Exome sequencing in fetuses with congenital diaphragmatic hernia in a nationwide cohort.

OBJECTIVE: To evaluate the diagnostic yield of exome sequencing (ES) in fetuses and neonates with prenatally detected congenital diaphragmatic hernia (CDH) and normal copy number variant (CNV) analysis. METHODS: We conducted a retrospective cohort study of prenatally diagnosed CDH cases seen between 2019 and 2022. All cases who underwent prenatal or postnatal genetic testing were reviewed. The results from the ES analysis that identified pathogenic or likely pathogenic single nucleotide variants are described. RESULTS: In total, 133 fetuses with CDH were seen, of whom 98 (74%) had an isolated CDH and 35 (26%) had a complex CDH (associated structural anomalies) on prenatal examination. ES was performed in 68 cases, and eight pathogenic or likely pathogenic variants were found, accounting for a 12% diagnostic yield (10% [5/50] in isolated cases and 17% [3/18] in complex CDH). CONCLUSIONS: In 12% of fetuses and neonates with CDH and normal CNV analysis results, pathogenic or likely pathogenic variants were identified with ES. These data indicate that there is a substantial diagnostic yield when offering ES in prenatally detected CDH, both in complex and isolated cases.

Prenatal assessment of pulmonary vasculature development in fetuses with congenital diaphragmatic hernia: A literature review.

Pathophysiological studies have shown that pulmonary vascular development is impaired in fetuses with a congenital diaphragmatic hernia (CDH), leading to a simplified vascular tree and increased vascular resistance. Multiple studies have described prenatal ultrasound parameters for the assessment of the pulmonary vasculature, but none of these parameters are used in daily clinical practice. We provide a comprehensive review of the literature published between January 1990 and February 2022 describing these parameters, and aim to explain the clinical relevance of these parameters from what is known from pathophysiological studies. Prenatal detection of a smaller diameter of the contralateral (i.e. contralateral to the diaphragmatic defect) first branch of the pulmonary artery (PA), higher pulsatility indices (PI), higher peak early diastolic reverse flow values, and a lower vascularization index seem of added value for the prediction of survival and, to a lesser extent, morbidity. Integration within the routine evaluation is complicated by the lack of uniformity of the methods used. To address the main components of the pathophysiological changes, we recommend future prenatal studies in CDH with a focus on PI values, PA diameters and pulmonary vascular branching.

Prenatal stomach position and volume in relation to postnatal outcomes in left-sided congenital diaphragmatic hernia.

OBJECTIVE: To examine the association between prenatal stomach position (SP) grade and stomach volume (SV) and the need for pulmonary hypertension (PH) treatment after birth in prenatally diagnosed left-sided congenital diaphragmatic hernia (CDH), live born >34 weeks. METHODS: In retrospect, SP grade and SV were determined in fetuses with isolated left-sided CDH from 19 weeks gestational age (GA) onwards at three different time periods (≤24 weeks' GA: US1, 24-30 weeks' GA: US2; ≥30 weeks' GA: US3). Primary outcome was need for treatment of PH after birth. Secondary analyses included the predictive value of SP and SV for other respiratory outcomes and postnatal defect size. RESULTS: A total of 101 fetuses were included. SP grade was significantly associated with need for treatment of PH (US1, US2, and US3: p < 0.02). Also, prenatal SP grade was positively associated with defect size and development of chronic lung disease (CLD) in survivors. No association was found between SV and respiratory morbidities or postnatal defect size. CONCLUSION: SP grade in left-sided CDH fetuses is associated with an increased need for PH treatment, a larger postnatal defect size and CLD in survivors. We consider SP determination a valuable contribution to the prenatal assessment of left-sided CDH.

Maternal perception of fetal movements: Views, knowledge and practices of women and health providers in a low-resource setting.

The study assessed perception, knowledge, and practices regarding maternal perception of fetal movements (FMs) among women and their healthcare providers in a low-resource setting. Semi-structured interviews, questionnaires and focus group discussions were conducted with 45 Zanzibar women (18 antenatal, 28 postpartum) and 28 health providers at the maternity unit of Mnazi Mmoja Hospital, Zanzibar, Tanzania. Descriptive and thematic analyses were conducted to systematically extract subthemes within four main themes 1) knowledge/awareness, 2) behavior/practice, 3) barriers, and 4) ways to improve practice. Within the main themes it was found that 1) Women were instinctively aware of (ab)normal FM-patterns and healthcare providers had adequate knowledge about FMs. 2) Women often did not know how to monitor FMs or when to report concerns. There was inadequate assessment and management of (ab)normal FMs. 3) Barriers included the fact that women did not feel free to express concerns. Healthcare providers considered FM-awareness among women as low and unreliable. There was lack of staff, time and space for FM-education, and no protocol for FM-management. 4) Women and health providers recognised the need for education on assessment and management of (ab)normal FMs. In conclusion, women demonstrated adequate understanding of FMs and perceived abnormalities of these movements better than assumed by health providers. There is a need for more evidence on the effect of improving knowledge and awareness of FMs to construct evidence-based guidelines for low resource settings.

Development of a clinical prediction model for perinatal deaths in low resource settings.

BACKGROUND: Most pregnancy-related deaths in low and middle income countries occur around the time of birth and are avoidable with timely care. This study aimed to develop a prognostic model to identify women at risk of intrapartum-related perinatal deaths in low-resourced settings, by (1) external validation of an existing prediction model, and subsequently (2) development of a novel model. METHODS: A prospective cohort study was conducted among pregnant women who presented consecutively for delivery at the maternity unit of Zanzibar's tertiary hospital, Mnazi Mmoja Hospital, the Republic of Tanzania between October 2017 and May 2018. Candidate predictors of perinatal deaths included maternal and foetal characteristics obtained from routine history and physical examination at the time of admission to the labour ward. The outcomes were intrapartum stillbirths and neonatal death before hospital discharge. An existing stillbirth prediction model with six predictors from Nigeria was applied to the Zanzibar cohort to assess its discrimination and calibration performance. Subsequently, a new prediction model was developed using multivariable logistic regression. Model performance was evaluated through internal validation and corrected for overfitting using bootstrapping methods. FINDINGS: 5747 mother-baby pairs were analysed. The existing model showed poor discrimination performance (c-statistic 0·57). The new model included 15 clinical predictors and showed promising discriminative and calibration performance after internal validation (optimism adjusted c-statistic of 0·78, optimism adjusted calibration slope =0·94). INTERPRETATION: The new model consisted of predictors easily obtained through history-taking and physical examination at the time of admission to the labour ward. It had good performance in predicting risk of perinatal death in women admitted in labour wards. Therefore, it has the potential to assist skilled birth attendance to triage women for appropriate management during labour. Before routine implementation, external validation and usefulness should be determined in future studies. FUNDING: The study received funding from Laerdal Foundation, Otto Kranendonk Fund and UMC Global Health Fellowship. TD acknowledges financial support from the Netherlands Organisation for Health Research and Development (grant 91617050).