Carrier Screening for Cystic Fibrosis : Costs and Clinical Outcomes

Outcome of pregnancy after amniocentesis was studied in a randomised controlled trial of 4606 women, age-range 25-34 years, without known risk of genetic disease. Spontaneous abortion rate was 1.7% in the study group after amniocentesis and 0.7% in the control group after ultrasound (relative risk 2.3). In the study group, increased levels of maternal serum alpha-fetoprotein before amniocentesis, perforation of the placenta during amniocentesis, and withdrawal of discoloured amniotic fluid were associated with an increased risk of spontaneous abortion. In the first six weeks after amniocentesis/ultrasound scan, amniotic fluid leakage occurred more often in the study group but there was no difference in the rate of vaginal bleeding. Frequency of postural malformations in the infants in the two groups was the same. In the study group, respiratory distress syndrome was diagnosed more often (relative risk 2.1) and more babies were treated for pneumonia (relative risk 2.5).

We analyzed 3000 consecutive amniocenteses for prenatal diagnosis to assess the frequency of abnormalities, safety of the procedure, technical and interpretive difficulties and overall diagnostic accuracy. Chromosomal abnormalities were detected in 2.4 per cent of the 2404 pregnancies tested because of advanced maternal age (greater than or equal to 35 years), in 1.2 per cent of 240 monitored because of prior trisomy 21 and in 9.1 per cent of 55 examined for other cytogenetic indications. Mosaicism was detected in 0.4 per cent, and unexpected translocations in 0.4 per cent. Amniotic fluid was obtained on the first attempt in 99.3 per cent of the last 1000 cases, and cultures established from 99.7 per cent of patients attending our clinic. The fluid was discolored in 1.2 per cent of patients, a quarter of whom had missed abortions. The rate of spontaneous abortion after amniocentesis was 1.5 per cent. There were 14 diagnostic errors, six serious enough to affect the outcome of pregnancy. The karyotyping error rate was 0.07 per cent. We conclude that prenatal diagnosis is safe, highly reliable and extremely accurate.