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. Author manuscript; available in PMC: 2016 Jun 1.
Published in final edited form as: J Perinatol. 2016 Jan 7;36(4):284–290. doi: 10.1038/jp.2015.199

Breastmilk from obese mothers has pro-inflammatory properties and decreased neuroprotective factors

PG Panagos 1, R Vishwanathan 2, A Penfield-Cyr 3, NR Matthan 2, N Shivappa 4,5, MD Wirth 4,5, JR Hebert 4,5, S Sen 2,3
PMCID: PMC4888773  NIHMSID: NIHMS784562  PMID: 26741571

Abstract

OBJECTIVE

To determine the impact of maternal obesity on breastmilk composition.

STUDY DESIGN

Breastmilk and food records from 21 lean and 21 obese women who delivered full-term infants were analyzed at 2 months post-partum. Infant growth and adiposity were measured at birth and 2 months of age.

RESULT

Breastmilk from obese mothers had higher omega-6 to omega-3 fatty acid ratio and lower concentrations of docosahexaenoic acid, eicosapentaenoic acid, docasapentaenoic acid and lutein compared with lean mothers (P < 0.05), which were strongly associated with maternal body mass index. Breastmilk saturated fatty acid and monounsaturated fatty acid concentrations were positively associated with maternal dietary inflammation, as measured by dietary inflammatory index. There were no differences in infant growth measurements.

CONCLUSION

Breastmilk from obese mothers has a pro-inflammatory fatty acid profile and decreased concentrations of fatty acids and carotenoids that have been shown to have a critical role in early visual and neurodevelopment. Studies are needed to determine the link between these early-life influences and subsequent cardiometabolic and neurodevelopmental outcomes.

INTRODUCTION

An abnormal metabolic environment during fetal life, early infancy, childhood and puberty can influence the risk of obesity through the lifespan.1 A primary driver of early infant growth and metabolism is the type and amount of feeding provided to an infant. Given the numerous benefits of breastfeeding and breastmilk (BM) feeding, there have been public health campaigns to encourage exclusive breastfeeding during infants’ first 6 months. In 1972, only 22% of women initiated breastfeeding which has steadily increased to 74.6% in 2013.2 During the same time period, the prevalence of pre-pregnancy obesity increased 1% every 2 years; currently over one-third of reproductive-age women are obese.3 Maternal nutritional status, mainly studied in the context of maternal underweight, influences BM nutritional composition, and therefore infant growth. Studies of breastfeeding mothers who are underweight have found lower levels of maternal serum and BM micronutrients, such as carotenoids, compared with adequately nourished mothers.4

At the other end of the body mass index (BMI) spectrum, we have shown that obese pregnant women have lower serum concentrations of antioxidant micronutrients compared with lean pregnant women in mid-gestation, but were not able to comment on BM composition.5 Other studies have measured individual components of BM and found that maternal obesity is associated with higher BM omega (n)-6 to n-3 ratio, inflammatory markers, differences in macronutrient composition, microbiota and immunological profile.6–8 Existing literature provides limited comment on the role of diet in these findings. Rodent models additionally suggest that BM from obese dams may have a different inflammatory and immunologic profile, specifically higher levels of leptin.9 Investigators have also linked a high-fat maternal diet, independent of maternal obesity, in humans and in non-human primates, with differences in key neuroprotective fatty acids (FA) eicosapentaenoic acid and docosapentaenoic acid.10,11

Obesity is intrinsically a pro-inflammatory state and is additionally associated with differences in dietary intake,12 which can also exert an effect on inflammation.13 Given the interdependence of obesity and dietary patterns, and a paucity of studies that are able to quantify the relative contributions of maternal obesity and maternal diet on BM composition, we chose to assess the impact of both obesity and diet-associated inflammation on BM composition in our cohort. We used maternal BMI as a measure of adiposity and the Dietary Inflammatory Index (DII), which has been developed in non-pregnant adults to assess aggregate dietary inflammatory potential, as a measure of dietary inflammation. The DII is a literature-derived, population-based dietary tool developed to measure inflammatory potential of diet that has been previously validated with various inflammatory markers, including C-reactive protein,13 interleukin-6 (ref. 14) and homocysteine.15

Among its many benefits, recent studies have linked BM feeding to improved childhood neurodevelopment. BM components that have been suggested to have a role in infant neurodevelopment include docosahexaenoic acid (DHA), arachidonic acid and carotenoids. DHA and arachidonic acid, along with other polyunsaturated fatty acids (PUFAs), rapidly accumulate in the infant brain and have been shown to be important for neural and visual development. The dietary carotenoids lutein and zeaxanthin preferentially accumulate in the retina to form macular pigment, where they protect the retina from blue light damage and oxidative stress while influencing visual function.16 The impact of maternal obesity and dietary inflammation on the concentration of these anti-inflammatory, neuroprotective factors in BM has not been investigated.

Another benefit of BM feeding is decreased rates of rapid early infant weight gain and childhood obesity.17 Anti-inflammatory, immunomodulatory and hormonal properties of BM may all contribute to this link.18 Owing to the role of n-6 PUFAs in promoting differentiation of preadipocyte to adipocytes, and the antagonistic role of n-3 PUFAs in this process, the ratio of these FAs has been characterized as a factor in both inflammation and obesity development.19 Previous studies have linked n-3 PUFA content of BM with decreased childhood adiposity.20 In addition, impaired antioxidant defenses can increase systemic inflammation and oxidative burden in infancy, which has been shown in animal models to predispose to later obesity.21

Given the worldwide burden of maternal obesity and the potential long-term effects of early-life feeding practices, there is a need to understand how maternal obesity affects BM composition and thus infant growth. We hypothesized that BM from obese (Ob) mothers would differ from lean control (Lc) mothers by having (1) increased caloric density, fat and lactose content; (2) lower concentration of anti-inflammatory micronutrients; and (3) a pro-inflammatory FA profile. We further hypothesized that infants born to Ob mothers would have accelerated weight gain and increased adiposity compared with infants born to Lc mothers.

METHODS

Subjects

With Institutional Review Board approval, 21 women with pre-pregnancy BMI ≥ 30 kg m−2 (Ob group) and 21 women with pre-pregnancy BMI 18 to 25 kg m−2 (Lc group) were recruited at their Tufts Medical Center obstetrician visit between 34 and 40 weeks gestational age. BMI was calculated from the earliest weight and height during the current pregnancy. Women who planned to provide BM as the primary form of nutrition to their infants and were willing to provide one BM sample at a study visit between 4 to 10 weeks post-partum signed informed consent. Women with the following criteria were excluded from the study: delivery before 35 weeks gestational age, multiple gestation, tobacco use, intrauterine growth restriction, fetal anomalies, fetal demise or still birth. If one of these exclusions developed after consent was obtained, the subject was withdrawn from the study.

Infant measurements

Growth measurements. Birth measurements were obtained from the newborn nursery medical record. The measurements at 2 months of age were obtained at the study visit or from the pediatrician. Skinfold thickness (SFT): bicep, tricep, suprailiac and subscapular SFT were measured in the newborn nursery and at the study visit in triplicate on the left side of the body using a skinfold caliper using a standard protocol.22 Two study investigators performed all of the measurements. Ponderal index of the infants was calculated at birth using the formula: weight (kg)/length(m)3 and infant weight-for-length z-scores were calculated using the World Health Organization anthropometric calculator based on the infants’ weight and length at 2 months of age (WHO Anthro, version 3.2.2, 2011).

Maternal and infant diet composition

Subjects completed an infant diet questionnaire at the study visit. Subjects kept a 3-day food record (one weekend day and two weekdays for maternal diet) 1 week before the study visit. Subjects were instructed to log food, drink and supplements over this 3-day period. A handout describing how to determine and record portion size was provided. The food records were analyzed using the Nutrition Data System for Research software version, 2012 (Minneapolis, MN, USA). Individual dietary components were analyzed and DII scores calculated for each mother. A complete description of the DII is available elsewhere.23

Briefly, based on a search of the literature from 1950 to the end of 2010, 45 food parameters were identified among foods, nutrients and other food components that were associated with six plasma inflammatory markers (IL-1β, IL-4, IL-6, IL-10, TNF-α and CRP). A specific DII score was defined for each food parameter on the basis of the literature review (1943 articles were reviewed and scored). For each study participant, the dietary data were first linked to a global database which was developed based on 11 data sets from around the world.23 Each participant's exposure relative to the ‘standard global mean’ was expressed as a z-score. The participant's DII score was computed by multiplying this value by the specific DII score for each food parameter and by summing together all these 45 values. A higher DII score indicates a more pro-inflammatory diet.

BM analysis

BM collection

A one-time pumped BM sample was collected at the study visit. Subjects were instructed to pump a complete feed in the morning into a large container, mix the container of milk, then pour 15 to 20 ml into a small bottle provided, store the milk in their home refrigerator and then transport the milk on ice. After the study visit, the BM was stored at − 80 °C until analysis was performed on whole or diluted BM, based on assay requirement.

Macronutrient concentration

The Julie Z7 Automatic MilkoScope (2007 Electric, Regensburg, Germany) was used to measure total concentrations (g dl−1) of fat, protein and lactose by ultrasound technique. The limitations of the measurement ranges are fat 0 to 50%, protein 0 to 15%, and lactose 0 to 20%. The accuracy of this technique is ± 0.01%.

Micronutrient concentration

Vitamin A and vitamin E were measured in the BM simultaneously by a reversed-phase high-pressure liquid chromatography (Waters HPLC Empower Network system with the 717plus Wisp, 515 pump, Waters Corporation, Milford, MA, USA) procedure after extraction of the vitamins into a suitable solvent according to Bieri et al.24 Vitamin B12 was measured in diluted BM with a preliminary heat denaturation step followed by a chemiluminescent, competitive immunometric assay, (IMMULITE Vitamin B12, Catalog Number: LKVB1, Siemens Healthcare Diagnostics, Los Angeles, CA, USA).25 25-Hydroxy vitamin D was measured in BM after extraction by an equilibrium 125I radioimmunoassay procedure (25(OH) vitamin D, Catalog: 68100E. DiaSorin, Stillwater, MN, USA) using a Packard Cobra II Gamma Counter according to the technical document and Hart et al.26 Total folate was measured in BM with a preliminary heat denaturation step followed by a trienzyme extraction. The total folate in extract was analyzed by microbial L casei assay.27 The intra- and inter-assay coefficients of variation for vitamins A and E, B12 and (25(OH) D) are 4.5 and 5.5%, 7.5 and 9.0, and 9.0% and 11.0%, respectively.24–26 The inter-assay coefficients of variation for folate are 3.03%.27

Carotenoids

Carotenoids were extracted from BM by a method adapted from Giuliano et al.28 The dried extract was reconstituted and analyzed using reverse-phase high-pressure liquid chromatography using a method described by Yeum et al.29 with a C30 carotenoid column (3 μm, 150 × 4.6 mm, YMC, Wilmington, NC, USA). The concentrations of lutein, β-carotene and lycopene in BM are reported as the sum of cis and trans isomers and the concentrations were expressed per volume of BM sample analyzed.

FA profiles

Total lipids were extracted from BM samples by a modified Folch method,30 followed by saponification and methylation. The resulting FA methyl esters were analyzed using an established gas chromatography method.31 Peaks of interest were identified by comparison with authentic FA standards (Nu-Chek Prep, Elysian, MN, USA) and expressed as molar percentage (mol%) proportions of total FA. Interassay coefficients of variation were <4.5% for FA present at levels >1%. Plasma desaturase enzyme activities were estimated as product to precursor ratios of individual FAs and included stearoyl-CoA-desaturase (SCD-16; 16:1n-7/16:0 and SCD-18; 18:1n-9/18:0), delta-6-desaturase (D6D; 18:3n-6/18:2n-6) and delta-5-desaturase (D5D; 20:4n-6/20:3n-6).32

Statistical analysis

A sample size of 21 Lc subjects and 21 Ob subjects was predetermined with the primary outcome of infant weight and height at 2 months of life. With 21 subjects in each group and an overall α of 0.05, there is 80% power to detect a difference of one standard deviation at 2 months for weight and length measurements. Categorical data were analyzed with the Fisher's exact test. Continuous data that were normally distributed were analyzed with Student's t-test. The Mann–Whitney test was used for data that were not normally distributed. Composition of BM was analyzed first without adjustment for dietary intake. BM vitamin D concentrations were adjusted for self-reported maternal race using multivariate linear regression. Next, multivariate linear regression was used to determine the relative contribution (the standardized coefficient, β) of independent variables: DII and BMI, on BM composition. All the tests were two-sided and statistical significance was set at P < 0.05. All data were analyzed using STATA (StataCorp LP, College Station, TX, USA).

RESULTS

Subjects

A total of 74 (35 Lc and 39 Ob) eligible subjects were recruited from November 2012 to April 2014. Of these, one Lc subject and 14 Ob subjects dropped out owing to unsuccessful breastfeeding (P < 0.0001). There were no significant differences in baseline characteristics, including BMI, between the subjects who completed the study versus those who dropped out (data not shown). Table 1 summarizes the characteristics of the study population of subjects and their infants.

Table 1.

Subject characteristics

Lc (n = 21) Ob (n = 21) P
Maternal characteristics
    Maternal BMI (kg m–2), mean (s.d.) 22 (1.9) 35 (4.0)
    Maternal age (years), mean (s.d.) 31 (3.7) 30 (5.7) 0.64
        Race or ethnic group, number
        Caucasian 12 11 1
        African American 1 6 0.09
        Hispanic 1 1 1
        Asian 7 3 0.27
    Total gestation weight gain (kg), mean (s.d.) 13.3 (4.3) 11.7 (7.6) 0.42
    Gestational diabetes type A1, number 1 1 1.00
    Prenatal vitamin intake at study visit, number 20 14 0.05a
Infant characteristics
    Gestational age in weeks, mean (s.d.) 39 (1) 39 (1) 1
    Mode of delivery C-section, number 0 6 0.02a
    Male sex, number 8 10 0.76
        Apgar score, mean (s.d.)
        1 min 8 (1.5) 8 (0.6) 0.95
        5 min 9 (0.3) 8 (0.4) 0.41
        Exclusive breastfeeding, number
        In nursery 19 18 0.24
        At time of study visit 15 10 0.02a
        Formula supplementation at time of study visit
        Volume per feed (ounces) 3.3 (0.7) 4.2 (2.7) 0.41
        Duration of time between feeds (hours) 3 (1) 3 (2) 0.79
    Infant days of life at study visit, mean (s.d.) 50 (10.7) 52 (11.4) 0.66
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Abbreviations: BMI, body mass index; Lc, lean control; Ob, obese.

a

Statistically significant differences (P < 0.05, determined by Fisher's exact test for categorical variables or Student's t-test for continuous variables).

Infant measurements

The growth measurements are shown in Table 2. There were no statistically significant differences in mean weight, length, ponderal index, SFT and head circumference measured at birth and 2 months of age between infants born to Ob and Lc subjects or in infants who were exclusively breastfeeding.

Table 2.

Infant measurements

Lc
Ob
P
Mean (s.d.) Mean (s.d.)
Measurement
    Birth n = 21 n = 21
        Weight (kg) 3.3 (0.5) 3.4 (0.5) 0.55
        Length (cm) 50.8 (2.4) 50.2 (2.8) 0.37
        Ponderal index (kg m–3) 25.4 (2.2) 27.1 (3.4) 0.05
        Head circumference (cm) 34.3 (0.9) 34.9 (1.3) 0.11
        Weight-for-length z-score –0.72 (1.0) –0.05 (1.5) 0.06
    2 months of age n = 19 n = 14
        Weight (kg) 5.12 (0.57) 5.4 (0.77) 0.45
        Length (cm) 58.4 (2.5) 58.1 (3) 0.81
        Ponderal index (kg m–3) 25.9 (2.4) 26.9 (3.3) 0.29
        Head circumference (cm) 38.7 (1.3) 39.4 (1.3) 0.22
        Weight-for-length z-score –0.79 (1.0) –0.06 (1.3) 0.09
SFT (skinfold thickness)
    Birth n = 18 n = 14
        Bicep SFT (mm) 10.7 (0.93) 11 (1.1) 0.47
        Tricep SFT (mm) 11.2 (1) 11.6 (1.5) 0.59
        Suprailiac SFT (mm) 11 (1.1) 11.4 (1.1) 0.34
        Subscapular SFT (mm) 11.2 (1.4) 11.5 (1.6) 0.93
    Study visit n = 21 n = 21
        Bicep SFT (mm) 12.2 (1.2) 12.1 (1.2) 0.96
        Tricep SFT (mm) 13.1 (1.3) 13.2 (1.7) 0.94
        Suprailiac SFT (mm) 13.9 (2.3) 14.7 (3.3) 0.68
        Subscapular SFT (mm) 13.2 (1.7) 13.7 (2.4) 0.63
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Abbreviations: Lc, lean control; Ob, obese.

Maternal dietary intake

Table 3 shows the maternal diet composition for energy, macronutrients, micronutrients and FA. There were no differences in intake of total macronutrients (total fat, protein and sugars) or intake of vitamin E, vitamin D, total saturated fatty acids, monounsaturated fatty acids (MUFAs), PUFA and trans-FA between groups. Most dietary databases report combined lutein and zeaxanthin content of foods and hence maternal intake of lutein and zeaxanthin are reported together. Dietary intake of lutein +zeaxanthin was significantly higher in Lc compared with Ob subjects. Ob women had a trend towards a more pro-inflammatory diet, as indicated by a higher DII score (P = 0.06).

Table 3.

Maternal diet composition

Maternal dietary intake (mean of 3 days) Lean (n = 21)
 Obese (n = 21)
 P*
Mean (s.d.) Mean (s.d.)
Energy (kcal) 2090.5 2068.8 0.89
Macronutrients (g per 1000 kcal)
    Total fat 37.5 (8.8) 39.0 (6.0) 0.52
    Total protein 44.0 (9.0) 42.5 (12.7) 0.67
    Total carbohydrate 125.0 (22.7) 122.0 (21.4) 0.66
    Total sugars 48.1 (14.8) 48.7 (16.7) 0.90
Micronutrients (per 1000 kcal)
    Retinol (mcg) 209.4 (135.1) 230.5 (100.5) 0.57
    Vitamin E, alpha-tocopherol (mg) 5.9 (3.9) 4.8 (3.1) 0.16
    Vitamin E, gamma-tocopherol (mg) 6.4 (3.1) 6.2 (2.6) 0.80
    Vitamin B12 (mcg) 2.1 (0.9) 2.0 (0.9) 0.79
    Vitamin D2 (mcg) 0.2 (0.4) 0.2 (0.7) 0.91
    Vitamin D3 (mcg) 1.7 (2.3) 1.8 (1.8) 0.60
    Total folate (mcg) 237.7 (79.0) 182.2 (50.0) 0.01*
Carotenoids (mg per 1000 kcal)
    Lutein and zeaxanthin 2.08 (2.92) 0.58 (0.48) 0.002*
    Cryptoxanthin 0.11 (0.15) 0.04 (0.04) 0.33
    α-Carotene 0.31 (0.35) 0.17 (0.29) 0.13
    β-Carotene 2.35 (3.19) 0.95 (0.75) 0.09
    Lycopene 1.63 (1.55) 1.64 (1.65) 0.86
Total FA (g per 1000 kcal)
    SFA 12.2 (3.8) 12.7 (3.0) 0.66
    MUFA 13.6 (4.2) 14.6 (3.3) 0.42
    PUFA 8.4 (3.0) 8.5 (1.5) 0.85
    PUFA n-3 2.5 (0.7) 2.2 (0.7) 0.12
    Trans-FA 2.7 (1.2) 3.3 (1.4) 0.13
SFA profiles (% total fat)
    8:0 (caprylic acid) 0.5 (0.3) 0.3 (0.2) 0.03*
    10:0 (capric acid) 0.7 (0.4) 0.6 (0.3) 0.25
    12:0 (lauric acid) 2.1 (1.9) 0.9 (1.0) 0.004*
    14:0 (myristic acid) 3.0 (1.5) 2.8 (1.3) 0.62
    16:0 (palmitic acid) 16.9 (3.4) 18.0 (1.8) 0.21
    18:0 (stearic acid) 7.5 (2.1) 7.7 (1.2) 0.70
    20:0 (arachidic acid) 0.2 (0.1) 0.2 (0.08) 0.17
    22:0 (behenic acid) 0.2 (0.2) 0.2 (0.2) 0.20
MUFA profiles (% total fat)
    14:1 (myristoleic acid) 0.07 (0.06) 0.09 (0.13) 0.95
    16:1 (palmitoleic acid) 1.5 (0.6) 1.8 (0.7) 0.12
    18:1 (oleic acid) 34.0 (5.4) 34.7 (5.2) 0.67
    20:1 (gadoleic acid) 0.3 (0.2) 0.3 (0.2) 0.81
    22:1 (erucic acid) 0.07 (0.14) 0.01 (0.01) 0.10
PUFA profiles (% total fat)
    18:3 (linolenic acid) 2.3 (0.7) 1.9 (0.7) 0.14
    18:2 (linoleic acid) 19.4 (5.3) 19.5 (3.7) 0.93
    20:4 (AA) 0.2 (0.09) 0.2 (0.1) 0.12
    20:5 (EPA) 0.06 (0.08) 0.05 (0.07) 0.75
    22:5 (DPA) 0.03 (0.05) 0.04 (0.05) 0.66
    22:6 (DHA) 0.2 (0.2) 0.2 (0.2) 0.73
Trans-FA profiles (% total fat)
    18:1 (elaidic acid) 2.1 (1.1) 2.6 (1.4) 0.16
    18:2 (linolelaidic acid) 0.4 (0.2) 0.5 (0.2) 0.11
    16:1 (trans 7-hexadecenoic acid) 0.06 (0.05) 0.05 (0.04) 0.86
Dietary Inflammatory Index (DII) –0.68 (1.01) –0.13 (0.82) 0.06
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Abbreviations: AA, arachadonic acid; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; FA, fatty acid; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; SFA, saturated fatty acid.

*

P < 0.05, by Student's t-test or Mann–Whitney test. More negative DII scores represent more anti-inflammatory diets.

BM composition

Table 4 shows the BM composition of macronutrients, micronutrients, FA and carotenoids for Lc and Ob subjects. BM composition and time of collection were not related. There were no significant differences in the caloric density, total fat, total protein and total lactose concentrations of the BM between the two groups (Table 4).

Table 4.

BM composition

Lc BM
Ob BM
P
Mean (s.d.) Mean (s.d.)
Energy n = 21 n = 21
    Calories per ounce 19.6 (4.8) 19.6 (5.3) 0.79
Macronutrients (g per 100 ml) n = 21 n = 21
    Total fat 4.0 (1.8) 3.5 (1.9) 0.32
    Total protein 1.3 (0.04) 1.3 (0.1) 0.73
    Total lactose 6.9 (0.3) 7.0 (0.5) 0.78
Micronutrients n = 20 n = 21
    Retinol (μg dl–1) 4.6 (1.7) 5.5 (6.6) 0.31
    Vitamin E, alpha-tocopherol (μg dl–1) 378.1 (171.7) 325.1 (267.9) 0.069
    Vitamin E, gamma-tocopherol (μg dl–1) 80.0 (56.4) 109.0 (55.6) 0.054
    Vitamin B12 (pg ml–1) 488.0 (451.8) 671.8 (933.0) 0.79
    25-OH vitamin D (ng ml–1) (Lc n = 14, Ob n = 17) 1.3 (0.6) 0.8 (0.7) 0.0025**
    Total folate (ng ml–1) 46.4 (42.2) 41.3 (29.5) 0.63
Carotenoids (μg l–1) n = 17 n = 20
    Lutein 36.6 (24.2) 18.5 (10.9) 0.006*
    Zeaxanthin 9.1 (7.0) 5.7 (2.4) 0.048*
    Cryptoxanthin 32.3 (40.5) 7.7 (5.0) 0.011*
    α-Carotene 7.4 (5.9) 2.4 (1.8) 0.001*
    β-Carotene 54.4 (44.9) 14.4 (7.0) < 0.001*
    Lycopene 43.1 (38.8) 29.8 (21.4) 0.196
Total FA (mol%) n = 21 n = 21
    SFA 42.3 (6.7) 44.6 (5.8) 0.50
    MUFA 35.4 (4.3) 34.2 (4.8) 0.36
    PUFA n-6 18.1 (3.5) 18.5 (3.1) 0.72
    PUFA n-3 2.0 (0.5) 1.6 (0.3) 0.0033*
    Trans-FA 1.1 (0.4) 1.1 (0.4) 0.88
SFA profiles (mol%) n = 21 n = 21
    8:0 (caprylic acid) 0.2 (0.1) 0.2 (0.7) 0.26
    10:0 (capric acid) 2.5 (0.6) 2.3 (0.6) 0.20
    12:0 (lauric acid) 8.9 (3.4) 8.5 (3.0) 0.86
    14:0 (myristic acid) 7.7 (2.8) 7.7 (2.8) 0.95
    16:0 (palmitic acid) 16.7 (3.1) 19.5 (2.3) 0.0001*
    18:0 (stearic acid) 6.5 (1.8) 5.8 (1.0) 0.14
    20:0 (arachidonic acid) 0.3 (0.2) 0.2 (0.05) 0.70
    22:0 (behenic acid) 0.08 (0.003) 0.06 (0.02) 0.0025*
MUFA profiles (mol%) n = 21 n = 21
    14:1n-5 (myristoleic acid) 0.3 (0.9) 0.2 (0.1) 0.29
    16:1n-7 (palmitoleic acid) 2.4 (0.8) 2.5 (0.9) 0.84
    18:1n-9 (oleic acid) 30.3 (3.7) 29.0 (4.6) 0.28
    20:1n-9 (gondoic acid) 0.4 (0.7) 0.3 (0.08) 0.0001*
    22:1n-9 (erucic acid) 0.07 (0.03) 0.05 (0.01) 0.0098*
PUFA profiles (mol%) n = 21 n = 21
        PUFA n-6
        18:2n-6 (linoleic acid) 16.6 (3.4) 17.0 (3.0) 0.74
        18:3n-6 (gamma-linolenic acid) 0.16 (0.06) 0.16 (0.07) 0.91
        20:4n-6 (AA) 0.5 (0.08) 0.5 (0.1) 0.7
        PUFA n-3
        18:3n-3 (ALA) 1.7 (0.6) 1.2 (0.3) 0.008*
        20:5n-3 (EPA) 0.8 (0.04) 0.6 (0.03) 0.013*
        22:5n-3 (DPA) 0.2 (0.03) 0.1 (0.05) 0.0025*
        22:6n-3 (DHA) 0.3 (0.1) 0.2 (0.06) 0.001*
    PUFA n-6 to PUFA n-3 ratio 9.3 (2.3) 12.0 (3.3) 0.0034*
Trans-FA profiles (mol%) n = 21 n = 21
    16:1n- 9T (trans-7-hexadecenoic acid) 0.03 (0.01) 0.05 (0.02) 0.0012*
    18:1T (petroselinic+elaidic+trans-vaccenic) 0.084 (0.04) 0.085 (0.03) 0.75
    18:2T (linolelaidic acid) 0.09 (0.04) 0.1 (0.03) 0.23
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Abbreviations: AA, arachadonic acid; BM, breastmilk; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; FA, fatty acid; Lc, lean control; MUFA, monounsaturated fatty acid; Ob, obese; PUFA, polyunsaturated fatty acid; SFA, saturated fatty acid.

*

P < 0.05 by Student's t-test or Mann–Whitney test. Molar % is calculated based on the sum of 37 individual FAs of which 23 are reported in this table.

**

P < 0.05, adjusted P-value, determined by multivariate linear regression models controlling for maternal race.

Vitamin D was lower in Ob BM (38%, P < 0.05), with or without adjustment for maternal race. Concentrations of lutein, zeaxanthin, cryptoxanthin, α-carotene and β-carotene were significantly lower in BM from Ob mothers compared with Lc mothers (50%, 37%, 76%, 67%, 74%, respectively, all P < 0.05). This difference remained statistically significant for lutein and zeaxanthin combined (P = 0.017), as well as α-carotene (P = 0.001) and β-carotene (P = 0.001), after adjusting for dietary intakes of these carotenoids.

There were no differences in BM total SFA, MUFA or n-6 PUFA, however, the Ob BM had significantly lower content of n-3 PUFA (20%, P = 0.003). Ob BM had less alpha linolenic (ALA; 29%, P = 0.008), eicosapentaenoic acid (25%, P = 0.013), docosapentaenoic acid (50% = 0.003) and DHA (33%, P = 0.001). The n-6:n-3 FA ratio was higher in BM from Ob mothers (P = 0.003). The following desaturase indices were estimated using BM FA concentrations: SCD1 (16:1n-7/16:0), SCD2 (18:1n-9/18:0), D5D (20:4n-6/20:3n-6) and D6D (18:3n-6/18:2n-6 2, 20:3n-6/18:2n-6). These reflect mammary gland synthesis of MUFAs and PUFAs and were not statistically significantly different between the two groups.

As shown in Figure 1, maternal DII and maternal BMI were associated with different components of BM composition. Maternal DII score (and not maternal obesity) was strongly associated with BM: SFAs (β = 0.44% molar increase for every 1 point increase in DII, P < 0.01) and MUFAs (β = − 0.41% molar decrease for every 1 point increase in DII, P < 0.01) (Figure 1a). Maternal BMI (and not the DII) was strongly associated with with BM: n-6/n-3 ratio (β = 0.33 decrease in n-6/n-3 ratio for every 1 kg m−2 increase in BMI, P = 0.01, Figure 1b), eicosapentaenoic acid (β = − 0.36% molar decrease for every 1 kg m−2 increase in BMI, P < 0.01, Figure 1c), DHA (β = − 0.41 molar decrease for every 1 kg m−2 increase in BMI, P < 0.01, Figure 1d), Lutein (β = − 0.46-μg l−1 decrease for every 1 kg m−2 increase in BMI, P = 0.01, Figure 1e) and had a trend toward significance with BM zeaxanthin (β = − 0.3046 μg l−1 decrease for every 1 kg m−2 increase in BMI, P = 0.08) and BM docosapentaenoic acid (β = − 0.28% molar decrease for every 1 kg m−2 increase in BMI, P = 0.07). BM n-3 PUFA concentration was associated with both maternal obesity (r = − 0.33, P = 0.01) and the DII (r = − 0.34, P = 0.01). BM n6:n3 ratio was positively associated with infant weight-for-length z-score at study visit (r = 0.43, P < 0.05).

Figure 1.

Figure 1

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Associations of breastmilk fatty acid and carotenoid composition. (a) Maternal DII is associated with the concentration of breastmilk saturated fatty acids (SFAs) and breastmilk monounsaturated fatty acids (MUFAs). (b–e) Maternal BMI is associated with breastmilk concentrations of n6:n3 fatty acid ratio (b), EPA (c), DHA (d) and lutein (e). BM, breastmilk; BMI, body mass index; DHA, docosahexaenoic acid; DII, Dietary Inflammatory Index; EPA, eicosapentaenoic acid.

DISCUSSION

In our cohort, BM composition differed between Ob and Lc women. A higher n-6:n-3 PUFA ratio suggests a relatively pro-inflammatory profile of Ob compared with Lc BM. In addition, concentrations of DHA, lutein and zeaxanthin, all of which have been implicated in infant neural development, were lower in the BM of Ob compared with Lc women. Nutrition provided during early infancy can have life-long effects and this study provides early evidence that breastfed infants born to Ob mothers may not be receiving the same diet quality as infants born to Lc mothers.

A pro-inflammatory diet, such as a standard Western diet, with a high n-6:n-3 ratio, is thought to promote inflammation and disease.33 In contrast, a diet rich in n-3 PUFAs, such as a Mediterranean diet and many non-Western diets, has been shown to suppress inflammatory markers interleukin-1 beta, tumor necrosis factor and interleukin-6, and protect against cardiovascular disease.34 Three studies underscore the importance of optimal BM composition in early infancy. In 2002, Plagemann et al.35 reported that infants fed BM from mothers with diabetes had a higher rate of obesity at 2 years compared with infants of diabetic mothers fed donor BM in the first week of life. Similarly, Fields and Demerath36 found a negative association between BM concentration of the pro-inflammatory cytokine TNFα and infant lean mass at 1 month. Pederson et al.20 found an inverse association between BM DHA content and childhood fat mass. It is possible that BM with a pro-inflammatory profile during the critical period of early infancy may further contribute to metabolic dysregulation in offspring. Interestingly, we did see a positive correlation between BM n6:n3 ratio and infant weight-for-length z-score at 2 months, suggesting a link between BM inflammatory composition and accelerated infant growth. Infants who cross weight-for-length percentiles by 6 months of age are known to have increased risk for obesity.37 Future studies should specifically examine the impact of these differences in BM composition on long-term growth, adiposity and metabolism of children.

We report for the first time that BM from Ob mothers may differ from Lc mothers in the concentrations of FAs (eicosapentaenoic acid, docosapentaenoic acid and DHA) and carotenoids (lutein and zeaxanthin) that are all critical for infant neurodevelopment. In animal models, extremely low concentrations of n-3 PUFA have been shown to impair neurogenesis.38 The concentration of DHA in human milk varies widely, and higher concentrations have been positively correlated with visual and language development.39 DHA insufficiency in pregnancy has been associated with higher risk of delayed language development in one study, although other studies have had mixed findings.40 Lutein preferentially accumulates in the neural retina and brain, which undergo rapid maturation and development in the first 6 to 12 months of life. Lower levels of lutein in Ob BM may be due to accumulation of carotenoids in adipose tissues, which may impede transport into BM.41 Future studies should evaluate the impact of these early nutritional differences on development, cognition and vision in childhood.

The mechanisms underlying the observed differences in BM composition between groups could be attributed to differences in (1) mammary gland synthesis of BM; (2) maternal metabolic status; or (3) dietary differences between groups. Mammary gland production of MUFAs and PUFAs did not differ between groups based on desaturase indices, suggesting that the differences in BM FAs were not because of altered mammary function. Our findings raise the question of whether specific maternal metabolic markers might be predictive of BM composition. In our cohort, maternal obesity and maternal pro-inflammatory diet were associated with different components of BM. Future studies may investigate whether specific dietary alterations or maternal supplementation might be beneficial in optimizing BM quality of obese lactating women.

In our cohort, Ob women were less likely to provide exclusive BM compared with Lc women by the time of the follow-up study visit, despite all women initially intending to breastfeed. It has been previously reported that Ob women have lower breastfeeding rates and are less likely to initiate and maintain breastfeeding.42 In our study, we were able to confirm these observations with higher rates of breastfeeding failure in the Ob vs Lc groups. Higher rates of cesarean section delivery in Ob women may partially explain this.43 Recently, maternal obesity-related inflammation has also been implicated in lactation failure in an animal model.44

There are limitations to our study. Mothers did not have controlled diets or vitamin regimens. Women in the Ob cohort were less likely to take prenatal vitamins at their study visit than the Lc cohort. This may influence inflammatory status, although our diet history included supplement intake. Our dietary history was limited to a 3- day recall and previous studies have shown that dietary recall from Ob women underestimates intake more than from Lc women.45 We were not able to directly assess maternal inflammatory status with blood biomarkers in this study; although we have shown previously that obese women do have higher levels of inflammation and oxidative stress as well as decreased concentrations of specific antioxidant micronutrients.5 We also were not able to assess additional sources of inflammation beyond dietary inflammation and maternal BMI. Infants who were partially breastfed were included in the analysis which may confound growth results. There were differences in racial composition between groups, but race did not impact dietary intake. In addition, BM was provided as a one-time sample at various times of the day, which is known to vary within a feeding and throughout the day.46 However, owing to the nature of the sample collection, we were not able to collect 24-hour samples. Finally, our study provides a thorough investigation of many nutritional components of breastmilk, but we were not able to comment on other immunologic or microbiomic components that may be altered by maternal obesity.

We have shown that the composition of BM from Ob women differs in FA and carotenoid composition compared with the BM of Lc women. Specifically, BM from Ob mothers had lower DHA and lutein+zeaxanthin content, which are critical for neurodevelopment. Future studies should determine whether these differences impact infant serum DHA levels, serum and retinal lutein, and subsequent visual and neurodevelopment. We also found that BM from Ob women had a pro-inflammatory FA profile compared with BM from Lc women. These findings raise the concern that Ob mothers may be propagating a pro-inflammatory state to their infants, and long-term metabolic outcomes for these infants should be investigated. Further studies are needed to determine strategies by which we can optimize maternal, and therefore infant, nutrition. Improving maternal pre- and post-pregnancy health and optimizing infant nutrition should be a public health priority, given its impact on the life-long health of the next generation.

ACKNOWLEDGEMENTS

This work is supported by Tufts Medical Center Department of Pediatrics, Susan Saltonstall Foundation Grant Program, Pilot Project Award 2012, NICHD K23HD074648 (SS), NIDDK R44DK103377 (NS, MDW and JRH).

Footnotes

CONFLICT OF INTEREST

JRH owns controlling interest in Connecting Health Innovations LLC (CHI), a company planning to license the right to his invention of the dietary inflammatory index (DII) from the University of South Carolina to develop computer and smart phone applications for patient counseling and dietary intervention in clinical settings. MDW and NS are employees of CHI. The subject matter of this paper will not have any direct bearing on that work, nor has that activity exerted any influence on this project. The remaining authors declare no conflict of interest.

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