We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 November 2013), CENTRAL (The Cochrane Library 2013, Issue 11),Embase (1988 to November 2013), MEDLINE (PubMed 1970 to November 2013), LILACS (1982 to November 2013), the WHO International Clinical Trials Registry Platform (ICTRP) (November 2013) and reference lists of retrieved studies.
SELECTION CRITERIA: Two review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted data. Data were checked for accuracy.
MAIN RESULTS: We included 14 studies (in 18 trial reports), involving 1047 pregnant women at risk of
preterm birth with 1077 newborns. However, three of the included studies did not report on this review's outcomes of interest. We carried out two main comparisons:
ambroxol versus antenatal
corticosteroids (
betamethasone); and
ambroxol versus placebo or no treatment. Seven RCTs provided data for our comparison of
ambroxol versus
corticosteroid (
betamethasone) and two trials contributed data to our comparison of
ambroxol compared to placebo or no treatment.The included studies were generally judged as having either 'low' risk of bias or 'unclear' risk of bias (because the trial reports provided insufficient details about methods of sequence generation, allocation concealment and blinding). Primary outcomesThere was no clear evidence of a difference in the incidence of RDS among newborns born to women who received
ambroxol when compared to newborns of women who were given the
corticosteroid,
betamethasone (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.59 to 1.07, seven RCTs, 728 women/758 newborns, moderate quality evidence) or placebo/no treatment (average RR 0.74; 95% CI 0.46 to 1.20, two studies, 204 women/204 newborns,T2= 0.07; I(2)= 53%, low-quality evidence). Results were imprecise and consistent with appreciable benefit as well as negligible effect.Similarly, there was no clear evidence of a difference in the rates of perinatal mortality between the group of women who received
ambroxol and women in the
corticosteroid (
betamethasone) group (RR 0.51, 95% CI 0.23 to 1.12, six studies, 648 women/657 newborns, moderate quality evidence) or the placebo/no treatment group (RR 0.61; 95% CI 0.19 to 1.98, one study, 116 women/116 newborns, low-quality evidence).In terms of maternal adverse effects, there was no clear differences (in
nausea or
vomiting) between those women who received
ambroxol compared to either those women who received
corticosteroids (
betamethasone) (average RR 3.45; 95% CI 0.34 to 35.51, three studies, 305 women, T(2)= 2.82; I(2)= 67%, very low-quality evidence), or women who received placebo or no treatment (RR 1.79; 95% CI 0.45 to 7.13, one study, 116 women, low-quality evidence). No other adverse effects (e.g. diarrhoea, gastric irritation and
headache) were reported in the included studies. Secondary outcomesFor the review's secondary outcomes, none of the included studies reported on the incidence of
bronchopulmonary dysplasia, periventricular haemorrhage, necrotising
enterocolitis or rate of maternal mortality.One small trial (involving 88 women) comparing
ambroxol with placebo or no treatment, reported no difference between groups in terms of the need for
mechanical ventilation in the neonate (RR 0.94; 95% CI 0.73 to 1.21, 88 women/88 babies, low-quality evidence) or the administration of
pulmonary surfactant (RR 1.19; 95% CI 0.61 to 2.30, one RCT, 88 women/88 babies, low-quality evidence).
AUTHORS' CONCLUSIONS: