Am J Perinatol 2021; 38(12): 1217-1222
DOI: 10.1055/s-0041-1730435
SMFM Fellowship Series Article

Congenital Malformation Risk According to Hemoglobin A1c Values in a Contemporary Cohort with Pregestational Diabetes

Robert B. Martin
1   Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
,
Elaine L. Duryea
1   Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
,
Anne Ambia
1   Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
,
Alexandra Ragsdale
1   Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
,
Donald Mcintire
1   Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
,
Chet Edward Wells
1   Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
,
Catherine Y. Spong
1   Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
,
Jodi S. Dashe
1   Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
,
David B. Nelson
1   Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
› Author Affiliations
Funding None.

Abstract

Objective The study aimed to evaluate the association between hemoglobin A1c values and likelihood of fetal anomalies in women with pregestational diabetes.

Study Design Women with pregestational diabetes who delivered at a single institution that serves a nonreferred population from May 1, 2009 to December 31, 2018 were ascertained. Hemoglobin A1c values were obtained at the first prenatal visit. Women who delivered a singleton live- or stillborn infant with a major malformation as defined by European Surveillance of Congenital Anomalies criteria were identified. In infants with multiple system anomalies, each malformation was considered separately. Hemoglobin A1c values were analyzed categorically by using Mantel–Haenszel method and continuously with linear regression for trend for fetal anomalies.

Results A total of 1,676 deliveries to women with pregestational diabetes were delivered at our institution, and hemoglobin A1c was assessed in 1,573 deliveries (94%). There were 129 deliveries of an infant with at least one major malformation, an overall anomaly rate of approximately 8%. Mean hemoglobin A1c concentration was significantly higher in pregnancies with anomalous infants, 9.3 ± 2.1% versus 8.0 ± 2.1%, and p <0.001. There was no difference in gestational age at the time hemoglobin A1c was obtained, 13 ± 8.3 versus 14 ± 8.7 weeks. Hemoglobin A1c was associated with increased probability of a congenital malformation. This reached 10% with a hemoglobin A1c concentration of 10%, and 20% with a hemoglobin A1c of 13%. Similar trends were seen when examining risk of anomalies by organ system with increasing hemoglobin A1c levels, with the greatest increase in probability for both cardiac and genitourinary anomalies.

Conclusion In women with pregestational diabetes, hemoglobin A1c is strongly associated with fetal anomaly risk. Data from a contemporary cohort may facilitate counseling and also highlight the need for preconceptual care and glycemic optimization prior to entry to obstetric care.

Key Points

  • Infants of diabetic mothers had an 8% major anomaly rate.

  • HbA1c of 10% in pregnancy associated with 10% anomaly rate.

  • HbA1c of 13% in pregnancy associated with 20% anomaly rate.

  • Preconceptual care is important to reduce prevalence.

Note

Portions of this manuscript were presented at the Society for Maternal-Fetal Medicine 40th Annual Pregnancy Meeting on February 7, 2020 (abstract 957).


Supplementary Material



Publication History

Received: 10 November 2020

Accepted: 21 April 2021

Article published online:
04 June 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 American College of Obstetricians and Gynecologists. Pregestational diabetes mellitus. practice bulletin no. 201. Obstet Gynecol 2018; 132 (06) e228-e248
  • 2 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
  • 3 Peterson C, Grosse SD, Li R. et al. Preventable health and cost burden of adverse birth outcomes associated with pregestational diabetes in the United States. Am J Obstet Gynecol 2015; 212 (01) 74.e1-74.e9
  • 4 Centers for Disease Control and Prevention. National diabetes statistics report, 2017: estimates of diabetes and its burden in the United States. Atlanta (GA): CDC. Available at: https://dev.diabetes.org/sites/default/files/2019-06/cdc-statistics-report-2017.pdf 2017
  • 5 Sheffield JS, Butler-Koster EL, Casey BM, McIntire DD, Leveno KJ. Maternal diabetes mellitus and infant malformations. Obstet Gynecol 2002; 100 (5 Pt 1): 925-930
  • 6 Gabbe SG. Congenital malformations in infants of diabetic mothers. Obstet Gynecol Surv 1977; 32 (03) 125-132
  • 7 Kitzmiller JL, Wallerstein R, Correa A, Kwan S. Preconception care for women with diabetes and prevention of major congenital malformations. Birth Defects Res A Clin Mol Teratol 2010; 88 (10) 791-803
  • 8 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
  • 9 Leirgul E, Brodwall K, Greve G. et al. Maternal diabetes, birth weight, and neonatal risk of congenital heart defects in Norway. 1993–2009. Obstet Gynecol 2016; 128 (05) 1116-1125
  • 10 Rosenn B, Miodovnik M, Combs CA, Khoury J, Siddiqi TA. Glycemic thresholds for spontaneous abortion and congenital malformations in insulin-dependent diabetes mellitus. Obstet Gynecol 1994; 84 (04) 515-520
  • 11 Baack ML, Wang C, Hu S, Segar JL, Norris AW. Hyperglycemia induces embryopathy, even in the absence of systemic maternal diabetes: an in vivo test of the fuel mediated teratogenesis hypothesis. Reprod Toxicol 2014; 46: 129-136
  • 12 Ewart-Toland A, Yankowitz J, Winder A. et al. Oculoauriculovertebral abnormalities in children of diabetic mothers. Am J Med Genet 2000; 90 (04) 303-309
  • 13 Moore LL, Singer MR, Bradlee ML, Rothman KJ, Milunsky A. A prospective study of the risk of congenital defects associated with maternal obesity and diabetes mellitus. Epidemiology 2000; 11 (06) 689-694
  • 14 Nielsen GL, Nørgard B, Puho E, Rothman KJ, Sørensen HT, Czeizel AE. Risk of specific congenital abnormalities in offspring of women with diabetes. Diabet Med 2005; 22 (06) 693-696
  • 15 Lisowski LA, Verheijen PM, Copel JA. et al. Congenital heart disease in pregnancies complicated by maternal diabetes mellitus. An international clinical collaboration, literature review, and meta-analysis. Herz 2010; 35 (01) 19-26
  • 16 Becerra JE, Khoury MJ, Cordero JF, Erickson JD. Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study. Pediatrics 1990; 85 (01) 1-9
  • 17 Loffredo CA, Wilson PD, Ferencz C. Maternal diabetes: an independent risk factor for major cardiovascular malformations with increased mortality of affected infants. Teratology 2001; 64 (02) 98-106
  • 18 Spilson SV, Kim HJ, Chung KC. Association between maternal diabetes mellitus and newborn oral cleft. Ann Plast Surg 2001; 47 (05) 477-481
  • 19 Wren C, Birrell G, Hawthorne G. Cardiovascular malformations in infants of diabetic mothers. Heart 2003; 89 (10) 1217-1220
  • 20 Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner RE. Pre-conception care of diabetes, congenital malformations, and spontaneous abortions. Diabetes Care 1996; 19 (05) 514-541
  • 21 Greene MF, Hare JW, Cloherty JP, Benacerraf BR, Soeldner JS. First-trimester hemoglobin A1 and risk for major malformation and spontaneous abortion in diabetic pregnancy. Teratology 1989; 39 (03) 225-231
  • 22 Wender-Ozegowska E, Wróblewska K, Zawiejska A, Pietryga M, Szczapa J, Biczysko R. Threshold values of maternal blood glucose in early diabetic pregnancy--prediction of fetal malformations. Acta Obstet Gynecol Scand 2005; 84 (01) 17-25
  • 23 Starikov R, Bohrer J, Goh W. et al. Hemoglobin A1c in pregestational diabetic gravidas and the risk of congenital heart disease in the fetus. Pediatr Cardiol 2013; 34 (07) 1716-1722
  • 24 American Diabetes Association. Introduction: standards of medical care in diabetes-2019. Diabetes Care 2019; 42 (Suppl. 01) S1-S2
  • 25 Tennant PW, Glinianaia SV, Bilous RW, Rankin J, Bell R. Pre-existing diabetes, maternal glycated haemoglobin, and the risks of fetal and infant death: a population-based study. Diabetologia 2014; 57 (02) 285-294
  • 26 Texas health and human services. gestational diabetes in Medicaid: prevalence, outcomes, and costs. Accessed 2014 at: https://www.dshs.state.tx.us/legislative/2019-Reports/2019-State-Plan-for-Diabetes-and-Obesity-Treatment-and-Education.pdf
  • 27 Mills JL, Knopp RH, Simpson JL. et al. Lack of relation of increased malformation rates in infants of diabetic mothers to glycemic control during organogenesis. N Engl J Med 1988; 318 (11) 671-676
  • 28 Combs CA, Kitzmiller JL. Spontaneous abortion and congenital malformations in diabetes. Baillieres Clin Obstet Gynaecol 1991; 5 (02) 315-331
  • 29 Gabbe SG, Graves CR. Management of diabetes mellitus complicating pregnancy. Obstet Gynecol 2003; 102 (04) 857-868
  • 30 Allen AJ, Snowden JM, Lau B, Cheng Y, Caughey AB. Type-2 diabetes mellitus: does prenatal care affect outcomes?. J Matern Fetal Neonatal Med 2018; 31 (01) 93-97
  • 31 Center for Disease Control. National diabetes statistics report 2020 estimates of diabetes and its burden in the united states. Accessed September 1, 2020 at https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf
  • 32 Byrne JJ, Morgan JL, Twickler DM, McIntire DD, Dashe JS. Utility of follow-up standard sonography for fetal anomaly detection. Am J Obstet Gynecol 2020; 222 (06) 615.e1-615.e9