Experience with 500 prenatal diagnoses of sickle cell diseases: The effect of gestational age on affected pregnancy outcome

Prenatal diagnosis of sickle cell diseases is obtained rapidly and precisely by polymerase chain reaction (PCR) with Ddel restriction analysis and dot-blotting with alllele-specific oligonucleotides (ASO). Prenatal diagnosis of HgbSS and HgbSC was performed in 500 pregnancies, 196 by Southern blot and 304 by PCR. PCR drastically shortened the interval from sampling to reporting, allowing acceptance even of samples with unknown paternal phenotype, and resulted in an overall four-fold increase in diagnoses. In 108 pregnancies, the diagnosis was an affected fetus; 25 were HgbSC: 3 (12 per cent) were terminated; 83 were HgbSS: four ended in miscarriage; 40/79 (51 per cent) were terminated. The gestational age at the time of report to the mother appeared to be a major outcome determinant when the fetal diagnosis was HgbSS. The change-point in the maternal decision was found at 20 weeks of gestation. Before the 20th week, most mothers (64 per cent) chose termination; thereafter, the majority (72 per cent) chose continuation. The odds ratio of termination in earlier relative to later reporting was 4·7. In order to offer a choice to the mothers at risk of delivering a fetus affected by sickle cell disease, the diagnosis should be reported before the 20th week of gestation.