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.

Placenta accreta spectrum: Management and outcomes in a tertiary centre in India: An observational cross-sectional study.

Our observational cross-sectional study looked at the risk factors, diagnosis, management and outcomes of placenta accrete spectrum at the Christian Medical College and Hospital, Vellore, India, between January 2013 and December 2018. A total of 21 cases of placenta accrete spectrum are described among whom a preop diagnosis was available in 14 cases. A previous history of Caesarean section and placenta previa was present in 90%. Caesarean hysterectomy was carried out in 80%, but none of those managed conservatively required interval hysterectomy. Urinary tract injury was the most common surgical complication, seen in over 50%. The mean blood loss was 3.5 l and 14 patients required intensive care unit admission, but no maternal mortality ensued. Thus, we conclude that the conservative management in carefully selected cases is feasible.

Enzyme-linked immunosorbent assay (ELISA) versus Venereal Disease Research Laboratory test (VDRL) and rapid plasma reagin test (RPR) for screening of syphilis in pregnant women.

OBJECTIVE: To evaluate a treponemal enzyme-linked immunosorbent assay (ELISA) as an alternative screening test for syphilis in pregnant women. METHODS: A cross-sectional study of diagnostic test accuracy was carried out in a large volume laboratory from a tertiary care center. A total of 416 serum samples, including 102 archived syphilis Treponema pallidum hemagglutination (TPHA)-positive samples and 314 samples from pregnant women, were used to determine the sensitivity and specificity of ELISA. All the samples were subjected to Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), ELISA, and TPHA tests. Performance characteristics of VDRL, RPR, and ELISA were calculated with TPHA as a reference standard test. RESULTS: VDRL and RPR exhibited higher false positivity of 10.5% and 9.6%, respectively, compared to 2.5% by ELISA. The sensitivity and specificity of ELISA were 98% and 97.5%, of VDRL were 71.6% and 89.5%, and of RPR were 73.5% and 90.5%, respectively. Moreover, ELISA had an excellent agreement (kappa=0.9) with TPHA compared to VDRL/RPR which had a moderate agreement (kappa=0.6) only. CONCLUSION: ELISA has the potential to replace VDRL/RPR as a screening test for syphilis in centers that can perform ELISA, especially for antenatal screening.

Benign metastasising leiomyoma after hysterectomy and bilateral salpingo-oophorectomy.

Benign metastasising leiomyomatosis is a rare condition affecting women in the reproductive age-group with a history of uterine fibroids, who have undergone treatment by myomectomy or hysterectomy. It is characterised by development of multiple, indolent, smooth muscle tumours outside the uterus, most commonly in the lungs, and manifests several years after the uterine surgery. We describe the case of a young woman, who had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy for multiple fibroids and a right ovarian cyst. After 5 years of being on oestrogen replacement therapy, she was detected to have benign metastasising leiomyoma, for which an additional laparotomy was performed. At laparotomy, removal of the pelvic mass was associated with several complications. The metastatic lesions in the lung responded well to progestogens (megestrol acetate) alone as evidenced by regression of the lesions detected at follow-up after 6 months and 1 year.