Abstract: We included two RCTs, that randomised 514 pregnant women (347 women analysed) at a mean gestational age of 22 weeks. Both trials were conducted in the outpatient department of the same two hospitals in the USA between 1993 and 2001, and had a follow-up of 14 days. One of the trials was sponsored by a drug company. We considered both trials to be at a high risk of bias. One trial compared ceftriaxone (125 mg, intramuscular) with cefixime (400 mg, oral); the other trial had three arms, and assessed ceftriaxone (250 mg, intramuscular) versus either amoxicillin (3 g, oral) plus probenecid (1 g, oral) or spectinomycin (2 g, intramuscular). We did not include the spectinomycin data because this medication is no longer produced. We were unable to conduct meta-analysis because the trials compared different medications. We found inconclusive evidence that there were clear differences in the cure of gonococcal infections (genital, extragenital, or both) between intramuscular ceftriaxone versus oral amoxicillin plus oral probenecid (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.98 to 1.16; one RCT; 168 women; very low-quality evidence) or intramuscular ceftriaxone versus oral cefixime (RR 0.99, 95% CI 0.91 to 1.08; one RCT; 95 women; very low-quality evidence). Neither of the trials reported on two of this review's primary maternal outcomes: incidence of obstetric complications (miscarriage, premature rupture of membranes, preterm delivery, or fetal death), or disseminated gonococcal infection, or on the incidence of neonatorum ophthalmia in the neonates. One trial reported one case of vomiting in the oral amoxacillin plus probenecid group. Trials reported pain at the injection sites, but did not quantify it. Hyperberbilurrubinemia was more frequent in neonates whose mothers were exposed to ceftriaxone. There were no clear differences between groups for neonatal malformation. This Cochrane Review found high levels of cure of gonococcal infections in pregnancy with the given antibiotic regimens. However, the evidence in this review is inconclusive as it does not support one particular regimen over another. This conclusion was based on very low-quality evidence (downgraded for poor trial design, imprecision) from two trials (involving 514 women), which we assessed to be at a high risk of bias for a number of domains. The harm profiles of the antibiotic regimes featured in this review remain unknown. High-quality RCTs are needed, with sufficient power to assess the clinical effectiveness and potential harms of antibiotics in pregnant women with gonorrhoea. These should be planned according to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT),conducted following CONSORT recommendations, and based on Patient-Centered Outcomes Research Institute (PCORI) outcomes.

Plain-language summary: We searched for evidence in April 2017 and found two randomised controlled trials, conducted in outpatient departments of the same two hospitals in the USA, between 1993 and 2001. One trial was sponsored by a drug company. The trials randomised a total of 514 pregnant women (347 women analysed), at an average gestational age of 22 weeks. Both trials had a follow-up of 14 days. We were unable to pool the results because the trials used different comparisons. One trial compared ceftriaxone (125 mg, intramuscular) with cefixime (400 mg, oral), and the other trial assessed a higher dose of ceftriaxone (250 mg, intramuscular) versus either amoxicillin (3 g, oral) plus probenecid (1 g, oral) or spectinomycin (2 g, intramuscular). We did not include data from the spectinomycin group because this medication is no longer produced. We found no clear difference in the rate of cure of gonococcal infection (both genital and unrelated to the genital organs) for the different treatment groups, which was in the order of 89% to 96% (very low-quality evidence). Trials did not report on the incidence of obstetric complications, disseminated gonococcal infection in the mother, or ophthalmia neonatorum in the baby. They provided little information on side effects of the antibiotic regimens. One trial reported one case of vomiting in the oral amoxacillin plus probenecid group. Trials reported pain at the injection sites, but did not report numbers or severity. Hyperberbilurrubinemia (where the baby has too much bilirubin in the blood) was more frequent in newborns whose mothers were exposed to ceftriaxone. There was no clear difference between groups for neonatal malformation. We found high levels of cure of gonococcal infection in pregnancy with the given antibiotic regimens, but here was not enough evidence to support one particular regimen over another. Despite high levels of cure, our confidence in the results of this review is very low because both included trials were small, did not blind women to which treatment they received, and had a high number of withdrawals (28% and 41%), meaning they were at high risk of bias. Therefore, there is a need for high-quality trials to be conducted to assess the clinical effectiveness and potential harms of antibiotics for treating gonorrhoea in pregnancy women.