Attitudes towards prenatal diagnosis and termination of pregnancy for thalassaemia in pregnant Pakistani women in the North of England

OBJECTIVES: Most births of children affected with beta-thalassaemia major in the United Kingdom are to parents of Pakistani origin. A popular explanation for this is that Pakistanis decline termination of pregnancy on religious grounds. However, various factors influence people's attitudes towards prenatal diagnosis and termination of pregnancy, which have not been investigated in a UK Pakistani sample. This study is aimed at exploring the attitudes of pregnant Pakistani women towards prenatal diagnosis and termination of pregnancy for beta-thalassaemia major in the North of England. METHODS: Forty-three pregnant women tested for thalassaemia carrier status were interviewed following receipt of their test results. Interviews were analysed using the grounded theory approach. RESULTS: Findings showed: (1) women's awareness of and attitudes towards prenatal diagnosis; (2) the relationship between attitudes towards prenatal diagnosis and termination of an affected foetus; (3) the relationship between attitudes towards termination of pregnancy and religious beliefs, perceptions of severity of the condition, influence of significant others, and (4) the impact of gestational age at the time of the offer of termination of pregnancy. CONCLUSIONS: Pakistani women's attitudes towards prenatal diagnosis and termination of pregnancy are influenced by various factors, and therefore their religion should not be taken as a proxy for their attitudes either for or against termination of pregnancy.     

Termination of pregnancy: attitudes and behavior of women in a traditional society

OBJECTIVES: The Bedouin Arabs, a Muslim traditional ethnic minority in Israel, are faced with difficult choices when offered prenatal diagnosis as part of the universally provided prenatal care in Israel. This paper is to examine attitudes towards and practice of pregnancy termination, following an unfavorable prenatal diagnosis. METHODS: Semistructured interviews with 83 women were conducted to study attitudes. Data from the Soroka Medical Center, where all births in the area take place, were used to assess the rate of terminations of pregnancies following a diagnosis of a chromosomal anomaly. RESULTS: While divided on the question of termination, many women believed that a second medical opinion is needed, preferably from an Arab physician. The reasons for termination are both child- and mother-related. Opposing termination is based on both the suspicion that the diagnosis might be wrong and on religious reasons. Between 1995 and 1999, 686 Bedouin women had undergone amniocentesis (2.4% of all pregnancies). Six of 11 pregnancies with the diagnosis of a trisomy were terminated (54.5%). All cases in which a trisomy was terminated were trisomy 21. CONCLUSIONS: Culturally acceptable prenatal diagnostic services for Muslim populations should be based on early testing, and should involve Muslim physicians and religious authorities.     

Attitudes towards prenatal diagnosis and termination in women who have a sibling with Down's syndrome

This study surveyed the views of 78 women who had a sibling with Down's syndrome towards using prenatal diagnosis and termination. Other data were collected, including participants' perceptions of the difficulty of caring for a child with Down's syndrome, perceived familial approval of selective termination, and the quality of the sibling relationship. Fifty‐four per cent of respondents said they would use diagnostic tests for Down's syndrome in a future pregnancy, 37% would not, and 9% were unsure. In contrast, 33% would consider terminating a pregnancy for Down's syndrome, 53% would not consider termination, and 14% were unsure. Logistic regression showed that the perceived difficulty of caring for a child with Down's syndrome and perceived parental approval of selective termination were the strongest overall predictors of both attitudes. However, women who were younger than their affected sibling were more likely to want to use prenatal diagnosis, and a generally favourable attitude towards abortion predicted a favourable view towards terminating a pregnancy for Down's syndrome. In general, a positive picture emerged of having a sibling with Down's syndrome although around one‐third of the women viewed the impact on themselves and their family as negative and this was reflected in their attitudes towards prenatal testing and termination.     

Prenatal diagnosis using deletion studies in Duchenne muscular dystrophy

Accurate carrier testing and prenatal diagnosis in Duchenne muscular dystrophy (DMD) families is facilitated when an Xp21 deletion is found to be segregating within a family. We discuss the results of the DNA testing in two families, one in which DNA from affected males was available for study and the other in which no DNA from an affected male was available. Factors complicating the counselling of DMD deletion families are outlined.     

In utero fetal muscle biopsy: a precious aid for the prenatal diagnosis of Duchenne muscular dystrophy.

Prenatal diagnosis for Duchenne muscular dystrophy can usually be performed using DNA analysis. This approach would be impossible when there is only one prior affected male and no identifiable gene deletion. Therefore, in utero fetal thigh muscle biopsy with direct examination of muscle by dystrophin analysis may provide the only means of prenatal diagnosis. We report such a case in which fetal muscle biopsy was able to exclude Duchenne muscular dystrophy. A detailed literature review of the topic is provided.     

Attitudinal ambivalence towards Down’s syndrome and uncertainty in prenatal testing and termination intentions

This study aimed to investigate the relationship between attitudinal ambivalence towards Down’s syndrome (DS) and prenatal testing and termination intentions. Intentions towards using a screening test, a diagnostic test and termination of pregnancy for DS were collected from 140 pregnant women along with their attitudes and attitudinal ambivalence towards the condition. Women who were unsure about diagnostic testing and termination were more likely to hold ambivalent attitudes towards DS than were women who gave a definite yes or no response. In particular, a higher level of ambivalence about how a child with DS might impact on parental quality of life was significantly associated with an uncertain attitude towards termination of pregnancy. Qualitative data suggested that ambivalence towards DS was associated with a desire to make diagnostic testing and termination decisions with a significant other. The findings from this study inform debate on the link between ambivalence and informed choice and have implications for supporting prenatal testing decisions in women who hold ambivalent attitudes towards parenting a child with DS.     

A report of two linked studies of knowledge and attitudes to prenatal screening and testing in adults of reproductive age in Japan and the UK

BACKGROUND: prenatal screening for fetal abnormality is being offered routinely in many countries. The need for informed consent demands that the nature of screening is understood by prospective parents, but the opportunities for providing information early in pregnancy before decision-making may be limited. OBJECTIVE: to assess the knowledge about, and attitudes to, prenatal screening in adults of reproductive age in two countries. DESIGN: two groups of adults were surveyed using a specifically designed tool to assess knowledge about fetal abnormalities and potential screening tests, attitudes to screening and termination of pregnancy, and information required by parents before making decisions. SETTING AND PARTICIPANTS: 90 participants were surveyed in Japan, 72% of whom were pregnant or had a partner who was pregnant; 93 participants were surveyed in the UK, none of whom were pregnant. All respondents were aged between 18 and 45 years. MEASUREMENTS: demographic data were collected and analysed. Frequencies were calculated for each questionnaire response. A series of t-tests and chi(2) tests were used to assess differences between the two groups. Free-text data were analysed using content analysis. FINDINGS: overall knowledge of prenatal tests and the conditions for which screening is offered was low in both groups. Significant differences exist between the perception of the conditions for which screening or testing can be offered and the types of conditions that can actually be detected prenatally. Most respondents in both countries would consider termination of pregnancy for fetal abnormality. The information most frequently cited by respondents as important when deciding about testing were the chances of damage to the health of fetus, mother, or both. KEY CONCLUSIONS: women and men of reproductive age in the groups studied are not well-prepared to make decisions about screening or testing in pregnancy. IMPLICATIONS FOR PRACTICE: improvements in preconceptual education on prenatal screening and testing may be required to ensure prospective parents can make informed decisions in early pregnancy.     

Rapid prenatal diagnosis of Duchenne muscular dystrophy with gene duplications by ion-pair reversed-phase high-performance liquid chromatography coupled with competitive multiplex polymerase chain reaction strategy

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by various mutations in the dystrophin gene. Rapid prenatal diagnosis of DMD with gene duplications is difficult due to limitation in gene dosage determination and the requirement for a known disease-causing mutation in the pedigree to achieve a rapid and accurate diagnosis. We report, here, a case with rapid prenatal diagnosis of DMD-affected male with gene duplications in the absence of a known disease-causing variation in the pedigree by using ion-pair reversed-phase high-performance liquid chromatography (IP-RP-HPLC) coupled with competitive multiplex polymerase chain reaction (PCR) protocol. In cases with clinical diagnosis of DMD/BMD, this test should identify greater than 92% of disease-causing DNA variants. The postnatal genetic diagnosis of this case and the same disease-causing mutations subsequently identified in other members of the pedigree confirmed the accuracy of competitive multiplex PCR/IP-RP-HPLC assay in direct prenatal diagnosis of DMD.     

Prenatal diagnosis of myotonic muscular dystrophy with linked deoxyribonucleic acid probes

Since the localization of the myotonic muscular dystrophy gene, closer deoxyribonucleic acid markers have been discovered. These now facilitate both presymptomatic and prenatal diagnosis of myotonic muscular dystrophy. We report our prenatal diagnosis experience with six cases in five families. Obstetricians are advised to inform their patients with a family history of myotonic muscular dystrophy of these testing opportunities. The fetus of the mother with myotonic muscular dystrophy who remains in utero until term is at considerable risk, as is the mother herself, of serious obstetric complications.     

Pitfalls in prenatal diagnosis of DMD due to placental mosaicism of the X-chromosomes: prenatal and postnatal findings in a fetus with a deletion of exons 67-71 of the dystrophin gene

Prenatal diagnosis of Duchenne and Becker muscular dystrophy (DMD) is performed as a routine procedure in many laboratories. The major potential problem is an incorrect diagnosis that could be obtained due to contamination with maternal tissue. We report a case of mosaicism of the X-chromosomes confined to the placenta as a possible source of confusing results in prenatal diagnosis of DMD. To the best of our knowledge, this is the first reported case of this problem in a prenatal DMD diagnosis.     

Perinatal outcomes of prenatal cases testing positive for trisomy 9 by noninvasive prenatal testing

ObjectivesTo evaluate the performance of non-invasive prenatal testing (NIPT) for the detection of fetal trisomy 9 in prenatal screening and to investigate the prenatal appearances and genetic counseling of trisomy 9 fetuses.Materials and methodsThe ultrasonography information, laboratory detection and pregnancy outcome of 16 cases of single pregnancy with trisomy 9 identified by NIPT who received amniocentesis in our prenatal diagnosis center from January 2018 to December 2020 were retrospectively analyzed.ResultsAmong the 16 cases, 2 cases of trisomy 9, 3 cases of trisomy 9 mosaicism, 2 cases reporting of regions of homozygosity and 9 cases of false positive were diagnosed. Among the true positive cases, 4 cases showed abnormal ultrasonic finding: 3 cases terminated pregnancy and 1 case was lost to follow-up. Another 1 case was in utero fetal demise in the second trimester without structural abnormality, and 2 cases were normal live birth without developmental abnormalities. In the 9 cases with normal kayrotyping, 1 case had termination of pregnancy and 1 case with mental retardation and poor cognitive ability, other 7 had good pregnancy outcomes.ConclusionOur results may be helpful for the selection of prenatal diagnostic strategies and genetic counseling for pregnant women with trisomy 9 revealed by NIPT.     

Prenatal diagnosis in a female carrying a deletion close to the Duchenne locus

Family studies including the proband are usually needed before a prenatal diagnosis may be performed for Duchenne muscular dystrophy. We report here on prenatal diagnosis in a family where the solitary index case was dead, and where the consultand and her mother were assumed to be carriers by independent evidence. DNA analysis revealed that both the consultand and her mother had an X chromosome deleted for DNA material in the Xp21 region. The female fetus also carried the deleted X chromosome.     

Beyond race or ethnicity and socioeconomic status: predictors of prenatal testing for Down syndrome

OBJECTIVE: To identify predictors of prenatal genetic testing decisions and explore whether racial or ethnic and socioeconomic differences are explained by knowledge, attitudes, and preferences. METHODS: This was a prospective cohort study of 827 English-, Spanish-, or Chinese-speaking pregnant women presenting for care by 20 weeks of gestation at 1 of 23 San Francisco Bay-area obstetrics clinics and practices. Our primary outcome measure for women aged less than 35 years was any prenatal genetic testing use compared with none, and for women aged 35 years or older, prenatal testing strategy (no testing, screening test first, straight to invasive diagnostic testing). Baseline questionnaires were completed before any prenatal test use; test use was assessed after 30 gestational weeks. RESULTS: Among women aged less than 35 years, no racial or ethnic differences in test use emerged. Multivariable analyses yielded three testing predictors: prenatal care site (P = .024), inclination to terminate pregnancy of a Down-syndrome-affected fetus (odds ratio 2.94, P = .002) and belief that modern medicine interferes too much in pregnancy (odds ratio .85, P = .036). Among women aged 35 years or older, observed racial or ethnic and socioeconomic differences in testing strategy were mediated by faith and fatalism, value of testing information, and perceived miscarriage risk. Multivariable predictors of testing strategy included these 3 mediators (P = .035, P < .001, P = .037, respectively) and health care system distrust (P = .045). A total of 29.5% of screen-positive women declined amniocentesis; 6.6% of women screening negative underwent amniocentesis. CONCLUSION: Racial or ethnic and socioeconomic differences in prenatal testing strategy are mediated by risk perception and attitudes. Screening is not the best choice for many women. Optimal prenatal testing counseling requires clarification of risks and consideration of key attitudes and preferences regarding the possible sequence of events after testing decisions.     

Detection of a novel dystrophin gene mutation through carrier analysis performed during prenatal diagnosis in a case with intragenic recombination

OBJECTIVES: To report a multi-technical approach to Duchenne muscular dystrophy (DMD) mutation testing through carrier analysis, in the prenatal diagnosis of a male foetus without a known mutation segregating in the family and with inconclusive results of linkage analysis. METHODS: Haplotype analysis with the DMD region markers for assigning the carrier status of the mother and for prenatal diagnosis of foetal DNA; semiquantitative multiplex analysis of maternal and foetal DNA for the promoter and for 34 exons of the DMD gene; sequencing analysis of the maternal and foetal DNA for confirmation of the results. RESULTS: Because of an intragenic recombination of the DMD gene in foetal DNA, haplotype analysis gave inconclusive results. Semiquantitative PCR analysis displayed a pattern compatible with a heterozygous exon 60 mutation in the mother's DNA, while foetal DNA showed a normal migration pattern. Sequencing analysis confirmed the presence of a novel 7 base-pair deletion in exon 60 of the DMD gene in the mother and excluded the deletion in the foetus. CONCLUSION: Semiquantitative PCR results allowed the DMD mutation detection in the mother and the exclusion in the foetus, showing its crucial importance in prenatal diagnosis in those cases where linkage analysis is not conclusive.     

PGD for X-linked and gender-dependent disorders using a robust,flexible single-tube PCR protocol

X-linked genetic diseases include a wide range of disorders such as the dystrophinopathies. Additionally in some rare genetic diseases, severity of expression is gender dependent. Prevention of such disorders usually involves prenatal diagnosis and termination of affected pregnancies, while preimplantation genetic diagnosis (PGD) represents a specialized alternative that avoids pregnancy termination. To preclude the rejection of unaffected male embryos that cannot be differentiated from those affected when using fluorescence in-situ hybridization, a flexible protocol based on multiplex fluorescence polymerase chain reaction (PCR) was standardized and validated for gender determination in single cells, which can potentially incorporate any disease-specific locus. The final panel of nine loci included four loci on the Y chromosome, two on the X chromosome plus up to three microsatellite markers to either support the gender diagnosis or to further monitor extraneous contamination. The protocol, standardized on single lymphocytes, established a PCR efficiency of >93% for all loci with maximum allele dropout rates of 4%. Microsatellite analysis excluded external contamination and confirmed biallelic inheritance. Proof of principle for the simplicity and flexibility of the assay was demonstrated through its application to clinical PGD cycles for lipoid congenital adrenal hyperplasia, which presents a more severe clinical course in males, and Duchenne muscular dystrophy.     

The future of prenatal diagnosis: rapid testing or full karyotype? An audit of chromosome abnormalities and pregnancy outcomes for women referred for Down's Syndrome testing

OBJECTIVE: To assess the implications of a change in prenatal diagnosis policy from full karyotype analysis to rapid trisomy testing for women referred primarily for increased risk of Down's Syndrome. DESIGN: Retrospective collection and review of data. SETTING: The four London Regional Genetics Centres. POPULATION: Pregnant women (32,674) in the London area having invasive prenatal diagnosis during a six-year three-month period. METHODS: Abnormal karyotypes and total number of samples referred for raised maternal age, raised risk of Down's Syndrome following serum screening or maternal anxiety were collected. Abnormal karyotypes detected by molecular trisomy detection were removed, leaving cases with residual abnormal karyotypes. These were assessed for their clinical significance. Pregnancy outcomes were ascertained by reviewing patient notes or by contacting obstetricians or general practioners. MAIN OUTCOME MEASURES: Proportion of prenatal samples with abnormal karyotypes that would not have been detected by rapid trisomy testing, and the outcome of those pregnancies with abnormal karyotypes. RESULTS: Results from 32,674 samples were identified, of which 24,891 (76.2%) were from women referred primarily for Down's Syndrome testing. There were 118/24,891 (0.47%) abnormal sex chromosome karyotypes. Of the samples with autosomal abnormalities that would not be detected by rapid trisomy testing, 153/24,891 (0.61%) were in pregnancies referred primarily for Down's Syndrome testing. Of these, 98 (0.39%) had a good prognosis (46/98 liveborn, 3/98 terminations, 1/98 intrauterine death, 1/98 miscarriage, 47/98 not ascertained); 37 (0.15%) had an uncertain prognosis (20/37 liveborn, 5/37 terminations; 12/37 not ascertained) and 18 (0.07%) had a poor prognosis (1/18 liveborn, 2/18 miscarriage, 11/18 terminations, 4/18 not ascertained). CONCLUSIONS: For pregnant women with a raised risk of Down's Syndrome, a change of policy from full karyotype analysis to rapid trisomy testing would result in the failure to detect chromosome abnormalities likely to have serious clinical significance in approximately 0.06% (1 in 1659) cases. However, it should be noted that this figure may be higher (up to 0.12%; 1 in 833) if there were fetal abnormalities in some of the pregnancies in the uncertain prognosis group for which outcome information was not available.     

Abortion attitudes of pregnant women in prenatal care

OBJECTIVE: This study was undertaken to describe abortion attitudes in a diverse cohort of pregnant women enrolled in prenatal care. STUDY DESIGN: A cross-sectional interview study of 1082 demographically diverse gravid women enrolled in prenatal care at less than 20 weeks' gestation was performed. RESULTS: Most participants (92%) supported abortion availability. Half (50%) who were willing to consider an abortion would do so only in the first trimester. Among the gravid women willing to consider an abortion in the first or second trimester, 84% would do so after rape/incest or if their life was endangered and 76% would if their fetus had Down syndrome. Gravid women considering abortion were more likely to be white, older, have had a previous abortion, and to express distrust in the health care system. Women who would not consider abortion were more likely to be multiparous, married/living with partner, and to express greater faith and fatalism about their pregnancy outcome. CONCLUSION: Although most pregnant women enrolled in prenatal care support abortion availability, about half would only consider a first-trimester procedure. These findings underscore the need for early prenatal genetic counseling, screening, and testing.     

In utero fetal muscle biopsy for the diagnosis of Duchenne muscular dystrophy

Deoxyribonucleic acid techniques can be used to diagnose Duchenne muscular dystrophy prenatally in male fetuses that are at risk. Deoxyribonucleic acid-based prenatal diagnosis can be impossible when there is only one prior affected male and there is no identifiable deletion or alteration. We performed fetal muscle biopsy in utero in such a case and documented the presence of dystrophin, thereby confirming normality in a male fetus at risk. This first in utero experience adds fetal muscle biopsy to the available procedures for fetal tissue diagnosis.     

How do women of diverse backgrounds value prenatal testing outcomes?

OBJECTIVES: To describe women's preferences for prenatal testing outcomes and to explore their association with sociodemographic characteristics and attitudes. METHODS: We conducted a cross-sectional study of 584 racially/ethnically and socioeconomically diverse pregnant women aged 16 to 47 years recruited from 23 San Francisco Bay Area practices. We assessed preferences for 12 potential prenatal testing outcomes using the time trade-off metric for all outcomes and the standard gamble metric for two outcomes. Preferences were calculated on a scale of 0 (death) to 1 (perfect health). Participants also completed a sociodemographic and attitude survey. RESULTS: Highest preference scores were assigned to outcomes resulting in the birth of a chromosomally normal infant (mean = 0.91-0.93; median = 0.99-1.00). Lower scores were obtained for outcomes involving pregnancy loss (mean = 0.69-0.87; median = 0.76-0.92), which were correlated with attitudes regarding miscarriage, pregnancy termination, and Down syndrome. The lowest scores were assigned to Down syndrome-affected births (mean = 0.67-0.69; median = 0.73-0.75), which also were correlated with attitudes toward Down syndrome. We did not find a statistically significant relationship between participants' preference scores and age. CONCLUSION: Preferences for prenatal testing outcomes vary according to the pregnant women's underlying attitudes about pregnancy loss and Down syndrome, and not according to her age. Current age/risk-based guidelines should account for individual variation in patient preferences.     

Fetal muscle biopsy as a diagnostic tool in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a relentless progressive disorder, leading to severe disability during childhood and death in adolescence or early adulthood. In most families, prenatal diagnosis is readily achieved by molecular detection of DNA deletions using chorionic villi or amniocytes, or by linkage analysis. In some cases, however, molecular methods fail to provide a definitive diagnosis and in such cases in utero fetal muscle biopsy may serve as a diagnostic option. We describe three families in whom fetal muscle biopsy was performed, focusing on the prenatal diagnostic dilemmas, the indications and timing for in utero fetal muscle biopsy, and the difficulties encountered.