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      Effect of maternal diabetes on fetal heart function on echocardiography: systematic review and meta‐analysis

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          ABSTRACT

          Objective

          Maternal diabetes in pregnancy is associated with structural anomalies of the fetal heart, as well as hypertrophy and functional impairment. This systematic review and meta‐analysis aimed to estimate the effect of maternal diabetes on fetal cardiac function as measured by prenatal echocardiography.

          Methods

          We performed a search of the EMBASE, PubMed and The Cochrane Library databases, from inception to 4 July 2019, for studies evaluating fetal cardiac function using echocardiography in pregnancies affected by diabetes compared with uncomplicated pregnancies. Outcome measures were cardiac hypertrophy and diastolic, systolic and overall cardiac function as assessed by various ultrasound parameters. The quality of the studies was assessed using the Newcastle–Ottawa Scale. Data on interventricular septal (IVS) thickness, myocardial performance index (MPI) and E/A ratio were pooled for the meta‐analysis using random‐effects models. For pregnancies with diabetes, results were reported overall and according to whether diabetes was pregestational (PDM) or gestational (GDM). Results were also stratified according to the trimester in which fetal cardiac assessment was performed.

          Results

          Thirty‐nine studies were included, comprising data for 2276 controls and 1925 women with pregnancy affected by diabetes mellitus (DM). Of these, 1120 had GDM, 671 had PDM and in 134 cases diabetes type was not specified. Fetal cardiac hypertrophy was more prevalent in diabetic pregnancies than in non‐diabetic controls in 21/26 studies, and impaired diastolic function was observed in diabetic pregnancies in 22/28 studies. The association between DM and systolic function was inconsistent, with 10/25 studies reporting no difference between cases and controls, although more recent studies measuring cardiac deformation, i.e. strain, did show decreased systolic function in diabetic pregnancies. Of the studies measuring overall fetal cardiac function, the majority (14/21) found significant impairment in diabetic pregnancies. Results were similar when stratified according to GDM or PDM. These effects were already present in the first trimester, but were most profound in the third trimester. Meta‐analysis of studies performed in the third trimester showed, compared with controls, increased IVS thickness in both PDM (mean difference, 0.75 mm (95% CI, 0.56–0.94 mm)) and GDM (mean difference, 0.65 mm (95% CI, 0.39–0.91 mm)) pregnancies, decreased E/A ratio in PDM pregnancies (mean difference, –0.09 (95% CI, –0.15 to –0.03)), no difference in E/A ratio in GDM pregnancies (mean difference, –0.01 (95% CI, –0.02 to 0.01)) and no difference in MPI in either PDM (mean difference, 0.04 (95% CI, –0.01 to 0.09)) or GDM (mean difference, 0.03 (95% CI, –0.01 to 0.06)) pregnancies.

          Conclusions

          The findings of this review show that maternal diabetes is associated with fetal cardiac hypertrophy, diastolic dysfunction and overall impaired myocardial performance on prenatal ultrasound, irrespective of whether diabetes is pregestational or gestational. Further studies are needed to demonstrate the relationship with long‐term outcomes. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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          Most cited references89

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045

            Since the year 2000, IDF has been measuring the prevalence of diabetes nationally, regionally and globally.
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              Gestational diabetes mellitus

              Hyperglycaemia that develops during pregnancy and resolves after birth has been recognized for over 50 years, but uniform worldwide consensus is lacking about threshold hyperglycaemic levels that merit a diagnosis of 'gestational diabetes mellitus' (GDM) and thus treatment during pregnancy. GDM is currently the most common medical complication of pregnancy, and prevalence of undiagnosed hyperglycaemia and even overt diabetes in young women is increasing. Maternal overweight and obesity, later age at childbearing, previous history of GDM, family history of type 2 diabetes mellitus and ethnicity are major GDM risk factors. Diagnosis is usually performed using an oral glucose tolerance test (OGTT), although a non-fasting, glucose challenge test (GCT) is used in some parts of the world to screen women for those requiring a full OGTT. Dietary modification and increased physical activity are the primary treatments for GDM, but pharmacotherapy, usually insulin, is used when normoglycaemia is not achieved. Oral hypoglycaemic agents, principally metformin and glibenclamide (glyburide), are also used in some countries. Treatment improves immediate pregnancy outcomes, reducing excess fetal growth and adiposity and pregnancy-related hypertensive disorders. GDM increases the risk of long-term complications, including obesity, impaired glucose metabolism and cardiovascular disease, in both the mother and infant. Optimal management of mother and infant during long-term follow-up remains challenging, with very limited implementation of preventive strategies in most parts of the world.
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                Author and article information

                Contributors
                m.n.bekker-3@umcutrecht.nl
                Journal
                Ultrasound Obstet Gynecol
                Ultrasound Obstet Gynecol
                10.1002/(ISSN)1469-0705
                UOG
                Ultrasound in Obstetrics & Gynecology
                John Wiley & Sons, Ltd. (Chichester, UK )
                0960-7692
                1469-0705
                01 April 2021
                April 2021
                : 57
                : 4 ( doiID: 10.1002/uog.v57.4 )
                : 539-550
                Affiliations
                [ 1 ] Department of Obstetrics and Gynaecology, University Medical Center Utrecht Utrecht University Utrecht The Netherlands
                [ 2 ] Department of Pediatric Cardiology, University Medical Center Utrecht Utrecht University Utrecht The Netherlands
                [ 3 ] Department of Obstetrics and Fetal Medicine, Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands
                Author notes
                [*] [* ] Correspondence to: Dr M. N. Bekker, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands (e‐mail: m.n.bekker-3@ 123456umcutrecht.nl )
                [#]

                A.L.D. and L.d.W. contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-7372-4291
                Article
                UOG22163 UOG-2020-0291.R1
                10.1002/uog.22163
                8048940
                32730637
                654d40ce-b9fc-476b-af0a-b278aa629f27
                © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 20 June 2020
                : 20 March 2020
                : 22 July 2020
                Page count
                Figures: 4, Tables: 3, Pages: 12, Words: 6561
                Categories
                Systematic Review
                Systematic Reviews
                Custom metadata
                2.0
                April 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:15.04.2021

                Obstetrics & Gynecology
                cardiac function,diabetes,fetus,meta‐analysis,pregnancy,prenatal,systematic review,ultrasound

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