The Impact of Pregestational Diabetes on Maternal Morbidity and Mortality: Trends, Challenges, and Future Directions

Abstract

Maternal mortality in the United States is on the rise, demonstrating a concerning trend that stands in stark contrast to the falling rates in other developed countries. A key challenge facing the improvement of maternal care is the mounting prevalence of chronic health conditions such as hypertension and diabetes, which are often linked to poor diet and sedentary lifestyle. Pregestational diabetes now impacts 1 to 2% of pregnancies, while gestational diabetes affects another 7.8%. Both type 1 and type 2 diabetes elevate the risk of severe maternal morbidity and mortality (SMM), including severe cardiac morbidity, hypertensive disorders of pregnancy, hemorrhage, infection, and mental health conditions. The increase in diabetes is thought to account for 17% of the increase in maternal mortality between 1997 and 2012. Another critical issue facing maternal care is the significant disparity in pregnancy outcomes among populations facing greater burdens of adverse social determinants of health, including socioeconomic characteristics, chronic stress, and systemic racism. For example, non-Hispanic Black women are 2.5 times more likely to die during pregnancy and the postpartum period than non-Hispanic White women. Vulnerable populations, often minorities, are also more likely to develop risk factors for SMM, such as type 2 diabetes. As pregestational diabetes is a particularly morbid condition in pregnancy, examining its complications and evidence-based treatments could significantly impact both maternal mortality rates and disparities in pregnancy outcomes in the United States. This review explores the relationship between pregestational diabetes and SMM, how the risk of SMM can be modified by disparities, and avenues for advancing care through future research.

Key Points

• Diabetes during pregnancy greatly increases the risk of SMM.

• Comprehensive care can improve outcomes in high-risk pregnancies with diabetes.

• Adverse social determinants of health worsen outcomes in pregnancies affected by diabetes.

• Improving diabetes care in pregnancy offers an opportunity to enhance maternal outcomes.

Keywords

pregestational diabetes mellitus - maternal morbidity and mortality - social determinants of health - disparities - hypertension - nephropathy - pregnancy

Publication History

Received: 25 April 2024

Accepted: 25 November 2024

Accepted Manuscript online:
26 November 2024

Article published online:
24 December 2024

• References

• 1 Silva CM, Arnegard ME, Maric-Bilkan C. Dysglycemia in pregnancy and maternal/fetal outcomes. J Womens Health (Larchmt) 2021; 30 (02) 187-193
• 2 Davidson KW, Terry MB, Braveman P, Reis PJ, Timmermans S, Epling Jr JW. Maternal mortality: a National Institutes of Health pathways to prevention panel report. Obstet Gynecol 2024; 143 (03) e78-e85
• 3 Bornstein E, Eliner Y, Chervenak FA, Grünebaum A. Concerning trends in maternal risk factors in the United States: 1989-2018. EClinicalMedicine 2020; 29–30: 100657
• 4 Neerland C, Slaughter-Acey J, Behrens K. et al. An evidence map for social and structural determinants for maternal morbidity and mortality: a systematic review. Obstet Gynecol 2024; 143 (03) 383-392
• 5 Wang E, Glazer KB, Howell EA, Janevic TM. Social determinants of pregnancy-related mortality and morbidity in the United States: a systematic review. Obstet Gynecol 2020; 135 (04) 896-915
• 6 GBD 2015 Maternal Mortality Collaborators. Global, regional, and national levels of maternal mortality, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016; 388 (10053): 1775-1812
• 7 Hoyert D. Maternal mortality rates in the United States, 2021. NCHS Health E-Stats; 2023. Accessed April 29 2024 at: https://www.cdc.gov/nchs/data/hestat/maternal-mortality/2021/maternal-mortality-rates-2021.htm/
• 8 The White House. Fact Sheet: Biden-Harris Administration Announces Additional Actions in Response to Vice President Harris's Call to Action on Maternal Health. April 13, 2022
• 9 Chakhtoura N, Chinn JJ, Grantz KL. et al. Importance of research in reducing maternal morbidity and mortality rates. Am J Obstet Gynecol 2019; 221 (03) 179-182
• 10 Joseph KS, Lisonkova S, Boutin A. et al. Maternal mortality in the United States: are the high and rising rates due to changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance?. Am J Obstet Gynecol 2024; 230 (04) 440.e1-440.e13
• 11 O'Neil SS, Platt I, Vohra D. et al. Societal cost of nine selected maternal morbidities in the United States. PLoS One 2022; 17 (10) e0275656
• 12 Nelson DB, Moniz MH, Davis MM. Population-level factors associated with maternal mortality in the United States, 1997-2012. BMC Public Health 2018; 18 (01) 1007
• 13 Schaefer-Graf U, Napoli A, Nolan CJ. Diabetes in pregnancy: a new decade of challenges ahead. Diabetologia 2018; 61 (05) 1012-1021
• 14 Gorsch LP, Wen T, Lonier JY. et al. Trends in delivery hospitalizations with pregestational and gestational diabetes mellitus and associated outcomes: 2000-2019. Am J Obstet Gynecol 2023; 229 (01) 63.e1-63.e14
• 15 Center for Disease Control and Prevention. Behavioral risk factor surveillance system. 2023.
• 16 Gregory EC, Ely DM. Trends and characteristics in gestational diabetes: United States, 2016–2020. Natl Vital Stat Rep 2022; 71 (03) 1-15
• 17 Admon LK, Winkelman TNA, Zivin K, Terplan M, Mhyre JM, Dalton VK. Racial and ethnic disparities in the incidence of severe maternal morbidity in the United States, 2012-2015. Obstet Gynecol 2018; 132 (05) 1158-1166
• 18 Zahn C.. Despite New Manuscript, Incontrovertible Evidence Proves the Unacceptably High U.S. Maternal Mortality Rate. Accessed April 1, 2024 at: www.acog.org/news/news-releases/2024/03/despite-new-manuscript-incontrovertible-evidence-proves-unacceptably-high-us-maternal-mortality-rate
• 19 Bashir M, Fagier Y, Ahmed B. , C Konje J An overview of diabetes mellitus in pregnant women with obesity. Best Pract Res Clin Obstet Gynaecol 2024; 93: 102469
• 20 Moaddab A, Dildy GA, Brown HL. et al. Health care disparity and pregnancy-related mortality in the United States, 2005-2014. Obstet Gynecol 2018; 131 (04) 707-712
• 21 Venkatesh KK, Fareed N, Kiefer MK. et al. Differences in hemoglobin A1c during pregnancy between non-Hispanic Black versus White women with prepregnancy diabetes. Am J Perinatol 2022; 39 (12) 1279-1287
• 22 Joseph KS, Boutin A, Lisonkova S. et al. Maternal mortality in the United States: recent trends, current status, and future considerations. Obstet Gynecol 2021; 137 (05) 763-771
• 23 Centers for Disease Control and Prevention. National Diabetes Statistics Report. 2024.
• 24 Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin Diabetes 2008; 26 (02) 77-82
• 25 Haw JS, Shah M, Turbow S, Egeolu M, Umpierrez G. Diabetes complications in racial and ethnic minority populations in the USA. Curr Diab Rep 2021; 21 (01) 2
• 26 Committee on Health Care for Underserved Women. ACOG Committee Opinion No. 729: Importance of social determinants of health and cultural awareness in the delivery of reproductive health care. Obstet Gynecol 2018; 131 (01) e43-e48
• 27 Venkatesh KK, Germann K, Joseph J. et al. Association between social vulnerability and achieving glycemic control among pregnant individuals with pregestational diabetes. Obstet Gynecol 2022; 139 (06) 1051-1060
• 28 Janevic T, McCarthy K, Liu SH. et al. Racial and ethnic inequities in development of type 2 diabetes after gestational diabetes mellitus. Obstet Gynecol 2023; 142 (04) 901-910
• 29 Valerio VC, Downey J, Sgaier SK, Callaghan WM, Hammer B, Smittenaar P. Black-White disparities in maternal vulnerability and adverse pregnancy outcomes: an ecological population study in the United States, 2014-2018. Lancet Reg Health Am 2023; 20: 100456
• 30 Traylor CS, Johnson JD, Kimmel MC, Manuck TA. Effects of psychological stress on adverse pregnancy outcomes and nonpharmacologic approaches for reduction: an expert review. Am J Obstet Gynecol MFM 2020; 2 (04) 100229
• 31 Bower JK, Butler BN, Bose-Brill S, Kue J, Wassel CL. Racial/ethnic differences in diabetes screening and hyperglycemia among US women after gestational diabetes. Prev Chronic Dis 2019; 16: E145
• 32 Rodríguez JE, Campbell KM. Racial and ethnic disparities in prevalence and care of patients with type 2 diabetes. Clin Diabetes 2017; 35 (01) 66-70
• 33 March of Dimes. Nowhere to Go: Maternity Care Deserts Across the US. 2022 Report. 2022.
• 34 Venkatesh KK, Powe CE, Buschur E. et al. Disparities in continuous glucose monitoring use among women of reproductive age with type 1 diabetes in the T1D exchange. Diabetes Technol Ther 2023; 25 (03) 201-205
• 35 Center for Health Care Strategies. Continuous Glucose Monitor Access for Medicaid Beneficiaries Living with Diabetes: State-By-State Coverage. 2023
• 36 The Commonwealth Fund. Maternal mortality in the United States: A Primer. December 16, 2020.
• 37 Cauldwell M, Baris L, Roos-Hesselink JW, Johnson MR. Ischaemic heart disease and pregnancy. Heart 2019; 105 (03) 189-195
• 38 Nguyen AH, Murrin E, Moyo A. et al. Ischemic heart disease in pregnancy: a practical approach to management. Am J Obstet Gynecol MFM 2024; 6 (03) 101295
• 39 Weissgerber TL, Mudd LM. Preeclampsia and diabetes. Curr Diab Rep 2015; 15 (03) 9
• 40 Ghulmiyyah L, Sibai B. Maternal mortality from preeclampsia/eclampsia. Semin Perinatol 2012; 36 (01) 56-59
• 41 American College of Obstetricians and Gynecologists. Gestational hypertension and preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol 2020; 135 (06) e237-e260
• 42 Broni EK, Ndumele CE, Echouffo-Tcheugui JB, Kalyani RR, Bennett WL, Michos ED. The diabetes-cardiovascular connection in women: understanding the known risks, outcomes, and implications for care. Curr Diab Rep 2022; 22 (01) 11-25
• 43 Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ 2006; 332 (7533): 73-78
• 44 Kealey A. Coronary artery disease and myocardial infarction in pregnancy: a review of epidemiology, diagnosis, and medical and surgical management. Can J Cardiol 2010; 26 (06) 185-189
• 45 Petrie JR, Guzik TJ, Touyz RM. Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms. Can J Cardiol 2018; 34 (05) 575-584
• 46 Jovanovič L, Liang Y, Weng W, Hamilton M, Chen L, Wintfeld N. Trends in the incidence of diabetes, its clinical sequelae, and associated costs in pregnancy. Diabetes Metab Res Rev 2015; 31 (07) 707-716
• 47 Naseri MWEH, Esmat HA, Bahee MD. Prevalence of hypertension in Type-2 diabetes mellitus. Ann Med Surg (Lond) 2022; 78: 103758
• 48 American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 203: Chronic hypertension in pregnancy. Obstet Gynecol 2019; 133 (01) e26-e50
• 49 Tita AT, Szychowski JM, Boggess K. et al; Chronic Hypertension and Pregnancy (CHAP) Trial Consortium. Treatment for mild chronic hypertension during pregnancy. N Engl J Med 2022; 386 (19) 1781-1792
• 50 Dhesi S, Savu A, Ezekowitz JA, Kaul P. Association between diabetes during pregnancy and peripartum cardiomyopathy: a population-level analysis of 309,825 women. Can J Cardiol 2017; 33 (07) 911-917
• 51 Arany Z. Peripartum cardiomyopathy. N Engl J Med 2024; 390 (02) 154-164
• 52 Hawthorne G. Maternal complications in diabetic pregnancy. Best Pract Res Clin Obstet Gynaecol 2011; 25 (01) 77-90
• 53 Bradley PK, Duprey M, Castorino K. Identifying key intervention opportunities during a pregnancy complicated by diabetes: a review of acute complications of diabetes during pregnancy. Curr Diab Rep 2016; 16 (02) 17
• 54 Mathiesen ER, Ringholm L, Feldt-Rasmussen B, Clausen P, Damm P. Obstetric nephrology: pregnancy in women with diabetic nephropathy–the role of antihypertensive treatment. Clin J Am Soc Nephrol 2012; 7 (12) 2081-2088
• 55 Kapustin R, Kopteeva E, Tiselko A. et al. Diabetes and pregnancy study (DAPSY): a 10-year single-center cohort study of pregnancies affected by diabetes. Arch Gynecol Obstet 2024; 309: 2643-2651
• 56 Knorr S, Juul S, Bytoft B. et al. Impact of type 1 diabetes on maternal long-term risk of hospitalisation and mortality: a nationwide combined clinical and register-based cohort study (The EPICOM study). Diabetologia 2018; 61 (05) 1071-1080
• 57 Klemetti MM, Laivuori H, Tikkanen M, Nuutila M, Hiilesmaa V, Teramo K. Obstetric and perinatal outcome in type 1 diabetes patients with diabetic nephropathy during 1988-2011. Diabetologia 2015; 58 (04) 678-686
• 58 Relph S, Patel T, Delaney L, Sobhy S, Thangaratinam S. Adverse pregnancy outcomes in women with diabetes-related microvascular disease and risks of disease progression in pregnancy: a systematic review and meta-analysis. PLoS Med 2021; 18 (11) e1003856
• 59 Critchley JA, Carey IM, Harris T, DeWilde S, Hosking FJ, Cook DG. Glycemic control and risk of infections among people with type 1 or type 2 diabetes in a large primary care cohort study. Diabetes Care 2018; 41 (10) 2127-2135
• 60 Abu-Ashour W, Twells L, Valcour J. et al. The association between diabetes mellitus and incident infections: a systematic review and meta-analysis of observational studies. BMJ Open Diabetes Res Care 2017; 5 (01) e000336
• 61 Hodgson K, Morris J, Bridson T, Govan B, Rush C, Ketheesan N. Immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections. Immunology 2015; 144 (02) 171-185
• 62 Stamler EF, Cruz ML, Mimouni F. et al. High infectious morbidity in pregnant women with insulin-dependent diabetes: an understated complication. Am J Obstet Gynecol 1990; 163 (4 Pt 1): 1217-1221
• 63 Carey IM, Critchley JA, DeWilde S, Harris T, Hosking FJ, Cook DG. Risk of infection in type 1 and type 2 diabetes compared with the general population: a matched cohort study. Diabetes Care 2018; 41 (03) 513-521
• 64 Bauer ME, Bateman BT, Bauer ST, Shanks AM, Mhyre JM. Maternal sepsis mortality and morbidity during hospitalization for delivery: temporal trends and independent associations for severe sepsis. Anesth Analg 2013; 117 (04) 944-950
• 65 Trost SLBJ, Njie F. et al. Pregnancy-Related Deaths: Data from Maternal Mortality Review Committees in 36 US States, 2017–2019. Atlanta, GA: Center for Disease Control and Prevention; 2022
• 66 Chin K, Wendt A, Bennett IM, Bhat A. Suicide and maternal mortality. Curr Psychiatry Rep 2022; 24 (04) 239-275
• 67 Mangla K, Hoffman MC, Trumpff C, O'Grady S, Monk C. Maternal self-harm deaths: an unrecognized and preventable outcome. Am J Obstet Gynecol 2019; 221 (04) 295-303
• 68 Ducat L, Philipson LH, Anderson BJ. The mental health comorbidities of diabetes. JAMA 2014; 312 (07) 691-692
• 69 Attanasio LB, Ranchoff BL, Cooper MI, Geissler KH. Postpartum visit attendance in the United States: a systematic review. Womens Health Issues 2022; 32 (04) 369-375
• 70 Gregory ECW, Ely DM. Trends and characteristics in prepregnancy diabetes: United States, 2016–2021. Natl Vital Stat Rep 2023; 72 (06) 1-13
• 71 López-de-Andrés A, Perez-Farinos N, Hernández-Barrera V. et al. A population-based study of diabetes during pregnancy in Spain (2009-2015): trends in incidence, obstetric interventions, and pregnancy outcomes. J Clin Med 2020; 9 (02) 582
• 72 Persson M, Norman M, Hanson U. Obstetric and perinatal outcomes in type 1 diabetic pregnancies: a large, population-based study. Diabetes Care 2009; 32 (11) 2005-2009
• 73 Mourad M, Wen T, Friedman AM, Lonier JY, D'Alton ME, Zork N. Postpartum readmissions among women with diabetes. Obstet Gynecol 2020; 135 (01) 80-89
• 74 Anderson PO. Treating diabetes during breastfeeding. Breastfeed Med 2018; 13 (04) 237-239
• 75 Pope CJ, Mazmanian D. Breastfeeding and postpartum depression: an overview and methodological recommendations for future research. Depress Res Treat 2016; 2016: 4765310
• 76 Davidson AJF, Park AL, Berger H. et al. Risk of severe maternal morbidity or death in relation to elevated hemoglobin A1c preconception, and in early pregnancy: A population-based cohort study. PLoS Med 2020; 17 (05) e1003104
• 77 Davidson AJF, Park AL, Berger H. et al. Association of improved periconception hemoglobin A1c with pregnancy outcomes in women with diabetes. JAMA Netw Open 2020; 3 (12) e2030207
• 78 Correa A, Gilboa SM, Besser LM. et al. Diabetes mellitus and birth defects. Am J Obstet Gynecol 2008; 199 (03) 237.e1-237.e9
• 79 Diguisto C, Strachan MWJ, Churchill D, Ayman G, Knight M. A study of diabetic ketoacidosis in the pregnant population in the United Kingdom: investigating the incidence, aetiology, management and outcomes. Diabet Med 2022; 39 (04) e14743
• 80 American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 201: Pregestational diabetes mellitus. Obstet Gynecol 2018; 132 (06) e228-e248
• 81 Amiel SA. The consequences of hypoglycaemia. Diabetologia 2021; 64 (05) 963-970
• 82 Pregnancy in women with type 1 and type 2 diabetes in 2002–2003. England, Wales and Northern Ireland. London: CEMACH; 2005
• 83 Frier BM, Schernthaner G, Heller SR. Hypoglycemia and cardiovascular risks. Diabetes Care 2011; 34 (Suppl. 02) S132-S137
• 84 Chinn JJ, Eisenberg E, Artis Dickerson S. et al. Maternal mortality in the United States: research gaps, opportunities, and priorities. Am J Obstet Gynecol 2020; 223 (04) 486-492.e6
• 85 International Classification of Diseases and Related Health Problems. Geneva: World Health Organization; 1992
• 86 MacDorman MF, Declercq E, Cabral H, Morton C. Recent increases in the U.S. maternal mortality rate: disentangling trends from measurement issues. Obstet Gynecol 2016; 128 (03) 447-455
• 87 MacDorman MF, Declercq E, Thoma ME. Trends in Texas maternal mortality by maternal age, race/ethnicity, and cause of death, 2006-2015. Birth 2018; 45 (02) 169-177
• 88 Snowden JM, Lyndon A, Kan P, El Ayadi A, Main E, Carmichael SL. Severe maternal morbidity: a comparison of definitions and data sources. Am J Epidemiol 2021; 190 (09) 1890-1897
• 89 MacDorman MF, Thoma M, Declcerq E, Howell EA. Racial and ethnic disparities in maternal mortality in the united states using enhanced vital records, 2016–2017. Am J Public Health 2021; 111 (09) 1673-1681
• 90 Maric-Bilkan C, Abrahams VM, Arteaga SS. et al. Research recommendations from the National Institutes of Health Workshop on predicting, preventing, and treating preeclampsia. Hypertension 2019; 73 (04) 757-766
• 91 Vounzoulaki E, Khunti K, Abner SC, Tan BK, Davies MJ, Gillies CL. Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis. BMJ 2020; 369: m1361
• 92 MacDorman MF, Declercq E, Thoma ME. Trends in maternal mortality by sociodemographic characteristics and cause of death in 27 states and the District of Columbia. Obstet Gynecol 2017; 129 (05) 811-818
• 93 Ringholm L, Damm P, Mathiesen ER. Improving pregnancy outcomes in women with diabetes mellitus: modern management. Nat Rev Endocrinol 2019; 15 (07) 406-416
• 94 Patton SR, Clements MA. Psychological reactions associated with continuous glucose monitoring in youth. J Diabetes Sci Technol 2016; 10 (03) 656-661
• 95 Sanusi AA, Xue Y, McIlwraith C. et al. Association of continuous glucose monitoring metrics with pregnancy outcomes in patients with preexisting diabetes. Diabetes Care 2024; 47 (01) 89-96
• 96 Reece EA. Perspectives on obesity, pregnancy and birth outcomes in the United States: the scope of the problem. Am J Obstet Gynecol 2008; 198 (01) 23-27
• 97 Siddiqui A, Azria E, Egorova N, Deneux-Tharaux C, Howell EA. Contribution of prepregnancy obesity to racial and ethnic disparities in severe maternal morbidity. Obstet Gynecol 2021; 137 (05) 864-872
• 98 Williams J. The clinical significance of glycosuria in pregnant women. Am J Med Sci 1909; 137: 1-26
• 99 Ayman G, Strachan JA, McLennan N. et al. The top 10 research priorities in diabetes and pregnancy according to women, support networks and healthcare professionals. Diabet Med 2021; 38 (08) e14588
• 100 Yu Y, Arah OA, Liew Z. 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