Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden

Abstract

Background: Group B streptococcus (GBS) colonisation during pregnancy can lead to invasive GBS disease (iGBS) in infants, including meningitis or sepsis, with a high mortality risk. Other outcomes include stillbirths, maternal infections, and prematurity. There are data gaps, notably regarding neurodevelopmental impairment (NDI), especially after iGBS sepsis, which have limited previous global estimates. In this study, we aimed to address this gap using newly available multicountry datasets.

Methods: We collated and meta-analysed summary data, primarily identified in a series of systematic reviews published in 2017 but also from recent studies on NDI and stillbirths, using Bayesian hierarchical models, and estimated the burden for 183 countries in 2020 regarding: maternal GBS colonisation, iGBS cases and deaths in infants younger than 3 months, children surviving iGBS affected by NDI, and maternal iGBS cases. We analysed the proportion of stillbirths with GBS and applied this to the UN-estimated stillbirth risk per country. Excess preterm births associated with maternal GBS colonisation were calculated using meta-analysis and national preterm birth rates.

Findings: Data from the seven systematic reviews, published in 2017, that informed the previous burden estimation (a total of 515 data points) were combined with new data (17 data points) from large multicountry studies on neurodevelopmental impairment (two studies) and stillbirths (one study). A posterior median of 19·7 million (95% posterior interval 17·9-21·9) pregnant women were estimated to have rectovaginal colonisation with GBS in 2020. 231 800 (114 100-455 000) early-onset and 162 200 (70 200-394 400) late-onset infant iGBS cases were estimated to have occurred. In an analysis assuming a higher case fatality rate in the absence of a skilled birth attendant, 91 900 (44 800-187 800) iGBS infant deaths were estimated; in an analysis without this assumption, 58 300 (26 500-125 800) infant deaths from iGBS were estimated. 37 100 children who recovered from iGBS (14 600-96 200) were predicted to develop moderate or severe NDI. 40 500 (21 500-66 200) maternal iGBS cases and 46 200 (20 300-111 300) GBS stillbirths were predicted in 2020. GBS colonisation was also estimated to be potentially associated with considerable numbers of preterm births.

Interpretation: Our analysis provides a comprehensive assessment of the pregnancy-related GBS burden. The Bayesian approach enabled coherent propagation of uncertainty, which is considerable, notably regarding GBS-associated preterm births. Our findings on both the acute and long-term consequences of iGBS have public health implications for understanding the value of investment in maternal GBS immunisation and other preventive strategies.

Funding: Bill & Melinda Gates Foundation.

Figure 1

Overview of GBS colonisation in pregnancy and relevant outcomes During pregnancy, GBS can cause stillbirths, be associated with prematurity, and lead to maternal infection or, more rarely, death. Some newborn babies born to mothers who are GBS colonised develop invasive disease during the first week of life. Infants can also develop GBS disease between days 7 and 89. The fatality risk is high, and depends on adequate access to care. Of those children who survive the acute episode, some will be diagnosed with neurodevelopmental impairment. Neurodevelopmental impairment risks after GBS meningitis and GBS sepsis differ and were modelled separately. This figure was adapted from a study by Lawn and colleagues, with permission. GBS=group B streptococcus.

Figure 2

Global burden of outcomes related to GBS in pregnancy and infancy (A) Number of pregnant women who were GBS colonised by Sustainable Development Goal regions. The height of the orange bars represents the median, and 2·5–97·5%, 25–70%, and 40–60% percentile intervals are presented by error bars with different widths. The blue bars correspond to the total number of births in each region. (B) Estimated global burden of GBS cases, deaths, and NDIs. In the top panel, global numbers (posterior median and 95% percentile interval) of patients with iGBS (maternal, EOGBS, and LOGBS) are shown. The bottom left plot presents the number of children estimated to develop moderate and severe NDI after iGBS in 2020; and the bottom right panel shows the estimated numbers of stillbirths and deaths in infants with iGBS in 2020. In the top panel, EOGBS (2) corresponds to estimates that included both direct and indirect data on incidence; and in the bottom right panel, deaths (2) corresponds to the sensitivity analysis that did not assume a higher mortality in EOGBS cases in the absence of skilled birth attendance. EOGBS=early-onset iGBS. GBS=group B streptococcus. iGBS=invasive GBS. LOGBS=late-onset iGBS. NDI=neurodevelopmental impairment.

Figure 3

Region-specific relative distribution of GBS burden (A) Cases of EOGBS and LOGBS as well as maternal iGBS. (B) Deaths during EOGBS or LOGBS and stillbirths. The map is coloured showing Sustainable Development Goal regions. The areas of the pie charts are proportional to region-specific numbers. The pie charts present the proportions of cases in different regions that affect babies and women. Posterior medians were used for each of the outcomes; uncertainty in the proportions is therefore not presented. EOGBS=early-onset iGBS. GBS=group B streptococcus. iGBS=invasive GBS. LOGBS=late-onset iGBS.