Showing papers in "Ultrasound in Obstetrics & Gynecology in 2006"

Prenatal detection of heart defects in a non-selected population of 30,149 fetuses--detection rates and outcome.

Abstract: Objectives To evaluate the detection rate of congenital heart defects (CHD) in a non-selected population and to follow outcome after diagnosis. Methods All 30 149 fetuses/newborns that were scheduled to deliver at our hospital between February 1991 and December 2001 were registered prospectively. Of these, 29 460 (98%) fetuses had a prenatal ultrasound scan at our center. The routine fetal examination at approximately 18 weeks' gestation included the four-chamber view and the great arteries of the fetal heart. The follow-up period was 2–13 years. Results Of 97 major CHDs, 55 (57%) were detected prenatally, 16% (9/55) prior to, 66% (36/55) at and 18% (10/55) after the routine scan. Forty-four percent (19/43) of the isolated CHDs, 67% (36/54) of those with associated malformations and 48% (11/23) of the isolated ductal-dependent CHDs were detected. Thirty-eight percent (37/97) had an abnormal karyotype. Of the 55 major CHDs detected, 44% (24) of the pregnancies with lethal/serious fetal malformations were terminated, 15% (8) died in utero, 42% (23) were born alive and 27% (15) were still alive after 2 years. Of the 42 CHDs detected postnatally, 2% (1) were terminated for other reasons, 98% (41) were born alive and 81% (34) were still alive after 2 years. Conclusions Prenatal detection of CHD is still a challenge, with a 57% detection rate only. Isolated defects are detected less frequently. The overall outcome suggests that the most severe defects are detected with the present screening setting; only 27% of the babies with major CHDs detected were still alive after 2 years. Data from long-term follow-up will be of importance for the counseling process. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Real-time elastography - an advanced method of ultrasound : first results in 108 patients with breast lesions

Abstract: Objectives To evaluate whether real-time elastography, a new, non-invasive method for the diagnosis of breast cancer, improves the differentiation and characterization of benign and malignant breast lesions. Methods Real-time elastography was carried out in 108 potential breast tumor patients with cytologically or histologically confirmed focal breast lesions (59 benign, 49 malignant; median age, 53.9 years; range, 16–84 years). Tumor and healthy tissue were differentiated by measurement of elasticity based on the correlation between tissue properties and elasticity modulus. Evaluation was performed using the three-dimensional (3D) finite element method, in which the information is color-coded and superimposed on the B-mode ultrasound image. A second observer evaluated the elastography images, in order to improve the objectivity of the method. The results of B-mode scan and elastography were compared with those of histology and previous sonographic findings. Sensitivities and specificities were calculated, taking histology as the gold standard. Results B-mode ultrasound had a sensitivity of 91.8% and a specificity of 78%, compared with sensitivities of 77.6% and 79.6% and specificities of 91.5% and 84.7%, respectively, for the two observers evaluating elastography. Agreement between B-mode ultrasound and elastography was good, yielding a weighted kappa of 0.67. Conclusions Our initial clinical results suggest that real-time elastography improves the specificity of breast lesion diagnosis and is a promising new approach for the diagnosis of breast cancer. Elastography provides additional information for differentiating malignant BI-RADS (breast imaging reporting and data system) category IV lesions. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Fetal cardiac output, distribution to the placenta and impact of placental compromise

Abstract: Objectives Intrauterine growth restriction is a common clinical problem, but the underlying hemodynamic changes are not well known. Our aim was to determine the normal distribution of fetal cardiac output to the placenta during the second half of pregnancy, and to assess the changes imposed by growth restriction with various degrees of placental compromise. Methods A cross-sectional study of 212 low-risk pregnancies with a gestational age of 18–41 weeks constituted the reference population. A second group of 64 pregnancies with an estimated fetal weight ⩽ 2.5th percentile constituted the study group. Ultrasound measurements of inner diameters and velocities at the fetal left and right ventricular outlets and intra-abdominal umbilical vein were used to determine combined left and right cardiac output (CCO) and the fraction distributed to the placenta. Placental compromise was graded according to umbilical artery waveform: pulsatility index normal, > 97.5th percentile, or absent/reversed end-diastolic velocity. Regression analysis and Z-score (SD-score) statistics were used to establish normal ranges and to compare groups. Results During gestational weeks 18–41 the normal CCO/kg was on average 400 mL/min/kg and the fraction directed to the placenta was on average 32%, while after 32 weeks it was 21%. In intrauterine growth restriction the CCO/kg was not significantly different, but the fraction to the placenta was lower (P < 0.001). This effect was more pronounced in severe placental compromise (P < 0.001). Conclusions Normally, one third of the fetal CCO is distributed to the placenta in most of the second half of pregnancy, and one fifth near term. In placental compromise this fraction is reduced while CCO/kg is maintained at normal levels, signifying an increased recirculation of umbilical blood in the fetal body. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

The examiner's ultrasound experience has a significant impact on the detection rate of congenital heart defects at the second‐trimester fetal examination

Abstract: Objectives To determine whether training and experience in performing ultrasound examinations are factors that influence the prenatal detection of congenital heart defects (CHDs) in a non-selected population, in order to evaluate and improve the current training program. Methods All pregnant women who received a routine second-trimester ultrasound scan by a sonographer/midwife and delivered at our hospital between February 1991 and December 2001 were registered prospectively. Less experienced sonographer/midwives who had performed between 200 and 2000 routine examinations were compared with experienced sonographer/midwives who had carried out more than 2000 examinations. During the first 5 years of the study the heart structures obtained were registered in detail. Results Of 29 035 fetuses, 35/82 (43%) major CHDs were prenatally detected at the routine examination. The experienced sonographer/midwives obtained both the four-chamber view and the great arteries in 75%; the figure for the less experienced sonographer/midwives was 36% (P < 0.001). The differences in detecting major heart defects were 22/42 (52%) and 13/40 (32.5%), isolated CHDs 8/18 (44%) and 6/22 (27%) and CHDs with associated malformations 14/24 (58%) and 7/18 (39%), respectively. In both groups some CHDs with an abnormal four-chamber view were missed, although the experienced sonographer/midwives recognized significantly more of the abnormal views than did the less experienced sonographer/midwives (P = 0.002). Conclusions Experience has a significant impact on the examination of the fetal heart and the prenatal detection rate of major CHDs. To avoid a relatively long learning curve, ultrasound education needs to intensify the teaching of the basic four-chamber view. The great arteries should be included after additional training. Those basic views of the fetal heart must be mastered before new views and advanced technology are added to the fetal heart examination. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Prediction of patient‐specific risk of early preterm delivery using maternal history and sonographic measurement of cervical length: a population‐based prospective study

Abstract: Objective To develop a model for calculating the patient-specific risk of spontaneous early preterm delivery by combining maternal factors and the transvaginal sonographic measurement of cervical length at 22 + 0 to 24 + 6 weeks, and to compare the detection rate of this method to that achieved from screening by cervical length or maternal characteristics alone. Methods This was a population-based prospective multicenter study involving 40 995 unselected women with singleton pregnancies attending for routine hospital antenatal care in London, UK. Complete follow-up was obtained from 39 284 (95.8%) cases. The main outcomes were detection rate, false-positive rate and accuracy of predicting spontaneous delivery before 32 weeks' gestation. Results Spontaneous delivery before 32 weeks occurred in 235 (0.6%) cases. The detection rate of screening for early preterm delivery, at a fixed false-positive rate of 10%, was 38% for maternal factors, 55% for cervical length and 69% for combined testing. There was good agreement between the model estimates and the observed probabilities of preterm delivery. Conclusions This study provides a model that can give an accurate patient-specific risk of preterm delivery. The detection rate of screening by a combination of maternal factors and the measurement of cervical length was substantially higher than that of screening by each method alone. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Intrapartum translabial ultrasound (ITU) : sonographic landmarks and correlation with successful vacuum extraction

Abstract: Objective Having studied intrapartum translabial ultrasound (ITU) to define easily obtainable sonographic criteria during maternal pushing, we used it dynamically immediately before vacuum extraction to determine its use in predicting successful operative vaginal delivery Methods In a pilot study, maternal and fetal landmarks were determined sonographically during maternal pushing from a mid-sagittal translabial insonation using a curved array transducer in women delivering singleton fetuses in cephalic presentation spontaneously With this transducer placed infrapubically (‘infrapubic plane’), easily obtainable landmarks and signs were: (i) the ‘infrapubic line’, perpendicular to the long axis of the pubic joint and extending dorsally from its inferior margin in a mid-sagittal plane, (ii) the widest fetal head diameter and its movement with regard to the infrapubic line during pushing, and (iii) the ‘head direction’ with respect to the long axis of the symphysis A three-dimensional reconstruction from a computed tomographic (CT) dataset of a normal female pelvis was then used to quantify accurately the spatial relationship between the infrapubic line and the anatomical landmarks Finally, 20 pregnant women in spontaneous term labor with normal singleton fetuses in cephalic presentation and clinical indication for vacuum extraction were studied by ITU immediately before operative vaginal delivery Results CT reconstruction demonstrated the infrapubic line to be 3 cm cranial to the parallel interspinous plane Eleven of the 20 vacuum deliveries with the ‘head-up’ sign (head pointing ventrally) and objective descent of the fetal head below the infrapubic line, both noted at the height of pushing, resulted in successful (‘simple’ or ‘moderately difficult’) operative delivery Lack of descent or lack of passage below the infrapubic line and horizontal or downward head direction were poor prognostic signs Conclusions ITU provides objective information on the dynamics of the second stage of labor, head station and head direction ITU may be used to assess the prognosis for operative vaginal delivery Copyright  2006 ISUOG Published by John Wiley & Sons, Ltd

Detailed screening for fetal anomalies and cardiac defects at the 11–13‐week scan

Abstract: Objective To assess the diagnostic efficacy of the first-trimester anomaly scan including first-trimester fetal echocardiography as a screening procedure in a ‘medium-risk’ population. Methods In a prospective study, we evaluated 3094 consecutive fetuses with a crown–rump length (CRL) of 45–84 mm and gestational age between 11 + 0 and 13 + 6 weeks, using transabdominal and transvaginal ultrasonography. The majority of patients were referred without prior abnormal scan or increased nuchal translucency (NT) thickness, the median maternal age was, however, 35 (range, 15–46) years, and 53.8% of the mothers (1580/2936) were 35 years or older. This was therefore a self-selected population reflecting an increased percentage of older mothers opting for prenatal diagnosis. The follow-up rate was 92.7% (3117/3363). Results The prevalence of major abnormalities in 3094 fetuses was 2.8% (86/3094). The detection rate of major anomalies at the 11 + 0 to 13 + 6-week scan was 83.7% (72/86), 51.9% (14/27) for NT < 2.5 mm and 98.3% (58/59) for NT ≥ 2.5 mm. The prevalence of major congenital heart defects (CHD) was 1.2% (38/3094). The detection rate of major CHD at the 11 to 13 + 6-week scan was 84.2% (32/38), 37.5% (3/8) for NT < 2.5 mm and 96.7% (29/30) for NT ≥ 2.5 mm. Conclusion The overall detection rate of fetal anomalies including fetal cardiac defects following a specialist scan at 11 + 0 to 13 + 6 weeks' gestation is about 84% and is increased when NT ≥ 2.5 mm. This extends the possibilities of a first-trimester scan beyond risk assessment for fetal chromosomal defects. In experienced hands with adequate equipment, the majority of severe malformations as well as major CHD may be detected at the end of the first trimester, which offers parents the option of deciding early in pregnancy how to deal with fetuses affected by genetic or structural abnormalities without pressure of time. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Normal fetal motility: an overview.

Abstract: After 35 years of real-time two-dimensional sonography, and now that 4D sonography is within our grasp, this article presents an overview of present-day knowledge of normal fetal motility. A literature search was carried out on articles from 1970, using the keywords: 'fetal', 'movements', 'motility', 'movement patterns', 'ultrasound' and 'sonography'. Inclusion criteria were human studies and use of real-time sonography. Articles were screened for type of motor assessment procedure, in terms of whether they: specified movements for participating body parts (specific movement pattern, SMP), were qualitative (performance in terms of speed and amplitude), were quantitative, identified behavioral states, stated the duration of observation, and specified gestational age. We noted developmental milestones obtained for each study aim. One of four aims was identified for each article, depending on whether it focused on emergence, development, or continuity after birth of the movement patterns, or on the relationship of various motor aspects to other parameters that evaluate fetal condition, such as blood flow and fetal heart rate. A total of 109 relevant articles was identified, examining 9862 fetuses. Assessment was performed primarily with analysis of SMPs (89%); 52% also included non-SMPs (NSMPs), 78% included quantification, 24% assessment of quality, and 32% behavioral states. The duration of observation was 1 h or longer in 50% of the studies. The focus in 28 studies was on emergence, in 44 it was on development, in five it was on continuity and in 32 it was on relationship of the movements with other parameters of fetal well-being. A few milestones identified were determination of the strictly age-related emergence of SMPs and behavioral states, the highly reproducible quality of SMPs throughout gestation, the age-related trends in quantified SMPs, the continuity in quality and quantity after birth, and the close relationship between motility and heart-rate variability, flow parameters, and behavioral states. Periods of longest inactivity recorded before 20 weeks were 13 min; after 30 weeks they were 45 min. Much insight was obtained into the development of motility and its relationship to other parameters from those articles applying comparable assessment procedures. An assessment procedure with well-defined SMPs, qualitative and quantitative aspects of SMPs and NSMPs, and an observation period dependent on age are advocated for future research.

Prediction of labor and delivery by transperineal ultrasound in pregnancies with prelabor rupture of membranes at term.

Abstract: Objective To evaluate whether engagement of the fetal head or cervical length in women with premature rupture of membranes (PROM) at term, are associated with time from PROM to delivery or need for operative delivery. Methods A transperineal ultrasound examination was performed in 152 women with a single live fetus in cephalic presentation after PROM (at > 37 gestational weeks). The shortest distance from the outer bony limit of the fetal skull to the skin surface of the perineum was measured in a transverse view, and the cervical length was measured in a sagittal view. The time from PROM to delivery was tested in a Cox regression analysis with ultrasound measurements, parity, maternal age, body mass index and birth weight as possible predictive factors. Results The head-perineal distance was associated with the time from PROM to delivery (log rank test, P < 0.001). Thirty-six hours after PROM, 32% (95% CI, 15–49) of women with a short head–perineal distance (< 45 mm) and 43% (95% CI, 24–62) of women with a long distance (≥ 45 mm) were still in labor. Women with a short head–perineal distance had fewer Cesarean sections, less use of epidural analgesia and a shorter time in active labor, and their babies had a higher pH in the umbilical artery. The measured cervical length was not associated independently with time to delivery. Conclusion Transperineal ultrasound measurements of fetal head engagement may help clinicians to predict the course of labor in women with PROM. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

French fetal biometry: reference equations and comparison with other charts.

Abstract: Objectives To construct new reference charts and equations for fetal biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL), using a large sample of fetuses examined at 15–40 weeks in France, and to compare them with previous references. Methods The study data were obtained over a continuous 1-year period from a population of pregnant women undergoing ultrasound examination. Excluded were those with a known abnormal karyotype or congenital malformation, multiple pregnancies, and those with no first-trimester dating based on crown–rump length. No fetuses were excluded on the basis of abnormal biometry or birth weight. For each measurement, separate regression models were fitted to estimate both the mean and the SD at each gestational age. Results Full biometric measurements were obtained for 19 647 fetuses. New charts and reference equations are reported for BPD, HC, AC and FL. Prediction intervals for the new reference charts were similar to those of previous ones, whereas there were some differences in predicted centiles. Conclusion We present new French reference charts and equations for fetal biometry. They can be used easily to compute centiles and Z-scores to control the quality of biometric assessments and to evaluate their performance relative to other references. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings and is there a way of making a correct diagnosis

Abstract: Objectives To determine which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings, and to determine if the use of logistic regression models for calculation of individual risk of malignancy would improve the diagnostic accuracy in difficult tumors. Methods In a prospective, international, European multicenter study involving nine centers, 1066 women with a pelvic mass judged to be of extrauterine origin underwent transvaginal ultrasound examination by an experienced ultrasound examiner before surgery. A standardized examination technique and predefined definitions of ultrasound characteristics were used. On the basis of subjective evaluation of ultrasound findings, the examiner classified each mass as being certainly benign, probably benign, unclassifiable, probably malignant or certainly malignant. Even when the examiner found the mass unclassifiable (i.e. difficult mass) he or she was obliged to state whether the mass was more likely to be benign or malignant. Borderline tumors were classified as malignant. Results There were 90 (8%) unclassifiable masses. Multiple logistic regression analysis showed papillary projections, >10 locules in a cyst without solid components, low-level echogenicity of cyst fluid, and moderate vascularization as assessed subjectively at color Doppler examination to be ultrasound variables independently associated with unclassifiable mass. Borderline malignant tumors (n = 55) proved to be most difficult to assess with only 47% being correctly classified (i.e. classified as malignant), 29% being incorrectly classified (i.e. classified as benign) and 24% being unclassifiable vs. 90% of non-borderline tumors being correctly classified, 3% being incorrectly classified and 8% being unclassifiable (P < 0.0001). Papillary cystadeno(fibro)mas, myomas and cases of struma ovarii were also more common among the unclassifiable masses than among the classifiable ones (5.6% vs. 1.1%, P = 0.008; 4.4% vs. 0.9%, P = 0.02; 4.4% vs. 0.2%, P = 0.0006). No ultrasound variable or clinical variable (including CA 125) entered a logistic regression model to predict malignancy in difficult masses. A model could be constructed for difficult masses containing papillary projections but this model performed no better than subjective evaluation of the ultrasound image. Sensitivity and specificity of subjective evaluation with regard to malignancy in the group of unclassifiable masses were 56% (14/25) and 77% (50/65) vs. 91% (220/241) and 97% (712/735) in the classifiable masses. Conclusions Borderline tumors cause great diagnostic difficulties, but so do papillary cystadeno(fibro)mas, struma ovarii and some myomas. Logistic regression models do not solve the diagnostic problem in difficult pelvic masses. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Sequential changes in uterine artery blood flow pattern between the first and second trimesters of gestation in relation to pregnancy outcome

Abstract: Objective To describe sequential changes in uterine artery waveform between the first and second trimesters of gestation and to analyze their association with the subsequent risk of hypertensive disorders and fetal growth restriction (IUGR). Methods Sequential uterine artery Doppler recordings were obtained in a final cohort of 870 singleton pregnancies over two gestational age intervals: 11–14 weeks and 19–22 weeks. The left and right uterine arteries were examined by color and pulsed Doppler and the mean pulsatility index (PI) as well as the presence of a bilateral protodiastolic notch were recorded during both intervals. Pregnancies were followed for occurrence of hypertensive disorders and IUGR. Results Mean uterine artery PI showed a significant linear decrease within each of the two intervals considered, while the prevalence of a bilateral notch showed decreasing values only throughout 11–14 weeks of gestation. Sixty-four (7.3%) pregnancies developed a hypertensive disorder and/or IUGR, including three (0.34%) cases of gestational hypertension, 24 cases of pre-eclampsia (2.75%) and 37 (4.25%) of IUGR. Compared with pregnancies with a normal outcome, complicated pregnancies showed a significantly higher prevalence of a bilateral notch and a higher mean PI in each of the two intervals studied. Compared with normal pregnancies, complicated pregnancies had a significantly higher persistence of a bilateral notch (30% vs. 8%), a higher proportion of women with an abnormal first-trimester uterine artery PI shifting to normal in the second trimester (14% vs. 4%) and a higher incidence of a normal first-trimester mean PI that shifted to abnormal in the second trimester (13% vs. 4%). Persistence of an abnormal mean PI from the first to the second trimester identified the group with the greatest risk for adverse perinatal outcome (OR, 10.7; 95% CI, 3.7–30.9). In addition, women in whom the uterine artery mean PI shifted from abnormal to normal between the two trimesters and women in whom the reverse shift occurred showed a similar intermediate risk (OR, 5; 95% CI, 2.1–10.6), comparable to that in women with persistence of a bilateral notch (OR, 5.6; 95% CI, 2.9–10.7). Conclusions The sequence of changes in uterine flow between the first and second trimesters correlates with the subsequent development of hypertensive disorders and IUGR. Women with a persistent abnormal mean PI represent the group with the greatest risk for adverse perinatal outcome. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Ductus venosus shunting in growth-restricted fetuses and the effect of umbilical circulatory compromise.

Abstract: Objective To determine the degree of ductus venosus (DV) shunting in fetuses with intrauterine growth restriction (IUGR) and the effect of various degrees of umbilical circulatory compromise. Methods This was a cross-sectional observational study. Sixty-four fetuses with IUGR (estimated weight ≤ 2.5th percentile) underwent ultrasound examination. The diameter, velocity, and blood flow were determined in the DV and intra-abdominal umbilical vein (UV), and the fraction of shunting and DV : UV diameter ratios were calculated. Placental compromise was classified according to either normal umbilical artery (UA) pulsatility index (PI), UA-PI > 97.5th percentile, or absent or reversed end-diastolic flow velocity (A/REDV). Regression analysis was used to construct mean values, and SD scores were used to determine differences compared with a reference population (n = 212) after ln- or power-transformation. Results In the 64 growth-restricted fetuses, the average DV shunting was 39% compared with 25% in the reference group (overall P 97.5th percentile, and A/REDV were 31%, 35%, and 57%, respectively. Fetuses with IUGR and normal UA-PI (SD score: mean, 0.48; 95% CI, 0.04–0.92) did not shunt significantly more than did the reference fetuses (SD score: mean, 0.0; 95% CI, − 0.15 to 0.15), but those with UA-PI > 97.5th percentile (SD score: mean, 0.85; 95% CI, 0.41–1.29), and particularly those with A/REDV (SD score: mean, 1.56; 95% CI, 1.0–2.12) did shunt significantly more. With more DV shunting, these fetuses distributed correspondingly less umbilical blood to the liver, one of the mechanisms being a lower perfusion pressure as reflected in the lower DV blood velocity (P < 0.0001). Conclusions DV shunting is higher and the umbilical blood flow to the liver is less in fetuses with IUGR, particularly in those with the most severe umbilical hemodynamic compromise. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Twin reversed arterial perfusion: fetoscopic laser coagulation of placental anastomoses or the umbilical cord.

Abstract: Objective To assess the feasibility and outcome of fetoscopic laser coagulation in pregnancies with twin reversed arterial perfusion (TRAP) sequence Methods In a prospective multicenter study, percutaneous fetoscopic laser coagulation of placental anastomoses (n = 18) or the umbilical cord of the acardiac twin (n = 42) was performed in 60 consecutive pregnancies at a median gestational age of 183 (range, 143–247) weeks under local or locoregional anesthesia Results Vascular coagulation with arrest of blood flow was achieved in 82% (49/60) of cases by laser alone and in a further 15% (9/60) by laser coagulation in combination with bipolar forceps The overall survival rate of the pump twin was 80% (48/60) Median gestational age at delivery was 374 (range, 237–414) weeks and the median interval between the procedure and delivery was 182 (range, 11–257) weeks Median birth weight was 2720 (range, 540–3840) g Preterm premature rupture of membranes before 34 weeks' gestation occurred in 18% (11/60) at a median of 62 (range, 1–102) days after the procedure However, only two (3%) women delivered within 28 days of the procedure Conclusions Fetoscopic laser coagulation of placental vascular anastomoses or the umbilical cord of the acardiac twin is an effective treatment of TRAP sequence, with a survival rate of 80%, and 67% of pregnancies with surviving pump twins going beyond 36 weeks' gestation without further complications Copyright © 2006 ISUOG Published by John Wiley & Sons, Ltd

Sonographic findings of placental lacunae and the prediction of adherent placenta in women with placenta previa totalis and prior Cesarean section

Abstract: Objective To investigate the value of transvaginal sonographic findings of intraplacental lacunae for predicting adherent placenta and clinical outcome in patients with placenta previa totalis and a history of Cesarean section. Methods Fifty-one patients with placenta previa totalis diagnosed by transvaginal sonography and with a history of Cesarean section who delivered at our hospital were included in the study. The sonographic findings of intraplacental lacunae were classified into one of four grades. Pathological analysis of the placenta was performed for all patients who delivered, and in cases of hysterectomy, examination of the uterus was also performed. The placental findings and obstetric complications, including massive transfusion, intensive care unit admission and Cesarean hysterectomy, were compared with the grade of lacuna. Results Lacunae were classified as Grade 1+ in 10 cases, Grade 2+ in 11 cases, Grade 3+ in five cases and as Grade 0 (i.e. lacunae were absent) in the remaining 25 cases. When lacunae of ≥ Grade 1+ were considered, the sensitivity, specificity, positive predictive value and negative predictive value of diagnosing adherent placenta were 86.9%, 78.6%, 76.9% and 88.0%, respectively. When lacunae of ≥ Grade 2+ were considered, the sensitivity, specificity, positive predictive value and negative predictive value of diagnosing placenta increta or percreta were 100%, 97.2%, 93.8% and 100%, respectively. Hysterectomy was performed in 18 cases, among whom two cases showed Grade 1+ lacunae, 11 cases showed Grade 2+ lacunae, and five cases showed Grade 3+ lacunae. No hysterectomy was performed in any case in which lacunae were absent. Compared to those without lacunae, the number of massive transfusions and intensive care unit admissions and cases of disseminated intravascular coagulopathy and Cesarean hysterectomy were significantly greater in those with lacunae (P < 0.0001). Conclusion Transvaginal sonographic findings of intraplacental lacunae in patients with placenta previa totalis and a history of Cesarean section are useful in the prediction of adherent placenta and may have a role in the prediction of clinical outcome. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Comparison between three-dimensional placental volume at 12 weeks and uterine artery impedance/notching at 22 weeks in screening for pregnancy-induced hypertension, pre-eclampsia and fetal growth restriction in a low-risk population.

Abstract: Objectives To compare the value of three-dimensional placental volume at 12 weeks and uterine artery Doppler at 22 weeks for predicting pregnancy-induced hypertension (PIH), pre-eclampsia and fetal growth restriction in a low-risk population. Methods Over a 20-month period we calculated the placental quotient (PQ = placental volume/crown–rump length) at 11–13 weeks' gestation in all women with singleton pregnancies who booked for delivery in our hospital. At 22 weeks, in the same population, we calculated the mean pulsatility index (PI) of both uterine arteries and the presence of an early diastolic notch was noted. Logistic regression models, the PQ and Doppler parameters were used to compare the two screening methods for subgroups of pregnancy outcome. Results Complete outcome data were obtained in 2489 consecutive singleton pregnancies. Logistic regression models for the detection of pre-eclampsia had a sensitivity of 38.5% (PQ) vs. 44.8% (Doppler); for the detection of small-for-gestational age (SGA) the sensitivity was 27.1% (PQ) vs. 28.1% (Doppler) at a specificity of 90%. Taking a PQ of ≤ 10th centile, a mean uterine PI of ≥ 90th centile and a bilateral notch, the sensitivity for detection of SGA was 25.0%, 20.2% and 22.0%, respectively; for PIH it was 9.5%, 4.8% and 4.8%; for pre-eclampsia without SGA it was 20.0%, 28%, 12%; for PIH/pre-eclampsia with SGA it was 30.8%, 46.1% and 69.2%. In the group with the most severe complications, in which delivery took place before 34 weeks, the sensitivity was 50.0%, 50.0% and 38.9%, respectively. Conclusions PQ at 12 weeks and uterine artery Doppler at 22 weeks have similar sensitivities for predicting pre-eclampsia and fetal growth restriction, although uterine artery Doppler is marginally more sensitive for the prediction of pre-eclampsia. While both methods are insufficient for screening in a low-risk population, the PQ method has the potential advantage of being performed in the first trimester. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

A systematic review of the accuracy of first-trimester ultrasound examination for detecting major congenital heart disease.

Abstract: Objective To evaluate the accuracy of first-trimester ultrasound examination in detecting major congenital heart disease (CHD) using a systematic review of the literature. Methods General bibliographic and specialist computerized databases along with manual searching of reference lists of primary and review articles were used to search for relevant citations. Studies were included if a first-trimester ultrasound scan was carried out to detect CHD that was subsequently verified by a reference standard. Data were extracted on study characteristics and quality, and 2 × 2 tables were constructed to calculate sensitivity and specificity. Results Ten studies (involving 1243 patients) were suitable for inclusion. Of these, four used transabdominal ultrasonography, four used transvaginal and two used a combination. Pooled sensitivity and specificity were 85% (95% CI, 78–90%) and 99% (95% CI, 98–100%), respectively. Conclusion Ultrasound examination of the fetus in the first trimester is feasible for accurately detecting major CHD. It may be offered to women at high risk of having children with CHD. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Diagnosis of midline anomalies of the fetal brain with the three-dimensional median view

Abstract: Objective To investigate the effectiveness of a simplified approach to the evaluation of the midline structures of the fetal brain using three-dimensional (3D) ultrasound. Methods Sonographic examinations were performed in normal fetuses and in cases with anomalies involving the midline cerebral structures. Two-dimensional (2D) median planes were obtained by aligning the transducer with the anterior fontanelle and midline sutures by either transabdominal or transvaginal scans. Median planes were also reconstructed using 3D ultrasonography from volumes acquired from transabdominal axial planes of the fetal head (3D median planes), by either multiplanar analysis of static volumes or volume contrast imaging in the coronal plane (VCI-C). 2D and 3D median planes were compared qualitatively and quantitatively by measuring the corpus callosum and cerebellar vermis. Results 2D median planes could be visualized in 54/56 normal fetuses. 3D median planes were obtained in all, usually more easily and rapidly. There was a good correlation between 2D and 3D images. Measurements of the corpus callosum and cerebellar vermis were highly correlated, with mean variations of 6% and 14%, respectively. The abnormal group included 13 fetuses (five with partial or complete agenesis of the corpus callosum, six with posterior fossa malformations, two with a combination of these two anomalies). In all cases the diagnosis could be made by both 2D and 3D views and was always confirmed by postnatal investigation. Although 2D median views were of better quality, 3D images were always adequate for diagnosis, both in normal and abnormal fetuses. Conclusions 3D median planes are obtained more easily than 2D ones, and allow an accurate diagnosis of normal cerebral anatomy and anomalies. The 3D approach may be valuable particularly for rapid assessment of fetal cerebral anatomy in standard examinations. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Prediction of pre-eclampsia by uterine artery Doppler ultrasonography and maternal serum pregnancy-associated plasma protein-A, free β-human chorionic gonadotropin, activin A and inhibin A at 22 + 0 to 24 + 6 weeks' gestation

Abstract: Objective To investigate the potential value of combining uterine artery Doppler ultrasonography with the measurement of maternal serum pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (β-hCG), activin A and inhibin A at 22 + 0 to 24 + 6 weeks’ gestation, in the prediction of pregnancies that subsequently develop pre-eclampsia. Methods The maternal serum PAPP-A, free β-hCG, activin A and inhibin A concentrations at 22 + 0 to 24 + 6 weeks’ gestation were measured in samples obtained from women with singleton pregnancies who participated in a screening study for pre-eclampsia by transvaginal color flow Doppler measurement of the uterine artery pulsatility index (PI). A search was made of the database to identify those who subsequently developed pre-eclampsia (n = 24) and a group of controls with normal outcome (n = 144). Regression analysis was performed to establish any relationship between the biochemical markers themselves and between the biochemical markers and uterine artery mean PI. A multivariate Gaussian model combining various biochemical markers with uterine artery mean PI was developed using standard statistical modeling techniques and the performance of such models in discriminating cases with pre-eclampsia was evaluated by receiver–operating characteristics curve (ROC) analysis. Results In the pre-eclampsia group, compared to the controls, the uterine artery mean PI and the maternal serum levels of PAPP-A, free β-hCG, activin A and inhibin A were significantly increased. The predicted detection rates of pre-eclampsia, for a false positive rate of 5%, was 50% by uterine artery mean PI, 5% by PAPP-A, 10% by free β-hCG, 35% by inhibin A and 44% by activin A. Screening by a combination of uterine artery mean PI and maternal serum activin A and inhibin A could detect 75% and 92% of patients who subsequently developed pre-eclampsia, for false positive rates of 5% and 10%, respectively. Conclusion Screening for pre-eclampsia by uterine artery PI at 22 + 0t o 24+ 6 weeks’ gestation can be improved by measurement of activin A and inhibin A levels. Copyright  2006 ISUOG. Published by John Wiley & Sons, Ltd.

Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12–32 weeks' gestation

Abstract: Objective To establish reference intervals for the fetal right, left and total lung volumes and heart volume between 12 and 32 weeks of gestation. Methods Fetal lung and heart volumes were measured using three-dimensional (3D) ultrasound in 650 normal singleton pregnancies at 12–32 weeks. The VOCAL (Virtual Organ Computer-aided AnaLysis) technique was used to obtain a sequence of six sections of each lung and the heart around a fixed axis, each after a 30 ◦ rotation from the previous one. The rotation axis for the lungs extended from the apex to the upper limit of the diaphragm dome, and the rotation axis for the heart extended from its apex to its connection to the great vessels. The contour of each of these organs was drawn manually in the six different rotation planes to obtain the 3D volume measurement. In 60 cases the fetal lungs and heart volumes were measured by the same sonographer twice and also by a second sonographer once in order to compare the measurements and calculate intra- and interobserver agreement. Results The total lung volume and heart volume increased with gestation, from respective mean values of 1.6 and 0.6 mL at 12 weeks to 10.9 and 4.3 mL at 20 weeks and 49.3 and 26.6 mL at 32 weeks. The right to left lung volume ratio did not change significantly with gestation (median, 0.7), whereas the heart to total lung volume ratio increased with gestation from about 0.3 at 12 weeks to 0.5 at 32 weeks. In the Bland–Altman plot, the difference between paired measurements by two sonographers was, in 95% of the cases, less than 0.05, 0.5 and 1.9 mL for each lung at 12–13, 19–22 and 29–32 weeks, respectively, and the corresponding values for the heart volumes were 0.04, 0.4 and 2.3 mL. Conclusions In normal fetuses the lung and heart volumes increase between 12 and 32 weeks of gestation. The extent to which in pathological pregnancies possible deviations in these measurements from normal prove to be useful in the prediction of outcome remains to be determined. Copyright  2005 ISUOG. Published by John Wiley & Sons, Ltd.

Characteristics, associations and outcome of partial agenesis of the corpus callosum in the fetus.

Abstract: Objectives To report, in a population of fetuses diagnosed with partial agenesis of the corpus callosum (PACC), the sonographic characterization, incidence of cerebral, extracerebral and chromosomal anomalies, and outcome. In addition, in some of our cases a comparison was made between findings on ultrasound and fetal magnetic resonance imaging (MRI). Methods This was a retrospective study of all cases of PACC seen at two referral centers for prenatal diagnosis of congenital anomalies over a 10-year period. The following variables were assessed: indication for referral, additional cerebral and extracerebral malformations, chromosomal abnormalities, and pregnancy and fetal/neonatal outcome. Results Among 54 cases of fetal agenesis of the corpus callosum detected in the referral centers during the observation period, PACC was diagnosed at prenatal sonography in 20 cases and confirmed at pre/postnatal MRI and necropsy examinations in 19 cases (35%). These 19 constituted the study group. The diagnosis was made in the sagittal planes and in 12 cases it was made prior to 24 weeks. In most cases the indication for referral was the presence of indirect signs of callosal anomalies, such as colpocephaly. In 10 cases PACC occurred in association with other anomalies and in nine it was isolated. MRI was particularly useful for demonstrating some additional cerebral anomalies such as late sulcation, migrational pathological conditions and heterotopia. Regarding pregnancy outcome, of those diagnosed before 24 weeks which had associated anomalies, all except two were terminated. Of the nine cases with isolated PACC, all were liveborn. Follow-up was available in eight, and two of these (25%) showed evidence of significant developmental delay. In our series the outcome of isolated PACC was not better than that of complete agenesis of the corpus callosum reported in other series. Conclusions PACC can be diagnosed reliably and characterized in prenatal life. The sonographic sign present in most cases is colpocephaly. Prenatal MRI can be performed to confirm the diagnosis. It is particularly useful to demonstrate some additional cerebral anomalies such as late sulcation, migrational pathological conditions and heterotopia. The relatively poor survival rate is due to the high rate of terminations and associated major anomalies. Copyright  2006 ISUOG. Published by John Wiley & Sons, Ltd.

The impact of two‐dimensional versus three‐dimensional ultrasound exposure on maternal–fetal attachment and maternal health behavior in pregnancy

Abstract: Objective To explore the impact of timing and type of ultrasound, particularly three-dimensional (3D), exposure on maternal–fetal attachment and maternal health behavior during pregnancy. Methods Subjects were 68 women aged 18 years or older expecting their first child who presented for a routine ultrasound scan at around either 12 or 18 weeks' gestation in Nepean Hospital, Western Sydney. Women completed questionnaires assessing maternal–fetal attachment and health behavior, and were then allocated arbitrarily to either two-dimensional (2D) or 3D ultrasound examination. Repeat questionnaires were completed 1 week later. Results Maternal–fetal attachment increased after both 2D and 3D ultrasound exposure, and the effect was moderated by the timing of exposure, with women receiving their first ultrasound examination at around 12 weeks showing the greatest change. Alcohol consumption was the only behavior to show significant change following ultrasound exposure, with a reduction in the reported average number of drinks per week. There was no significant difference in the pattern of change for 2D compared with 3D ultrasound exposure, and no effect of ultrasound exposure on maternal perception of the fetus. Conclusions Ultrasound has a positive impact on maternal–fetal attachment, particularly in the first trimester. 3D ultrasound did not offer enhanced benefits. Associations between ultrasound exposure and alcohol consumption warrant further investigation. Larger samples are needed to clarify the moderating effects of gestational age and type of ultrasound exposure. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Pregnancies of unknown location: consensus statement

Abstract: *Early Pregnancy Unit, Nepean Centre for Perinatal Care and Research, Western Clinical School, Nepean Campus, University of Sydney, Nepean Hospital, Penrith, Sydney, Australia, †Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, K.U. Leuven, Leuven, Belgium, ‡Department of Obstetrics and Gynecology, New York University Medical Center, New York, USA, §Department of Obstetrics and Gynecology, Malmo University Hospital, Malmo, Lund University, Sweden, ¶Early Pregnancy and Gynaecology Assessment Unit, King’s College Hospital and **Early Pregnancy, Gynaecological Ultrasound and Minimal Access Surgery Unit, St George’s Hospital Medical School, London, UK (e-mail: gcondous@hotmail.com)

Prenatal diagnosis of open and closed spina bifida.

Abstract: Objective To identify criteria useful for differentiating closed from open spina bifida antenatally. Patients and methods A retrospective study of cases of spina bifida diagnosed in a referral center between 1997 and 2004. Results Of 66 cases of fetal spina bifida diagnosed at a median gestational age of 21 (range, 16–34) weeks, detailed follow-up was available for 57. Of these, open defects were found in 53 (93.0%) and closed defects in four (7.0%). Closed spina bifida was associated in two cases with a posterior cystic mass with thick walls and a complex appearance, while in two cases the spinal lesion could not be clearly differentiated from an open defect, particularly at mid-gestation. Open spina bifida was always associated with typical alterations of cranial anatomy, including the so-called ‘banana’ and ‘lemon’ signs, while in closed spina bifida the cranium was unremarkable. When the data were available, levels of amniotic fluid alpha-fetoprotein were always abnormally elevated with open spina bifida and within normal limits with closed forms. Conclusion In this study 7% of cases of spina bifida diagnosed in utero were closed. The differentiation between open and closed forms is best shown by the sonographic demonstration of abnormal or normal cranial anatomy. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

The conservative management of cervical ectopic pregnancies.

Abstract: Objective To evaluate the role of conservative management in the treatment of cervical ectopic pregnancies. Methods This was a retrospective analysis of all cervical ectopic pregnancies diagnosed in women attending our early pregnancy unit between April 1997 and September 2004 inclusive. The diagnosis of cervical ectopic pregnancy was made using transvaginal ultrasound. Clinical and demographic data were recorded in all cases. Serum human chorionic gonadotropin levels were measured at presentation and monitored subsequently to determine the rate of successful resolution. Conservative management was in the form of medical or expectant management. Medical management involved administration of systemic or intra-amniotic methotrexate, with or without intra-amniotic potassium chloride. Systemic methotrexate was either a single dose of 50 mg/m2 or an alternate-day regimen of methotrexate at 1 mg/kg (days 1,3,5) with folinic acid rescue (days 2,4,6). If intra-amniotic treatment was required, this was either 50 mg methotrexate or 5 mmol/L potassium chloride. Results Seven cervical ectopic pregnancies were diagnosed during the study period. Three cases were managed successfully with a single dose of methotrexate. One case was managed successfully using a multiple-dose methotrexate regimen. Another case failed medical management with both the single- and multiple-dose regimens but was successfully treated after potassium chloride was given intra-amniotically under ultrasound guidance. One case was successfully treated with intra-amniotic methotrexate and another was managed expectantly. There was no associated morbidity or mortality during the study period. We also performed a review of the current literature. Conclusion The conservative management of cervical ectopic pregnancy is effective and safe. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Prenatal screening for congenital heart disease with four‐chamber and outflow‐tract views: a multicenter study

Abstract: Objective Congenital heart diseases (CHD) are the most common congenital anomalies, and most cases occur in the low-risk population. Prenatal ultrasound screening based on visualization of the four-chamber view has had disappointing results in detecting these anomalies thus far. The aim of this study was to evaluate the diagnostic accuracy of ultrasound screening based on the combination of the four-chamber and outflow-tract views. Methods We conducted a multicenter prospective observational study in 15 obstetric units in the Piedmont Region, Italy. All operators received specific training. Data were recorded regarding visualization of the four-chamber view and the outflow tracts at each routine scan in pregnancies without any risk factor. When an anomaly was suspected, the patient was sent to the referral center. We obtained the follow-up data of the newborns until discharge from hospital and calculated the diagnostic accuracy of the test. Results 9074 ultrasound scans were performed on 7041 women and complete follow-up information was available for 6368 of them. Fifty-eight cases of CHD were observed at birth or postmortem (prevalence 9.1‰); 38 of them were diagnosed in utero. The sensitivity of the test was 65.5%, the specificity 99.7%, the positive predictive value 70.4% and the negative predictive value 99.7%. The sensitivity of the four-chamber view alone was 60.3%. Conclusions The sensitivity was significantly higher than that in a similar study performed in 1997 in the same setting. This improvement can be attributed in part to extension of the examination to the outflow-tract view, but also to technological developments and better training of the operators. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Examination of the fetal heart by four-dimensional (4D) ultrasound with spatio-temporal image correlation (STIC).

Abstract: Three-dimensional (3D) and four-dimensional (4D) ultrasound have been proposed to be valuable tools for the examination of the fetal heart1–52. The ultimate goal of 3D and 4D ultrasound is to improve the detection rates of congenital heart disease53–63 by decreasing the dependency on operator skills required by twodimensional (2D) ultrasound64,65. This is important since congenital heart disease is the leading cause of death among infants with congenital anomalies66, and prenatal diagnosis is associated with decreased neonatal morbidity and mortality rates67–70. Several techniques for prenatal examination of the fetal heart by 3D/4D ultrasound have been proposed using a variety of technologies, including free-hand 3D ultrasound with and without position sensors1,3,7–9,12,30, 3D ultrasound with automated mechanical acquisition4,5,7,16,26, 4D ultrasound with a variety of gating algorithms (temporal Fourier analysis of heart motion3, M-Mode1, Doppler11,17–19,39,49, spatio-temporal image correlation (STIC)27,28,34), as well as real-time 4D ultrasound with 2D matrix-array transducers10,15,24,31,46,52. In this article, we describe a practical approach for the examination of the fetal heart using 4D ultrasound with STIC.

Longitudinal reference ranges for ductus venosus flow velocities and waveform indices

Abstract: OBJECTIVES: Serial Doppler measurements of the ductus venosus are used increasingly for monitoring fetuses at risk of hemodynamic compromise, but existing reference ranges are based on cross-sectional studies and thus are less suitable for comparison with serial measurements. We aimed to establish longitudinal reference ranges for ductus venosus flow velocities and waveform indices and to provide the necessary terms for calculating conditional reference ranges for serial measurements. METHODS: This was a longitudinal study of 160 low-risk pregnancies. Pulsed Doppler ultrasound was used to record ductus venosus blood flow velocities at 4-week intervals from 20-22 weeks of gestation onwards. RESULTS: With a success rate of 93%, 547 measurements (four or five in each fetus) were used to establish reference ranges. The time-averaged maximum velocity was 50 cm/s at 21 weeks of gestation, increased to 60 cm/s at 32 weeks, and remained so until term. Similarly, the peak systolic velocity increased from 59 cm/s at 21 weeks to 71 cm/s at 31 weeks and remained so until term. The end-diastolic velocity showed a continuous increase from 31 cm/s at 21 weeks to 43 cm/s at 40 weeks. The pulsatility index for veins decreased from 0.57 at 21 weeks to 0.44 at 40 weeks. When conditioned by a previous measurement, the reference ranges for the next observation became narrower and commonly shifted compared with those of the entire population. CONCLUSION: The new longitudinal reference ranges presented here reflect the development of the ductus venosus flow velocities and velocity indices and are thus appropriate for serial measurements, particularly if conditional terms are included

Absence of ductus venosus-importance of umbilical venous drainage site.

Abstract: Objective To evaluate the conditions associated with absent ductus venosus (ADV) diagnosed by prenatal ultrasonography. Methods Retrospective review of 23 cases with ADV diagnosed in two tertiary referral centers with a general screening policy concerning Doppler assessment of the ductus venosus. The results are discussed together with 63 cases from a review of the literature. Results In 19 fetuses the umbilical vein connected to the portal sinus, while the remaining four fetuses had extrahepatic umbilical venous drainage. Associated anomalies were present in 15 out of 23 fetuses: complex malformation syndromes (n = 6), chromosomal anomalies (n = 4), isolated cardiac defects (n = 4) and isolated extracardiac anomalies (n = 1). Eight fetuses had either no associated anomalies or minor anomalies. Hydropic changes were present in 12 of the 23 fetuses. In common with the reviewed cases, the presence of cardiac malformations,complexnon-chromosomalmalformation syndromes and hydrops was significantly associated with intrauterine or postnatal death while the type of umbilical venous drainage was not significantly different between survivors and non-survivors. However, among fetuses with no or minor associated anomalies the outcome was significantly better in the group without liver bypass. Conclusions ADV is significantly associated with fetal cardiac and extracardiac anomalies, aneuploidies and hydrops. Fetuses with liver bypass have an additional risk of developing congestive heart failure that significantly affects outcome, even if the fetal cardiovascular anatomy is otherwise normal. ADV without liver bypass seems to have a more favorable prognosis if it is not associated

First-trimester ultrasound and biochemical markers of aneuploidy and the prediction of impending fetal death

Abstract: Objectives To examine the clinical utility of the firsttrimester markers of aneuploidy in their ability to predict future fetal loss. Methods Weexamined54722singletonpregnancieswith no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness, maternal serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks’ gestation. The biochemical markers were converted to multiples of the expected normal median for a pregnancy of the same gestation (MoM) and the measurements of fetal NT were expressed as the difference (delta) from the normal median NT for crown‐rump length (CRL). The association between free β-hCG, PAPP-A and delta NT and the incidence of fetal loss prior to 24 weeks, at or after 24 weeks or at any time, was assessed by comparing the relative incidence at a number of MoM or delta NT cut-offs and at various centile cut-offs. At various marker levels the likelihood ratio (LR) for fetal loss was also calculated. Results The rate of fetal loss increased with decreasing maternal serum free β-hCG and PAPP-A and increasing delta NT. At the 5 th centile of the normal outcome group for free β-hCG (0.41 MoM) the odds ratio for fetal loss before 24 weeks, at or above 24 weeks and at any gestation was 3.1, 1.8 and 2.6, respectively. The respective values for the 5 th centile of PAPP-A (0.415 MoM) were 3.3, 1.9 and 2.8 and for the 95 th centile of delta NT they were 2.5, 1.9 and 2.2, respectively. There was almost no correlation between reduced levels (≤0.50 MoM) of PAPP-A and reduced levels of free β-hCG in either the normal pregnancy group (r = 0.041) or the group with fetal death (r = 0.072), indicating relatively independent prediction by either biochemical marker. Conclusions Low levels of maternal serum PAPP-A and free β-hCG and increased fetal NT are associated, in the absence of an abnormal karyotype, with an increased risk of impending fetal death. The likelihood ratio profiles provided at various levels of PAPP-A or free β-hCG may be of some help in counseling women with such results and raise awareness among health-care professionals for increased surveillance in such cases. Copyright  2006 ISUOG. Published by John Wiley & Sons, Ltd.