Maternal group B Streptococcus decreases infant length and alters the early-life microbiome: a prospective cohort study

Abstract

Background: Maternal colonization with Group B Streptococcus (GBS) disrupts the vaginal microbiota, potentially affecting infant microbiota assembly and growth. While the gut microbiota's importance in infant growth is recognized, the specific effects of maternal GBS on growth remain unclear. This study aimed to explore the effects of maternal vaginal GBS during pregnancy on early infant growth, microbiome, and metabolomics.

Methods: We recruited and classified 453 pregnant women from southern China into GBS or healthy groups based on GBS vaginal colonization. Their infants were categorized as GBS-exposed or GBS-unexposed groups. We comprehensively analyzed infant growth, gut microbiota, and metabolites during early life, along with maternal vaginal microbiota during pregnancy, using 16S rDNA sequencing and targeted metabolomics.

Results: GBS-exposed infants exhibited lower length-for-age z-scores (LAZ) than GBS-unexposed infants, especially at 2 months. Altered gut microbiota and metabolites in GBS-exposed infants correlated with growth, mediating the impact of maternal GBS on infant LAZ. Changes in the vaginal microbiota of the GBS group during the third trimester correlated with infant LAZ. Additionally, differences in neonatal gut microbiota, metabolites, and vaginal microbiota during pregnancy were identified between infants with overall LAZ<-1 within 8 months after birth and their counterparts, enhancing the discriminatory power of fundamental data for predicting the occurrence of LAZ<-1 during the first 8 months of life.

Conclusions: GBS exposure is associated with decreased infant length growth, with altered microbiota and metabolites potentially mediating the effects of maternal GBS on offspring length growth, offering potential targets for predicting and addressing growth impairment.

Keywords: Group B Streptococcus; gut microbiota; infant growth; length-for-age z-score; vaginal microbiota.

Figure 1.

Impact of maternal GBS colonization during pregnancy on infant LAZ. (A) Kaplan–Meier curve depicting the occurrences of LAZ ≤ 0 in 387 infants, stratified by maternal GBS exposure and divided into 2 groups (GBS-exposed, and GBS-unexposed infants). P-value is displayed (log-rank test) without adjustment. (B) LAZ of GBS-exposed infants adjusted for maternal age, intrapartum antibiotic prophylaxis (IAP) and gestational age at delivery. (C, D) Effects of IAP(C) and feeding patterns (D) on infant LAZ after adjustment. The feeding patterns included artificial feeding (AF), breast feeding (BF), and mixed feeding.

Figure 2.

Relationship between altered gut microbiota in GBS-exposed infants and LAZ at 2–3 days and 2 months old. (A, B) Mean relative abundances of the 5 predominant phyla (A) and 20 predominant genera (B) in both groups at 2 time points. (C, D) Identification of differentially abundant bacterial taxa between the GBS-exposed and GBS-unexposed groups (|LDA| > 3.0) at 2–3 days(C) and 2 months (D). Red and green bars indicate taxa enriched in the GBS-exposed and GBS-unexposed groups, respectively. (E) Spearman correlation between differentially abundant bacterial taxa (|LDA|>2.0) and the LAZ at 2 months old (BH-adjusted). The correlation effect is indicated by a colour gradient from blue (negative correlation) to red (positive correlation). * P < 0.05, ** P < 0.01.

Figure 3.

Association of altered gut metabolites in GBS-exposed infants with LAZ. (A-D) Orthogonal partial least squares discriminant analysis (OPLS-DA) (A), relative abundance of each metabolite class (B), different metabolites (C) and different metabolic pathways (D) in the two groups at 2 months of age. (E) Spearman correlation between gut metabolites and LAZ at 2 months (BH-adjusted). The correlation effect is indicated by a colour gradient from blue (negative correlation) to red (positive correlation). * P < 0.05, ** P < 0.01.

Figure 4.

Mediation effect of altered microbiota and metabolites in GBS-exposed infants on the association between maternal GBS and infant LAZ at 2 months of age. (A) Spearman correlation between the altered bacteria and metabolites (BH-adjusted). The correlation effect is indicated by a colour gradient from blue (negative correlation) to red (positive correlation). *** P < 0.001, * P < 0.05, ** P < 0.01. (B) Mediation analysis of altered microbiota and metabolites in the association between maternal GBS and infant LAZ. Each line style represents a univariate mediation analysis (all results are provided in Table S4).

Figure 5.

Associations between the gut microbiota, and metabolites levels in offspring aged 2–3 days and the occurrence of LAZ<-1 in infants aged 1-8 months. (A, B) The ROC curve depicts the identification of LAZ<-1 among all offspring aged 1-8 months. The data included baseline data, offspring data post birth, additional 16S rDNA data (A), and metabolite data (B) at 2–3 days of age. AUC, area under the curve.

Figure 6.

Association between the vaginal microbiota of the GBS group in the third trimester and infant length. (A) Spearman correlations between infant growth at birth and altered vaginal bacterial taxa of the GBS group in the third trimester (BH-adjusted). The colour gradient represents the correlation effect, ranging from blue (negative correlation) to red (positive correlation). * P < 0.05, ** P < 0.01. (B) The difference of vaginal bacterial taxa in third trimester between the High and Low groups (|LDA| > 3.5). High and Low refer to infants with 1< overall LAZ and overall LAZ<-1, respectively, in the age range of 0-8 months. Red, and green bars indicate bacterial taxa enriched in the High and Low groups, respectively. (C, D) ROC curve displaying the discriminatory power of LAZ<-1 in infants aged 0-8 months using baseline data and paired maternal vaginal microbiota in the third trimester (C), and in infants aged 1-8 months using baseline data, paired maternal vaginal microbiome in the third trimester, and offspring data after birth (D). AUC, area under the curve.