Beta2-agonists use during pregnancy and perinatal outcomes: a systematic review

Respir Med. 2014 Jan;108(1):9-33. doi: 10.1016/j.rmed.2013.07.009. Epub 2013 Dec 17.


Background: Short and long-acting beta2-agonists (SABA and LABA) have a crucial role in asthma management during pregnancy, as stated in the current guidelines.

Objective: To systematically review the evidence on beta2-agonists use during pregnancy and adverse perinatal outcomes.

Data sources and study selection: Six databases were searched before January 1, 2013 for beta2-agonists use during pregnancy and congenital malformations, small for gestational age, mean and low birth weight, gestational age and preterm delivery. Original English language articles were included with no cut-off date. Quality assessment and post-hoc power calculations were performed.

Results: Twenty-one original studies were identified. Four studies reported a significant increased risk of congenital malformations with SABA, while one study reported a significant decreased risk with high doses of SABA. One study reported a significant increased risk of congenital malformations with LABA and four studies reported a significant increased risk of congenital malformations with beta2-agonists (SABA and/or LABA). One study reported a decrease in birth weight centiles among LABA users.

Limitations: All studies reporting significant results, except two, used non-asthmatic women as reference group, making it difficult to differentiate between the effect of the disease from the one of the beta2-agonists. Non-significant results should be interpreted with caution due to the low statistical power of several studies.

Conclusion: Methodological limitations and lack of power of several studies prevent us to conclude on the perinatal safety of beta2-agonists. Until further evidence is available, physicians should continue prescribing them as recommended in the guidelines whenever needed to attain asthma control.

Keywords: Asthma; Beta-2-agonists; Birth weight; Congenital defects; Gestational age; Pregnancy.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Drug Therapy, Combination
  • Evidence-Based Medicine
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use*
  • Humans
  • Pregnancy
  • Pregnancy Complications
  • Treatment Outcome


  • Adrenergic beta-2 Receptor Agonists
  • Anti-Asthmatic Agents
  • Glucocorticoids