The genetic landscape of chromosomal aberrations in 3776 Vietnamese fetuses with clinical anomalies during pregnancy.

Background: Copy number variation sequencing (CNV-seq) is a powerful tool to discover structural genomic variation, but limitations associated with its retrospective study design and inadequate diversity of participants can be impractical for clinical application. Aim: This study aims to use CNV-seq to assess chromosomal aberrations in pregnant Vietnamese women. Materials & methods: A large-scale study was conducted on 3776 pregnant Vietnamese women with abnormal ultrasound findings. Results: Chromosomal aberrations were found in 448 (11.86%) women. Of these, 274 (7.26%) had chromosomal aneuploidies and 174 (4.61%) carried pathogenic/likely pathogenic CNVs. Correlations were established between chromosomal aberrations and various phenotypic markers. Conclusion: This comprehensive clinical study illuminates the pivotal role of CNV-seq in prenatal diagnosis for pregnancies featuring fetal ultrasound anomalies.

De novo variants of dominant monogenic disorders in Vietnam detected by a noninvasive prenatal test: a case series.

Background: Noninvasive prenatal tests for monogenic diseases (NIPT-SGG) have recently been reported as helpful in early-stage antenatal screening. Our study describes the clinical and genetic features of cases identified by NIPT-SGG. Materials & methods: In a cohort pregnancy with abnormal sonograms, affected cases were confirmed by invasive diagnostic tests concurrently, with NIPT-SGG targeting 25 common dominant single-gene diseases. Results: A total of 13 single-gene fetuses were confirmed, including Noonan and Costello syndromes, thanatophoric dysplasia, achondroplasia, osteogenesis imperfecta and Apert syndrome. Two novel variants seen were tuberous sclerosis complex (TSC2 c.4154G>A) and Alagille syndrome (JAG1 c.3452del). Conclusion: NIPT-SGG and standard tests agree on the results for 13 fetuses with monogenic disorders. This panel method of screening can benefit high-risk Vietnamese pregnancies, but further research is encouraged to expand on the causative gene panel.

Developing and validating noninvasive prenatal testing for de novo autosomal dominant monogenic diseases in Vietnam.

Background: Over 60% of single-gene diseases in newborns are autosomal dominant variants. Noninvasive prenatal testing for monogenic conditions (NIPT-SGG) is cost-effective and timesaving, but not widely applied. This study introduces and validates NIPT-SGG in detecting 25 monogenic conditions. Methods: NIPT-SGG with a 30-gene panel applied next-generation sequencing and trio assays to confirm de novo variants. Diagnostic tests confirmed NIPT-detected cases. Results: Among 93 pregnancies with ultrasound findings, 11 (11.8%) fetuses were screened and diagnosed with monogenic diseases, mostly with Noonan syndrome. NIPT-SGG determined >99.99% of actual positive and negative cases, confirmed by diagnostic tests. No false-negatives or false-positives were reported. Conclusion: NIPT-SGG effectively identifies the fetuses affected with monogenic diseases, which is a promisingly safe and timely antenatal screening option for high-risk pregnancies.

Detection of maternal carriers of common α-thalassemia deletions from cell-free DNA.

α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening of α-thalassemia carrier state is therefore of vital importance. This study presents a novel method for identifying female carriers of common α-thalassemia deletions using samples routinely taken for non-invasive prenatal tests for screening of fetal chromosomal aneuploidies. A total of 68,885 Vietnamese pregnant women were recruited and α-thalassemia statuses were determined by gap-PCR, revealing 5344 women (7.76%) carried deletions including αα/--SEA (4.066%), αα/-α3.7 (2.934%), αα/-α4.2 (0.656%), and rare genotypes (0.102%). A two-stage model was built to predict these α-thalassemia deletions from targeted sequencing of the HBA gene cluster on maternal cfDNA. Our method achieved F1-scores of 97.14-99.55% for detecting the three common genotypes and 94.74% for detecting rare genotypes (-α3.7/-α4.2, αα/--THAI, -α3.7/--SEA, -α4.2/--SEA). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/--SEA, 94.87% for αα/-α3.7, and 96.51% for αα/-α4.2; and the negative predictive values were 97.63%, 99.99%, 99.99%, and 100.00%, respectively. As NIPT is increasingly adopted for pregnant women, utilizing cfDNA from NIPT to detect maternal carriers of common α-thalassemia deletions will be cost-effective and expand the benefits of NIPT.

Combined Gap-Polymerase Chain Reaction and Targeted Next-Generation Sequencing Improve α- and ß-Thalassemia Carrier Screening in Pregnant Women in Vietnam.

Vietnam has a high thalassemia burden. We collected blood samples from 5880 pregnant Vietnamese women during prenatal health checks to assess thalassemia carrier frequency using combined gap-polymerase chain reaction (gap-PCR) and targeted next-generation sequencing (NGS). Thalassemia carriers were identified with prevalence of 13.13% (772), including 7.82% (460) carriers of α-thalassemia (α-thal), 5.31% (312) carriers of ß-thalassemia (ß-thal), and 0.63% (37) concurrent α-/ß-thal carriers. Deletional mutations (368) accounted for 80.0% of α-thal carriers, of which, --SEA (Southeast Asian) (n = 254; 55.0%) was most prevalent, followed by the -α3.7 (rightward) (n = 66; 14.0%) and -α4.2 (leftward) (n = 45; 9.8%) deletions. Hb Westmead (HBA2: c.369C>G) (n = 53) and Hb Constant Spring (Hb CS or HBA2: c.427T>C) (in 28) are the two most common nondeletional α-globin variants, accounting for 11.5 and 6.0% of α-thal carriers. We detected 11 different ß-thal genotypes. Hb E (HBB: c.79G>A) (in 211) accounted for 67.6% of ß-thal carriers. The most common ß-thal genotypes were associated with mutations at codon 17 (A>T) (HBB: c.52A>T), codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), and codon 71/72 (+A) (HBB: c.217_218insA) (prevalence 0.70%, 0.68%, and 0.2%, respectively). Based on mutation frequencies calculated in this study, estimates of 5021 babies in Vietnam are affected with clinically severe thalassemia annually. Our data suggest a higher thalassemia carrier frequency in Vietnam than previously reported. We established that combining NGS with gap-PCR creates an effective large-scale thalassemia screening method that can detect a broad range of mutations.

The Association Between Gender Inequalities and Women's Utilization of Maternal Health Services: A Cross-Sectional Survey in Eight South Central Coast Provinces, Vietnam.

BACKGROUND: Gender inequalities influence the utilization of maternal health services in Vietnam, but little research has been published. This study, therefore, aimed to explore the association between gender inequalities and women's utilization of maternal health services in Vietnam. METHODS: The study was conducted in 8 provinces in the South Central Coast region of Vietnam during August 2013 to May 2014. A total of 907 women who delivered a year prior to the date of interview participated in the study. A multiple logistic regression model was used to examine the association between gender inequalities (including sociodemographic determinants of health) and utilization of 4 or more antenatal care (ANC4+) services, institutional delivery, and ever used contraceptive methods. RESULTS: The utilization rate of maternal health services was varied, from 53.9% for ANC4+ to 87.7% for ever used a contraceptive method and 97% for institutional delivery. Ethnicity was identified as the most influential variable out of all sociodemographic determinants of health. Regarding gender inequalities, couple communication was the only variable having significant association with women's utilization of maternal health services. CONCLUSION: Women's equal role within context of their daily life and relations with their husbands (discussing maternal care with husband and having equal income to husband) supported their use of maternal health services. Therefore, there should be concerted efforts from all relevant stakeholders including the health system to focus on disadvantaged women in planning and delivery of maternal health services, especially to ethnic minority women. Male involvement strategy should be implemented to promote maternal health care, especially during the prenatal and postpartum period. To provide more culturally sensitive and right-based approaches in delivery of maternal health services to disadvantaged women in Vietnam, interventions are recommended that promote male involvement, that is, to engage men in service delivery to adapt and ensure the most appropriate and effective maternal health care.

Utilization of Services Provided by Village-Based Ethnic Minority Midwives in Vietnam: Lessons From Implementation Research.

BACKGROUND: Global progress in reducing maternal mortality requires improving access to maternal and child health services for the most vulnerable groups. This article reports results of implementation research that aimed to increase the acceptability of village-based ethnic minority midwives (EMMs) by local communities in Vietnam through implementing an integrated interventions package. METHODS: The study was carried out in 2 provinces in Vietnam, Dien Bien and Kon Tum. A quasi-experimental survey with pretest/posttest design was adopted, which included 6 months of intervention implementation. The interventions package included introductory "launch" meetings, monthly review meetings at community health centers, and 5-day refresher training for EMMs. A mixed-methods approach was used involving both quantitative and qualitative data. A structured questionnaire was used in the pre- and posttest surveys, complemented by in-depth interviews and focus group discussions with EMMs, relatives of pregnant women, community representatives, and health managers. RESULTS: Introductions of EMMs to their local communities by local authorities and supervision of performance of EMMs contributed to significant increases in utilization of services provided by EMMs, from 58.6% to 87.7%. Key facilitators included information on how to contact EMMs, awareness of services provided by EMMs, and trust in services provided by EMMs. The main barriers to utilization of EMM services, which may affect sustainability of the EMM scheme, were low self-esteem of EMMs and small allowances to EMMs, which also affected the recognition of EMMs in the community. CONCLUSIONS: Providing continuous support and integration of EMMs within frontline service provision and ensuring adequate local budget for monthly allowances are the key factors that should allow sustainability of the EMM scheme and continued improvement of access to maternal and child health care among poor ethnic minority people living in mountainous areas in Vietnam.