Clinical utility of expanded non-invasive prenatal screening compared with chromosomal microarray analysis in over 8000 pregnancies without major structural anomaly.

OBJECTIVES: To evaluate the theoretical added value of two types of non-invasive prenatal screening (NIPS) expansions in pregnancies without major structural anomalies over the commonly used NIPS for chromosomes 13, 18, 21, X and Y (5-NIPS) and to compare them with the added value of chromosomal microarray analysis (CMA). METHODS: This was a retrospective cohort study based on CMA results of all pregnancies with normal ultrasound (including pregnancies with soft markers and with abnormal maternal serum screening) that had undergone amniocentesis between January 2013 to February 2022 and were registered in the database of the Rabin Medical Center genetic laboratory. We calculated the theoretical yield of 5-NIPS and compared the added value of expanded 5-NIPS for common microdeletions (1p36.3-1p36.2, 4p16.3-4p16.2, 5p15.3-5p15.1, 15q11.2-15q13.1 and 22q11.2) and genome-wide NIPS (including variants > 5 Mb) with the added value of CMA in the overall cohort and in subgroups according to indication for invasive testing. RESULTS: Among the 8605 examined pregnancies, 122 (1.4%) clinically significant CMA results were demonstrated. Of these, 44 (36.1%) were theoretically detectable on 5-NIPS, with the rates of 1.56% in 642 pregnancies with abnormal maternal serum screening, 0.63% in 318 pregnancies with soft markers, 0.62% in 4378 women with advanced maternal age (≥ 35 years) and 0.15% in 3267 women younger than 35 years. In addition to aneuploidies detectable on 5-NIPS, three (0.03%) cases detectable on 5-NIPS expanded for common microdeletions and nine (0.10%) cases detectable on genome-wide NIPS (excluding common microdeletions) were identified in the overall cohort. The added value of expanded NIPS tools over 5-NIPS was significantly lower compared with that of CMA, for the overall cohort and subgroups. CONCLUSIONS: 5-NIPS and even genome-wide NIPS would miss 63.9% and 54.1% of clinically significant CMA findings, respectively. The added value of 5-NIPS expanded to detect common microdeletions over 5-NIPS is about 0.035%, and the overall added value of genome-wide NIPS aimed at large CNVs is about 0.14%, both much lower compared with the added value of CMA (0.91%). These findings should assist healthcare practitioners in guiding couples towards informed decision-making regarding the choice between prenatal invasive testing and NIPS. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Microarray analysis has no additional value in fetal aberrant right subclavian artery: description of 268 pregnancies and systematic literature review.

OBJECTIVES: Fetal aberrant right subclavian artery (ARSA) is a relatively common sonographic finding. Several studies have reported a significant association between ARSA and Down syndrome, as well as 22q11.2 microdeletion. The objective of this study was to assess the risk of abnormal chromosomal microarray analysis (CMA) findings in a large cohort of pregnancies with fetal ARSA as an isolated, as well as a non-isolated, sonographic anomaly. A secondary objective was to review the literature, examining the frequency of chromosomal microarray aberrations in fetuses with isolated ARSA. METHODS: Data from all pregnancies referred for invasive testing and CMA due to sonographic diagnosis of fetal ARSA, between 2013 and 2017, were obtained retrospectively from the computerized database of the Israeli Ministry of Health. The rate of clinically significant CMA findings in these fetuses was compared to that in a local control population of 2752 low-risk pregnancies with normal ultrasound and serum screening results. In addition, a literature search was conducted in PubMed, from inception to February 2018, of original studies in the English language describing the frequency and nature of microscopic and submicroscopic aberrations in fetuses with isolated ARSA. RESULTS: Of 246 pregnancies with isolated ARSA that underwent CMA analysis, a clinically significant finding was detected in one (0.4%) pregnancy (trisomy 21). This rate did not differ significantly from that in the control population (P = 0.1574). Of 22 fetuses with non-isolated ARSA, one (4.5%) additional case of trisomy 21 was noted. The frequency of trisomy 21 in this cohort also did not differ from that in the control population (relative risk, 5.5 (95% CI, 0.8-37.6)). The literature search yielded 13 additional relevant papers, encompassing 333 cases of isolated ARSA. Of 579 cases overall (including those of the present study), 13 (2.2%) cases of trisomy 21 were detected, with no cases of 22q11.2 microdeletion. CONCLUSION: While an association may exist between non-isolated ARSA and Down syndrome, isolated ARSA might better serve as a soft marker for Down syndrome, rather than a routine indication for invasive prenatal testing. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Indications for episiotomy performance - a cross-sectional survey and review of the literature.

Our objective was to assess the reported reasons for episiotomy performance in Israel and to review the relevant professional literature. Using anonymous questionnaires, a survey was conducted among obstetricians and midwives in four northern Israel hospitals, and the accoucheurs were asked to score their agreement with 13 proposed indications for episiotomy. Overall, 84 doctors and 32 midwives completed the questionnaires. 86.1% of the responders reported performing episiotomy in all or most cases of shoulder dystocia, and more than half reported performing it in most cases of vacuum deliveries, fetal macrosomia and advanced perineal tear in previous delivery. Subjective assessment of perineal characteristics constituted a justified reason for episiotomy for 15.8-43.9% of the accoucheurs. In conclusion, there is a wide variation in reported reasons for episiotomy between the obstetricians, and many of these indications are not congruent with international practice guidelines. Uniform protocols and educational programmes are needed to guide episiotomy practice.

Morbidity associated with episiotomy in vacuum delivery: a systematic review and meta-analysis.

BACKGROUND: The role of episiotomy in vacuum deliveries is controversial. OBJECTIVES: To perform a meta-analysis of the literature examining this subject. SEARCH STRATEGY: The search was conducted in four databases. SELECTION CRITERIA: Two investigators independently selected original research examining the effects of episiotomy on any neonatal and maternal outcomes during vacuum delivery. DATA COLLECTION AND ANALYSIS: The effect estimates were presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). MAIN RESULTS: Fifteen articles were included, encompassing a total of 350 764 vacuum deliveries. A non-significant relationship was shown between mediolateral episiotomy and obstetric anal sphincter injuries (OASIS) in nulliparous women (OR 0.68, 95% CI 0.43-1.07; six studies), whereas an increased risk was demonstrated in parous women (OR 1.27, 95% CI 1.05-1.53; two reports). A higher risk of OASIS with median episiotomy use was shown in nulliparous (OR 5.11, 95% CI 3.23-8.08; two studies) as well as in parous (OR 89.4, 95% CI 11.8-677.1; one study) women. Lateral episiotomy was related to lower OASIS risk in nullipara (OR 0.59, 95% CI 0.49-0.70; single paper). Mediolateral episiotomy was linked to increased rates of postpartum haemorrhage (OR 1.82, 95% CI 1.16-2.86) and analgesia use (OR 2.10, 95% CI 1.39-3.17; two reports). Overall, the quality of evidence was rated as low to very low. AUTHOR'S CONCLUSIONS: Mediolateral and median episiotomy in parous woman may increase the rate of OASIS at vacuum delivery, whereas lateral episiotomy in nulliparous women could be associated with a decreased risk of OASIS. The suboptimal quality of the available evidence necessitates high-quality well-designed randomised trials. TWEETABLE ABSTRACT: Episiotomy in vacuum delivery does not appear to be of benefit, and might even increase maternal morbidity.