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Figure 1.
Meta-analysis Showing Association Between Breastfeeding and Diabetes
Meta-analysis Showing Association Between Breastfeeding and Diabetes

Breastfeeding for 12 months or more was associated with a reduced risk of diabetes. The size of the data markers indicates the weight of the odds ratio (OR), using random-effects analysis with instrumental variables.

Figure 2.
Meta-analysis Showing Association Between Breastfeeding and Hypertension
Meta-analysis Showing Association Between Breastfeeding and Hypertension

Breastfeeding for 12 months or more was associated with a reduced risk of hypertension. The size of the data markers indicates the weight of the odds ratio (OR), using random-effects analysis with instrumental variables.

Table.  
Characteristics of Studies Included in the Meta-analysis for Hypertension and Diabetes
Characteristics of Studies Included in the Meta-analysis for Hypertension and Diabetes
1.
Benjamin  EJ, Virani  SS, Callaway  CW,  et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee.  Heart disease and stroke statistics—2018 update: a report from the American Heart Association.  Circulation. 2018;137(12):e67-e492. doi:10.1161/CIR.0000000000000558PubMedGoogle ScholarCrossref
2.
Goff  DC  Jr, Lloyd-Jones  DM, Bennett  G,  et al.  2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.  J Am Coll Cardiol. 2014;63(25, pt B):2935-2959. doi:10.1016/j.jacc.2013.11.005PubMedGoogle ScholarCrossref
3.
De Backer  G, Ambrosioni  E, Borch-Johnsen  K,  et al; European Society of Cardiology; American Heart Association; American College of Cardiology.  European guidelines on cardiovascular disease prevention in clinical practice: Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of eight societies and by invited experts).  Atherosclerosis. 2004;173(2):381-391. doi:10.1016/j.atherosclerosis.2004.02.013PubMedGoogle ScholarCrossref
4.
Xu  J, Murphy  SL, Kochanek  KD, Bastian  B, Arias  E.  Deaths: final data for 2016.  Natl Vital Stat Rep. 2018;67(5):1-76.PubMedGoogle Scholar
5.
Mosca  L, Benjamin  EJ, Berra  K,  et al; American Heart Association.  Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the American Heart Association.  J Am Coll Cardiol. 2011;57(12):1404-1423. doi:10.1016/j.jacc.2011.02.005PubMedGoogle ScholarCrossref
6.
Stuebe  AM, Rich-Edwards  JW.  The reset hypothesis: lactation and maternal metabolism.  Am J Perinatol. 2009;26(1):81-88. doi:10.1055/s-0028-1103034PubMedGoogle ScholarCrossref
7.
Stroup  DF, Berlin  JA, Morton  SC,  et al.  Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.  JAMA. 2000;283(15):2008-2012. doi:10.1001/jama.283.15.2008PubMedGoogle ScholarCrossref
8.
Rao  G, Lopez-Jimenez  F, Boyd  J,  et al; American Heart Association Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology; Council on Functional Genomics and Translational Biology; Stroke Council.  Methodological standards for meta-analyses and qualitative systematic reviews of cardiac prevention and treatment studies: a scientific statement from the American Heart Association.  Circulation. 2017;136(10):e172-e194. doi:10.1161/CIR.0000000000000523PubMedGoogle ScholarCrossref
9.
The Ottawa Hospital Research Institute. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed February 11, 2019.
10.
DerSimonian  R, Laird  N.  Meta-analysis in clinical trials.  Control Clin Trials. 1986;7(3):177-188. doi:10.1016/0197-2456(86)90046-2PubMedGoogle ScholarCrossref
11.
Higgins  JPT, Thompson  SG, Deeks  JJ, Altman  DG.  Measuring inconsistency in meta-analyses.  BMJ. 2003;327(7414):557-560. doi:10.1136/bmj.327.7414.557PubMedGoogle ScholarCrossref
12.
Sterne  JA, Sutton  AJ, Ioannidis  JP,  et al.  Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials.  BMJ. 2011;343:d4002. doi:10.1136/bmj.d4002PubMedGoogle ScholarCrossref
13.
Egger  M, Davey Smith  G, Schneider  M, Minder  C.  Bias in meta-analysis detected by a simple, graphical test.  BMJ. 1997;315(7109):629-634. doi:10.1136/bmj.315.7109.629PubMedGoogle ScholarCrossref
14.
Liu  B, Jorm  L, Banks  E.  Parity, breastfeeding, and the subsequent risk of maternal type 2 diabetes.  Diabetes Care. 2010;33(6):1239-1241. doi:10.2337/dc10-0347PubMedGoogle ScholarCrossref
15.
Schwarz  EB, Ray  RM, Stuebe  AM,  et al.  Duration of lactation and risk factors for maternal cardiovascular disease.  Obstet Gynecol. 2009;113(5):974-982. doi:10.1097/01.AOG.0000346884.67796.caPubMedGoogle ScholarCrossref
16.
Zhang  BZ, Zhang  HY, Liu  HH, Li  HJ, Wang  JS.  Breastfeeding and maternal hypertension and diabetes: a population-based cross-sectional study.  Breastfeed Med. 2015;10(3):163-167. doi:10.1089/bfm.2014.0116PubMedGoogle ScholarCrossref
17.
Choi  SR, Kim  YM, Cho  MS, Kim  SH, Shim  YS.  Association between duration of breast feeding and metabolic syndrome: the Korean National Health and Nutrition Examination Surveys.  J Womens Health (Larchmt). 2017;26(4):361-367. doi:10.1089/jwh.2016.6036PubMedGoogle ScholarCrossref
18.
Chetwynd  EM, Stuebe  AM, Rosenberg  L, Troester  M, Rowley  D, Palmer  JR.  Cumulative lactation and onset of hypertension in African-American women.  Am J Epidemiol. 2017;186(8):927-934. doi:10.1093/aje/kwx163PubMedGoogle ScholarCrossref
19.
Lupton  SJ, Chiu  CL, Lujic  S, Hennessy  A, Lind  JM.  Association between parity and breastfeeding with maternal high blood pressure.  Am J Obstet Gynecol. 2013;208(6):454.e1-454.e7. doi:10.1016/j.ajog.2013.02.014PubMedGoogle ScholarCrossref
20.
Moher  D, Liberati  A, Tetzlaff  J, Altman  DG; PRISMA Group.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.  PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097PubMedGoogle ScholarCrossref
21.
Schwarz  EB, Brown  JS, Creasman  JM,  et al.  Lactation and maternal risk of type 2 diabetes: a population-based study  [published correction appears in Am J Med. 2011;124(10):e9].  Am J Med. 2010;123(9):863.e1-863.e6. doi:10.1016/j.amjmed.2010.03.016PubMedGoogle ScholarCrossref
22.
Stuebe  AM, Rich-Edwards  JW, Willett  WC, Manson  JE, Michels  KB.  Duration of lactation and incidence of type 2 diabetes.  JAMA. 2005;294(20):2601-2610. doi:10.1001/jama.294.20.2601PubMedGoogle ScholarCrossref
23.
Stuebe  AM, Kleinman  K, Gillman  MW, Rifas-Shiman  SL, Gunderson  EP, Rich-Edwards  J.  Duration of lactation and maternal metabolism at 3 years postpartum.  J Womens Health (Larchmt). 2010;19(5):941-950. doi:10.1089/jwh.2009.1660PubMedGoogle ScholarCrossref
24.
Villegas  R, Gao  YT, Yang  G,  et al.  Duration of breast-feeding and the incidence of type 2 diabetes mellitus in the Shanghai Women’s Health Study.  Diabetologia. 2008;51(2):258-266. doi:10.1007/s00125-007-0885-8PubMedGoogle ScholarCrossref
25.
Kim  H-J, Kim  H-S.  Differences in prevalence of metabolic syndrome by breastfeeding experience of women in their 30s and 40s.  Asian Nurs Res (Korean Soc Nurs Sci). 2016;10(2):136-142.PubMedGoogle Scholar
26.
Kirkegaard  H, Bliddal  M, Støvring  H,  et al.  Breastfeeding and later maternal risk of hypertension and cardiovascular disease—the role of overall and abdominal obesity.  Prev Med. 2018;114:140-148. doi:10.1016/j.ypmed.2018.06.014PubMedGoogle ScholarCrossref
27.
Lee  SY, Kim  MT, Jee  SH, Yang  HP.  Does long-term lactation protect premenopausal women against hypertension risk? a Korean women’s cohort study.  Prev Med. 2005;41(2):433-438. doi:10.1016/j.ypmed.2004.11.025PubMedGoogle ScholarCrossref
28.
Park  S, Choi  NK.  Breastfeeding and maternal hypertension.  Am J Hypertens. 2018;31(5):615-621. doi:10.1093/ajh/hpx219PubMedGoogle ScholarCrossref
29.
Stuebe  AM, Schwarz  EB, Grewen  K,  et al.  Duration of lactation and incidence of maternal hypertension: a longitudinal cohort study.  Am J Epidemiol. 2011;174(10):1147-1158. doi:10.1093/aje/kwr227PubMedGoogle ScholarCrossref
30.
Jäger  S, Jacobs  S, Kröger  J,  et al.  Breast-feeding and maternal risk of type 2 diabetes: a prospective study and meta-analysis.  Diabetologia. 2014;57(7):1355-1365. doi:10.1007/s00125-014-3247-3PubMedGoogle ScholarCrossref
31.
Moradi  S, Zamani  F, Pishgar  F, Ordookhani  S, Nateghi  N, Salehi  F.  Parity, duration of lactation and prevalence of maternal metabolic syndrome: a cross-sectional study.  Eur J Obstet Gynecol Reprod Biol. 2016;201:70-74. doi:10.1016/j.ejogrb.2016.03.038PubMedGoogle ScholarCrossref
32.
Bajaj  H, Ye  C, Hanley  AJ,  et al.  Prior lactation reduces future diabetic risk through sustained postweaning effects on insulin sensitivity.  Am J Physiol Endocrinol Metab. 2017;312(3):E215-E223. doi:10.1152/ajpendo.00403.2016PubMedGoogle ScholarCrossref
33.
Gunderson  EP, Quesenberry  CP  Jr, Ning  X,  et al.  Lactation duration and midlife atherosclerosis.  Obstet Gynecol. 2015;126(2):381-390. doi:10.1097/AOG.0000000000000919PubMedGoogle ScholarCrossref
34.
Gunderson  EP, Lewis  CE, Lin  Y,  et al.  Lactation duration and progression to diabetes in women across the childbearing years: the 30-year CARDIA study.  JAMA Intern Med. 2018;178(3):328-337. doi:10.1001/jamainternmed.2017.7978PubMedGoogle ScholarCrossref
35.
Martens  PJ, Shafer  LA, Dean  HJ,  et al.  Breastfeeding initiation associated with reduced incidence of diabetes in mothers and offspring.  Obstet Gynecol. 2016;128(5):1095-1104. doi:10.1097/AOG.0000000000001689PubMedGoogle ScholarCrossref
36.
Ram  KT, Bobby  P, Hailpern  SM,  et al.  Duration of lactation is associated with lower prevalence of the metabolic syndrome in midlife—SWAN, the Study of Women’s Health Across the Nation.  Am J Obstet Gynecol. 2008;198(3):268.e1-268.e6. doi:10.1016/j.ajog.2007.11.044PubMedGoogle ScholarCrossref
37.
Nurses’ Health Study. History. https://www.nurseshealthstudy.org/about-nhs/history. Accessed September 9, 2019.
38.
Garcia  M, Mulvagh  SL, Merz  CN, Buring  JE, Manson  JE.  Cardiovascular disease in women: clinical perspectives.  Circ Res. 2016;118(8):1273-1293. doi:10.1161/CIRCRESAHA.116.307547PubMedGoogle ScholarCrossref
39.
Pencina  MJ, D’Agostino  RB  Sr, Larson  MG, Massaro  JM, Vasan  RS.  Predicting the 30-year risk of cardiovascular disease: the Framingham Heart Study.  Circulation. 2009;119(24):3078-3084. doi:10.1161/CIRCULATIONAHA.108.816694PubMedGoogle ScholarCrossref
40.
Kurth  T, Moore  SC, Gaziano  JM,  et al.  Healthy lifestyle and the risk of stroke in women.  Arch Intern Med. 2006;166(13):1403-1409. doi:10.1001/archinte.166.13.1403PubMedGoogle ScholarCrossref
41.
Ip  S, Chung  M, Raman  G,  et al.  Breastfeeding and maternal and infant health outcomes in developed countries.  Evid Rep Technol Assess (Full Rep). 2007;(153):1-186.PubMedGoogle Scholar
42.
Perrine  CG, Nelson  JM, Corbelli  J, Scanlon  KS.  Lactation and maternal cardio-metabolic health.  Annu Rev Nutr. 2016;36:627-645. doi:10.1146/annurev-nutr-071715-051213PubMedGoogle ScholarCrossref
43.
Light  KC, Smith  TE, Johns  JM, Brownley  KA, Hofheimer  JA, Amico  JA.  Oxytocin responsivity in mothers of infants: a preliminary study of relationships with blood pressure during laboratory stress and normal ambulatory activity.  Health Psychol. 2000;19(6):560-567. doi:10.1037/0278-6133.19.6.560PubMedGoogle ScholarCrossref
44.
Light  KC, Grewen  KM, Amico  JA,  et al.  Oxytocinergic activity is linked to lower blood pressure and vascular resistance during stress in postmenopausal women on estrogen replacement.  Horm Behav. 2005;47(5):540-548. doi:10.1016/j.yhbeh.2004.12.010PubMedGoogle ScholarCrossref
45.
Peters  SA, van der Schouw  YT, Wood  AM,  et al.  Parity, breastfeeding and risk of coronary heart disease: a pan-European case-cohort study  [published correction appears in Eur J Prev Cardiol. 2017;21(1):NP1].  Eur J Prev Cardiol. 2016;23(16):1755-1765. doi:10.1177/2047487316658571PubMedGoogle ScholarCrossref
46.
Natland  ST, Nilsen  TI, Midthjell  K, Andersen  LF, Forsmo  S.  Lactation and cardiovascular risk factors in mothers in a population-based study: the HUNT-study.  Int Breastfeed J. 2012;7(1):8. doi:10.1186/1746-4358-7-8PubMedGoogle ScholarCrossref
47.
McClure  CK, Catov  JM, Ness  RB, Schwarz  EB.  Lactation and maternal subclinical cardiovascular disease among premenopausal women.  Am J Obstet Gynecol. 2012;207(1):46.e1-46.e8. doi:10.1016/j.ajog.2012.04.030PubMedGoogle ScholarCrossref
48.
McClure  CK, Catov  J, Ness  R, Schwarz  EB.  Maternal visceral adiposity by consistency of lactation.  Matern Child Health J. 2012;16(2):316-321. doi:10.1007/s10995-011-0758-0PubMedGoogle ScholarCrossref
49.
Natland Fagerhaug  T, Forsmo  S, Jacobsen  GW, Midthjell  K, Andersen  LF, Ivar Lund Nilsen  T.  A prospective population-based cohort study of lactation and cardiovascular disease mortality: the HUNT study.  BMC Public Health. 2013;13:1070. doi:10.1186/1471-2458-13-1070PubMedGoogle ScholarCrossref
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    1 Comment for this article
    Women and breastfeeding
    Frederick Rivara, MD, MPH | University of Washington
    I always worry when studies like this provide more evidence for the beneficial effects of breastfeeding. This study examined the protective effects on mothers for breast-feeding for more than 12 months. My worries are that it might make mothers who are unable to breastfeed or do not choose to breastfeed for whatever reason feel worse, and that somehow their decision was "wrong."
    CONFLICT OF INTEREST: Editor in Chief, JAMA Network Open
    Original Investigation
    Obstetrics and Gynecology
    October 16, 2019

    Association of Maternal Lactation With Diabetes and Hypertension: A Systematic Review and Meta-analysis

    Author Affiliations
    • 1Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio
    • 2Department of Pulmonary and Critical Care Medicine, Cleveland Clinic, Cleveland, Ohio
    • 3Department of Internal Medicine, Cleveland Clinic–Fairview Hospital, Cleveland, Ohio
    • 4Department of Internal Medicine, John H. Stroger Jr Hospital of Cook County, Chicago, Illinois
    • 5Dow Medical College, Karachi, Pakistan
    • 6Floyd D. Loop Alumni Library, Cleveland Clinic, Cleveland, Ohio
    • 7Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
    • 8AdvantageCare Physicians, Brooklyn, New York
    JAMA Netw Open. 2019;2(10):e1913401. doi:10.1001/jamanetworkopen.2019.13401
    Key Points español 中文 (chinese)

    Question  Is breastfeeding associated with lower risk of maternal diabetes or hypertension?

    Findings  This meta-analysis of 6 studies including more than 200 000 participants found that breastfeeding was associated with a relative risk reduction of 30% for diabetes and 13% for hypertension in the mothers studied.

    Meaning  These findings suggest that breastfeeding is associated with long-term cardiovascular health benefits for women.

    Abstract

    Importance  Lactation has been shown to be associated with lower rates of diabetes and hypertension in mothers. However, the strength of association has varied between studies, and sample sizes are relatively small.

    Objective  To conduct a systematic review and meta-analysis to determine whether lactation is associated with a lower risk of diabetes and hypertension.

    Data Sources  Ovid MEDLINE, Ovid Embase, Cochrane CENTRAL, and CINAHL databases were searched from inception to July 2018 with manual search of the references.

    Study Selection  Studies of adult women that specified duration of breastfeeding for at least 12 months, evaluated primary hypertension and diabetes as outcomes, were full-text articles in English, and reported statistical outcomes as odds ratios were included.

    Data Extraction and Synthesis  Study characteristics were independently extracted using a standard spreadsheet template and the data were pooled using the random-effects model. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline for reporting was followed.

    Main Outcomes and Measures  Diabetes and hypertension.

    Results  The search yielded 1558 articles, from which a total of 6 studies met inclusion criteria for association between breastfeeding and diabetes and/or hypertension. The 4 studies included in the meta-analysis for the association between lactation and diabetes had a total of 206 204 participants, and the 5 studies included in the meta-analysis for the association between lactation and hypertension had a total of 255 271 participants. Breastfeeding for more than 12 months was associated with a relative risk reduction of 30% for diabetes (pooled odds ratio, 0.70 [95% CI, 0.62-0.78]; P < .001) and a relative risk reduction of 13% for hypertension (pooled odds ratio, 0.87 [95% CI, 0.78-0.97]; P = .01).

    Conclusions and Relevance  This study suggests that education about the benefits of breastfeeding for prevention of diabetes and hypertension in women is a low-risk intervention that can be easily included in daily practice and may have a positive impact on cardiovascular outcomes in mothers.

    Introduction

    Atherosclerotic cardiovascular diseases are the leading cause of death globally, with an estimated 17.3 million deaths per year.1 Hypertension and diabetes are associated with an increased risk of atherosclerotic cardiovascular diseases and cardiovascular mortality,2 and presence of diabetes may be considered a coronary artery disease equivalent in terms of cardiovascular risk.3 Moreover, both diabetes and hypertension independently account for the 7th and 13th leading causes of death in the United States, respectively.4

    Cardiovascular disease remains the leading cause of death in women as well.5 Women share many of the traditional risk factors for cardiovascular disease; however, they also have unique cardiovascular and metabolic stresses in the setting of pregnancy and the puerperium.5 Lactation has been thought to be associated with positive effects on the postpartum state and is thought to work as a physiological reset to the adverse effects of pregnancy.6 However, sample sizes from various studies of lactation and cardiovascular risk have been relatively small, and there is disparity in the outcomes reported. The aim of this systematic review and meta-analysis was to determine whether lactation is associated with reduced rates of maternal diabetes and hypertension.

    Methods

    This systematic review and meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline and the American Heart Association guideline.7,8 As a meta-analysis, the study was considered exempt by our institutional review board.

    Data Sources and Search Strategy

    The search strategy for electronic databases was developed in conjunction with a medical librarian experienced in systematic reviews. Electronic searches were performed in July 2018 in the following databases: Ovid MEDLINE, Ovid Embase, Cochrane CENTRAL, and CINAHL Plus.

    A combination of Medical Subject Heading terms, other controlled vocabulary, and keywords were used to search reports published in English for “cardiovascular diseases,” “metabolic syndrome,” “type 2 diabetes,” “risk factors,” “breastfeeding,” and “women.” In addition, we manually searched reference lists of selected articles to find any other relevant citations that were not detected by the electronic searches. The complete search strategies for each database are provided in the eAppendix in the Supplement.

    Two of us (R.M.R. and S.K.) independently extracted data and were blinded. Disputes were resolved by mutual discussion or by a third investigator (H.M.A.). Relevant articles were initially selected on the basis of the title and abstract, after which the full text was read to confirm relevance. The reference lists of the retrieved articles and the relevant reviews were then screened to identify pertinent studies.

    Study Selection

    We used the following inclusion criteria: studies of adult women that specified duration of breastfeeding for at least 12 months, investigated primary hypertension and/or diabetes as outcomes, were full-text articles in the English language, and reported statistical outcomes as odds ratios (ORs) adjusted for confounding variables. However, we collected data from studies that reported results as unadjusted ORs, relative risk (RR), or hazard ratios (HRs) to use in a separate subanalysis. Exclusion criteria included studies that did not specify duration of breastfeeding, those that studied breastfeeding duration for less than 12 months, or those that reported gestational diabetes or other gestational disorders only, such as preeclampsia or eclampsia. Although we made an effort to qualitatively review studies that reported outcomes as raw data, we did not include them in the final meta-analysis because it was not possible to adjust the calculated OR RR for confounding variables in each of these studies.

    Data Extraction and Quality Assessment

    The following data were extracted by 2 of us (R.M.R. and S.K.) on a standardized data collection form: name of authors, study name, region, year of publication, journal, type of study, total number of participants, age group of participants, follow-up, duration of breastfeeding, primary outcome (hypertension or diabetes), statistical outcome used (OR, RR, or HR; both adjusted and unadjusted when available), and variables adjusted for in each study. Where data were missing or clarifications were needed, the authors were contacted. Quality of the included studies was appraised using the standardized Newcastle-Ottawa Scale (eTable 1 in the Supplement).9

    Statistical Analysis

    The principal summary statistic was OR with 95% confidence intervals. To account for potential study variance, we performed a DerSimonian-Laird random-effects model meta-analysis of extracted data using the metan package in Stata statistical software version 15.1 (StataCorp).10 Cochrane Q statistics and I2 tests were used to assess for heterogeneity. Values of 25%, 50%, and 75% were considered low, moderate, and high degrees of heterogeneity, respectively.11 Statistical significance was assumed at P < .05 using 2-tailed tests. To assess for publication bias, an Egger test was used.12,13 We did not use a funnel plot for this purpose because fewer than 10 studies were included.

    Results
    Literature Search

    The initial literature search yielded a total of 1558 records; after removing 442 duplicates, 1116 studies remained (eFigure 1 in the Supplement). The reviewers screened the titles and abstracts of the 1116 studies, and a total of 107 full-text articles were reviewed for eligibility. Twenty-two studies went through a qualitative analysis, and 6 of the studies met full inclusion criteria and underwent quantitative synthesis or meta-analysis.14-19 A Preferred Reporting Items for Systematic Review and Meta-Analyses statement (PRISMA) flowchart20 is provided in eFigure 1 in the Supplement.

    Systematic Review of 22 Studies

    The details and characteristics of the 22 studies14-19,21-37 included in the qualitative analysis are shown in eTable 2 in the Supplement. Each study was designed differently. The 16 studies that were not included in the final meta-analysis still provided valuable information in support of the results, so we discuss them here.

    Bajaj et al32 found that the prevalence of diabetes was lower in women who had breastfed for more than 12 months compared with women who had breastfed for less than 3 months. Liu and colleagues14 used data from the Australian 45 and Up Cohort Study. The authors found that total breastfeeding duration and duration per child was associated with a reduction in the risk of development of diabetes by approximately 14% per year of breastfeeding. Schwarz et al15 concluded that breastfeeding for 12 or more months was associated with a decreased risk of hypertension, diabetes, hyperlipidemia, and cardiovascular disease. Unusually, the study population included women aged 50 to 79 years who were followed up for 7.9 years. On closer inspection, however, it was found that in addition to prospectively analyzing outcomes, retrospective analysis of data gathered on recruitment was also performed. In a cross-sectional study, Zhang and colleagues16 showed that women who breastfed were less likely to develop hypertension and diabetes. This remained significant when results were analyzed based on breastfeeding intervals of 0 to 6, 6 to 12, and more than 12 months, as well as when results were adjusted for confounding variables.

    Choi and colleagues17 showed that breastfeeding for 12 or more months was associated with a lower risk of diabetes and metabolic syndrome. The Shanghai Women’s Health Study24 found that not only did women who breastfed have a lower risk of diabetes, increasing duration of breastfeeding was associated with a lower risk as well. Similarly, Jäger et al30 concluded that breastfeeding for 6 or more months may be associated with a lower risk of diabetes. Breastfeeding was associated with protective effects against the development of atherosclerotic disease, with shorter duration of lactation associated with subclinical atherosclerosis as determined by measuring carotid intima media thickness.33 Stuebe et al23 found that at 3 years post partum, women who breastfed for more than 6 months had lower weight retention. However, in a multivariate analysis, no consistent trend was found relating the association between breastfeeding and maternal metabolism in general. Schwarz and colleagues21 compared parous women who breastfed for 1 month or more and nulliparous women, and concluded that parous women who never breastfed had a higher risk of developing diabetes. Interestingly, women who engaged in exclusive breastfeeding for 1 to 3 months had a lower risk of developing diabetes compared with those who engaged in nonexclusive breastfeeding.

    Breastfeeding initiation was associated with a reduced risk of diabetes in women with and without a history of gestational diabetes in a study by Martens et al.35 This association also remained significant after adjusting for confounding variables. Kirkegaard and colleagues26 concluded there was a strong, graded inverse association between lactation and incidence of diabetes when looking at various breastfeeding durations ranging from 0 to 6 months, 6 to 12 months, and longer than 12 months. Similarly, the Study of Women’s Health Across the Nation (SWAN)36 found that breastfeeding was associated with a lower prevalence of diabetes in a dose-response manner as well.

    Using data from the Nurses’ Health Study, a large prospective cohort with more than 44 000 participants, Stuebe et al29 found that exclusive breastfeeding for longer than 6 months or total breastfeeding for longer than 12 months was associated with a lower risk of developing hypertension later in life compared with no breastfeeding or breastfeeding for less than 6 months. These findings remained significant after adjusting for confounders. Similarly, the Korean Women’s Study27 suggested that breastfeeding for 1 to 6 months or longer was associated with a lower risk of hypertension compared with no history of lactation. This study also found that the combination of obesity and gestational hypertension was associated with a higher risk of developing hypertension.

    Park and Choi28 found that a greater number of breastfed children and longer duration of breastfeeding were associated with a lower risk of hypertension. This association was moderated by the degree of obesity and insulin resistance. A study by Kirkegaard et al26 studied the association between breastfeeding and hypertension as well as the development of cardiovascular disease and found that longer duration of breastfeeding was associated with a lower risk of hypertension and cardiovascular disease. Kim and Kim25 showed that any breastfeeding was better than none when assessing the association between breastfeeding and metabolic syndrome. Interestingly, a cross-sectional study31 of more 900 women in Iran did not support the protective associations of breastfeeding with development of metabolic syndrome.

    Chetwynd et al18 used data from the Black Women’s Health Study and found that breastfeeding was associated with reduced risk of hypertension at ages 40 to 49 years, but not necessarily at older ages. Increasing the duration of breastfeeding was associated with a lower risk of developing hypertension in this age group, with the strongest association seen in women who breastfed for a cumulative time of 24 months or more. Lupton and colleagues19 used data from the Australian 45 and Up Study. Data from more than 74 000 women aged 45 years and older were analyzed to determine the association of parity and breastfeeding with maternal hypertension. The authors observed that lifetime breastfeeding for longer than 6 months or more than 3 months per child was associated with lower odds of having high blood pressure.

    Meta-analysis of 6 Final Studies

    Six studies14-19 reported diabetes or primary hypertension as an outcome and were included in the meta-analysis (4 reported diabetes as the outcome and 5 reported primary hypertension as the outcome). The 4 studies14-17 included in the final meta-analysis for the association between lactation and diabetes had a total of 206 204 participants. The 5 studies15-19 that were included in the meta-analysis for association between lactation and hypertension included a total of 255 271 women. Characteristics of the included studies are shown in the Table. For breastfeeding and risk of either hypertension or diabetes after 12 months, an Egger test revealed P values of .51 and .93, respectively, indicating that publication bias did not alter the results. Mean (range) follow-up duration was 9.6 (3-18) years.

    Diabetes Risk After 12 Months of Breastfeeding

    For meta-analysis of the outcomes, we used adjusted ORs to account for confounding by variables such as obesity, smoking, and family history on the association of breastfeeding with hypertension and diabetes. We observed that breastfeeding for longer than 12 months was associated with a relative risk reduction of 30% for diabetes compared with breastfeeding for less than 12 months, with a pooled OR of 0.70 (95% CI, 0.62-0.78; P < .001; I2 = 33%) (Figure 1). We found no difference in the results when we pooled together the results of studies reporting RR, OR, and HR (eFigure 2 and eFigure 3 in the Supplement).

    Hypertension Risk After 12 Months of Breastfeeding

    Breastfeeding for longer than 12 months was associated with a relative risk reduction of 13% for hypertension compared with breastfeeding for less than 12 months (pooled OR, 0.87 [95% CI, 0.78-0.97]; P = .01; I2 = 60.6%) (Figure 2). Again, no difference in results was found when we conducted a pooled analysis of studies that reported RR and OR (eFigure 4 in the Supplement).

    Discussion

    The results of this meta-analysis with more than 200 000 participants suggest that breastfeeding for longer than 12 months is associated with decreased maternal risk of developing hypertension and diabetes. This was true even after adjusting for traditional cardiovascular confounders, as we used the adjusted summary estimates from each study. Cardiovascular disease is the leading cause of death in women,38 and hypertension and diabetes are both preventable diseases that are strong risk factors associated with atherosclerotic cardiovascular diseases.39 Lifestyle modifications such as weight loss, smoking cessation, reduction in alcohol intake, exercise, and diet are well-established means of reducing risk of cardiovascular disease and stroke.40

    Pregnancy is associated with an adverse metabolic profile. Pregnant women are more likely to have an atherogenic lipid profile owing to an elevation of total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels, which are essential for the nutrition of the developing fetus. Pregnancy is also associated with insulin resistance and glucose intolerance. Insulin resistance and glucose intolerance increase as part of a normal pregnancy. A 2007 review found that nonobese pregnant women have a 44% increase in insulin resistance by 36 weeks of gestation.41 By slowing maternal glucose absorption and increasing fat reserves, the fetus is preferentially supported.42

    Lactation results in consumption of 500 calories per day.17 Breast milk is rich in cholesterol and mobilizes fat stores, enhances catabolism, and increases high-density lipoprotein levels. It has been thought that breastfeeding is a reset mechanism to the adverse metabolic profile in pregnancy, so women who do not breastfeed may be at risk for a persistently dysmetabolic state.42 Several studies have shown that lactation is associated with a decreased risk of diabetes and hypertension after adjusting for confounding variables such as age, smoking, obesity, and family history.42

    Oxytocin is a neuropeptide that plays an important role in breastfeeding and uterine contractions during childbirth. It has also been associated with reduced stress, vascular resistance, and decreased blood pressure and may play a critical role in the association between lactation and decreased blood pressure post partum in women who breastfeed.43,44

    In addition to diabetes and hypertension, breastfeeding has been associated with a lower risk of cardiovascular disease,45-47 obesity,48 and metabolic syndrome17,36 as well as decreased overall cardiovascular mortality49 in women in several studies, which demonstrates the great potential for further research in this area.

    Limitations

    Our study faced limitations inherent to meta-analysis studies, which use pooled data without access to original patient data. None of the studies that we used were randomized clinical trials, so there may be an element of confounding bias. We used adjusted ORs because there are many confounding factors associated with cardiovascular outcomes, such as obesity, socioeconomic factors, smoking, and family history, in each of the included studies. However, there was heterogeneity for the confounding variables that each study adjusted for. Another issue is that the ascertainment of lactation history was usually self-reported in the studies using structured interviews, questionnaires, or open-ended questions, which could have led to recall bias as many studies were conducted years after the participants had given birth. None of the studies included reported blinding in any way to the exposure of interest (lactation). Outcome assessment was not always validated by record linkage or objective assessment, with some studies using an individual’s report of having hypertension or diabetes.

    There was variability in the follow-up times in each study, which ranged from 3 to 18 years, and none of the studies reported the point for the development of outcome of interest. This does raise uncertainty about the proportion of association that breastfeeding has with the development of diabetes and hypertension over time. Additionally, owing to the heterogeneity of the statistical outcomes reported in studies, which included HR, OR, and RR, we had to exclude a number of studies from the final meta-analysis. On balance, all the studies analyzed showed a signal toward benefit of lactation, and the pooled outcomes and subanalysis that included studies that otherwise met inclusion criteria but reported results as RR and HR showed a strong, statistically significant protective association with little heterogeneity.

    Conclusions

    Breastfeeding for longer than 12 months was associated with a 30% lower risk of diabetes and a 13% lower risk of hypertension in mothers after adjusting for confounding variables. The prenatal and antenatal period is an important opportunity to educate women about lifestyle interventions that may protect their health in the future. In addition to weight loss, smoking cessation, and exercise, breastfeeding should also be recommended owing to its benefits for the mother. Because this meta-analysis showed association but not causation, further research is needed to better understand this result. However, given the low-risk nature of this intervention, educating mothers about the potential benefits of breastfeeding for their cardiovascular health can be easily introduced into clinical practice when addressing prevention of cardiovascular outcomes in women.

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    Article Information

    Accepted for Publication: August 28, 2019.

    Published: October 16, 2019. doi:10.1001/jamanetworkopen.2019.13401

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Rameez RM et al. JAMA Network Open.

    Corresponding Author: Haitham M. Ahmed, MD, MPH, AdvantageCare Physicians, 101 Pennsylvania Ave, Brooklyn, NY 11207 (ahmedh@acpny.com).

    Author Contributions: Dr Rameez had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Rameez, Sadana, Kaur, Simonson, Riaz, H. M. Ahmed.

    Acquisition, analysis, or interpretation of data: Rameez, Sadana, Kaur, T. Ahmed, Patel, Khan, Misbah, Simonson.

    Drafting of the manuscript: Rameez, Sadana, Kaur, T. Ahmed, Simonson, Riaz.

    Critical revision of the manuscript for important intellectual content: Rameez, Sadana, Kaur, T. Ahmed, Patel, Khan, Misbah, Simonson, H. M. Ahmed.

    Statistical analysis: Sadana, Kaur, Khan, Misbah.

    Administrative, technical, or material support: Rameez, T. Ahmed, Patel, Simonson.

    Supervision: Khan, Riaz, H. M. Ahmed.

    Conflict of Interest Disclosures: None reported.

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