Article Figures & Data
Figures
- Fig 1.
DTI TBSS results for the comparison of FA values between 2-week-old neonates born by cesarean delivery or vaginal delivery in cohort 1. Green represents major white matter tracts in the brain; orange shows voxels that have different FA values between groups. A, Group differences (P < .05, corrected for the voxelwise multiple comparisons) when no covariates were added. B, Group differences (P < .05, corrected for the voxelwise multiple comparisons) when 3 demographic parameters that were different between groups (gestational weight gain, infant sex, and birth length) were added as covariates. C, Trend of group differences (P < .15, corrected for the voxelwise multiple comparisons) when an additional 2 potential confounders (gestational age at MR imaging and maternal BMI at early pregnancy) were included as covariates. D, Illustration of ROIs (red outlined) selected for further post hoc analysis. E, Group comparison of mean FA values in these white matter ROIs. L indicates left; R, right; ACR, anterior corona radiata; ALIC, anterior limb of internal capsule; PLIC, posterior limb of internal capsule; AF, arcuate fasciculus; BCC, body of the corpus callosum; SAF, short association fibers; SCR, superior corona radiata; asterisk, P < .05 without controlling for covariates; double asterisks, P < .05 with and without controlling for covariates.
- Fig 2.
Resting-sate fMRI analyses of functional connectivity in the DMN in 2-week-old neonates in cohort 1. A, The DMN for vaginal and cesarean delivery groups obtained from respective independent component analysis (ICA). B, Regions in which the vaginal delivery group had higher functional connectivity (z score) in the DMN than the cesarean delivery group (P < .05, corrected for the voxelwise multiple comparisons) when excluding or including potential confounders as covariates. C, Illustration of ROI (precuneus selected) for further post hoc analysis. D, Comparison of the mean z score values in the precuneus between the 2 groups. Double asterisks indicate P < .05 with and without controlling for covariates.
- Fig 3.
Longitudinal MWF in different brain regions for the vaginal delivery (blue) and cesarean delivery (green) groups in cohort 3. Children born by vaginal delivery had higher MWF (indicative of better white matter development) in most of the brain regions at young infancy, while the differences between groups gradually disappeared with age.
- Fig 4.
Illustration of a hypothetic model for mechanisms that drive differences in brains between infants with vaginal birth and cesarean delivery. Under this model, birth mode–associated changes to the gut microbiome lead to alterations in signals to the brain that regulate normal remodeling processes. Because microglia are implicated in this process, the model emphasizes this cell type as a major player in cell-cell cross-talk (red arrows) that modifies overall brain structure and function during the neonatal period. The model provides a theoretic framework for how birth mode contributes to normal neonatal brain development. The figure was generated, in part, by using components from the Servier Medical Art Powerpoint image bank (https://smart.servier.com/), which is under an open-use Creative Commons license.
Tables
Vaginal Delivery (Mean ± SD) (n = 32) Cesarean Delivery (Mean ± SD) (n = 11) P Value DTI TBSS study (n = 43) 32 11 RS-fMRI study (n = 37) 27 10 Mother's age at delivery (yr) 29.0 ± 3.9 30.6 ± 4.4 .26 29.2 ± 4.1 30.6 ± 4.6 .35 Mother's body fat % at early/prepregnancy 33.4 ± 8.6 36.9 ± 8.5 .24 34.5 ± 8.8 38.4 ± 7.3 .23 Mother's BMI at 12 wk of pregnancy 25.1 ± 5.2 28.8 ± 5.1 .04 25.5 ± 5.5 29.2 ± 5.1 .08 Mother's gestational weight gain (kg) 11.79 ± 3.07 9.02 ± 3.37 .02c 11.51 ± 2.75 8.87 ± 3.51 .03c Mother's IQa 107.7 ± 9.6 104.2 ± 6.9 .18 108.6 ± 9.2 104.8 ± 6.9 .22 Gestational age at MRIb (days) 290 ± 6 287 ± 6 .20 291 ± 6 288 ± 5 .22 Sex (M/F) 20/12 3/8 .04c 19/8 3/7 .03c Birth weight (kg) 3.51 ± 0.46 3.56 ± 0.54 .79 3.49 ± 0.36 3.63 ± 0.52 .35 Birth length (cm) 51.1 ± 2.6 49.3 ± 2.6 .05c 51.2 ± 2.1 49.3 ± 2.7 .02c Head circumference (cm) 36.2 ± 1.1 35.9 ± 0.5 .22 36.3 ± 0.9 35.9 ± 0.6 .31 Diet for the first 2 wk (breastmilk/formula) 29/3 10/1 .98 24/3 9/1 .92 For each cell in the table, the first row is for the DTI TBSS study, the second row is for the RS-fMRI study.
↵a Not available for 1 subject with vaginal delivery.
↵b Defined as gestational age at birth plus postnatal age at MRI.
↵c Consistently different between groups for both TBSS and RF-fMRI and therefore included as a covariate in the analysis.
Vaginal Delivery (n = 37) Cesarean Delivery (n = 23) P Value DTI TBSS study (n = 56) 35 21 VBM study (n = 57) 36 21 Birth weight (mean ± SD) (kg) 3.37 ± 0.40 3.44 ± 0.49 .79 3.34 ± 0.43 3.45 ± 0.48 .55 Gestational age at birth (mean ± SD) (days) 276 ± 9 275 ± 9 .43 275 ± 10 274 ± 10 .75 Age at MRI (mean ± SD) (yr) 7.93 ± 0.26 7.87 ± 0.24 .42 7.94 ± 0.26 7.92 ± 0.27 .94 Sex (M/F) 13/22 11/10 .26 14/22 9/12 .77 Infant diet (breastmilk/formula) 14/21 4/17 .10 15/21 4/17 .08 BMI (mean ± SD) 16.8 ± 2.9 17.1 ± 2.3 .49 16.7 ± 2.9 17.4 ± 2.8 .27 SESa mother's education: high school/college/graduate degree 4/15/8 2/5/3 .99 SESa father's education: high school/college/graduate degree 7/17/3 3/6/1 .99 SESa mother's annual income: NA/<$20k/$20k–$50k/>$50k 12/5/9/1 1/2/3/4 .03 SESa father's annual income: NA/<$20k/$20k–$50k/>$50k 1/0/11/15 0/0/3/7 .79 IQ (mean ± SD) 110 ± 10 112 ± 17 .53 112 ± 11 112 ± 16 .72 CELF-4 language scores (mean ± SD)b 103 ± 14 104 ± 16 .31 103 ± 12 105 ± 14 .24 CMS general memory index (mean ± SD)b 113 ± 12 109 ± 13 .14 115 ± 11 111 ± 13 .24 Note:—SES indicates socioeconomic status; CELF-4, Clinical Evaluation of Language Fundamentals; CMS, Childhood Memory Scale; NA, not applicable. For each cell in the table, the first row is for the DTI TBSS study, the second row is for the VBM study.
↵a Only partial socioeconomic status data were available for all subjects (n = 27 for vaginal delivery, n = 10 for cesarean delivery).
↵b Not available for 1 subject with cesarean delivery.
Vaginal Delivery (Mean ± SD) Cesarean Delivery (Mean ± SD) P Value MWF study (n = 203) 164 39 Mother's post-secondary education (yr) 5.8 ± 1.0 6.0 ± 0.9 .22 Mother's age at pregnancy (yr) 29.0 ± 5.6 33.8 ± 5.1 <.001 Sex (M/F) 93/71 23/16 .86 Gestational age at birth (days) 277 ± 8 273 ± 4 .001 Birth weight (kg) 3.54 ± 0.45 3.37 ± 0.48 .06 Birth length (cm) 50.8 ± 4.1 50.8 ± 4.1 .63 No. of scans 2.2 ± 1.2 2.4 ± 1.3 .32 Mean interscan period (days) 296 ± 144 333 ± 147 .12
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