380 - Associations between the human milk metabolome and infant temperament

Publication Number: 3367.380

Chloe Andrews, Women & Infants Hospital, Boston, MA, United States; Kyu Ha Lee, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Shilpa N. Bhupathiraju, Harvard Medical School, Boston, MA, United States; Fang Fang Zhang, Tufts University, Boston, MA, United States; Kari E. Wong, Metabolon, Inc., Morrisville, NC, United States; Asimenia Angelidou, Harvard Medical School, Boston, MA, United States; Carmen Monthe-Dreze, Women & Infants Hospital of Rhode Island, Providence, RI, United States; Sarbattama Sen, Women & Infants Hospital of Rhode Island, providence, RI, United States; Camilia R. Martin, Weill Cornell Medicine, New York, NY, United States

Background: Breastfeeding is associated with improved neurodevelopmental outcomes (NDO) and specific components of human milk (HM) may underpin this association. Few studies have comprehensively characterized the HM metabolome and analyzed its association with infant temperament, a predictor of later psychopathology.

Objective: To determine the associations between the HM metabolome at six weeks with infant temperament at six months.

Design/Methods: This was a secondary analysis of 71 mothers and their term infants enrolled in a lactation study in Boston, MA. Mothers self-collected HM samples at six weeks as an aliquot of a full expression of one breast. We quantified HM metabolomics using untargeted mass-spectrometry and identified 451 annotated metabolites (excluding chemicals and drugs). Mothers reported on infant temperament at six months using the Infant Behavior Questionnaire - Revised Very Short Form which provided scores in three domains: surgency (i.e. positive affect), negative affect, and effortful control (i.e. ability to inhibit a dominant response to perform a subdominant response). For each domain, we fit a separate elastic net regression model with all metabolites as candidate predictors and maternal age, household income, infant gestational age at delivery, and exclusive breastfeeding status at 6 weeks as unpenalized covariates.

Results: Median maternal age was 35 years, 79% of mothers were White, 82% had a household income > $100,000, and 72% of infants were exclusively breastfeeding at six weeks (Table 1). HM lacto-N-fucopentaose V was positively associated with surgency and S-methylcysteine sulfoxide, 7-methylguanine, hydroxyasparagine, UDP-N-acetylglucosamine, and UDP-glucoronate were negatively associated with surgency. HM malate and kynurenate were both positively associated with effortful control and hydroxy-N6,N6,N6-trimethyllysine was negatively associated with effortful control (Figure 1). No HM metabolites were associated with negative affect. The pathway and sub-pathway of significant metabolites are presented in Table 2.

Conclusion(s): HM metabolites, including HM oligosaccharides, nucleotide sugars, and metabolites involved in the TCA cycle, amino acid metabolism, and purine metabolism, may be associated with infant surgency and effortful control. Some of these metabolites have previously been found to be associated with NDO, but many of these associations in HM are novel. Future analyses will examine later infant NDO.

Table 1. Maternal and infant characteristics


Figure 1. Elastic net coefficients of metabolites associated with a) surgency and b) effortful control
Elastic net regression adjusted for maternal age, household income, gestational age at delivery, and exclusive breastfeeding status at 6 weeks.
Level *2b (metabolite was identified by ruling out other data on the same platform) and **2c (homologues are also detected on the same platform) metabolite identification according to the levels defined by the Metabolomics Standards Initiative.

Table 2. Super pathways and sub-pathways of metabolites significantly associated with infant temperament