[A prospective birth cohort study on the association between human milk osteopontin and infant physical growth]

Objective: To explore the association between human milk osteopontin and infant physical growth, and to examine its differences between full-term and preterm infants. Methods: A prospective cohort study was conducted. From November 2023 to June 2025, a total of 196 mother-infant dyads who provided human milk samples and participated in follow-up visits were enrolled at the Third Affiliated Hospital of Guangzhou Medical University. All participants were divided according to gestational age at birth into a preterm group (32-<37 weeks) and a term group (37-<42 weeks). Human milk samples were collected at 0-7, 8-14, and 35-49 d after birth, and osteopontin concentrations were measured using enzyme-linked immunosorbent assay. Combined with feeding information, the average daily intake of osteopontin within 6 months of age was estimated. Infant length, weight, and head circumference were measured at 1, 3, 6, 8, and 12 months of age, and length-for-age Z-score (LAZ), weight-for-age Z-score (WAZ), head circumference-for-age Z-score (HCZ), and weight-for-length Z-score (WLZ) were calculated. Generalized estimating equations were used to evaluate the associations of osteopontin concentrations and intake with infant physical growth. Stratified analyses were performed by preterm and term birth status, and differences in the associations between strata were evaluated. Results: Among the 115 mother-infant dyads, 59 infants were in the full-term group and 56 infants in the preterm group. The osteopontin concentrations in colostrum, transitional milk, and mature milk were (235±47), (160±30), and (105±27) mg/L, respectively. Transitional milk osteopontin concentrations were positively associated with LAZ (β=0.19, 95%CI 0.04-0.35), and mature milk osteopontin concentrations were both positively associated with WAZ (β=0.19, 95%CI 0.04-0.35) and WLZ (β=0.20, 95%CI 0.06-0.34). The average daily intake of osteopontin during the mature milk period within 6 months of age was also positively associated with WAZ (β=0.27, 95%CI 0.13-0.40), WLZ (β=0.25, 95%CI 0.09-0.40), and HCZ (β=0.13, 95%CI 0-0.25). The overall average daily intake of osteopontin within 6 months of age with WAZ, WLZ, and HCZ were also observed (all P<0.05). Moreover, the positive associations of osteopontin concentrations and intake with LAZ, WAZ, and WLZ were observed in both term and preterm infants (all P<0.05), with no statistically difference in the associations between the two groups (all P>0.05). However, the positive associations of transitional and mature milk osteopontin concentrations, as well as daily intake of osteopontin during the mature milk period and overall within 6 months of age, with HCZ were all stronger in preterm infants than those in term infants (all P<0.05). Conclusions: Human milk osteopontin concentrations and intake are positively associated with infant physical growth. The associations with length and weight did not differ between term and preterm infants, whereas the positive association with head circumference was stronger in preterm than in term infants.