Annette Gilfillan

Prenatal screening for cystic fibrosis

Screening for carriers of CF (cystic fibrosis) is now possible but the best way of delivering such a service is unknown. In one model 4348 women attending antenatal clinics in an Edinburgh maternity hospital were invited to participate in a trial of prenatal screening. Mouthwash samples were tested for six CF alleles (85% of mutant genes) and when a woman was found to be a CF carrier her partner was also tested. Heterozygous couples were offered prenatal diagnosis. 609 (14%) women declined to enter the trial and another 574 (13%) were not screened, usually because of late booking. Among the remaining 3165 women there were 111 carriers of a CF gene (1 in 29). 4 of these 111 had carrier partners and these couples opted for prenatal diagnosis, the 1 pregnancy with an affected fetus being terminated. The psychological impact of screening was assessed by the general health questionnaire. There was a significant increase in stress at the time of the test result among women identified as carriers. However, this disappeared when their male partners tested normal and did not reappear later in the pregnancy. By providing time for couples to discuss the possibility of screening and by offering the test at a point (the antenatal booking clinic) at which most pregnant women are seen, this approach has advantages, provided that counselling is readily available.

Antenatal screening for cystic fibrosis: a trial of the couple model

Abstract Objective : To assess the delivery and acceptability of antenatal couple screening for cystic fibrosis. Carrier status was notified only when both members of a partnership had cystic fibrosis alleles and therefore a one in four risk of having an affected child. Design: Mouthwash samples were tested when both partners participated. Results were returned only to positive couples. Setting : Two large maternity hospitals in Edinburgh. Subjects : Screening was offered to all couples who booked at one of the two hospitals. Main outcome measures :(a) The take up of screening, carriers and carrier couples identified, take up of prenatal diagnosis, and numbers of affected fetuses detected; (b) questionnaire measures of patient satisfaction and stress. Results : Screening was offered to 8536 couples. 714 (8.4%) were regarded as ineligible, usually because of late booking or absence of a partner. 1900 (24.3%) of the remainder declined screening. Among the 5922 screened couples, four tested positive - that is, both partners were cystic fibrosis heterozygotes. All four elected to have prenatal diagnosis. There were three terminations of pregnancy because of an affected fetus, one couple having two successive pregnancies with affected fetuses. The participation rate was 76% for eligible couples (5922/7822) and 69% for all couples (5922/8536). Only 89 screened couples (1.5%) requested information on individual carrier status. No anxiety was detected among a cohort of the screened population, and 99% of questioned participants expressed satisfaction with the concept of couple screening. Conclusions : Antenatal couple screening is a20satisfactory and acceptable way of screening for cystic fibrosis and has been adopted as routine in the two trial hospitals.

Prenatal screening for cystic fibrosis: attitudes and responses of participants

Mennie M, Compton M, Gilfillan A, Axton RA, Liston WA, Pullen I, Whyte D, Brock DJH. Prenatal screening for cystic fibrosis: attitudes and responses of participants.

The incidence of cystic fibrosis in Scotland calculated from heterozygote frequencies.

The incidence of cystic fibrosis (CF) has previously been calculated from epidemiological surveys and from neonatal screening. With the cloning of the CF gene it has become possible to derive incidence figures from heterozygote frequencies, provided that the distribution of mutant alleles among healthy carriers is the same as among affected people. We have estimated the allele frequencies for four CF mutations, AF508, G551D, G542X and R117H, in 14360 unselected women undergoing antenatal heterozygote screening. The proportion of R117H, an allele of known mild effect, was much greater for het‐erozygotes than for homozygotes. The incidence of CF was therefore calculated from the heterozygote frequencies of AF508, G551D and G542X in a larger cohort of 27 161 successively screened women. The point estimate for the incidence of CF in the Scottish population was 1 in 1984, with 95% confidence intervals of 1 in 1692 to 1 in 2336.

The haplotype distribution of the delta F508 mutation in cystic fibrosis families in Scotland.

SummaryThe gene defective in cystic fibrosis (CF) has recently been isolated and the major mutation identified. The haplotype distribution of this mutation (ΔF508) has been determined for 215 CF chromosomes in the Scottish population. ΔF508 represents 73% of all CF mutations in this group. There remains considerable linkage disequilibrium between XV2c and KM19 and other mutations in the CF gene.