Maternal pregestational diabetes as an factor in the genesis of congenital malformations of the fetus

Abstract

This review article summarizes the results of modern clinical studies performed domestically or abroad, which provide information on maternal pregestational diabetes (type 1 or 2) shaping a spectrum of congenital malformations of the fetus. Advances in the treatment of diabetes mellitus have reduced the risk of fetal congenital malformations in pregnant women with the disease, but an increase in its incidence among women of childbearing age indicates that this cause of congenital malformations is becoming more relevant every year. This review article presents four diabetes-mediated pathways for the genesis of fetal congenital malformations: those associated with metabolic imbalance or oxidative stress, genetically mediated and caused by insufficient inhibition of apoptosis. Thus, based on clinical studies and meta-analysis over the past ten years, it has been demonstrated that women with pregestational diabetes mellitus are at the highest risk of developing fetal congenital malformations. Achievement of diabetes compensation and physiological nutritional status in such patients determines the favorable course of all stages of pregnancy.

Keywords

congenital malformations of the fetus / pregnancy / late induced miscarriage / reproductive loss

References

[1] Holmes LB, Driscoll SG, Atkins L. Etiologic heterogeneity of neural-tube defects. N Engl J Med. 1976;294(7):365−369. DOI: 10.1056/NEJM197602122940704

[2] Holmes L.B., Driscoll S.G., Atkins L. Etiologic heterogeneity of neural-tube defects // N. Engl. J. Med. 1976. Vol. 294. No. 7. P. 365−369. DOI: 10.1056/NEJM197602122940704

[3] Gabbe SG. Pregnancy in women with diabetes mellitus. The beginning. Clin Perinatol. 1993;20(3):507−515.

[4] Gabbe S.G. Pregnancy in women with diabetes mellitus. The beginning // Clin. Perinatol. 1993. Vol. 20. No. 3. P. 507−515.

[5] Hod M, Jovanovic L, Di Renzo GC, de Leiva A, editors. Textbook of diabetes and pregnancy. 2nd edition. London: Informa Healthcare; 2008.

[6] Hod M., Jovanovic L., Di Renzo G.C., de Leiva A., editors. Textbook of diabetes and pregnancy. 2nd edition. London: Informa Healthcare, 2008.

[7] Freinkel N. Banting lecture 1980. Of pregnancy and progeny. Diabetes. 1980;29(12):1023−1035. DOI: 10.2337/diab.29.12.1023

[8] Freinkel N. Banting Lecture 1980. Of pregnancy and progeny // Diabetes. 1980;29(12):1023−1035. DOI: 10.2337/diab.29.12.1023

[9] Fahed AC, Gelb BD, Seidman JG, Seidman CE. Genetics of congenital heart disease: the glass half empty. Circ Res. 2013;112(4):707−720. [Corrected and republished from: Circ Res. 2013;112(12):e182]. DOI: 10.1161/CIRCRESAHA.112.300853

[10] Fahed A.C., Gelb B.D., Seidman J.G., Seidman C.E. Genetics of congenital heart disease: the glass half empty // Circ. Res. 2013. Vol. 112. No. 4. P. 707−720. [Corrected and republished from: Circ. Res. 2013. Vol. 112. No. 12. P. e182]. DOI: 10.1161/CIRCRESAHA.112.300853

[11] Kappen C, Kruger C, MacGowan J, Salbaum JM. Maternal diet modulates the risk for neural tube defects in a mouse model of diabetic pregnancy. Reprod Toxicol. 2011;31(1):41−49. DOI: 10.1016/j.reprotox.2010.09.002

[12] Kappen C., Kruger C., MacGowan J., Salbaum J.M. Maternal diet modulates the risk for neural tube defects in a mouse model of diabetic pregnancy // Reprod. Toxicol. 2011. Vol. 31. No. 1. P. 41−49. DOI: 10.1016/j.reprotox.2010.09.002

[13] Salbaum JM, Kappen C. Diabetic embryopathy: a role for the epigenome? Birth Defects Res A Clin Mol Teratol. 2011;91(8):770−780. DOI: 10.1002/bdra.20807

[14] Salbaum J.M., Kappen C. Diabetic embryopathy: a role for the epigenome? // Birth Defects Res. A Clin. Mol. Teratol. 2011. Vol. 91. No. 8. P. 770−780. DOI: 10.1002/bdra.20807

[15] Wang L, Lin S, Yi D, et al. Apoptosis, expression of PAX3 and P53, and caspase signal in fetuses with neural tube defects. Birth Defects Res. 2017;109(19):1596−1604. DOI: 10.1002/bdr2.1094

[16] Wang L., Lin S., Yi D., et al. Apoptosis, expression of PAX3 and P53, and caspase signal in fetuses with neural tube defects // Birth Defects Res. 2017. Vol. 109. No. 19. P. 1596−1604. DOI: 10.1002/bdr2.1094

[17] Lin S, Ren A, Wang L, et al. Aberrant methylation of Pax3 gene and neural tube defects in association with exposure to polycyclic aromatic hydrocarbons. Clin Epigenetics. 2019;11(1):13. DOI: 10.1186/s13148-019-0611-7

[18] Lin S., Ren A., Wang L., et al. Aberrant methylation of Pax3 gene and neural tube defects in association with exposure to polycyclic aromatic hydrocarbons // Clin. Epigenetics. 2019. Vol. 11. No. 1. P. 13. DOI: 10.1186/s13148-019-0611-7

[19] Pani L, Horal M, Loeken MR. Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3-dependent development and tumorigenesis. Genes Dev. 2002;16(6):676−680. DOI: 10.1101/gad.969302

[20] Pani L., Horal M., Loeken M.R. Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3- dependent development and tumorigenesis // Genes Dev. 2002. Vol. 16. No. 6. P. 676−680. DOI: 10.1101/gad.969302

[21] Bennett GD, An J, Craig JC, et al. Neurulation abnormalities secondary to altered gene expression in neural tube defect susceptible Splotch embryos. Teratology. 1998;57(1):17−29. DOI: 10.1002/(SICI)1096-9926(199801)57:1<17::AID-TERA4>3.0.CO;2-4

[22] Bennett G.D., An J., Craig J.C., et al. Neurulation abnormalities secondary to altered gene expression in neural tube defect susceptible Splotch embryos // Teratology. 1998. Vol. 57. No. 1. P. 17−29. DOI: 10.1002/(SICI)1096-9926(199801)57:1<17::AID-TERA4>3.0.CO;2-4

[23] Floris I, Descamps B, Vardeu A, et al. Gestational diabetes mellitus impairs fetal endothelial cell functions through a mechanism involving microRNA-101 and histone methyltransferase enhancer of zester homolog-2. Arterioscler Thromb Vasc Biol. 2015;35(3):664−674. DOI: 10.1161/ATVBAHA.114.304730

[24] Floris I., Descamps B., Vardeu A., et al. Gestational diabetes mellitus impairs fetal endothelial cell functions through a mechanism involving microRNA-101 and histone methyltransferase enhancer of zester homolog-2 // Arterioscler. Thromb. Vasc. Biol. 2015. Vol. 35. No. 3. P. 664−674. DOI: 10.1161/ATVBAHA.114.304730

[25] Zabihi S, Loeken MR. Understanding diabetic teratogenesis: where are we now and where are we going? Birth Defects Res A Clin Mol Teratol. 2010;88(10):779−790. DOI: 10.1002/bdra.20704

[26] Zabihi S., Loeken M.R. Understanding diabetic teratogenesis: where are we now and where are we going? // Birth Defects Res. A Clin. Mol. Teratol. 2010. Vol.88. No. 10. P. 779−790. DOI: 10.1002/bdra.20704

[27] Agha MM, Glazier RH, Moineddin R, Booth G. Congenital abnormalities in newborns of women with pregestational diabetes: A time-trend analysis, 1994 to 2009. Birth Defects Res A Clin Mol Teratol. 2016;106(10):831−839. DOI: 10.1002/bdra.23548

[28] Agha M.M., Glazier R.H., Moineddin R., Booth G. Congenital abnormalities in newborns of women with pregestational diabetes: A time-trend analysis, 1994 to 2009 // Birth Defects Res. A Clin. Mol. Teratol. 2016. Vol. 106. No. 10. P. 831−839. DOI: 10.1002/bdra.23548

[29] Billionnet C, Mitanchez D, Weill A, et al. Gestational diabetes and adverse perinatal outcomes from 716,152 births in France in 2012. Diabetologia. 2017;60(4):636−644. DOI: 10.1007/s00125-017-4206-6

[30] Billionnet C., Mitanchez D., Weill A., et al. Gestational diabetes and adverse perinatal outcomes from 716,152 births in France in 2012 // Diabetologia. 2017. Vol. 60. No. 4. P. 636−644. DOI: 10.1007/s00125-017-4206-6

[31] Liu S, Rouleau J, León JA, et al. Canadian perinatal surveillance system. Impact of pre-pregnancy diabetes mellitus on congenital anomalies, Canada, 2002−2012. Health Promot Chronic Dis Prev Can. 2015;35(5):79−84. DOI: 10.24095/hpcdp.35.5.01

[32] Liu S., Rouleau J., León J.A., et al; Canadian Perinatal Surveillance System. Impact of pre-pregnancy diabetes mellitus on congenital anomalies, Canada, 2002−2012 // Health Promot. Chronic Dis. Prev. Can. 2015. Vol. 35. No. 5. P. 79−84. DOI: 10.24095/hpcdp.35.5.01.

[33] Parimi M, Nitsch D. A systematic review and meta-analysis of diabetes during pregnancy and congenital genitourinary abnormalities. Kidney Int Rep. 2020;5(5):678−693. DOI: 10.1016/j.ekir.2020.02.1027

[34] Parimi M., Nitsch D. A systematic review and meta-analysis of diabetes during pregnancy and congenital genitourinary abnormalities // Kidney Int. Rep. 2020. Vol. 5. No. 5. P. 678−693. DOI: 10.1016/j.ekir.2020.02.1027

[35] Minakova E, Warner BB. Maternal immune activation, central nervous system development and behavioral phenotypes. Birth Defects Res. 2018;110(20):1539−1550. DOI: 10.1002/bdr2.1416.

[36] Minakova E., Warner B.B. Maternal immune activation, central nervous system development and behavioral phenotypes // Birth Defects Res. 2018. Vol. 110. P. 20. P. 1539−1550. DOI: 10.1002/bdr2.1416

[37] Kappen C, Salbaum JM. Gene expression in teratogenic exposures: a new approach to understanding individual risk. Reprod Toxicol. 2014;45:94−104. DOI: 10.1016/j.reprotox.2013.12.008

[38] Kappen C., Salbaum J.M. Gene expression in teratogenic exposures: a new approach to understanding individual risk // Reprod. Toxicol. 2014. Vol. 45. P. 94−104. DOI: 10.1016/j.reprotox.2013.12.008

[39] HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358(19):1991−2002. DOI: 10.1056/NEJMoa0707943

[40] HAPO Study Cooperative Research Group; Metzger B.E., Lowe L.P. et al. Hyperglycemia and adverse pregnancy outcomes // N. Engl. J. Med. 2008. Vol. 358. No. 19. P. 1991−2002. DOI: 10.1056/NEJMoa0707943

[41] Ornoy A, Becker M, Weinstein-Fudim L, Ergaz Z. Diabetes during pregnancy: A maternal disease complicating the course of pregnancy with long-term deleterious Effects on the offspring. A clinical review. Int J Mol Sci. 2021;22(6):2965. DOI: 10.3390/ijms22062965

[42] Ornoy A., Becker M., Weinstein-Fudim L., Ergaz Z. Diabetes during pregnancy: A Maternal disease complicating the course of pregnancy with long-term deleterious effects on the offspring. A clinical review // Int. J. Mol. Sci. 2021. Vol. 22. No. 6. P. 2965. DOI: 10.3390/ijms22062965

[43] Wahabi H, Fayed A, Esmaeil S, et al. Prevalence and complications of pregestational and gestational diabetes in Saudi women: analysis from Riyadh mother and baby cohort study (RAHMA). Biomed Res Int. 2017;2017:6878263.

[44] Wahabi H., Fayed A., Esmaeil S., et al. Prevalence and complications of pregestational and gestational diabetes in Saudi women: analysis from Riyadh mother and baby cohort study (RAHMA) // Biomed. Res. Int. 2017. Vol. 2017. P. 6878263.

[45] Ornoy A, Reece EA, Pavlinkova G, et al. Effect of maternal diabetes on the embryo, fetus, and children: congenital anomalies, genetic and epigenetic changes and developmental outcomes. Birth Defects Res C Embryo Today. 2015;105(1):53−72. DOI: 10.1002/bdrc.21090

[46] Ornoy A., Reece E.A., Pavlinkova G., et al. Effect of maternal diabetes on the embryo, fetus, and children: congenital anomalies, genetic and epigenetic changes and developmental outcomes // Birth Defects Res. C. Embryo Today. 2015. Vol. 105. No. 1. P. 53−72. DOI: 10.1002/bdrc.21090

[47] Liu S, Evans J, MacFarlane AJ, et al. Association of maternal risk factors with the recent rise of neural tube defects in Canada. Paediatr Perinat Epidemiol. 2019;33(2):145−153. DOI: 10.1111/ppe.12543

[48] Liu S., Evans J., MacFarlane A.J., et al. Association of maternal risk factors with the recent rise of neural tube defects in Canada // Paediatr. Perinat. Epidemiol. 2019. Vol. 33. No. 2. P. 145−153. DOI: 10.1111/ppe.12543

[49] Nakano H, Fajardo VM, Nakano A. The role of glucose in physiological and pathological heart formation. Dev Biol. 2021;475:222−233. DOI: 10.1016/j.ydbio.2021.01.020

[50] Nakano H., Fajardo V.M., Nakano A. The role of glucose in physiological and pathological heart formation // Dev. Biol. 2021. Vol. 475. P. 222−233. DOI: 10.1016/j.ydbio.2021.01.020

[51] Corrigan N, Brazil DP, McAuliffe F. Fetal cardiac effects of maternal hyperglycemia during pregnancy. Birth Defects Res A Clin Mol Teratol. 2009;85(6):523−530. DOI: 10.1002/bdra.20567

[52] Corrigan N., Brazil D.P., McAuliffe F. Fetal cardiac effects of maternal hyperglycemia during pregnancy // Birth Defects Res. A Clin. Mol. Teratol. 2009. Vol. 85. No. 6. P. 523−530. DOI: 10.1002/bdra.20567

[53] Burns JS, Manda G. Metabolic pathways of the warburg effect in health and disease: perspectives of choice, chain or chance. Int J Mol Sci. 2017;18(12):2755. DOI: 10.3390/ijms18122755

[54] Burns J.S., Manda G. Metabolic pathways of the warburg effect in health and disease: perspectives of choice, chain or chance // Int. J. Mol. Sci. 2017. Vol. 18. No. 12. P. 2755. DOI: 10.3390/ijms18122755

RIGHTS & PERMISSIONS

Eсо-Vector