Background: The relationship between human milk oligosaccharides (HMO) and child growth has been investigated only insufficiently with ambiguous results. Therefore, this study examines potential influencing factors of HMO concentrations and how HMOs are associated with child growth parameters.
Methods: Milk samples from the German LIFE Child cohort of healthy children were analyzed for 9 HMOs. Putative associations with maternal and child cofactors and child height, head circumference and BMI between three months and seven years of age were examined. Secretor status, defined as the presence of 2’-fucosyllactose, was investigated for associations with infant outcomes.
Results: Our population consisted of 21 (14.7%) non-secretor and 122 (85.3%) secretor mothers. Maternal age was significantly associated with higher 3’SL concentrations; gestational age was associated with LNT, 6’SL and LNFP-I. Pre-pregnancy BMI was negatively associated with LNnT only in non-secretors. The growth velocity of non-secretors’ children was inversely associated with LNnT at 3 months to 1 year (R=0.95 [0.90, 0.99], p=0.014), 1 to 2 years (R=0.80 [0.72, 0.88], p<0.001) and 5 to 6 years (R=0.71 [0.57, 0.87], p=0.002). 2’FL was negatively associated with BMI consistently, reaching statistical significance at 3 months and 4 and 5 years. Children of non-secretors showed higher BMI at 3 months, 6 months, and 3, 6, and 7 years of age.
Conclusion: We found that some associations between HMOs and infant growth may extend beyond the infancy and breastfeeding periods. They highlight the importance of both maternal and infant parameters in the understanding of the underlying associations.
Trial registration: The study is registered with ClinicalTrial.gov: NCT02550236.

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Figure 3
Competing interest reported. Aristea Binia, Sean Austin and Norbert Sprenger are employees of Société des Produits Nestlé. All other authors declare no conflict of interest.
This is a list of supplementary files associated with this preprint. Click to download.
File: Additional_File_Supplementary_Table_S1-S5.docx Description of data: Supplementary Table S1 - Associations between Human Milk Oligosaccharides at 3 months and maternal and birth parameter are presented as ratio, 95% confidence interval, and p-value. If the effects differed between the secretor and the non-secretor group, both effects are given. Otherwise the overall effect is reported. Supplementary Table S2 - Associations between Human Milk Oligosaccharides at 3 months and height-SDS at the different time points are presented as ratio, 95% confidence interval, and p-value. If the effects differed between the secretor and the non-secretor group, both effects are given. Otherwise the overall effect is reported. Supplementary Table S3 - Associations between Human Milk Oligosaccharides at 3 months and growth velocity at the different time points are presented as ratio, 95% confidence interval, and p-value. If the effects differed between the secretor and the non-secretor group, both effects are given. Otherwise the overall effect is reported. Supplementary Table S4 - Associations between Human Milk Oligosaccharides at 3 months and BMI-SDS at the different time points are presented as ratio, 95% confidence interval, and p-value. If the effects differed between the secretor and the non-secretor group, both effects are given. Otherwise the overall effect is reported. Supplementary Table S5 - Associations between Human Milk Oligosaccharides at 3 months and Head Circumference SDS at the different time points are presented as ratio, 95% confidence interval, and p-value. If the effects differed between the secretor and the non-secretor group, both effects are given. Otherwise the overall effect is reported.
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Posted 13 Apr, 2021
On 30 Jul, 2021
Received 23 Jul, 2021
On 09 Jul, 2021
Received 09 Jun, 2021
On 29 May, 2021
Invitations sent on 06 May, 2021
On 04 May, 2021
On 09 Apr, 2021
On 09 Apr, 2021
On 08 Apr, 2021
Posted 13 Apr, 2021
On 30 Jul, 2021
Received 23 Jul, 2021
On 09 Jul, 2021
Received 09 Jun, 2021
On 29 May, 2021
Invitations sent on 06 May, 2021
On 04 May, 2021
On 09 Apr, 2021
On 09 Apr, 2021
On 08 Apr, 2021
Background: The relationship between human milk oligosaccharides (HMO) and child growth has been investigated only insufficiently with ambiguous results. Therefore, this study examines potential influencing factors of HMO concentrations and how HMOs are associated with child growth parameters.
Methods: Milk samples from the German LIFE Child cohort of healthy children were analyzed for 9 HMOs. Putative associations with maternal and child cofactors and child height, head circumference and BMI between three months and seven years of age were examined. Secretor status, defined as the presence of 2’-fucosyllactose, was investigated for associations with infant outcomes.
Results: Our population consisted of 21 (14.7%) non-secretor and 122 (85.3%) secretor mothers. Maternal age was significantly associated with higher 3’SL concentrations; gestational age was associated with LNT, 6’SL and LNFP-I. Pre-pregnancy BMI was negatively associated with LNnT only in non-secretors. The growth velocity of non-secretors’ children was inversely associated with LNnT at 3 months to 1 year (R=0.95 [0.90, 0.99], p=0.014), 1 to 2 years (R=0.80 [0.72, 0.88], p<0.001) and 5 to 6 years (R=0.71 [0.57, 0.87], p=0.002). 2’FL was negatively associated with BMI consistently, reaching statistical significance at 3 months and 4 and 5 years. Children of non-secretors showed higher BMI at 3 months, 6 months, and 3, 6, and 7 years of age.
Conclusion: We found that some associations between HMOs and infant growth may extend beyond the infancy and breastfeeding periods. They highlight the importance of both maternal and infant parameters in the understanding of the underlying associations.
Trial registration: The study is registered with ClinicalTrial.gov: NCT02550236.

Figure 1

Figure 2

Figure 3
Competing interest reported. Aristea Binia, Sean Austin and Norbert Sprenger are employees of Société des Produits Nestlé. All other authors declare no conflict of interest.
This is a list of supplementary files associated with this preprint. Click to download.
File: Additional_File_Supplementary_Table_S1-S5.docx Description of data: Supplementary Table S1 - Associations between Human Milk Oligosaccharides at 3 months and maternal and birth parameter are presented as ratio, 95% confidence interval, and p-value. If the effects differed between the secretor and the non-secretor group, both effects are given. Otherwise the overall effect is reported. Supplementary Table S2 - Associations between Human Milk Oligosaccharides at 3 months and height-SDS at the different time points are presented as ratio, 95% confidence interval, and p-value. If the effects differed between the secretor and the non-secretor group, both effects are given. Otherwise the overall effect is reported. Supplementary Table S3 - Associations between Human Milk Oligosaccharides at 3 months and growth velocity at the different time points are presented as ratio, 95% confidence interval, and p-value. If the effects differed between the secretor and the non-secretor group, both effects are given. Otherwise the overall effect is reported. Supplementary Table S4 - Associations between Human Milk Oligosaccharides at 3 months and BMI-SDS at the different time points are presented as ratio, 95% confidence interval, and p-value. If the effects differed between the secretor and the non-secretor group, both effects are given. Otherwise the overall effect is reported. Supplementary Table S5 - Associations between Human Milk Oligosaccharides at 3 months and Head Circumference SDS at the different time points are presented as ratio, 95% confidence interval, and p-value. If the effects differed between the secretor and the non-secretor group, both effects are given. Otherwise the overall effect is reported.
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