Abstract: The review included eight randomised controlled trials. Approximately 4300 women were recruited to detect the effect of prophylactic antibiotic administration on pregnancy outcomes. Primary outcomes Antibiotic prophylaxis did not reduce the risk of preterm prelabour rupture of membranes (risk ratio (RR) 0.31; 95% confidence interval (CI) 0.06 to 1.49 (one trial, 229 women), low quality evidence) or preterm delivery (RR 0.88; 95% CI 0.72 to 1.09 (six trials, 3663 women), highquality evidence). However, preterm delivery was reduced in the subgroup of pregnant women with a previous preterm birth who had bacterial vaginosis (BV) during the current pregnancy (RR 0.64; 95% CI 0.47 to 0.88 (one trial, 258 women)), but there was no reduction in the subgroup of pregnant women with previous preterm birth without BV during the pregnancy (RR 1.08; 95% CI 0.66 to 1.77 (two trials, 500 women)). A reduction in the risk of postpartum endometritis (RR 0.55; 95% CI 0.33 to 0.92 (one trial, 196 women)) was observed in high-risk pregnant women (women with a history of preterm birth, low birthweight, stillbirth or early perinatal death) and in all women (RR 0.53; 95% CI 0.35 to 0.82 (three trials, 627 women), moderate quality evidence). There was no difference in low birthweight (RR 0.86; 95% CI 0.53 to 1.39 (four trials; 978 women)) or neonatal sepsis (RR 11.31; 95% CI 0.64 to 200.79) (one trial, 142 women)); and blood culture confirming sepsis was not reported in any of the studies. Secondary outcomes Antibiotic prophylaxis reduced the risk of prelabour rupture of membranes (RR 0.34; 95% CI 0.15 to 0.78 (one trial, 229 women), low quality evidence) and gonococcal infection (RR 0.35; 95% CI 0.13 to 0.94 (one trial, 204 women)). There were no differences observed in other secondary outcomes (congenital abnormality; small-for-gestational age; perinatal mortality), whilst many other secondary outcomes (e.g. intrapartum fever needing treatment with antibiotics) were not reported in included trials. Regarding the route of antibiotic administration, vaginal antibiotic prophylaxis during pregnancy did not prevent infectious pregnancy outcomes. The overall risk of bias was low, except that incomplete outcome data produced high risk of bias in some studies. The quality of the evidence using GRADE was assessed as low for preterm prelabour rupture of membranes, high for preterm delivery, moderate for postpartum endometritis, low for prelabour rupture of membranes, and very low for chorioamnionitis. Intrapartum fever needing treatment with antibiotics was not reported in any of the included studies. Antibiotic prophylaxis did not reduce the risk of preterm prelabour rupture of membranes or preterm delivery (apart from in the subgroup of women with a previous preterm birth who had bacterial vaginosis). Antibiotic prophylaxis given during the second or third trimester of pregnancy reduced the risk of postpartum endometritis, term pregnancy with pre-labour rupture of membranes and gonococcal infection when given routinely to all pregnant women. Substantial bias possibly exists in the review's results because of a high rate of loss to follow-up and the small numbers of studies included in each of our analyses. There is also insufficient evidence on possible harmful effects on the baby. Therefore, we conclude that there is not enough evidence to support the use of routine antibiotics during pregnancy to prevent infectious adverse effects on pregnancy outcomes.

Plain-language summary: Antibiotics are administered to pregnant women during the second and third trimester of pregnancy (before labour) to prevent bacteria in the vagina and cervix affecting the pregnancy. Infection by some infectious organisms in a woman’s genital tract can cause health problems for the mother and her baby, and has been associated with preterm births. This review of eight randomised trials involved approximately 4300 women in their second or third trimester. We found that antibiotics did not reduce the risk of preterm prelabour rupture of the membranes (one trial, low quality of evidence), or the risk of preterm birth (six trials, highquality of evidence). Preterm delivery was reduced in pregnant women who had a previous preterm birth and an imbalance of bacteria in the vagina (bacterial vaginosis) during the current pregnancy. There was no reduction in preterm delivery in pregnant women with previous preterm birth without a bacterial imbalance during the current pregnancy (two trials). Postpartum endometritis, or infection of the uterus following birth, was reduced overall (three trials, moderate quality of evidence), as well as in a trial of high-risk women who had a previous preterm birth (one trial, moderate quality of evidence). No reduction in neonatal illness was observed. Outcomes of interest were available in trials with high losses to follow-up. We could not estimate the side effects of antibiotics since side effects were rare; however, antibiotics may still have serious side effects on women and their babies. There is, therefore, no justification to give antibiotics to all pregnant women during the second or third trimester to prevent adverse infectious effects on pregnancy outcomes.