A nutritional supplement taken during preconception and pregnancy influences human milk macronutrients in women with overweight/obesity and gestational diabetes mellitus

Abstract

Rational: Maternal overweight/obesity and gestational diabetes mellitus (GDM) are associated with an increased risk of their offspring developing overweight/obesity or type 2 diabetes later in life. However, the impacts of maternal overweight/obesity and dysglycemia on human milk (HM) macronutrient composition are not well understood.

Objective: Through a double-blind randomised controlled trial, we investigated the effects of maternal supplementation from preconception throughout pregnancy until birth on HM macronutrient concentrations, in association with maternal and infant factors including maternal pre-pregnancy body mass index (BMI) and GDM status. In addition, we aimed to characterise longitudinal changes in HM macronutrients.

Methods: The control supplement contained calcium, iodine, iron, β-carotene, and folic acid. The intervention supplement additionally contained zinc, vitamins B₂, B₆, B₁₂, and D₃, probiotics, and myo-inositol. HM samples were collected across seven time points from 1 week to 12 months from Singapore and/or New Zealand. HM macronutrient concentrations were measured using a MIRIS Human Milk Analyser. Potential differences in HM macronutrient concentrations were assessed using linear mixed models with a repeated measures design.

Results: Overall, HM macronutrient concentrations were similar between control and intervention groups. Among the control group, overweight/obesity and GDM were associated with higher HM fat and energy concentrations over the first 3 months. Such associations were not observed among the intervention group. Of note, mothers with GDM in the intervention group had lower HM fat by 10% (p = 0.049) and energy by 6% (p = 0.029) than mothers with GDM in the control group. Longitudinal changes in HM macronutrient concentrations over 12 months of lactation in New Zealand showed that HM fat and energy decreased in the first 6 months then increased until 12 months. HM lactose gradually decreased from 1 week to 12 months while crude protein decreased from 1 week to 6 months then remained relatively constant until 12 months of lactation.

Conclusion: Maternal overweight/obesity or GDM were associated with increased HM fat and energy levels. We speculate the intervention taken during preconception and pregnancy altered the impact of maternal BMI or GDM status on HM macronutrient composition. Further studies are required to identify the mechanisms underlying altered HM macronutrient concentration in the intervention group and to determine any long-term effects on offspring health.

Clinical trial registration: ClinicalTrials.gov, NCT02509988, Universal Trial Number U1111-1171-8056. Registered on 16 July 2015. This is an academic-led study by the EpiGen Global Research Consortium.

Keywords: gestational diabetes mellitus; human milk; macronutrients; maternal BMI; maternal nutrition.

Figure 1

CONSORT diagram for the number of human milk (HM) samples analysed for macronutrients in the NiPPeR study. Reasons for exclusion during the preconception phase have been published previously (53), while reasons for exclusion during pregnancy and birth in Singapore (SGP) and New Zealand (NZL) are provided in Supplementary Table 2. ^‡There were no HM samples collected in the United Kingdom (UK), so all participants from that site were excluded from this diagram. ^*Number of participants who provided at least one HM sample during the first 12 months of lactation. ^†Number of participants who provided at least one HM sample during the first 3 months of lactation. Diagram adapted from Han et al. (48).

Figure 2

Macronutrient concentrations in human milk (HM) in control and intervention groups in the NiPPeR study, during the first 3 months of lactation: (A) fat, (B) energy, (C) lactose, and (D) crude protein. Data are the least-squares means (i.e., adjusted means) for each group, adjusted for randomisation group, visit, an interaction term (group*visit), study site, maternal pre-pregnancy body mass index, gestational age at birth, and adherence. Error bars represent the respective 95% confidence intervals.

Figure 3

Average macronutrient concentrations in human milk (HM) in control and intervention groups by maternal pre-pregnancy body mass index (BMI) status in the NiPPeR study over the first 3  months of lactation: (A) fat, (B) energy, (C) lactose, and (D) crude protein. Data are the least-squares means (i.e., adjusted means) for each group, adjusted for randomisation group, BMI status, group*BMI interaction term, visit, study site, gestational age at birth, and adherence. Error bars represent the respective 95% confidence intervals. ^*p < 0.05. Overwt/Obesity, Overweight/Obesity BMI; Under/Normal, Underweight/Normal weight BMI.

Figure 4

Average macronutrient concentrations in human milk (HM) in control and intervention groups by maternal gestational diabetes mellitus (GDM) status in the NiPPeR study over the first 3 months of lactation: (A) fat, (B) energy, (C) lactose, and (D) crude protein. Data are the least-squares means (i.e., adjusted means) for each group, adjusted for randomisation group, GDM status, group*GDM interaction term, visit, study site, gestational age at birth, and adherence. Error bars represent the respective 95% confidence intervals. ^*p < 0.05.

Figure 5

Macronutrient concentrations in human milk (HM) in control and intervention groups in New Zealand in the NiPPeR study during 12 months of lactation: (A) fat, (B) energy, (C) lactose, and (D) crude protein. Data are the least-squares means (i.e., adjusted means) for each group, adjusted for randomisation group, visit, an interaction term (group*visit), maternal pre-pregnancy body mass index, gestational age at birth, and adherence. Error bars represent the respective 95% confidence intervals. ^*p < 0.05 for a difference between intervention and control groups at a given time point.