Prenatal diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in a family with a previous fatal case of sudden unexpected death in childhood

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a potentially fatal inherited disease with a carrier frequency of approximately 1:100 in most Caucasian populations. The disease is implicated in sudden unexpected death in childhood. A prevalent disease-causing point mutation (A985G) in the MCAD gene has been characterized, thus rendering diagnosis easy in the majority of cases. Since the clinical spectrum of MCAD deficiency ranges from death in the first days of life to an asymptomatic life, there are probably other genetic factors—in addition to MCAD mutations—involved in the expression of the disease. Thus, families who have experienced the death of a child from MCAD deficiency might have an increased risk of a seriously affected subsequent child. In such a family we have therefore performed a prenatal diagnosis on a chorionic villus sample by a highly specific and sensitive polymerase chain reaction (PCR) assay for the G985 mutation. The analysis was positive and resulted in abortion. We verified the diagnosis by direct analysis on blood spots and other tissue material from the aborted fetus and from family members.     

The safety of fetoscopy: (I). Effect of umbilical vessel puncture on the fetal heart rate and cord histology

The fetal heart rate (FHR) was continuously monitored during 42 umbilical vessel punctures performed at the placental insertion of the cord in 24 diagnostic fetoscopies in which pure fetal blood was obtained. In only one patient did a deceleration first appear during puncture and aspiration of fetal blood. In two patients decelerations preceded fetoscopy and in two others they began during the fetoscopy but before puncture of an umbilical vessel. In 19 patients, the FHR did not change at all during the procedure. Fetal haemorrhage after sampling was either absent or minimal. Six pregnancies were terminated because a positive diagnosis had been made and 18 healthy babies were born. Umbilical cords were examined after 7 terminations of pregnancy and after 6 deliveries. In the former group the puncture could just be seen with the naked eye and the needle track was demonstrated histologically in 6. No traces of the puncture or other abnormalities were found in the cords after delivery. Fetal blood sampling from umbilical cord vessels, particularly at the placental insertion of the cord, is the technique of choice since pure fetal blood can be obtained without increasing the risk of fetoscopy.     

Recurrence risk of neural tube defects following a miscarriage

Data from 280 sibships in three published series were used to see if the increased risk of neural tube defect (NTD) associated with having had a miscarriage in the immediately preceding pregnancy was also found in women with a previous affected pregnancy. A statistically significant relative risk of 4.0 (2-tail P=0.0111, Fisher exact test) was found among such women, and this could not be accounted for by the effect of parity or of a history of miscarriage in general. The finding may be useful when counselling patients.