Risks of congenital malformations and perinatal events among infants exposed to calcium channel and beta‐blockers during pregnancy

Abstract

Purpose Calcium channel blockers and beta-blockers are widely used during pregnancy, but data on their safety for the developing infant is scarce. We used population-based data from 5 HMOs to study risks for perinatal complications and congenital defects among infants exposed in-utero. Methods We studied women older than 15 years delivering an infant between 1/1/96 to 12/31/00, who had been continuously enrolled with prescription drug coverage for >= one year prior to delivery. Information on prescription drug dispensings, inpatient and outpatient diagnoses and procedures was obtained from automated databases at each HMO. Results There were 584 full-term infants exposed during pregnancy to beta-blockers and 804 full-term infants exposed to calcium-channel blockers, and over 75,000 unexposed mother-infant pairs with >= 30 days follow-up. Infants exposed to beta-blockers in the third trimester of pregnancy had over three-fold increased risk for hypoglycemia (RR 3.1; 95% CI 2.2, 4.2) and an approximately two-fold increased risk for feeding problems (RR 1.8; 95% CI 1.3, 2.5). Infants exposed to calcium-channel blockers in the third trimester had an increased risk for seizures (RR 3.6 95% CI 1.3, 10.4). Chart review confirmed the majority of the exposed seizure and hypoglycemia cases. There were no increased risks for congenital anomalies among either group of infants, except for the category of upper alimentary tract anomalies; this increased risk was based on only two exposed cases. Conclusions Infants whose mothers receive beta-blockers are at increased risk for neonatal hypoglycemia, while those whose mothers take calcium-channel blockers are at increased risk for neonatal seizures.

Late Pregnancy β Blocker Exposure and Risks of Neonatal Hypoglycemia and Bradycardia

“…25 Although data from RCTs on the risk of neonatal hypoglycemia associated with β blockers is inconclusive, with a wide CI in the pooled estimate (RR, 0.81; 95% CI, 0.44-1.49) and unclear exposure status for the participant around the time of delivery, 25 a recent observational study reported a threefold increased risk in association with third-trimester exposure (RR, 3.1; 95% CI, 2.2-4.2). 11 These findings have physiologic plausibility, because β blockers are known to cross the placenta and have the potential to cause sympathetic blockade in exposed infants.…”

“…10 Although generally considered safe for use in pregnancy, β blockers can cross the placenta and have the potential to cause physiologic changes in neonates exposed in utero. 11 Sympathetic blockade in the exposed neonates leads to 2 potential risks after delivery, neonatal hypoglycemia and neonatal bradycardia, and previous studies have suggested an association between late pregnancy β blocker exposure and these outcomes. 7,11 The magnitude of these risks and how they may vary as a function of type of β blocker remain poorly defined.…”

“…11 Sympathetic blockade in the exposed neonates leads to 2 potential risks after delivery, neonatal hypoglycemia and neonatal bradycardia, and previous studies have suggested an association between late pregnancy β blocker exposure and these outcomes. 7,11 The magnitude of these risks and how they may vary as a function of type of β blocker remain poorly defined. In particular, there are very few data on whether these risks extend to the combined α-β blocker labetalol.…”

“…12 Understanding these risks is important because both of these outcomes, particularly prolonged neonatal hypoglycemia, have been tied to adverse fetal outcomes, including neurologic injury. 11,13,14 If these drugs confer excess risk for these outcomes, neonates exposed in utero may benefit from more intensive monitoring after delivery.…”

Hypertension in Pregnancy: Natural History and Treatment Options

“…However, the use of intravenous labetalol close to delivery has been associated with a few cases of neonatal bradycardia, hypotonia, respiratory distress, hypoglycaemia, circulatory collapse and feeding problems [110,111]. For severe hypertension, intravenous labetalol has been observed to produce less maternal symptoms such as hypotension, palpitations and tachycardia than intravenous hydralazine but is more associated with foetal bradycardia [112,113].…”