LONG -TERM INFLUENCE OF BREASTFEEDING TO MOTHER’S HEALTH: A SYSTEMATIC REVIEW

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1 LITHUANIAN UNIVERSITY OF HEALTH SCIENCES

FACULTY OF MEDICINE DEPARTMENT OF NEONATOLOGY

LONG -TERM INFLUENCE OF BREASTFEEDING TO MOTHER’S HEALTH: A SYSTEMATIC REVIEW

Author: Sharon Charles Trott Supervisors: Dr. Egle Markuniene

Kaunas 2021

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SUMMARY OF THE THESIS

Author’s Name: Sharon Charles Trott

Title: Long-term influence of Breastfeeding to Mother’s health: A Systematic Review

Aim: This literature review aims to study the long-term health benefits of Breastfeeding to Mother’s health

Objectives: The goal of this literature review is:

1. To analyze the influence of breastfeeding with reduced incidence of Diabetes among women.

2. To analyze the influence of breastfeeding with reduced incidence of Cardiovascular diseases among women.

3. To analyze the influence of breastfeeding with reduced incidence of Breast cancer among women.

Methods: PubMed, ScienceDirect, were used to search for literature review. The literature was identified by searching a combination of the following terms, “Breastfeeding” OR “Lactation” OR

“Lactogenesis” OR “benefits of Breastfeeding” WITH “Cardiovascular diseases” OR “Atherosclerosis”

OR “Myocardial Infarction” OR “Type 2 Diabetes” OR “Hypertension” OR “Breast Cancer” OR

“Malignancy” OR “Duration”.

Results: By using the combination of the above-mentioned terms, the search returned n=7477 articles. After using the filter and application of inclusion and exclusion criteria, n= 43 articles were found, of which n=15 articles were used in the review.

Conclusion: Pregnancy is associated with physiological changes in a women’s body.

Breastfeeding is an important process postpartum. Women are not well aware of the benefits that Breastfeeding has on their bodies. Most education is given on the importance of breastfeeding and human milk on the infant’s growth and health. Therefore, there is a need for better educational programs to bring awareness to women on the importance of breastfeeding, for their long-term health. Breastfeeding is shown to have a reduced risk for adult diseases like Type 2 diabetes, hypertension, breast cancer, ovarian cancer.

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ACKNOWLEDGEMENT

I would like to thank my supervisor Dr. Egle Markuniene, MD, for her support.

CONFLICT OF INTEREST

The author reports no conflict of interest

PERMISSION ISSUED BY THE ETHICS APPROVAL

There was no Ethics Committee permission required

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ABBREVIATIONS

 BF - Breastfeeding

 CVD - Cardiovascular disease

 T2DM – Type 2 Diabetes Mellitus

 BP – Blood Pressure

 BRCA – Breast Cancer Gene

 TGF β – Transforming Growth Factor Beta

 ER + Oestrogen Receptor Positive

 ER – oestrogen Receptor Negative

 HER2 – Human Epidermal Growth factor receptor 2

 BMI – Body Mass Index

 WHR – Waist Hip Ratio

 HDL – High Density Lipoprotein

 LDL – Low Density Lipoprotein

 SBP – Systolic Blood pressure

 DBP – Diastolic Blood pressure

 ACTH – Adrenocorticotropic Hormone

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INTRODUCTION

Breastfeeding saves lives” and “Breast milk is best!” are well-known slogans for physicians and women [1].

Breast milk is the most natural and unadulterated source of primary nutrition for newborns.

Breast milk may very well be the most potent, sustaining, symbiotic, wholesome, and attainable elixir of life for a newborn [2]. However, for mother’s lactation proffers paramount short-term and long-term benefits. Impermanent efficacious consequences comprise uterine involution, facilitates maternal metabolic changes, aids in maternal weight loss, prolongs ovulation. Long-term benefits of lactation for women’s health comprise curtailment in risk of reproductive cancers, hypertension, cardiovascular disease (CVD), and possibly mitigates the risk of T2DM in the long run [3].

Lactation has been in conjunction with conducive effects on maternal glucose homeostasis, blood lipid profiles, body weight, and fat distribution. Lactating women manifest lower plasma glucose and insulin levels, a less atherogenic lipid profile, and weight loss just after childbirth, in comparison to that of nonlactating women [4]. Several prospective studies and a scanty number of epidemiological studies have observed a reverse action between a longer duration of BF and the incidence of T2DM [5]

[6].

A neoteric systematic review of 21 studies concluded that BF has shown improvements in various CV risks such as hypertension, T2DM. Although there have been studies investigating the link between BF and long-term markers of CVD and morbidity in the general population, outcomes were usually measured decades after delivery, rendering it arduous to conclude direct associations [7].

Many studies were conducted that showed the relation that lactation has on breast cancer risk and its subtypes. It showed a beneficial association between lactation and breast cancer subtypes (ER+

and PR+; or ER− and PR−), but these studies have not shown any link to HER2 subtypes. Since then, many prospective and cohort studies have been done, in order to find the relation that lactation has on breast cancer [8]. This review is purposed to traverse and explore the influence of BF with long-term (Type 2 Diabetes, Cardiovascular diseases (CVD) and breast carcinoma) on maternal health outcomes.

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AIMS AND OBJECTIVES

In this literature review, we aim to know potential long-term health benefits to mothers from breastfeeding.

Objectives raised include:

1. To analyze the association of breastfeeding with reduced incidence of Diabetes among women.

2. To analyze the association of breastfeeding with reduced incidence of Cardiovascular diseases among women.

3. To analyze the association of breastfeeding with reduced incidence of Breast cancer among women.

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LITERATURE REVIEW

Overview on Breastfeeding

“In all mammalian species the reproductive cycle comprises both pregnancy and breast-feeding:

in the absence of latter, none of these species, man included, could have survived”, as written by pediatrician Bo Vahlquist in 1981 [9].

Lactogenesis is the process of secretion of milk through the alterations in mammary epithelium which involves the maturation of alveolar cells. It has been categorized into 2 stages: secretory initiation and secretory activation.

 Stage 1 lactogenesis (secretory stage): occurs during pregnancy. As a consequence of alterations to the mammary gland by the action of the hormone progesterone secreted from the placenta which impedes further differentiation as the gland is adequately differentiated to secrete milk. In this stage, low quantities of specific milk components are secreted.

 Stage 2 lactogenesis (secretory activation): is the onset of copious milk production right after delivery. Since post-delivery, the placenta is removed and thus progesterone is no longer at high levels in the mother’s plasma but the progesterone levels don’t drop immediately after delivery, rather gradually over the initial days after birth, this is coupled with changes in mammary cells which leads to the formation of 500-750ml/d of milk [10].

Prepregnancy weight gain, diabetes, difficult vaginal deliveries, are known risk factors for the delay in lactogenesis. It has been documented that mothers who experienced a delay in their lactogenesis were reported to have shorter period of BF [11].

Overview on Influence of Breastfeeding on maternal health

BF has garnered attention from the previous two decades, as a prospective beneficial factor in reducing the mortality caused by adult diseases in the 21^st century among women. In various studies, mothers who breastfed have shown to have a reduced risk of developing adult diseases such as T2DM, Hypertension, Obesity, CVD, and Breast cancer [12].

It has been evaluated that 366 million individuals had diabetes (most of which are type 2) in 2011, while the numbers have been predicted to be extended to 552 million by 2030. The prevalence of type 2 diabetes is quickly increasing around the world in conjunction with the increment in weight, diminishment in physical activity, and dietary changes [13]. We are aware of the risk that hypertension, high cholesterol, and diabetes have on CVD such as Myocardial Infarction and Coronary Artery disease.

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9 [14]. Cardiovascular disease (CVD) is the most common cause of mortality around the world; between 2006 and 2016 there was an increase of 14.5% in deaths caused by Cardiovascular disease, which recorded about 17.1 million deaths in 2016 [15].

Many studies have used metabolic risk factors as covariates and determined the effect of lactation before and after adjusting these risk factors. Even, after these adjustments were made, it was found that lactating in comparison with nonlactating women, metabolic risk factors made none to little significant difference in concluding that lactation has shown to have favorable outcomes on maternal health [3].

Lactation has been suggested in many studies to have reset the metabolic system after pregnancy through various changes in maternal weight gain and insulin sensitivity [16]. It has been proved that pregnancy has a long-term effect on maternal health. An increase in the number of parities in many studies has directly linked CVD as a risk for women over the years. A high number of pregnancies is related to affect BMI and withhold gestational weight gain which is found to have detrimental outcomes in the following pregnancies as well as with long-term obesity risk for the mother [17] [18]. However, in several studies conducted it has been shown that breastfeeding has favorable outcomes for women [19].

To explain the relationship between breastfeeding and maternal health outcomes, studies have suggested the “reset” hypotheses. It generally explains, that during pregnancy women prepare their body for metabolizing the demand for two. The changes involve a surge in energy stores by the accumulation of fat, therefore there is an increase in abdominal fat, insulin production, insulin resistance, and circulating lipid levels. These changes help nourish the growing fetus. After birth, it has been hypothesized that lactation confers a beneficial role in resetting these accumulated fat stores and thereby resetting the maternal metabolism. Longer duration of breastfeeding in many studies has shown to be even more effective, wherein the longer a mother lactates, the more completely she off-loads these accumulated fat stores [17].

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10 Fig 1: Picture demonstrating “reset” hypothesis by Alison M Stuebe et al (2009) [17].

Talking about lactation and its effect on Breast cancer, it has been recorded that reproductive factors, which consist of late age at menarche, pregnancy frequency, and BF, have shown positive and potential advantageous effects on the development of breast cancer [20].

Breast cancer is the most common cancer in women worldwide with nearly 1,000,000 new cases every year, representing over 20% of all malignancies [21].

A decline in progress for reproductive cancers has been observed among women who have breastfed, it possibly abates their life span exposure to the hormone oestrogen. Oestrogen has been known to be a causative factor in carcinogenesis for women. According to a 2002 meta-analysis, women who prolong their time of BF had a diminished risk of breast cancer, in comparison with women who had not breastfed. Also, further risk of breast cancer has been known to be decreased by 4.3% for every year of BF, this only supports the evidence that a longer duration of BF further reduces the risk of breast cancer [1].

In Marilyn L. Kwan et al. study any prior BF was in conjunction with lower risks of breast cancer-specific death. The sheltering associations were analytically significant among women with luminal A tumors, and while women with luminal B and basal-like tumors also had sheltering effects, they were not analytically significant [22].

Along with subtypes of breast cancers, Joanne Kotsopoulos et al. conducted a case study on the association between BF and breast cancer risk among women with BRCA1 and BRCA2 mutation. They concluded that parous women who ever breastfed along with women who breastfed for longer duration had shown reduced risk of developing breast cancer risk among BRAC1, but apparently not so much for BRAC2 mutation carriers [20].

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11 We are yet to know the protective effect that BF has on potential breast cancer risk. Several hypotheses have been proposed, among which prolonged BF has been positively shown to influence lactational amenorrhoea and thus exposure to total oestrogens, is reduced. These levels of oestrogen were found low in premenopausal BF mothers compared with women (parous or nulliparous) who never lactated [21].

Overview of Benefits of lactation to Mothers

Table 1: Maternal Benefits of Breastfeeding by Christine M. Dieterich et al (2014) [1]

Breastfeeding may confer both immediate and long-term benefits to mothers, especially if recommendations for exclusivity and duration are met. Such benefits may strengthen motivation or commitment to breastfeeding.

Reasons to initiate breastfeeding:

 Reduce maternal bleeding after delivery

 Involute uterus

 Facilitate positive metabolic changes

 Facilitate postpartum weight loss

 Reduce stress

 Delay ovulation

Reasons to continue breastfeeding:

 Increase postpartum weight loss

 Prolong lactational amenorrhea

 Decrease visceral adiposity

 Reduce type 2 diabetes risk

 Reduce cardiovascular risk

 Reduce breast cancer risk

 Reduce ovarian cancer risk

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RESEARCH METHODOLOGY AND METHODS

Literature Search

The literature review was searched using PubMed, Literature was identified by searching a combination of the following terms, “Breastfeeding” OR “Lactation” OR “Lactogenesis” OR “benefits of Breastfeeding” WITH “Cardiovascular diseases” OR “Type 2 Diabetes” OR “Hypertension” OR

“Coronary Artery Disease” OR “Atherosclerosis” OR “Breast cancer” OR “Malignancy”.

Table 1: It has extensive list of terms that were used in the initial search

 Breastfeeding

 Lactation

 Lactogenesis

 Effects of Breastfeeding

 Breast Milk

 Human Milk

AND

 Women

 Maternal

 Postpartum

 Cardiovascular Diseases

 Type 2 Diabetes

 Hypertension

 Coronary Artery Disease

 Atherosclerosis

 Breast cancer

 Malignancy

These terms were used alone or in combination with the below in the initial search.

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13 Table 2: Filters applied

 Article types: Clinical trials, Clinical Study, Case Reports, Meta- Analysis

 Publication Dates: 2014-2021

 Species: Human

 Language: English

Table 3: Inclusion and Exclusion Criteria Inclusion Criteria

 Free text (external link)

 Free full text Exclusion Criteria

 Reviews

 Systematic reviews

 Literature reviews

 Abstracts with no external links

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RESULTS

The search was done by combining the following terms: “Breastfeeding” OR “Lactation” OR

“Lactogenesis” OR “benefits of Breastfeeding” WITH “Cardiovascular diseases” OR “Type 2 Diabetes”

OR “Hypertension” OR “Breast cancer” OR “Malignancy” OR “Duration” (Table 1). With the combination of the above terms, 7475 articles were found. After the application of filters (Table 2) and the inclusion and exclusion criteria (Table 3), the search narrowed down to 15 articles.

The table below summarizes the studies included on Breastfeeding and incidence of Type 2 Diabetes, Cardiovascular diseases, Breast Carcinoma

Table 1: Characteristics of Included studies Author,

Year Study Design Period Sample Size Category of

Breastfeeding Incidence or Trends of Disease

Bing-Zhen Zhang et al;

2015 [23]

Cross- sectional study

Not known 9,128 Breastfed 0-6 vs >6-12 months

Incidence of DM decreases with longer duration of breastfeeding

Ga Eun

Nam et al;

2019 [6]

Population-

based study 2010-2013 9,960 Ever

Breastfed Incidence of DM decreases with

Breastfeeding Martens et

al; 2016 [24]

Retrospective study

1987-2011 334,553 Breastfeeding with GDM vs without GDM

Incidence of DM is lower with non GDM women

Erica P Gunderson et al; 2018 [25]

Cohort study 1986-2016 1238 ≥6-12 months

vs ≥12

months

Incidence of DM decreases with longer duration of breastfeeding Luo, Juhua

PhD et al;

2019 [26]

Cohort study 1993-1998 data collected after 14 years

136,652 Breastfed vs Never

Breastfed

Breastfeeding decreases the risk of Diabetes

Monica Mazariegos et al; 2019 [27]

Cohort study 2006-2008 66,573 3-6 months vs

6-12 months Breastfeeding reduces the risk of Diabetes Erica P.

Gunderson

Prospective cohort study

1985-1986 data

2,787 0<1 vs ≥10 months

Shorter

duration of BF

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15 et al; 2015

[28]

collected after 20 years

is associated with

subclinical Atherosclerosis Sanne A.E

Peters et al;

2016 [29]

Case-cohort

study 1991-1999 520,000 Breastfed vs Never

Breastfed

Incidence of CHD is lower in Breastfed women

Ellen M Chetwynd et al; 2017 [30]

Case-Control study

1995-2011 59,001 Breastfed vs Never

Breastfed

Longer

duration of BF reduces risk of Hypertension Ling Yang

et al; 2017 [31]

Prospective

study 2004-2008

along with 8 years follow up

0.5 million

individuals Breastfed vs Never

Breastfed

BF associated with lower risk of CVD

Milena IIlic et al; 2014 [32]

Case-control study

1999-2010 382 Ever

breastfed vs

≥13 months

BF found to be a risk factor for breast cancer Min-Min

Tan et al;

2018 [33]

Case-control

study 2002-2016 3,683 cases 3,980 controls

Ever

breastfed vs Never

BF had the strongest protective effect against breast cancer Marilyn L.

Kwan et al;

2015 [22]

Cohort study 1997-2000 with 9 years of follow up

1636 Ever

Breastfed

BF decreases the incidence of breast cancer recurrence Seok Hun

Jeong et al;

2017 [34]

Database study

2004-2012 25,778 sets 1-12 vs >25 months breastfed

The longer duration had reduced risk of breast cancer Salma Butt

et al; 2014 [35]

Prospective

cohort study 2004 14,092 <4, ≥4, <8,

≥8, <13, ≥13 months breastfed

BF duration not associated with Breast cancer risk

DM – Diabetes Mellitus GDM – Gestational Diabetes BF – Breastfeeding

CHD – Coronary Heart Disease CVD – Cardiovascular Disease CAD – Coronary Artery Disease

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16 Results of Incidences

Diabetes

The study of Bing-Zhen Zhang et al. researched the influence of BF on maternal hypertension and diabetes. They found that women who had not breastfed had an increased risk of diabetes, compared with women who had previously BF. In contrast, studies of Monica Mazariegos et al. found that women who breastfed on average for 6-12 months had a potentially lower risk of developing T2DM compared with women who did not breastfeed. But it was also found that ≥12 months of lactation, did not confer any risk reduction in developing diabetes among mothers.

Both the studies researched the relationship between BF and potential influence on T2DM, but Bing-Zhen Zhang et al. found that when breastfeeding was categorized into four levels (none, >0 to 6 months, >6 to 12 months, and >12 months), women with prolong time of breastfeeding >0 to 6 (OR=0.81; 95% CI, 0.67–0.98) and >6 to 12 months (OR=0.46; 95% CI, 0.26–0.84), respectively had a lower incidence of risk of developing T2DM in comparison with women who did not breastfeed. The results found even after the adjustment of potential cofounders which included age, BMI, WHR, working status, educational level, smoking, drinking, family history of diabetes, age of menarche, menopause, use of contraceptive, age of child-bearing, and postpartum BMI, the ORs of diabetes for >0 to 6 months and >6 to 12 months of BF were 0.81 (95% CI, 0.67–0.98) and 0.47 (95% CI, 0.26–0.86) respectively.

Ga Eun Nam et al also support that having ever breastfed was inversely associated with prevalent T2DM after adjusting for potential confounders. When they compared with women who had never breastfed, women who had breastfed 1, 2, 3, 4, 5, 6, or ≥7 children had lower odds of T2DM, and the ORs tended to decrease as the number of children breastfed increased.

In Ga Eun Nam et al. study any and all duration of lactation was associated inversely with the occurrence of T2DM. In Erica P. Gunderson et al. study of BF influence of diabetes was done comparing black women with white women, which previous studies haven’t done. In this comparison, they found that black women (African-American) were at a higher risk of developing diabetes but also atherosclerosis and later leading up to Cardiovascular diseases. They found that the prevalence of diabetes was higher in women who were black, had multiple pregnancies, reach menarche earlier, and had higher BMI, waist circumference, fasting glucose, and triglycerides.

In the follow up of their study Erica P. Gunderson et al. found the no lactation group (none) had lower education and diet quality, higher occurrence of metabolic syndrome; treatment for hypertension, and a family history of diabetes; along with advanced weight gain developed GD, gestational hypertension during their pregnancy.

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17 Luo et al. along with lactation also studied parity with the occurrence of diabetes among women. Compared with nulliparous women, parous women with more than five births who did not breastfeed had a higher risk of diabetes, these women were found to be likely older, Hispanic, less educated, non-smokers, drink less, have a higher family history of diabetes, use more cholesterol- reducing medications, have higher BMIs, have higher Waist circumference, engage in low physical activity compared with women who breastfed for more than 6 months, the risk from parity was not significantly increased. Women with five or more births had increased diabetes risk regardless of breastfeeding. The results were similar when the number of months breastfed per child was analyzed.

Hypertension and Cardiovascular Disease

In another Erica P. Gunderson et al. study, they analyzed the association of BF on Atherosclerosis which is a risk in women’s life for developing CVD. They found that shorter lactation duration was associated with Black race, nulliparity, younger age, higher prepregnancy BMI, and lower prepregnancy plasma HDL-cholesterol and physical activity. They found the presence of Atherosclerosis plaque which is a common risk factor for Cardiovascular disease (CVD), that occurs with a shorter duration of lactation in contrast with women who breastfed longer.

Similarly, Ellen M. Chetwynd et al. study also analyzed the duration of lactation with the incidence of hypertension among Black African-American women. It is found that Black women lag behind in BF and that hypertension is a common factor found in those women. They used a multivariate model that adjusted for age, survey cycle, parity, age at first birth, diet, exercise, adolescent BMI, smoking, and family history of myocardial infarction. They found that after these adjustments any BF was associated with reduced risk of hypertension at ages 40–49 years (odds ratio (OR) = 0.92, 95% CI: 0.85, 0.99), and risk decreased with increasing duration of BF (for ≥24 months, OR = 0.82, 95% CI: 0.69, 0.98).

Although Sanne A.E. Peters et al. conducted a study to analyze both Parity and BF influence on CHD. This combination of Parity and BF found parous women who had never breastfed were at a significantly higher risk of CHD compared to nulliparous women. But this study did not find any significant difference between never BF and any duration of BF on the incidence of CHD. In contrast, Ling Yang et al. study found there were no significant differences in the risk of CVD between nulliparous women and parous women who had never breastfed. Compared with women who had never breastfed, women who had breastfed between 0 to 6 months, 6 to 12 months, 12 to 18 months, 18 to 24 months, or

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18 over 24 months had a 1%, 7%, 11%, 13%, and 18% lower risk of CHD, respectively, with each additional 6 months of breastfeeding per child associated with 4% (2–5%) lower CHD risk.

Breast Carcinoma

In Min-Min Tan et al. study BF had the strongest protective effect against breast cancer. Among parous women, those who ever breastfed had 35% reduced risk in their study; compared with those who did not breastfeed, the reduction of risk for those who breastfed between 1–12 months and those who breastfed more than 12 months was 30% and 70% respectively.

However, in Milena IIlic et al. study no notable differences were seen in the risk reduction of breast cancer by the past period of BF.

The BC risk of nulliparous women was higher than that of parous women, especially in postmenopausal women, this effect was stronger for HR+ BC in Seok Hun Jeong et al. study. Likewise, Seok Hun Jeong et al. also found prolonged time of BF to be in conjunction with a reduced risk of BC.

Women who breastfed for a longer period (25+ months) had a 56% reduced risk for BC, regardless of menopausal status. Relatively, when premenopausal women and postmenopausal women were compared, premenopausal women who breastfed for 1-12 months had a reduced risk for BC, while postmenopausal women with the same breastfeeding duration had no reduced risk. The protective effect of BF on BC risk was not significantly different according to HR status or pathological subtype.

In comparison with Marilyn L. Kwan et al. ever BF was associated with a reduced risk of breast cancer recurrence compared with never BF, and it was slightly more protective among those who breastfed six months or more compared with those who never breastfed. BF six months or more compared with never BF again conferred slightly greater risk reductions for all outcomes in the luminal A subtype recurrence. While no statistically significant associations were observed in the luminal B or basal-like groups forever BF and duration of BF, reduced risks of these outcomes were noted. However, BF was not associated with a reduced risk of recurrence among women with HER2-E tumors.

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DISCUSSION

Influence of breastfeeding on Type 2 Diabetes among women

In most of the studies included in this review, BF women had a reduced risk of developing maternal diabetes when compared with women who had no history of breastfeeding [23]. The association between breastfeeding and diabetes was previously confirmed in several cohort studies. Meta-analyses of these observational studies concluded that there is an inverse association between BF and maternal T2DM risk and that the risk reduction was greater as breastfeeding duration increased [6].

In several cohort studies, it has been observed that a longer duration of breastfeeding is associated with a greater risk reduction of type 2 diabetes among women [25] [26] [36] [37] [38]. Results confirm previous work suggesting that parous women who breastfeed can lower their risk of developing T2DM in later life and that this exponentially multiplies the benefits that BF has on mothers [37]. It is found that women who breastfed an average of 6 to <12 months per child had a 27% lower rate to develop diabetes. Similarly, many other studies found potential benefits from BF to risk of developing T2DM, this risk reduction ranged from 25% for 6 months or less to 47% for 6 or more months of lactation, but a study by Luo Juhua et al. found that reduced risk for diabetes was observed only for women who had a total BF history of at least 24 months [26].

The underlying mechanisms by which BF could lower diabetes risk are still unknown, although several hypotheses of dependence on weight development and metabolic pathways have been suggested.

BF is well observed to show weight loss along with less long-term weight gain during childbearing years (Stuebe & Rich‐Edwards, 2009) [27]. In lactation, mothers are required with higher energy to support milk production, this explains how BF could lower postpartum weight loss [6]. Therefore, a shorter duration of BF has not shown to reduce the risk of diabetes as significant as a longer duration of BF has shown, as shorter duration may not be able to lose the visceral fat gained during pregnancy [6].

Meanwhile, another mechanism brought to light in many studies is that BF may improve insulin sensitivity and glucose tolerance. Lactating women have lower circulating glucose in both fasting and postabsorptive states, as well as lower insulin secretion. The glucose produced in 24 hours approximately 50g is used up into the mammary gland for the synthesis of milk via the non-insulin mediated pathways. These processes for milk production have been linked with lower basal and glucose- stimulated β-cell secretory activity for a standardized glucose load and beneficial effects that unload the pancreatic β-cells [25] [36].

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20 In summary, studies have shown BF duration to inversely influence the risk of developing type 2 diabetes. Clinical data and studies reveal improvement in glucose tolerance in breastfeeding women when compared with non-breastfeeding women further proving the fact that BF has potential influence on reducing the risk of type 2 diabetes [36].

Influence of breastfeeding on Hypertension and Cardiovascular disease

Parous women who breastfed compared with parous women who did not breastfeed, studies showed they had ≈a 10% lower risk of major CVD subtypes. Adding to this, additional 6 months of breastfeeding was associated with a further ≈3% to 4% lower CVD risk among those who ever breastfed [31].

Multiple studies have individually investigated the impact of lactation on CVD risk such as obesity, T2DM, hypertension, and total cholesterol [39]. In prospective and several retrospective studies, it was found that lactation was shown to reduce the occurrence of metabolic risk of high blood pressure, T2DM, and prevalent CVD in the general population [7]. In a retrospective study, when the blood pressure in each group (BF, formula feeding, mixed feeding) was compared, one-month postpartum SBP in the breastfeeding group was significantly lower than that in the other groups. Jonas et al and Altemus et al. reported that when they measured the blood pressure of women after BF there was a significant reduction in SBP and DBP. Lee et al. also reported that women who breastfeed, for a duration of 1-6 months have been known to have decreased risk of hypertension [40].

Possible mechanisms observed behind these benefits of lactation on CVD can only be assumed, more studies are required to confirm these mechanisms in the long-term influence of lactation on maternal health. Women’s bodies undergo hormonal changes during the process of pregnancy and postpartum lactogenesis. These changes include the release of the hormone oxytocin, which is released from the anterior pituitary gland as a result of the nipple/areolar stimulation. We all know the function of oxytocin, which involves the maintenance of lactogenesis, diminishes post-delivery bleeding, and more rapid uterine involution. But the function of oxytocin in possibly lowering the risk of blood pressure, include its inhibitory action on ACTH and cortisol secretion in human. Oxytocin is released as an action of the baby suckling, which in turn influences the blood pressure reduction and/or the increase in central α2-adrenergic activity, both of which would be influenced by oxytocin or female hormones.

[41].

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21 Fig. 2 The hypothetical mechanism of the long-term effect of breast-feeding on blood pressure by Soon Young Lee et al. 2005 [41]

It is found that in animal studies when oxytocin was administered frequently it induced a calm and stress-free effect, that of lowering blood pressure among rats [40]. Similarly, as mothers frequently breastfeed their infant so is oxytocin released frequently. Therefore, these findings suggest that due to oxytocin blood pressure may be reduced, and thus BF could have a potential benefit for mothers from the risk of hypertension and CVD [40].

Influence of breastfeeding on Breast carcinoma

It has been identified that in the general population, several factors have been known to shelter women from breast cancer, which consists of late age at menarche, parity, and BF [20]. In the studies used in this review influence of breastfeeding on breast cancer risk and types and subtypes were analyzed. In a study where BRCA mutation carriers’ risk for development of breast cancer after BF was analyzed, the majority of BRCA1-related tumors are basal-like breast cancers characterized by ER, PR, and HER2 negativity while BRCA2-tumors resemble sporadic cases. They found BF independent of parity to have influenced a risk reduction in the development of basal-like or ER-negative/PR-negative breast cancers [20].

In another study, results suggested that having children and BF was linked to reduced risk of ER+ breast cancer, but increased risk of ER- disease [42]. Recently, studies have shown that BRCA protein has an important role in mammary cell differentiation and proliferation. Rajan and colleagues have shown that BRCA1 and BRCA2 mRNA expression in mice is high during the proliferative and differentiation stage, in process of puberty, embryogenesis, and pregnancy, but proliferation is low during lactation. [20].

In general, several mechanisms have been proposed to explain the possible effect that lactation has on breast cancer risk, these include: (1) longer period of BF contributed to low levels of hormone

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22 estrogen, due to suppression of ovulation during BF; (2)a protective effect from direct physical changes in the breast that accompany milk production; (3) a reduction in the concentrations of toxic organochlorines in the breast with increasing cumulative duration of breastfeeding; and (4) an expression of transforming growth factor-b during breastfeeding, a hormonally regulated negative growth factor in human breast cancer cells [43].

A longer duration of lactation has been associated with delayed ovulation and thus prolongs lactational amenorrhoea. This in turn reduces the exposure to oestrogen which has been linked to proliferative and carcinogenic effects in women. In several studies, it has been analyzed that oestrogen is likely involved in the development of breast cancer in BRAC1 mutation carriers, while late age at menarche, BF, and bilateral salpingo-oophorectomy are considered protective [21] [20].

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CONCLUSION

This review supports the objectives where breastfeeding has beneficial long-term benefits for women’s health as well as short-term benefits.

1. In this review, most studies showed that when the mother breastfed for a longer duration, usually >

6 months the incidence of diabetes was reduced by almost 20-30%.

2. During pregnancy, a mother’s body accumulates fat stores, to provide adequate nutrition for her baby. This increase in the fat stores for every pregnancy is considered in many researches a risk factor to develop aortic and coronary calcification over time. However, the energy required to produce human milk postpartum, and also the process of breastfeeding has been shown to inverse the effect of pregnancy-related risk for Cardiovascular diseases. Most studies in this review showed that women who breastfed for the duration of 4, 6, 12 months had a 5-10% lower risk for the incidence of CVD, but also studies have shown that women who breastfed longer duration of 12-24 months had additional 5% lower incidence of CVD.

3. For Breast Cancer, new recent studies done specifically on types and subtypes show that ER, PR subtypes had a 30-50% lower incidence of cancer among breastfeeding women compared with women who didn’t breastfeed. While breastfeeding women showed no benefits to the incidence of HER2-E tumor recurrence. In conclusion, a longer duration of ≥ 6 months of breastfeeding has been shown to significantly improve T2DM, Cardiovascular diseases, and Breast cancer.

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PRACTICAL RECOMMENDATIONS

 Breastfeeding has proven in many studies to be an important factor for promoting benefits to maternal health outcomes and therefore we need to make it our priority to educate mothers on the importance of breastfeeding as doctors and to help them initiate breastfeeding when lactogenesis is delayed in women.

 To encourage and support working mothers, on educating them on the importance of breastfeeding both to infant’s health as well as mothers health.

 To encourage the hospital nurses and doctors, to support strategies that promote breastfeeding.

REVIEW LIMITATIONS

The data was collected only by one person, also only the English language was used as a filter which may have limited the number of articles reviewed. Most of the studies conducted followed the women after several years to determine the long-term effect of lactation, but due to the longer period of follow up many participants fail to remember their lactation history, and thus not all studies are able to reach a definitive conclusion.

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LONG -TERM INFLUENCE OF BREASTFEEDING TO MOTHER’S HEALTH: A SYSTEMATIC REVIEW