Advertisement

Archives of Gynecology and Obstetrics

, Volume 300, Issue 6, pp 1491–1506 | Cite as

Risk of congenital heart defects in offspring exposed to maternal diabetes mellitus: an updated systematic review and meta-analysis

  • Letao Chen
  • Tubao Yang
  • Lizhang Chen
  • Lesan Wang
  • Tingting Wang
  • Lijuan Zhao
  • Ziwei Ye
  • Senmao Zhang
  • Liu Luo
  • Zan Zheng
  • Jiabi QinEmail author
Review
  • 88 Downloads

Abstract

Purpose

A systematic review and meta-analysis was performed to assess the risk of congenital heart defects (CHDs) and its specific phenotypes associated with maternal diabetes mellitus (DM) including pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM).

Methods

PubMed, Embase, Medline, Google Scholar, Cochrane Libraries, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journals Fulltext Database and China Biology Medicine disc were searched from the inception dates to 15 December 2018, to identify case–control or cohort studies assessing the association between maternal DM and risk of CHDs. The exposure of interest was maternal DM; the outcomes of interest were CHDs and its specific phenotypes. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analyses were performed to explore potential heterogeneity moderators.

Results

Total 52 studies, which involved 259,917 patients with CHDs among 16,929,835 participants, were included for analysis. Overall, mothers with DM compared with those without DM had a significantly higher risk of CHDs in offspring [odds ratios (OR) = 2.71, 95% confidence intervals (CI) 2.28–3.23]. When data were restricted to different types of DM, a significantly increased risk of CHDs was observed among mothers with PGDM (OR = 3.18, 95% CI 2.77–3.65) and GDM (OR = 1.98, 95% CI 1.66–2.36). Our study suggested the risk of CHDs was significantly higher among mothers with PGDM than those with GDM. Additionally, this study suggested maternal DM was significantly associated with most phenotypes of CHDs; of these, double outlet of the right ventricle (OR = 10.89; 95% CI 8.77–13.53), atrioventricular septal defect (OR = 5.74; 95% CI 3.20–10.27) and truncus arteriosus (OR = 5.06; 95% CI 2.65–9.65) were identified as the first three of the most common phenotypes of CHDs associated with maternal DM.

Conclusions

The maternal DM including PGDM and GDM are significantly associated with risk of CHDs and its most phenotypes. The PGDM seems to be more likely to cause CHDs in offspring than GDM. Further studies are needed to clarify the underlying mechanisms.

Keywords

Maternal diabetes mellitus Congenital heart defects Pregestational diabetes mellitus Gestational diabetes mellitus Phenotypes Meta-analysis 

Notes

Acknowledgements

The authors would like to thank the editors and reviewers for their suggestions.

Author contribution

LTC: literature searching, data collection and manuscript writing. TBY: manuscript writing. LZC: manuscript revision. LSW: data management. TTW: data analysis. LJZ: data collection. ZWY: data interpretation. SMZ: literature searching. LL: data collection. ZZ: data analysis. JBQ: conception, design and revise the manuscript.

Funding

This work was supported by the Project Funded by Natural Science Foundation of Hunan Province [Grant numbers 2018JJ2551], National Natural Science Foundation Program of China [Grant numbers 81803313], Hunan Provincial Key Research and Development Program [Grant numbers 2018SK2063; 2018SK2062], and New Teachers’ Scientific Research Driven Foundation of Central South University [Grant numbers 502045001].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Not applicable.

Informed consent

Not applicable.

References

  1. 1.
    Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N et al (2008) Heart disease and stroke statistics–2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117:e25–146PubMedGoogle Scholar
  2. 2.
    van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ et al (2011) Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol 58:2241–2247PubMedGoogle Scholar
  3. 3.
    Gilboa SM, Salemi JL, Nembhard WN, Fixler DE, Correa A (2010) Mortality resulting from congenital heart disease among children and adults in the United States, 1999 to 2006. Circulation 122:2254–2263PubMedPubMedCentralGoogle Scholar
  4. 4.
    Hoffman JIE (2013) The global burden of congenital heart disease. Cardiovasc J Afr 24:141–145PubMedPubMedCentralGoogle Scholar
  5. 5.
    Patel SS, Burns TL (2013) Nongenetic risk factors and congenital heart defects. Pediatr Cardiol 34:1535–1555PubMedGoogle Scholar
  6. 6.
    Muntean I, Togănel R, Benedek T (2017) Genetics of Congenital Heart Disease: Past and Present. Biochem Genet 55:105–123PubMedGoogle Scholar
  7. 7.
    Fung A, Manlhiot C, Naik S, Rosenberg H, Smythe J, Lougheed J et al (2013) Impact of prenatal risk factors on congenital heart disease in the current era. J Am Heart Assoc 2:e000064PubMedPubMedCentralGoogle Scholar
  8. 8.
    Basu M, Zhu JY, LaHaye S, Majumdar U, Jiao K, Han Z et al (2017) Epigenetic mechanisms underlying maternal diabetes-associated risk of congenital heart disease. JCI Insight 2:e95085PubMedCentralGoogle Scholar
  9. 9.
    Jenkins KJ, Correa A, Feinstein JA, Botto L, Britt AE, Daniels SR et al (2007) Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of. Pediatrics 115:2995–3014Google Scholar
  10. 10.
    Wu Y, Reece EA, Zhong J, Dong D, Shen WB, Harman CR et al (2016) Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress, and apoptosis. Am J Obstet Gynecol 215:366.e1–366.e10Google Scholar
  11. 11.
    Kumar SD, Dheen ST, Tay SS (2007) Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development. Cardiovasc Diabetol 6:34PubMedPubMedCentralGoogle Scholar
  12. 12.
    Øyen N, Diaz LJ, Leirgul E, Boyd HA, Priest J, Mathiesen ER et al (2016) Prepregnancy Diabetes and Offspring Risk of Congenital Heart Disease: A Nationwide Cohort Study. Circulation 133:2243–2253PubMedPubMedCentralGoogle Scholar
  13. 13.
    Sharpe PB, Chan A, Haan EA, Hiller JE (2005) Maternal diabetes and congenital anomalies in South Australia 1986–2000: a population-based cohort study. Birth Defects Res A Clin Mol Teratol 73:605–611PubMedGoogle Scholar
  14. 14.
    Eidem I, Stene LC, Henriksen T, Hanssen KF, Vangen S, Vollset SE et al (2010) Congenital anomalies in newborns of women with type 1 diabetes: nationwide population-based study in Norway, 1999–2004. Acta Obstet Gynecol Scand 89:1403–1411PubMedGoogle Scholar
  15. 15.
    Liu S, Joseph KS, Lisonkova S, Rouleau J, Van den Hof M, Sauve R et al (2013) Canadian Perinatal Surveillance System (Public Health Agency of Canada). Association between maternal chronic conditions and congenital heart defects: a population-based cohort study. Circulation 128:583–589PubMedGoogle Scholar
  16. 16.
    Tain YL, Luh H, Lin CY, Hsu CN (2016) Incidence and Risks of Congenital Anomalies of Kidney and Urinary Tract in Newborns: A Population-Based Case-Control Study in Taiwan. Medicine (Baltimore) 95:e2659Google Scholar
  17. 17.
    Moore LL, Singer MR, Bradlee ML, Rothman KJ, Milunsky A (2000) A prospective study of the risk of congenital defects associated with maternal obesity and diabetes mellitus. Epidemiology 11:689–694PubMedGoogle Scholar
  18. 18.
    Peticca P, Keely EJ, Walker MC, Yang Q, Bottomley J (2009) Pregnancy outcomes in diabetes subtypes: how do they compare? A province-based study of Ontario, 2005–2006. J Obstet Gynaecol Can 31:487–496PubMedGoogle Scholar
  19. 19.
    Correa A, Gilboa SM, Besser LM, Botto LD, Moore CA, Hobbs CA et al (2008) Diabetes mellitus and birth defects. Am J Obstet Gynecol 199:237.e1–9Google Scholar
  20. 20.
    Sheffield JS, Butler-Koster EL, Casey BM, McIntire DD, Leveno KJ (2002) Maternal diabetes mellitus and infant malformations. Obstet Gynecol 100:925–930PubMedGoogle Scholar
  21. 21.
    Lisowski LA, Verheijen PM, Copel JA, Kleinman CS, Wassink S, Visser GH et al (2010) Congenital heart disease in pregnancies complicated by maternal diabetes mellitus. An international clinical collaboration, literature review, and meta-analysis. Herz 35:19–26PubMedGoogle Scholar
  22. 22.
    Simeone RM, Devine OJ, Marcinkevage JA, Gilboa SM, Razzaghi H, Bardenheier BH et al (2015) Diabetes and congenital heart defects: a systematic review, meta-analysis, and modeling project. Am J Prev Med 48:195–204PubMedGoogle Scholar
  23. 23.
    Hoang TT, Marengo LK, Mitchell LE, Canfield MA, Agopian AJ (2017) Original Findings and Updated Meta-Analysis for the Association Between Maternal Diabetes and Risk for Congenital Heart Disease Phenotypes. Am J Epidemiol 186:118–128PubMedPubMedCentralGoogle Scholar
  24. 24.
    Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMAP) 2015 statement. Syst Rev 4:1. https://www.prisma-statement.org/. Accessed 20 November 20 2015.
  25. 25.
    Chung CS, Myrianthopoulos NC (1975) Factors affecting risks of congenital malformations. II. Effect of maternal diabetes on congenital malformations. Birth Defects Orig Artic Ser 11:23–38PubMedGoogle Scholar
  26. 26.
    McCarter RJ, Kessler II, Comstock GW (1987) Is diabetes mellitus a teratogen or a coteratogen? Am J Epidemiol 125:195–205PubMedGoogle Scholar
  27. 27.
    Adams MM, Mulinare J, Dooley K (1989) Risk factors for conotruncal cardiac defects in Atlanta. J Am Coll Cardiol 14:432–442PubMedGoogle Scholar
  28. 28.
    Ferencz C, Rubin JD, McCarter RJ, Clark EB (1990) Maternal diabetes and cardiovascular malformations: predominance of double outlet right ventricle and truncus arteriosus. Teratology 41:319–326PubMedGoogle Scholar
  29. 29.
    Becerra JE, Khoury MJ, Cordero JF, Erickson JD (1990) Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study. Pediatrics 85:1–9PubMedGoogle Scholar
  30. 30.
    Erickson JD (1991) Risk factors for birth defects: data from the Atlanta Birth Defects Case-Control Study. Teratology 43:41–51PubMedGoogle Scholar
  31. 31.
    Pradat P (1992) A case-control study of major congenital heart defects in Sweden–1981-1986. Eur J Epidemiol 8:789–796PubMedGoogle Scholar
  32. 32.
    Martínez-Frías ML (1994) Epidemiological analysis of outcomes of pregnancy in diabetic mothers: identification of the most characteristic and most frequent congenital anomalies. Am J Med Genet 51:108–113PubMedGoogle Scholar
  33. 33.
    Khoury MJ, James LM, Erickson JD (1994) On the use of affected controls to address recall bias in case-control studies of birth defects. Teratology 49:273–281PubMedGoogle Scholar
  34. 34.
    Janssen PA, Rothman I, Schwartz SM (1996) Congenital malformations in newborns of women with established and gestational diabetes in Washington State, 1984–91. Paediatr Perinat Epidemiol 10:52–63PubMedGoogle Scholar
  35. 35.
    Loffredo CA, Wilson PD, Ferencz C (2001) Maternal diabetes: an independent risk factor for major cardiovascular malformations with increased mortality of affected infants. Teratology 64:98–106PubMedGoogle Scholar
  36. 36.
    Wren C, Birrell G, Hawthorne G (2003) Cardiovascular malformations in infants of diabetic mothers. Heart 89:1217–1220PubMedPubMedCentralGoogle Scholar
  37. 37.
    Yauck JS, Malloy ME, Blair K, Simpson PM, McCarver DG (2004) Proximity of residence to trichloroethylene-emitting sites and increased risk of offspring congenital heart defects among older women. Birth Defects Res A Clin Mol Teratol 70:808–814PubMedGoogle Scholar
  38. 38.
    Martínez-Frías ML, Frías JP, Bermejo E, Rodríguez-Pinilla E, Prieto L, Frías JL (2005) Pre-gestational maternal body mass index predicts an increased risk of congenital malformations in infants of mothers with gestational diabetes. Diabetes Med 22:775–781Google Scholar
  39. 39.
    Nielsen GL, Nørgard B, Puho E, Rothman KJ, Sørensen HT, Czeizel AE (2005) Risk of specific congenital abnormalities in offspring of women with diabetes. Diabetes Med 22:693–696Google Scholar
  40. 40.
    Kuehl KS, Loffredo CA (2006) A cluster of hypoplastic left heart malformation in Baltimore, Maryland. Pediatr Cardiol 27:25–31PubMedGoogle Scholar
  41. 41.
    Xiaofei N (2008) Case-control study of risk factors of congenital heart disease. Dissertation, Lanzhou University.Google Scholar
  42. 42.
    Jinhua Wu, Chen H, Chen K, Liao F (2008) Nested case-control study of risk factors of congenital heart disease in Zhoushan archipelagoe. Dis Surveill 23:510–514Google Scholar
  43. 43.
    Xueyong Y (2009) The prevention of congenital heart disease. Dissertation, Chinese Academy of Medical Sciences and Peking Union Medical College.Google Scholar
  44. 44.
    Guo G, Hong X, Yao M (2010) Analysis of the risk factors of congenital heart disease. Chin J Neonatol 25:76–79Google Scholar
  45. 45.
    Alverson CJ, Strickland MJ, Gilboa SM, Correa A (2011) Maternal smoking and congenital heart defects in the Baltimore-Washington Infant Study. Pediatrics 127:e647–e653PubMedGoogle Scholar
  46. 46.
    Chen L, Zheng X (2012) Analysis on risks factors of congenital heart diseases. Pract Prevent Med 19:32–34Google Scholar
  47. 47.
    Agopian AJ, Moulik M, Gupta-Malhotra M, Marengo LK, Mitchell LE (2012) Descriptive epidemiology of non-syndromic complete atrioventricular canal defects. Paediatr Perinat Epidemiol 26:515–524PubMedPubMedCentralGoogle Scholar
  48. 48.
    Bell R, Glinianaia SV, Tennant PW, Bilous RW, Rankin J (2012) Peri-conception hyperglycaemia and nephropathy are associated with risk of congenital anomaly in women with pre-existing diabetes: a population-based cohort study. Diabetologia.  https://doi.org/10.1007/s00125-012-2455-y CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Ping Wu, Song J (2013) The analysis of pregnancy blood indexes and pregnancy outcome of diabetic pregnant women. Med Innov China 10:113–115Google Scholar
  50. 50.
    Zhang X, Zhao Z, You A, Zhao W, Chai C, Guo J et al (2013) Case-control study of maternal risk factors for perinatal congenital heart defects. Chin J Birth Health Heredity 21:86–88Google Scholar
  51. 51.
    Madsen NL, Schwartz SM, Lewin MB, Mueller BA (2013) Prepregnancy body mass index and congenital heart defects among offspring: a population-based study. Congenit Heart Dis 8:131–141PubMedGoogle Scholar
  52. 52.
    Csáky-Szunyogh M, Vereczkey A, Kósa Z, Gerencsér B, Czeizel AE (2014) Risk factors in the origin of congenital left-ventricular outflow-tract obstruction defects of the heart: a population-based case-control study. Pediatr Cardiol 35:108–120PubMedGoogle Scholar
  53. 53.
    Guo M, Shi J, Yi B, Liu D (2014) Risk factors of neonatal congenital heart disease: a case-control study. Chin J Neonatol 29:390–393Google Scholar
  54. 54.
    Vereczkey A, Gerencsér B, Czeizel AE, Szabó I (2014) Association of certain chronic maternal diseases with the risk of specific congenital heart defects: a population-based study. Eur J Obstet Gynecol Reprod Biol 182:1–6PubMedGoogle Scholar
  55. 55.
    Brite J, Laughon SK, Troendle J, Mills J (2014) Maternal overweight and obesity and risk of congenital heart defects in offspring. Int J Obes (Lond) 38:878–882Google Scholar
  56. 56.
    Vinceti M, Malagoli C, Rothman KJ, Rodolfi R, Astolfi G, Calzolari E et al (2014) Risk of birth defects associated with maternal pregestational diabetes. Eur J Epidemiol 29:411–418PubMedGoogle Scholar
  57. 57.
    Guo Y, Liu J, Zheng L, Li X, Yuan N, Xue J et al (2016) Analysis of risk factors of congenital heart disease in Xi’an and Xianyang area from 2011 to 2014. Clin Misdiagn Misther 29:80–83Google Scholar
  58. 58.
    Li J, Li L, Wang S, Liu H (2016) Incidence and maternal risk factor of congenital heart disease in Huairou area of Beijing, China. Mater Child Health Care China 31:1435–1437Google Scholar
  59. 59.
    Yan J, Yan X, Yang J, Chen X, Liang B, Luo J et al (2016) Analysis of the clinical significance and the risk factors of prenatal ultrasound screening for fetal congenital heart disease. Chin J Gen Pract 14(114–115):160Google Scholar
  60. 60.
    Ou Y, Mai J, Zhuang J, Liu X, Wu Y, Gao X et al (2016) Risk factors of different congenital heart defects in Guangdong, China. Pediatr Res 79:549–558PubMedGoogle Scholar
  61. 61.
    Zhang H, Zhang Y (2017) Application of prenatal ultrasound in screening of fetal congenital heart disease and analysis of the risk factors. Maternal and Child Health Care of China 32:1245–1247Google Scholar
  62. 62.
    Jun C, Chuan W (2017) Analysis on risk factors of congenital heart diseases in Deyang city. China Modern Doctor 55(24):108–110Google Scholar
  63. 63.
    Li Y (2017) The application of spatio-temporal image for screening of congenital heart disease and the analysis of risk factors. J Qiqihar Med Univ 38:1391–1392Google Scholar
  64. 64.
    Akbariasbagh P, Shariat M, Akbariasbagh N, Ebrahim B (2017) Cardiovascular Malformations in Infants of Diabetic Mothers: A Retrospective Case-Control Study. Acta Med Iran 55:103–108PubMedGoogle Scholar
  65. 65.
    Arjmandnia M, Besharati M, Rezvan S (2018) Studying the determinant factors leading to congenital heart disease in newborns. J Educ Health Promot 7:53PubMedPubMedCentralGoogle Scholar
  66. 66.
    Ludvigsson JF, Neovius M, Söderling J, Gudbjörnsdottir S, Svensson AM, Franzén S et al (2018) Periconception glycaemic control in women with type 1 diabetes and risk of major birth defects: population based cohort study in Sweden. BMJ 362:k2638PubMedPubMedCentralGoogle Scholar
  67. 67.
    Mills JL, Baker L, Goldman AS (1979) Malformations in infants of diabetic mothers occur before the seventh gestational week. Implications for treatment. Diabetes 28:292–293PubMedGoogle Scholar
  68. 68.
    American Diabetes Association (2017) 2. Classification and Diagnosis of Diabetes. Diabetes Care 40:S11–S24Google Scholar
  69. 69.
    Neeb Z, Lajiness JD, Bolanis E, Conway SJ (2013) Cardiac outflow tract anomalies. Wiley Interdiscip Rev Dev Biol 2:499–530PubMedPubMedCentralGoogle Scholar
  70. 70.
    Morgan SC, Relaix F, Sandell LL, Loeken MR (2008) Oxidative stress during diabetic pregnancy disrupts cardiac neural crest migration and causes outflow tract defects. Birth Defects Res A Clin Mol Teratol 82:453–463PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Epidemiology and Health StatisticsXiangya School of Public Health, Central South UniversityHunanChina

Personalised recommendations