The timing of initiation of pharmacotherapy for women with gestational diabetes mellitus

Harrison et al. BMC Pregnancy and Childbirth https://doi.org/10.1186/s12884-020-03449-y (2020) 20:773 RESEARCH ARTICLE Open Access The timing of initiation of pharmacotherapy for women with gestational diabetes mellitus Rachel K. Harrison1* , Meredith Cruz1, Ashley Wong2, Caroline Davitt2 and Anna Palatnik1,3 Abstract Background: The decision to initiate pharmacotherapy is integral in the care for pregnant women with gestational diabetes mellitus (GDM). We sought to compare pregnancy outcomes between two threshold percentages of elevated glucose values prior to initiation of pharmacotherapy for GDM. We hypothesized that a lower threshold at pharmacotherapy initiation will be associated with lower rates of adverse perinatal outcomes. Methods: This was a retrospective cohort study of women with GDM delivering in a single tertiary care center. Pregnancy outcomes were compared using bivariable and multivariable analyses between women who started pharmacotherapy (insulin or oral hypoglycemic agent) after a failed trial of dietary modifications at two different ranges of elevated capillary blood glucose (CBG) values: Group 1 when 20–39% CBG values were above goal; Group 2 when ≥40% CBG values were above goal. The primary outcome was a composite GDM-associated neonatal adverse outcome that included: macrosomia, large for gestational age (LGA), shoulder dystocia, hypoglycemia, hyperbilirubinemia requiring phototherapy, respiratory distress syndrome, stillbirth, and neonatal demise. Secondary outcomes included cesarean delivery, preterm birth (< 37 weeks), neonatal intensive care unit (NICU) admission, and small for gestational age (SGA). Results: A total of 417 women were included in the study. In univariable analysis, the composite neonatal outcome was statistically significantly higher in Group 2 compared to Group 1 (47.9% vs. 31.4%, p = 0.001). In addition, rates of preterm birth (15.7% vs 7.4%, p = 0.011), NICU admission (11.7% vs 4.0%, p = 0.006), and LGA (21.2% vs 9.1% p = 0.001) were higher in Group 2. In contrast, higher rates of SGA were noted in Group 1 (8.0% vs. 2.9%, p = 0.019). There was no difference in cesarean section rates. These findings persisted in multivariable analysis after adjusting for confounding factors (composite neonatal outcome aOR = 0.50, 95%CI [0.31–0.78]). Conclusions: Initiation of pharmacotherapy for GDM when 20–39% of CBG values are above goal, compared to ≥40%, was associated with decreased rates of adverse neonatal outcomes attributable to GDM. This was accompanied by higher rates of SGA among women receiving pharmacotherapy at the lower threshold. Additional studies are required to identify the optimal threshold of abnormal CBG values to initiate pharmacotherapy for GDM. Keywords: Gestational diabetes mellitus, Pharmacotherapy, Glycemic threshold, Insulin, Oral hypoglycemic agent * Correspondence: 1 Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Medical College of Wisconsin, 9200 W. Wisconsin Ave, Milwaukee, WI 53226, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Harrison et al. BMC Pregnancy and Childbirth (2020) 20:773 Background Gestational diabetes mellitus (GDM) is characterized by abnormal glucose tolerance and is a product of heightened insulin resistance in pregnancy [1, 2]. High-quality evidence has long demonstrated the association of GDM and resulting maternal hyperglycemia with adverse perinatal outcomes [1–8]. Monitoring and treating GDM reduces these adverse outcomes [1–9]. Notably, the extent of treatment needed is based upon the woman’s glycemic response to diet and exercise alone, with nearly 90% of women failing an initial trial of prescribed diet and exercise [2]. However, the definition of what constitutes an unsuccessful attempt at diet and exercise has not yet been established. No randomized controlled trials — or, in fact, any prospective or retrospective studies — have evaluated the optimal glycemic threshold for initiation of pharmacotherapy, in addition to diet and exercise. It is likely that each provider caring for women with GDM decides individually what proportion of elevated capillary blood glucose (CBG) values merits initiation of pharmacotherapy and how rigorously these CBG values should be controlled [2]. The need to solve this clinical question is further elucidated after review of society recommendations, including those of the American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) [1, 9]. In effect, there is no clear consensus on how to manage the initiation and adjustment of pharmacotherapy for GDM. ACOG states that “...treatment is recommended when target glucose levels cannot be consistently achieved through nutrition therapy and exercise” [1]. ACOG further states that there is “no conclusive evidence for a specific threshold value at which medical therapy should be started” [1, 10]. The ADA is similarly vague regarding recommendations for initiating and titrating pharmacotherapy for GDM including statements such as: “there are no adequately powered randomized trials comparing different fasting and post-meal glycemic targets in diabetes in pregnancy” [9]. In light of this identified gap of knowledge and lack of consensus, we designed a retrospective cohort study to compare two different thresholds for pharmacotherapy initiation in women with GDM. We hypothesized that a lower threshold for pharmacotherapy initiation will be associated with improved perinatal outcomes and will not be associated with higher rates of complications. Methods This was a retrospective chart review of women with GDM that were started on pharmacotherapy during pregnancy between 2011 and 2019 at a single academic center. Institutional review board approval was obtained and maternal and neonatal chart review was performed to extract all data perti (...truncated)