Pneumococcal vaccination during pregnancy for preventing infant infection

Background: Approximately 450,000 children worldwide die of pneumococcal infections each year. The development of bacterial resistance to antimicrobials adds to the difficulty of treatment of diseases and emphasizes the need for a preventive approach. Newborn vaccination schedules could substantially reduce the impact of pneumococcal disease in immunized children, but do not have an effect on the morbidity and mortality of infants less than three months of age. Pneumococcal vaccination during pregnancy may be a way of preventing pneumococcal disease during the first months of life before the pneumococcal vaccine administered to the infant starts to produce protection. Objectives: To assess the effect of pneumococcal vaccination during pregnancy for preventing infant infection. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014) and reference lists of retrieved studies. Selection criteria: Randomized controlled trials in pregnant women comparing pneumococcal vaccine with placebo or doing nothing, or with another vaccine to prevent infant infections. Data collection and analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We contacted study authors for additional information. Main results: Seven trials were included, but only six trials (919 participants) contributed data. There was no evidence that pneumococcal vaccination during pregnancy reduces the risk of neonatal infection (risk ratio (RR) 0.66; 95% confidence interval (CI) 0.30 to 1.46; two trials, 241 pregnancies, low quality evidence). Although the data suggest an effect in reducing pneumococcal colonization in infants by 16 months of age (average RR 0.33; 95% CI 0.11 to 0.98; one trial, 56 pregnancies), there was no evidence of this effect in infants at two to three months of age (average RR 1.13; 95% CI 0.46 to 2.78; two trials, 146 pregnancies, low quality evidence) or by six to seven months of age (average RR 0.67, 95% CI 0.22 to 2.08; two trials, 148 pregnancies, low quality evidence). None of the trials included in this review reported neonatal death as a result of pneumococcal infection. Neonatal antibody levels were reported as geometric mean and 95% CI. There were inconsistent results between studies. Two studies showed significantly higher immunoglobulin G (IgG) levels in cord blood in the pneumococcal vaccine group when compared with the control group for all serotypes. In contrast, another trial showed no difference in neonatal antibody levels between the pneumococcal vaccine group and the control group. Maternal antibody levels were also reported as geometric mean and 95% CI. One study showed significantly higher IgG levels in maternal serum in women immunized with pneumococcal vaccine when compared with control vaccine regardless of any serotypes. Another study showed significantly higher maternal antibody levels only for serotype 14, but no evidence of an effect for other serotypes. The percentage of women with seroprotection was measured in one trial at delivery and at 12 months post-delivery. At delivery, results favored the intervention group for serotype 6 (RR 1.49, 95% CI 1.31 to 1.69), serotype 14 (RR 1.40, 95% CI 1.25 to 1.56) and serotype 19 (RR 2.29, 95% CI 1.89 to 2.76). There were no group differences seen at 12 months post-delivery for serotypes 6 or 14 (RR 1.06, 95% CI 1.00 to 1.12 and RR 1.06, 95% CI 0.98 to 1.15, respectively), but results favored the intervention group for serotype 19 (RR 1.59, 95% CI 1.37 to 1.85). No significant difference for tenderness at the injection site between women who received pneumococcal vaccine and those who received control vaccine (average RR 3.20; 95% CI 0.32 to 31.54; two trials, 130 women). The overall quality of evidence is low for primary outcomes. Most outcomes had wide confidence intervals crossing the line of no effect, and most of the included trials had small numbers of participants and few events which led to downgrading evidence for imprecision of findings. Authors' conclusions: There is insufficient evidence to assess whether pneumococcal vaccination during pregnancy could reduce infant infections.