Neonatal side effects of maternal labetalol treatment in severe preeclampsia Karst Y. Heida a , Gerda G. Zeeman a , Teelkien R. Van Veen a , Christian V. Hulzebos b, ⁎ a Department of Obstetrics and Gynecology, University Medical Center Groningen, The Netherlands b Department of Neonatology, University Medical Center Groningen, The Netherlands abstract article info Article history: Received 14 March 2011 Received in revised form 7 November 2011 Accepted 17 December 2011 Keywords: Labetalol Hypotension Bradycardia Hypoglycemia Patent ductus arteriosus (PDA) Objective: Labetalol is often used in severe preeclampsia (PE). Hypotension, bradycardia and hypoglycemia are feared neonatal side effects, but may also occur in (preterm) infants regardless of labetalol exposure. We analyzed the possible association between intrauterine labetalol exposure and such side effects. Study design: From 1 January 2003 through 31 March 2008, all infants from mothers suffering severe PE admitted to one tertiary care center were included. Severe PE was defined according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria. Infants exposed to labetalol in utero (labetalol infants) were compared with infants, who were not exposed to labetalol (controls). Neonatal records were reviewed for hypotension (RR b mean gestational age in weeks), bradycardia (heartrate b 100/ min) and hypoglycaemia (glucose b 2.7 mmol/L) in the first 48 postnatal hours. Results: Of 109 infants, 55 had been exposed to labetalol, whereas 54 were not (controls). Gestational age at delivery and birthweight were similar in both groups (31.8 vs. 32.8 weeks (p = 0.06) and 1510 vs. 1639 grams (p=0.25), respectively for the labetalol vs. control group). Hypotension occurred significantly more in conjunction with labetalol exposure (16, (29.1%) vs. 4 (7.4%); p = 0.003), irrespective of the route of administra- tion. Patent ductus arteriosus (PDA) was present in 9 (56%) of hypotensive labetalol infants compared to 1 (24%) infant in the hypotensive control group (NS). In a multivariate regression model, labetalol exposure, the need for intubation and PDA appeared independently associated with hypotension (P b 0.001). Hypoglycemia occurred in 26 (47.3%) of labetalol infants and in 23 (42.6%) of control infants (p = 0.62). Bradycardia occurred in 4 (7.3%) of labetalol infants and in 1 (1.9%) of control infants (p = 0.18). Hypoglycemia was more common in premature infants (n = 45 (48,9%) vs. n = 4 (23.5%), p = 0.05) in both labetalol and control infants. Conclusion: Hypotension is more common after maternal labetalol exposure, regardless of the dosage and route of administration. The need for intubation and the presence of a PDA also play a role. Hypoglycemia is a very common finding in this population and is merely related to prematurity and independent of labetalol exposure as was the incidental occurrence of bradycardia. These findings on the neonatal side effects of maternal labetalol treatment in preeclampsia underline the importance of frequent blood glucose and blood pressure measurements in the first days of life, especially in intubated preterm infants with a PDA. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Hypertensive disorders represent the most common medical compli- cation during pregnancy, affecting 3 to 10% of gestations, depending on the population and definitions used [1]. In women with severe preeclampsia perinatal neonatal as well as maternal mortality and morbidity are substantially increased. For neonates, the risk of death and morbidity, including fetal growth restriction, depends mainly on gestational age at onset of preeclampsia as well as on gestational age at delivery and the severity of the disease process [2]. Prolongation of a preeclamptic pregnancy may, depending on the gestational age and anticipated risk to the mother, be favorable for the fetus. Antihypertensive drugs are commonly used for the acute management of hypertensive episodes in preeclampsia and, in general, are considered safe and effective. However, significant maternal and neonatal side effects have been described for such drugs [3,4]. Labetalol, a non-selective β and α1 antagonist, is often favored in the Netherlands and is also worldwide one of the most commonly administered drugs for both long-term treatment as well as the acute management of severe maternal hypertension in preeclampsia [5,6]. Because labetalol has not been associated with clinically signifi- cant β-blockade, it is, considered a safe drug in term pregnancies [7,8]. However, β-blockers have been associated with severe symptoms of β-adrenergic blockade in neonates, especially in preterm infants, such as hypotension, bradycardia and hypoglycemia, as described in several case reports [9–14]. However, such symptoms may also occur in preterm and small for gestational age infants’ regardless of labetalol exposure [15,16]. It has been suggested that labetalol may interfere with catecholamine-mediated circulatory responses and Early Human Development 88 (2012) 503–507 ⁎ Corresponding author at: Department of Pediatrics, Division of Neonatology, Beatrix Children's Hospital, University Medical Center Groningen, Hanzeplein 1, CA 51, 9700 RB Groningen, The Netherlands. E-mail address: c.v.hulzebos@umcg.nl (C.V. Hulzebos). 0378-3782/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.earlhumdev.2011.12.012 Contents lists available at SciVerse ScienceDirect Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev