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Aims/hypothesis: In this study we investigated whether chronic fetal hypoxia, as indicated by amniotic fluid erythropoietin levels, is associated with perinatal morbidity in type 1 diabetic pregnancies., Methods: A total of 331 women with type 1 diabetes had at least one childbirth between 1995 and 2000. The amniotic fluid erythropoietin concentration was measured in 156 diabetic singleton pregnancies at a median time of 1 day before Caesarean section without labour contractions and in 19 healthy control subjects at Caesarean section., Results: The median amniotic fluid erythropoietin level was 14.0 mU/ml (range 2.0-1975.0) in diabetic pregnancies and 6.3 mU/ml (range 1.7-13.7) in controls (p<0.0001). Of the 156 diabetic patients, 21 (13.5%) had amniotic fluid erythropoietin levels higher than 63.0 mU/ml. Amniotic fluid erythropoietin levels correlated negatively with umbilical artery pH (r=-0.49, p<0.0001) and pO2 (r=-0.62, p<0.0001) at birth and neonatal lowest blood glucose level (r=-0.47, p<0.0001). Positive correlations were found between amniotic fluid erythropoietin levels and umbilical artery pCO2 (r=0.49, p<0.0001) and last maternal HbA1c (r=0.43, p<0.0001). Furthermore, a U-shaped correlation was demonstrated between amniotic fluid erythropoietin levels and birthweight z score (z score below -0.6 SD units: r=-0.63, p=0.0007; z score above +1.0 SD units: r=0.32, p=0.0014). Neonatal hypoglycaemia, hypertrophic cardiomyopathy and admission to the neonatal intensive care unit occurred significantly more often in cases with high amniotic fluid erythropoietin levels (>63.0 mU/ml) than in those with normal levels. Multivariate logistic regression analysis revealed that amniotic fluid erythropoietin was the only variable independently related to low umbilical artery pH (<7.21; p<0.0001) and neonatal hypoglycaemia (p=0.002). Low umbilical artery pO2 (<15.0 mm Hg) was explained by amniotic fluid erythropoietin (p<0.0001) and birthweight z score (p=0.004)., Conclusions/interpretation: Antenatal high amniotic fluid erythropoietin levels can identify type 1 diabetic pregnancies at increased risk of severe perinatal complications.

Objective: The objectives of this follow-up study of 292 fetuses with various cardiac arrhythmias were to estimate the incidence of structural heart defects and fetal compromise, to investigate the effects of antiarrhythmic medication, and to evaluate perinatal mortality and morbidity and long-term outcome., Methods: The arrhythmias were classified into atrial extrasystoles (n = 200), atrial tachycardias (n = 35), atrioventricular block (n = 36), sinus bradycardia (n = 14), and ventricular extrasystoles (n = 7), and outcome of the infants was analyzed., Results: The incidence of cardiac anomalies was 12% in the study population. In utero cardiac failure was noted in 11%. Among fetuses with atrial extrasystoles, 1% developed supraventricular tachycardia after birth. During antiarrhythmic therapy, sinus rhythm was achieved in 92% of nonhydropic and in 63% of hydropic fetuses. The latter had higher mortality and risk for neurologic morbidity than did nonhydropic fetuses; 38% versus 3.7% and 40% versus 12%, respectively. Among fetuses with atrioventricular block only, the survival rate was 82%, with a heart defect, prognosis was poor: 50% survived. Sinus bradycardia and ventricular extrasystoles were associated with survival rates of 75% and 67%. In the follow-up of the whole study population lasting a median 5 years, 93% are alive and 3% have a neurologic disorder., Conclusion: All fetal arrhythmias except atrial extrasystoles were associated with a moderately high risk for fetal distress. In cases of compromise, fetal and neonatal prognosis was poor and was an indication for perinatal medication. After the newborn period, the prognosis has been good. However, the risk for neurologic morbidity must be taken into consideration.

Objective: The aim of the study was to review the outcome of fetuses with structural heart disease detected by echocardiography., Methods: A total of 99 fetuses with different types of cardiac defects, diagnosed at a median gestational age of 28.4 weeks (range 16-41 weeks), were included. The inclusion criteria were a structural heart defect confirmed postnatally or at post-mortem examination, and a complete, long-term follow-up in utero and after birth in the Hospital for Children and Adolescents, Helsinki, Finland from 1983 to 1999., Results: Of 99 fetuses with in utero diagnosed cardiac anomalies, 6 (6%) showed normal cardiac status postnatally. Thirty-five percent of fetuses (n = 10) with heart disease diagnosed before 24 weeks of gestation were terminated. Of 83 fetuses, 7 (8%) with a heart defect died in utero at a median gestational age of 33 weeks. Chromosomal abnormality was found in 28% of cases. Fetuses with normal chromosomes had extracardiac anomalies in 40% of cases. Mortality due to chromosomal abnormality was 73% and from extracardiac anomaly 48%. Intrauterine heart failure was detected in 27% of fetuses and was frequently associated with univentricular heart (UVH) and intracardiac tumors, in 36 and 67%, respectively; 12 fetuses (13%) were found to have associated arrhythmia; 4 of these died. Of 76 live births (median gestational age 38 weeks, birth weight 2878 g), a total of 37 (49%) neonates died. Twenty-four neonates (32%) underwent cardiac surgery or invasive procedure; six infants (25%) died after the procedure. Neonatal mortality was highest in fetuses with hypoplastic left heart syndrome (HLHS), ventricular septal defect (VSD), and UVH (87, 64, and 50%, respectively). In long-term follow-up (median 3.8 years), 34 children of 76 live births (45%) were alive, 59% of them were without symptoms., Conclusion: Our data indicate that despite elective, planned delivery the prognosis for fetuses with in utero diagnosed heart defect was poor. The outcome was largely attributable to associated extracardiac malformations and chromosomal abnormalities.

Congenital heart block (CHB) can result in intrauterine cardiac failure leading to fetal or neonatal loss. To establish perinatal hemodynamic factors which might predict adverse outcome, six fetuses with CHB diagnosed between 20 and 30 gestational weeks were examined by echocardiography at 2-week intervals. Neonatal morbidity and outcome in infancy are detailed. The fetuses showed a significant decrease in ventricular rate (VR) with advancing gestation (60 +/- 7 vs 51 +/- 4 beats/min, p = 0.03). Cardiac decompensation defined as hydrops or pericardial effusion was associated with VR of lower than 55 beats/min in two fetuses. Three mothers had a therapeutic trial with a sympathomimetic and digoxin. Salbutamol increased VR 10% in one of three fetuses treated. Digoxin decreased pericardial effusion in one hydropic fetus with autoimmune myocarditis. In this fetus, poor left ventricular fractional shortening (LVFS) was accompanied with high umbilical artery resistance index (RI). High amniotic fluid erythropoietin indicated severe hypoxia preceding death. Pacemaker was indicated in all the newborns. At the age of 2 weeks all the surviving infants had tricuspid regurgitation and a shunt through foramen ovale due to asynchronized atrioventricular contraction. During the 12-month follow-up two of five surviving infants had no symptoms. One had symptomatic neonatal lupus. Two infants had patent ductus arteriosus, one with dilated cardiomyopathy. In conclusion, poor fetal outcome was associated with low VR, low LVFS, and high RI. Despite early pacing, morbidity was high in infancy due to cardiomyopathy and associated heart defects. Regular echocardiographic monitoring during pregnancy and after delivery is required in order to optimize care and timing of any interventions.

Objective: To assess the impact of increased nuchal translucency observed during early pregnancy on the subsequent health of children with normal chromosomes, with special attention to cardiac anatomy and function., Methods: Clinical examination and detailed cardiac evaluation were carried out in 50 chromosomally normal children at the age of 2.4-7.1 years who had had a nuchal translucency measurement of > or = 3 mm at 13-15 weeks' gestation. The data of two babies who died of heart defects were also included., Results: Major cardiac defects were identified in four (8%) of the children. The growth of all children was within normal limits. One child had Noonan syndrome, one had a cleidocranial dysplasia and a third had a developmental delay together with an unrecognized syndrome. Webs in the neck region were noticed in two children, with no associated pathology., Conclusions: In chromosomally normal fetuses with increased nuchal translucency, fetal echocardiography is necessary to identify major cardiac defects. In general, the parents can be reassured that, in the great majority, postnatal development is normal.

Objective: To review the outcomes of 193 fetuses with cardiac abnormalities detected by echocardiography., Methods: A total of 422 fetuses between 16 and 41 gestational weeks, referred to paediatric cardiologists for detailed echocardiography, were included in this study., Results: Structural heart defects were found in 55 (28%), isolated arrhythmia in 105 (54%), and other non-structural abnormalities (dilated cardiomyopathy, hypertrophic cardiomyopathy, aneurysm of the foramen ovale, isolated pericardial effusion or echogenic foci) in 33 (17%) of 193 fetuses. Total mortality was 26%. The prognosis was poor in fetuses with structural heart defects; 37 of 55 cases (67%) died in utero or postnatally. Chromosomal abnormality was associated with structural heart defect in 38% of fetuses, of whom 38% died. Among fetuses with isolated arrhythmia survival was 95%. Poor outcome was associated with complete heart block (n = 14) in 2 (14%) fetuses with hydrops and heart rate of less than 55 per minute, and with supraventricular tachycardia (n = 21) in three (14%) neonates delivered prematurely at a mean gestational age of 33 weeks. Furthermore, nine of 12 fetuses (75%) with structural heart defects and arrhythmia died. Among fetuses with non-structural cardiac abnormalities, survival was 73%. Poor outcome was evident in fetuses with dilated cardiomyopathy in eight of 13 (62%) and with hypertrophic cardiomyopathy in one of eight (13%) of cases., Conclusions: Factors associated with a poor prognosis were: structural heart defect associated with chromosomal abnormality or arrhythmia, congestive heart failure associated with supraventricular tachycardia or complete heart block, especially if delivery occurs preterm; and fetal hydrops with congestive heart failure and atrioventricular valve regurgitation.

There is insufficient data on the value of absent or retrograde end-diastolic flow (AREDF) in the fetal umbilical artery, descending aorta and aortic arch to predict perinatal outcome. In this prospective investigation, 65 pregnant women between 24 and 34 weeks' gestation with pregnancy-induced hypertension were studied by color Doppler echocardiography. Pregnancies leading to birth at or before 34.0 gestational weeks (23 with and 19 without AREDF) were included in the outcome analysis. Fetuses with AREDF were delivered at earlier gestational ages (p = 0.006). They had a higher incidence of gastrointestinal complications (p = 0.01), bronchopulmonary dysplasia (p = 0.03), intraventricular hemorrhage (p = 0.03) and vascular hypotension (p = 0.03) than those without AREDF. The presence of AREDF was associated with a mortality rate of 30%, whereas in fetuses without AREDF there was no mortality (p = 0.01). Using logistic regression and taking into consideration various perinatal factors, the presence of AREDF (p = 0.03) and early gestational age (p = 0.0001) were associated with serious neonatal diseases or death. A reverse diastolic flow in the aortic isthmus was registered in five fetuses; three died during the perinatal period and one was severely damaged. According to our results, AREDF, particularly with the appearance of reverse diastolic flow in the isthmus of the aortic arch, is a predictor of poor neonatal outcome.