Choline Composition in Breast Milk–A Systematic Review and Meta‐Analysis
Authors: Chen Monica Yipu , Northington Robert , Yan Jian 
Published: April 2022

Background & ObjectiveCholine is an essential nutrient supporting optimal brain development. In breast milk, choline exists in water‐soluble (free choline, glycerophosphocholine, phosphocholine) and lipid‐soluble forms (phosphatidylcholine, sphingomyelin). Despite emerging evidence showing that these forms have different biologic effects, no systematic review has been conducted to elucidate the exact choline composition in breast milk.MethodsA comprehensive literature search using PubMed, Scopus, Cochrane, Agricola and Google Scholar was conducted for studies published through August 8, 2016 with search terms: “choline” and “human milk” or “breast milk” or “lactation”. Human studies reporting choline concentration and composition of breast milk in healthy mothers were included in the screening and assessment. For each eligible article, reported group means were extracted and converted to the same unit. Choline composition was expressed as percentage of total choline contributed by each form, based on studies that reported the full choline profile. Sample‐size weighted estimates and 95% confidence intervals (CI) of choline concentration and composition were then calculated. For articles reporting multiple measurements of the same subjects longitudinally, the average of group means over time was calculated and used in the analysis. Student's t‐test was used for group comparisons. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guideline.ResultsThe literature search yielded 259 articles for initial screening of titles and abstracts; of these, 39 articles qualified for full‐text review yielding 11 peer‐reviewed original research articles that contained extractable data and sufficient information on study population. However, only 7 articles provided concentrations of total choline and at least one choline form and thus were included in the meta‐analysis (Figure 1). For term infants, choline concentration in mature milk was substantially higher (p<0.001) than that of colostrum, and choline composition also appeared to differ (although only 1 colostrum study reported the full profile). Specifically, water‐soluble phosphocholine was the most abundant form in mature milk but the least abundant in colostrum; lipid‐soluble forms (phosphatidylcholine, sphingomyelin) represented <15 % total choline in mature milk and >40% total choline in colostrum. Data for preterm infants was limited but suggested that mature milk also had higher total choline concentration compared to colostrum. Phosphocholine was the most abundant form in both mature milk and colostrum for preterm infants, and lipid‐soluble choline represented a smaller percentage of total choline in mature milk compared with colostrum (approximately 15% vs. 26.7%).ConclusionTotal choline concentrations are substantially higher in mature milk compared to that in colostrum for both term and preterm infants. Water‐soluble choline appears to be predominant in breast milk although the extent varies according to type of breast milk and limited data availability precludes a quantitative comparison. Further research elucidating the breast milk composition and biologic effects of different choline forms on infant development is needed.Support or Funding InformationSupported and funded by Nestlé Nutrition Research, King of Prussia, PA, USA.
Weighted means and 95% confidence intervals of choline concentration and composition in breast milk

Publications included (N)
Total Subjects (n)
Total Choline (μmol/L)
Choline composition (%)

Water‐soluble choline
Lipid‐soluble choline

FC
GPC
Pcho
Total
PC
SM
Total

Term infants, colostrum
2#
74#
523 (486, 560)
19.5
26.0
13.8
59.3
21.6
19.1
40.7

Term infants, mature milk
5*
299*
1394 (1378, 1410)
11.2 (10.7,11.6)
32.4 (32.1, 32.6)
42.1 (41.4, 42.9)
85.7 (85.4, 85.9)
7.2 (71, 7.4)
7.1 (67,7.5)
14.3 (14.1, 14.6)

Preterm infants, colostrum
1
8
600
18.3
16.7
38.3
73.3
11.7
15
26.7

Preterm infants, mature milk
2
25
1300 (1295. 1306)
10.3 (8.6, 12.0)
29.8 (29.3, 30.3)
45.0 (42.7, 47.3)
85.0 (84.9, 85.1)
7.1 (70, 7.3)
7.9 (78, 7.9)
15.0 (14.9, 15.1)

1 Reported group means of total choline concentration were extracted and were converted to μmol/L. Choline composition was expressed as percentage of total choline concentration for each form; the percentage was calculated using reported group means from articles reporting the full choline profile. Sample‐size weighted means and 95% confidence intervals of choline concentration and composition were calculated when N≥2.
2 publications reported total choline concentration (n=74) of which 1 reported full composition (n=21)
5 publications reported total choline concentration (n=299) of which 4 reported full composition (n=238)
Abbreviations: FC, free choline; GPC, glycerophosphocholine; Pcho, phosphocholine: PC, phosphatidylcholine; SM, sphingomyelin.