| | Breastfeeding in Infancy and Adult Cardiovascular Disease Risk FactorsAbstract BackgroundPublic health recommendations advocate breastfeeding in infancy as a means to reduce obesity in later life. Several prior studies relating breastfeeding to cardiovascular risk factors have been limited by lack of adjustment for maternal and participant confounding factors. MethodsWe ascertained breastfeeding history via questionnaire from mothers enrolled in the Framingham Offspring Study. In their young to middle-aged adult children enrolled in the Framingham Third Generation, we examined the relations between maternal breastfeeding history (yes, no) and cardiovascular risk factors, including body mass index (BMI), high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, fasting blood glucose, and systolic and diastolic blood pressure levels. We applied generalized estimating equations to account for sibling correlations and adjusted for maternal and participant lifestyle, education, and cardiovascular risk factors. ResultsIn Third Generation participants (n = 962, mean age = 41 years, 54% were women), 26% of their mothers reported breastfeeding. Compared with non-breastfed individuals, breastfed adult participants had lower multivariable-adjusted BMI (26.1 kg/m2 vs 26.9 kg/m2, P = .04) and higher HDL cholesterol levels (HDL 56.6 mg/dL vs 53.7 mg/dL, P = .01). On additional adjustment for BMI, the association between breastfeeding and HDL cholesterol was attenuated (P = .09). Breastfeeding was not associated with total cholesterol, triglycerides, fasting blood glucose, systolic blood pressure, or diastolic blood pressure. ConclusionBreastfeeding in infancy is inversely associated with adult BMI and positively associated with HDL cholesterol. Associations between breastfeeding and BMI may mediate the association between breastfeeding and HDL cholesterol. Recent US and World Health Organization recommendations strongly advocate breastfeeding in infancy as a means toward not only reducing infant infections but also protecting against adverse adult health outcomes such as obesity.1, 2, 3 Prior epidemiologic evidence suggests that breastfeeding in infancy also may have protective effects on cardiovascular disease risk factor profiles4, 5, 6, 7, 8, 9 and cardiovascular disease risk4, 10 in adulthood. Previous studies have demonstrated that breastfeeding in infancy can lead to small reductions in adolescent and adult blood pressure levels,4, 6, 11 decreased total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels in adulthood,4, 5, 8 and modest decreases in adult body mass index (BMI).4 Clinical Significance•Being breastfed in infancy for 1 month or more is associated with higher adult HDL levels and lower mean adult body mass index. •Our study suggests that the benefits of breastfeeding extend beyond childhood to adult health outcomes. Some prior studies have been limited by self-reported as opposed to directly measured maternal12 and offspring cardiovascular disease risk factors.12 Furthermore, some prior studies have been limited by the failure to account for potential maternal and offspring confounders, including socioeconomic status.8 Highlighting the importance of accounting for socioeconomic status, a recent investigation in the Nurses Health Study did not demonstrate a significant association between breastfeeding and BMI on adjustment for socioeconomic status.12 Detailed risk factor ascertainment, sociodemographic data collection, and maternal breastfeeding report among Framingham Heart Study Offspring mothers and their adult children in the Third Generation cohort allowed the opportunity to extend previous data on the association of breastfeeding in infancy with several cardiovascular disease risk factors in adulthood. We hypothesized that breastfeeding in infancy would be protective for cardiovascular disease risk factors, but that these associations would be attenuated after accounting for maternal and participant socioeconomic and lifestyle characteristics. Materials and Methods  Study Sample Participants for this study were part of the Third Generation cohort of the Framingham Heart Study; their mothers were members of the Offspring cohort. The Original Framingham Heart Study Cohort13 and Framingham Offspring cohorts have been described.14 Between July 1996 and May 1997, a breast health survey was mailed to Offspring cohort women that included questions regarding breastfeeding history of each of their children. The design and selection criteria for women chosen to receive the breast health survey have been described.15 Briefly, women free of breast cancer with a first-degree female relative enrolled in the Framingham Heart Study were sampled on the basis of 1 of 3 criteria: women having a mother or sister with documented breast cancer; women having a mother or sister with a non-gynecologic cancer; and women with mothers or sisters free of documented cancer. A total of 683 participants (77%) returned the questionnaire (Figure). Among these 683 offspring participants, participants were excluded who completed the questionnaire who did not have a child (n = 60), whose children did not attend the Third Generation study (n = 142), or who returned the questionnaire with incomplete or inconsistent information (n = 88). Because of these exclusion criteria, only 393 (44%) of the offspring women survey sample were included in the analysis. These 393 mothers provided the source for the Third Generation cohort participants (n = 962) (Figure). The 393 offspring women included in this study when compared with offspring women with children enrolled in the Third Generation cohort who are not included in this study (n = 1114) had similar cardiovascular disease risk factor profiles at enrollment in the Framingham Heart Study with the exception of a slightly higher diastolic blood pressure (77 vs 75 mm Hg) and lower rates of cigarette smoking (42% vs 53%) (P < .05) (Appendix, available online). The Boston University Medical Center Institutional Review Board approved the main study protocols for the Framingham Offspring and Third Generation cohort, and all participants signed written informed consent. Risk Factor Collection In the current study, we used information on cardiovascular risk factors from the first and second offspring examinations (Offspring cohort mothers) and the first Third Generation examination (adult progeny). Details regarding the ascertainment of risk factors have been described.16 Diabetes was defined as fasting plasma glucose ≥ 126 mg/dL or treatment with either insulin or oral hypoglycemic agents. Lipids were measured on 12-hour fasting venous blood samples collected in tubes containing 0.1% EDTA. Plasma was separated by ultracentrifugation, and plasma lipid concentrations (total cholesterol and HDL-C) were measured as previously described.17 HDL-C was measured after precipitation of apo B-containing lipoproteins, and low-density lipoprotein cholesterol concentrations were estimated using the Friedewald formula.18 Intra-assay coefficients of variation for the Third Generation cohort cholesterol, triglycerides, and high-density lipoprotein were 0.5%, 1.1%, and 1.4%, respectively; interassay coefficients of variation were 1.1%, 1.8%, and 3.0%, respectively. Seated blood pressure was measured by a trained physician after the participant had rested for 5 minutes, and the average of 2 physician-obtained readings was used. Hypertension was defined as systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≥ 90 mm Hg, or use of blood pressure-lowering medications. Medication use was ascertained by physicians by detailed review of participant medication lists, and Third Generation participants were asked to bring medication bottles to the clinic examination, including lipid-lowering medications, oral contraceptive pills, and hormone therapy use. Participants were considered to be current smokers if they smoked at least 1 cigarette per day for the year before examination. Categories of BMI were defined according to National Heart Lung and Blood Institute and the World Health Organization guidelines19, 20 as follows: normal weight (BMI 18.5-25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obese (≥30 kg/m2). Data regarding highest educational degree obtained were gathered via questionnaire and categorized as follows: high school diploma or equivalent or less, Associate's degree/junior college, Bachelor's degree, and Master's degree or doctorate. The physical activity index was reflective of physical activity performed in a typical 24-hour period using a structured questionnaire that asked participants to report the number of hours asleep; at rest; and in slight, moderate, and heavy activity in a typical day.21, 22 Moderate-to heavy alcohol intake was defined as consumption of more than 14 drinks per week in men or 7 drinks per week in women. Prevalent cardiovascular disease was defined as recognized myocardial infarction, coronary insufficiency (prolonged chest pain accompanied by reversible ischemic electrocardiographic changes), angina pectoris, stroke, transient ischemic attack, or intermittent claudication using previously described criteria.23 Statistical Methods Descriptive statistics of Third Generation participant characteristics were grouped by maternal breastfeeding status (age- and sex-adjusted generalized estimated equation models were used to compare characteristics of participants by breastfeeding status). Descriptive statistics of maternal characteristics were presented according to whether mothers breastfed none, some, or all of their children. We examined cardiovascular risk factors described above as end points in the Third Generation Cohort. No cardiovascular events were examined in our study sample. Generalized estimated equation models were used to assess relations between dichotomous (ever vs never) breastfeeding status and the following Third Generation participant cardiovascular disease risk factors: BMI, total cholesterol, HDL cholesterol, triglycerides, fasting blood glucose, systolic blood pressure, and diastolic blood pressure. The intraclass correlation of BMI was 0.02 (P = .47) among Third Generation Cohort siblings. We applied generalized estimated equation models to account for related observations given the presence of siblings in the Third Generation cohort. Statistical models were constructed with adjustment for the following: model 1—age, sex, hypertension treatment, lipid treatment, smoking status, birth order, oral contraceptive use, hormone replacement use, physical activity index, and education level; model 2—model 1 covariates plus maternal smoking status, maternal education level, and maternal BMI at study entry. In secondary analyses, the dependent variable BMI was additionally adjusted for HDL cholesterol level, and the outcome HDL cholesterol was additionally adjusted for the following covariates: participant BMI, participant alcohol intake, and maternal HDL cholesterol. We also analyzed the dependent variables of cardiovascular disease risk factors dichotomously using clinically meaningful cut points. We tested potential effect modification by educational level. Finally, to assess the association of breastfeeding in infancy with an overall healthy lifestyle, we related breastfeeding status with participant higher education, smoking status, and physical activity. All statistical analyses were performed using SAS statistical software (version 8.1). A P value of less than .05 was considered to be statistically significant. Results Third Generation Participant Characteristics Study sample characteristics grouped by breastfeeding status are shown in Table 1. Twenty-six percent of participants were reported by mothers to have been breastfed in infancy. Of those individuals who were breastfed, the median breastfeeding duration was 4 months (range 1-22 months), and 29.6% were breastfed for more than 6 months. A higher prevalence of breastfed individuals had higher education levels and a lower prevalence of diabetes (Table 1). | | |  | Characteristics | Third Generation Participant Breastfeeding Status | |
|---|
| Means (SD) or (%) | No n = 712 | Yes n = 250 | |
|---|
| Age (y) | 41 ±7 | 41±9 | | | Women (%) | 54.8 | 50.0 | | | Birth order (among siblings) | 2.4+1.4 | 2.0±1.2 | | | Systolic blood pressure (mm Hg) | 117±15 | 118±15 | | | Diastolic blood pressure (mm Hg) | 76±10 | 75±10 | | | Fasting blood glucose (mg/dL) | 95±19.5 | 94±10 | | | Total cholesterol (mg/dL) | 190±34 | 190±32.5 | | | HDL cholesterol (mg/dL)a | 54±16 | 56±15 | | | Triglycerides (mg/dL) | 116±90.5 | 108±79 | | | BMI (kg/m2) | 26.9±5.4 | 26.3±5.0 | | | Waist circumference (cm) | 93±15 | 93±14 | | | Physical activity index | 37.6±8 | 37.6±8 | | | Hypertension, % | 7.8 | 8.0 | | | Lipid treatment, % | 5.9 | 7.2 | | | Diabetes mellitus, % | 3.0 | 1.2 | | | Obesity (BMI ≥ 30), % | 23.5 | 20.4 | | | Overweight (25 ≤ BMI < 30), % | 35.8 | 32.0 | | | Total cholesterol > 200, % | 36.5 | 36.3 | | | Triglyceride > 150, % | 21.4 | 16.0 | | | Fasting glucose > 126, % | 2.7 | 0.8 | | | Oral contraceptive use, % | 20.4 | 14.8 | | | Hormone replacement therapy use, % | 3.8 | 3.2 | | | Smoking, % | 17.0 | 15.3 | | | Moderate alcohol intake,b % | 15.4 | 18.2 | | | Education levela | | | | | High school or less, % | 17.5 | 9.6 | | | Some college, % | 32.3 | 30.9 | | | Bachelor's degree, % | 35.7 | 41.0 | | | Master's degree or higher, % | 14.5 | 18.5 | | | | |
| a Age- and sex-adjusted P < .05. bDefined as > 7 drinks per week in women and > 14 drinks per week in men. |
Maternal Characteristics Characteristics of mothers by whether they breastfed none, all, or some of their children are shown in Table 2. Mothers who breastfed all of their children also had the highest education levels, were the leanest, and were least likely to smoke. Breastfeeding Status and Cardiovascular Disease Risk Factors in Adulthood In model 1, which adjusted for participant cardiovascular disease risk factors, physical activity, and education, breastfeeding (ever vs never) was associated with a lower BMI (P = .03) (Table 3). Additionally adjusting for maternal factors in model 2 (maternal smoking, education, and BMI) did not materially change the association between breastfeeding status and BMI (P = .04; adjusted mean BMI among those breastfed vs not breastfed was 26.1 vs 26.9 kg/m2, respectively). | | | | | Model 1a | Model 2b | |
|---|
| Risk Factor | Not Breastfed N=712 | Breastfed N=250 | P Value | Not Breastfed N=712 | Breastfed N=250 | P Value | |
|---|
| BMI, kg/m2 | 27.0(26.6–27.4) | 26.1(25.5–26.8) | .03 | 26.9(26.4–27.3) | 26.1(25.4–26.7) | .04 | | | HDL cholesterol, mg/dL | 53.8(52.5–54.8) | 56.1(54.5–58.2) | .01 | 53.7(52.5–54.9) | 56.6(54.7–58.5) | .01 | | | Total cholesterol, mg/dL | 190.7(187.6–193.2) | 190.7(186.9–195.4) | .8 | 190.4(187.3–193.2) | 189.2(185.0–194.3) | .8 | | | Triglycerides, mg/dL | 117.2(110.1–124.1) | 109.1(99.1–119.6) | .2 | 115.7(108.3–123.0) | 109.4(97.8–121.1) | .4 | | | Fasting blood glucose, mg/dL | 94.8(93.5–96.2) | 93.9(92.3–95.1) | .3 | 94.8(93.4–96.4) | 93.5(91.8–95.0) | .2 | | | Systolic blood pressure, mm Hg | 117.6(116.3–118.8) | 117.1(115.8–119.1) | .9 | 117.6(116.3–118.8) | 117.5(115.9–119.6) | .9 | | | Diastolic blood pressure, mm Hg | 75.9(75.1–76.6) | 74.8(73.7–76.1) | .2 | 75.8(74.9–76.5) | 74.9(73.7–76.3) | .3 | | | | |
| a Model 1 covariates: age, sex, hypertension treatment, lipid treatment, smoking status, birth order, oral contraceptive use, hormone replacement use, physical activity, and education level. bModel 2 covariates: model 1 variables plus maternal smoking status, maternal education level, and maternal BMI at study entry. |
In model 1, adjusting for participant cardiovascular disease risk factors, physical activity, and education, breastfeeding was associated with a higher HDL cholesterol level (P = .01). Additionally adjusting for maternal factors (smoking, education, and maternal BMI) did not materially change the association between breastfeeding status and HDL cholesterol level (P = .01; adjusted mean HDL cholesterol concentrations among those breastfed vs not breastfed were 56.6 mg/dL relative to 53.7 mg/dL, respectively). Breastfeeding (ever vs never) was not associated with participant total cholesterol, triglycerides, fasting blood glucose, systolic blood pressure, or diastolic blood pressure in either model 1 or model 2 (Table 3). Secondary Analyses Association between Breastfeeding Status and Body Mass Index and High-density Lipoprotein Cholesterol Categories Breastfeeding was inversely associated with low HDL cholesterol levels (<40 mg/dL in men and < 50 mg/dL in women) even after accounting for participant and maternal cardiovascular disease risk factors, lifestyle, and socioeconomic characteristics (multivariable-adjusted odds ratio = 0.63 [0.42-0.96], P = .03) (Table 4). Breastfeeding was not significantly associated with any other dichotomized risk factors in fully adjusted models. (Table 4). | | | | | Model 1a | Model 2b | |
|---|
| | OR (95% CI) | OR (95% CI) | |
|---|
| BMI > 30 kg/m2 | 0.78(0.52–1.16) | 0.75(0.47–1.21) | | | Total cholesterol > 200 mg/dL | 1.01(0.73–1.40) | 0.91(0.63–1.32) | | | HDL cholesterol < 40 mg/dL in men or < 50 mg/dL in women | 0.64(0.43–0.94) | 0.63(0.42–0.96) | | | Triglycerides > 150 mg/dL | 0.64(0.42–0.97) | 0.68(0.44–1.05) | | | Fasting glucose > 126 mg/dL | 0.30(0.08–1.17) | 0.40(0.09–1.70) | | | | |
| a Model 1 covariates: age, sex, hypertension treatment, lipid treatment, smoking status, birth order, oral contraceptive use, hormone replacement use, physical activity, and education level. bModel 2 covariates: model 1 variables plus maternal smoking status, maternal education level, and maternal BMI at study entry. |
Additional Model Adjustments Additionally adjusting multivariable model 2 for participant alcohol intake did not materially change the positive association between breastfeeding status and HDL cholesterol. Similarly, additionally adjusting model 2 for maternal HDL cholesterol did not materially change the positive association between breastfeeding status and HDL cholesterol. Effect Modification There was no evidence of effect modification by educational level on the associations between breastfeeding with HDL or with BMI. Association between Breastfeeding and Healthy Lifestyle In fully adjusted models there were no significant associations between breastfeeding and having achieved a Bachelor's or higher degree (odds ratio = 1.20 [0.84-1.72]), having a physical activity score of 37 or more (1.20 [0.84-1.73]), or current cigarette smoking (1.17 [0.75-1.52]). Discussion Summary of Findings In a community-based sample of 962 men and women in early to middle age, maternal report of breastfeeding was associated with modestly lower participant BMI and higher participant HDL cholesterol concentrations. Maternal report of breastfeeding was not significantly associated with offspring total cholesterol, triglycerides, fasting blood glucose, or systolic or diastolic blood pressure levels. Breastfeeding was associated with higher mean HDL cholesterol concentrations even after accounting for participant and maternal education, lifestyle factors, and cardiovascular disease risk factors. However, the association between maternal breastfeeding and participant HDL cholesterol appeared to be attenuated by adjustment for participant BMI. Breastfeeding and Body Mass Index In keeping with our data, prior studies have found an inverse association between breastfeeding in infancy and adolescent and adult adiposity.4, 7, 12, 24, 25, 26, 27 Higher growth rates in early infancy among formula-fed compared with breastfed infants have been demonstrated in randomized trials of low birth weight and preterm infants,28 as well as in observational studies among normal birth weight babies.29, 30, 31 In contrast with some prior reports, a significant attenuation in the association between breastfeeding and lower BMI was not found on adjustment for maternal and participant socioeconomic status defined using educational attainment. Furthermore, BMI is a moderately heritable trait,32 yet adjustment for maternal BMI did not significantly diminish the associations. One prior study also demonstrated a significant inverse association between breastfeeding and childhood overweight even after adjusting for maternal obesity.33 Our BMI data were ascertained directly in both mothers and study sample participants rather than self-reported.12 Self-reported data used in prior studies may have led to some outcome misclassification with resultant biasing of measures toward the null value. Finally, our study was conducted in a sample unselected for sex and occupation, in contrast with prior investigations conducted among female registered nurses.12 Exact mechanisms by which breast milk confers protection against offspring weight gain are not known, but aggregate data from several recent studies suggest that adipokines may potentially mediate the association. A recent laboratory study in rats has suggested that delayed weaning (meaning continuation of breast milk and delayed introduction of solid food) reduces plasma levels of the appetite-related peptide, ghrelin, and gastric ghrelin cell development.34 Ghrelin concentration increases during specific stages in rat infancy were formerly thought to be age related as opposed to diet related.34 Furthermore, leptin concentrations in human breast milk have been demonstrated to inversely correlate with human infant weight gain up until 2 years of age.35, 36 In a separate randomized prospective study of feeding among preterm infants, serum leptin to fat mass ratio measured in adolescence was demonstrated to be lower in those randomized to donated banked breast milk compared with formula feeding while in infancy.37 Levels of other novel adipokines in human breast milk, including epidermal and adipocyte fatty acid binding protein, have been demonstrated to positively correlate with infant birth weight.38 Breastfeeding and High-density Lipoprotein Cholesterol Whereas prior data suggest that breastfeeding is related to increases in total and LDL-cholesterol levels in infancy and adulthood,5 fewer studies have specifically examined the association between breastfeeding and later-life HDL cholesterol levels. A recent study in a British birth cohort born in 1958 did not demonstrate an association between breastfeeding for more than 1 month and adult levels of HDL cholesterol.27 A Dutch prospective study of adults aged 48 to 53 years demonstrated a lower total to HDL cholesterol ratio among breastfed compared with formula-fed individuals.8 In a randomized prospective study of feeding among preterm infants, serum total to HDL cholesterol ratio measured in adolescence was lower among those previously randomized to banked donated breast milk compared with formula feeding.39 Choice of Covariates for Adjustment We thought it was particularly important to adjust for education, BMI, and smoking status. Breastfeeding is more prevalent among women with a higher education, which in turn is associated with a number of positive health indicators, including increased HDL cholesterol,40 lower BMI,41 and abstinence from smoking. Lower BMI and abstinence from smoking in turn are associated with higher HDL cholesterol levels.42 Breastfeeding and Other Cardiovascular Disease Risk Factors The absence of a significant association between breastfeeding in infancy and later-life blood pressure in our sample is consistent with several prior investigations that did not find a significant association between breastfeeding and adult blood pressure.8, 43, 44 Furthermore, findings from a recent meta-analysis of several previously published studies raise the concern that the inverse association between breastfeeding and blood pressure from other studies may have been subject to selection or publication bias.6 We found no association between breastfeeding status and fasting blood glucose levels. This is in keeping with prior studies in adolescents45 and middle-aged men4 showing no association between breastfeeding in infancy and later-life insulin resistance (as measured by homeostasis model assessment). We did not specifically study differences in rates of diabetes by breastfeeding status because the prevalence of diabetes was too low in our sample for meaningful analysis. Given the lack of association between breastfeeding status and several cardiovascular disease risk factors studied, we assessed our statistical power to detect modest effects for associations between breastfeeding and the cardiovascular disease risk factors for which we did not detect significant associations. Taking sibling correlation into account, we had 80% power to detect a systolic blood pressure difference of 2.9 mm Hg, diastolic blood pressure difference of 2.0 mm Hg, total cholesterol difference of 7.0 mg/dL, triglyceride difference of 17.2 mg/dL, and fasting glucose difference of 2.9 mg/dL. We had more modest power to detect smaller mean differences. Strengths and Limitations Direct and routine assessment of cardiovascular risk factors for 2 generations of participants to account for both maternal covariates and offspring cardiovascular disease risk factors is a unique strength of our study. Risk factors were measured in offspring in adulthood, whereas most prior reports examined the relation of breastfeeding to childhood risk factors. Several limitations should be acknowledged as well. Breastfeeding assessment was done decades after the birth of participants, which could have led to recall bias. However, the recall of whether or not a women breastfed her child has been shown to be accurate for ≥ 20 years later.46 Furthermore, our study relied on maternal compared with self-reported breastfeeding history, which has been demonstrated to be more accurate.47 We did not adjust for other components of infant diet or account for birth weight in our multivariable analysis. It has been demonstrated that low birth weight infants tend to breastfeed for shorter durations and tend to have rapid catch-up growth, which is associated with later-life obesity.48 We also did not account for paternal factors because not all Third Generation participants have fathers in the Framingham Offspring cohort. Our study participants are of white European ancestry; therefore, these findings may not be generalizable to other ethnic populations. We accounted for socioeconomic status by means of highest education degree obtained, which might not have fully accounted for socioeconomic differences.49 HDL subfractions, which have demonstrated accuracy in predicting cardiovascular disease,50 were not measured in this study. Although the incubation period between exposure and outcome in our study is relatively long, it is being increasingly recognized that exposures in early life affect adult health. In turn, evidence suggests that cholesterol and BMI measured in middle age confer later higher lifetime cardiovascular disease risk.51 Potential selection bias from the breast health survey sampling scheme cannot be excluded; however, Offspring mothers with adult children enrolled in the Third Generation cohort not included in our study did not differ with respect to BMI and HDL cholesterol levels from the Offspring mothers included in the study. Because the alternatives to breastfeeding in the 1960s and 1970s differed from what is available today, these comparisons might not be relevant to current long-term breastfeeding effects. We did not assess the exclusivity of breastfeeding within our study framework and were unable to carry out an analysis of risk factor levels among siblings discordant for breastfeeding because we had few of these in our study sample to permit a meaningful analysis. A discordant sibling pair analysis may have permitted better control of unmeasured potentially confounding maternal and family level factors. We did not account for the dietary intake of participants (ie, fat, carbohydrate, and protein intake). We may have limited power to detect very modest differences in blood pressure, total cholesterol, triglycerides, and fasting glucose. We did not account for multiple testing in our interpretation of results. By using the most conservative approach, given that model 1 and model 2 adjustments were highly correlated, and there were 7 separate dependent variables, the Bonferroni correction would have yielded an α level for significance of 0.05/7 = 0.007. Finally, this is an observational study, and therefore we cannot infer causality. Implications and Directions for Future Study Our findings confirm previous reports of a protective association between breastfeeding and later-life adiposity (as measured by BMI). Although the net reductions in BMI demonstrated in our study are modest, the beneficial effect at the population level may have important public health relevance. The risk of death from cardiovascular disease and congestive heart failure has been demonstrated to increase even with small incremental increases in BMI,52, 53 suggesting that even modest differences in excess adiposity may increase cardiovascular disease mortality risks. Furthermore, the mechanisms underlying the association between lower adulthood BMI among individuals breastfed in infancy are arguably of considerable importance. Our findings taken in conjunction with recent experimental evidence linking adipokines to breast milk and infant weight suggest that further elucidating mechanisms relating nutrition in early life and cardiometabolic risk factor profile in later life is an important area of research. Furthermore, informed decisions about whether or not to breastfeed affect more than 4 million women annually54 who give birth in the United States. Thus, understanding the association of breastfeeding with cardiovascular disease risk factors in later life remains an important public health issue. Conclusions Breastfeeding in infancy was associated with a modestly reduced BMI and elevated HDL cholesterol levels in adulthood after accounting for several participant and maternal characteristics. The association between breastfeeding and HDL cholesterol was attenuated on accounting for participant BMI. Studies elucidating the mechanisms underlying nutrition in early life and adiposity in later life are warranted. References 1. 1Gartner LM, Morton J, Lawrence RA, et al. Breastfeeding and the use of human milk. Pediatrics. 2005;115:496–506. 2. 2Office of Women's Health. US Department of Health and Human Services 2006. http://www.womenshealth.gov/breastfeeding/index.cfm?page=Campaign. 3. 3Primary care interventions to promote breastfeeding: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149:560–564. 4. 4Martin RM, Ben Shlomo Y, Gunnell D, et al. Breast feeding and cardiovascular disease risk factors, incidence, and mortality: the Caerphilly study. J Epidemiol Community Health. 2005;59:121–129.
CrossRef
5. 5Owen CG, Whincup PH, Odoki K, et al. Infant feeding and blood cholesterol: a study in adolescents and a systematic review. Pediatrics. 2002;110:597–608. 6. 6Owen CG, Whincup PH, Gilg JA, Cook DG. Effect of breast feeding in infancy on blood pressure in later life: systematic review and meta-analysis. BMJ. 2003;327:1189–1195. 7. 7Owen CG, Martin RM, Whincup PH, et al. The effect of breastfeeding on mean body mass index throughout life: a quantitative review of published and unpublished observational evidence. Am J Clin Nutr. 2005;82:1298–1307. MEDLINE 8. 8Ravelli AC, van der Meulen JH, Osmond C, et al. Infant feeding and adult glucose tolerance, lipid profile, blood pressure, and obesity. Arch Dis Child. 2000;82:248–252.
CrossRef
9. 9Rudnicka AR, Owen CG, Strachan DP. The effect of breastfeeding on cardiorespiratory risk factors in adult life. Pediatrics. 2007;119:e1107–e1115. 10. 10Rich-Edwards JW, Stampfer MJ, Manson JE, et al. Breastfeeding during infancy and the risk of cardiovascular disease in adulthood. Epidemiology. 2004;15:550–556. MEDLINE |
CrossRef
11. 11Martin RM, Ness AR, Gunnell D, et al. Does breast-feeding in infancy lower blood pressure in childhood? (The Avon Longitudinal Study of Parents and Children (ALSPAC)). Circulation. 2004;109:1259–1266.
CrossRef
12. 12Michels KB, Willett WC, Graubard BI, et al. A longitudinal study of infant feeding and obesity throughout life course. Int J Obes (Lond). 2007;31:1078–1085.
CrossRef
13. 13Dawber TR, Kannel WB. An approach to longitudinal studies in a community: the Framingham Study. Ann N Y Acad Sci. 1963;107:539–556. MEDLINE |
CrossRef
14. 14Feinleib M, Kannel WB, Garrison RJ, et al. The Framingham Offspring Study (Design and preliminary data). Prev Med. 1975;4:518–525. MEDLINE |
CrossRef
15. 15Murabito JM, Evans JC, Larson MG, et al. Family breast cancer history and mammography: Framingham Offspring Study. Am J Epidemiol. 2001;154:916–923. MEDLINE |
CrossRef
16. 16Kannel WB, Feinleib M, McNamara PM, et al. An investigation of coronary heart disease in families (The Framingham Offspring Study). Am J Epidemiol. 1979;110:281–290. MEDLINE 17. 17McNamara JR, Schaefer EJ. Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions. Clin Chim Acta. 1987;166:1–8. MEDLINE |
CrossRef
18. 18Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502. MEDLINE 19. 19Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—The Evidence Report (National Institutes of Health). Obes Res. 1998;6(Suppl 2):51S–209S. 20. 20WHO Consultation on Obesity. Obesity: Preventing and Managing the Global Epidemic. Geneva, Switzerland: World Health Organization: WHO Technical Report Series 894; 2000;. 21. 21Kannel WB, Sorlie P. Some health benefits of physical activity (The Framingham Study). Arch Intern Med. 1979;139:857–861. MEDLINE 22. 22Sherman SE, D'Agostino RB, Cobb JL, Kannel WB. Physical activity and mortality in women in the Framingham Heart Study. Am Heart J. 1994;128:879–884. MEDLINE |
CrossRef
23. 23Cupples LA, D'Agostino RB. Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Study, 30-year follow-up. In: Kannel WB, Wolf PA, Garrison RJ editor. The Framingham Heart Study: An Epidemiologic Investigation of Cardiovascular Disease. Washington, DC: NIH Publication; 1987;p. 87–203. 24. 24Arenz S, Ruckerl R, Koletzko B, von Kries R. Breast-feeding and childhood obesity—a systematic review. Int J Obes Relat Metab Disord. 2004;28:1247–1256. MEDLINE |
CrossRef
25. 25Gillman MW, Rifas-Shiman SL, Berkey CS, et al. Breast-feeding and overweight in adolescence. Epidemiology. 2006;17:112–114. MEDLINE |
CrossRef
26. 26Victora CG, Barros F, Lima RC, et al. Anthropometry and body composition of 18 year old men according to duration of breast feeding: birth cohort study from Brazil. BMJ. 2003;327:901. 27. 27Rudnicka AR, Owen CG, Strachan DP. The effect of breastfeeding on cardiorespiratory risk factors in adult life. Pediatrics. 2007;119:e1107–e1115. 28. 28McGuire W, Anthony MY. Formula milk versus term human milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev. 2001;. 29. 29Butte NF, Wong WW, Hopkinson JM, et al. Infant feeding mode affects early growth and body composition. Pediatrics. 2000;106:1355–1366. 30. 30Dewey KG, Heinig MJ, Nommsen LA, et al. Growth of breast-fed and formula-fed infants from 0 to 18 months: the DARLING Study. Pediatrics. 1992;89(6 Pt 1):1035–1041. 31. 31Michaelsen KF, Larsen PS, Thomsen BL, Samuelson G. The Copenhagen Cohort Study on Infant Nutrition and Growth: breast-milk intake, human milk macronutrient content, and influencing factors. Am J Clin Nutr. 1994;59:600–611. MEDLINE 32. 32Coady SA, Jaquish CE, Fabsitz RR, et al. Genetic variability of adult body mass index: a longitudinal assessment in Framingham families. Obes Res. 2002;10:675–681. MEDLINE 33. 33Mayer-Davis EJ, Rifas-Shiman SL, Zhou L, et al. Breast-feeding and risk for childhood obesity: does maternal diabetes or obesity status matter?. Diabetes Care. 2006;29:2231–2237. MEDLINE |
CrossRef
34. 34Fak F, Friis-Hansen L, Westrom B, Wierup N. Gastric ghrelin cell development is hampered and plasma ghrelin is reduced by delayed weaning in rats. J Endocrinol. 2007;192:345–352. MEDLINE |
CrossRef
35. 35Miralles O, Sanchez J, Palou A, Pico C. A physiological role of breast milk leptin in body weight control in developing infants. Obesity (Silver Spring). 2006;14:1371–1377. MEDLINE |
CrossRef
36. 36Dundar NO, Anal O, Dundar B, et al. Longitudinal investigation of the relationship between breast milk leptin levels and growth in breast-fed infants. J Pediatr Endocrinol Metab. 2005;18:181–187. 37. 37Singhal A, Farooqi IS, O'Rahilly S, et al. Early nutrition and leptin concentrations in later life. Am J Clin Nutr. 2002;75:993–999. MEDLINE 38. 38Bronsky J, Karpisek M, Bronska E, et al. Adiponectin, adipocyte fatty acid binding protein, and epidermal fatty acid binding protein: proteins newly identified in human breast milk. Clin Chem. 2006;52:1763–1770. MEDLINE |
CrossRef
39. 39Singhal A, Cole TJ, Fewtrell M, Lucas A. Breastmilk feeding and lipoprotein profile in adolescents born preterm: follow-up of a prospective randomised study. Lancet. 2004;363:1571–1578. Abstract | Full Text |
Full-Text PDF (393 KB)
|
CrossRef
40. 40Demakakos P, Nazroo J, Breeze E, Marmot M. Socioeconomic status and health: the role of subjective social status. Soc Sci Med. 2008;67:330–340.
CrossRef
41. 41Maty SC, Lynch JW, Raghunathan TE, Kaplan GA. Childhood socioeconomic position, gender, adult body mass index, and incidence of type 2 diabetes mellitus over 34 years in the Alameda County Study. Am J Public Health. 2008;98:1486–1494.
CrossRef
42. 42Linn S, Fulwood R, Carroll M, et al. Serum total cholesterol: HDL cholesterol ratios in US white and black adults by selected demographic and socioeconomic variables (HANES II). Am J Public Health. 1991;81:1038–1043. MEDLINE |
CrossRef
43. 43Kolacek S, Kapetanovic T, Luzar V. Early determinants of cardiovascular risk factors in adults (B. Blood pressure). Acta Paediatr. 1993;82:377–382. MEDLINE |
CrossRef
44. 44Leeson CP, Kattenhorn M, Deanfield JE, Lucas A. Duration of breast feeding and arterial distensibility in early adult life: population based study. BMJ. 2001;322:643–647. 45. 45Lawlor DA, Riddoch CJ, Page AS, et al. Infant feeding and components of the metabolic syndrome: findings from the European Youth Heart Study. Arch Dis Child. 2005;90:582–588.
CrossRef
46. 46Kark JD, Troya G, Friedlander Y, et al. Validity of maternal reporting of breast feeding history and the association with blood lipids in 17 year olds in Jerusalem. J Epidemiol Community Health. 1984;38:218–225.
CrossRef
47. 47Troy LM, Michels KB, Hunter DJ, et al. Self-reported birthweight and history of having been breastfed among younger women: an assessment of validity. Int J Epidemiol. 1996;25:122–127. MEDLINE |
CrossRef
48. 48Lande B, Andersen LF, Henriksen T, et al. Relations between high ponderal index at birth, feeding practices and body mass index in infancy. Eur J Clin Nutr. 2005;59:1241–1249. MEDLINE |
CrossRef
49. 49Braveman PA, Cubbin C, Egerter S, et al. Socioeconomic status in health research: one size does not fit all. JAMA. 2005;294:2879–2888.
CrossRef
50. 50Buring JE, O'Connor GT, Goldhaber SZ, et al. Decreased HDL2 and HDL3 cholesterol, Apo A-I and Apo A-II, and increased risk of myocardial infarction. Circulation. 1992;85:22–29. MEDLINE 51. 51Lloyd-Jones DM, Leip EP, Larson MG, et al. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation. 2006;113:791–798.
CrossRef
52. 52Calle EE, Thun MJ, Petrelli JM, et al. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341:1097–1105. MEDLINE |
CrossRef
53. 53Kenchaiah S, Evans JC, Levy D, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347:305–313.
CrossRef
54. 54Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2004. Natl Vital Stat Rep. 2006;55:1–101. MEDLINE a The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Mass b Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, Mass c National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md d Preventive Medicine and Cardiology Sections, Boston University School of Medicine, Boston, Mass e Epidemiology Section, Boston University School of Public Health, Boston, Mass f Brigham and Women's Hospital, Harvard Medical School, Boston, Mass j Section of General Internal Medicine, Boston University School of Medicine, Boston, Mass  Requests for reprints should be addressed to Joanne M. Murabito, MD, ScM, 73 Mount Wayte Ave, #2, Framingham, MA 01702
Funding: Supported by a National Institute of Health/National Heart, Lung, and Blood Institute, contract N01-HC-25195, 2K24 HL 04334 (RSV). Conflict of Interest: None. Authorship: All authors had access to the data and played a role in writing this manuscript. PII: S0002-9343(09)00290-3 doi:10.1016/j.amjmed.2008.11.034 © 2009 Elsevier Inc. All rights reserved. | |
|
FULL TEXT00290-3/journalimage?img=PIIS0002934309002903.gr1.lrg.gif&fig=fig1&kwhquery=&issn=0002-9343&ishighres=false&allhighres=false&free=yes','journalimage');)
