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Intrapartum Caesarean Delivery Linked to Higher BMI Trajectories in Female Children Only
Intrapartum caesarean delivery — but not antepartum caesarean delivery — was associated with a substantially higher BMI percentile trajectory exclusively in female children, representing a difference of approximately 31.8 percentage points compared with vaginal delivery (Δ=31.8%; 95% CI 16.25%–47.55%; P=0.001). Early-life gut microbiota composition appears to mediate this relationship, with predictive models achieving strong discriminatory performance for overweight and obesity risk in this specific subgroup.
What Was Studied
This study investigated whether the type of caesarean delivery — distinguishing between intrapartum caesarean (performed during active labour) and antepartum caesarean (performed before labour onset) — differentially affects childhood BMI trajectories, and whether the infant gut microbiome mediates any such association. Understanding this distinction is important because labour itself exposes the newborn to the birth canal microenvironment, potentially influencing early microbial colonisation and downstream metabolic development.
How It Was Studied
Researchers conducted a secondary analysis of data drawn from the VDAART prospective birth cohort, which was originally structured as a randomised, double-blind, placebo-controlled trial. The analysis included 683 children followed from birth to age 8, with BMI percentiles recorded between ages 2 and 8 years. Gut microbiome composition was characterised using 1,672 stool samples collected between 3 months and 5 years of age. The primary comparator was vaginal delivery, against which both intrapartum and antepartum caesarean delivery groups were evaluated. Analytical methods included permutation testing for BMI trajectory differences, PERMANOVA for microbiota community-level comparisons, Random Forest classification for predictive modelling of overweight and obesity, and Generalised Microbe Phenotype Triangulation (GMPT) to identify specific taxa potentially mediating the observed associations.
What Was Observed
- Intrapartum caesarean delivery was associated with higher BMI trajectories in female children only. Compared with vaginal delivery, iCD was linked to a roughly 31.8 percentage-point elevation in BMI percentile trajectory (Δ=31.8%; 95% CI 16.25%–47.55%; P=0.001, permutation test). Antepartum caesarean delivery showed no such association, and neither delivery type produced a detectable effect in male children.
- Delivery mode significantly shaped early-life gut microbiota composition, again exclusively in females. Community-level microbiome differences between delivery groups were statistically meaningful at 3–6 months and at age 1 (F=2.15 and F=2.47; P=0.035 and P=0.007, PERMANOVA), suggesting that the window of divergent microbial colonisation occurs in the first year of life.
- Early microbiota data predicted later overweight and obesity with high accuracy in iCD-born females. Random Forest models trained on early-life microbiome profiles performed best in this subgroup, achieving an AUROC of 0.88 (95% CI 0.83–0.94) for overweight and obesity prediction at age 2, pointing to the first year of life as a potentially important intervention window.
- GMPT identified 24 early-life bacterial taxa as potential mediators of iCD-associated obesity risk. Of these, 11 taxa appeared to be protective (preventive) and 13 appeared to be permissive of excess weight gain, including species such as Bacteroides ovatus, Bifidobacterium bifidum, Clostridium leptum, and Eggerthella lenta.
Why This Matters
The distinction between intrapartum and antepartum caesarean delivery has rarely been examined in the context of childhood obesity, yet this study suggests it may be central to resolving the ongoing scientific debate about whether caesarean delivery in general increases overweight risk. The additional finding that effects are confined to female children offers a potential biological explanation for why prior studies have produced inconsistent results across mixed-sex populations. Together, these observations suggest that delivery type and child sex are both key modifiers that should be accounted for in future investigations and intervention designs.
How to Read This Result
While the effect sizes are notable and the predictive models are strong, this is a medium-quality secondary analysis of a cohort not originally designed for this purpose, and the proposed gut microbiota mediation is inferred through statistical triangulation rather than experimental manipulation — making causal interpretation premature, particularly given that the sex-specific findings have yet to be independently replicated.
Limitations
The VDAART cohort was designed as a vitamin D supplementation trial, not a study of delivery mode or obesity, introducing the possibility that the sample does not fully represent the general birth population and that residual confounding has not been entirely eliminated. The restriction of all key findings to female children, while scientifically interesting, substantially limits the generalisability of the results to broader populations. Additionally, observational designs cannot establish causality, and the identification of mediating taxa through GMPT relies on statistical inference rather than direct experimental manipulation of the microbiome.