Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Antenatal maternal hypoglycemia in women with gestational diabetes mellitus and neonatal outcomes

Journal of Perinatology volume 42, pages 1091–1096 (2022)Cite this article

Subjects

Abstract

Objective

To examine the prevalence of antenatal maternal hypoglycemia after initiation of pharmacotherapy for gestational diabetes mellitus (GDMA2) and its association with pregnancy outcomes.

Study Design

Retrospective cohort of GDMA2 women receiving either insulin or oral hypoglycemic agents. Composite neonatal outcome included macrosomia, jaundice, respiratory distress syndrome, large for gestational age, shoulder dystocia, birth trauma, 5-minute Apgar < 7, and neonatal hypoglycemia, and was compared between women with and without hypoglycemia using bivariate and multivariate analyses.

Results

Of 489 women included in the study, 95 (19.4%) had at least one episode of hypoglycemia, most often in the setting of glyburide. Newborns exposed to maternal hypoglycemia had higher rates of the composite neonatal outcome (54.7% vs. 38.3%, p = 0.004). After controlling for confounding factors, maternal hypoglycemia remained independently associated with the composite neonatal outcome (aOR = 1.69, 95% CI 1.04–2.72).

Conclusion

Maternal hypoglycemia in GDMA2 was associated with higher rates of adverse neonatal outcomes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Gestational Diabetes. https://www.cdc.gov/diabetes/basics/gestational.html. Accessed December 27, 2020.

  2. Nicholson W, Bolen S, Witkop CT, Neale D, Wilson L, Bass E. Benefits and risks of oral diabetes agents compared with insulin in women with gestational diabetes: a systematic review. Obstet Gynecol. 2009;113:193–205.

    Article  Google Scholar 

  3. Dhulkotia JS, Ola B, Fraser R, Farrell T. Oral hypoglycemic agents vs insulin in management of gestational diabetes: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010;203:457.e1–457.e9. https://doi.org/10.1016/j.ajog.2010.06.044

    Article  CAS  Google Scholar 

  4. Langer O, Conway D, Berkus M, Xenakis EMJ, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N. Engl J Med. 2000;343:1134–8.

    Article  CAS  Google Scholar 

  5. Yogev Y, Ben-Haroush A, Chen R, Rosenn B, Hod M, Langer O. Undiagnosed asymptomatic hypoglycemia: diet, insulin, and glyburide for gestational diabetic pregnancy. Obstet Gynecol. 2004;104:88–93.

    Article  CAS  Google Scholar 

  6. Jacobson GF, Ramos GA, Ching JY, Kirby RS, Ferrara A, Field DR. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J Obstet Gynecol. 2005;193:118–24. https://doi.org/10.1016/j.ajog.2005.03.018

    Article  CAS  PubMed  Google Scholar 

  7. Mathiesen ER, Kinsley B, Amiel SA, Heller S, McCance D, Duran S, et al. Maternal glycemic control and hypoglycemia in type 1 diabetic pregnancy: a randomized trial of insulin aspart versus human insulin in 322 pregnant women. Diabetes Care. 2007;30:771–6. https://doi.org/10.2337/dc06-1887

    Article  CAS  PubMed  Google Scholar 

  8. Rosenn BM, Miodovnik M. Glycemic control in the diabetic pregnancy: is tighter always better?. J Matern Neonatal Med. 2000;9:29–34. https://doi.org/10.3109/14767050009020509.

    Article  CAS  Google Scholar 

  9. Rosenn BM, Miodovnik M, Holcberg G, Khoury J, Siddiqi T. Hypoglycemia: the price of intensive insulin therapy for pregnant women with insulin-dependent diabetes mellitus. Obstet Gynecol. 1995;85:417–22. https://doi.org/10.1016/0029-7844(94)00415-A

    Article  CAS  PubMed  Google Scholar 

  10. Ter Braak EWMT, Evers IM, Erkelens DW, Visser GHA. Maternal hypoglycemia during pregnancy in type 1 diabetes: maternal and fetal consequences. Diabetes Metab Res Rev. 2002;18:96–105. https://doi.org/10.1002/dmrr.271

    Article  PubMed  Google Scholar 

  11. Vadakekut ES, McCoy SJB, Payto ME. Association of maternal hypoglycemia with low birth weight and low placental weight: a retrospective investigation. J Am Osteopath Assoc. 2011;111:148–52. https://doi.org/10.7556/jaoa.2011.111.3.148

    Article  PubMed  Google Scholar 

  12. Pugh SK, Doherty DA, Magann EF, Chauhan SP, Hill JB, Morrison JC. Does hypoglycemia following a glucose challenge test identify a high risk pregnancy? Reprod Health. 2009;6:1–7. https://doi.org/10.1186/1742-4755-6-10

    Article  CAS  Google Scholar 

  13. Feinberg JH, Magann EF, Morrison JC, Holman JR, Polizzotto MJ. Does maternal hypoglycemia during screening glucose assessment identify a pregnancy at-risk for adverse perinatal outcome? J Perinatol. 2005;25:509–13. https://doi.org/10.1038/sj.jp.7211336

    Article  PubMed  Google Scholar 

  14. Abell DA, Beischer NA. Evaluation of the three hour oral glucose tolerance test in detection of significant hyperglycemia and hypoglycemia in pregnancy. Diabetes. 1975;24:874–80. https://doi.org/10.2337/diab.24.10.874

    Article  CAS  PubMed  Google Scholar 

  15. Raviv S, Wilkof-Segev R, Maor-Sagie E, Naeh A, Yoeli Y, Hallak M, et al. Hypoglycemia during the oral glucose tolerance test in pregnancy-maternal characteristics and neonatal outcomes. Int J Gynaecol Obstet. 2021; 18. https://doi.org/10.1002/ijgo.14037.

  16. Langer O, Levy J, Brustman L, Anyaegbunam A, Merkatz R, Divon M. Glycemic control in gestational diabetes mellitus-How tight is tight enough: small for gestational age versus large for gestational age? Am J Obstet Gynecol. 1989;161:646–53. https://doi.org/10.1016/0002-9378(89)90371-2

    Article  CAS  PubMed  Google Scholar 

  17. Kuwata C, Saeki N, Honda K, Matsuoka T, Tsuchiya Y, Shimomura K. Effects of maternal hypoglycemia on fetal eye and skeleton development in rats. Reprod Toxicol. 2017;71:135–41. https://doi.org/10.1016/j.reprotox.2017.05.009

    Article  CAS  PubMed  Google Scholar 

  18. Tanigawa K, Kawaguchi M, Tanaka O, Kato Y. Skeletal malformations in rat offspring: long-term effect of maternal insulin-induced hypoglycemia during organogenesis. Diabetes. 1991;40:1115–21. https://doi.org/10.2337/diab.40.9.1115

    Article  CAS  PubMed  Google Scholar 

  19. Jensen VFH, Mølck AM, Lykkesfeldt J, Bøgh IB. Effect of maternal hypoglycaemia during gestation on materno-foetal nutrient transfer and embryo-foetal development: evidence from experimental studies focused primarily on the rat. Reprod Toxicol. 2018;77:1–24. https://doi.org/10.1016/j.reprotox.2018.01.007

    Article  CAS  PubMed  Google Scholar 

  20. ACOG. PB216 Macrosomia (2020). Obstet Gynecol. 2019;133:168–86.

    Google Scholar 

  21. Duryea EL, Hawkins JS, McIntire DD, Casey BM, Leveno KJ. A revised birth weight reference for the United States. Obstet Gynecol. 2014;124:16–22. https://doi.org/10.1097/AOG.0000000000000345

    Article  PubMed  Google Scholar 

  22. ACOG. ACOG Practice Bulletin Shoulder Dystocia. ACOG. 2017;2017:1118–32.

    Google Scholar 

  23. Yuen L. Gestational diabetes mellitus: challenges for different ethnic groups. World J Diabetes. 2015;6:1024 https://doi.org/10.4239/wjd.v6.i8.1024

    Article  PubMed  PubMed Central  Google Scholar 

  24. Hedderson M, Ehrlich S, Sridhar S, Darbinian J, Moore S, Ferrara A. Racial/ethnic disparities in the prevalence of gestational diabetes mellitus by BMI. Diabetes Care. 2012;35:1492–8. https://doi.org/10.2337/dc11-2267

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ferrara A, Hedderson MM, Quesenberry CP, Selby JV. Prevalence of gestational diabetes mellitus detected by the National Diabetes Data Group or the Carpenter and Coustan plasma glucose thresholds. Diabetes Care. 2002;25:1625–30. https://doi.org/10.2337/diacare.25.9.1625

    Article  PubMed  Google Scholar 

  26. Huddle K, England M, Nagar A. Outcome of pregnancy in diabetic women in Soweto, South Africa 1983-1992. Diabet Med. 1993;10:290–4.

    Article  CAS  Google Scholar 

  27. Bentley-Lewis R, Powe C, Ankers E, Wenger J, Ecker J, Thadhani R. Effect of race/ethnicity on hypertension risk subsequent to gestational diabetes mellitus. Am J Cardiol. 2014;113:1364–70. https://doi.org/10.1016/j.amjcard.2014.01.411

    Article  PubMed  PubMed Central  Google Scholar 

  28. Nguyen BT, Cheng YW, Snowden JM, Esakoff TF, Frias AE, Caughey AB. The effect of race/ethnicity on adverse perinatal outcomes among patients with gestational diabetes mellitus. Am J Obstet Gynecol. 2012;207:322.e1–322.e6. https://doi.org/10.1016/j.ajog.2012.06.049

    Article  Google Scholar 

  29. Mocarski M, Savitz DA. Ethnic differences in the association between gestational diabetes and pregnancy outcome. Matern Child Health J. 2012;16:364–73. https://doi.org/10.1007/s10995-011-0760-6

    Article  CAS  PubMed  Google Scholar 

  30. Schmella MJ, Ferrell RE, Gallaher MJ, Lykins DL, Althouse AD, Roberts JM, et al. The −93T/G LPL promoter polymorphism is associated with lower third-trimester triglycerides in pregnant African American Women. Biol Res Nurs. 2015;17:429–37. https://doi.org/10.1177/1099800414561475

    Article  CAS  PubMed  Google Scholar 

  31. Agarwal M. Consensus in gestational diabetes MELLITUS: looking for the holy grail. J Clin Med. 2018;7:123 https://doi.org/10.3390/jcm7060123

    Article  PubMed Central  Google Scholar 

  32. Caissutti C, Berghella V, Scientific evidence for different options for GDM screening and management: controversies and review of the literature. Biomed Res Int. 2017;2017. https://doi.org/10.1155/2017/2746471

  33. Harris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr. 2012;161:787–91. https://doi.org/10.1016/j.jpeds.2012.05.022

    Article  CAS  PubMed  Google Scholar 

  34. Cho HY, Jung I, Kim SJ, The association between maternal hyperglycemia and perinatal outcomes in gestational diabetes mellitus patients: a retrospective cohort study. Medicine. 2016;95. https://doi.org/10.1097/MD.0000000000004712

  35. Hamel MS, Kanno LM, Has P, Beninati MJ, Rouse DJ, Werner EF. Intrapartum glucose management in women with gestational diabetes mellitus: a randomized controlled trial. Obstet Gynecol. 2019;133:1171–7. https://doi.org/10.1097/AOG.0000000000003257

    Article  PubMed  Google Scholar 

  36. Schwartz RA, Rosenn B, Aleksa K, Koren G. Glyburide transport across the human placenta. Obstet Gynecol. 2015;125:583–8. https://doi.org/10.1097/AOG.0000000000000672.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Maternal Fetal Medicine, Advocate Medical Group, 4400W. 95th St, Suite 207, Chicago, IL, 60453, USA

    Rachel K. Harrison

  2. Department of Obstetrics and Gynecology, Medical College of Wisconsin, 9200W. Wisconsin Ave, Milwaukee, WI, 53226, USA

    Vishmayaa Saravanan, Caroline Davitt, Meredith Cruz & Anna Palatnik

Authors
  1. Rachel K. Harrison
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vishmayaa Saravanan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caroline Davitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meredith Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anna Palatnik
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RH generated the research question, did chart abstraction, collected patient data, cleaned the data set, designed the analysis plan, perform the statistical analysis, and wrote the first draft of the manuscript. V.S. did chart abstraction, literature review, and wrote the first draft of the introduction and results section. CD did chart abstraction, reviewed and edited the final draft. MC did chart abstraction, reviewed and edited the final draft. AP help generate the research question, design the analysis plan, and edited the final manuscript several times.

Corresponding author

Correspondence to Anna Palatnik.

Ethics declarations

Ethics approval and consent to participate

This work was done in full alignment with ethical and consent guidelines and was performed in accordance with the Declaration of Helsinki. The study was approved by the Medical College of Wisconsin’s Institutional Review Board.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This research was previously presented on February 5th, 2020 at the Society for Maternal Fetal Medicine 40th Annual Pregnancy Meeting in Grapevine, Texas.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harrison, R.K., Saravanan, V., Davitt, C. et al. Antenatal maternal hypoglycemia in women with gestational diabetes mellitus and neonatal outcomes. J Perinatol 42, 1091–1096 (2022). https://doi.org/10.1038/s41372-022-01350-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-022-01350-4

Search

Advanced search

Quick links