetal cardiac structures and measurements using spatiotemporal image correlation (STIC) technology in each trimester of pregnancy. METHODS: Four-dimensional (4D)-STIC volumes from 150 low-risk pregnancies were acquired at first-, second- or third-trimester scan for later analysis by two different reviewers. A total of 19 items, including the evaluation of 14 structures as well as five measurements of the fetal heart, were evaluated. The reliability of qualitative variables was evaluated using Cohen's kappa and absolute agreement analysis while that of quantitative parameters was assessed using the intraclass correlation coefficient (ICC). RESULTS: Forty-five, 47 and 47 STIC volumes were included in the final analysis from the first, second and third trimesters, respectively. For the evaluation of cardiac structures, good or excellent intra- and interobserver agreement (kappa > 0.6) was obtained in 12/14 and 9/14, respectively, while absolute agreement was > 90% for most structures evaluated. Regarding the quantitative cardiac measurements, ICC values were above 0.90 for all but cardiac axis (intraobserver ICC, 0.81 and interobserver ICC, 0.61). There were no significant differences in the repeatability values observed for qualitative or quantitative parameters among the trimesters of pregnancy. CONCLUSION: Cardiac examination from 4D-STIC volumes showed a high repeatability between and within observers in each trimester of pregnancy.

Contribution of intrapulmonary artery Doppler to improve prediction of survival in fetuses with congenital diaphragmatic hernia treated with fetal endoscopic tracheal occlusion.

OBJECTIVE: To evaluate the contribution of intrapulmonary artery Doppler in predicting the survival of fetuses with congenital diaphragmatic hernia (CDH) treated with fetoscopic tracheal occlusion (FETO). METHODS: A cohort of 41 fetuses (between 24 and 28 weeks of gestation) with CDH was treated with FETO. The observed/expected lung-to-head ratio (O/E-LHR), pulmonary artery pulsatility index (PI), peak early diastolic reversed flow (PEDRF) and peak systolic velocity (PSV) were evaluated before FETO, and their isolated and combined value to predict survival using multiple logistic regression and decision-tree analysis was assessed. RESULTS: O/E-LHR and intrapulmonary artery PI and PEDRF were significantly associated with the probability of survival (O/E-LHR > or = 26%, OR 14.2; PI < 1 Z-score, OR 8.4; and PEDRF < 3.5 Z-scores, OR 5.7). Decision-tree analysis showed that O/E-LHR was the best initial predictor of prognosis (O/E-LHR > or = 26%, 90% survival; O/E-LHR < 26%, 45% survival). For fetuses with an O/E-LHR of < 26%, Doppler parameters allowed discrimination of cases with moderate (66-71% survival) and very poor (0% survival) prognosis. CONCLUSION: Intrapulmonary artery Doppler evaluation helps to refine the prediction of survival after FETO in fetuses with severe CDH.

Abnormal first-trimester ductus venosus blood flow: a marker of cardiac defects in fetuses with normal karyotype and nuchal translucency.

OBJECTIVE: To evaluate the independent contribution of ductus venosus (DV) blood flow assessment at 11-14 weeks' gestation to the prediction of congenital heart defects (CHD) in chromosomally normal fetuses, irrespective of the value of the nuchal translucency thickness (NT). METHODS: During a 4-year period, all singleton pregnancies from 11 + 0 to 13 + 6 weeks' gestation were scanned for NT and DV blood flow in a tertiary center. Abnormal DV blood flow was defined as either absent or reversed flow during atrial contraction (AR-DV). Fetal echocardiography was performed in all cases with either NT > 99(th) percentile or AR-DV. Follow-up was assessed by postnatal examination or autopsy in cases of termination of pregnancy or perinatal death. RESULTS: A total of 6120 pregnancies were scanned at a median gestational age of 12 weeks, and 45 cases of CHD were detected. AR-DV was found in 206 fetuses, of which 145 (70.4%) had a normal karyotype. Among fetuses with AR-DV and normal karyotype, 11 cases of CHD were diagnosed, giving a sensitivity of 24.4%, a positive predictive value of 7.6% and an odds ratio of 9.8. Increased NT (> 99(th) centile) was present in 55 of the 145 (37.9%) cases with AR-DV and normal karyotype, and in 6/11 (54.5%) of those with CHD. Thus, the group of 90 fetuses with abnormal DV blood flow and normal NT contained five cases of CHD, for a sensitivity of 11.1%, a positive predictive value of 5.5% and an odds ratio of 8.5. Right-heart anomalies were predominant in those cases with isolated AR-DV (4/5), but no specific CHD pattern was found in those with increased NT. The detection rate of CHD by the combined use of increased NT and/or AR-DV in the first trimester improved from 28.9% (13/45) to 40.0% (18/45). CONCLUSIONS: In experienced hands, abnormal DV blood flow in the first trimester is an independent predictor of CHD and should constitute an indication for early echocardiography. In this study, the use of DV blood flow assessment increased early detection of CHD by 11% with respect to the use of NT measurement alone.

Feasibility and accuracy of fetal echocardiography using four-dimensional spatiotemporal image correlation technology before 16 weeks' gestation.

OBJECTIVES: To evaluate the potential value of early fetal echocardiography (EFE) by means of four-dimensional (4D) spatiotemporal image correlation (STIC) technology for either reassurance of normality or prenatal diagnosis of major congenital heart defects (CHDs). METHODS: Sixty-nine pregnant women from 11 to 15 weeks' gestation underwent EFE. 4D-STIC volumes were acquired by the transvaginal approach for later review by two different examiners. STIC evaluation was considered complete when the four-chamber view, and the origin and double-crossing of the great arteries were identified correctly. Color Doppler imaging was used to detect either septal shunts or transvalvular regurgitation/aliasing suggesting abnormalities. STIC diagnoses were compared with those of conventional EFE. Reliability was assessed by postnatal examination, or autopsy in cases of termination of pregnancy or perinatal death. RESULTS: The median gestational age at volume acquisition was 13 + 3 weeks. Eleven (15.9%) cases of CHD were diagnosed. A complete EFE was possible in 64 cases. We were able to provide reassurance of normality in 51 of the 53 confirmed normal hearts, with no false-positive results for major defects, although two minor defects (one ventricular septal defect (VSD) and one persistent left superior vena cava) were falsely suspected. The only false negative was a significant VSD at birth overlooked by both observers. Therefore, the total accuracy of STIC-EFE was 95.3% (61/64), with sensitivity, specificity, and positive and negative predictive values of 90.9%, 96.2%, 83.3% and 98.1%. The accuracy of conventional EFE (98.4%, 63/64) was slightly better than that of STIC, with no false-positive results recorded. CONCLUSIONS: Offline evaluation of 4D-STIC acquired volumes of the fetal heart in the first and early second trimester of pregnancy is reliable not only for early reassurance of normal cardiac anatomy but also to diagnose most major structural heart defects.

Reference ranges for uterine artery mean pulsatility index at 11-41 weeks of gestation.

OBJECTIVES: To construct gestational age (GA)-based reference ranges for the uterine artery (UtA) mean pulsatility index (PI) at 11-41 weeks of pregnancy. METHODS: A prospective cross-sectional observational study was carried out of 20 consecutive singleton pregnancies for each completed gestational week at 11-41 weeks. UtAs were examined by color and pulsed Doppler imaging, and the mean PI, as well as the presence or absence of a bilateral protodiastolic notch, were recorded. Polynomials were fitted by means of least-square regression to estimate the relationship between the mean UtA-PI and GA. RESULTS: A total of 620 women were included. A second-degree polynomial (Log(e) mean UtA-PI = 1.39 - 0.012 x GA + GA(2) x 0.0000198, with GA measured in days), after a natural logarithmic transformation, was selected to model our data. There was a significant decrease in the mean UtA-PI between 11 weeks (mean PI, 1.79; 95(th) centile, 2.70) and 34 weeks (mean PI, 0.70; 95(th) centile, 0.99). It then became more stable up until 41 weeks (mean PI, 0.65; 95(th) centile, 0.89). CONCLUSIONS: The mean UtA-PI shows a progressive decrease until the late stages of pregnancy. Reference ranges for mean UtA-PI may have clinical value in screening for placenta-associated diseases in the early stages of pregnancy, and in evaluating patients with pregnancy-induced hypertension and/or small-for-gestational age fetuses during the third trimester.