Monogenic conditions and central nervous system anomalies:A prospective study, systematic review and meta-analysis

Objectives: Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities.Methods: Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model. Results: Thirty studies were included (n = 1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%–36%; I2 = 72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%–34%; I2 = 74%]; (b) single CNS anomaly; 16% [95% CI 10%–23%; I2 = 41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%–40%; I2 = 56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%–57%; I2 = 68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus. Conclusions: Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.</p

Do Regular Ultrasound Scans Reduce the Incidence of Stillbirth in Women with Apparently Normal Pregnancies?

OBJECTIVE: To determine the incidence of stillbirth in women who have regular ante-natal ultrasound compared to those that have infrequent scans in a low risk population. STUDY DESIGN: A retrospective observational study was performed in a tertiary center with 5,700 deliveries per annum. Data on all deliveries was collected via the Northern Ireland Maternity System Database. Only women with an apparently low risk pregnancy were included. Women who had private antenatal care often had frequent scans in the third trimester. Women who did not have private antenatal care often had scans infrequently. The still birth rate was calculated for both groups of women from 2007 to 2011 and compared using a Chi-squared analysis RESULTS: Our study included 23,519 ‘low-risk’ deliveries spanning 2007-2011. This included 2,088 (9%) patients who had frequent ultrasound surveillance and delivery at term and 21,431 (91%) patients who did not. The overall stillbirth rate was 0.34% and 0.20% respectively which was not statistically different (p=0.31). CONCLUSION: There is no difference in the rate of stillbirth between patients who have more frequent ante-natal ultrasound surveillance compared with those who do not in a low risk population