Prenatal diagnosis of beta-thalassaemia in Pakistan: experience in a Muslim country.

A service for prenatal diagnosis of beta-thalassaemia was introduced in Pakistan in May 1994. Two renowned Islamic scholars, consulted before the service was introduced, ruled that a pregnancy can be terminated if the fetus is affected by a serious genetic disorder, and if termination is before 120 days (17 weeks) of gestation. During the first 3(1/2) years of the service 300 couples requested the test. Almost all the couples had been informed by their treating doctors. Most diagnoses were made between 10 and 16 weeks of gestation, and only 15 (5%) were reached after the 16th week. DNA analysis was by the amplification refractory mutation system (ARMS). A multiplex ARMS was developed in which three primer combinations identified the mutations in 91.5% of the couples. In 13 couples (4. 3%) linkage analysis was required for the fetal diagnosis. In 47/53 (88.7%) women carrying an affected fetus the pregnancy was terminated. In six cases it was declined principally on religious grounds. Postnatal confirmation of the prenatal diagnosis was possible in 117 unaffected children. One year after the start of the service, interviews with 141 couples with an affected child showed that 72% knew of the availability of prenatal diagnosis. Thirty-two of the informed couples had had a pregnancy, but only 18 (56%) used prenatal diagnosis. The main reasons for non-utilization of prenatal diagnosis were the cost of the test and fear of undergoing the test, though some gave no clear explanation. This study demonstrates that prenatal diagnosis is feasible and acceptable in a Muslim country such as Pakistan.

Prenatal diagnosis of haemophilia-A: a basis for the Pakistani families.

OBJECTIVE: To determine the feasibility of a PCR based strategy for prenatal diagnosis of Haemophilia-A in Pakistani Families. DESIGN: Prospective. SETTING: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi. SUBJECTS: Five families with at least one child affected with Haemophilia-A. Each family comprised of father, mother, affected child and fetus when present. MAIN OUTCOME MEASURES: Short Tandem Repeat (STR) analysis in the Intron 22 of factor VIII gene. RESULTS: PCR based analysis of the STR in intron 22 of factor VIII gene showed that the marker was informative in 4/5 study families and could be used in these families for the prenatal diagnosis of Haemophilia-A. In two families prenatal diagnosis was carried out by Chorionic Villus Sampling at 10-13 weeks gestation and the results in both the cases showed a carrier female fetus. CONCLUSION: Linkage based prenatal diagnosis of Haemophilia-A by an intragenic STR marker is feasible in most of the Pakistani families. The long term response of the Haemophiliac families to the availability of prenatal diagnosis remains to be seen. The STR marker can also be used for carrier detection of female subjects in the affected families.

A case for comprehensive antenatal screening for blood group antibodies.

OBJECTIVES: To determine the frequency of various blood group antibodies responsible for haemolytic disease of the new born (HDN). DESIGN: A prospective study of all neonates and still born foetuses suspected to have haemolytic disease of the new born and their mothers. SUBJECTS: Neonates suspected to have HDN as per study criteria along with their mothers and mothers of still born foetuses with hydrops foetalis. METHODS: Pertinent serological tests, serum bilirubin estimation, haemoglobin estimation and reticulocyte count on neonate's blood samples and demonstration/titration of blood group specific antibodies in maternal blood samples. RESULTS: Six cases of HDN due to blood group antibodies were detected so far. Four were due to anti-D and all were of mild severity as per study criteria. Two cases were of severe haemolytic disease (hydrops foetalis). Both were due to anti Kell. Both women had history of previous blood transfusion and abortions. CONCLUSION: Comprehensive antibody screening should be performed during antenatal period in women who have received blood transfusion and/or have history of un-explained abortions.