Association of maternal postpartum depression symptoms with infant neurodevelopment and gut microbiota

Abstract

Introduction: Understanding the mechanisms underlying maternal postpartum depression (PPD) and its effects on offspring development is crucial. However, research on the association between maternal PPD, gut microbiota, and offspring neurodevelopment remains limited. This study aimed to examine the association of maternal PPD symptoms with early gut microbiome, gut metabolome, and neurodevelopment in infants at 6 months.

Methods: Maternal PPD symptoms were assessed using the Edinburgh Postpartum Depression Scale (EPDS) at 42 days postpartum. Infants stool samples collected at 42 days after birth were analyzed using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS) detection. Infant neurodevelopment was measured at 6 months using the Ages and Stages Questionnaire, Third Edition (ASQ-3). Correlations between gut microbiota, metabolites and neurodevelopment were identified through co-occurrence network analysis. Finally, mediation analyses were conducted to determine potential causal pathways.

Results: A total of 101 mother-infant dyads were included in the final analysis. Infants born to mothers with PPD symptoms at 42 days postpartum had lower neurodevelopmental scores at 6 months. These infants also had increased alpha diversity of gut microbiota and were abundant in Veillonella and Finegoldia, while depleted abundance of Bifidobacterium, Dialister, Cronobacter and Megasphaera. Furthermore, alterations were observed in metabolite levels linked to the Alanine, aspartate, and glutamate metabolic pathway, primarily characterized by decreases in N-Acetyl-L-aspartic acid, L-Aspartic acid, and L-Asparagine. Co-occurrence network and mediation analyses revealed that N-Acetyl-L-aspartic acid and L-Aspartic acid levels mediated the relationship between maternal PPD symptoms and the development of infant problem-solving skills.

Conclusions: Maternal PPD symptoms are associated with alterations in the gut microbiota and neurodevelopment in infants. This study provides new insights into potential early intervention for infants whose mother experienced PPD. Further research is warranted to elucidate the biological mechanisms underlying these associations.

Keywords: gut metabolome; gut microbiome; gut-brain axis; neurodevelopment; postpartum depression.

Figure 1

Flowchart of mother-infant dyads included in the study.

Figure 2

Comparison of infant neurodevelopment between PPD and non-PPD groups based on ASQ-3 scores at 6 months after birth. [Model 1 was the crude model, model 2 was adjusted for pre-pregnancy BMI, gestational age, NICU care, mode of delivery (intervention factor included), and introduction of complementary food at 6 months.].

Figure 3

Associations between maternal PPD symptoms at 42 days and infant gut microbiota and metabolome at 42 days after birth. (A) Comparison of Shannon diversity index between infants in the PPD and non-PPD groups at 42 days using Wilcoxon test. (B) Relative abundances of the 14 predominant genera between groups. Dissimilarities in gut microbiota composition at genus level between PPD and non-PPD groups at 42 days. (C) LEfSe (LDA>2) illustrating taxa that are significantly different in infants between PPD and non-PPD groups. (D) Metabolite composition of infants in non-PPD and PPD groups. The metabolites with the top 20 concentrations are shown. (E) Heatmap of associations between differentially abundant genera and the top 20 concentrations metabolites (Spearman’s rank correlation analysis). *** P<0.001, **P<0.01, *P<0.05 (FDR<0.25). (F) Volcano chart of fold changes in metabolites in stool samples of infants in the PPD and non-PPD groups. The dotted line represents P = 0.05. Red dots show enriched metabolites in non-PPD group, while blue dots show opposite. Notable metabolites are labeled.

Figure 4

Association between differentially abundant genera, metabolites, and infant neurodevelopment at 6 months of age. (A) A co-occurrence network constructed from the relative abundances of differential microbial genus, fecal metabolites as well as neurodevelopment score in infants in PPD group and non-PPD group. The spearman correlation analysis was used to explore the co-occurrence network. The node size signifies its degree, representing the number of network connections. The shape of node denotes the components (ellipse: neurodevelopment domains, triangle: microbial genera, and cut-rectangle: metabolites). Deep and light colors indicate increased and decreased relative abundances in non-PPD compared to PPD, respectively. Solid and dashed edges represent positive and negative correlations, respectively. The colors and shapes of nodes indicate the categories of nodes. Edges thickness indicate the magnitude of correlation. FM, fine motor; GM, gross motor; CM, communication; CG, problem solving skills; PS, personal-social skills. (B, C) Mediation analysis assessing the role of (B) N-Acetyl-L-aspartic acid and (C) L-Aspartic acid in the association between maternal PPD symptoms and infant problem-solving skill scores. The model was adjusted for gestational age, mode of delivery, feeding type at day 42, NICU care, and maternal pre-pregnancy BMI.