Table 1.

Summary of predominantly human studies of novel factors focusing on studies during the window of lactation and programming outcomes

Bioactive Component	Author (Year)	Species (n)	Milk Collection Standardized	Lactation Time Point(s)	Maternal Influence	Infant Outcomes	Weakness/Limitations
miRNA	Xi (2016)	Human (n=86)	No	2-5d, 3 mo	miRNA-30B, let-7a, miRNA-378 in colostrum & mature milk are negatively correlated with maternal BMI (pre-pregnancy & late pregnancy), weight Let-7a in mature milk is negative correlated with late pregnancy maternal weight No miRNA differences with gestational diabetes mellitus or gestational age.	miRNA-30B & miRNA-378 were higher in colostrum for girls	No maternal diet data No infant anthropometrics
	Zamanillo (2019)	Human (n=59)	Yes	1mo, 2mo, 3mo	NW mothers had negative correlations between milk miRNAs expression Leptin/adiponectin levels observed in NW but not in OW/OB mothers	In NW mothers, infant BMI at 2 years negatively correlated with miRNA at 2m (miR-103, miR-17, miR-181a, miR-222, miR-let7c, miR-146b). No infant growth correlations with OW/OB mothers	No maternal diet data Infant growth at 2 years & maternal BMI were obtained by maternal recall
	Shah (2021)	Human (n=60)	Yes	1mo & 3mo	Decreased miRNA (miR-148a, miR-30b) abundance at 1mo in OW/OB mothers compared to NW mothers	miR-184a was negatively associated with infant weight, FM and FFM at 1m miR-32 was negatively associated with 1m infant weight miR-30b abundance was positively associated with 1m weight, %fat & fat mass. No significant associations were observed with 1m milk miRNA & 6m infant anthropometrics, or between 3m milk miRNA and infant anthropometrics at 3m or 6m	No maternal diet data
Lipokines&Signaling lipids	Brezinova (2018)	Human (n=53) & Mouse	No	72 hr	PAHSAs levels were positively associated with weight gain in pregnancy. Obese mothers had lower total PAHSA and 5-PAHSA levels	No outcomes examined	No maternal diet data. No infant outcomes examined
	Bruun (2018)	Human (n=100)	No	4mo	Only adjusted for maternal BMI	The low weight z-score group had higher concentrations of oleoylethanolamide, steroylethanolamide, palitoylethanolamide vs infants in the high weight z-score. Lower skinfold thickness & weight gain per day were associated with higher milk steroylethanolamide	No early lactation samples. No maternal diet data. Storage techniques altered concentration of N-acylethanolamides.
	Wolfs (2021)	Human (n=58)	Yes	1mo, 3mo, 6mo	12,13-diHOME positively associated with height, however no association with maternal pre-pregnancy BMI or gestational weight gain 12,13-diHOME concentration increased in milk after exercise at 1mo postpartum	12,13-diHOME was positively associated with birth weight for length and BMI z-score, and negatively associated with in BMI & weight for length z-score over the first 6 months of life 12,13-diHOME was negatively associated with subcutaneous and overall adiposity at 1mo No association between infant sex and milk 12,13-diHOME levels High milk succinate was associated with lower infant BMI at 6mo	No maternal diet data.
Small molecules & Metabolites	Isganaitis (2019)	Human (n=35)	Yes	1mo, 6mo	Maternal BMI was associated with 10 differing metabolites at 1mo 20 differing metabolites at 6mo 1mo, maternal obesity was linked to differences in human milk orotate & 1,5-anhydroglucitol 6mo maternal obesity was associated with increased acylcarnitine, monosaccharide, & 1,5-anhydroglucitol	Adenine positively correlated with infant weight at 1mo, while X-19656 (an unidentified metabolite) was negative correlated 1mo, 5-methylthioadenosine was positively correlated with infant %fat and maternal BMI. No correlations between milk metabolites with infant weight or adiposity and maternal BMI at 6mo	No maternal diet data.
	Prentice (2019)	Human (n=619)	Yes	4-8wks	SCFAs were not associated with maternal BMI Mothers exclusively breastfeeding had higher milk butyrate	Butyrate was negatively associated with infant weight between 3mo-12mo Milk formic acid levels were negative associated with BMI over the first 2 years of life Acetate was negatively associated with skinfold thickness at 3mo	No maternal diet data.
	Saben (2020)	Human (n=159)	Yes	2wk, 2mo, 6mo	Maternal BMI & %fat positively correlated with amount of human milk monosaccharides & sugar alcohols	6mo milk mannose, lyxitol & shikimic acid showed a positive association with infant fat mass & %fat	No maternal diet data.
	Ribo (2021)	Human (n=143) & Mouse	Yes	1mo	Did not report maternal influence on milk betaine	Human milk betaine concentration was inversely associated with infant weight-for-length z-score at 1mo & 12mo	No maternal diet data
					In mice supplemented with betaine, a fivefold increase in betaine milk content was observed	In mice, early-exposure to betaine in lactation was associated with decreased adiposity & improved glucose homeostasis in adult mice. Betaine intake transiently increases offspring Akkermansia species during early life, which is linked to lower gut inflammation in mice
Fructose	Goran (2017)	Human (n=25)	Yes	1mo, 6mo	Maternal BMI was used as a covariate	Milk fructose was associated with high infant body weight, lean mass, FM, weight for length z-score, & bone mineral content at 6mo	No maternal diet data.
	Berger (2018)	Human (n=41)	Yes	6 wks	HFCS-sweetened beverage increased milk fructose for up to 5 hrs without an impact on milk glucose or lactose.	None were collected	No infant outcomes No maternal diet data
	Berger (2020)	Human (n=88)	NA	NA	No differences in maternal fructose or sugar-sweetened beverage + juice intake based on maternal pre-pregnancy BMI	Infant 24mo cognitive development scores were inversely correlated with fructose consumption by their mothers at 1mo postpartum No association at 6mo postpartum	Homogenous sample (limited to Hispanic mother-infant dyads) No milk compositional analysis was performed