Increased Incidence of Gestational Diabetes in Women Receiving Prophylactic 17α-Hydroxyprogesterone Caproate for Prevention of Recurrent Preterm Delivery

Abstract

OBJECTIVE -Progesterone has a known diabetogenic effect. We sought to determine whether the incidence of gestational diabetes mellitus (GDM) is altered in women receiving weekly 17␣-hydroxyprogesterone caproate (17P) prophylaxis for the prevention of recurrent preterm birth.RESEARCH DESIGN AND METHODS -Singleton gestations in women having a history of preterm delivery were identified from a database containing prospectively collected information from women receiving outpatient nursing services related to a high-risk pregnancy. Included were patients enrolled for outpatient management at Ͻ27 weeks' gestation with documented pregnancy outcome and delivery at Ͼ28 weeks. Patients with preexisting diabetes were excluded. The incidence of GDM was compared between patients who received prophylactic intramuscular 17P (250-mg weekly injection initiated between 16.0 and 20.9 weeks' gestation) and those who did not.RESULTS -Maternal BMI and age were similar. The incidence of GDM was 12.9% in the 17P group (n ϭ 557) compared with 4.9% in control subjects (n ϭ 1,524, P Ͻ 0.001; odds ratio 2.9 [95% CI 2.1-4.1]).CONCLUSIONS -The use of 17P for the prevention of recurrent preterm delivery is associated with an increased risk of developing GDM. Early GDM screening is appropriate for women receiving 17P prophylaxis. Diabetes Care 30:2277-2280, 2007P reterm birth is the leading cause of perinatal mortality and morbidity for nonanomalous infants in the U.S. where Ͼ12% of infants, ϳ480,000, are born prematurely each year (1). Although past studies of progestational agents for the prevention of preterm delivery reported varied results, there has been renewed interest in the use of 17␣-hydroxyprogesterone caproate (17P) as a secondary preterm birth prevention strategy after a recent study from the National Institute of Child Health and Human 3). This study examined the effectiveness of 17P in reducing the rate of preterm delivery in women with a singleton gestation and a history of prior preterm delivery. 17P was administered via weekly injections initiated between 16 and 20 weeks' gestation and was shown to decrease the incidence of recurrent preterm birth in the study population by 33% (3). Meta-analysis including both older and current studies has provided further support for the use of 17P for preterm birth prevention (4), although the mechanism of action by which 17P prevents preterm birth remains poorly understood.The metabolic changes of normal pregnancy are essential to provide adequate nutrients to the growing fetus. As pregnancy progresses, increased levels of human chorionic sommatomammotropin, cortisol, prolactin, progesterone, and estrogen lead to insulin resistance. Studies in animal models demonstrate that progesterone plays an important role in signaling insulin release and pancreatic function (5). The relatively diabetogenic properties of progesterone, which peak at 32 weeks' gestation, have been described in humans (6). The American Diabetes Association (ADA) recommends screening all women at risk for gestational dia...

Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism

“…Accordingly, it seems especially relevant to evaluate the potential effects of progesterone-based medications on mother and foetus. Considering the diabetogenic effect of progesterone, Rebarber et al (2007) reported that the use of 17a-hydroxyprogesterone caproate (17P), in the micromolar range, by women having a history of preterm delivery, increased the risk of development of GD. Another study involving women of hispanic descent with no previous history of diabetes showed that the use of an injectable progestagen-based contraceptive for long periods of time was associated with an increased risk of developing GD (Xiang et al 2006).…”

“…However, considering that apoptosis is involved in the pathophysiology of type 1 and 2 diabetes and also contributes to the involution of the b-cell mass in the postpartum phase (Scaglia et al 1995), we first proposed the hypothesis that progesterone might be involved in b-cell death, also contribute to the development of gestational diabetes (GD). Both progesterone's diabetogenic effect and its potential to induce b-cell death require attention with the increasing pharmacological use of progestagens throughout pregnancy for prevention of recurrent preterm delivery (Sanchez-Ramos et al 2005, Dodd et al 2008, Jayasooriva & Lamont 2009), which has been correlated to the enhanced incidence of GD (Rebarber et al 2007).…”

246: Maternal characteristics influencing the development of gestational diabetes in obese women receiving 17 alpha-hydroxyprogesterone caproate

“…While in general progesterone is known to exhibit diabetogenic properties, early reports are conflicting as to whether the use of 17OHPC increases a woman's risk for the development of gestational diabetes (GDM) [6][7][8]. These conflicting results may be related to differences in study design or particularly in maternal characteristics of the populations.…”

“…Rebarber et al retrospectively compared 557 patients receiving 17OHPC for preterm labor prophylaxis to 1524 controls who similarly had a history of preterm delivery. The frequency of gestational diabetes in the 17OHPC group was 12.9% versus 4.9% for the controls (OR 2.9 (95% CI 2.1-4.1)) [6]. Interestingly, while overall no differences were observed in the use of maintenance tocolysis, fewer patients in the 17OHPC group received beta agonists for tocolysis (18%) versus no controls (25.1%) ( < 0.002).…”

“…The degree to which administration of 17OHPC contributes to this impairment in glycemic control and detrimentally affects pregnancy remains controversial [6][7][8]. Modest abnormalities in maternal glucose control create increasing risk for adverse pregnancy outcomes including large birth weight, cesarean delivery, and neonatal hypoglycemia [16].…”