Accepted Manuscript

Breastfeeding and maternal age-related cataract

Sangshin Park, Nam-Kyong Choi

PII: S0002-9394(18)30235-6
DOI: 10.1016/j.ajo.2018.05.017
Reference: AJOPHT 10529

To appear in: American Journal of Ophthalmology

Received Date: 5 May 2017

Revised Date: 17 May 2018
Accepted Date: 18 May 2018

Please cite this article as: Park S, Choi N-K, Breastfeeding and maternal age-related cataract, American
Journal of Ophthalmology (2018), doi: 10.1016/j.ajo.2018.05.017.

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 ACCEPTED MANUSCRIPT
ABSTRACT

PURPOSE: No studies addressed the influence of breastfeeding on cataract formation. The objectives of this study was to

address the relationship between breastfeeding and maternal age-related cataract.

DESIGN: A nationwide cross-sectional study.

METHODS: This study analyzed data for 3,821 parous women aged 50 years or above in the Korea National Health and

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Nutrition Examination Survey 2010-2012. Participants were aggregated into quartiles according to the number of

breastfed children and duration of breastfeeding. Logistic regression analysis was used to examine the relationships less or

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short breastfeeding and increased risks of cataract.

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RESULTS: A total of 2,197 women (57.5%) were classified as having age-related cataract. Women who breastfed 4-12

children [odds ratio (OR)=0.56; 95% confidence interval (CI)=0.35-0.89] had significantly lower risks for cortical cataract,

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compared to those breastfed none or one child (P for trend across quartiles=0.010). Women who breastfed for 36-60
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months (OR=0.61, 95% CI=0.42-0.90) or 61-324 months (OR=0.53, 95% CI=0.33-0.83) had lower risks for cortical

cataract compared to those breastfed 16 months or less (P for trend across tertiles=0.003). The population-attributable
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fractions of cortical cataract induced by number of children breastfed less than 3 and duration of breastfeeding less than

36 months were 9.4% (95% CI=1.3%-17.6%) and 10.7% (95% CI=3.0%-18.4%), respectively.
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CONCLUSIONS: Breastfeeding more children and long-term breastfeeding were associated with lower risk of cortical
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cataract formation in parous women.

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Breastfeeding and maternal age-related cataract

Sangshin Park,1,2 and Nam-Kyong Choi3,4*

1
Center for International Health Research, Rhode Island Hospital, The Warren Alpert Medical School of Brown

University, Providence, RI, United States

2
Department of Pediatrics, The Warren Alpert Medical School of Brown University, Providence, RI, United States

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3
Department of Health Convergence, Ewha Womans University, Seoul, Republic of Korea

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Short title: Breastfeeding and cataract

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Keywords: breastfeeding; lactation; cataract.

Numbers: - Numbers of words: Abstract- 220, Total-2,228 (introduction, method, results, discussion)
- Number of references: 43

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- Number of tables and figures: 3 Tables and 1 Figures
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Address for reprints: Not needed.
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* Correspondence to: Nam-Kyong Choi, Ph.D.

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Department of Health Convergence, Ewha Womans University. 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, South

Korea [nchoi@ewha.ac.kr]; Tel: +82-2-3277-6585; Fax: +82-2-3277-2867.

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INTRODUCTION

Age-related cataract, a loss of transparency of the crystalline lens, is the world’s primary cause of visual impairment.

Cataract caused 33% of blindness and 18% of severe or moderate visual impairment worldwide in 2010.1 In the 48

contiguous states of United States, 1.74 million on Medicare standard fee-for-service beneficiaries were performed for

cataract surgeries in 2004.2 A recent study reported 24% greater number of cataract surgeries in 2014 compared to 2004

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among Medicare beneficiaries.3 Moreover, cataract is the most costly eye diseases in Medicare claims.4, 5 Age-related

cataract may be one of major continuing threats to public health worldwide.

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Although breastfeeding is a time-limited condition, it leads to long-term benefits to maternal health. Because of

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beneficial effects of breastfeeding on children’s and mothers’ health status, the World Health Organization and many

countries recommends breastfeeding.6 For example, in the United States, the National Healthy People 2020 aims to have

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34% of mothers breastfeed their infants until 12 months of age.7 Numerous studies have provided strong evidence on the
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beneficial effects of breastfeeding on child health.6 However, compared to children, the effects on maternal health have

not been well established.

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Some epidemiologic studies have recently documented that absent or early cessation of lactation is associated

with increased risks of mothers for diabetes mellitus,8-11 hypertension,8, 11, 12 dyslipidemia,11 metabolic syndrome,13 and
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other cardiovascular diseases.11 Several mechanisms triggered by breastfeeding were suggested to explain the protective
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effects of breastfeeding on these metabolic diseases: “reset” of maternal metabolism, such as fat accumulation,14

oxytocin,15 ghrelin, and peptide YY.16 Some other epidemiologic studies reported the relationship between these
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metabolic diseases and age-related cataract.17-20 These diseases may act on the development of cataract through

mechanisms associated with oxidative stress,21 inflammation,22 and insulin resistance and subsequent accumulation of
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advanced glycation end products of lens protein.23

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Although the above study findings may imply the protective effect of breastfeeding on age-related cataract, to our

knowledge, no previous studies investigated the relationship between breastfeeding and age-related cataract. We therefore

hypothesized that increased number of breastfed children and longer breastfeeding duration would relate to the decreased

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risks for age-related cataract. This study was performed to test our hypotheses using a nationwide representative

population.

METHODS

We performed an analysis of data obtained from the cross-sectional Korea National Health and Nutrition Examination

Survey (KNHANES) 2010-2012 which investigates the nationally representative health and nutrition status of South

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Korean. In KNHANES, a stratified multi-stage probability sampling design was employed to select households based on

geographical area, gender, and age groups using household registries. This survey is comprised of a health interview, a

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nutrition survey, and a health examination survey. Detailed information about KNHANES are provided elsewhere.24 The

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KNHANES was performed according to ‘Ethical Principles for Medical Research Involving Human Subjects,’ Helsinki

Declaration. Each participant of KNHANES signed and provided an informed consent form. This survey was approved by

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the Ethics Committee of the Korea Centers for Disease Control and Prevention. Of 25,534 participants of KNHANES
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2010-2012, 13,918 were women participants. Our study used the data of parous women ≥50 years or above who have

history of delivery, who provided information of their breastfeeding experience, and who were examined for age-related
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cataract. This study included only participants who had not undergone any eyes surgeries. This study excluded

participants who had pseudophakic or aphakic eyes, because it was not clear whether these previous eyes status was
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affected by breastfeeding or other previous lifestyles.

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The independent variables of interest were number of breastfed children and lifetime breastfeeding duration. This

information was acquired from a self-reported questionnaire. The dependent variable of interest was subtypes of age-
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related cataract which were classified using a Haag-Streit BQ-900 slit-lamp (Haag-Streit AG, Koeniz, Switzerland) and

standardized Lens Opacities Classification System (LOCS) III photographic images: ≥4 for cortical cataract, ≥4 of nuclear
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opalescence or color for nuclear cataract, ≥4 for anterior subcapsular cataract, ≥4 for posterior subcapsular cataract, and
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more than one type in an eye for mixed cataract. “Any” cataract was defined as the presence of any subtype(s) in either

eye. The quality of ophthalmologic examinations of KNHANES was verified by the Korean Ophthalmologic Society.

Acting staff members of this committee periodically trained ophthalmology residents and ophthalmologists who

participated in the KNAHNES as ophthalmologic examiners.25

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Self-reported questionnaires and face-to-face interviews were used to investigate the following covariates: age (5-

year group), smoking status (former/current smoking with at least 100 cigarettes in life or never), alcohol consumption

status (current consumption with at least once a month or not), education level (middle school or less, high school, or

college or above), household income (at least US$2,000 a month or less), sun exposure (less than 2-h, 2- to 5-h, or more

than 5-h a day), and family history of any eye diseases. Diabetes mellitus was defined as use of antihyperglycemic agents

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or 8-h fasting glucose ≥126 mg/dL.26

Participants were subdivided into quartiles according to the number of breastfed children (0 to 1, 2, 3, and 4 to 12)

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and breastfeeding duration in months (0 to 16, 17 to 35, 36 to 60, and 61 to 324 months). First, relationships of subtypes

of age-related cataract with quartiles of the number of breastfed children and breastfeeding duration were analyzed using

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age- and multivariable-adjusted logistic regression models. Multivariable models adjusted for all covariates described

above. Second, this study performed multivariable logistic regression analysis using continuous predictors, the number of

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breastfed children and breastfeeding duration. Third, with adjustments for the same covariates, we estimated population
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attributable fraction (PAF) as a measure of the degree of cataract formation related to number of breastfed children <3 and

breastfeeding duration <36 months using R package version 3.4.3 (R Foundation for Statistical Computing).27 In the
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statistical analysis, participants with only one subtype of cataract were compared with those without any other subtype of
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cataract. For example, those with cortical cataract were compared with those without any other cataract in either eye. This
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study did not perform any analysis for anterior and posterior subcapsular cataract, due to their low prevalence in our study

population [1.4% (n=52) and 0.5% (n=20), respectively]. However, anterior and posterior subscapular cataract was
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considered as an outcome when we performed the analysis for any cataract as the outcome. With exception of PAF

estimation, we performed all statistical analyses using SAS 9.4 (SAS Institute, Cary, NC, USA). A P value less than 0.05
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was considered to be statistically significant.

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RESULTS

Of 13,918 women participants in the KNHANES 2010-2012, 4,076 of whom were 50 years old or above who had not

undergone cataract or any other eyes surgeries. This study excluded women who had never given birth (n=107), who did

not provide their parity information (n=135), who did not provide any of their breastfeeding information (n=2), or who

were not examined for age-related cataract (n=11). Therefore, 3,821 participants were analyzed in this study.
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Participants’ mean age was 62.2 years (Table 1). Mean number of breastfed children was 2.8, and mean

breastfeeding duration was 46.8 months (Table 1). A total of 470 (12.3%), 1,345 (35.2%), and 417 (10.9%) participants

had cortical, nuclear, and mixed cataract, respectively. Participants with age-related cataract were older and more exposed

to sunlight; they were more likely to have diabetes mellitus, more children breastfed, longer breastfeeding duration

compared to those without cataract. Participants with cataract were less likely to drink alcohol, have high education, have

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low income, and have family history of eye disease.

Women who breastfed 4 to 12 children [odds ratio (OR)=0.56; 95% confidence interval (CI)=0.35-0.89] had

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significantly lower risks for cortical cataract, compared to those breastfed none or one child (Table 2). A significant linear

trend was observed across quartiles (P for trend=0.010). Women who breastfed for 36 to 60 months (OR=0.61, 95%

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CI=0.42-0.90) or 61 to 324 months (OR=0.53, 95% CI=0.33-0.83) had significantly lower risks for cortical cataract

compared to those breastfed 16 months or less (Table 3). We observed significant linear trend across quintiles (P for

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trend=0.003). Regarding the linear breastfeeding variables, we found the significantly decreased risks for cortical cataract
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with increasing breastfeeding duration (OR per year=0.95, 95% CI=0.91-<1.00) (Figure 1).
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With adjustments for covariates, the PAF of cortical cataract related to the number of breastfed children <3 was

9.4% (95% CI=1.3%-17.6%), compared to the number ≥3 (data not shown). The PAF of cortical cataract related to the
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breastfeeding duration <36 months was 10.7% (95% CI=3.0%-18.4%), compared to the duration ≥36 months. This
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indicates that 10.7% of cortical cataract in our study population are attributable to the short-term breastfeeding <36

months. However, PAFs of the other subtypes of cataract were not significant (data not shown).
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DISCUSSION
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This study demonstrated that increased number of breastfed children and longer breastfeeding duration were significantly

related to decreased risks for cortical cataract. The estimated PAFs of our study population, caused by number of
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breastfed children <3 and breastfeeding duration <36 months, were 9.4% and 10.7%, respectively. Our findings propose

that careful observation for age-related cataract is required for women who breastfed a few children or shortly breastfed in

their later life.

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It is difficult to demonstrate the mechanisms of the direct association between breastfeeding and age-related

cataract, because age-related cataract may occur after a substantial time period after breastfeeding. We presumed that

some metabolic diseases are likely to mediate the protective role of breastfeeding on age-related cataract.

Several pathways have been proposed to explain the decreased risks of metabolic diseases in women who

breastfed relatively many children or long-term period. The fat accumulated during pregnancy could be used to produce

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energy of lactation, and changes of weight during lactation may reduce the risk of metabolic diseases. Mothers need more

than 600 kcal of energy per day for exclusive breastfeeding,28 which may contribute to the improved insulin sensitivity

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during lactation period.29, 30 In contrast, weight gains caused by non-breastfeeding and short breastfeeding duration may

increase the insulin resistance resulting in diabetes mellitus,31 hypertension,32 and metabolic syndrome.17, 33 Release of the

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oxytocin hormone while breastfeeding may also be directly associated with the inhibition of developing metabolic

diseases in later life. A previous study showed that oxytocin had an effect of improving weight control and insulin

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resistance in human, and oxytocin had the anti-diabetic effects in diabetic mouse models.34 Another animal study showed
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that oxytocin neuron activation prevented hypertension.35 High levels of prolactin, which is another representative

breastfeeding-related hormone, were associated with low risks of diabetes mellitus in a Chinese prospective study.36
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A previous study found parous women who breastfed or breastfed during longer period had a significantly lower
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risk of diabetes mellitus, compared to those who did not.8 Other recent studies confirmed this breastfeeding-diabetes
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mellitus relationship.37, 38 The beneficial effects of breastfeeding have also been observed against maternal hypertension,8,
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dyslipidemia,11 and metabolic syndrome.13
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These metabolic diseases may act on age-related cataract through mechanisms associated with accumulation of

advanced glycation end products of lens protein,23 endothelial dysfunction,22 oxidative stress,21, 39 and inflammation.22, 39
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Olafsdottir et al. showed that patients with diabetes mellitus had 2.6 times higher risk of cortical cataract, compared to
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control subjects.18 Another showed that diabetes mellitus at baseline predicted nuclear cataract, and impaired fasting

glucose predicted cortical cataract over a period of 10 years.20 Moreover, a recent meta-analysis study showed that

hypertension increases the risk of age-related cataract, particularly posterior subcapsular cataract.19 Despite inconsistent

and controversial in statin cataractogenicity,40, 41 use of statin for the treatment of dyslipidemia, resulting from absent or

early cessation of breastfeeding, can be associated with increased risk of developing age-related cataract.40
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This study is, to our knowledge, the first attempt to examine the relationship between breastfeeding and age-

related cataract. Another notable strength of our study is that our findings were derived from nationally representative

population. However, this study has some important limitations. First, causality cannot be inferred, because KNHANES

employed a cross-sectional design. Second, information on breastfeeding was based on self-report questionnaires, which

may be influenced by recall bias. Although previous studies showed the reliability and validity of the long-term recall of

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breastfeeding in a certain period,42, 43 recall bias in our study was highly anticipated because most of the participants

breastfed their children in 20-30s and examined for age-related cataract at least 50 years old. Moreover, breastfeeding

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questionnaires of KNHANES were not validated between breastfeeding practice and maternal recall on it. Third,

researchers should be cautious in applying our study findings to today’s women in a period of lactation or in other cultures,

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because it is possible that our participants’ lifestyle relevant to breastfeeding is different from those. Lastly, the

mechanism for breastfeeding to be related only to cortical cataracts and not to other cataract subtypes is unclear.

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In our study, decreased number of breastfed children and breastfeeding duration were significantly related to
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increased risks for cortical cataract in parous postmenopausal women. Our study findings should be confirmed from the

similar studies in other populations. Moreover, prospective and longitudinal studies are required to clarify the mechanisms
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breastfeeding-related cataract formation.

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FUNDING/SUPPORT: NO FUNDING OR GRANT SUPPORT.

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FINANCIAL DISCLOSURES: No financial disclosures.

All authors attest that they meet the current ICMJE criteria for authorship.
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Figure 1. Odds ratios (95% confidence intervals) of cataract formation according to (A) the number of breastfed children

(unit: number of children) and (B) the breastfeeding duration (unit: year). Each model adjusted for age, smoking status,

alcohol drinking, education level, income status, diabetes mellitus, sun exposure, and family history of eye disease.

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Table 1. Characteristics of study participants.

No cataract Any cataract P value

No. of participants (%) 1,624 (42.5%) 2,197 (57.5%)
Age, yr 56.9±5.8 66.1±8.5 <0.001
Lifestyle variable
Former or current smoking, % 4.7 6.3 0.033
Alcohol consumption (≥ once a mo), % 31.9 22.7 <0.001
Socioeconomic status variable

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Education level, %
≤ Middle school 59.3 81.3 <0.001
High school 29.8 14.6

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≥ College 11.0 4.1
Household income (≥2,000 US$/mo), % 68.6 45.0 <0.001
Eye-related variable
Sun exposure, %

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<2 h/d 67.3 60.3 <0.001
2-5 h/d 21.7 24.1
>5 h/d 11.0 15.6
Family history of eye disease, % 21.0 14.6 <0.001

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Diabetes mellitus, % 7.3 16.4 <0.001
Reproductive and breastfeeding variable
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Parity, n 2.5±1.1 3.5±1.7 <0.001
Breastfed children, no 2.2±1.3 3.2±1.8 <0.001
Breastfeeding duration, mo 31.4±30.8 58.3±50.4 <0.001
Subtype of cataracta
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Cortical 12.3
Nuclear 35.2
Anterior subscapular 1.4
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Posterior subscapular 0.5

Mixed 10.9
Data are presented as % and mean±SD. aThe percentage of participants in each category who had each age-related cataract
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subtype, regardless of the presence of other subtypes.

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Table 2. Odds ratios (95% confidence intervals) of cataract formation according to number of breastfed children.

Quartile of number of breastfed children (range, no.)

Q1 (0-1) Q2 (2) Q3 (3) Q4 (4-12) P for trend

No. of total participants 643 1,252 872 1,054
Cortical cataract
No.a 69/424 129/850 115/450 157/370
Age-adjusted Model Reference 1.01 (0.71-1.43) 0.91 (0.62-1.33) 0.73 (0.48-1.12) 0.13

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Multivariable-adjusted Model Reference 0.90 (0.62-1.31) 0.73 (0.48-1.11) 0.56 (0.35-0.89) 0.010
Nuclear cataract
No.a 188/543 334/1,055 331/666 492/705
Age-adjusted Model Reference 0.95 (0.75-1.20) 1.09 (0.84-1.43) 1.20 (0.90-1.60) 0.13

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Multivariable-adjusted Model Reference 0.92 (0.72-1.19) 0.96 (0.72-1.27) 1.11 (0.80-1.53) 0.51
Mixed cataract
No.a 35/390 74/795 95/430 213/426

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Age-adjusted Model Reference 1.12 (0.67-1.85) 1.08 (0.65-1.79) 1.20 (0.73-2.00) 0.51
Multivariable-adjusted Model Reference 1.05 (0.61-1.81) 0.91 (0.52-1.59) 1.06 (0.60-1.88) 0.92
Any cataract
No.b 288/643 531/1,252 537/872 841/1,054

U
Age-adjusted Model Reference 1.01 (0.81-1.24) 1.10 (0.87-1.40) 1.14 (0.88-1.49) 0.24
Multivariable-adjusted Model Reference 0.96 (0.76-1.21) 0.95 (0.73-1.23) 1.00 (0.74-1.35) 0.97
AN
Multivariable-adjusted model included age, smoking status, alcohol consumption, education level, household income,

diabetes mellitus, sun exposure, and family history of eye disease. aNumber of participants having each cataract subtype
M

among those having only one cataract subtype in each quartile group. bNumber of participants having any subtype of

cataract among those in each quartile group. Bold numbers indicated P <0.05.
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Table 3. Odds ratios (95% confidence intervals) of cataract formation according to breastfeeding duration.

Quartile of duration of breastfeeding (range, mo)

Q1 (0-16) Q2 (17-35) Q3 (36-60) Q4 (61-324) P for trend

No. of total participants 952 853 1,050 934
Cortical cataract
No.a 95/651 93/570 126/523 152/343
Age-adjusted Model Reference 0.98 (0.70-1.37) 0.83 (0.59-1.17) 0.75 (0.50-1.13) 0.13

PT
Multivariable-adjusted Model Reference 0.79 (0.55-1.13) 0.61 (0.42-0.90) 0.53 (0.33-0.83) 0.003
Nuclear cataract
No.a 260/816 227/704 420/817 422/613
Age-adjusted Model Reference 0.94 (0.74-1.18) 1.14 (0.90-1.44) 0.99 (0.74-1.32) 0.60

RI
Multivariable-adjusted Model Reference 0.82 (0.63-1.05) 0.94 (0.73-1.22) 0.87 (0.63-1.21) 0.56
Mixed cataract
No.a 45/601 55/532 126/523 182/373

SC
Age-adjusted Model Reference 1.12 (0.69-1.83) 1.15 (0.73-1.80) 1.03 (0.64-1.67) 0.93
Multivariable-adjusted Model Reference 0.92 (0.54-1.56) 0.96 (0.57-1.60) 0.87 (0.50-1.53) 0.68
Any cataract
No.b 396/952 376/853 653/1,050 743/934

U
Age-adjusted Model Reference 1.00 (0.81-1.23) 1.10 (0.89-1.36) 1.02 (0.79-1.33) 0.59
Multivariable-adjusted Model Reference 0.86 (0.69-1.08) 0.91 (0.72-1.15) 0.85 (0.63-1.14) 0.32
AN
Multivariable-adjusted model included age, smoking status, alcohol consumption, education level, household income,

diabetes mellitus, sun exposure, and family history of eye disease. aNumber of participants having each cataract subtype
M

among those having only one cataract subtype in each quartile group. bNumber of participants having any subtype of

cataract among those in each quartile group. Bold numbers indicated P <0.05.
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