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Effect of maternal pregestational diabetes mellitus on congenital heart diseases

  • Review Article
  • Published:
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Abstract

Background

The increasing population of diabetes mellitus in adolescent girls and women of childbearing age contributes to a large number of pregnancies with maternal pregestational diabetes mellitus. Congenital heart diseases are a common adverse outcome in mothers with pregestational diabetes mellitus. However, there is little systematic information between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring.

Data sources

Literature selection was performed in PubMed. One hundred and seven papers were cited in our review, including 36 clinical studies, 26 experimental studies, 31 reviews, eight meta-analysis articles, and six of other types.

Results

Maternal pregestational diabetes mellitus poses a high risk of congenital heart diseases in the offspring and causes variety of phenotypes of congenital heart diseases. Factors such as persistent maternal hyperglycemia, oxidative stress, polymorphism of uncoupling protein 2, polymorphism of adiponectin gene, Notch 1 pathway, Nkx2.5 disorders, dysregulation of the hypoxia-inducible factor 1, and viral etiologies are associated with the occurrence of congenital heart diseases in the offspring of mothers with pregestational diabetes mellitus. Treatment options including blood sugar-reducing, anti-oxidative stress drug supplements and exercise can help to prevent maternal pregestational diabetes mellitus from inducing congenital heart diseases.

Conclusions

Our review contributes to a better understanding of the association between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring and to a profound thought of the mechanism, preventive and therapeutic measurements of congenital heart diseases caused by maternal pregestational diabetes mellitus.

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The authors confirm that the data supporting the findings of this study are available within the article.

References

  1. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the international diabetes federation diabetes atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843.

    Article  PubMed  Google Scholar 

  2. Zimmet PZ, Magliano DJ, Herman WH, Shaw JE. Diabetes: a 21st century challenge. Lancet Diabetes Endocrinol. 2014;2:56–64.

    Article  PubMed  Google Scholar 

  3. Mayer-Davis EJ, Dabelea D, Lawrence JM. Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012. N Engl J Med. 2017;377:301.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Menke A, Casagrande S, Cowie CC. Contributions of A1c, fasting plasma glucose, and 2-hour plasma glucose to prediabetes prevalence: NHANES 2011–2014. Ann Epidemiol. 2018;28:681-5.e2.

    Article  PubMed  Google Scholar 

  5. Andes LJ, Cheng YJ, Rolka DB, Gregg EW, Imperatore G. Prevalence of prediabetes among adolescents and young adults in the United States, 2005–2016. JAMA Pediatr. 2020;174:e194498.

    Article  PubMed  Google Scholar 

  6. Rughani A, Friedman JE, Tryggestad JB. Type 2 diabetes in youth: the role of early life exposures. Curr Diab Rep. 2020;20:45.

    Article  PubMed  Google Scholar 

  7. Chivese T, Werfalli MM, Magodoro I, Chinhoyi RL, Kengne AP, Norris SA, et al. Prevalence of type 2 diabetes mellitus in women of childbearing age in Africa during 2000–2016: a systematic review and meta-analysis. BMJ Open. 2019;9:e024345.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Peters TM, Brazeau AS. Exercise in pregnant women with diabetes. Curr Diab Rep. 2019;19:80.

    Article  PubMed  Google Scholar 

  9. Rezai S, LoBue S, Henderson CE. Diabetes prevention: reproductive age women affected by insulin resistance. Womens Health (Lond). 2016;12:427–32.

    Article  PubMed  Google Scholar 

  10. Arendt LH, Pedersen LH, Pedersen L, Ovesen PG, Henriksen TB, Lindhard MS, et al. Glycemic control in pregnancies complicated by pre-existing diabetes mellitus and congenital malformations: a Danish population-based study. Clin Epidemiol. 2021;13:615–26.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Eidem I, Stene LC, Henriksen T, Hanssen KF, Vangen S, Vollset SE, et al. Congenital anomalies in newborns of women with type 1 diabetes: nationwide population-based study in Norway, 1999–2004. Acta Obstet Gynecol Scand. 2010;89:1403–11.

    Article  PubMed  Google Scholar 

  12. Zegkos T, Ntiloudi D, Giannakoulas G. Parental alcohol exposure and congenital heart diseases in offspring: a causal link with controversial evidence. Eur J Prev Cardiol. 2020;27:407–9.

    Article  PubMed  Google Scholar 

  13. van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ, et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58:2241–7.

    Article  PubMed  Google Scholar 

  14. Chen Z, Li S, Guo L, Peng X, Liu Y. Prenatal alcohol exposure induced congenital heart diseases: from bench to bedside. Birth Defects Res. 2021;113:521–34.

    Article  CAS  PubMed  Google Scholar 

  15. Vincent F, Ternacle J, Denimal T, Shen M, Redfors B, Delhaye C, et al. Transcatheter aortic valve replacement in bicuspid aortic valve stenosis. Circulation. 2021;143:1043–61.

    Article  CAS  PubMed  Google Scholar 

  16. Engineer A, Saiyin T, Greco ER, Feng Q. Say NO to ROS: their roles in embryonic heart development and pathogenesis of congenital heart defects in maternal diabetes. Antioxidants (Basel). 2019;8:436.

    Article  CAS  PubMed  Google Scholar 

  17. Faraoni D, Nasr VG, DiNardo JA. Overall hospital cost estimates in children with congenital heart disease: analysis of the 2012 kid’s inpatient database. Pediatr Cardiol. 2016;37:37–43.

    Article  PubMed  Google Scholar 

  18. Bhatt AB, Foster E, Kuehl K, Alpert J, Brabeck S, Crumb S, et al. Congenital heart disease in the older adult: a scientific statement from the American heart association. Circulation. 2015;131:1884–931.

    Article  PubMed  Google Scholar 

  19. Ntiloudi D, Zegkos T, Bazmpani MA, Parcharidou D, Panagiotidis T, Hadjimiltiades S, et al. Pregnancy outcome in women with congenital heart disease: a single-center experience. Hellenic J Cardiol. 2018;59:155–9.

    Article  PubMed  Google Scholar 

  20. Ntiloudi D, Zegkos T, Koutsakis A, Giannakoulas G, Karvounis H. Pregnancy in patients with congenital heart disease: a contemporary challenge. Cardiol Rev. 2017;25:326–30.

    Article  PubMed  Google Scholar 

  21. Blue GM, Kirk EP, Sholler GF, Harvey RP, Winlaw DS. Congenital heart disease: current knowledge about causes and inheritance. Med J Aust. 2012;197:155–9.

    Article  PubMed  Google Scholar 

  22. Fung A, Manlhiot C, Naik S, Rosenberg H, Smythe J, Lougheed J, et al. Impact of prenatal risk factors on congenital heart disease in the current era. J Am Heart Assoc. 2013;2:e000064.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Catalano PM, Tyzbir ED, Roman NM, Amini SB, Sims EA. Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women. Am J Obstet Gynecol. 1991;165:1667–72.

    Article  CAS  PubMed  Google Scholar 

  24. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2005;28(Suppl 1):S37-42.

    Article  Google Scholar 

  25. Mills JL, Baker L, Goldman AS. Malformations in infants of diabetic mothers occur before the seventh gestational week Implications for treatment. Diabetes. 1979;28:292–3.

    Article  CAS  PubMed  Google Scholar 

  26. Ejdesjo A, Wentzel P, Eriksson UJ. Influence of maternal metabolism and parental genetics on fetal maldevelopment in diabetic rat pregnancy. Am J Physiol Endocrinol Metab. 2012;302:E1198–209.

    Article  CAS  PubMed  Google Scholar 

  27. Hoang TT, Marengo LK, Mitchell LE, Canfield MA, Agopian AJ. Original findings and updated meta-analysis for the association between maternal diabetes and risk for congenital heart disease phenotypes. Am J Epidemiol. 2017;186:118–28.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Aberg A, Westbom L, Källén B. Congenital malformations among infants whose mothers had gestational diabetes or preexisting diabetes. Early Hum Dev. 2001;61:85–95.

    Article  CAS  PubMed  Google Scholar 

  29. Sylva M, van den Hoff MJ, Moorman AF. Development of the human heart. Am J Med Genet A. 2014;164A:1347–71.

    Article  PubMed  Google Scholar 

  30. Brade T, Pane LS, Moretti A, Chien KR, Laugwitz KL. Embryonic heart progenitors and cardiogenesis. Cold Spring Harb Perspect Med. 2013;3:a013847.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Buckingham M, Meilhac S, Zaffran S. Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet. 2005;6:826–35.

    Article  CAS  PubMed  Google Scholar 

  32. Buijtendijk MFJ, Barnett P, van den Hoff MJB. Development of the human heart. Am J Med Genet C Semin Med Genet. 2020;184:7–22.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Dhanantwari P, Lee E, Krishnan A, Samtani R, Yamada S, Anderson S, et al. Human cardiac development in the first trimester: a high-resolution magnetic resonance imaging and episcopic fluorescence image capture atlas. Circulation. 2009;120:343–51.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Eriksen NB, Damm P, Mathiesen ER, Ringholm L. The prevalence of congenital malformations is still higher in pregnant women with pregestational diabetes despite near-normal HbA1c: a literature review. J Matern Fetal Neonatal Med. 2019;32:1225–9.

    Article  PubMed  Google Scholar 

  35. Liu S, Joseph KS, Lisonkova S, Rouleau J, Van den Hof M, Sauve R, et al. Association between maternal chronic conditions and congenital heart defects: a population-based cohort study. Circulation. 2013;128:583–9.

    Article  PubMed  Google Scholar 

  36. Øyen N, Diaz LJ, Leirgul E, Boyd HA, Priest J, Mathiesen ER, et al. Prepregnancy diabetes and offspring risk of congenital heart disease: a nationwide cohort study. Circulation. 2016;133:2243–53.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Wang H, Wender-Ozegowska E, Garne E, Morgan M, Loane M, Morris JK, et al. Insulin analogues use in pregnancy among women with pregestational diabetes mellitus and risk of congenital anomaly: a retrospective population-based cohort study. BMJ Open. 2018;8:e014972.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Yu Y, Arah OA, Liew Z, Cnattingius S, Olsen J, Sorensen HT, et al. Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: population based cohort study with 40 years of follow-up. BMJ. 2019;367:l6398.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Luo L, Zhang S, Wang T, Diao J, Li J, Li Y, et al. Associations of maternal diabetes mellitus and adiponectin gene polymorphisms with congenital heart disease in offspring: a case-control study. Medicine (Baltimore). 2021;100:e24672.

    Article  PubMed  Google Scholar 

  40. Dervisoglu P, Kosecik M, Kumbasar S. Effects of gestational and pregestational diabetes mellitus on the foetal heart: a cross-sectional study. J Obstet Gynaecol. 2018;38:408–12.

    Article  PubMed  Google Scholar 

  41. Pavlinkova G, Salbaum JM, Kappen C. Maternal diabetes alters transcriptional programs in the developing embryo. BMC Genomics. 2009;10:274.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Culshaw LH, Savery D, Greene NDE, Copp AJ. Mouse whole embryo culture: evaluating the requirement for rat serum as culture medium. Birth Defects Res. 2019;111:1165–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Roest PA, van Iperen L, Vis S, Wisse LJ, Poelmann RE, Steegers-Theunissen RP, et al. Exposure of neural crest cells to elevated glucose leads to congenital heart defects, an effect that can be prevented by N-acetylcysteine. Birth Defects Res A Clin Mol Teratol. 2007;79:231–5.

    Article  CAS  PubMed  Google Scholar 

  44. Engineer A, Lim YJ, Lu X, Kim MY, Norozi K, Feng Q. Sapropterin reduces coronary artery malformation in offspring of pregestational diabetes mice. Nitric Oxide. 2020;94:9–18.

    Article  CAS  PubMed  Google Scholar 

  45. Saiyin T, Engineer A, Greco ER, Kim MY, Lu X, Jones DL, et al. Maternal voluntary exercise mitigates oxidative stress and incidence of congenital heart defects in pre-gestational diabetes. J Cell Mol Med. 2019;23:5553–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Moazzen H, Lu X, Ma NL, Velenosi TJ, Urquhart BL, Wisse LJ, et al. N-acetylcysteine prevents congenital heart defects induced by pregestational diabetes. Cardiovasc Diabetol. 2014;13:46.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Wang F, Reece EA, Yang P. Superoxide dismutase 1 overexpression in mice abolishes maternal diabetes-induced endoplasmic reticulum stress in diabetic embryopathy. Am J Obstet Gynecol. 2013;209:e1-7.

    Google Scholar 

  48. Wu Y, Reece EA, Zhong J, Dong D, Shen WB, Harman CR, et al. Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress, and apoptosis. Am J Obstet Gynecol. 2016;215:e1-10.

    Google Scholar 

  49. Kumar SD, Dheen ST, Tay SS. Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development. Cardiovasc Diabetol. 2007;6:34.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Fahed AC, Gelb BD, Seidman JG, Seidman CE. Genetics of congenital heart disease: the glass half empty. Circ Res. 2013;112:707–20.

    Article  CAS  PubMed  Google Scholar 

  51. Codazzi AC, Ippolito R, Novara C, Tondina E, Cerbo RM, Tzialla C. Hypertrophic cardiomyopathy in infant newborns of diabetic mother: a heterogeneous condition, the importance of anamnesis, physical examination and follow-up. Ital J Pediatr. 2021;47:197.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Bolin EH, Spray BJ, Mourani PM, Porter C, Collins RT 2nd. Mortality among infants of diabetic mothers with hypertrophic cardiomyopathy. J Matern Fetal Neonatal Med. 2022. https://doi.org/10.1080/14767058.2022.2066993.

    Article  PubMed  Google Scholar 

  53. Corrigan N, Treacy A, Brazil DP, McAuliffe FM. Cardiomyopathy and diastolic dysfunction in the embryo and neonate of a type 1 diabetic mouse model. Reprod Sci. 2013;20:781–90.

    Article  PubMed  Google Scholar 

  54. Han SS, Wang G, Jin Y, Ma ZL, Jia WJ, Wu X, et al. Investigating the mechanism of hyperglycemia-induced fetal cardiac hypertrophy. PLoS One. 2015;10:e0139141.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Levy PT, Tissot C, Horsberg Eriksen B, Nestaas E, Rogerson S, McNamara PJ, et al. Application of neonatologist performed echocardiography in the assessment and management of neonatal heart failure unrelated to congenital heart disease. Pediatr Res. 2018;84(Suppl 1):78–88.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Gheen KM, Reeves JT. Effect of size of ventricular septal defect and age on pulmonary hemodynamics at sea level. Am J Cardiol. 1995;75:66–70.

    Article  CAS  PubMed  Google Scholar 

  57. Otterstad JE, Nitter-Hauge S, Myhre E. Isolated ventricular septal defect in adults. Clinical and haemodynamic findings. Br Heart J. 1983;50:343–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Contractor T, Mandapati R. Arrhythmias in patients with atrial defects. Card Electrophysiol Clin. 2017;9:235–44.

    Article  PubMed  Google Scholar 

  59. Godt RE, Fogaca RT, Nosek TM. Alterations of myocardial contraction associated with a structural heart defect in embryonic chicks. Adv Exp Med Biol. 1998;453:453–8; discussion 9.

    Article  CAS  PubMed  Google Scholar 

  60. Russell NE, Foley M, Kinsley BT, Firth RG, Coffey M, McAuliffe FM. Effect of pregestational diabetes mellitus on fetal cardiac function and structure. Am J Obstet Gynecol. 2008;199:e1-7.

    Google Scholar 

  61. Russell NE, Higgins MF, Kinsley BF, Foley ME, McAuliffe FM. Heart rate variability in neonates of type 1 diabetic pregnancy. Early Hum Dev. 2016;92:51–5.

    Article  PubMed  Google Scholar 

  62. Maron BJ. Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Circulation. 2010;121:445–56.

    Article  PubMed  Google Scholar 

  63. Alcalai R, Seidman JG, Seidman CE. Genetic basis of hypertrophic cardiomyopathy: from bench to the clinics. J Cardiovasc Electrophysiol. 2008;19:104–10.

    PubMed  Google Scholar 

  64. Morton SU, Pereira AC, Quiat D, Richter F, Kitaygorodsky A, Hagen J, et al. Genome-wide de novo variants in congenital heart disease are not associated with maternal diabetes or obesity. Circ Genom Precis Med. 2022;15:e003500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Eriksson UJ, Cederberg J, Wentzel P. Congenital malformations in offspring of diabetic mothers–animal and human studies. Rev Endocr Metab Disord. 2003;4:79–93.

    Article  CAS  PubMed  Google Scholar 

  66. Zhao Z, Reece EA. New concepts in diabetic embryopathy. Clin Lab Med. 2013;33:207–33.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Jin YM, Zhao SZ, Zhang ZL, Chen Y, Cheng X, Chuai M, et al. High glucose level induces cardiovascular dysplasia during early embryo development. Exp Clin Endocrinol Diabetes. 2013;121:448–54.

    Article  CAS  PubMed  Google Scholar 

  68. Liu Y, Feng Q. NOing the heart: role of nitric oxide synthase-3 in heart development. Differentiation. 2012;84:54–61.

    Article  CAS  PubMed  Google Scholar 

  69. Liu Y, Lu X, Xiang FL, Poelmann RE, Gittenberger-de Groot AC, Robbins J, et al. Nitric oxide synthase-3 deficiency results in hypoplastic coronary arteries and postnatal myocardial infarction. Eur Heart J. 2014;35:920–31.

    Article  CAS  PubMed  Google Scholar 

  70. Schmidt TS, McNeill E, Douglas G, Crabtree MJ, Hale AB, Khoo J, et al. Tetrahydrobiopterin supplementation reduces atherosclerosis and vascular inflammation in apolipoprotein E-knockout mice. Clin Sci (Lond). 2010;119:131–42.

    Article  CAS  PubMed  Google Scholar 

  71. Heitzer T, Krohn K, Albers S, Meinertz T. Tetrahydrobiopterin improves endothelium-dependent vasodilation by increasing nitric oxide activity in patients with type II diabetes mellitus. Diabetologia. 2000;43:1435–8.

    Article  CAS  PubMed  Google Scholar 

  72. Cai S, Khoo J, Mussa S, Alp NJ, Channon KM. Endothelial nitric oxide synthase dysfunction in diabetic mice: importance of tetrahydrobiopterin in eNOS dimerisation. Diabetologia. 2005;48:1933–40.

    Article  CAS  PubMed  Google Scholar 

  73. Edgar K, Gardiner TA, van Haperen R, de Crom R, McDonald DM. eNOS overexpression exacerbates vascular closure in the obliterative phase of OIR and increases angiogenic drive in the subsequent proliferative stage. Invest Ophthalmol Vis Sci. 2012;53:6833–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Edgar KS, Matesanz N, Gardiner TA, Katusic ZS, McDonald DM. Hyperoxia depletes (6R)-5,6,7,8-tetrahydrobiopterin levels in the neonatal retina: implications for nitric oxide synthase function in retinopathy. Am J Pathol. 2015;185:1769–82.

    Article  CAS  PubMed  Google Scholar 

  75. Koenig SN, Bosse K, Majumdar U, Bonachea EM, Radtke F, Garg V. Endothelial Notch1 is required for proper development of the semilunar valves and cardiac outflow tract. J Am Heart Assoc. 2016;5:e003075.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Kerstjens-Frederikse WS, van de Laar IM, Vos YJ, Verhagen JM, Berger RM, Lichtenbelt KD, et al. Cardiovascular malformations caused by NOTCH1 mutations do not keep left: data on 428 probands with left-sided CHD and their families. Genet Med. 2016;18:914–23.

    Article  CAS  PubMed  Google Scholar 

  77. Basu M, Zhu JY, LaHaye S, Majumdar U, Jiao K, Han Z, et al. Epigenetic mechanisms underlying maternal diabetes-associated risk of congenital heart disease. JCI Insight. 2017;2:e95085.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Terada R, Warren S, Lu JT, Chien KR, Wessels A, Kasahara H. Ablation of Nkx2-5 at mid-embryonic stage results in premature lethality and cardiac malformation. Cardiovasc Res. 2011;91:289–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, et al. Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science. 1998;281:108–11.

    Article  CAS  PubMed  Google Scholar 

  80. Ouyang P, Saarel E, Bai Y, Luo C, Lv Q, Xu Y, et al. A de novo mutation in NKX2.5 associated with atrial septal defects, ventricular noncompaction, syncope and sudden death. Clin Chim Acta. 2011;412:170–5.

    Article  CAS  PubMed  Google Scholar 

  81. Zhao M, Diao J, Huang P, Li J, Li Y, Yang Y, et al. Association of maternal diabetes mellitus and polymorphisms of the NKX2.5 gene in children with congenital heart disease: a single centre-based case-control study. J Diabetes Res. 2020;2020:3854630.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Bohuslavova R, Skvorova L, Sedmera D, Semenza GL, Pavlinkova G. Increased susceptibility of HIF-1alpha heterozygous-null mice to cardiovascular malformations associated with maternal diabetes. J Mol Cell Cardiol. 2013;60:129–41.

    Article  CAS  PubMed  Google Scholar 

  83. Souza BM, Assmann TS, Kliemann LM, Gross JL, Canani LH, Crispim D. The role of uncoupling protein 2 (UCP2) on the development of type 2 diabetes mellitus and its chronic complications. Arq Bras Endocrinol Metabol. 2011;55:239–48.

    Article  PubMed  Google Scholar 

  84. de Souza BM, Brondani LA, Boucas AP, Sortica DA, Kramer CK, Canani LH, et al. Associations between UCP1 -3826A/G, UCP2 -866G/A, Ala55Val and Ins/Del, and UCP3 -55C/T polymorphisms and susceptibility to type 2 diabetes mellitus: case-control study and meta-analysis. PLoS One. 2013;8:e54259.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Hou G, Jin Y, Liu M, Wang C, Song G. UCP2-866G/A polymorphism is associated with prediabetes and type 2 diabetes. Arch Med Res. 2020;51:556–63.

    Article  CAS  PubMed  Google Scholar 

  86. Xu L, Chen S, Zhan L. Association of uncoupling protein-2 -866G/A and Ala55Val polymorphisms with susceptibility to type 2 diabetes mellitus: a meta-analysis of case-control studies. Medicine (Baltimore). 2021;100:e24464.

    Article  CAS  PubMed  Google Scholar 

  87. Luo L, Huang P, Wang TT, Zhao LJ, Ye ZW, Zhang SM, et al. Association of maternal diabetes mellitus and UCP2 gene polymorphisms with congenital heart disease in offspring: a case-control study. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22:1092–9 (in Chinese).

    PubMed  Google Scholar 

  88. Takahashi M, Arita Y, Yamagata K, Matsukawa Y, Okutomi K, Horie M, et al. Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord. 2000;24:861–8.

    Article  CAS  PubMed  Google Scholar 

  89. Sun P, Liu L, Chen J, Chen Y, Shi L, Imam MU, et al. The polymorphism of rs266729 in adiponectin gene and type 2 diabetes mellitus: a meta-analysis. Medicine (Baltimore). 2017;96:e8745.

    Article  CAS  PubMed  Google Scholar 

  90. Cui M, Gao Y, Zhao Y, Pang H, Chen L, Wang Z, et al. Association between adiponectin gene polymorphism and environmental risk factors of type 2 diabetes mellitus among the Chinese population in Hohhot. Biomed Res Int. 2020;2020:6383906.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Cai Y, Zeng T, Chen L. Association of adiponectin polymorphisms with the risk of diabetic nephropathy in type 2 diabetes: a meta-analysis. J Diabetes. 2015;7:31–40.

    Article  CAS  PubMed  Google Scholar 

  92. Carvajal HG, Brar AK, Eghtesady P. Maternal gut virome in pregestational diabetes-possible cause of congenital heart disease? Open Forum Infect Dis. 2020;7:ofaa013.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Sharma V, Goessling LS, Brar AK, Joshi CS, Mysorekar IU, Eghtesady P. Coxsackievirus B3 infection early in pregnancy induces congenital heart defects through suppression of fetal cardiomyocyte proliferation. J Am Heart Assoc. 2021;10:e017995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Wook Kim K, Allen DW, Briese T, Couper JJ, Barry SC, Colman PG, et al. Distinct gut virome profile of pregnant women with type 1 diabetes in the ENDIA study. Open Forum Infect Dis. 2019;6:ofz025.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Lin SF, Kuo CF, Chiou MJ, Chang SH. Maternal and fetal outcomes of pregnant women with type 1 diabetes, a national population study. Oncotarget. 2017;8:80679–87.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Wahabi HA, Alzeidan RA, Bawazeer GA, Alansari LA, Esmaeil SA. Preconception care for diabetic women for improving maternal and fetal outcomes: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2010;10:63.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Bishop KC, Harris BS, Boyd BK, Reiff ES, Brown L, Kuller JA. Pharmacologic treatment of diabetes in pregnancy. Obstet Gynecol Surv. 2019;74:289–97.

    Article  PubMed  Google Scholar 

  98. Bergel R, Hadar E, Toledano Y, Hod M. Pharmacological management of gestational diabetes mellitus. Curr Diab Rep. 2016;16:118.

    Article  PubMed  Google Scholar 

  99. Toledano Y, Hadar E, Hod M. Safety of insulin analogues as compared with human insulin in pregnancy. Expert Opin Drug Saf. 2016;15:963–73.

    Article  CAS  PubMed  Google Scholar 

  100. Lv S, Wang J, Xu Y. Safety of insulin analogs during pregnancy: a meta-analysis. Arch Gynecol Obstet. 2015;292:749–56.

    Article  CAS  PubMed  Google Scholar 

  101. Wyatt JW, Frias JL, Hoyme HE, Jovanovic L, Kaaja R, Brown F, et al. Congenital anomaly rate in offspring of mothers with diabetes treated with insulin lispro during pregnancy. Diabet Med. 2005;22:803–7.

    Article  CAS  PubMed  Google Scholar 

  102. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP, MiG trial investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008;358:2003–15.

    Article  CAS  PubMed  Google Scholar 

  103. Guo L, Ma J, Tang J, Hu D, Zhang W, Zhao X. Comparative efficacy and safety of metformin, glyburide, and insulin in treating gestational diabetes mellitus: a meta-analysis. J Diabetes Res. 2019;2019:9804708.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Kusuyama J, Alves-Wagner AB, Makarewicz NS, Goodyear LJ. Effects of maternal and paternal exercise on offspring metabolism. Nat Metab. 2020;2:858–72.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Zheng J, Zhou LY, Xiao XH. Maternal exercise and its beneficial effects on glucose metabolism in offspring. Chin Med J (Engl). 2020;133:863–7.

    Article  CAS  PubMed  Google Scholar 

  106. Barakat R, Pelaez M, Cordero Y, Perales M, Lopez C, Coteron J, et al. Exercise during pregnancy protects against hypertension and macrosomia: randomized clinical trial. Am J Obstet Gynecol. 2016;214:e1-8.

    Google Scholar 

  107. May LE, Scholtz SA, Suminski R, Gustafson KM. Aerobic exercise during pregnancy influences infant heart rate variability at one month of age. Early Hum Dev. 2014;90:33–8.

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank Yan-Qiu Chen for her expert assistance with the image processing technology.

Funding

This work was supported by Sichuan Vocational College of Health and Rehabilitation (No. CWKY-2020Z-02), the Department of Science and Technology of Sichuan Province (No. 2019YJ0079), and the National Natural Science Foundation of China (No. 81900283).

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Authors and Affiliations

  1. Department of Basic Medical Sciences, Sichuan Vocational College of Health and Rehabilitation, Zigong, 643000, China

    Zhi-Yan Chen, Shuang-Fa Mao, Jian Qin, Li-Xin Yang & Yin Liu

  2. Department of Pharmacology, West China School of Basic Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, China

    Ling-Hong Guo & Yin Liu

  3. Department of Anesthesiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, China

    Yin Liu

  4. Animal Research Institute, Sichuan University, Chengdu, China

    Yin Liu

Authors
  1. Zhi-Yan Chen
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  2. Shuang-Fa Mao
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  3. Ling-Hong Guo
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  4. Jian Qin
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  5. Li-Xin Yang
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  6. Yin Liu
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Contributions

CZY contributed to conceptualization and writing of the original draft. MSF and GLH contributed to validation. QJ and YLX contributed to software. LY contributed to reviewing and editing, and funding acquisition. All authors have made substantial contributions to the conception and design of the study, drafting the article, or revising it critically for important intellectual content. All authors have provided approval for the final version to be submitted and published. Each author has agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Yin Liu.

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No financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. The authors have no conflict of interest to declare.

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Chen, ZY., Mao, SF., Guo, LH. et al. Effect of maternal pregestational diabetes mellitus on congenital heart diseases. World J Pediatr 19, 303–314 (2023). https://doi.org/10.1007/s12519-022-00582-w

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