Incidence and risk factors of neonatal hypoglycemia after ritodrine therapy in premature labor: a retrospective cohort study

Abstract

Background Ritodrine hydrochloride (RD), a β2-adrenergic agonist, is widely used as a tocolytic medication to suppress premature labor, but can cause neonatal hypoglycemia, a potentially severe side effect. We examined the incidence and risk factors of neonatal hypoglycemia following maternal intravenous administration of RD. Methods This was a retrospective study of neonates, who had birth weight of ≥2000 g and were delivered at 36 weeks gestation or later in Kanazawa University Hospital from August 2013 to July 2016. We defined neonatal hypoglycemia as blood glucose level < 50 mg/dL. Neonates who were delivered without maternal intravenous RD or who were delivered 8 days or more after stopping maternal RD or who received oral RD were defined as the RD non-administration group, while those delivered within 7 days after stopping maternal RD were defined as the RD intravenous administration group. We examined the incidence and risk factors of RD-induced neonatal hypoglycemia by comparing these two groups. Results We enrolled 603 neonates in this study; 504 (83.6%) showed no neonatal hypoglycemia, while 99 (16.4%) exhibited neonatal hypoglycemia. The incidence of neonatal hypoglycemia was significantly higher (61.7%; 58/94) in the RD intravenous administration group than in the RD non-administration group (8.1%; 41/509) ( p < 0.001). Binomial logistic regression analysis in the RD intravenous administration group showed that maternal age over 35 years (AOR: 3.385; 95% CI, 1.082–10.588, p = 0.036) and the interval to delivery from stopping intravenous administration of RD (AOR: 0.974; 95% CI, 0.953–0.996, p = 0.020) were independent factors associated with neonatal hypoglycemia. The cut-off value of the interval to predict the incidence of neonatal hypoglycemia was about 6 h (sensitivity 82.8%, specificity 63.9%). Conclusions The incidence of neonatal hypoglycemia was significantly increased by maternal intravenous administration of RD. We newly identified maternal age (over 35 years) and the interval to delivery from stopping intravenous administration of RD (within 6 h) as independent risk factors for neonatal hypoglycemia following maternal intravenous administration of RD. In cases with these risk factors, careful blood glucose monitoring is recommended for early detection and treatment of neonatal hypoglycemia.

The Role of Early Pregnancy Maternal pGCD59 Levels in Predicting Neonatal Hypoglycemia—Subanalysis of the DALI Study

“…Doctor et al (29) found that SGA infants are 5 times more likely to develop hypoglycemia compared to AGA infants. The link between low birth weight and infant hypoglycemia has been confirmed in other studies as well (30)(31)(32). This is most likely due to decreased energy deposits and perinatal compromise.…”

Development of a prediction model for neonatal hypoglycemia risk factors: a retrospective study

“…Belonging to the class of drugs known as β2-adrenergic receptor agonists, ritodrine’s primary mechanism of action is to stimulate β2-receptors on smooth muscles in the uterus, leading to relaxation and reduced contractions. However, its use has been linked to an increased risk of neonatal hypoglycemia due to its ability to inhibit insulin secretion from pancreatic beta cells, which may result in decreased glucose uptake by tissues ( 32 , 33 ). Therefore, when considering the use of ritodrine during labor and delivery, it is critical to weigh its potential risks against benefits and make informed clinical decisions.…”

Drug-Induced Hypoglycemia in Neonates Born to Nondiabetic Women Treated with Medications during the Pregnancy or the Labor: A Systematic Review of the Literature

“…71 The time interval to predict the incidence of neonatal hypoglycemia was approximately 6 hours after delivery (sensitivity 82.8%, specificity 63.9%). 68 Sustained hypoglycemia has not been observed in babies delivered 5 or more days after the end of tocolytic therapy. 71 In one case, hypoglycemia was severe and recurrent.…”

“…67 The prevalence of hypoglycemia was 41.4 to 61.7% in newborns exposed to ritodrine alone, 42.9% in the ones exposed to both MgSo4 and ritodrine, and 8.2 to 22.2% in nonexposed controls. 67,68 No patient had hypoglycemia in a case series of neonates exposed to salbutamol or terbutaline. 69 Risk factors and potential confounders: a multivariable logistic regression analysis using the "Hypoglycemia set" listed among the independent risk factors for hypoglycemia cesarean section, SGA infants, and delivery to a mother treated with ritodrine alone or in combination with MgSO4.…”