TY - JOUR
T1 - Breast milk exposure is associated with cortical maturation in preterm infants
AU - Sullivan, Gemma
AU - Vaher, Kadi
AU - Blesa, Manuel
AU - Galdi, Paola
AU - Stoye, David Q
AU - Quigley, Alan J
AU - Thrippleton, Michael J
AU - Norrie, John
AU - Bastin, Mark E
AU - Boardman, James P
N1 - Funding Information:
The authors are grateful to the families who consented to take part in the study and to the radiographers at the Edinburgh Imaging Facility at the Royal Infirmary of Edinburgh for infant scanning. This work was supported by Theirworld ( www.theirworld.org ) and was undertaken in the MRC Centre for Reproductive Health, which is funded by MRC Centre Grant (MRC G1002033). K.V. is funded by the Wellcome Translational Neuroscience PhD Programme at the University of Edinburgh (108890/Z/15/Z). P.G. is partly supported by the Wellcome University of Edinburgh ISSF3 (IS3‐R1.1320/21). M.J.T. is supported by NHS Lothian Research and Development Office.
Publisher Copyright:
© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2022/11/22
Y1 - 2022/11/22
N2 - OBJECTIVE: Breast milk exposure is associated with improved neurocognitive outcomes following preterm birth but the neural substrates linking breast milk with outcome are uncertain. We tested the hypothesis that high versus low breast milk exposure in preterm infants results in cortical morphology that more closely resembles that of term-born infants.METHODS: We studied 135 preterm (<32 weeks' gestation) and 77 term infants. Feeding data were collected from birth until hospital discharge and brain magnetic resonance imaging (MRI) was performed at term-equivalent age. Cortical indices (volume, thickness, surface area, gyrification index, sulcal depth, and curvature) and diffusion parameters (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], axial diffusivity [AD], neurite density index [NDI], and orientation dispersion index [ODI]) were compared between preterm infants who received exclusive breast milk for <75% of inpatient days, preterm infants who received exclusive breast milk for ≥75% of inpatient days and term-born controls. To investigate a dose response effect, we performed linear regression using breast milk exposure quartile weighted by propensity scores.RESULTS: In preterm infants, high breast milk exposure was associated with reduced cortical gray matter volume (d = 0.47, 95% confidence interval [CI] = 0.14 to 0.94, p = 0.014), thickness (d = 0.42, 95% CI = 0.08 to 0.84, p = 0.039), and RD (d = 0.38, 95% CI = 0.002 to 0.77, p = 0.039), and increased FA (d = -0.38, 95% CI = -0.74 to -0.01, p = 0.037) after adjustment for age at MRI, which was similar to the cortical phenotype observed in term-born controls. Breast milk exposure quartile was associated with cortical volume (ß = -0.192, 95% CI = -0.342 to -0.042, p = 0.017), FA (ß = 0.223, 95% CI = 0.075 to 0.372, p = 0.007), and RD (ß = -0.225, 95% CI = -0.373 to -0.076, p = 0.007) following adjustment for age at birth, age at MRI, and weighted by propensity scores, suggesting a dose effect.INTERPRETATION: High breast milk exposure following preterm birth is associated with a cortical imaging phenotype that more closely resembles the brain morphology of term-born infants and effects appear to be dose-dependent. ANN NEUROL 2022.
AB - OBJECTIVE: Breast milk exposure is associated with improved neurocognitive outcomes following preterm birth but the neural substrates linking breast milk with outcome are uncertain. We tested the hypothesis that high versus low breast milk exposure in preterm infants results in cortical morphology that more closely resembles that of term-born infants.METHODS: We studied 135 preterm (<32 weeks' gestation) and 77 term infants. Feeding data were collected from birth until hospital discharge and brain magnetic resonance imaging (MRI) was performed at term-equivalent age. Cortical indices (volume, thickness, surface area, gyrification index, sulcal depth, and curvature) and diffusion parameters (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], axial diffusivity [AD], neurite density index [NDI], and orientation dispersion index [ODI]) were compared between preterm infants who received exclusive breast milk for <75% of inpatient days, preterm infants who received exclusive breast milk for ≥75% of inpatient days and term-born controls. To investigate a dose response effect, we performed linear regression using breast milk exposure quartile weighted by propensity scores.RESULTS: In preterm infants, high breast milk exposure was associated with reduced cortical gray matter volume (d = 0.47, 95% confidence interval [CI] = 0.14 to 0.94, p = 0.014), thickness (d = 0.42, 95% CI = 0.08 to 0.84, p = 0.039), and RD (d = 0.38, 95% CI = 0.002 to 0.77, p = 0.039), and increased FA (d = -0.38, 95% CI = -0.74 to -0.01, p = 0.037) after adjustment for age at MRI, which was similar to the cortical phenotype observed in term-born controls. Breast milk exposure quartile was associated with cortical volume (ß = -0.192, 95% CI = -0.342 to -0.042, p = 0.017), FA (ß = 0.223, 95% CI = 0.075 to 0.372, p = 0.007), and RD (ß = -0.225, 95% CI = -0.373 to -0.076, p = 0.007) following adjustment for age at birth, age at MRI, and weighted by propensity scores, suggesting a dose effect.INTERPRETATION: High breast milk exposure following preterm birth is associated with a cortical imaging phenotype that more closely resembles the brain morphology of term-born infants and effects appear to be dose-dependent. ANN NEUROL 2022.
U2 - 10.1002/ana.26559
DO - 10.1002/ana.26559
M3 - Article
C2 - 36412221
SN - 0364-5134
VL - 93
SP - 591
EP - 603
JO - Annals of Neurology
JF - Annals of Neurology
IS - 3
ER -