3.2.1 Maternal adverse events
The incidence of overall maternal adverse events in atosiban group and control group were 4.0% and 12.4%, respectively. The incidence of treatment discontinuation due to adverse events was 10 times lower in atosiban group (1.4%) than in control group (14%). The risk of maternal adverse events and the discontinuation of treatment due to adverse events were significantly lower with atosiban compared with controls (RR 0.38, 95% CI [0.23, 0.61], P < 0.0001; RR 0.11, 95% CI [0.04, 0.29], P < 0.00001; respectively). According to the classification of different control groups, the risk of maternal adverse events was significantly lower in patients treated with atosiban compared with beta-agonists and CCBs (RR 0.35, 95% CI [0.19, 0.68], P = 0.002; RR 0.44, 95% CI [0.20, 0.95], P = 0.04; respectively). Additionally, compared to atosiban, beta-agonists had a significantly increased risk of treatment discontinuation due to adverse events (RR 0.07, 95% CI [0.04, 0.14], P < 0.00001) and was significantly different from CCBs (P = 0.001).
For cardiac disorders, the incidence was lower in atosiban group than in control group, except for arrhythmia. Among them, the risk of palpitation, chest pain and tachycardia was significantly lower in patients treated with atosiban compared with controls (RR 0.15, 95% CI [0.08, 0.28], P < 0.00001; RR 0.27, 95% CI [0.16, 0.45], P < 0.00001; RR 0.09, 95% CI [0.06, 0.15], P < 0.00001; respectively). In terms of different types of control group, CCBs significantly increased the risk of palpitation and tachycardia (RR 0.37, 95% CI [0.10, 1.33], P < 0.00001; RR 0.19, 95% CI [0.06, 0.66], P = 0.008; respectively), and beta-agonists significantly increased the risk of chest pain and tachycardia (RR 0.27, 95% CI [0.14, 0.55], P = 0.0003; RR 0.08, 95% CI [0.05, 0.13], P < 0.00001; respectively). In addition, the incidence of chest pain was also significantly higher in the placebo group than in the atosiban group (RR 0.22, 95% CI [0.09, 0.51], P = 0.0004).
As for gastrointestinal disorders, the overall incidence of vomiting was significantly lower in atosiban group (5.0%) than in control group (18.5%) with an RR of 0.28 (95% CI [0.17, 0.46], P < 0.00001), and there was a significant difference between the different controls (P = 0.006). Beta-agonists significantly increased the risk of nausea and vomiting compared to atosiban (RR 0.77, 95% CI [0.59, 0.99], P < 0.00001; RR 0.32, 95% CI [0.24, 0.43], P < 0.00001; respectively). Conversely, according to 1 study, atosiban group had a higher incidence of constipation than beta-agonist group (5.7% vs. 2.9%).
In terms of nervous system disorders, a significant lower incidence of headache and tremor was observed in atosiban group compared to control group (RR 0.51, 95% CI [0.40, 0.64], P < 0.00001; RR 0.10, 95% CI [0.06, 0.19], P < 0.00001; respectively). Beta-agonists significantly increased the risk of headache and tremor compared with atosiban (RR 0.53, 95% CI [0.41, 0.69], P < 0.00001; RR 0.10, 95% CI [0.06, 0.19], P < 0.00001; respectively). Besides, one study showed that the atosiban group had a significant lower incidence of headache compared to placebo (4.9% vs. 13.8%, RR 0.36, 95% CI [0.15, 0.83], P = 0.02).
As for vascular disorders, a significant lower incidence of hypotension was found in atosiban group compared to control group (1.8% vs. 4.7%, RR 0.49, 95% CI [0.29, 0.82], P = 0.007). Both beta-agonists and CCBs significantly increased the risk of hypotension compared with atosiban (RR 0.60, 95% CI [0.36, 0.98], P = 0.04; RR 0.35, 95% CI [0.13, 0.92], P = 0.03; respectively).
For general disorders and administration site conditions, the incidence of injection site reactions was significantly higher in patients administrated with atosiban compared with placebo/no comparator (34.9% vs. 21.1%, RR 1.59, 95% CI [1.37, 1.83], P < 0.00001). Beta-agonists substantially increased the risk of chest tightness compared with atosiban with an RR of 0.18 (95% CI [0.06, 0.59], P = 0.005).
Compared to beta-agonists, patients treated with atosiban had a significantly lower risk of dysponea in respiratory thoracic and mediastinal disorders (RR 0.09, 95% CI [0.04, 4.98], P < 0.00001); hyperglycaemia and hypokalemia in metabolic and nutritional disorders (RR 0.58, 95% CI [0.37, 0.90], P = 0.02; RR 0.14, 95% CI [0.06, 0.30], P < 0.00001; respectively); and anxiety/nervousness in psychiatric disorders (RR 0.34, 95% CI [0.17, 0.70], P = 0.003).
Finally, for skin and subcutaneous tissue disorders, ear and labyrinth disorders, and pregnancy, puerperium and perinatal conditions, we did not find a significant relationship between any drug and the occurrence of adverse events.