Echogenic intracardiac foci detection and location in the second-trimester ultrasound and association with fetal outcomes: A systematic literature review

Introduction

Congenital heart disease (CHD) is the most common congenital abnormality in infants and the leading cause of infant mortality. Improvements in detection and diagnosis in the foetal period would greatly improve the support and service provision for families when the infant is born, developing early preventative interventions, and putting in place enhanced monitoring and care for the infant. A foetal anomaly scan is offered to all pregnant women in the UK between weeks 18-to-20 of pregnancy which includes routine screening for CHD. Echogenic intracardiac foci (EIF) are incidental findings on foetal ultrasound and it is unclear what, if any, significance they have on foetal outcomes. The aim of this literature review is to examine the association between EIF and infant outcomes.

Methods

This review follows the Population-Interest-Comparator-Outcome (PICO) criteria to guide the scope and breadth of the literature review and set the inclusion criteria. The population was defined as the foetus at the 18-20-week ultrasound scan. The interest was where EIF was identified in the scan (as identified by the sonographer) compared to the comparator of those with no EIF. The infant outcomes include preterm delivery, death, structural cardiac abnormality, and chromosomal abnormalities. Inclusion criteria were peer-reviewed cohort studies in English, with full-text availability, published between 2013-2023. Studies included prospective and retrospective cohort studies with the assessment of EIF (with or without other markers) recorded by ultrasound at 18-20 weeks gestation and recording through follow-up (e.g., birth and post-birth up to 5 years) with one of the outcome variables of interest. Studies that only followed up EIF pregnancies without a comparison group were included in selected studies.

Exclusion criteria were studies that did not have full-text availability in English, examined non-cardiac echogenic focus (e.g. identified within the kidneys, liver, bowel, thyroid, hepatic, and pancreas), or those not performed during the second-trimester ultrasound scan or those studies predicting echogenic foci as the outcome rather than the exposure. The primary outcome measure is preterm birth (before 37 weeks) or death of the foetus. Secondary outcomes include chromosomal abnormality and cardiac abnormality.

The literature search was carried out in three stages: stage one was an initial search on Pubmed to identify the index terms which best identify relevant articles. This initial search used the first 10 relevant primary studies and collated the search terms that were used. The second stage took these updated search terms to apply to the; Web of Science online tool which searches the following databases: Web of Science Core Collection, BIOSIS Citation Index, Current Contents Connects, Data Citation Index, Derwent Innovations Index, and MEDLINE (Medical Literature Analysis and Retrieval System Online). This search was repeated on Pubmed and Scopus individually. The final stage reviewed the reference list of the included studies and reviews in the area. Grey literature was also reviewed including the National Congenital Heart Disease Audit (NCHDA). The literature search was carried out in June 2023 and imported onto Covidence software.

Initial screening based on the title and abstract was carried out by two independent reviewers based on the inclusion and exclusion criteria. For those publications selected to take forward, a second screening based on the full text was conducted and those selected as relevant were taken forward to data extraction. A data extraction form was designed which included the Critical Appraisal Skills Programme (CASP) quality review to assess risk of bias. Quality was assessed to include methods of addressing confounding variables, quality of measurement of outcome and exposure and if outcomes by exposure and loss to follow-up. The data includes study identification (number, first author), study demographic information (country, size of study, study design), total number of pregnancies, number with EIF recorded, duration of follow-up, recording of outcomes of interest, position (left/right) of EIF and number of EIF (single/multiple).

The outcomes for those with no EIF were recorded in the same way as those with EIF reporting the number of preterm births, deaths, congenital abnormalities and cardiac abnormalities.

Results

There were 243 studies identified and screened for eligibility with 19 studies included in this review [27-45]. These studies were published between 2014-2022 and were undertaken in Europe (n=5), Asia (n=4), South America (n=2), North America (n=2), and Africa (n=2). The studies included a total of 78,345 pregnancies and recorded EIF in 4385 of these pregnancies. Four studies were prospective [28, 34, 35, 45] and 15 were retrospective [27, 29, 30, 31, 32, 33, 36, 37, 38, 39, 40, 41, 42, 43, 44]. Six studies assessed EIF on its own [27, 29, 34, 35, 38, 45] and 13 assessed EIF with additional soft markers [28, 30, 31, 32, 33, 36, 37, 39, 40, 41, 42, 43, 44]. The duration of follow-up ranged from 10 weeks to 10 years.

The location of EIF was recorded as left (n=4385), right

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