b -Blocker treatment during pregnancy and adverse pregnancy outcomes: a nationwide population-based cohort study

Objective: To investigate the association between exposure to b -blockers during pregnancy and the risk of being born small for gestational age (SGA), preterm birth and perinatal mortality in a nationwide cohort. Design: A population-based retrospective cohort study, using the Danish Fertility Database. The authors identified all pregnant women redeeming a prescription for b -blockers using the National Prescription Registry. Multivariate logistic regression models were used to assess the association between exposure and our outcomes. Setting: Register-based survey. Participants: 911’685 births between 1995 and 2008 obtained from the Danish Fertility Database. Outcome measures: Being born SGA was defined as having a birth weight below the 10th percentile for the corresponding gestational week. Preterm birth was defined as birth before the 37th gestational week. Perinatal mortality was defined as either death occurring within the first 28 days of life or stillbirth. Before 2004, fetal deaths were recorded as stillbirths if they occurred after 28 weeks of gestation, but since then stillbirth is recorded for deaths after 22 gestational weeks. Results: The authors identified 2459 pregnancies exposed to b -blockers. b -Blocker exposure during pregnancy was found to be associated with increased risk of SGA (adjusted OR 1.97, 95% CI 1.75 to 2.23), preterm birth (adjusted OR 2.26, 95% CI 2.03 to 2.52) and perinatal mortality (adjusted OR 1.89, 95% CI 1.25 to 2.84). Analyses were adjusted for socioeconomic and maternal variables. The authors found similar risk profiles for pregnancies exposed to labetalol and for pregnancies exposed to other b -blockers. Conclusions: The authors found that exposure to b -blockers during pregnancy was associated with being born SGA, preterm birth and perinatal mortality. Our findings show that labetalol is not safer than other b -blockers during pregnancy.

[1]  S. Bull,et al.  Risks and benefits of beta-receptor blockers for pregnancy hypertension: overview of the randomized trials. , 2000, European journal of obstetrics, gynecology, and reproductive biology.

[2]  Vibeke Jensen,et al.  Danish education registers , 2011, Scandinavian journal of public health.

[3]  B. Sibai,et al.  A comparison of labetalol plus hospitalization versus hospitalization alone in the management of preeclampsia remote from term , 1987, Obstetrics and gynecology.

[4]  W. Künzel,et al.  Impact of fetal growth restriction on mortality and morbidity in a very preterm birth cohort. , 2010, The Journal of pediatrics.

[5]  L. Magee,et al.  Oral beta-blockers for mild to moderate hypertension during pregnancy. , 2003, The Cochrane database of systematic reviews.

[6]  L. Knudsen,et al.  Monitoring perinatal mortality and perinatal care with a national register: content and usage of the Danish Medical Birth Register. , 1986, Community medicine.

[7]  L. de Jong-van den Berg,et al.  Do Pregnant Women Report Use of Dispensed Medications? , 2001, Epidemiology.

[8]  G. Lip,et al.  Atenolol and fetal growth in pregnancies complicated by hypertension. , 1999, American journal of hypertension.

[9]  G. Lip,et al.  Hypertension in pregnancy: pathophysiology and management strategies. , 2007, Current pharmaceutical design.

[10]  A. Bérard,et al.  Antihypertensive medication use during pregnancy and the risk of major congenital malformations or small-for-gestational-age newborns. , 2010, Birth defects research. Part B, Developmental and reproductive toxicology.

[11]  B. Källén,et al.  Maternal use of antihypertensive drugs in early pregnancy and delivery outcome, notably the presence of congenital heart defects in the infants , 2009, European Journal of Clinical Pharmacology.

[12]  P. Mortensen,et al.  The Danish Civil Registration System. A cohort of eight million persons. , 2006, Danish medical bulletin.

[13]  L. Knudsen,et al.  The Danish Fertility Database. , 1998, Danish medical bulletin.

[14]  P. August,et al.  Update on the use of antihypertensive drugs in pregnancy. , 2008, Hypertension.

[15]  Seema Modi,et al.  Medications for migraine prophylaxis. , 2006, American family physician.

[16]  Mikkel Baadsgaard,et al.  Danish registers on personal income and transfer payments , 2011, Scandinavian journal of public health.

[17]  S. Lye,et al.  Understanding Preterm Labor , 2001, Annals of the New York Academy of Sciences.

[18]  D. Henderson-smart,et al.  Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. , 2014, The Cochrane database of systematic reviews.

[19]  B. Sibai Treatment of hypertension in pregnant women. , 1996, The New England journal of medicine.

[20]  D. Churchill,et al.  Pharmacological treatment of hypertension in pregnancy. , 2003, Current pharmaceutical design.

[21]  G. Koren,et al.  The safety of calcium channel blockers in human pregnancy: a prospective, multicenter cohort study. , 1996, American journal of obstetrics and gynecology.

[22]  T. F. Andersen,et al.  The Danish National Hospital Register. A valuable source of data for modern health sciences. , 1999, Danish medical bulletin.

[23]  H. Sørensen,et al.  The Danish prescription registries. , 1997, Danish medical bulletin.