Genetics in prenatal diagnosis

The options for prenatal genetic testing have evolved rapidly in the past decade, and advances in sequencing technology now allow genetic diagnoses to be made down to the single-base-pair level, even before the birth of the child. This offers women the opportunity to obtain information regarding the foetus, thereby empowering them to make informed decisions about their pregnancy. As genetic testing becomes increasingly available to women, clinician knowledge and awareness of the options available to women is of great importance. Additionally, comprehensive pretest and posttest genetic counselling about the advantages, pitfalls and limitations of genetic testing should be provided to all women. This review article aims to cover the range of genetic tests currently available in prenatal screening and diagnosis, their current applications and limitations in clinical practice as well as what the future holds for prenatal genetics.

Battling COVID-19 pandemic waves in six South-East Asian countries: A real-time consensus review

@#health concerns, triggering an escalated burden to healthsystems worldwide. The pandemic has altered people’sliving norms, yet coherently escalating countries’ socio-economic instability. This real-time consensus review aimsto describe the epidemiological trends of COVID-19pandemic across six South-East Asian nations, and country-specific experiences on pandemic preparedness, responsesand interventions.Methods: Consensus-driven approach between authorsfrom the six selected countries was applied. Countryspecific policy documents, official government mediastatements, mainstream news portals, global statisticsdatabases and latest published literature available betweenJanuary-October 2020 were utilised for information retrieval.Situational and epidemiological trend analyses wereconducted. Country-specific interventions and challengeswere described. Based on evidence appraised, a descriptiveframework was considered through a consensus. Theauthors subsequently outlined the lessons learned,challenges ahead and interventions that needs to be in placeto control the pandemic. Results: The total number of people infected with COVID-19between 1 January and 16 November 2020 had reached48,520 in Malaysia, 58,124 in Singapore, 3,875 in Thailand,470,648 in Indonesia, 409,574 in Philippines and 70,161 inMyanmar. The total number of people infected with COVID-19 in the six countries from January to 31 October 2020 were936,866 cases and the mortality rate was 2.42%. Indonesiahad 410,088 cases with a mortality rate of 3.38%, Philippineshad 380,729 cases with a mortality rate of 1.90%, Myanmarhad 52,706 cases with a mortality rate of 2.34%, Thailand had3,780 cases with a mortality rate of 1.56%, Malaysia had31,548 cases with a mortality rate of 0.79%, and Singaporehad 58,015 cases with a mortality rate of 0.05% over the 10-month period. Each country response varied depending onits real-time situations based on the number of active casesand economic situation of the country. Conclusion: The number of COVID-19 cases in thesecountries waxed and waned over the 10-month period, thenumber of cases may be coming down in one country, andvice versa in another. Each country, if acting alone, will notbe able to control this pandemic. Sharing of information andresources across nations is the key to successful control ofthe pandemic. There is a need to reflect on how thepandemic affects individuals, families and the community asa whole. There are many people who cannot afford to beisolated from their families and daily wage workers whocannot afford to miss work. Are we as a medical community,only empathising with our patients or are we doing ourutmost to uphold them during this time of crisis? Are thereany other avenues which can curb the epidemic whilereducing its impact on the health and socio-economiccondition of the individual, community and the nation?

Evaluation of preferences of women and healthcare professionals in Singapore for implementation of noninvasive prenatal testing for Down syndrome

<p><b>INTRODUCTION</b>Invasive prenatal diagnosis (IPD) has long been used to prenatally diagnose Down syndrome (DS), but it is associated with a small risk of miscarriage. Noninvasive prenatal testing (NIPT) is a highly sensitive screening test using cell-free DNA in maternal blood for detection of DS without the risk of miscarriage, but it confers a small risk of false-positive and false-negative results. The implementation of these procedures into clinical practice requires an understanding of stakeholder preferences.</p><p><b>METHODS</b>A total of 69 health professionals (HPs) and 301 women took part in a discrete choice experiment (DCE) in which preferences for four prenatal test attributes - accuracy, time of results, risk of miscarriage and amount of information provided - were assessed. Conditional logit regression was used to analyse the data. Data on demographics and ranked preferences for test attributes was collected, and a direct choice question regarding NIPT, IPD or neither test was posed to participants.</p><p><b>RESULTS</b>The women showed a preference for test safety, whereas HPs prioritised test accuracy above all other attributes. When offered a direct choice of NIPT, IPD or neither test, women aged 35 years and older, those with previous miscarriage or who knew a child with DS were more likely to choose NIPT. Chinese women preferred NIPT, whereas Indian women preferred IPD.</p><p><b>CONCLUSION</b>Our data highlights the need for patient-specific counselling, taking into account previous experiences and cultural factors. Since women and HPs prioritise different test attributes, it is essential that HPs recognise these differences in order to provide non-biased counselling.</p>

The assessment of combined first trimester screening in women of advanced maternal age in an Asian cohort

<p><b>INTRODUCTION</b>First trimester screening (FTS) is a validated screening tool that has been shown to achieve detection rates of 84%-90% for trisomies 21, 18 and 13. However, its effectiveness for different maternal ages has not been assessed. The present study aimed to assess the performance of FTS in an Asian population, and to compare its effectiveness in older (≥ 35 years) and younger (< 35 years) women. The potential use of noninvasive prenatal test (NIPT) as a contingent screening test is also examined.</p><p><b>METHODS</b>Data on cases of FTS performed on singleton pregnancies over a six-year period was collated from two Singapore maternal centres, National University Hospital and Singapore General Hospital. Cases that had a 1:250 risk of trisomy were considered to be screen-positive. Pregnancy outcomes were obtained from birth records or karyotype test results.</p><p><b>RESULTS</b>From 10,289 FTS cases, we obtained a sensitivity of 87.8%, a specificity of 97.6%, a false positive rate of 2.4% and a false negative rate of 0.06% for the detection of aneuploidy. The overall detection rate for trisomy 21 was 86.5%-85.7% for older women and 87.5% for younger women. The mean number of invasive tests required per case of trisomy 21 was 9.3 in younger women, 8.6 in older women and 13.5 in women with intermediate risk (1:250-1,000).</p><p><b>CONCLUSION</b>While the performance of FTS was similar in younger and older women, more invasive procedures were required to diagnose trisomy 21 in women with intermediate risk. It may be advantageous to offer contingent NIPT to this group of women to reduce the risk of iatrogenic fetal loss.</p>

Comparison of risk of malignancy indices in evaluating ovarian masses in a Southeast Asian population

<p><b>INTRODUCTION</b>The risk of malignancy index (RMI) is a scoring system used to triage benign from malignant ovarian masses. We compared the specificity and sensitivity of the four indices (RMI 1, RMI 2, RMI 3 and RMI 4) to discriminate a benign ovarian mass from a malignant one in a Southeast Asian population.</p><p><b>METHODS</b>This was a five-year retrospective study of women who were admitted for surgery due to ovarian masses. RMI scores were calculated based on standardised preoperative cancer antigen (CA)-125 levels, ultrasonography findings, menopausal status and tumour size based on ultrasonography. Postoperative histopathologic diagnosis was regarded as the definite outcome. Data were analysed using the Statistical Package for the Social Sciences, and Mann-Whitney U test was used to compare the individual RMI scores between the benign and malignant cases.</p><p><b>RESULTS</b>Out of the 480 patients reviewed, 228 women aged 10-65 years were included in the study. Of these, 17 (7.5%) had malignant disease and 211 (92.5%) had benign pathology. There was no statistical difference in the RMI 1, 2, 3 and 4 scores between the benign and malignant cases. Individual variables that were analysed showed significant differences in median CA-125 level and tumour size (p = 0.044 and p < 0.0005, respectively) between the benign and malignant cases.</p><p><b>CONCLUSION</b>Our study shows that RMI is not a valuable triage tool for our Southeast Asian population. Further prospective validation, with regard to standardising results in different patient populations and centres, is required.</p>

Combined panel of serum human tissue kallikreins and CA-125 for the detection of epithelial ovarian cancer / 부인종양

OBJECTIVE: To determine the predictive accuracy of the combined panels of serum human tissue kallikreins (hKs) and CA-125 for the detection of epithelial ovarian cancer. METHODS: Serum specimens collected from 5 Indonesian centers and 1 Vietnamese center were analyzed for CA-125, hK6, and hK10 levels. A total of 375 specimens from patients presenting with ovarian tumors, which include 156 benign cysts, 172 epithelial ovarian cancers (stage I/II, n=72; stage III/IV, n=100), 36 germ cell tumors and 11 borderline tumors, were included in the study analysis. Receiver operating characteristic analysis were performed to determine the cutoffs for age, CA-125, hK6, and hK10. Sensitivity, specificity, negative, and positive predictive values were determined for various combinations of the biomarkers. RESULTS: The levels of hK6 and hK10 were significantly elevated in ovarian cancer cases compared to benign cysts. Combination of 3 markers, age/CA-125/hk6 or CA-125/hk6/hk10, showed improved specificity (100%) and positive predictive value (100%) for prediction of ovarian cancer, when compared to the performance of single markers having 80-92% specificity and 74-87% positive predictive value. Four-marker combination, age/CA-125/hK6/hK10 also showed 100% specificity and 100% positive predictive value, although it demonstrated low sensitivity (11.9%) and negative predictive value (52.8%). CONCLUSION: The combination of human tissue kallikreins and CA-125 showed potential for improving prediction of epithelial ovarian cancer in patients presenting with ovarian tumors.

Patients' perception of risk: informed choice in prenatal testing for foetal aneuploidy

Each of us perceives risk differently, and so do our patients. This perception of risk gets even more complex when multiple individuals and interactions are involved: the doctor, the patient-pregnant mother, the spouse-father and the foetus-unborn child. In this review, we address the relationship between different levels of information gathering, from clinical data to experiential knowledge - data, information, knowledge, perception, attitude, wisdom - and how these would impact the perception of risk and informed consent. We discuss how patients might interpret the risks of the same event differently based upon past experiences, and suggest how risk data could be presented more meaningfully for patients and family to assimilate for informed decision making. Finally, we demonstrate how patients' expectations and risk management can impact scientific research and clinical progress by way of the most topical subject of risk screening in pregnancy - non-invasive prenatal testing using cell-free DNA in maternal plasma.

Preimplantation genetic diagnosis of chromosome translocations by analysis of polymorphic short tandem repeats

<p><b>INTRODUCTION</b>We aimed to develop and implement a short tandem repeat (STR) polymerase chain reaction alternative to fluorescence in situ hybridisation (FISH) for the preimplantation genetic diagnosis (PGD) of chromosomal translocations.</p><p><b>METHODS</b>Selected informative STRs located on translocated arms of relevant chromosomes were used to discriminate between normal and unbalanced chromosome states in each embryo.</p><p><b>RESULTS</b>PGD cycles were performed on five couples where one spouse carried a balanced translocation. 27 embryos were analysed, of which 12 were normal/balanced, 12 were abnormal/unbalanced and three were indeterminate. Four PGD cycles proceeded to embryo transfer, of which two led to pregnancy. The first pregnancy showed a normal male karyotype, and a healthy baby was delivered at term. A second pregnancy unexpectedly miscarried in the second trimester from unknown causes.</p><p><b>CONCLUSION</b>STR analysis is a simple and suitable alternative to FISH for detecting unbalanced chromosomal states in preimplantation embryos.</p>

Menopause, hormone therapy and cardiovascular and cerebrovascular disease

<p><b>INTRODUCTION</b>Cardiovascular disease is the leading cause of death and morbidity among postmenopausal women, and oestrogen deficiency may be an important factor in its development. The role of oestrogen replacement in preventing cardiovascular disease is controversial. The aim of this descriptive review is to analyse the available data and to recommend evidence-based practice guidelines pertaining to hormone therapy in the context of cardiovascular and cerebrovascular health.</p><p><b>MATERIALS AND METHODS</b>Relevant clinical trials were identified by computerised literature search. The collated data were presented to fellow gynaecologists for review, analysis of results and discussion in a series of meetings dedicated to finding the best evidence in menopause management. The evidence was used to formulate clinical practice guidelines for the management of women with significant cardiovascular risk factors.</p><p><b>RESULTS</b>Evidence from animal studies and observational trials supported a cardio-protective effect of postmenopausal hormone therapy. More recent randomised clinical trial data have shown no significant reduction of coronary heart disease, and have confirmed a higher incidence of stroke and venous thromboembolism.</p><p><b>CONCLUSIONS</b>The evidence is widely divergent regarding postmenopausal hormone therapy and cardiovascular risk. More consistent data are available reporting an increased risk in the incidence of venous thromboembolism and stroke. It is important to be clear about the indications of hormone use and to utilise alternative modalities to promote cardiovascular health in the postmenopausal population.</p>

Care of women in menopause: sexual function, dysfunction and therapeutic modalities

<p><b>INTRODUCTION</b>The physiological changes that occur in menopause alter sexual function and affect well-being. Hormonal changes contribute significantly to reduced sexual function in older women and sexual dysfunction may well be amenable to treatment with exogenous hormones or other agents.</p><p><b>MATERIALS AND METHODS</b>Relevant clinical studies were identified by a computerised literature search. The collated data were presented to fellow gynaecologists for review, analysis of results and discussion in a series of meetings dedicated to finding the best evidence in menopause management. The evidence was assessed and used to prepare guidelines around the management of women who are affected by sexual dysfunction in menopause.</p><p><b>RESULTS</b>Hormone therapy benefits many women who have dyspareunia related to vaginal atrophy, reduced libido and decreased satisfaction, particularly if these symptoms adversely affect their quality of life. Alternative agents such as tibolone and sildenafil citrate can be useful adjuncts.</p><p><b>CONCLUSIONS</b>It is increasingly important to recognise postmenopausal sexual dysfunction. Treatment of this syndrome must be individualised to the specific complaints of each woman. Hormones and other agents are relevant treatment options for properly-selected women.</p>