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

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

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.

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.

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.

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.