Exploring the clinical utility of exome sequencing/Mono, Duo, Trio in prenatal testing: a retrospective study in a tertiary care centre in South India.

OBJECTIVES: With the availability of Next Generation Sequencing (NGS) diagnosis of genetic disorders has improved significantly. Its use is also applicable to ascertain diagnosis and management in a perinatal setting. The study aims to detect the genetic aetiology of various congenital structural and functional defects using NGS technology in the reproductive cohort at a tertiary centre. The secondary objective is to address challenges in the interpretation of variants. METHODS: This was a retrospective study of couples who underwent exome sequencing (Mono-testing proband only or Duo-testing parents only or Trio-testing proband and parents) for suspected single gene disorders between years 2020-2022 at a tertiary care perinatal center in the South India. American College of Medical Genetics (ACMG) guidelines were followed to classify the pathogenicity of the variants identified by exome sequencing. RESULTS: The overall diagnostic yield as defined by pathogenic/likely pathogenic variants obtained was (23/43) 53.4 %. The individual subsets have the following diagnostic yield viz., Mono 5/6 (83 %); Carrier 16/32 (50 %); Trio 2/5 (40 %). Diagnostic yield was significantly higher in consanguineous couples. However, miscarriage history, and organ system involvement did not have a significant effect on the diagnostic yield. Prenatal diagnosis was offered for seven patients based on the exome result. One fetus was confirmed with a compound heterozygous pathogenic variant. CONCLUSIONS: Diagnostic yield of exome sequencing in our cohort was 53 %. The detection of pathogenic variants was maximum in those cases undergoing Mono exome sequencing. In places where there is a high prevalence of consanguinity and endogamy, NGS may be offered as first line test in the context of prenatal diagnosis.

Comparing Obstetric and Perinatal Outcomes Following Elective and Emergency Cervical Cerclage in Singleton and Multiple Pregnancies in a Tertiary Care Perinatal Centre.

Objective: To compare the success, failure rates and perinatal outcomes following emergency and elective cervical cerclage in singleton and twin pregnancies at a tertiary care perinatal centre over half a decade. Methods: All pregnant women, both with singleton and twin pregnancies, who had cervical cerclage between June 2014 and May 2019 were included in the retrospective study. Success rates, failure rates, maternal complications and perinatal outcomes were compared in both groups. Results: There were 129 women enrolled in the study, 48 in the emergency and 81 in the elective group. A significantly greater number of multiparous women were in the elective group (97.5% versus 68.7%; p-value < 0.001). Twins were nearly four times more in the emergency group as compared to  the elective group. The mean cervical length at time of cerclage was 2.05 cm and 1.5 cm; (p-value < 0.001) respectively in the elective and emergency groups. Almost half of the women in the emergency group had bulging membranes. (52.2%). Following cerclage, mean gestational age at delivery was similar in both groups. However, more women in the elective group delivered at or beyond 34 weeks in comparison to the emergency groups (71% versus 53.3%. P-value 0.05). Preterm labour leading to preterm births was almost twice in the emergency group than elective group (49% versus 22%, P-value 0.002). Rates of maternal chorioamnionitis were similar in both groups. The overall live birth rates were comparable (81.3% versus 84.4% P-value 0.85) in both the groups. These results were also seen on doing subgroup analysis of elective versus emergency cerclage in singleton pregnancies only. Failure rates were also similar in both groups (18.7% versus 15.6%, P-value 0.85) Composite neonatal morbidity was more in the emergency group than in the elective group (35.5 versus 14%, P-value 0.01). Conclusion: Live birth rates and failure rates were comparable following elective and emergency cerclage both overall and in singleton pregnancies. Maternal chorioamnionitis and neonatal sepsis  rates were similar in both the groups. However, composite neonatal morbidity was higher in the emergency cerclage group.