Maternal Health, Breastfeeding,Breast Milk Components andChildhood Growth

Background: Normal growth and body composition during infancy and childhood are crucial for both short- and long-term physical and mental well-being. Evidence suggests that the first 1000 days from conception to the age of two are critical in affecting appetite regulation and metabolic programming, which subsequently influence growth and body composition later in life.

Males and females exhibit different growth patterns during fetal life, infancy, and childhood. Additionally, higher morbidity and mortality rates are observed among males, both in fetal life and early childhood, suggesting that nutritional needs differ between male and female infants to compensate for the increased “male vulnerability” and differences in growth.

Aim: This PhD thesis aims to investigate the associations between maternal glucose metabolism during pregnancy, early infant nutrition (exclusively and partially breastfeeding with infant formula supplementation), macronutrient content in mother’s own milk, growth, and body composition in infancy and childhood up to 7 years of age. Additionally, to investigate whether the macronutrient content in mother’s own milk differs according to infant sex.

Methods: To investigate this, we analyzed data from the ongoing prospective pre-birth child cohort, the Odense Child Cohort. Women were recruited from the municipality of Odense early in pregnancy between January 2010 and December 2012. The data comprises information from questionnaires, SMS questionnaires, biological material (maternal blood and milk samples), and infant/child anthropometrics from standardized physical examinations at 3 and 18 months, 3 to 7 years of age, including DXA scans at the age of 7.

In Study I, we used data on maternal fasting plasma glucose, s-insulin, Homeostatic Model Assessment of Insulin Resistance, (HOMA-IR), and Hemoglobin A1c, as well as their infant/children’s anthropometric measures from birth to 5 years of age, to investigate associations between 3rd trimester maternal blood glucose, insulin resistance, and longitudinal childhood anthropometric measures of obesity up to the age of 5.

In Study II, we analyzed data on nesfatin-1 levels in mother’s own milk collected 3 months postpartum and infants’ anthropometric measures from birth to 3 months of age to determine if there is a possible association between nesfatin-1 levels and infant growth.

In Study III, we analyzed data on the macronutrient content in mother’s own milk from exclusively breastfeeding mothers in the Odense Child Cohort and exclusively breastfeeding Australian mothers, and data on Australian infant intakes to investigate sex-specific differences.

In Study IV, we analyzed data from the SMS questionnaires on the duration of exclusive and partial breastfeeding and anthropometric measures from birth to 7 years, including body composition at 7 years of age from DXA scans. This was done to investigate whether longitudinal growth depends on feeding type and the association between estimated protein intake during infancy and body composition at 7 years of age.

Results: In Study I, we found that higher fasting plasma glucose in the 3rd trimester was strongly associated with higher birth anthropometric measures in both male and female infants. This association disappeared at 3 months, but fasting plasma glucose was associated with larger skinfold measures in girls from 3 years of age. Increased insulin resistance was significantly associated with higher anthropometric measures in boys and girls from the age of 3, most pronounced in girls.

In Study II, we found no differences in nesfatin-1 levels in mother’s own milk, regardless of whether the infants had a high or low weight-for-age z-score at the time of milk sampling. We also found no associations between nesfatin-1 levels, change in growth from birth to 3 months, or anthropometric measures at 3 months of age.

In Study III, we found no sex-specific difference in macronutrient content in mother’s own milk from exclusively breastfeeding Danish and Australian mothers. We found no sex-specific difference in milk intake, and intake of macronutrients, and energy in exclusively breastfed Australian infants.

In Study IV, we found no difference in longitudinal growth from birth to 7 years of age, regardless of whether the children were exclusively or partially breastfed in infancy. Partially breastfed infants had a higher estimated protein intake compared to exclusively breastfed infants, but estimated protein intake in infancy was not associated with body composition at 7 years of age.

Conclusion: In the Odense Child Cohort, blood glucose and increased insulin resistance in the 3rd trimester of pregnancy were associated with longitudinal anthropometric measures in both boys and girls. We found no association between nesfatin-1 levels (an appetite-regulating hormone) in mother’s own milk, infant growth from birth, and current anthropometric measures. The macronutrient content in mother’s own milk did not differ according to infant sex. The type of breastfeeding (exclusive or partial) was not associated with longitudinal growth from birth to 7 years, and estimated protein intake during infancy was not associated with body composition at 7 years. Despite the challenges of investigating the relationships between maternal glucose metabolism, human milk components, and anthropometric measures in childhood, our results indicate that higher glucose levels and insulin resistance during pregnancy increase the risk of developing overweight in childhood.