TY - JOUR

T1 - Associations between maternal adiposity and appetite-regulating hormones in human milk are mediated through maternal circulating concentrations and might affect infant outcomes

AU - Christensen, Sophie Hilario

AU - Lewis, Jack Ivor

AU - Larnkjær, Anni

AU - Frøkiær, Hanne

AU - Allen, Lindsay H

AU - Mølgaard, Christian

AU - Michaelsen, Kim F.

N1 - CURIS 2022 NEXS 270

PY - 2022

Y1 - 2022

N2 - Background: Appetite-regulating hormones (ARH) in human milk (HM) are suggested to affect infants’ milk intake and possibly infant growth. Maternal adiposity might contribute to higher levels of ARH in HM, either from the mammary gland or from raised circulating levels due to higher adiposity. Counterfactual-based mediation analysis can define indirect and direct effects between HM ARH and maternal and infant factors, and might be an important tool when investigating the mother-milk-infant triad.Objective: We aim to investigate whether potential associations between (1) maternal adiposity and HM ARH and (2) HM ARH and infant milk intake and growth are mediated through maternal and infant plasma ARH, respectively.Materials and methods: Maternal and infant anthropometry and body composition, HM and blood samples were collected from 223 mother-infant dyads participating in the Mother, Infant and Lactation Quality study at three postpartum visits from 1 to 8.49 months. Leptin, insulin and adiponectin were analyzed using immunoassays. Mediation analyses using linear mixed-effect models were applied to investigate the direct and indirect effects through maternal and infant plasma hormone concentrations.Results: A positive association between maternal body-mass-index (BMI) and HM leptin was mediated by maternal plasma leptin by 29% when fixing BMI to < 25 kg/m2, and through 51% when fixing BMI to ≥ 25 kg/m2 (pinteraction < 0.01). There was no mediated effect through plasma insulin in the association between BMI and HM insulin (p = 0.068). We found negative and positive associations between HM insulin and total milk intake and infant weight, respectively, however, these diminished in mediation analyses with reduced sample sizes.Conclusion: Our main results suggest that the association between maternal adiposity and HM leptin was mediated through circulating leptin to a stronger degree for mothers with overweight compared to mothers with normal-weight. This indicates that excess maternal adiposity, and the resulting rise of circulating leptin and possible concomitant low-grade inflammation, may be reflected in HM composition.Clinical trials registry number: NCT03254329.

AB - Background: Appetite-regulating hormones (ARH) in human milk (HM) are suggested to affect infants’ milk intake and possibly infant growth. Maternal adiposity might contribute to higher levels of ARH in HM, either from the mammary gland or from raised circulating levels due to higher adiposity. Counterfactual-based mediation analysis can define indirect and direct effects between HM ARH and maternal and infant factors, and might be an important tool when investigating the mother-milk-infant triad.Objective: We aim to investigate whether potential associations between (1) maternal adiposity and HM ARH and (2) HM ARH and infant milk intake and growth are mediated through maternal and infant plasma ARH, respectively.Materials and methods: Maternal and infant anthropometry and body composition, HM and blood samples were collected from 223 mother-infant dyads participating in the Mother, Infant and Lactation Quality study at three postpartum visits from 1 to 8.49 months. Leptin, insulin and adiponectin were analyzed using immunoassays. Mediation analyses using linear mixed-effect models were applied to investigate the direct and indirect effects through maternal and infant plasma hormone concentrations.Results: A positive association between maternal body-mass-index (BMI) and HM leptin was mediated by maternal plasma leptin by 29% when fixing BMI to < 25 kg/m2, and through 51% when fixing BMI to ≥ 25 kg/m2 (pinteraction < 0.01). There was no mediated effect through plasma insulin in the association between BMI and HM insulin (p = 0.068). We found negative and positive associations between HM insulin and total milk intake and infant weight, respectively, however, these diminished in mediation analyses with reduced sample sizes.Conclusion: Our main results suggest that the association between maternal adiposity and HM leptin was mediated through circulating leptin to a stronger degree for mothers with overweight compared to mothers with normal-weight. This indicates that excess maternal adiposity, and the resulting rise of circulating leptin and possible concomitant low-grade inflammation, may be reflected in HM composition.Clinical trials registry number: NCT03254329.

KW - Faculty of Science

KW - Human milk

KW - Infant growth

KW - Body composistion

KW - Maternal adiposity

KW - Appetite-regulating hormones

KW - Leptin

KW - Insulin

KW - Adiponectin

U2 - 10.3389/fnut.2022.1025439

DO - 10.3389/fnut.2022.1025439

M3 - Journal article

C2 - 36407523

VL - 9

JO - Frontiers in Nutrition

JF - Frontiers in Nutrition

SN - 2296-861X

M1 - 1025439

ER -