U. Gembruch

Predictors of neonatal outcome in early-onset placental dysfunction

OBJECTIVE: To identify specific estimates and predictors of neonatal morbidity and mortality in early onset fetal growth restriction due to placental dysfunction. METHODS: Prospective multicenter study of prenataly diagnosed growth-restricted liveborn neonates of less than 33 weeks of gestational age. Relationships between perinatal variables (arterial and venous Dopplers, gestational age, birth weight, acid-base status, and Apgar scores) and major neonatal complications, neonatal death, and intact survival were analyzed by logistic regression. Predictive cutoffs were determined by receiver operating characteristic curves. RESULTS: Major morbidity occurred in 35.9% of 604 neonates: bronchopulmonary dysplasia in 23.2% (n=140), intraventricular hemorrhage in 15.2% (n=92), and necrotizing enterocolitis in 12.4% (n=75). Total mortality was 21.5 % (n=130), and 58.3% survived without complication (n=352). From 24 to 32 weeks, major morbidity declined (56.6% to 10.5%), coinciding with survival that exceeded 50% after 26 weeks. Gestational age was the most significant determinant (P<.005) of total survival until 266/7 weeks (r2=0.27), and intact survival until 292/7 weeks (r2=0.42). Beyond these gestational-age cutoffs, and above birth weight of 600 g, ductus venosus Doppler and cord artery pH predicted neonatal mortality (P<.001, r2=0.38), and ductus venosus Doppler alone predicted intact survival (P<.001, r2=0.34). CONCLUSION: This study provides neonatal outcomes specific for early-onset placenta-based fetal growth restriction quantifying the impact of gestational age, birth weight, and fetal cardiovascular parameters. Early gestational age and birth weight are the primary quantifying parameters. Beyond these thresholds, ductus venosus Doppler parameters emerge as the primary cardiovascular factor in predicting neonatal outcome. LEVEL OF EVIDENCE: II

The cerebroplacental Doppler ratio revisited

To evaluate the distribution of Doppler pulsatility index (PI) measurements of the umbilical and middle cerebral arteries in singleton fetuses of women with normal uterine artery blood flow and to construct reference ranges for the cerebroplacental PI Doppler ratio.

World experience of percutaneous ultrasound-guided balloon valvuloplasty in human fetuses with severe aortic valve obstruction

Prenatal alleviation of severe fetal aortic valve obstructions by percutaneous ultrasound-guided balloon valvuloplasty has been performed to improve the fate of affected fetuses. The purpose of this study was to analyze the current world experience of these procedures in human fetuses. Data from 12 human fetuses were available for analysis. The mean gestational age at intervention was 29.2 weeks (range 27 to 33). The mean time period between initial presentation and intervention was 3.3 weeks (range 3 days to 9 weeks). Technically successful balloon valvuloplasties were achieved in 7 fetuses, none of whom had an atretic valve. Only 1 of these fetuses remains alive today. Of the 5 remaining technical failures, 1 patient with severe aortic stenosis underwent successful postnatal intervention and remains alive. Six patients who survived prenatal intervention died from cardiac dysfunction or at surgery in the first days or weeks after delivery. Four fetuses died early within 24 hours after the procedure, 1 from a bleeding complication, 2 from persistent bradycardias, and 1 at valvotomy after emergency delivery. Thus, the early clinical experience of percutaneous ultrasound-guided fetal balloon valvuloplasty in human fetuses with severe aortic valve obstruction has been poor due to selection of severe cases, technical problems during the procedure, and high postnatal operative mortality in fetuses who survived gestation. Improved patient selection and technical modifications in interventional methods may hold promise to improve outcome in future cases.

Progression of Doppler abnormalities in intrauterine growth restriction

To identify the sequence of progression of arterial and venous Doppler abnormalities from the onset of placental insufficiency in intrauterine growth restriction (IUGR).

Qualitative venous Doppler waveform analysis improves prediction of critical perinatal outcomes in premature growth-restricted fetuses.

Our aim was to test the hypothesis that qualitative ductus venosus and umbilical venous Doppler analysis improves prediction of critical perinatal outcomes in preterm growth‐restricted fetuses with abnormal placental function.

Doppler and biophysical assessment in growth restricted fetuses: distribution of test results

Multi‐vessel Doppler ultrasonography and biophysical profile scoring (BPS) are used in the surveillance of growth restricted fetuses (IUGR). The interpretation of both tests performed concurrently may be complex. This study examines the relationship between Doppler ultrasonography and biophysical test results in IUGR fetuses.

Review of diagnosis, treatment, and outcome of fetal atrial flutter compared with supraventricular tachycardia.

Objective: To review the diagnosis, treatment, and outcome of fetal atrial flutter compared with supraventricular tachycardia. Design: Retrospective review of published reports: 11 papers about fetal tachyarrhythmia published between 1991 and 2002 were selected for review. Main outcome measures: All selected studies were analysed for the type of arrhythmia, degree of atrioventricular block in atrial flutter, occurrence of hydrops fetalis, gestational age at diagnosis, first and second line drug treatment, associated cardiac and extracardiac malformations, and mortality of the fetuses. Results: Atrial flutter accounted for 26.2% of all cases of fetal tachyarrhythmias, and supraventricular tachycardia for 73.2%. Hydrops fetalis was reported in 38.6% and 40.5% of fetuses with atrial flutter and supraventricular tachycardia, respectively (NS). Hydropic fetuses with atrial flutter had higher ventricular rates (median 240 beats/min, range 240–300) than non-hydropic fetuses (220 beats/min, range 200–310) (p = 0.02), whereas the atrial rates were not significantly different (median 450 beats/min, range 370–500). Digoxin treatment resulted in a higher conversion rate in non-hydropic fetuses with fetal tachyarrhythmias than in hydropic fetuses (p < 0.001). The overall mortality of atrial flutter was similar to that of supraventricular tachycardia, at 8.0% v 8.9% (p = 0.7). Conclusions: The prevalence of hydrops fetalis did not differ in fetal atrial flutter and supraventricular tachycardia with 1:1 conduction. There was no difference between the response rate to digoxin in fetus with atrial flutter or supraventricular tachycardia. Mortality was similar in the two types of tachyarrhythmia.

Biometry of the fetal heart between 10 and 17 weeks of gestation

Objectives: Assessment of the dimensions of the cardiac chambers and the great arteries in the human fetus may be helpful in the prenatal diagnosis of congenital heart disease. The purpose of this prospective cross-sectional study was to compile normative data in fetal cardiac measurements in early pregnancy. The structure of the fetal heart was examined in 136 normal singleton fetuses between 10 and 17 weeks of gestation. Methods: The transversal heart diameter, both ventricular dimensions, interventricular septal thickness, heart area, heart circumference, thoracic diameter, thoracic circumference and thoracic area were measured in the four-chamber view during diastole. Diameters of the pulmonary trunk and ascending aorta were obtained in the short axis and long axis view during systole. Ultrasound examinations were performed with a 5.0-MHz transvaginal and/or transabdominal phased-array sector scanner. Results: The four-chamber view and the cross-over of the pulmonary artery and the aorta were adequately visualized in 44% of the fetuses at 10 weeks of gestation, in 75% at 11 weeks of gestation, in 93% at 12 weeks of gestation and in 100% of the fetuses at 13–17 weeks of gestation. Before 14 weeks of gestation transvaginal sonography was superior to the transabdominal sonography in visualization of the fetal heart and great arteries. After 14 weeks of gestation transabdominal sonography accurately demonstrated the structure of the fetal heart. The ratio of right and left ventricle (RV/LV) and the ratio of the pulmonary trunk and aorta (PT/AO) were constant during this period of gestation (approximately 1.00 and 1.10, respectively). The ratio of the cardiac and thoracic area showed only a slight increase with advancing gestational age, but with significant correlation. The fetal heart rate showed a slow decrease from 167 to 150 bpm in this period of gestation. The transversal heart diameter, both ventricular dimensions, interventricular septal thickness, heart area, cardiothoracic diameter ratio, aortic diameter and the pulmonary trunk diameter showed a highly significant linear correlation to the gestational age and the biparietal diameter. Conclusion: The advancing quality of ultrasound images allows fetal echocardiography in the first and early second trimester. Our normative data could be the basis of studying the development of cardiac structures in congenital heart disease and it might be helpful in the detection of some congenital heart defects in early pregnancy.

Differential Maturation of the Innate Immune Response in Human Fetuses

Newborns and especially preterm infants show a unique susceptibility to severe bacterial infections that cause significant morbidity and mortality. As very few data are available on innate immune functions in human fetuses, we conducted a comprehensive study to investigate the expression of several adhesion molecules essentially involved in migration (CD11a, CD11b, CD11c, CD18, and CD62L). Furthermore, phagocytic activity, generation of respiratory burst products, and production of several proinflammatory cytokines were assessed. Various functions of the fetal innate immune system were demonstrated to be essentially different from those observed in term neonates or adults. Expression of several surface markers was significantly diminished on fetal granulocytes. Furthermore, a significantly reduced phagocytic activity of fetal granulocytes and monocytes was found, contrasted by an enhanced generation of reactive oxygen products. In addition, we demonstrate that significant numbers of fetal monocytes are capable of the production of proinflammatory cytokines in response to stimulation. However, the pattern of cytokine production is different from the more mature individuals: the number of IL-6 – and tumor necrosis factor-α–positive monocytes were significantly diminished, whereas more IL-8 –producing monocytes were found compared with adults. The results of our study add significantly to our understanding of the maturation and impairment of the innate immune response.

Prenatal diagnosis of congenital heart disease

Owing to the widely different levels of experience of examiners, there is a large discrepancy in study results of second trimester ultrasound screening for fetal malformations, which is a result of varying levels of obstetric scanning expertise prevalent at the reporting centre. This holds particularly true for the prenatal diagnosis of congenital heart disease where detection rates ranging from 0 per cent to 60 per cent are being reported. On the other hand, congenital heart disease affects about 4–8 per 1000 live births and is a leading cause of infant mortality, whereas prenatal diagnosis could possibly prevent death and long‐term morbidity in some of these neonates. Various screening concepts for more effective detection of congenital heart diseases are analysed in this article, including the more recent technique of early echocardiography between 13 and 15 weeks of gestation. High‐risk groups are defined and the group of fetuses with increased thickness of nuchal translucency seems to be of particular interest.