Modeling Down syndrome screening performance using first-trimester serum markers.

OBJECTIVE: To evaluate the modeled predictive value of three current screening markers (pregnancy-associated plasma protein-A (PAPP-A), free ß-human chorionic gonadotropin (free ß-hCG), and nuchal translucency (NT)) and four potential screening markers (a disintegrin and metalloprotease 12 (ADAM12), total hCG, placental protein 13 (PP13), and placental growth factor (PlGF)) for Down syndrome using different screening strategies. METHODS: All markers were measured in stored first-trimester serum of 151 Down syndrome cases and 847 controls. All marker levels were expressed as gestational age-specific multiples of the median (MoMs) and comparisons were made using the Mann-Whitney U-test. Detection rates (DRs) for fixed false-positive rates (FPRs) were modeled using different screening strategies. RESULTS: Significantly different median MoMs for Down syndrome cases compared to controls were found for PAPP-A (0.49 vs. 1.00; P < 0.0001), free ß-hCG (1.70 vs. 1.01; P < 0.0001), ADAM12 (0.89 vs. 1.00; P < 0.0001), total hCG (1.28 vs. 1.00; P < 0.0001), PlGF (0.80 vs. 1.00; P < 0.0001) and NT (1.74 vs. 1.01; P < 0.0001). The lower PP13 MoM in Down syndrome cases (0.91 vs. 1.00) was not statistically significant (P = 0.061). Adding the four new markers to the current screening strategy (i.e. first-trimester combined test) led to an increase in DR from 77% to 80% at a 5% FPR. The modeled application of a two-sample screening strategy (with some markers assessed early and others later in the first trimester) increased the DR to 89%. In a two-step contingent screening model, using an intermediate risk range of 1 in 100 to 1 in 2000 at biochemical screening (using all markers), the overall DR was 77%, but it was predicted that only 33% of women would require referral for NT measurement. CONCLUSIONS: First-trimester Down syndrome screening may be improved by adding new markers to the current screening test and by applying different screening strategies. The application of a two-sample screening model resulted in the highest predicted DR, but this should be confirmed in population-based prospective studies.

First-trimester placental protein 13 and placental growth factor: markers for identification of women destined to develop early-onset pre-eclampsia.

OBJECTIVE: To investigate the predictive value of maternal serum pregnancy-associated plasma protein A (PAPP-A), free ß subunit of human chorionic gonadotrophin (fß-hCG), placental protein 13 (PP13), placental growth factor (PlGF) and a desintegrin and metalloproteinase 12 (ADAM12), for first-trimester identification of early-onset pre-eclampsia. DESIGN: Nested case-control study. SETTING: Routine first-trimester screening for trisomy 21 in the Netherlands. POPULATION: Eighty-eight women who developed pre-eclampsia or haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 34 weeks of gestation and 480 controls. METHODS: PP13, PlGF and ADAM12 were measured in stored first-trimester serum, previously tested for PAPP-A and fß-hCG. All marker levels were expressed in multiples of the gestation-specific normal median (MoMs). Model predicted detection rates for fixed false-positive rates were obtained for statistically significant markers alone and in combination. MAIN OUTCOME MEASURES: Development of pre-eclampsia or HELLP syndrome. RESULTS: PP13 and PlGF were reduced in women with pre-eclampsia, with medians 0.68 MoM and 0.73 MoM respectively (P < 0.0001 for both). PAPP-A was reduced (median 0.82 MoM, P < 0.02) whereas ADAM12 and fß-hCG did not differ between control women and those with pre-eclampsia. In pre-eclampsia complicated by a small-for-gestational-age fetus, all markers except fß-hCG had lower values, compared with pregnancies involving fetuses of normal weight. The model-predicted pre-eclampsia detection rate for a combination of PP13 and PlGF was 44% and 54%, respectively, for a fixed 5% and 10% false-positive rate. CONCLUSION: This study demonstrates that PP13 and PlGF in the first-trimester might be promising markers in risk assessment for early pre-eclampsia/HELLP syndrome but for an adequate screening test additional characteristics are necessary.

Grade and symmetry of normal fetal cortical development: a longitudinal two- and three-dimensional ultrasound study.

OBJECTIVES: Recent studies have shown the capability of ultrasound to demonstrate fetal cortical development. For practical application, it would be useful to have more insight into the physiological progress of cortical folding. A longitudinal study was undertaken to grade fetal cortical development and to study physiological asymmetry by means of a simple scoring system. The reproducibility of the scoring system and the differences between two-dimensional (2D) and three-dimensional (3D) ultrasound were also examined. METHODS: A cohort of 28 patients was examined by 2D and 3D ultrasound from 20 to 40 weeks of gestation. The development of selected fissures, sulci and cortical areas were graded from 0 to 5. One examination per week of gestation was randomly selected for evaluation of intraobserver and interobserver variation. RESULTS: Two-hundred and fifteen ultrasound examinations were performed in 28 patients. The development of the different cortical areas is presented. The intraobserver and interobserver agreement for assessment of grade was good. Asymmetry was common between 24 and 28 weeks, especially in female fetuses. The right parieto-occipital fissure tended to be more advanced and the left calcarine and cingulate sulci tended to be more advanced. No clinically or statistically significant differences were found between 2D and 3D ultrasound. CONCLUSIONS: Evaluation of cortical development by means of a simple scoring system is feasible and reproducible. Asymmetrical development of sulci, previously only described in vitro, has now also been demonstrated in vivo. 3D ultrasound was equally accurate and repeatable and no more time consuming than 2D ultrasound.

Transvaginal ultrasound measurement of cervical length in the supine and upright positions versus Bishop score in predicting successful induction of labor at term.

OBJECTIVES: To examine the predictive value of cervical length as measured by transvaginal sonography (TVS) in supine and upright maternal positions for the mode of delivery and induction-to-delivery interval after induction of labor at term, and to compare these measurements with the Bishop score and its predictive value. METHODS: TVS for cervical length measurement in the supine and upright positions and digital examination of the cervix were performed in 68 nulliparous and 34 parous women before induction of labor at term. In assessing the predictive value of the Bishop score and TVS parameters for a vaginal delivery after labor induction only nulliparous women were included in the analysis, since all the parous women delivered vaginally. Both nulliparous and parous women were included in the analysis of the induction-to-delivery interval. The method of labor induction, oxytocin or prostaglandin, was determined on the basis of the pre-induction Bishop score. RESULTS: Logistic regression analysis showed in nulliparous women that only the cervical length measured in the upright position was a significant predictor of the need for Cesarean section (odds ratio 1.14; 95% CI, 1.02-1.27). The areas under the receiver-operating characteristics curve in predicting the need for Cesarean section because of failure to progress were higher for the cervical length, both in supine and upright positions, than for the Bishop score (0.66, 0.68 and 0.46, respectively). Only the Bishop score correlated significantly with the induction-to-delivery interval in both nulliparous and parous women. However, this may have been due to a selection bias, as no significant correlation with Bishop score was found when the oxytocin and prostaglandin induction-to-delivery intervals were analyzed separately. CONCLUSION: Our results suggest that maternal postural change might improve the accuracy of sonographically-measured cervical length for predicting a vaginal delivery after induction of labor at term. However, our results need to be confirmed in a larger and more homogeneous population.

Role of prenatal ultrasound in predicting survival and mental and motor functioning in children with spina bifida.

OBJECTIVE: To determine which prenatal ultrasound findings can predict survival and mental and motor functioning in children with spina bifida. METHODS: Prenatal ultrasound examinations of all liveborn children who were prenatally diagnosed with spina bifida between 1997 and 2002 at the University Medical Centre, Utrecht (n = 41) were retrospectively reviewed for lesion level, head circumference, ventriculomegaly, scoliosis and talipes. These measures were correlated with postnatal anatomical (as assessed by magnetic resonance imaging (MRI)) and functional lesion levels, survival and motor and mental outcome at 5 years of age. The capacity of prenatal ultrasonography to determine lesion level was also assessed in all fetuses diagnosed with spina bifida from 2006-2007 (n = 18). RESULTS: Nineteen infants died before the age of 5 years. Multivariate regression analysis showed that higher lesion level and head circumference > or = the 90th percentile on prenatal ultrasound examination were independent predictors of demise (P < 0.05 and P = 0.01, respectively). None of the ultrasound features was a predictor of motor or mental functioning. Ultrasound predicted anatomical lesion level within one level of the postnatal findings in 50% of the first cohort and 89% of the second cohort (P < 0.01). The level of the anatomical lesion as assessed by postnatal MRI differed from the functional lesion by as many as six vertebral levels. CONCLUSIONS: Lesion level and head circumference on prenatal ultrasound are predictive of survival in children with spina bifida. No predictors were found for mental or motor function at the age of 5 years.

Quality of nuchal translucency measurements in The Netherlands: a quantitative analysis.

OBJECTIVE: The Dutch Centre for Population Research has specified quality demands for nuchal translucency (NT) measurement in The Netherlands. We performed an analysis of the quality of NT measurement in 2005-2006 and its influence on screening performance. METHODS: This was a retrospective study of records of NT measurements (n = 27,738) obtained between January 2005 and December 2006 retrieved from the Dutch National Institute for Public Health and the Environment (RIVM). The performance of each individual operator was analyzed with regard to the quality standards, which involved calculation of operator-specific median NT-multiples of the median (MoM) values. For the entire population of operators, a curve was determined describing the relationship between crown-rump length and NT. Detection rates (DR) and false-positive rates (FPR) for Down syndrome were modeled with this new curve and compared to those originally obtained using previously published reference data. RESULTS: Only 22% of all operators met the quality requirement of performing more than 150 NT measurements per year. However, no relationship was found between the number of measurements per operator and their median NT-MoM. The mean of all operator-specific median NT-MoM values was 0.94 (target value 1.0). Overall, operators with The Fetal Medicine Foundation certificate measured a significantly higher median NT-MoM (mean of operator-specific medians, 0.98) as compared to the non-certified operators (0.92). During the study period, the monthly median NT-MoM of all operators rose steadily, from 0.86 in January 2005 to 0.96 in December 2006. Recalculation of the risk for Down syndrome after adjusting the reference NT medians using our own data led to a modeled 4% increase in DR at a 5% FPR. CONCLUSION: Improved monitoring of NT measurement put into effect during the study period seems to have led to an improvement in the accuracy of measurements. Strict quality demands, continued monitoring and scrupulous evaluation of individual operators is likely to lead to an even better performance.

ADAM12s as a first-trimester screening marker of trisomy.

OBJECTIVE: To evaluate the potential of maternal serum A Disintegrin And Metalloprotease 12-S (ADAM12s) as an additional marker for the combined test in the Dutch first-trimester national Down syndrome (DS) screening program. METHODS: Serum samples were collected between 2004 and 2007 as part of the national program. A total of 218 singleton cases of trisomy 21 (DS), 62 trisomy 18 (Edwards syndrome) and 29 trisomy 13 (Patau syndrome) were identified. All cases were matched with controls for gestation, maternal weight and maternal age. The serum concentration of ADAM12s was determined 'blind' to outcome and expressed in multiples of the gestation-specific median for controls (MoM). RESULTS: The median ADAM12s was 1.00 MoM in controls and in the DS cases at 8, 9, 10, 11, 12, 13 weeks it was 0.45 (n = 3), 0.73 (22), 0.74 (53), 0.85 (37), 0.92 (71), 1.06 (32) MoM, respectively. The median for trisomy 18 was 0.85 MoM and for trisomy 13 0.63 MoM. CONCLUSION: The ADAM12s MoM values were clearly reduced in early first-trimester for all trisomies. However, the screening performance for DS did not greatly improve adding ADAM12s. ADAM12s could be an additional biochemical marker for first-trimester screening for trisomies other than DS.

Transperineal versus transvaginal sonographic cervical length measurement in second- and third-trimester pregnancies.

OBJECTIVE: To investigate the reliability of, and patient satisfaction with, transperineal cervical length measurement during the third trimester of pregnancy and to compare these with measurement during the mid-trimester, using transvaginal sonographic imaging of the cervix as a reference. METHODS: Women attending an outpatient clinic for cervical length measurement before 29 weeks or after 35 weeks of gestation were examined by transvaginal and transperineal ultrasound and the results compared. Preference for either method was indicated by both sonographers and patients. RESULTS: Seventy-one patients participated in the study, 23 in the second and 48 in the third trimester of pregnancy. There was failure to obtain a clear image on transperineal ultrasound in 30% of mid-trimester pregnancies, and in 19% of third-trimester cases. Elevation of the patient's hips improved the image in five out of 10 women in whom the scan was repeated following a postural change. Transvaginal cervical length measurements could be obtained in all cases. There was a strong correlation between transvaginal and transperineal measured cervical length (Pearson's correlation coefficient = 0.85). Sonographers preferred transvaginal images of the cervix irrespective of whether they were obtained in the second or third trimester. Transperineal ultrasound was judged as not or mildly painful by most women, but transvaginal ultrasound was preferred. CONCLUSIONS: Transvaginal ultrasound is the least painful, most feasible, and probably most accurate method with which to measure cervical length in the third trimester of pregnancy. Transperineal ultrasound is a feasible alternative, although its application in clinical practice is restricted by the need for an experienced sonographer.

Sonographic longitudinal cervical length measurements in nulliparous women at term: prediction of spontaneous onset of labor.

OBJECTIVE: The aim of this study was to predict spontaneous onset of labor by serial transvaginal ultrasound measurement of cervical length (CL) in a homogeneous population of nulliparous women at term. METHODS: 162 nulliparous women with singleton fetuses in cephalic presentation were examined at weekly intervals from 36 weeks' gestation to delivery. CL was measured by transvaginal ultrasound in the supine and upright positions. RESULTS: There was a significant decrease in CL in the last 12 days prior to delivery. However, this decrease was small with substantial variation between individuals. Women with spontaneous onset of labor could be divided into three different groups: those with unchanged CL before delivery; those with a fall in CL in the last 2 weeks prior to delivery; and those with a gradual change in CL starting before the last 2 weeks prior to delivery. A single CL measurement below 30 mm between 37 and 38 weeks of gestation predicted spontaneous onset of labor before 41 weeks' gestation with a sensitivity of 46%, specificity of 78%, positive predictive value (PPV) of 82%, negative predictive value (NPV) of 40% in the supine position; and sensitivity of 53%, specificity of 72%, PPV of 81%, NPV of 40% in the upright position. CONCLUSION: Between 37 and 38 weeks' gestation, spontaneous onset of labor before 41 weeks can be predicted by a CL measurement, but with low sensitivity and NPV. Inter-individual variations in CL and in CL changes are large, which hampers the value of single and repeated CL measurements for the prediction of spontaneous onset of labor at term.

Lack of standardization in determining gestational age for prenatal screening.

OBJECTIVES: To determine whether estimation of gestational age (GA) in the context of first-trimester Down syndrome screening is standardized in the Netherlands. METHODS: This was a retrospective study, carried out between January 2005 and December 2006, of women who underwent first-trimester Down syndrome screening (n = 40,730) based on GA, maternal serum analysis and nuchal translucency (NT) measurement. Date of the last menstrual period (LMP), dating scan information including measurement of crown-rump length (CRL), NT thickness and name of the sonographer were recorded for all pregnancies. The accuracy of estimation of GA was evaluated by comparing the GA based on the LMP with that estimated from the CRL, using relevant subsets of the database. A survey of 104 sonographers was performed to further investigate the findings of the preceding analysis. RESULTS: In 44% of all first-trimester combined tests the estimation of GA was based on the dating scan; the method of determination of GA was unknown in 23%. In 15% of all cases a dating scan was recorded but was not used to provide the estimation of GA at blood sampling. Detailed analysis showed that a consistent methodology for the estimation of GA from CRL was not maintained within hospitals and obstetric practices. For a single CRL, the reported GA differed by up to 10 days. Finally, it was demonstrated that individual sonographers reported different GAs for a given CRL. CONCLUSIONS: Currently, estimation of GA in the first trimester in the Netherlands is not standardized. To improve the performance of prenatal screening for Down syndrome, estimation of GA should be based on ultrasound examination, with one nationally accepted CRL curve.

Aortico-right ventricular tunnel: prenatal diagnosis leading to neonatal survival.

In the 36th week of gestation a large aortico-right ventricular tunnel with an otherwise structurally normal heart was diagnosed by fetal echocardiography. This report describes for the first time the impact of the timely prenatal diagnosis of an aortico-right ventricular tunnel followed by successful management in early infancy.

Sotalol in the treatment of fetal dysrhythmias.

BACKGROUND: Fetal tachycardia may cause hydrops fetalis and lead to fetal death. No unanimity of opinion exists regarding the optimum treatment. This study evaluates our experience with transplacental sotalol therapy to treat fetal tachycardias in terms of safety and efficacy. METHODS AND RESULTS: The charts of 21 patients who were treated with sotalol for fetal tachycardia were reviewed. Ten fetuses had atrial flutter (AF), 10 had supraventricular tachycardia (SVT), and 1 had VT. Hydrops fetalis was present in 9 fetuses. Drug treatment was successful in establishing sinus rhythm in 8 of 10 fetuses with AF and in 6 of 10 fetuses with SVT. The mortality rate in this study was 19% (4 of 21 fetuses; 3 had SVT and 1 had AF); 3 deaths occurred just days after the initiation of sotalol therapy, and 1 occurred after a dosage increase. At birth, tachycardia was present in 6 infants. Two patients who converted to sinus rhythm in utero suffered from neurologic pathology postnatally. CONCLUSIONS: Fetal tachycardia is a serious condition in which treatment should be initiated, especially in the presence of hydrops fetalis. The high success rate in fetuses with AF suggests that sotalol should be considered a drug of first choice to treat fetal AF. The low conversion rate and the fact that 3 of the 4 deaths in this study occurred in fetuses with SVT indicate that the risks of sotalol therapy outweigh the benefits in this group and that sotalol should, therefore, be limited in the treatment of fetal SVT.

Management outcome and follow-up of fetal tachycardia.

OBJECTIVES: The aim of this study was to evaluate fetal tachycardia and the efficacy of maternally administered antiarrhythmic agents and the effect of this therapy on delivery and postpartum management. BACKGROUND: Sustained fetal tachycardia is a potentially life-threatening condition in which pharmacologic therapy is reported to be effective. There is ongoing discussion about optimal management. METHODS: A group of 51 patients with M-mode echocardiographically documented fetal tachycardia was studied retrospectively. RESULTS: Thirty-three fetuses had supraventricular tachycardia; 15 had atrial flutter; 1 had two episodes of both; and 2 had ventricular tachycardia. Fetal hydrops was seen in 22 patients. Thirty-four fetuses received maternal therapy with either digoxin or flecainide as the first administered drug (additional drugs were given in 12). Drug treatment was successful in establishing acceptable rhythm control in 82% (84% without, 80% with hydrops). In the latter group the median number of drugs and number of days to conversion were higher. Three patients with fetal hydrops died. In 50% of cases, tachycardia reappeared at delivery: 9 neonates presented with atrial flutter, 14 with supraventricular tachycardia and 1 with ventricular tachycardia. Seventy-eight percent of the group had pharmacologic therapy by 1 month of age and 14% by 3 years. CONCLUSIONS: Fetal tachycardia can be treated adequately in the majority of patients, even in the presence of hydrops, and therefore emergency delivery might not be indicated. Digoxin and flecainide were drugs of first choice and produced no serious adverse effects in this series of patients. The majority of patients do not require prolonged therapy.

Atrial flutter in the perinatal age group: diagnosis, management and outcome.

OBJECTIVES: The aim of this retrospective study was to evaluate perinatal atrial flutter (AF) and the efficacy of maternally administered antiarrhythmic agents, postpartum management and outcome. BACKGROUND: Perinatal AF is a potentially lethal arrhythmia, and management of this disorder is difficult and controversial. METHODS: Forty-five patients with documented AF were studied retrospectively. RESULTS: Atrial flutter was diagnosed prenatally in 44 fetuses and immediately postnatally in 1 neonate. Fetal hydrops was seen in 20 patients; 17 received maternal therapy, 2 were delivered and 1 was not treated because it had a severe nontreatable cardiac malformation. In the nonhydropic group of 24 patients, 18 were treated and the remaining 6 were delivered immediately. In the hydropic group, 10 received single-drug therapy (digoxin or sotalol) and 7 received multidrug therapy. In the nonhydropic group, 13 received a single drug (digoxin or sotalol) and 5 received multiple drugs. One patient with rapid 1:1 atrioventricular conduction (heart rate 480 beats/min) died in utero and another died due to a combination of severe hydrops because of the AF, sotalol medication, stenosis of the venous duct and hypoplastic placenta. Of the 43 live-born infants, 12 were in AF at birth. Electrical cardioversion was successful in eight of nine patients. No recurrences in AF have occurred beyond the neonatal period. Four patients with fetal flutter and hydrops showed significant neurological pathology immediately after birth. CONCLUSIONS: Fetal AF is a serious and threatening rhythm disorder, particularly when it causes hydrops, it may be associated with fetal death or neurological damage. Treatment is required and primarily aimed at reaching an adequate ventricular rate and preferably conversion to sinus rhythm. Digoxin failed in prevention of recurrence at time of delivery in a quarter of our patients, whereas with sotalol no recurrence of AF has been reported, suggesting that class III agents may be the future therapy. Once fetuses with AF survive without neurological pathology, their future is good and prophylaxis beyond the neonatal period is unnecessary.

Prenatal diagnosis of congenital heart disease affects preoperative acidosis in the newborn patient.

OBJECTIVES: Congenital heart disease is the leading cause of death in the first year after birth. Prenatal diagnosis of the disease can optimize the preoperative condition of the patient and may help in the prevention of acidosis. In this retrospective study we compared the occurrence of metabolic acidosis in patients with and without prenatal diagnosis of a congenital heart disease. METHODS: Data of 408 patients who needed an operation for congenital heart disease within 31 days of life were analyzed retrospectively. Arterial blood gases at fixed time intervals and worst blood gas of 81 patients with and 327 patients without a prenatal diagnosis were compared, categorizing the patients on ductus dependency, anticipated univentricular or biventricular repair, and left-sided, right-sided, or no heart obstruction. RESULTS: In the overall group significant differences in lowest pH, lowest base excess, and highest lactate level were found, with metabolic acidosis more common among the patients with a postnatal diagnosis. In the group of patients with ductus-dependent congenital heart disease, the difference between patients receiving a prenatal and those receiving a postnatal diagnosis was more significant than in the group with non-ductus-dependent lesions. Analyzing patients with right-sided, left-sided, and no obstruction separately, significant differences were found in the group with left-sided heart obstruction for lowest pH and base excess and in the group with right-sided heart obstruction for lowest base excess. CONCLUSIONS: Prenatal diagnosis of congenital heart disease minimizes metabolic acidosis in patients with congenital heart disease and may be associated with improved long-term outcome and prevention of cerebral damage among this fragile group of patients, although no significant effect on direct surgical outcome was encountered.

Isochromosome 1q as the sole chromosomal abnormality in two fetal teratomas. Possible trisomic or tetrasomic zygote rescue in fetal teratoma with an additional isochromosome 1q.

An isochromosome of the long arm of chromosome 1 leading to tetrasomy 1q was detected as the sole chromosomal aberration in two cases of fetal teratoma arising from the oral cavity. This type of teratoma is extremely rare and has seldom been investigated cytogenetically. Studies of DNA markers in the tumor, normal fetal skin, and parental cells demonstrated that in both cases the additional 1q material was of maternal origin. In one of the patients, the teratoma had maternal 1q marker alleles that were not found in the fetal body cells. This implies that the tumor was not derived in a direct way from the fetal body tissue; instead, the chromosomally-normal fetus might be the result of some trisomic or tetrasomic zygote rescue mechanism.

Doppler assessment of the fetoplacental circulation in normal and growth-retarded fetuses.

The Pulsatility Index (PI) of Doppler flow signals from umbilical arteries was used to study flow resistance of the placental villous circulation. A preliminary reference curve of PI values in normal pregnancy was composed from 23 healthy women examined every 2 wk from the 16th postmenstrual week until delivery. The gestational age-related decrease of PI values reflects a reduction of flow resistance in the placental villous circulation. In small-for-date fetuses significantly increased PI values were found, indicating that this simple technique may permit an early diagnosis of compromised fetoplacental circulation, even several weeks to months before fetal growth retardation is clinically presumed.

Characteristics of flow velocities in the umbilical arteries, assessed by Doppler ultrasound.

Measuring blood velocities by Doppler ultrasound has introduced a new noninvasive technique into obstetrical diagnostics. This study evaluates the information about fetoplacental hemodynamics that can be extracted from Doppler signals obtained from umbilical arteries. The most significant blood flow characteristic is blood flow pulsatility expressed as pulsatility index (PI). The PI is the difference between systolic and diastolic velocity, divided by the mean velocity. The PI strongly correlates with downstream impedance to flow. It is demonstrated that sophisticated spectral analysis of the Doppler signals has no practical advantages over the simple zero-crossing technique for establishing PI values, since blood flow in umbilical arteries has a blunt-to-flat profile. This study shows that the PI is a gestational-age-related, intra- and inter-observer-reproducible variable. The significant decrease of PI values with advancing gestational age reflects a progressive reduction of placental vascular resistance to umbilical blood flow. The PI holds promise as a simple method for early diagnosis of impaired umbilical circulation.

Persistent junctional reciprocating tachycardia in the fetus.

BACKGROUND: Persistent junctional reciprocating tachycardia (PJRT) tends to be a persistent arrhythmia and requires aggressive therapeutic management. Diagnosis and management of this infrequently occurring tachycardia in the fetus at an early stage is of importance for the prevention of congestive heart failure (CHF). METHODS: A retrospective study of four fetuses with supraventricular tachycardia (SVT) of the PJRT type was performed. RESULTS: All had sustained SVT (mean of 228 beats/min) at a mean gestational age of 34 + 5 weeks, with CHF present in two. Three fetuses had prenatal characteristics of PJRT on M-mode echocardiography with a ventriculoatrial (VA)/atrioventricular ratio of > 1 on M-mode echocardiography suggesting a slow conducting accessory pathway. All four fetuses had postnatal confirmation of the diagnosis. Transplacental treatment with flecainide was effective in one patient; sotalol as a single drug or in combination with digoxin was partially effective in the remaining three. Two developed sinus rhythm, with short intermittent periods of tachycardia and decreasing signs of CHF; one case showed a minimal decrease in heart rate. Oral propranolol therapy converted two patients postnatally; in the remaining two patients radiofrequency ablation was performed at the age of 5 months and 6 years. CONCLUSIONS: The characteristics of our prenatal PJRT cases included a sustained heart rate not exceeding 240 beats/min with a long VA interval, the presence of CHF and therapy resistance. Transplacental treatment should be initiated, possibly with a combination of sotalol and digoxin in non-hydropic cases, or flecainide, especially in case of fetal hydrops. Pharmacological therapy is to be preferred postnatally, but radiofrequency ablation seems to be indicated in therapy-resistant cases with CHF, even in the first months of life.